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Sample records for gene study strategy

  1. Studying Genes

    Science.gov (United States)

    ... NIGMS NIGMS Home > Science Education > Studying Genes Studying Genes Tagline (Optional) Middle/Main Content Area PDF Version (382 KB) Other Fact Sheets What are genes? Genes are segments of DNA that contain instructions ...

  2. Using the GEMM-ESC strategy to study gene function in mouse models.

    Science.gov (United States)

    Huijbers, Ivo J; Del Bravo, Jessica; Bin Ali, Rahmen; Pritchard, Colin; Braumuller, Tanya M; van Miltenburg, Martine H; Henneman, Linda; Michalak, Ewa M; Berns, Anton; Jonkers, Jos

    2015-11-01

    Preclinical in vivo validation of target genes for therapeutic intervention requires careful selection and characterization of the most suitable animal model in order to assess the role of these genes in a particular process or disease. To this end, genetically engineered mouse models (GEMMs) are typically used. However, the appropriate engineering of these models is often cumbersome and time consuming. Recently, we and others described a modular approach for fast-track modification of existing GEMMs by re-derivation of embryonic stem cells (ESCs) that can be modified by recombinase-mediated transgene insertion and subsequently used for the production of chimeric mice. This 'GEMM-ESC strategy' allows for rapid in vivo analysis of gene function in the chimeras and their offspring. Moreover, this strategy is compatible with CRISPR/Cas9-mediated genome editing. This protocol describes when and how to use the GEMM-ESC strategy effectively, and it provides a detailed procedure for re-deriving and manipulating GEMM-ESCs under feeder- and serum-free conditions. This strategy produces transgenic mice with the desired complex genotype faster than traditional methods: generation of validated GEMM-ESC clones for controlled transgene integration takes 9-12 months, and recombinase-mediated transgene integration and chimeric cohort production takes 2-3 months. The protocol requires skills in embryology, stem cell biology and molecular biology, and it is ideally performed within, or in close collaboration with, a transgenic facility.

  3. Multifactor dimensionality reduction: An analysis strategy for modelling and detecting gene - gene interactions in human genetics and pharmacogenomics studies

    Directory of Open Access Journals (Sweden)

    Motsinger Alison A

    2006-03-01

    Full Text Available Abstract The detection of gene - gene and gene - environment interactions associated with complex human disease or pharmacogenomic endpoints is a difficult challenge for human geneticists. Unlike rare, Mendelian diseases that are associated with a single gene, most common diseases are caused by the non-linear interaction of numerous genetic and environmental variables. The dimensionality involved in the evaluation of combinations of many such variables quickly diminishes the usefulness of traditional, parametric statistical methods. Multifactor dimensionality reduction (MDR is a novel and powerful statistical tool for detecting and modelling epistasis. MDR is a non-parametric and model-free approach that has been shown to have reasonable power to detect epistasis in both theoretical and empirical studies. MDR has detected interactions in diseases such as sporadic breast cancer, multiple sclerosis and essential hypertension. As this method is more frequently applied, and was gained acceptance in the study of human disease and pharmacogenomics, it is becoming increasingly important that the implementation of the MDR approach is properly understood. As with all statistical methods, MDR is only powerful and useful when implemented correctly. Concerns regarding dataset structure, configuration parameters and the proper execution of permutation testing in reference to a particular dataset and configuration are essential to the method's effectiveness. The detection, characterisation and interpretation of gene - gene and gene - environment interactions are expected to improve the diagnosis, prevention and treatment of common human diseases. MDR can be a powerful tool in reaching these goals when used appropriately.

  4. Multifactor dimensionality reduction: An analysis strategy for modelling and detecting gene - gene interactions in human genetics and pharmacogenomics studies

    Science.gov (United States)

    2006-01-01

    The detection of gene - gene and gene - environment interactions associated with complex human disease or pharmacogenomic endpoints is a difficult challenge for human geneticists. Unlike rare, Mendelian diseases that are associated with a single gene, most common diseases are caused by the non-linear interaction of numerous genetic and environmental variables. The dimensionality involved in the evaluation of combinations of many such variables quickly diminishes the usefulness of traditional, parametric statistical methods. Multifactor dimensionality reduction (MDR) is a novel and powerful statistical tool for detecting and modelling epistasis. MDR is a non-parametric and model-free approach that has been shown to have reasonable power to detect epistasis in both theoretical and empirical studies. MDR has detected interactions in diseases such as sporadic breast cancer, multiple sclerosis and essential hypertension. As this method is more frequently applied, and was gained acceptance in the study of human disease and pharmacogenomics, it is becoming increasingly important that the implementation of the MDR approach is properly understood. As with all statistical methods, MDR is only powerful and useful when implemented correctly. Concerns regarding dataset structure, configuration parameters and the proper execution of permutation testing in reference to a particular dataset and configuration are essential to the method's effectiveness. The detection, characterisation and interpretation of gene - gene and gene - environment interactions are expected to improve the diagnosis, prevention and treatment of common human diseases. MDR can be a powerful tool in reaching these goals when used appropriately. PMID:16595076

  5. Multifactor dimensionality reduction: an analysis strategy for modelling and detecting gene-gene interactions in human genetics and pharmacogenomics studies.

    Science.gov (United States)

    Motsinger, Alison A; Ritchie, Marylyn D

    2006-03-01

    The detection of gene-gene and gene-environment interactions associated with complex human disease or pharmacogenomic endpoints is a difficult challenge for human geneticists. Unlike rare, Mendelian diseases that are associated with a single gene, most common diseases are caused by the non-linear interaction of numerous genetic and environmental variables. The dimensionality involved in the evaluation of combinations of many such variables quickly diminishes the usefulness of traditional, parametric statistical methods. Multifactor dimensionality reduction (MDR) is a novel and powerful statistical tool for detecting and modelling epistasis. MDR is a non-parametric and model-free approach that has been shown to have reasonable power to detect epistasis in both theoretical and empirical studies. MDR has detected interactions in diseases such as sporadic breast cancer, multiple sclerosis and essential hypertension. As this method is more frequently applied, and was gained acceptance in the study of human disease and pharmacogenomics, it is becoming increasingly important that the implementation of the MDR approach is properly understood. As with all statistical methods, MDR is only powerful and useful when implemented correctly. Concerns regarding dataset structure, configuration parameters and the proper execution of permutation testing in reference to a particular dataset and configuration are essential to the method's effectiveness. The detection, characterisation and interpretation of gene-gene and gene-environment interactions are expected to improve the diagnosis, prevention and treatment of common human diseases. MDR can be a powerful tool in reaching these goals when used appropriately.

  6. CRISPR-based strategies for studying regulatory elements and chromatin structure in mammalian gene control.

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    Lau, Cia-Hin; Suh, Yousin

    2017-12-01

    The development of high-throughput methods has enabled the genome-wide identification of putative regulatory elements in a wide variety of mammalian cells at an unprecedented resolution. Extensive genomic studies have revealed the important role of regulatory elements and genetic variation therein in disease formation and risk. In most cases, there is only correlative evidence for the roles of these elements and non-coding changes within these elements in pathogenesis. With the advent of genome- and epigenome-editing tools based on the CRISPR technology, it is now possible to test the functional relevance of the regulatory elements and alterations on a genomic scale. Here, we review the various CRISPR-based strategies that have been developed to functionally validate the candidate regulatory elements in mammals as well as the non-coding genetic variants found to be associated with human disease. We also discuss how these synthetic biology tools have helped to elucidate the role of three-dimensional nuclear architecture and higher-order chromatin organization in shaping functional genome and controlling gene expression.

  7. Development and evaluation of different normalization strategies for gene expression studies in Candida albicans biofilms by real-time PCR

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    Deforce Dieter

    2006-08-01

    Full Text Available Abstract Background Candida albicans biofilms are commonly found on indwelling medical devices. However, the molecular basis of biofilm formation and development is not completely understood. Expression analysis of genes potentially involved in these processes, such as the ALS (Agglutinine Like Sequence gene family can be performed using quantitative PCR (qPCR. In the present study, we investigated the expression stability of eight housekeeping genes potentially useful as reference genes to study gene expression in Candida albicans (C. albicans biofilms, using the geNorm Visual Basic Application (VBA for Microsoft Excel. To validate our normalization strategies we determined differences in ALS1 and ALS3 expression levels between C. albicans biofilm cells and their planktonic counterparts. Results The eight genes tested in this study are ranked according to their expression stability (from most stable to least stable as follows: ACT1 (β-actin/PMA1 (adenosine triphosphatase, RIP (ubiquinol cytochrome-c reductase complex component, RPP2B (cytosolic ribosomal acidic protein P2B, LSC2 (succinyl-CoA synthetase β-subunit fragment, IMH3 (inosine-5'-monophosphate dehydrogenase fragment, CPA1 (carbamoyl-phosphate synthethase small subunit and GAPDH (glyceraldehyde-3-phosphate dehydrogenase. Our data indicate that five genes are necessary for accurate and reliable normalization of gene expression data in C. albicans biofilms. Using different normalization strategies, we found a significant upregulation of the ALS1 gene and downregulation of the ALS3 gene in C. albicans biofilms grown on silicone disks in a continous flow system, the CDC reactor (Centre for Disease Control, for 24 hours. Conclusion In conclusion, we recommend the use of the geometric mean of the relative expression values from the five housekeeping genes (ACT1, PMA1, RIP, RPP2B and LSC2 for normalization, when analysing differences in gene expression levels between C. albicans biofilm

  8. Study Strategies

    DEFF Research Database (Denmark)

    Nielsen, Camilla Kirketerp; Noer, Vibeke Røn

    module”. The projects differ in terms of both starting point and main focus of research (an alternative educational model and profession-orientated Game-based learning). However, in the on-going process of research, an empirical ´harmony´ on common recurrent themes related to students `study strategies......ID: 1277 / 22 SES 06 B: 2 22. Research in Higher Education Format of Presentation: Paper Alternative EERA Network: 19. Ethnography Topics: NW 22: Teaching, learning and assessment in higher education Keywords: Profession-oriented learning, study strategies, professionalisation processes......-class until graduation and entrance into the nursing field as professional nurses. Case 2: In the veterinary educational environment, a pedagogical development project on development, implementation and evaluation of game-based learning as a possible way of strengthening the interplay between practice...

  9. Expression of RNA-interference/antisense transgenes by the cognate promoters of target genes is a better gene-silencing strategy to study gene functions in rice.

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    Li, Jing; Jiang, Dagang; Zhou, Hai; Li, Feng; Yang, Jiawei; Hong, Laifa; Fu, Xiao; Li, Zhibin; Liu, Zhenlan; Li, Jianming; Zhuang, Chuxiong

    2011-03-03

    Antisense and RNA interference (RNAi)-mediated gene silencing systems are powerful reverse genetic methods for studying gene function. Most RNAi and antisense experiments used constitutive promoters to drive the expression of RNAi/antisense transgenes; however, several reports showed that constitutive promoters were not expressed in all cell types in cereal plants, suggesting that the constitutive promoter systems are not effective for silencing gene expression in certain tissues/organs. To develop an alternative method that complements the constitutive promoter systems, we constructed RNAi and/or antisense transgenes for four rice genes using a constitutive promoter or a cognate promoter of a selected rice target gene and generated many independent transgenic lines. Genetic, molecular, and phenotypic analyses of these RNAi/antisense transgenic rice plants, in comparison to previously-reported transgenic lines that silenced similar genes, revealed that expression of the cognate promoter-driven RNAi/antisense transgenes resulted in novel growth/developmental defects that were not observed in transgenic lines expressing constitutive promoter-driven gene-silencing transgenes of the same target genes. Our results strongly suggested that expression of RNAi/antisense transgenes by cognate promoters of target genes is a better gene-silencing approach to discovery gene function in rice.

  10. Preprocessing and Quality Control Strategies for Illumina DASL Assay-Based Brain Gene Expression Studies with Semi-Degraded Samples

    Directory of Open Access Journals (Sweden)

    Maggie L Chow

    2012-02-01

    Full Text Available Available statistical preprocessing or quality control analysis tools for gene expression microarray datasets are known to greatly affect downstream data analysis, especially when degraded samples, unique tissue samples or novel expression assays are used. It is therefore important to assess the validity and impact of the assumptions built in to preprocessing schemes for a dataset. We developed and assessed a data preprocessing strategy for use with the Illumina DASL-based gene expression assay with partially degraded postmortem prefrontal cortex samples. The samples were obtained from individuals with autism as part of an investigation of the pathogenic factors contributing to autism.Using statistical analysis methods and metrics such as those associated with multivariate distance matrix regression (MDMR and mean inter-array correlation, we developed a DASL-based assay gene expression preprocessing pipeline to accommodate and detect problems with microarray-based gene expression values obtained with degraded brain samples. Key steps in the pipeline included outlier exclusion, data transformation and normalization, and batch effect and covariate corrections. Our goal was to produce a clean dataset for subsequent downstream differential expression analysis. We ultimately settled on available transformation and normalization algorithms in the R/Bioconductor package lumi based on an assessment of their use in various combinations. A log2-transformed, quantile-normalized, and batch and seizure-corrected procedure was likely the most appropriate for our data. We empirically tested different components of our proposed preprocessing strategy and believe that our results suggest that a preprocessing strategy that effectively identifies outliers, normalizes the data, and corrects for batch effects, like ours can be applied to all studies, even those pursued with degraded samples.

  11. Exploring new gene integration sites for gene knock-in by gene-trapping strategy.

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    Nanchi, Isamu; Yoshimura, Yuki; Nakamura, Kazuomi; Masago, Yusaku; Ohbayashi, Tetsuya; Okuda, Tomohiko

    2015-06-01

    The knock-in mouse is a powerful tool for biological research, but the stability of expression of an integrated gene strongly depends on where it is integrated in the mouse genome. At present, there are an insufficient number of loci suitable for gene knock-in, such as the Rosa26 locus. Therefore, in this study, we developed an efficient strategy for identifying genome loci suitable for gene knock-in and characterized the properties of such loci for gene integration. For efficient discovery and characterization, we constructed a new gene-trapping vector that enables monitoring of the expression of both trapped and integrated genes using fluorescence. We successfully obtained fluorescent-positive mouse embryonic stem cell (mESC) clones with the vector. Thorough analysis of the expression of fluorescent proteins in chimera embryos generated with the obtained mESC clones, some of the gene-trapped chimera embryos showed stable and ubiquitous expression of the integrated gene. Furthermore, adult mice derived from one of the gene-trapped mESC clones showed ubiquitous expression of the integrated gene in various tissues without any unusual phenotype. This indicated that the identified locus possesses high potential for foreign gene integration. Our strategy allows for efficient discovery and characterization of mouse genome loci for gene integration.

  12. Adeno-Associated Virus (AAV) Mediated Dystrophin Gene Transfer Studies and Exon Skipping Strategies for Duchenne Muscular Dystrophy (DMD).

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    Kawecka, Klaudia; Theodoulides, Michael; Hasoglu, Yalin; Jarmin, Susan; Kymalainen, Hanna; Le-Heron, Anita; Popplewell, Linda; Malerba, Alberto; Dickson, George; Athanasopoulos, Takis

    2015-01-01

    Duchenne muscular dystrophy (DMD), an X-linked inherited musclewasting disease primarily affecting young boys with prevalence of between1:3,500- 1:5,000, is a rare genetic disease caused by defects in the gene for dystrophin. Dystrophin protein is critical to the stability of myofibers in skeletal and cardiac muscle. There is currently no cure available to ameliorate DMD and/or its patho-physiology. A number of therapeutic strategies including molecular-based therapeutics that replace or correct the missing or nonfunctional dystrophin protein have been devised to correct the patho-physiological consequences induced by dystrophin absence. We will review the current in vivo experimentation status (including preclinical models and clinical trials) for two of these approaches, namely: 1) Adeno-associated virus (AAV) mediated (micro) dystrophin gene augmentation/ supplementation and 2) Antisense oligonucleotide (AON)-mediated exon skipping strategies.

  13. Strategies in Gene Therapy for Glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Kwiatkowska, Aneta; Nandhu, Mohan S.; Behera, Prajna; Chiocca, E. Antonio; Viapiano, Mariano S., E-mail: mviapiano@partners.org [Department of Neurosurgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115 (United States)

    2013-10-22

    Glioblastoma (GBM) is the most aggressive form of brain cancer, with a dismal prognosis and extremely low percentage of survivors. Novel therapies are in dire need to improve the clinical management of these tumors and extend patient survival. Genetic therapies for GBM have been postulated and attempted for the past twenty years, with variable degrees of success in pre-clinical models and clinical trials. Here we review the most common approaches to treat GBM by gene therapy, including strategies to deliver tumor-suppressor genes, suicide genes, immunomodulatory cytokines to improve immune response, and conditionally-replicating oncolytic viruses. The review focuses on the strategies used for gene delivery, including the most common and widely used vehicles (i.e., replicating and non-replicating viruses) as well as novel therapeutic approaches such as stem cell-mediated therapy and nanotechnologies used for gene delivery. We present an overview of these strategies, their targets, different advantages, and challenges for success. Finally, we discuss the potential of gene therapy-based strategies to effectively attack such a complex genetic target as GBM, alone or in combination with conventional therapy.

  14. Strategies in Gene Therapy for Glioblastoma

    International Nuclear Information System (INIS)

    Kwiatkowska, Aneta; Nandhu, Mohan S.; Behera, Prajna; Chiocca, E. Antonio; Viapiano, Mariano S.

    2013-01-01

    Glioblastoma (GBM) is the most aggressive form of brain cancer, with a dismal prognosis and extremely low percentage of survivors. Novel therapies are in dire need to improve the clinical management of these tumors and extend patient survival. Genetic therapies for GBM have been postulated and attempted for the past twenty years, with variable degrees of success in pre-clinical models and clinical trials. Here we review the most common approaches to treat GBM by gene therapy, including strategies to deliver tumor-suppressor genes, suicide genes, immunomodulatory cytokines to improve immune response, and conditionally-replicating oncolytic viruses. The review focuses on the strategies used for gene delivery, including the most common and widely used vehicles (i.e., replicating and non-replicating viruses) as well as novel therapeutic approaches such as stem cell-mediated therapy and nanotechnologies used for gene delivery. We present an overview of these strategies, their targets, different advantages, and challenges for success. Finally, we discuss the potential of gene therapy-based strategies to effectively attack such a complex genetic target as GBM, alone or in combination with conventional therapy

  15. Exploring the optimal strategy to predict essential genes in microbes.

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    Deng, Jingyuan; Tan, Lirong; Lin, Xiaodong; Lu, Yao; Lu, Long J

    2011-12-27

    Accurately predicting essential genes is important in many aspects of biology, medicine and bioengineering. In previous research, we have developed a machine learning based integrative algorithm to predict essential genes in bacterial species. This algorithm lends itself to two approaches for predicting essential genes: learning the traits from known essential genes in the target organism, or transferring essential gene annotations from a closely related model organism. However, for an understudied microbe, each approach has its potential limitations. The first is constricted by the often small number of known essential genes. The second is limited by the availability of model organisms and by evolutionary distance. In this study, we aim to determine the optimal strategy for predicting essential genes by examining four microbes with well-characterized essential genes. Our results suggest that, unless the known essential genes are few, learning from the known essential genes in the target organism usually outperforms transferring essential gene annotations from a related model organism. In fact, the required number of known essential genes is surprisingly small to make accurate predictions. In prokaryotes, when the number of known essential genes is greater than 2% of total genes, this approach already comes close to its optimal performance. In eukaryotes, achieving the same best performance requires over 4% of total genes, reflecting the increased complexity of eukaryotic organisms. Combining the two approaches resulted in an increased performance when the known essential genes are few. Our investigation thus provides key information on accurately predicting essential genes and will greatly facilitate annotations of microbial genomes.

  16. Gene-environment Interactions in Human Health: Case Studies and Strategies for developing new paradigms and research methodologies

    Directory of Open Access Journals (Sweden)

    Fatimah L.C. Jackson

    2014-08-01

    Full Text Available The synergistic effects of genes and the environment on health are explored in three case studies: adult lactase persistence, autism spectrum disorders, and the metabolic syndrome, providing examples of the interactive complexities underlying these phenotypes. Since the phenotypes are the initial targets of evolutionary processes, understanding the specific environmental contexts of the genetic, epigenetic, and proteomic changes associated with these phenotypes is essential in predicting their health implications. Robust databases must be developed on the local scale to deconstruct both the population substructure and the unique components of the environment that stimulate geographically-specific changes in gene expression patterns. To produce these databases and make valid predictions, new, locally-focused and information-dense models are needed that incorporate data on evolutionary ecology, environmental complexity, local geographic patterns of gene expression, and population substructure.

  17. Nonviral Delivery Systems For Cancer Gene Therapy: Strategies And Challenges.

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    Shim, Gayong; Kim, Dongyoon; Le, Quoc-Viet; Park, Gyu Thae; Kwon, Taekhyun; Oh, Yu-Kyoung

    2018-01-19

    Gene therapy has been receiving widespread attention due to its unique advantage in regulating the expression of specific target genes. In the field of cancer gene therapy, modulation of gene expression has been shown to decrease oncogenic factors in cancer cells or increase immune responses against cancer. Due to the macromolecular size and highly negative physicochemical features of plasmid DNA, efficient delivery systems are an essential ingredient for successful gene therapy. To date, a variety of nanostructures and materials have been studied as nonviral gene delivery systems. In this review, we will cover nonviral delivery strategies for cancer gene therapy, with a focus on target cancer genes and delivery materials. Moreover, we will address current challenges and perspectives for nonviral delivery-based cancer gene therapeutics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Exploring the Optimal Strategy to Predict Essential Genes in Microbes

    Directory of Open Access Journals (Sweden)

    Yao Lu

    2011-12-01

    Full Text Available Accurately predicting essential genes is important in many aspects of biology, medicine and bioengineering. In previous research, we have developed a machine learning based integrative algorithm to predict essential genes in bacterial species. This algorithm lends itself to two approaches for predicting essential genes: learning the traits from known essential genes in the target organism, or transferring essential gene annotations from a closely related model organism. However, for an understudied microbe, each approach has its potential limitations. The first is constricted by the often small number of known essential genes. The second is limited by the availability of model organisms and by evolutionary distance. In this study, we aim to determine the optimal strategy for predicting essential genes by examining four microbes with well-characterized essential genes. Our results suggest that, unless the known essential genes are few, learning from the known essential genes in the target organism usually outperforms transferring essential gene annotations from a related model organism. In fact, the required number of known essential genes is surprisingly small to make accurate predictions. In prokaryotes, when the number of known essential genes is greater than 2% of total genes, this approach already comes close to its optimal performance. In eukaryotes, achieving the same best performance requires over 4% of total genes, reflecting the increased complexity of eukaryotic organisms. Combining the two approaches resulted in an increased performance when the known essential genes are few. Our investigation thus provides key information on accurately predicting essential genes and will greatly facilitate annotations of microbial genomes.

  19. SNP Variation in MicroRNA Biogenesis Pathway Genes as a New Innovation Strategy for Alzheimer Disease Diagnostics: A Study of 10 Candidate Genes in an Understudied Population From the Eastern Mediterranean.

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    Görücü Yilmaz, Şenay; Erdal, Mehmet E; Avci Özge, Aynur; Sungur, Mehmet A

    2016-01-01

    Alzheimer disease (AD) is a common complex neurodegenerative disorder accounting for nearly 50% to 70% of dementias worldwide. Yet the current diagnostic options for AD are limited. New diagnostic innovation strategies focusing on novel molecules and pathways are sorely needed. In this connection, microRNAs (miRNAs) are conserved small noncoding RNAs that regulate posttranscriptional gene expression and are vital for neuronal development and its functional sustainability. Conceivably, biological pathways responsible for the biogenesis of miRNAs represent a veritable set of upstream candidate genes that can be potentially associated with the AD pathophysiology. Notably, whereas functional single-nucleotide polymorphisms (SNPs) in miRNA biogenesis pathway genes have been studied in other complex diseases, surprisingly, virtually no such study has been conducted on their relevance in AD. Moreover, novel diagnostics identified in easily accessible peripheral tissues such as the whole blood samples represent the initial entry or gateway points on the biomarker discovery critical path for AD. To the best of our knowledge, we report here the first association study of functional SNPs, as measured by real-time PCR in 10 "upstream" candidate genes critically situated on the miRNA biogenesis pathway, in a large sample of AD patients (N=172) and healthy controls (N=109) in a hitherto understudied world population from the Mersin region of the Eastern Mediterranean. We observed a significant association between 2 candidate genes and AD, TARBP2 rs784567 genotype and AD (χ=6.292, P=0.043), and a trend for RNASEN rs10719 genotype (χ=4.528, P=0.104) and allele (P=0.035). Functional SNP variations in the other 8 candidate genes (DGCR8, XPO5, RAN, DICER1, AGO1, AGO2, GEMIN3, and GEMIN4) did not associate with AD in our sample. Given the putative biological importance of miRNA biogenesis pathways, these emerging data can provide a new foundation to stimulate future debate and

  20. The Songbird Neurogenomics (SoNG) Initiative: community-based tools and strategies for study of brain gene function and evolution.

    Science.gov (United States)

    Replogle, Kirstin; Arnold, Arthur P; Ball, Gregory F; Band, Mark; Bensch, Staffan; Brenowitz, Eliot A; Dong, Shu; Drnevich, Jenny; Ferris, Margaret; George, Julia M; Gong, George; Hasselquist, Dennis; Hernandez, Alvaro G; Kim, Ryan; Lewin, Harris A; Liu, Lei; Lovell, Peter V; Mello, Claudio V; Naurin, Sara; Rodriguez-Zas, Sandra; Thimmapuram, Jyothi; Wade, Juli; Clayton, David F

    2008-03-18

    Songbirds hold great promise for biomedical, environmental and evolutionary research. A complete draft sequence of the zebra finch genome is imminent, yet a need remains for application of genomic resources within a research community traditionally focused on ethology and neurobiological methods. In response, we developed a core set of genomic tools and a novel collaborative strategy to probe gene expression in diverse songbird species and natural contexts. We end-sequenced cDNAs from zebra finch brain and incorporated additional sequences from community sources into a database of 86,784 high quality reads. These assembled into 31,658 non-redundant contigs and singletons, which we annotated via BLAST search of chicken and human databases. The results are publicly available in the ESTIMA:Songbird database. We produced a spotted cDNA microarray with 20,160 addresses representing 17,214 non-redundant products of an estimated 11,500-15,000 genes, validating it by analysis of immediate-early gene (zenk) gene activation following song exposure and by demonstrating effective cross hybridization to genomic DNAs of other songbird species in the Passerida Parvorder. Our assembly was also used in the design of the "Lund-zfa" Affymetrix array representing approximately 22,000 non-redundant sequences. When the two arrays were hybridized to cDNAs from the same set of male and female zebra finch brain samples, both arrays detected a common set of regulated transcripts with a Pearson correlation coefficient of 0.895. To stimulate use of these resources by the songbird research community and to maintain consistent technical standards, we devised a "Community Collaboration" mechanism whereby individual birdsong researchers develop experiments and provide tissues, but a single individual in the community is responsible for all RNA extractions, labelling and microarray hybridizations. Immediately, these results set the foundation for a coordinated set of 25 planned experiments by 16

  1. The Songbird Neurogenomics (SoNG Initiative: Community-based tools and strategies for study of brain gene function and evolution

    Directory of Open Access Journals (Sweden)

    Lewin Harris A

    2008-03-01

    Full Text Available Abstract Background Songbirds hold great promise for biomedical, environmental and evolutionary research. A complete draft sequence of the zebra finch genome is imminent, yet a need remains for application of genomic resources within a research community traditionally focused on ethology and neurobiological methods. In response, we developed a core set of genomic tools and a novel collaborative strategy to probe gene expression in diverse songbird species and natural contexts. Results We end-sequenced cDNAs from zebra finch brain and incorporated additional sequences from community sources into a database of 86,784 high quality reads. These assembled into 31,658 non-redundant contigs and singletons, which we annotated via BLAST search of chicken and human databases. The results are publicly available in the ESTIMA:Songbird database. We produced a spotted cDNA microarray with 20,160 addresses representing 17,214 non-redundant products of an estimated 11,500–15,000 genes, validating it by analysis of immediate-early gene (zenk gene activation following song exposure and by demonstrating effective cross hybridization to genomic DNAs of other songbird species in the Passerida Parvorder. Our assembly was also used in the design of the "Lund-zfa" Affymetrix array representing ~22,000 non-redundant sequences. When the two arrays were hybridized to cDNAs from the same set of male and female zebra finch brain samples, both arrays detected a common set of regulated transcripts with a Pearson correlation coefficient of 0.895. To stimulate use of these resources by the songbird research community and to maintain consistent technical standards, we devised a "Community Collaboration" mechanism whereby individual birdsong researchers develop experiments and provide tissues, but a single individual in the community is responsible for all RNA extractions, labelling and microarray hybridizations. Conclusion Immediately, these results set the foundation for a

  2. Vectors and strategies for nonviral cancer gene therapy.

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    Pahle, Jessica; Walther, Wolfgang

    2016-01-01

    This review presents recent developments in the use of nonviral vectors and transfer technologies in cancer gene therapy. Tremendous progress has been made in developing cancer gene therapy in ways that could be applicable to treatments. Numerous efforts are focused on methods of attacking known and novel targets more efficiently and specifically. In parallel to progress in nonviral vector design and delivery technologies, important achievements have been accomplished for suicide, gene replacement, gene suppression and immunostimulatory therapies. New nonviral cancer gene therapies have been developed based on emerging RNAi (si/shRNA-, miRNA) or ODN. This review provides an overview of recent gene therapeutic strategies in which nonviral vectors have been used experimentally and in clinical trials. Furthermore, we present current developments in nonviral vector systems in association with important chemical and physical gene delivery technologies and their potential for the future. Nonviral gene therapy has maintained its position as an approach for treating cancer. This is reflected by the fact that more than 17% of all gene therapy trials employ nonviral approaches. Thus, nonviral vectors have emerged as a clinical alternative to viral vectors for the appropriate expression and delivery of therapeutic genes.

  3. Using evolutionary conserved modules in gene networks as a strategy to leverage high throughput gene expression queries.

    Directory of Open Access Journals (Sweden)

    Jeanne M Serb

    Full Text Available BACKGROUND: Large-scale gene expression studies have not yielded the expected insight into genetic networks that control complex processes. These anticipated discoveries have been limited not by technology, but by a lack of effective strategies to investigate the data in a manageable and meaningful way. Previous work suggests that using a pre-determined seed-network of gene relationships to query large-scale expression datasets is an effective way to generate candidate genes for further study and network expansion or enrichment. Based on the evolutionary conservation of gene relationships, we test the hypothesis that a seed network derived from studies of retinal cell determination in the fly, Drosophila melanogaster, will be an effective way to identify novel candidate genes for their role in mouse retinal development. METHODOLOGY/PRINCIPAL FINDINGS: Our results demonstrate that a number of gene relationships regulating retinal cell differentiation in the fly are identifiable as pairwise correlations between genes from developing mouse retina. In addition, we demonstrate that our extracted seed-network of correlated mouse genes is an effective tool for querying datasets and provides a context to generate hypotheses. Our query identified 46 genes correlated with our extracted seed-network members. Approximately 54% of these candidates had been previously linked to the developing brain and 33% had been previously linked to the developing retina. Five of six candidate genes investigated further were validated by experiments examining spatial and temporal protein expression in the developing retina. CONCLUSIONS/SIGNIFICANCE: We present an effective strategy for pursuing a systems biology approach that utilizes an evolutionary comparative framework between two model organisms, fly and mouse. Future implementation of this strategy will be useful to determine the extent of network conservation, not just gene conservation, between species and will

  4. UP Finder: A COBRA toolbox extension for identifying gene overexpression strategies for targeted overproduction

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    Xi Wang

    2017-12-01

    Full Text Available Overexpression of key genes is a basic strategy for overproducing target products via metabolic engineering. Traditionally, identifying those key genes/pathways largely relies on the knowledge of biochemistry and bioinformatics. In this study, a modeling tool named UP Finder was developed to facilitate the rapid identification of gene overexpression strategies. It was based on the COBRA toolbox under MATLAB environment. All the key gene/pathway targets are identified in one click after simply loading a Systems Biology Markup Language model and specifying a metabolite as the targeted product. The outputs are also quantitatively ranked to show the preference for determining overexpression strategies in pathway design. Analysis examples for overproducing lycopene precursor in Escherichia coli and fatty acyl-ACP in the cyanobacterium Synechocystis sp. PCC 6803 by the UP Finder showed high degree of agreement with the reported key genes in the literatures.

  5. Development of a gene therapy strategy to target hepatocellular carcinoma based inhibition of protein phosphatase 2A using the α-fetoprotein promoter enhancer and pgk promoter: an in vitro and in vivo study

    Directory of Open Access Journals (Sweden)

    Li Wei

    2012-11-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC is one of the leading causes of cancer-related deaths worldwide. Current therapies are insufficient, making HCC an intractable disease. Our previous studies confirmed that inhibition of protein phosphatase 2A (PP2A may provide a promising therapeutic strategy for cancer. Unfortunately, constitutive expression of PP2A in normal tissues limits the application of PP2A inhibition. Thus, a HCC-specific gene delivery system should be developed. The α-fetoprotein (AFP promoter is commonly used in HCC-specific gene therapy strategies; however, the utility of this approach is limited due to the weak activity of the AFP promoter. It has been shown that linking the AFP enhancer with the promoter of the non-tissue-specific, human housekeeping phosphoglycerate kinase (pgk gene can generate a strong and HCC-selective promoter. Methods We constructed a HCC-specific gene therapy system to target PP2A using the AFP enhancer/pgk promoter, and evaluated the efficiency and specificity of this system both in vitro and in vivo. Results AFP enhancer/pgk promoter-driven expression of the dominant negative form of the PP2A catalytic subunit α (DN-PP2Acα exerted cytotoxic effects against an AFP-positive human hepatoma cell lines (HepG2 and Hep3B, but did not affect AFP-negative human hepatoma cells (SK-HEP-1 or normal human liver cells (L-02. Moreover, AFP enhancer/pgk promoter driven expression of DN-PP2Acα inhibited the growth of AFP-positive HepG2 tumors in nude mice bearing solid tumor xenografts, but did not affect AFP-negative SK-HEP-1 tumors. Conclusions The novel approach of AFP enhancer/pgk promoter-driven expression of DN-PP2Acα may provide a useful cancer gene therapy strategy to selectively target HCC.

  6. Development of a gene therapy strategy to target hepatocellular carcinoma based inhibition of protein phosphatase 2A using the α-fetoprotein promoter enhancer and pgk promoter: an in vitro and in vivo study

    International Nuclear Information System (INIS)

    Li, Wei; Tao, Min; Li, Dao-Ming; Chen, Kai; Chen, Zheng; Zong, Yang; Yin, Hong; Xu, Ze-Kuan; Zhu, Yi; Gong, Fei-Ran

    2012-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Current therapies are insufficient, making HCC an intractable disease. Our previous studies confirmed that inhibition of protein phosphatase 2A (PP2A) may provide a promising therapeutic strategy for cancer. Unfortunately, constitutive expression of PP2A in normal tissues limits the application of PP2A inhibition. Thus, a HCC-specific gene delivery system should be developed. The α-fetoprotein (AFP) promoter is commonly used in HCC-specific gene therapy strategies; however, the utility of this approach is limited due to the weak activity of the AFP promoter. It has been shown that linking the AFP enhancer with the promoter of the non-tissue-specific, human housekeeping phosphoglycerate kinase (pgk) gene can generate a strong and HCC-selective promoter. We constructed a HCC-specific gene therapy system to target PP2A using the AFP enhancer/pgk promoter, and evaluated the efficiency and specificity of this system both in vitro and in vivo. AFP enhancer/pgk promoter-driven expression of the dominant negative form of the PP2A catalytic subunit α (DN-PP2Acα) exerted cytotoxic effects against an AFP-positive human hepatoma cell lines (HepG2 and Hep3B), but did not affect AFP-negative human hepatoma cells (SK-HEP-1) or normal human liver cells (L-02). Moreover, AFP enhancer/pgk promoter driven expression of DN-PP2Acα inhibited the growth of AFP-positive HepG2 tumors in nude mice bearing solid tumor xenografts, but did not affect AFP-negative SK-HEP-1 tumors. The novel approach of AFP enhancer/pgk promoter-driven expression of DN-PP2Acα may provide a useful cancer gene therapy strategy to selectively target HCC

  7. Improving Adenovirus Based Gene Transfer: Strategies to Accomplish Immune Evasion

    Directory of Open Access Journals (Sweden)

    Andrea Amalfitano

    2010-09-01

    Full Text Available Adenovirus (Ad based gene transfer vectors continue to be the platform of choice for an increasing number of clinical trials worldwide. In fact, within the last five years, the number of clinical trials that utilize Ad based vectors has doubled, indicating growing enthusiasm for the numerous positive characteristics of this gene transfer platform. For example, Ad vectors can be easily and relatively inexpensively produced to high titers in a cGMP compliant manner, can be stably stored and transported, and have a broad applicability for a wide range of clinical conditions, including both gene therapy and vaccine applications. Ad vector based gene transfer will become more useful as strategies to counteract innate and/or pre-existing adaptive immune responses to Ads are developed and confirmed to be efficacious. The approaches attempting to overcome these limitations can be divided into two broad categories: pre-emptive immune modulation of the host, and selective modification of the Ad vector itself. The first category of methods includes the use of immunosuppressive drugs or specific compounds to block important immune pathways, which are known to be induced by Ads. The second category comprises several innovative strategies inclusive of: (1 Ad-capsid-display of specific inhibitors or ligands; (2 covalent modifications of the entire Ad vector capsid moiety; (3 the use of tissue specific promoters and local administration routes; (4 the use of genome modified Ads; and (5 the development of chimeric or alternative serotype Ads. This review article will focus on both the promise and the limitations of each of these immune evasion strategies, and in the process delineate future directions in developing safer and more efficacious Ad-based gene transfer strategies.

  8. Improving adenovirus based gene transfer: strategies to accomplish immune evasion.

    Science.gov (United States)

    Seregin, Sergey S; Amalfitano, Andrea

    2010-09-01

    Adenovirus (Ad) based gene transfer vectors continue to be the platform of choice for an increasing number of clinical trials worldwide. In fact, within the last five years, the number of clinical trials that utilize Ad based vectors has doubled, indicating growing enthusiasm for the numerous positive characteristics of this gene transfer platform. For example, Ad vectors can be easily and relatively inexpensively produced to high titers in a cGMP compliant manner, can be stably stored and transported, and have a broad applicability for a wide range of clinical conditions, including both gene therapy and vaccine applications. Ad vector based gene transfer will become more useful as strategies to counteract innate and/or pre-existing adaptive immune responses to Ads are developed and confirmed to be efficacious. The approaches attempting to overcome these limitations can be divided into two broad categories: pre-emptive immune modulation of the host, and selective modification of the Ad vector itself. The first category of methods includes the use of immunosuppressive drugs or specific compounds to block important immune pathways, which are known to be induced by Ads. The second category comprises several innovative strategies inclusive of: (1) Ad-capsid-display of specific inhibitors or ligands; (2) covalent modifications of the entire Ad vector capsid moiety; (3) the use of tissue specific promoters and local administration routes; (4) the use of genome modified Ads; and (5) the development of chimeric or alternative serotype Ads. This review article will focus on both the promise and the limitations of each of these immune evasion strategies, and in the process delineate future directions in developing safer and more efficacious Ad-based gene transfer strategies.

  9. Fight fire with fire: Gene therapy strategies to cure HIV.

    Science.gov (United States)

    Huyghe, Jon; Magdalena, Sips; Vandekerckhove, Linos

    2017-08-01

    Human Immunodeficiency Virus (HIV) to date remains one of the most notorious viruses mankind has ever faced. Despite enormous investments in HIV research for more than 30 years an effective cure for HIV has been elusive. Areas covered: Combination antiretroviral therapy (cART) suppresses active viral replication, but is not able to eliminate the virus completely due to stable integration of HIV inside the host genome of infected cells and the establishment of a latent reservoir, that is insensitive to cART. Nevertheless, this latent HIV reservoir is fully capable to refuel viral replication when treatment is stopped, creating a major obstacle towards a cure for HIV. Several gene therapy approaches ranging from the generation of HIV resistant CD4 + T cells to the eradication of HIV infected cells by immune cell engineering are currently under pre-clinical and clinical investigation and may present a promising road to a cure. In this review, we focus on the status and the prospects of gene therapy strategies to cure/eradicate HIV. Expert commentary: Recent advances in gene therapy for oncology and infectious diseases indicate that gene therapy may be a feasible and very potent cure strategy, and therefore a potential game changer in the search for an effective HIV cure.

  10. Efficient strategy for detecting gene × gene joint action and its application in schizophrenia

    NARCIS (Netherlands)

    Won, Sungho; Kwon, Min-Seok; Mattheisen, Manuel; Park, Suyeon; Park, Changsoon; Kihara, Daisuke; Cichon, Sven; Ophoff, Roel; Nöthen, Markus M.; Rietschel, Marcella; Baur, Max; Uitterlinden, Andre G.; Hofmann, A.; Lange, Christoph; Kahn, René S.; Linszen, Don H.; van Os, Jim; Wiersma, Durk; Bruggeman, Richard; Cahn, Wiepke; de Haan, Lieuwe; Krabbendam, Lydia; Myin-Germeys, Inez

    2014-01-01

    We propose a new approach to detect gene × gene joint action in genome-wide association studies (GWASs) for case-control designs. This approach offers an exhaustive search for all two-way joint action (including, as a special case, single gene action) that is computationally feasible at the

  11. Gene therapy for carcinoma of the breast: Genetic ablation strategies

    International Nuclear Information System (INIS)

    Curiel, David T

    2000-01-01

    The gene therapy strategy of mutation compensation is designed to rectify the molecular lesions that are etiologic for neoplastic transformation. For dominant oncogenes, such approaches involve the functional knockout of the dysregulated cellular control pathways provoked by the overexpressed oncoprotein. On this basis, molecular interventions may be targeted to the transcriptional level of expression, via antisense or ribozymes, or post-transcriptionally, via intracellular single chain antibodies (intrabodies). For carcinoma of the breast, these approaches have been applied in the context of the disease linked oncogenes erbB-2 and cyclin D 1 , as well as the estrogen receptor. Neoplastic revision accomplished in modal systems has rationalized human trials on this basis

  12. Gene Tagging Strategies To Assess Protein Expression, Localization, and Function in Drosophila

    Science.gov (United States)

    Kanca, Oguz; Bellen, Hugo J.; Schnorrer, Frank

    2017-01-01

    Analysis of gene function in complex organisms relies extensively on tools to detect the cellular and subcellular localization of gene products, especially proteins. Typically, immunostaining with antibodies provides these data. However, due to cost, time, and labor limitations, generating specific antibodies against all proteins of a complex organism is not feasible. Furthermore, antibodies do not enable live imaging studies of protein dynamics. Hence, tagging genes with standardized immunoepitopes or fluorescent tags that permit live imaging has become popular. Importantly, tagging genes present in large genomic clones or at their endogenous locus often reports proper expression, subcellular localization, and dynamics of the encoded protein. Moreover, these tagging approaches allow the generation of elegant protein removal strategies, standardization of visualization protocols, and permit protein interaction studies using mass spectrometry. Here, we summarize available genomic resources and techniques to tag genes and discuss relevant applications that are rarely, if at all, possible with antibodies. PMID:28978772

  13. A strategy for obtaining social benefits from the gene revolution

    Directory of Open Access Journals (Sweden)

    L.A.B. de Castro

    2004-10-01

    Full Text Available The strategy described in the present paper offers details about the possibility for Brazil to play a more substantial role in the gene revolution. If successfully applied, the powerful science-based technology currently available in Brazil can contribute to extend the benefits of the gene revolution to the poorest countries, very much like the Green Revolution did in the past, thereby reducing the hunger syndrome which claimed the lives of millions of people in some Asian countries, particularly Pakistan and India, decades ago. In his visit to Brazil in February 2004, Norman Borlaug had the opportunity to witness the success of Brazilian agriculture. At a Conference held at ESALQ - Superior School of Agriculture Luiz de Queiroz in Piracicaba, SP, Brazil, he stated that the 21st century revolution will come from Brazil in the area of agriculture. He also said that reducing hunger is essential for the world to achieve socioeconomic stability. A central question remains unanswered: who will fund this revolution? The FAO 2003-2004 Annual Report listed the barriers preventing the gene revolution from reaching the poorest countries: inadequate regulatory procedures - Intellectual Property Rights and Biosafety, poorly functioning seed delivering systems and weak domestic plant breeding capacity; all are discussed in this paper.

  14. Expression of highly toxic genes in E. coli: special strategies and genetic tools.

    Science.gov (United States)

    Saïda, F; Uzan, M; Odaert, B; Bontems, F

    2006-02-01

    Escherichia coli (E. coli) remains the most efficient widely-used host for recombinant protein production. Well-known genetics, high transformation efficiency, cultivation simplicity, rapidity and inexpensiveness are the main factors that contribute to the selection of this host. With the advent of the post-genomic era has come the need to express in this bacterium a growing number of genes originating from different organisms. Unfortunately, many of these genes severely interfere with the survival of E. coli cells. They lead to bacteria death or cause significant defects in bacteria growth that dramatically decrease expression capabilities. In this paper, we review special strategies and genetics tools successfully used to express, in E. coli, highly toxic genes. Suppression of basal expression from leaky inducible promoters, suppression of read-through transcription from cryptic promoters, tight control of plasmids copy numbers and proteins production as inactive (but reversible) forms are among the solutions presented and discussed. Special expression vectors and modified E. coli strains are listed and their effectiveness illustrated with key examples, some of which are related to our study of the highly toxic phage T4 restriction endoribonuclease RegB. We mainly selected those strategies and tools that permit E. coli normal growth until the very moment of highly toxic gene induction. Expression then occurs efficiently before cells die. Because they do not target a particular toxic effect, these strategies and tools can be used to express a wide variety of highly toxic genes.

  15. Gene-Based Antibody Strategies for Prion Diseases

    Directory of Open Access Journals (Sweden)

    Alessio Cardinale

    2013-01-01

    Full Text Available Prion diseases or transmissible spongiform encephalopathies (TSE are a group of neurodegenerative and infectious disorders characterized by the conversion of a normal cellular protein PrPC into a pathological abnormally folded form, termed PrPSc. There are neither available therapies nor diagnostic tools for an early identification of individuals affected by these diseases. New gene-based antibody strategies are emerging as valuable therapeutic tools. Among these, intrabodies are chimeric molecules composed by recombinant antibody fragments fused to intracellular trafficking sequences, aimed at inhibiting, in vivo, the function of specific therapeutic targets. The advantage of intrabodies is that they can be selected against a precise epitope of target proteins, including protein-protein interaction sites and cytotoxic conformers (i.e., oligomeric and fibrillar assemblies. Herein, we address and discuss in vitro and in vivo applications of intrabodies in prion diseases, focussing on their therapeutic potential.

  16. Enhancement of HIV-1 VLP production using gene inhibition strategies.

    Science.gov (United States)

    Fuenmayor, Javier; Cervera, Laura; Rigau, Cristina; Gòdia, Francesc

    2018-03-24

    Gag polyprotein from HIV-1 is able to generate virus-like particles (VLPs) when recombinantly expressed in animal cell platforms. HIV-1 VLP production in HEK293 cells can be improved by the use of different strategies for increasing product titers. One of them is the so-called extended gene expression (EGE), based on repeated medium exchanges and retransfections of the cell culture to prolong the production phase. Another approach is the media supplementation with gene expression enhancers such as valproic acid and caffeine, despite their detrimental effect on cell viability. Valproic acid is a histone deacetylase inhibitor while caffeine has a phosphodiesterase inhibition effect. Here, the combination of the EGE protocol with additive supplementation to maximize VLP production is first tested. As an alternative to the direct additive supplementation, the replacement of these chemical additives by iRNA for obtaining the same inhibition action is also tested. The combination of the EGE protocol with caffeine and valproic acid supplementation resulted in a 1.5-fold improvement in HIV-1 VLP production compared with the EGE protocol alone, representing an overall 18-fold improvement over conventional batch cultivation. shRNAs encoded in the expression vector were tested to substitute valproic acid and caffeine. This novel strategy enhanced VLP production by 2.3 fold without any detrimental effect on cell viability (91.7%) compared with the batch cultivation (92.0%). Finally, the combination of shRNA with EGE resulted in more than 15.6-fold improvement compared with the batch standard protocol traditionally used. The methodology developed enables the production of high titers of HIV-1 VLPs avoiding the toxic effects of additives.

  17. A Potential Therapeutic Strategy for Malignant Mesothelioma with Gene Medicine

    Science.gov (United States)

    Tada, Yuji; Shimada, Hideaki; Hiroshima, Kenzo; Tagawa, Masatoshi

    2013-01-01

    Malignant mesothelioma, closely linked with occupational asbestos exposure, is relatively rare in the frequency, but the patient numbers are going to increase in the next few decades all over the world. The current treatment modalities are not effective in terms of the overall survival and the quality of life. Mesothelioma mainly develops in the thoracic cavity and infrequently metastasizes to extrapleural organs. A local treatment can thereby be beneficial to the patients, and gene therapy with an intrapleural administration of vectors is one of the potential therapeutics. Preclinical studies demonstrated the efficacy of gene medicine for mesothelioma, and clinical trials with adenovirus vectors showed the safety of an intrapleural injection and a possible involvement of antitumor immune responses. Nevertheless, low transduction efficiency remains the main hurdle that hinders further clinical applications. Moreover, rapid generation of antivector antibody also inhibits transgene expressions. In this paper, we review the current status of preclinical and clinical gene therapy for malignant mesothelioma and discuss potential clinical directions of gene medicine in terms of a combinatory use with anticancer agents and with immunotherapy. PMID:23484132

  18. Strategies to identify long noncoding RNAs involved in gene regulation

    Directory of Open Access Journals (Sweden)

    Lee Catherine

    2012-11-01

    Full Text Available Abstract Long noncoding RNAs (lncRNAs have been detected in nearly every cell type and found to be fundamentally involved in many biological processes. The characterization of lncRNAs has immense potential to advance our comprehensive understanding of cellular processes and gene regulation, along with implications for the treatment of human disease. The recent ENCODE (Encyclopedia of DNA Elements study reported 9,640 lncRNA loci in the human genome, which corresponds to around half the number of protein-coding genes. Because of this sheer number and their functional diversity, it is crucial to identify a pool of potentially relevant lncRNAs early on in a given study. In this review, we evaluate the methods for isolating lncRNAs by immunoprecipitation and review the advantages, disadvantages, and applications of three widely used approaches – microarray, tiling array, and RNA-seq – for identifying lncRNAs involved in gene regulation. We also look at ways in which data from publicly available databases such as ENCODE can support the study of lncRNAs.

  19. A Case Study about Communication Strategies

    Science.gov (United States)

    Lin, Grace Hui Chin

    2011-01-01

    The primary purpose of this case study was to identify what were Taiwanese University English as a Foreign Language (EFL) learners' perceptions about learning communication strategies. This study collected qualitative data about students' beliefs and attitudes as they learned communication strategies. The research question guiding the study was:…

  20. Nanoparticles for cancer gene therapy: Recent advances, challenges, and strategies.

    Science.gov (United States)

    Wang, Kui; Kievit, Forrest M; Zhang, Miqin

    2016-12-01

    Compared to conventional treatments, gene therapy offers a variety of advantages for cancer treatment including high potency and specificity, low off-target toxicity, and delivery of multiple genes that concurrently target cancer tumorigenesis, recurrence, and drug resistance. In the past decades, gene therapy has undergone remarkable progress, and is now poised to become a first line therapy for cancer. Among various gene delivery systems, nanoparticles have attracted much attention because of their desirable characteristics including low toxicity profiles, well-controlled and high gene delivery efficiency, and multi-functionalities. This review provides an overview on gene therapeutics and gene delivery technologies, and highlight recent advances, challenges and insights into the design and the utility of nanoparticles in gene therapy for cancer treatment. Copyright © 2016. Published by Elsevier Ltd.

  1. A novel strategy to activate cytoprotective genes in the injured brain

    International Nuclear Information System (INIS)

    Zhao, Jing; Redell, John B.; Moore, Anthony N.; Dash, Pramod K.

    2011-01-01

    Highlights: → A strategy to increase cytoprotective gene expression in injured tissue is outlined. → A peptide containing a DEETGE motif can increase Nrf2 responsive genes in vivo. → Gene expression in injured brains requires a calpain cleavage site. → This peptide decreases BBB compromise when infused pre- or post-brain injury. → Cleavage sites for disease-specific proteases could be used to treat that condition. -- Abstract: The transcription factor nuclear factor E2-related factor 2 (Nrf2) regulates the expression of multiple cytoprotective genes that have been shown to offer protection in response to a number of insults. The present study describes a novel strategy to increase expression of Nrf2-responsive genes in brain injured mice. Under normal conditions, the adapter protein Kelch-like ECH-associated protein 1 (Keap1) binds to Nrf2 and promotes its proteosomal degradation in the cytoplasm. The amino acid sequence DEETGE, located at amino acid 77-82 of Nrf2, is critical for Nrf2-Keap1 interaction, and synthetic peptides containing this sequence can be used to disrupt the complex in vitro. We observed that intracerebroventricular (i.c.v.) infusion of a peptide containing the DEETGE sequence along with the cell transduction domain of the HIV-TAT protein (TAT-DEETGE) into brain-injured mice did not increase the mRNA levels for Nrf2-driven genes. However, when a calpain cleavage sequence was introduced between the TAT sequence and the DEETGE sequence, the new peptide (TAT-CAL-DEETGE) increased the mRNA levels of these genes. Increased gene expression was not observed when the TAT-CAL-DEETGE peptide was injected into uninjured animals. Furthermore, injection of TAT-CAL-DEETGE peptides before or after brain injury reduced blood-brain barrier compromise, a prominent secondary pathology that negatively influences outcome. The present strategy to increase Nrf2-responsive gene expression can be adapted to treat other insults or diseases based on their

  2. Strategies for exome and genome sequence data analysis in disease-gene discovery projects.

    Science.gov (United States)

    Robinson, Peter N; Krawitz, P; Mundlos, S

    2011-08-01

    In whole-exome sequencing (WES), target capture methods are used to enrich the sequences of the coding regions of genes from fragmented total genomic DNA, followed by massively parallel, 'next-generation' sequencing of the captured fragments. Since its introduction in 2009, WES has been successfully used in several disease-gene discovery projects, but the analysis of whole-exome sequence data can be challenging. In this overview, we present a summary of the main computational strategies that have been applied to identify novel disease genes in whole-exome data, including intersect filters, the search for de novo mutations, and the application of linkage mapping or inference of identity-by-descent (IBD) in family studies. © 2011 John Wiley & Sons A/S.

  3. Gene Editing and CRISPR Therapeutics: Strategies Taught by Cell and Gene Therapy.

    Science.gov (United States)

    Ramirez, Juan C

    2017-01-01

    A few years ago, we assisted in the demonstration for the first time of the revolutionary idea of a type of adaptive-immune system in the bacteria kingdom. This system, named CRISPR, and variants engineered in the lab, have been demonstrated as functional with extremely high frequency and fidelity in almost all eukaryotic cells studied to date. The capabilities of this RNA-guided nuclease have added to the interest that was announced with the advent of previous technologies for genome editing tools, such as ZFN and TALEN. The capabilities exhibited by these gene editors, opens up a novel scenario that indicates the promise of a next-generation medicine based on precision and personalized objectives, mostly due to the change in the paradigm regarding gene-surgery. This has certainly attracted, like never before, the attention of the biotech business and investor community. This chapter offers a brief overview of some of the factors that have contributed to a rapid entry into the biotech and pharmaceutical company's pipeline, focusing on how cell and gene therapies (CGT), collectively known as advanced therapies, have become the driving forces toward the therapeutic uses of gene editing technology. The sum of all those efforts for more than 30years has contributed to the new paradigm of considering genes as medicines. Copyright © 2017. Published by Elsevier Inc.

  4. A strategy study on international nuclear cooperation

    International Nuclear Information System (INIS)

    Chang, Hong Rae; Kim, Kyung Pyo; Kim, Young Min; Shin, Kyung Hye; Yoon, Sung Won; Lee, Myung Ho; Lee, Jong Hee; Hong Young Don

    1995-12-01

    The implementing methodologies suggested from this study cover the following: 1) strategies for the promotion of the nation's leading roles in such international organizations as the IAEA and OECD/NEA; 2) strategies for the implementation of national nuclear policy, positively coping with international nuclear trends; 3) strategies for the promotion of technical cooperation with the Russian Federation to introduce essential nuclear technology by utilizing its new environment of science and technology. 39 tabs., 28 figs., 64 refs. (Author)

  5. A simple and accurate two-step long DNA sequences synthesis strategy to improve heterologous gene expression in pichia.

    Directory of Open Access Journals (Sweden)

    Jiang-Ke Yang

    Full Text Available In vitro gene chemical synthesis is a powerful tool to improve the expression of gene in heterologous system. In this study, a two-step gene synthesis strategy that combines an assembly PCR and an overlap extension PCR (AOE was developed. In this strategy, the chemically synthesized oligonucleotides were assembled into several 200-500 bp fragments with 20-25 bp overlap at each end by assembly PCR, and then an overlap extension PCR was conducted to assemble all these fragments into a full length DNA sequence. Using this method, we de novo designed and optimized the codon of Rhizopus oryzae lipase gene ROL (810 bp and Aspergillus niger phytase gene phyA (1404 bp. Compared with the original ROL gene and phyA gene, the codon-optimized genes expressed at a significantly higher level in yeasts after methanol induction. We believe this AOE method to be of special interest as it is simple, accurate and has no limitation with respect to the size of the gene to be synthesized. Combined with de novo design, this method allows the rapid synthesis of a gene optimized for expression in the system of choice and production of sufficient biological material for molecular characterization and biotechnological application.

  6. A simple and accurate two-step long DNA sequences synthesis strategy to improve heterologous gene expression in pichia.

    Science.gov (United States)

    Yang, Jiang-Ke; Chen, Fang-Yuan; Yan, Xiang-Xiang; Miao, Li-Hong; Dai, Jiang-Hong

    2012-01-01

    In vitro gene chemical synthesis is a powerful tool to improve the expression of gene in heterologous system. In this study, a two-step gene synthesis strategy that combines an assembly PCR and an overlap extension PCR (AOE) was developed. In this strategy, the chemically synthesized oligonucleotides were assembled into several 200-500 bp fragments with 20-25 bp overlap at each end by assembly PCR, and then an overlap extension PCR was conducted to assemble all these fragments into a full length DNA sequence. Using this method, we de novo designed and optimized the codon of Rhizopus oryzae lipase gene ROL (810 bp) and Aspergillus niger phytase gene phyA (1404 bp). Compared with the original ROL gene and phyA gene, the codon-optimized genes expressed at a significantly higher level in yeasts after methanol induction. We believe this AOE method to be of special interest as it is simple, accurate and has no limitation with respect to the size of the gene to be synthesized. Combined with de novo design, this method allows the rapid synthesis of a gene optimized for expression in the system of choice and production of sufficient biological material for molecular characterization and biotechnological application.

  7. A strategy to identify housekeeping genes suitable for analysis in breast cancer diseases.

    Science.gov (United States)

    Tilli, Tatiana M; Castro, Cláudio da Silva; Tuszynski, Jack A; Carels, Nicolas

    2016-08-15

    The selection of suitable internal control genes is crucial for proper interpretation of real-time PCR data. Here we outline a strategy to identify housekeeping genes that could serve as suitable internal control for comparative analyses of gene expression data in breast cancer cell lines and tissues obtained by high throughput sequencing and quantitative real-time PCR (qRT-PCR). The strategy proposed includes the large-scale screening of potential candidate reference genes from RNA-seq data as well as their validation by qRT-PCR, and careful examination of reference data from the International Cancer Genome Consortium, The Cancer Genome Atlas and Gene Expression Omnibus repositories. The identified set of reference genes, also called novel housekeeping genes that includes CCSER2, SYMPK, ANKRD17 and PUM1, proved to be less variable and thus potentially more accurate for research and clinical analyses of breast cell lines and tissue samples compared to the traditional housekeeping genes used to this end. These results highlight the importance of a massive evaluation of housekeeping genes for their relevance as internal control for optimized intra- and inter-assay comparison of gene expression. We developed a strategy to identify and evaluate the significance of housekeeping genes as internal control for the intra- and inter-assay comparison of gene expression in breast cancer that could be applied to other tumor types and diseases.

  8. Viral gene therapy strategies: from basic science to clinical application.

    Science.gov (United States)

    Young, Lawrence S; Searle, Peter F; Onion, David; Mautner, Vivien

    2006-01-01

    A major impediment to the successful application of gene therapy for the treatment of a range of diseases is not a paucity of therapeutic genes, but the lack of an efficient non-toxic gene delivery system. Having evolved to deliver their genes to target cells, viruses are currently the most effective means of gene delivery and can be manipulated to express therapeutic genes or to replicate specifically in certain cells. Gene therapy is being developed for a range of diseases including inherited monogenic disorders and cardiovascular disease, but it is in the treatment of cancer that this approach has been most evident, resulting in the recent licensing of a gene therapy for the routine treatment of head and neck cancer in China. A variety of virus vectors have been employed to deliver genes to cells to provide either transient (eg adenovirus, vaccinia virus) or permanent (eg retrovirus, adeno-associated virus) transgene expression and each approach has its own advantages and disadvantages. Paramount is the safety of these virus vectors and a greater understanding of the virus-host interaction is key to optimizing the use of these vectors for routine clinical use. Recent developments in the modification of the virus coat allow more targeted approaches and herald the advent of systemic delivery of therapeutic viruses. In the context of cancer, the ability of attenuated viruses to replicate specifically in tumour cells has already yielded some impressive results in clinical trials and bodes well for the future of this approach, particularly when combined with more traditional anti-cancer therapies. Copyright 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  9. A strategy of gene overexpression based on tandem repetitive promoters in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Li Mingji

    2012-02-01

    Full Text Available Abstract Background For metabolic engineering, many rate-limiting steps may exist in the pathways of accumulating the target metabolites. Increasing copy number of the desired genes in these pathways is a general method to solve the problem, for example, the employment of the multi-copy plasmid-based expression system. However, this method may bring genetic instability, structural instability and metabolic burden to the host, while integrating of the desired gene into the chromosome may cause inadequate transcription or expression. In this study, we developed a strategy for obtaining gene overexpression by engineering promoter clusters consisted of multiple core-tac-promoters (MCPtacs in tandem. Results Through a uniquely designed in vitro assembling process, a series of promoter clusters were constructed. The transcription strength of these promoter clusters showed a stepwise enhancement with the increase of tandem repeats number until it reached the critical value of five. Application of the MCPtacs promoter clusters in polyhydroxybutyrate (PHB production proved that it was efficient. Integration of the phaCAB genes with the 5CPtacs promoter cluster resulted in an engineered E.coli that can accumulate 23.7% PHB of the cell dry weight in batch cultivation. Conclusions The transcription strength of the MCPtacs promoter cluster can be greatly improved by increasing the tandem repeats number of the core-tac-promoter. By integrating the desired gene together with the MCPtacs promoter cluster into the chromosome of E. coli, we can achieve high and stale overexpression with only a small size. This strategy has an application potential in many fields and can be extended to other bacteria.

  10. Space Station end effector strategy study

    Science.gov (United States)

    Katzberg, Stephen J.; Jensen, Robert L.; Willshire, Kelli F.; Satterthwaite, Robert E.

    1987-01-01

    The results of a study are presented for terminology definition, identification of functional requirements, technolgy assessment, and proposed end effector development strategies for the Space Station Program. The study is composed of a survey of available or under-developed end effector technology, identification of requirements from baselined Space Station documents, a comparative assessment of the match between technology and requirements, and recommended strategies for end effector development for the Space Station Program.

  11. Gene transfer strategies for improving radiolabeled peptide imaging and therapy

    International Nuclear Information System (INIS)

    Rogers, B.E.; Buchsbaum, D.J.; Zinn, K.R.

    2000-01-01

    Utilization of molecular biology techniques offers attractive options in nuclear medicine for improving cancer imaging and therapy with radiolabeled peptides. Two of these options include utilization of phage-panning to identify novel tumor specific peptides or single chain antibodies and gene transfer techniques to increase the antibodies and gene transfer techniques to increase the number of antigen/receptor sites expressed on malignant cells. The group has focused on the latter approach for improving radiolabeled peptide imaging and therapy. The most widely used gene transfer vectors in clinical gene therapy trials include retrovirus, cationic lipids and adenovirus. It has been utilized adenovirus vectors for gene transfer because of their ability to accomplish efficient in vivo gene transfer. Adenovirus vectors encoding the genes for a variety of antigens/receptors (carcinoembryonic antigen, gastrin-releasing peptide receptor, somatostatin receptor subtype 2 (SSTr2) have all shown that their expression is increased on cancer cells both in vitro and in vivo following adenovirus infection. Of particular interest has been the adenovirus encoding for SSTr2 (AdCMVSSTr2). Various radioisotopes have been attached to somatostatin analogues for imaging and therapy of SSTr2-positive tumors both clinically and in animal models. The use of these analogues in combination with AdCMVSSTr2 is a promising approach for improving the detection sensitivity and therapeutic efficacy of these radiolabeled peptides against solid tumors. In addition, it has been proposed the use of SSTr2 as a marker for imaging the expression of another cancer therapeutic transgene (e.g. cytosine deaminase, thymidine kinase) encoded within the same vector. This would allow for non-invasive monitoring of gene delivery to tumor sites

  12. Empirical study of supervised gene screening

    Directory of Open Access Journals (Sweden)

    Ma Shuangge

    2006-12-01

    Full Text Available Abstract Background Microarray studies provide a way of linking variations of phenotypes with their genetic causations. Constructing predictive models using high dimensional microarray measurements usually consists of three steps: (1 unsupervised gene screening; (2 supervised gene screening; and (3 statistical model building. Supervised gene screening based on marginal gene ranking is commonly used to reduce the number of genes in the model building. Various simple statistics, such as t-statistic or signal to noise ratio, have been used to rank genes in the supervised screening. Despite of its extensive usage, statistical study of supervised gene screening remains scarce. Our study is partly motivated by the differences in gene discovery results caused by using different supervised gene screening methods. Results We investigate concordance and reproducibility of supervised gene screening based on eight commonly used marginal statistics. Concordance is assessed by the relative fractions of overlaps between top ranked genes screened using different marginal statistics. We propose a Bootstrap Reproducibility Index, which measures reproducibility of individual genes under the supervised screening. Empirical studies are based on four public microarray data. We consider the cases where the top 20%, 40% and 60% genes are screened. Conclusion From a gene discovery point of view, the effect of supervised gene screening based on different marginal statistics cannot be ignored. Empirical studies show that (1 genes passed different supervised screenings may be considerably different; (2 concordance may vary, depending on the underlying data structure and percentage of selected genes; (3 evaluated with the Bootstrap Reproducibility Index, genes passed supervised screenings are only moderately reproducible; and (4 concordance cannot be improved by supervised screening based on reproducibility.

  13. Poultry studies and anthropological research strategies

    International Nuclear Information System (INIS)

    Whyte, M.

    2002-01-01

    Poultry are not simply birds; they are also a human creation, a social and cultural practice. The human element is the justification for an anthropology of poultry. Such an anthropology combines the objective research strategies familiar to the natural sciences with what is often called 'subjective' or qualitative research. In the study of poultry management, it is important that both research strategies focus on differences and variation. The subjective approach is particularly useful in identifying and understanding how the motivations and strategies of local actors are dependent on the social positions, which they occupy in their specific societies. (author)

  14. An integrated in silico gene mapping strategy in inbred mice.

    Science.gov (United States)

    Cervino, Alessandra C L; Darvasi, Ariel; Fallahi, Mohammad; Mader, Christopher C; Tsinoremas, Nicholas F

    2007-01-01

    In recent years in silico analysis of common laboratory mice has been introduced and subsequently applied, in slightly different ways, as a methodology for gene mapping. Previously we have demonstrated some limitation of the methodology due to sporadic genetic correlations across the genome. Here, we revisit the three main aspects that affect in silico analysis. First, we report on the use of marker maps: we compared our existing 20,000 SNP map to the newly released 140,000 SNP map. Second, we investigated the effect of varying strain numbers on power to map QTL. Third, we introduced a novel statistical approach: a cladistic analysis, which is well suited for mouse genetics and has increased flexibility over existing in silico approaches. We have found that in our examples of complex traits, in silico analysis by itself does fail to uniquely identify quantitative trait gene (QTG)-containing regions. However, when combined with additional information, it may significantly help to prioritize candidate genes. We therefore recommend using an integrated work flow that uses other genomic information such as linkage regions, regions of shared ancestry, and gene expression information to obtain a list of candidate genes from the genome.

  15. Study Strategies for Engineering Students at DTU

    DEFF Research Database (Denmark)

    Christensen, Hans Peter

    2002-01-01

    The study strategies of first year Master students are investigated at DTU fall 1999 - spring 2002. The results show that the students study less than their teachers expect. And they spend most time on activities not leading to deep understanding and engineering competencies. The students spend...... activated the students, but not significantly increased their independent studying....

  16. Mapping calcium phosphate activated gene networks as a strategy for targeted osteoinduction of human progenitors.

    Science.gov (United States)

    Eyckmans, Jeroen; Roberts, Scott J; Bolander, Johanna; Schrooten, Jan; Chen, Christopher S; Luyten, Frank P

    2013-06-01

    Although calcium phosphate-containing biomaterials are promising scaffolds for bone regenerative strategies, the osteoinductive capacity of such materials is poorly understood. In this study, we investigated whether endogenous mechanisms of in vivo calcium phosphate-driven, ectopic bone formation could be identified and used to induce enhanced differentiation in vitro of the same progenitor population. To accomplish this, human periosteum derived cells (hPDCs) were seeded on hydroxyapatite/collagen scaffolds (calcium phosphate rich matrix or CPRM), or on decalcified scaffolds (calcium phosphate depleted matrix or CPDM), followed by subcutaneous implantation in nude mice to trigger ectopic bone formation. In this system, osteoblast differentiation occurred in CPRM scaffolds, but not in CPDM scaffolds. Gene expression was assessed by human full-genome microarray at 20 h after seeding, and 2, 8 and 18 days after implantation. In both matrices, implantation of the cell constructs triggered a similar gene expression cascade, however, gene expression dynamics progressed faster in CPRM scaffolds than in CPDM scaffolds. The difference in gene expression dynamics was associated with differential activation of hub genes and molecular signaling pathways related to calcium signaling (CREB), inflammation (TNFα, NFkB, and IL6) and bone development (TGFβ, β-catenin, BMP, EGF, and ERK signaling). Starting from this set of pathways, a growth factor cocktail was developed that robustly enhanced osteogenesis in vitro and in vivo. Taken together, our data demonstrate that through the identification and subsequent stimulation of genes, proteins and signaling pathways associated with calcium phosphate mediated osteoinduction, a focused approach to develop targeted differentiation protocols in adult progenitor cells can be achieved. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Non-viral gene delivery strategies for cancer therapy, tissue engineering and regenerative medicine

    Science.gov (United States)

    Bhise, Nupura S.

    Gene therapy involves the delivery of deoxyribonucleic acid (DNA) into cells to override or replace a malfunctioning gene for treating debilitating genetic diseases, including cancer and neurodegenerative diseases. In addition to its use as a therapeutic, it can also serve as a technology to enable regenerative medicine strategies. The central challenge of the gene therapy research arena is developing a safe and effective delivery agent. Since viral vectors have critical immunogenic and tumorogenic safety issues that limit their clinical use, recent efforts have focused on developing non-viral biomaterial based delivery vectors. Cationic polymers are an attractive class of gene delivery vectors due to their structural versatility, ease of synthesis, biodegradability, ability to self-complex into nanoparticles with negatively charged DNA, capacity to carry large cargo, cellular uptake and endosomal escape capacity. In this thesis, we hypothesized that developing a biomaterial library of poly(betaamino esters) (PBAE), a newer class of cationic polymers consisting of biodegradable ester groups, would allow investigating vector design parameters and formulating effective non-viral gene delivery strategies for cancer drug delivery, tissue engineering and stem cell engineering. Consequently, a high-throughput transfection assay was developed to screen the PBAE-based nanoparticles in hard to transfect fibroblast cell lines. To gain mechanistic insights into the nanoparticle formulation process, biophysical properties of the vectors were characterized in terms of molecular weight (MW), nanoparticle size, zeta potential and plasmid per particle count. We report a novel assay developed for quantifying the plasmid per nanoparticle count and studying its implications for co-delivery of multiple genes. The MW of the polymers ranged from 10 kDa to 100 kDa, nanoparticle size was about 150 run, zeta potential was about 30 mV in sodium acetate buffer (25 mM, pH 5) and 30 to 100

  18. A high-throughput, restriction-free cloning and screening strategy based on ccdB-gene replacement.

    Science.gov (United States)

    Lund, Bjarte Aarmo; Leiros, Hanna-Kirsti Schrøder; Bjerga, Gro Elin Kjæreng

    2014-03-10

    In high-throughput demanding fields, such as biotechnology and structural biology, molecular cloning is an essential tool in obtaining high yields of recombinant protein. Here, we address recently developed restriction-free methods in cloning, and present a more cost-efficient protocol that has been optimized to improve both cloning and clone screening. In our case study, three homologous β-lactamase genes were successfully cloned using these restriction-free protocols. To clone the genes, we chose a gene replacement strategy, where the recombinant genes contained overhangs that targeted a region of the expression vector including a cytotoxin-encoding ccdB-gene. We provide further evidence that gene replacement can be applied with high-throughput cloning protocols. Targeting a replacement of the ccdB-gene was found to be very successful for counterselection using these protocols. This eliminated the need for treatment with the restriction enzyme DpnI that has so far been the preferred clone selection approach. We thus present an optimized cloning protocol using a restriction-free ccdB-gene replacement strategy, which allows for parallel cloning at a high-throughput level.

  19. Gene pyramiding as a Bt resistance management strategy: How ...

    African Journals Online (AJOL)

    Reports on the emergence of insect resistance to Bacillus thuringiensis delta endotoxins have raised doubts on the sustainability of Bt-toxin based pest management technologies. Corporate industry has responded to this challenge with innovations that include gene pyramiding among others. Pyramiding entails stacking ...

  20. Classification across gene expression microarray studies

    Directory of Open Access Journals (Sweden)

    Kuner Ruprecht

    2009-12-01

    particular, the better predictive results of DV in across platform classification indicate higher robustness of the classifier when trained on single channel data and applied to gene expression ratios. Conclusions We present a systematic evaluation of strategies for the integration of independent microarray studies in a classification task. Our findings in across studies classification may guide further research aiming on the construction of more robust and reliable methods for stratification and diagnosis in clinical practice.

  1. An improved strategy for tandem affinity purification-tagging of Schizosaccharomyces pombe genes

    OpenAIRE

    Cipak, Lubos; Spirek, Mario; Novatchkova, Maria; Chen, Zhiming; Rumpf, Cornelia; Lugmayr, Wolfgang; Mechtler, Karl; Ammerer, Gustav; Csaszar, Edina; Gregan, Juraj

    2009-01-01

    Tandem affinity purification (TAP) is a method that allows rapid purification of native protein complexes. We developed an improved technique to fuse the fission yeast genes with a TAP tag. Our technique is based on tagging constructs that contain regions homologous to the target gene cloned into vectors carrying a TAP tag. We used this technique to design strategies for TAP-tagging of predicted Schizosaccharomyces pombe genes (http://mendel.imp.ac.at/Pombe_tagging/). To validate the approach...

  2. A PCR amplification strategy for unrestricted generation of chimeric genes

    NARCIS (Netherlands)

    Vos, Michel J.; Kampinga, Harm H.

    2008-01-01

    For analyzing protein function, protein dynamics, or protein-protein interactions, the use of chimeric proteins has become an indispensable tool. The generation of DNA constructs coding for such fused proteins can, however, be a tedious process. Currently used strategies often make use of available

  3. Instructor and student knowledge of study strategies.

    Science.gov (United States)

    Morehead, Kayla; Rhodes, Matthew G; DeLozier, Sarah

    2016-01-01

    Students' self-reported study skills and beliefs are often inconsistent with empirically supported (ES) study strategies. However, little is known regarding instructors' beliefs about study skills and if such beliefs differ from those of students. In the current study, we surveyed college students' and instructors' knowledge of study strategies and had both groups evaluate the efficacy of learning strategies described in six learning scenarios. Results from the survey indicated that students frequently reported engaging in methods of studying that were not optimal for learning. Instructors' responses to the survey indicated that they endorsed a number of effective study skills but also held several beliefs inconsistent with research in learning and memory (e.g., learning styles). Further, results from the learning scenarios measure indicated that instructors were moderately more likely than students to endorse ES learning strategies. Collectively, these data suggest that instructors exhibited better knowledge of effective study skills than students, although the difference was small. We discuss several notable findings and argue for the improvement of both students' and instructors' study skill knowledge.

  4. Identifying Language Learning Strategies: An Exploratory Study

    Science.gov (United States)

    Pineda, Jorge E.

    2010-01-01

    This is a small scale, inductive, ethnographic study whose objective is to explore the language learning strategies used by the students of different languages at a language program at the university level. Students of English, French, Portuguese, Mandarin Chinese, Japanese, Italian, and German participate in the study. Three instruments are used…

  5. Using Case Studies to Teach Courtesy Strategies.

    Science.gov (United States)

    Moore, Patrick

    1990-01-01

    Explains some courtesy techniques that technical professionals can use to deal with interpersonal problems that arise in writing situations. Presents three case studies with sample responses to show how case studies can teach these courtesy strategies to technical writing students. (MM)

  6. An integrative machine learning strategy for improved prediction of essential genes in Escherichia coli metabolism using flux-coupled features.

    Science.gov (United States)

    Nandi, Sutanu; Subramanian, Abhishek; Sarkar, Ram Rup

    2017-07-25

    Prediction of essential genes helps to identify a minimal set of genes that are absolutely required for the appropriate functioning and survival of a cell. The available machine learning techniques for essential gene prediction have inherent problems, like imbalanced provision of training datasets, biased choice of the best model for a given balanced dataset, choice of a complex machine learning algorithm, and data-based automated selection of biologically relevant features for classification. Here, we propose a simple support vector machine-based learning strategy for the prediction of essential genes in Escherichia coli K-12 MG1655 metabolism that integrates a non-conventional combination of an appropriate sample balanced training set, a unique organism-specific genotype, phenotype attributes that characterize essential genes, and optimal parameters of the learning algorithm to generate the best machine learning model (the model with the highest accuracy among all the models trained for different sample training sets). For the first time, we also introduce flux-coupled metabolic subnetwork-based features for enhancing the classification performance. Our strategy proves to be superior as compared to previous SVM-based strategies in obtaining a biologically relevant classification of genes with high sensitivity and specificity. This methodology was also trained with datasets of other recent supervised classification techniques for essential gene classification and tested using reported test datasets. The testing accuracy was always high as compared to the known techniques, proving that our method outperforms known methods. Observations from our study indicate that essential genes are conserved among homologous bacterial species, demonstrate high codon usage bias, GC content and gene expression, and predominantly possess a tendency to form physiological flux modules in metabolism.

  7. Molecular Studies on Preproinsulin Gene

    Directory of Open Access Journals (Sweden)

    Sabir Sarah

    2016-01-01

    Full Text Available Insulin plays an important role in maintaining the blood glucose level of the body. The β-cells of pancreas produce insulin in the form of precursor that is preproinsulin. The gene of preproinsulin provides an interesting system for addressing question related to molecular evolution. Recombinant DNA technology has made it possible to isolate and sequence the chromosomal genes coding for unique protein products. Although preproinsulin of various organism has been isolated and cloned, but there is no report from buffalo (Bubalus bubalis that is our major livestock. The genomic DNA of buffalo was isolated using Laura-Lee-Boodram method. The part of preproinsulin gene (596bp and 520bp using BPPI-UPS and bpiful_F as forward and BC1-C as reverse primer was amplified. Cloning of amplified fragments of gene were performed in pCR 2.1 vector. Positive clones were screened on the basis of blue white selection. The band obtained on 596bp and 520bp after colony PCR confirmed the successful cloning of preproinsulin gene in pCR 2.1 vector.

  8. Study strategies and approaches to learning

    DEFF Research Database (Denmark)

    Christensen, Hans Peter

    showed a weak correlation between the student’s main learning approach as defined by the ratio of the deep approach score to the surface approach score and the student’s study intensity as identified by the ratio of non-scheduled independent activities to scheduled teacher-controlled activities......In this study students’ study strategies have been compared to their approaches to learning. The time students spend on different study activities has been investigated at the Technical University of Denmark, and as a pilot project a few students also filled in a reduced version of Bigg's Study...... Process Questionnaire to identify their approach to learning. It was hypothesised that the students’ learning approach would depend more on the quality of the study work than on the quantity; that an active and reflective study strategy was required to obtain deep conceptual understanding. The result...

  9. Bioinformatics study of the mangrove actin genes

    Science.gov (United States)

    Basyuni, M.; Wasilah, M.; Sumardi

    2017-01-01

    This study describes the bioinformatics methods to analyze eight actin genes from mangrove plants on DDBJ/EMBL/GenBank as well as predicted the structure, composition, subcellular localization, similarity, and phylogenetic. The physical and chemical properties of eight mangroves showed variation among the genes. The percentage of the secondary structure of eight mangrove actin genes followed the order of a helix > random coil > extended chain structure for BgActl, KcActl, RsActl, and A. corniculatum Act. In contrast to this observation, the remaining actin genes were random coil > extended chain structure > a helix. This study, therefore, shown the prediction of secondary structure was performed for necessary structural information. The values of chloroplast or signal peptide or mitochondrial target were too small, indicated that no chloroplast or mitochondrial transit peptide or signal peptide of secretion pathway in mangrove actin genes. These results suggested the importance of understanding the diversity and functional of properties of the different amino acids in mangrove actin genes. To clarify the relationship among the mangrove actin gene, a phylogenetic tree was constructed. Three groups of mangrove actin genes were formed, the first group contains B. gymnorrhiza BgAct and R. stylosa RsActl. The second cluster which consists of 5 actin genes the largest group, and the last branch consist of one gene, B. sexagula Act. The present study, therefore, supported the previous results that plant actin genes form distinct clusters in the tree.

  10. Gene therapy for carcinoma of the breast: Therapeutic genetic correction strategies

    International Nuclear Information System (INIS)

    Obermiller, Patrice S; Tait, David L; Holt, Jeffrey T

    2000-01-01

    Gene therapy is a therapeutic approach that is designed to correct specific molecular defects that contribute to the cause or progression of cancer. Genes that are mutated or deleted in cancers include the cancer susceptibility genes p53 and BRCA1. Because mutational inactivation of gene function is specific to tumor cells in these settings, cancer gene correction strategies may provide an opportunity for selective targeting without significant toxicity for normal nontumor cells. Both p53 and BRCA1 appear to inhibit cancer cells that lack mutations in these genes, suggesting that the so-called gene correction strategies may have broader potential than initially believed. Increasing knowledge of cancer genetics has identified these and other genes as potential targets for gene replacement therapy. Initial patient trials of p53 and BRCA1 gene therapy have provided some indications of potential efficacy, but have also identified areas of basic and clinical research that are needed before these approaches may be widely used in patient care

  11. Amphiphilic polymers formed from ring-opening polymerization: a strategy for the enhancement of gene delivery.

    Science.gov (United States)

    Zhang, Yi-Mei; Huang, Zheng; Zhang, Ji; Wu, Wan-Xia; Liu, Yan-Hong; Yu, Xiao-Qi

    2017-03-28

    Cationic liposomes and polymers are both important candidates for use as non-viral gene vectors. However, both of them have special shortcomings and application limits. This work is devoted to the combination of advantages of liposomes and polymers. The ring-opening polymerization strategy was used for the preparation of amphiphilic polymers from cyclen-based cationic small lipids. The non-hydrophobic polymer and the corresponding lipids were also prepared for performing structure-activity relationship studies. Gel electrophoresis results reveal that both the lipopolymers and liposomes could effectively condense DNA into nanoparticles and protect DNA from degradation. Compared to polymers, the DNA binding ability of liposomes is more affected by hydrophobic tails. Under the same dosage, the synthetic polymers have stronger DNA binding ability than the liposomes. In vitro transfection experiments show that the polymers could give better transfection efficiency, which was much higher than those of the corresponding liposomes and non-hydrophobic polymer. The oleyl moiety is suitable for lipidic vectors, but things were different for polymers. Under optimized conditions, up to 14.2 times higher transfection efficiency than that for 25 kDa bPEI could be obtained. More importantly, the lipopolymers showed much better serum tolerance, which was further confirmed by protein adsorption, gel electrophoresis, flow cytometry, and CLSM assays. The results indicate that ring-opening polymerization is a promising strategy for the enhancement of the gene delivery efficiency and biocompatibility of cationic lipids.

  12. An Integrated in Silico Gene Mapping Strategy in Inbred Mice

    OpenAIRE

    Cervino, Alessandra C. L.; Darvasi, Ariel; Fallahi, Mohammad; Mader, Christopher C.; Tsinoremas, Nicholas F.

    2007-01-01

    In recent years in silico analysis of common laboratory mice has been introduced and subsequently applied, in slightly different ways, as a methodology for gene mapping. Previously we have demonstrated some limitation of the methodology due to sporadic genetic correlations across the genome. Here, we revisit the three main aspects that affect in silico analysis. First, we report on the use of marker maps: we compared our existing 20,000 SNP map to the newly released 140,000 SNP map. Second, w...

  13. Expression Study of Banana Pathogenic Resistance Genes

    Directory of Open Access Journals (Sweden)

    Fenny M. Dwivany

    2016-10-01

    Full Text Available Banana is one of the world's most important trade commodities. However, infection of banana pathogenic fungi (Fusarium oxysporum race 4 is one of the major causes of decreasing production in Indonesia. Genetic engineering has become an alternative way to control this problem by isolating genes that involved in plant defense mechanism against pathogens. Two of the important genes are API5 and ChiI1, each gene encodes apoptosis inhibitory protein and chitinase enzymes. The purpose of this study was to study the expression of API5 and ChiI1 genes as candidate pathogenic resistance genes. The amplified fragments were then cloned, sequenced, and confirmed with in silico studies. Based on sequence analysis, it is showed that partial API5 gene has putative transactivation domain and ChiI1 has 9 chitinase family GH19 protein motifs. Data obtained from this study will contribute in banana genetic improvement.

  14. New analytical strategies in studying drug metabolism.

    Science.gov (United States)

    Staack, Roland F; Hopfgartner, Gérard

    2007-08-01

    Identification and elucidation of the structures of metabolites play major roles in drug discovery and in the development of pharmaceutical compounds. These studies are also important in toxicology or doping control with either pharmaceuticals or illicit drugs. This review focuses on: new analytical strategies used to identify potential metabolites in biological matrices with and without radiolabeled drugs; use of software for metabolite profiling; interpretation of product spectra; profiling of reactive metabolites; development of new approaches for generation of metabolites; and detection of metabolites with increased sensitivity and simplicity. Most of the new strategies involve mass spectrometry (MS) combined with liquid chromatography (LC).

  15. Functional characterization of cotton genes responsive to Verticillium dahliae through bioinformatics and reverse genetics strategies.

    Science.gov (United States)

    Xu, Lian; Zhang, Wenwen; He, Xin; Liu, Min; Zhang, Kun; Shaban, Muhammad; Sun, Longqing; Zhu, Jiachen; Luo, Yijing; Yuan, Daojun; Zhang, Xianlong; Zhu, Longfu

    2014-12-01

    Verticillium wilt causes dramatic cotton yield loss in China. Although some genes or biological processes involved in the interaction between cotton and Verticillium dahliae have been identified, the molecular mechanism of cotton resistance to this disease is still poorly understood. The basic innate immune response for defence is somewhat conserved among plant species to defend themselves in complex environments, which makes it possible to characterize genes involved in cotton immunity based on information from model plants. With the availability of Arabidopsis databases, a data-mining strategy accompanied by virus-induced gene silencing (VIGS) and heterologous expression were adopted in cotton and tobacco, respectively, for global screening and gene function characterization. A total of 232 Arabidopsis genes putatively involved in basic innate immunity were screened as candidate genes, and bioinformatic analysis suggested a role of these genes in the immune response. In total, 38 homologous genes from cotton were singled out to characterize their response to V. dahliae and methyl jasmonate treatment through quantitative real-time PCR. The results revealed that 24 genes were differentially regulated by pathogen inoculation, and most of these genes responded to both Verticillium infection and jasmonic acid stimuli. Furthermore, the efficiency of the strategy was illustrated by the functional identification of six candidate genes via heterologous expression in tobacco or a knock-down approach using VIGS in cotton. Functional categorization of these 24 differentially expressed genes as well as functional analysis suggest that reactive oxygen species, salicylic acid- and jasmonic acid-signalling pathways are involved in the cotton disease resistance response to V. dahliae. Our data demonstrate how information from model plants can allow the rapid translation of information into non-model species without complete genome sequencing, via high-throughput screening and

  16. Validation of commonly used reference genes for sleep-related gene expression studies

    Directory of Open Access Journals (Sweden)

    Castro Rosa MRPS

    2009-05-01

    Full Text Available Abstract Background Sleep is a restorative process and is essential for maintenance of mental and physical health. In an attempt to understand the complexity of sleep, multidisciplinary strategies, including genetic approaches, have been applied to sleep research. Although quantitative real time PCR has been used in previous sleep-related gene expression studies, proper validation of reference genes is currently lacking. Thus, we examined the effect of total or paradoxical sleep deprivation (TSD or PSD on the expression stability of the following frequently used reference genes in brain and blood: beta-actin (b-actin, beta-2-microglobulin (B2M, glyceraldehyde-3-phosphate dehydrogenase (GAPDH, and hypoxanthine guanine phosphoribosyl transferase (HPRT. Results Neither TSD nor PSD affected the expression stability of all tested genes in both tissues indicating that b-actin, B2M, GAPDH and HPRT are appropriate reference genes for the sleep-related gene expression studies. In order to further verify these results, the relative expression of brain derived neurotrophic factor (BDNF and glycerol-3-phosphate dehydrogenase1 (GPD1 was evaluated in brain and blood, respectively. The normalization with each of four reference genes produced similar pattern of expression in control and sleep deprived rats, but subtle differences in the magnitude of expression fold change were observed which might affect the statistical significance. Conclusion This study demonstrated that sleep deprivation does not alter the expression stability of commonly used reference genes in brain and blood. Nonetheless, the use of multiple reference genes in quantitative RT-PCR is required for the accurate results.

  17. Strategy of gene silencing in cassava for validation of resistance genes

    International Nuclear Information System (INIS)

    Cortes, Simon; Lopez, Camilo

    2010-01-01

    Cassava (Manihot esculenta) is a major source of food for more than 1000 million people in the world and constitutes an important staple crop. Cassava bacterial blight, caused by the gram negative bacterium Xanthomonas axonopodis pv. manihotis, is one of the most important constraints for this crop. A candidate resistance gene against cassava bacterial blight, named RXam1, has been identified previously. In this work, we employed the gene silencing approach using the African cassava mosaic virus (ACMV) to validate the function of the RXam1 gene. We used as positive control the su gen, which produce photo blanching in leaves when is silenced. Plants from the SG10735 variety were bombardment with the ACMV-A-SU+ACMV-B y ACMV-A-RXam1+ACMV-B constructions. The silencing efficiency employing the su gene was low, only one of seven plants showed photo blanching. In the putative silenced plants for the RXam1 gene, no presence of siRNAs corresponding to RXam1 was observed; although a low diminution of the RXam1 gene expression was obtained. The growth curves for the Xam strain CIO136 in cassava plants inoculated showing a little but no significance difference in the susceptibility in the silenced plants compared to not silenced

  18. MOLECULAR STUDY OF NUCLEPROTEIN GENE OF RABIES ...

    African Journals Online (AJOL)

    Analysis of the 1400-b.p RT-PCR products of the N gene and the views by sequencing and restriction endonuclease analysis enabled division of isolates into 3 types. The conclusion from the study is that RT-PCR and restriction endonuclease analysis of the amplified products of the N gene would allow identification and ...

  19. A gene-trap strategy identifies quiescence-induced genes in ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR G

    domain protein. Our results demonstrate that expression of chromatin modulatory genes is induced in G0, providing support to the notion that this reversibly arrested state is actively ... Abbreviations used: βgal, βgalactosidase; CFU, colony forming units; ENT, EMSY N-terminus; FACS, fluorescent activated cell sorting;.

  20. Consilience and Life History Theory: From Genes to Brain to Reproductive Strategy

    Science.gov (United States)

    Figueredo, Aurelio Jose; Vasquez, Geneva; Brumbach, Barbara H.; Schneider, Stephanie M. R.; Sefcek, Jon A.; Tal, Ilanit R.; Hill, Dawn; Wenner, Christopher J.; Jacobs, W. Jake

    2006-01-01

    We describe an integrated theory of individual differences that traces the behavioral development of life history from genes to brain to reproductive strategy. We provide evidence that a single common factor, the K-Factor, underpins a variety of life-history parameters, including an assortment of sexual, reproductive, parental, familial, and…

  1. Effective enrichment strategy for EML4-ALK fusion gene screening in patients with non-small cell lung cancer.

    Science.gov (United States)

    Kobayashi, Makoto; Sakakibara, Tomohiro; Inoue, Akira; Fukuhara, Tatsuro; Sasano, Hironobu; Ichinose, Masakazu; Nukiwa, Toshihiro

    2014-01-01

    A novel fusion gene that comprises the echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) genes was recently identified in non-small cell lung cancer (NSCLC), particularly in adenocarcinoma. A specific ALK inhibitor has been shown to exert anti-tumor effects in NSCLC with the EML4-ALK fusion gene. Previous reports suggested an EML4-ALK incidence of approximately 5% in a pan-NSCLC population, with an increased frequency in younger patients, but an appropriate strategy for further selecting patients with the EML4-ALK fusion gene remains unknown. Patients, 55 years of age or younger, who were diagnosed with NSCLC without typical squamous cell carcinoma features at our institute were retrospectively evaluated. The tumor specimens were examined by immunohistochemistry for the EML4-ALK fusion gene and by polymerase chain reaction for epidermal growth factor receptor (EGFR) mutations. Between January 2004 and September 2011, the EML4-ALK fusion gene was detected in 19.6% (9/46) of patients. The fusion gene incidence increased to 31% (9/29) when patients with EGFR mutations were excluded. The EML4-ALK fusion gene was further detected in 2 cases of undifferentiated cell carcinoma. EML4-ALK fusion gene examinations could be more effectively performed by selecting young NSCLC patients without EGFR mutations, whereas selection on the basis of a non-smoking or adenocarcinoma history, as reported in previous studies, may not correctly identify the patient groups with potential EML4-ALK fusion gene. Copyright © 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  2. Supply chain strategy: empirical case study in Europe and Asia:

    OpenAIRE

    Sillanpää, Ilkka; Sillanpää, Sebastian

    2014-01-01

    The purpose of this case study research is to present a literature review of supply chain strategy approaches, develop supply chain strategy framework and to validate a framework in empirical case study. Literature review and case study research are the research methods for this research. This study presents the supply chain strategy framework which merges together business environment, corporate strategy, supply chain demand and supply chain strategy. Research argues that all the different c...

  3. Analytical strategies for studying stem cell metabolism.

    Science.gov (United States)

    Arnold, James M; Choi, William T; Sreekumar, Arun; Maletić-Savatić, Mirjana

    2015-04-01

    Owing to their capacity for self-renewal and pluripotency, stem cells possess untold potential for revolutionizing the field of regenerative medicine through the development of novel therapeutic strategies for treating cancer, diabetes, cardiovascular and neurodegenerative diseases. Central to developing these strategies is improving our understanding of biological mechanisms responsible for governing stem cell fate and self-renewal. Increasing attention is being given to the significance of metabolism, through the production of energy and generation of small molecules, as a critical regulator of stem cell functioning. Rapid advances in the field of metabolomics now allow for in-depth profiling of stem cells both in vitro and in vivo , providing a systems perspective on key metabolic and molecular pathways which influence stem cell biology. Understanding the analytical platforms and techniques that are currently used to study stem cell metabolomics, as well as how new insights can be derived from this knowledge, will accelerate new research in the field and improve future efforts to expand our understanding of the interplay between metabolism and stem cell biology.

  4. Advances in study of reporter gene imaging for monitoring gene therapy

    International Nuclear Information System (INIS)

    Mu Chuanjie; Zhou Jiwen

    2003-01-01

    To evaluate the efficiency of gene therapy, it is requisite to monitor localization and expression of the therapeutic gene in vivo. Monitoring expression of reporter gene using radionuclide reporter gene technique is the best method. Adenoviral vectors expressing reporter gene are constructed using gene fusion, bicistronic, double promoter or bidirectional transcriptional recombination techniques, and transferred into target cells and tissues, then injected radiolabeled reporter probes which couple to the reporter genes. The reporter genes can be imaged invasively, repeatedly, quantitatively with γ-camera, PET and SPECT. Recently, several reporter gene and reporter probe systems have been used in studies of gene therapy. The part of them has been used for clinic trials

  5. Gene set analysis for interpreting genetic studies

    DEFF Research Database (Denmark)

    Pers, Tune H

    2016-01-01

    Interpretation of genome-wide association study (GWAS) results is lacking behind the discovery of new genetic associations. Consequently, there is an urgent need for data-driven methods for interpreting genetic association studies. Gene set analysis (GSA) can identify aetiologic pathways...

  6. Supply Chain Strategy: Empirical Case Study in Europe and Asia

    Directory of Open Access Journals (Sweden)

    Ilkka Sillanpää

    2014-06-01

    Full Text Available The purpose of this case study research is to present a literature review of supply chain strategy approaches, develop supply chain strategy framework and to validate a framework in empirical case study. Literature review and case study research are the research methods for this research. This study presents the supply chain strategy framework which merges together business environment, corporate strategy, supply chain demand and supply chain strategy. Research argues that all the different concepts that are currently used as supply chain strategy can be condensed into a presented supply chain strategy framework. Developed supply chain strategy framework is a practical tool for business managers. Future research could be multiple case studies in the global environment to develop further the supply chain strategy framework.

  7. Multifactor dimensionality reduction for detecting gene-gene and gene-environment interactions in pharmacogenomics studies.

    Science.gov (United States)

    Ritchie, Marylyn D; Motsinger, Alison A

    2005-12-01

    In the quest for discovering disease susceptibility genes, the reality of gene-gene and gene-environment interactions creates difficult challenges for many current statistical approaches. In an attempt to overcome limitations with current disease gene detection methods, the multifactor dimensionality reduction (MDR) approach was previously developed. In brief, MDR is a method that reduces the dimensionality of multilocus information to identify polymorphisms associated with an increased risk of disease. This approach takes multilocus genotypes and develops a model for defining disease risk by pooling high-risk genotype combinations into one group and low-risk combinations into another. Cross-validation and permutation testing are used to identify optimal models. While this approach was initially developed for studies of complex disease, it is also directly applicable to pharmacogenomic studies where the outcome variable is drug treatment response/nonresponse or toxicity/no toxicity. MDR is a nonparametric and model-free approach that has been shown to have reasonable power to detect epistasis in both theoretical and empirical studies. This computational technology is described in detail in this review, and its application in pharmacogenomic studies is demonstrated.

  8. Selection of reference genes for gene expression studies in zucchini (Cucurbita pepo) using qPCR.

    Science.gov (United States)

    Obrero, Angeles; Die, Jose V; Román, Belén; Gómez, Pedro; Nadal, Salvador; González-Verdejo, Clara I

    2011-05-25

    The zucchini (Cucurbita pepo) is an important food crop, the transcriptomics of which are a fundamental tool to accelerate the development of new varieties by breeders. However, the suitability of reference genes for data normalization in zucchini has not yet been studied. The aim of this study was to assess the suitability of 13 genes for their potential use as reference genes in quantitative real-time PCR. Assays were performed on 34 cDNA samples representing plants under different stresses and at different developmental stages. The application of geNorm and NormFinder software revealed that the use of a combination of UFP, EF-1A, RPL36aA, PP2A, and CAC genes for the different experimental sets was the best strategy for reliable normalization. In contrast, 18S rRNA and TUA were less stable and unsuitable for use as internal controls. These results provide the possibility to allow more accurate use of qPCR in this horticultural crop.

  9. Evaluating Executive Strategies (Management Strategies and Teaching-Learning Strategies) of Graduate Curriculum: Case Study in Isfahan University

    Science.gov (United States)

    Rahmanpour, Muhammad; Ahmadi, Mojtaba; Hatami, Mostafa; Mirzaee, Hamzeh

    2017-01-01

    The present study seeks to evaluate executive strategies in graduate Curriculum of Isfahan University from the point of view of management and teaching-learning strategies. This study is an applied survey. The population comprised BA students and faculty members of the University of Isfahan. In order to do so, 141 professors and 278 students were…

  10. Development of a codon optimization strategy using the efor RED reporter gene as a test case

    Science.gov (United States)

    Yip, Chee-Hoo; Yarkoni, Orr; Ajioka, James; Wan, Kiew-Lian; Nathan, Sheila

    2018-04-01

    Synthetic biology is a platform that enables high-level synthesis of useful products such as pharmaceutically related drugs, bioplastics and green fuels from synthetic DNA constructs. Large-scale expression of these products can be achieved in an industrial compliant host such as Escherichia coli. To maximise the production of recombinant proteins in a heterologous host, the genes of interest are usually codon optimized based on the codon usage of the host. However, the bioinformatics freeware available for standard codon optimization might not be ideal in determining the best sequence for the synthesis of synthetic DNA. Synthesis of incorrect sequences can prove to be a costly error and to avoid this, a codon optimization strategy was developed based on the E. coli codon usage using the efor RED reporter gene as a test case. This strategy replaces codons encoding for serine, leucine, proline and threonine with the most frequently used codons in E. coli. Furthermore, codons encoding for valine and glycine are substituted with the second highly used codons in E. coli. Both the optimized and original efor RED genes were ligated to the pJS209 plasmid backbone using Gibson Assembly and the recombinant DNAs were transformed into E. coli E. cloni 10G strain. The fluorescence intensity per cell density of the optimized sequence was improved by 20% compared to the original sequence. Hence, the developed codon optimization strategy is proposed when designing an optimal sequence for heterologous protein production in E. coli.

  11. Gene selection heuristic algorithm for nutrigenomics studies.

    Science.gov (United States)

    Valour, D; Hue, I; Grimard, B; Valour, B

    2013-07-15

    Large datasets from -omics studies need to be deeply investigated. The aim of this paper is to provide a new method (LEM method) for the search of transcriptome and metabolome connections. The heuristic algorithm here described extends the classical canonical correlation analysis (CCA) to a high number of variables (without regularization) and combines well-conditioning and fast-computing in "R." Reduced CCA models are summarized in PageRank matrices, the product of which gives a stochastic matrix that resumes the self-avoiding walk covered by the algorithm. Then, a homogeneous Markov process applied to this stochastic matrix converges the probabilities of interconnection between genes, providing a selection of disjointed subsets of genes. This is an alternative to regularized generalized CCA for the determination of blocks within the structure matrix. Each gene subset is thus linked to the whole metabolic or clinical dataset that represents the biological phenotype of interest. Moreover, this selection process reaches the aim of biologists who often need small sets of genes for further validation or extended phenotyping. The algorithm is shown to work efficiently on three published datasets, resulting in meaningfully broadened gene networks.

  12. A Combinatory Approach for Selecting Prognostic Genes in Microarray Studies of Tumour Survivals

    Directory of Open Access Journals (Sweden)

    Qihua Tan

    2009-01-01

    Full Text Available Different from significant gene expression analysis which looks for genes that are differentially regulated, feature selection in the microarray-based prognostic gene expression analysis aims at finding a subset of marker genes that are not only differentially expressed but also informative for prediction. Unfortunately feature selection in literature of microarray study is predominated by the simple heuristic univariate gene filter paradigm that selects differentially expressed genes according to their statistical significances. We introduce a combinatory feature selection strategy that integrates differential gene expression analysis with the Gram-Schmidt process to identify prognostic genes that are both statistically significant and highly informative for predicting tumour survival outcomes. Empirical application to leukemia and ovarian cancer survival data through-within- and cross-study validations shows that the feature space can be largely reduced while achieving improved testing performances.

  13. Evaluation of suitable reference genes for gene expression studies ...

    Indian Academy of Sciences (India)

    2011-12-14

    Dec 14, 2011 ... MADS family of TFs control floral organ identity within each whorl of the flower by activating downstream genes. Measuring gene expression in different tissue types and developmental stages is of fundamental importance in TFs functional research. In last few years, quantitative real-time. PCR (qRT-PCR) ...

  14. Host-induced gene silencing: a tool for understanding fungal host interaction and for developing novel disease control strategies.

    Science.gov (United States)

    Nunes, Cristiano C; Dean, Ralph A

    2012-06-01

    Recent discoveries regarding small RNAs and the mechanisms of gene silencing are providing new opportunities to explore fungal pathogen-host interactions and potential strategies for novel disease control. Plant pathogenic fungi are a constant and major threat to global food security; they represent the largest group of disease-causing agents on crop plants on the planet. An initial understanding of RNA silencing mechanisms and small RNAs was derived from model fungi. Now, new knowledge with practical implications for RNA silencing is beginning to emerge from the study of plant-fungus interactions. Recent studies have shown that the expression of silencing constructs in plants designed on fungal genes can specifically silence their targets in invading pathogenic fungi, such as Fusarium verticillioides, Blumeria graminis and Puccinia striiformis f.sp. tritici. Here, we highlight the important general aspects of RNA silencing mechanisms and emphasize recent findings from plant pathogenic fungi. Strategies to employ RNA silencing to investigate the basis of fungal pathogenesis are discussed. Finally, we address important aspects for the development of fungal-derived resistance through the expression of silencing constructs in host plants as a powerful strategy to control fungal disease. © 2011 The Authors. Molecular Plant Pathology © 2011 BSPP and Blackwell Publishing Ltd.

  15. A single epidermal stem cell strategy for safe ex vivo gene therapy.

    Science.gov (United States)

    Droz-Georget Lathion, Stéphanie; Rochat, Ariane; Knott, Graham; Recchia, Alessandra; Martinet, Danielle; Benmohammed, Sara; Grasset, Nicolas; Zaffalon, Andrea; Besuchet Schmutz, Nathalie; Savioz-Dayer, Emmanuelle; Beckmann, Jacques Samuel; Rougemont, Jacques; Mavilio, Fulvio; Barrandon, Yann

    2015-04-01

    There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells before they are transplanted. To address this, we have developed a strategy that permits transplantation of a clonal population of genetically corrected autologous stem cells that meet stringent selection criteria and the principle of precaution. As a proof of concept, we have stably transduced epidermal stem cells (holoclones) obtained from a patient suffering from recessive dystrophic epidermolysis bullosa. Holoclones were infected with self-inactivating retroviruses bearing a COL7A1 cDNA and cloned before the progeny of individual stem cells were characterised using a number of criteria. Clonal analysis revealed a great deal of heterogeneity among transduced stem cells in their capacity to produce functional type VII collagen (COLVII). Selected transduced stem cells transplanted onto immunodeficient mice regenerated a non-blistering epidermis for months and produced a functional COLVII. Safety was assessed by determining the sites of proviral integration, rearrangements and hit genes and by whole-genome sequencing. The progeny of the selected stem cells also had a diploid karyotype, was not tumorigenic and did not disseminate after long-term transplantation onto immunodeficient mice. In conclusion, a clonal strategy is a powerful and efficient means of by-passing the heterogeneity of a transduced stem cell population. It guarantees a safe and homogenous medicinal product, fulfilling the principle of precaution and the requirements of regulatory affairs. Furthermore, a clonal strategy makes it possible to envision exciting gene-editing technologies like zinc finger nucleases, TALENs and homologous recombination for next-generation gene therapy. © 2015

  16. Strategy Maps in University Management: A Comparative Study

    Science.gov (United States)

    Han, Shuangmiao; Zhong, Zhou

    2015-01-01

    In this study, the conceptual use of the strategy map approach and the strategy map which it produces have been adapted from the business sector and introduced as tools for achieving more effective strategic planning and management in higher education institutions (HEIs). This study discusses the development of strategy maps as transformational…

  17. Winning strategies: A case study of Oyo State Lottery, Nigeria ...

    African Journals Online (AJOL)

    In this study, we investigated three common lottery strategies: random, low and high frequency strategies, usually employed by lottery players. The Oyo State Lottery, a type of lottery in Oyo State, Nigeria was used as a case study. For the three strategies, we considered whether the selection of numbers in Oyo State lottery ...

  18. Bioprospecting for β-lactam resistance genes using a metagenomics-guided strategy.

    Science.gov (United States)

    Yang, Chao; Yang, Ying; Che, You; Xia, Yu; Li, Liguan; Xiong, Wenguang; Zhang, Tong

    2017-08-01

    Emergence of new antibiotic resistance bacteria poses a serious threat to human health, which is largely attributed to the evolution and spread of antibiotic resistance genes (ARGs). In this work, a metagenomics-guided strategy consisting of metagenomic analysis and function validation was proposed for rapidly identifying novel ARGs from hot spots of ARG dissemination, such as wastewater treatment plants (WWTPs) and animal feces. We used an antibiotic resistance gene database to annotate 76 putative β-lactam resistance genes from the metagenomes of sludge and chicken feces. Among these 76 candidate genes, 25 target genes that shared 40~70% amino acid identity to known β-lactamases were cloned by PCR from the metagenomes. Their resistances to four β-lactam antibiotics were further demonstrated. Furthermore, the validated ARGs were used as the reference sequences to identify novel ARGs in eight environmental samples, suggesting the necessity of re-examining the profiles of ARGs in environmental samples using the validated novel ARG sequences. This metagenomics-guided pipeline does not rely on the activity of ARGs during the initial screening process and may specifically select novel ARG sequences for function validation, which make it suitable for the high-throughput screening of novel ARGs from environmental metagenomes.

  19. CACNA1C gene regulates behavioral strategies in operant rule learning.

    Science.gov (United States)

    Koppe, Georgia; Mallien, Anne Stephanie; Berger, Stefan; Bartsch, Dusan; Gass, Peter; Vollmayr, Barbara; Durstewitz, Daniel

    2017-06-01

    Behavioral experiments are usually designed to tap into a specific cognitive function, but animals may solve a given task through a variety of different and individual behavioral strategies, some of them not foreseen by the experimenter. Animal learning may therefore be seen more as the process of selecting among, and adapting, potential behavioral policies, rather than mere strengthening of associative links. Calcium influx through high-voltage-gated Ca2+ channels is central to synaptic plasticity, and altered expression of Cav1.2 channels and the CACNA1C gene have been associated with severe learning deficits and psychiatric disorders. Given this, we were interested in how specifically a selective functional ablation of the Cacna1c gene would modulate the learning process. Using a detailed, individual-level analysis of learning on an operant cue discrimination task in terms of behavioral strategies, combined with Bayesian selection among computational models estimated from the empirical data, we show that a Cacna1c knockout does not impair learning in general but has a much more specific effect: the majority of Cacna1c knockout mice still managed to increase reward feedback across trials but did so by adapting an outcome-based strategy, while the majority of matched controls adopted the experimentally intended cue-association rule. Our results thus point to a quite specific role of a single gene in learning and highlight that much more mechanistic insight could be gained by examining response patterns in terms of a larger repertoire of potential behavioral strategies. The results may also have clinical implications for treating psychiatric disorders.

  20. A Study on Genes of Bayanbulak Sheep

    Directory of Open Access Journals (Sweden)

    Beiyao Zuo

    2013-01-01

    Full Text Available The average twin lambing rate of Bayanbulak sheep is 2% to 3%. However, a flock of sheep with a close genetic relationship and an average of 2 to 3 lambs per birth has been found recently. To determine the major genes controlling the prolificacy of the flock in the present study, the flock was designated A while 100 normal Bayanbulak sheep were randomly selected to comprise the control flock B. Ligase detection reaction method was applied to detect and analyze the 10 mutational loci of the 3 candidate prolificacy genes including bone morphogenetic protein type I receptors, bone morphogenetic protein 15, and growth differentiation factor 9. The 10 mutational loci are as follows: FecB locus of the BMPR-IB gene; FecXI, FecXB, FecXL, FecXH, FecXG, and FecXR of the BMP15 gene; and G1, G8, and FecTT of the GDF9 gene. Two mutations including BMPR-IB/FecB and GDF9/G1 were found in Bayanbulak sheep. Independence test results of the two flocks demonstrate that the FecB locus has a significant effect on the lambing number of Bayanbulak sheep. However, the mutation frequency of the G1 locus in GDF9 is very low. Independence test results demonstrate that the GDF9 locus does not have a significant impact on the lambing performance of Bayanbulak sheep. Among the 10 detected loci, BMPR-IB/FecB is the major gene that influences the high lambing rate of Bayanbulak sheep.

  1. A Study on the Logistics Strategy of Retailing

    OpenAIRE

    金, 弘錫; Hong-seok, KIM

    2003-01-01

    The purpose of this paper is to discuss about how the logistics strategy must be carried out when it used as a means of management strategy in retailing. Therefore, in this study I showed some problems of logistics strategy for retailing by theory and case study. As the result, it concluded that building a supply chain logistics system for customer satisfaction by utilizing information technology is effective. In the future, to be successful logistics strategy of retailing, we must build an e...

  2. The Study of Teaching Effective Strategies on Student's Math Achievements

    OpenAIRE

    Mohammad-Hassan Behzadi; Farhad Hosseinzadeh Lotfi; Nasrin Mahboudi

    2014-01-01

    One of the most important factors in student's learning weakness and academic failure, is their unfamilarity or low awareness of the learning strategies and studying in mathematics. This study is performed to examine the students' math and reading skills and their study skills that impact on their academic progress. The main objective of the research is to study with emphasis on training study strategies versus ususal method (teaching without emphasis on training study strategies) to increase...

  3. A study of bacterial gene regulatory mechanisms

    DEFF Research Database (Denmark)

    Hansen, Sabine

    the different regulatory mechanisms affect system dynamics. We have designed a synthetic gene regulatory network (GRN) in bacterial cells that enables us to study the dynamics of GRNs. The results presented in this PhD thesis show that model equations based on the established mechanisms of action of each...... of a particular type of regulatory mechanism. The synthetic system presented in this thesis is, to our knowledge, the first of its kind to allow a direct comparison of the dynamic behaviors of gene regulatory networks that employ different mechanisms of regulation. In addition to studying the dynamic behavior...... switch off the expression of unfavorable proteins. This dynamic regulation requires a coordinated effort by a network of regulatory factors. The regulatory mechanisms employed by bacterial cell to regulate their protein expression have been extensively studied. However, little is known about how...

  4. Less is more: strategies to remove marker genes from transgenic plants

    Science.gov (United States)

    2013-01-01

    Selectable marker genes (SMGs) and selection agents are useful tools in the production of transgenic plants by selecting transformed cells from a matrix consisting of mostly untransformed cells. Most SMGs express protein products that confer antibiotic- or herbicide resistance traits, and typically reside in the end product of genetically-modified (GM) plants. The presence of these genes in GM plants, and subsequently in food, feed and the environment, are of concern and subject to special government regulation in many countries. The presence of SMGs in GM plants might also, in some cases, result in a metabolic burden for the host plants. Their use also prevents the re-use of the same SMG when a second transformation scheme is needed to be performed on the transgenic host. In recent years, several strategies have been developed to remove SMGs from GM products while retaining the transgenes of interest. This review describes the existing strategies for SMG removal, including the implementation of site specific recombination systems, TALENs and ZFNs. This review discusses the advantages and disadvantages of existing SMG-removal strategies and explores possible future research directions for SMG removal including emerging technologies for increased precision for genome modification. PMID:23617583

  5. With Reference to Reference Genes: A Systematic Review of Endogenous Controls in Gene Expression Studies.

    Science.gov (United States)

    Chapman, Joanne R; Waldenström, Jonas

    2015-01-01

    The choice of reference genes that are stably expressed amongst treatment groups is a crucial step in real-time quantitative PCR gene expression studies. Recent guidelines have specified that a minimum of two validated reference genes should be used for normalisation. However, a quantitative review of the literature showed that the average number of reference genes used across all studies was 1.2. Thus, the vast majority of studies continue to use a single gene, with β-actin (ACTB) and/or glyceraldehyde 3-phosphate dehydrogenase (GAPDH) being commonly selected in studies of vertebrate gene expression. Few studies (15%) tested a panel of potential reference genes for stability of expression before using them to normalise data. Amongst studies specifically testing reference gene stability, few found ACTB or GAPDH to be optimal, whereby these genes were significantly less likely to be chosen when larger panels of potential reference genes were screened. Fewer reference genes were tested for stability in non-model organisms, presumably owing to a dearth of available primers in less well characterised species. Furthermore, the experimental conditions under which real-time quantitative PCR analyses were conducted had a large influence on the choice of reference genes, whereby different studies of rat brain tissue showed different reference genes to be the most stable. These results highlight the importance of validating the choice of normalising reference genes before conducting gene expression studies.

  6. Tumor-targeted inhibition by a novel strategy - mimoretrovirus expressing siRNA targeting the Pokemon gene.

    Science.gov (United States)

    Tian, Zhiqiang; Wang, Huaizhi; Jia, Zhengcai; Shi, Jinglei; Tang, Jun; Mao, Liwei; Liu, Hongli; Deng, Yijing; He, Yangdong; Ruan, Zhihua; Li, Jintao; Wu, Yuzhang; Ni, Bing

    2010-12-01

    Pokemon gene has crucial but versatile functions in cell differentiation, proliferation and tumorigenesis. It is a master regulator of the ARF-HDM2-p53 and Rb-E2F pathways. The facts that the expression of Pokemon is essential for tumor formation and many kinds of tumors over-express the Pokemon gene make it an attractive target for therapeutic intervention for cancer treatment. In this study, we used an RNAi strategy to silence the Pokemon gene in a cervical cancer model. To address the issues involving tumor specific delivery and durable expression of siRNA, we applied the Arg-Gly-Asp (RGD) peptide ligand and polylysine (K(18)) fusion peptide to encapsulate a recombinant retrovirus plasmid expressing a siRNA targeting the Pokemon gene and produced the 'mimoretrovirus'. At charge ratio 2.0 of fusion peptide/plasmid, the mimoretrovirus formed stable and homogenous nanoparticles, and provided complete DNase I protection and complete gel retardation. This nanoparticle inhibited SiHa cell proliferation and invasion, while it promoted SiHa cell apoptosis. The binding of the nanoparticle to SiHa cells was mediated via the RGD-integrin α(v)β(3) interaction, as evidenced by the finding that unconjugated RGD peptide inhibited this binding significantly. This tumor-targeting mimoretrovirus exhibited excellent anti-tumor capacity in vivo in a nude mouse model. Moreover, the mimoretrovirus inhibited tumor growth with a much higher efficiency than recombinant retrovirus expressing siRNA or the K(18)/P4 nanoparticle lacking the RGD peptide. Results suggest that the RNAi/RGD-based mimoretrovirus developed in this study represents a novel anti-tumor strategy that may be applicable to most research involving cancer therapy and, thus, has promising potential as a cervical cancer treatment.

  7. Directed evolution combined with synthetic biology strategies expedite semi-rational engineering of genes and genomes.

    Science.gov (United States)

    Kang, Zhen; Zhang, Junli; Jin, Peng; Yang, Sen

    2015-01-01

    Owing to our limited understanding of the relationship between sequence and function and the interaction between intracellular pathways and regulatory systems, the rational design of enzyme-coding genes and de novo assembly of a brand-new artificial genome for a desired functionality or phenotype are difficult to achieve. As an alternative approach, directed evolution has been widely used to engineer genomes and enzyme-coding genes. In particular, significant developments toward DNA synthesis, DNA assembly (in vitro or in vivo), recombination-mediated genetic engineering, and high-throughput screening techniques in the field of synthetic biology have been matured and widely adopted, enabling rapid semi-rational genome engineering to generate variants with desired properties. In this commentary, these novel tools and their corresponding applications in the directed evolution of genomes and enzymes are discussed. Moreover, the strategies for genome engineering and rapid in vitro enzyme evolution are also proposed.

  8. Dual redundant sequencing strategy: Full-length gene characterisation of 1056 novel and confirmatory HLA alleles.

    Science.gov (United States)

    Albrecht, V; Zweiniger, C; Surendranath, V; Lang, K; Schöfl, G; Dahl, A; Winkler, S; Lange, V; Böhme, I; Schmidt, A H

    2017-08-01

    The high-throughput department of DKMS Life Science Lab encounters novel human leukocyte antigen (HLA) alleles on a daily basis. To characterise these alleles, we have developed a system to sequence the whole gene from 5'- to 3'-UTR for the HLA loci A, B, C, DQB1 and DPB1 for submission to the European Molecular Biology Laboratory - European Nucleotide Archive (EMBL-ENA) and the IPD-IMGT/HLA Database. Our workflow is based on a dual redundant sequencing strategy. Using shotgun sequencing on an Illumina MiSeq instrument and single molecule real-time (SMRT) sequencing on a PacBio RS II instrument, we are able to achieve highly accurate HLA full-length consensus sequences. Remaining conflicts are resolved using the R package DR2S (Dual Redundant Reference Sequencing). Given the relatively high throughput of this strategy, we have developed the semi-automated web service TypeLoader, to aid in the submission of sequences to the EMBL-ENA and the IPD-IMGT/HLA Database. In the IPD-IMGT/HLA Database release 3.24.0 (April 2016; prior to the submission of the sequences described here), only 5.2% of all known HLA alleles have been fully characterised together with intronic and UTR sequences. So far, we have applied our strategy to characterise and submit 1056 HLA alleles, thereby more than doubling the number of fully characterised alleles. Given the increasing application of next generation sequencing (NGS) for full gene characterisation in clinical practice, extending the HLA database concomitantly is highly desirable. Therefore, we propose this dual redundant sequencing strategy as a workflow for submission of novel full-length alleles and characterisation of sequences that are as yet incomplete. This would help to mitigate the predominance of partially known alleles in the database. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Mapping calcium phosphate activated gene networks as a strategy for targeted osteoinduction of human progenitors in vitro and in vivo

    Science.gov (United States)

    Eyckmans, J.; Roberts, S.J.; Bolander, J.; Schrooten, J.; Chen, C.S.; Luyten, F.P.

    2014-01-01

    Although calcium phosphate-containing biomaterials are promising scaffolds for bone regenerative strategies, the osteoinductive capacity of such materials is poorly understood. In this study, we investigated whether endogenous mechanisms of in vivo calcium phosphate-driven, ectopic bone formation could be identified and used to induce enhanced differentiation in vitro of the same progenitor population. To accomplish this, human periosteum derived cells (hPDCs) were seeded on hydroxyapatite/collagen scaffolds (calcium phosphate rich matrix or CPRM), or on decalcified scaffolds (calcium phosphate depleted matrix or CPDM), followed by subcutaneous implantation in nude mice to trigger ectopic bone formation. In this system, osteoblast differentiation occurred in CPRM scaffolds, but not in CPDM scaffolds. Gene expression was assessed by human full-genome microarray at 20 hours after seeding, and 2, 8 and 18 days after implantation. In both matrices, implantation of the cell constructs triggered a similar gene expression cascade, however, gene expression dynamics progressed faster in CPRM scaffolds than in CPDM scaffolds. The difference in gene expression dynamics was associated with differential activation of hub genes and molecular signaling pathways related to calcium signaling (CREB), inflammation (TNFα, NFkB, and IL6) and bone development (TGFβ, β-catenin, BMP, EGF, and ERK signaling). Starting from this set of pathways, a growth factor cocktail was developed that robustly enhanced osteogenesis in vitro and in vivo. Taken together, our data demonstrate that through the identification and subsequent stimulation of genes, proteins and signaling pathways associated with calcium phosphate mediated osteoinduction, a focused approach to develop targeted differentiation protocols in adult progenitor cells can be achieved. PMID:23537666

  10. Theoretical aspects of coping strategies study

    OpenAIRE

    Kabiyeva, M.; Kasen, G. A.

    2015-01-01

    In article based on a thorough analysis of classical and modern foreign and domestic literature examines the notion of coping strategies, approaches to the understanding of coping. Theoretically proved that coping is an individual way to interact with the situation according to its own logic, psychological capabilities and its importance in human life, the level of development of coping resources provides a successful adaptation to stress. From the analysis of theoretical literature, we saw t...

  11. The KCNE genes in hypertrophic cardiomyopathy: a candidate gene study

    DEFF Research Database (Denmark)

    Hedley, Paula L; Haundrup, Ole; Andersen, Paal S

    2011-01-01

    as well as the T-tubules of the sarcolemma. It has been suggested that minK forms part of an "electro-mechanical feed-back" which links cardiomyocyte stretching to changes in ion channel function. We examined whether mutations in KCNE genes were associated with hypertrophic cardiomyopathy (HCM), a genetic...

  12. Strategies for Diversity: SOARS, a Case Study

    Science.gov (United States)

    Windham, T. L.

    2001-12-01

    Achieving the goal of a diverse, internationally competitive, and globally engaged workforce of scientists, engineers, and well prepared citizens calls for renewed educational goals and strategies. In 1995 UCAR teamed up with NSF and established a program, SOARS, that extends science education and encourages university students from diverse backgrounds to nourish their interests, develop skills, and create paths that lead them to careers in the atmospheric and related sciences. SOARS integrates multi-summer research opportunities with a comprehensive mentoring component and other proven learning strategies to create a student (protégé) centered learning community. SOARS is having a positive impact on the scientific community. Already more that 60 protégés have traveled this pathway; several are successfully employed as scientists. Nine have attained graduate degrees, three are Ph.D. candidates, and 34 have received undergraduate degrees. In fall 2001, 17 SOARS protégés are enrolled in graduate programs in the atmospheric and related sciences. Many have participated in scientific conferences and coauthored papers published in peer-reviewed journals. SOARS sponsorship has expanded and includes DOE, NASA, and NOAA. Strategies contributing to the success of SOARS include an accrediting disposition that: 1) recognizes protégés as capable, competent, responsible, successful adults and 2) deploys organized activities designed to encourage protégés to see themselves as eligible to become successful scientists while being in good standing in their "home" communities. Relationships with professional scientists and scientific societies that share this disposition have been critical to the success of SOARS.

  13. Experimental strategies for studying transcription factor-DNA binding specificities.

    Science.gov (United States)

    Geertz, Marcel; Maerkl, Sebastian J

    2010-12-01

    Specific binding of transcription factors (TFs) determines in a large part the connectivity of gene regulatory networks as well as the quantitative level of gene expression. A multiplicity of both experimental and computational methods is currently used to discover and characterize the underlying TF-DNA interactions. Experimental methods can be further subdivided into in vitro- and in vivo-based approaches, each accenting different aspects of TF-binding events. In this review we summarize the flexibility and performance of a selection of both types of experimental methods. In conclusion, we argue that a serial combination of methods with different throughput and data type constitutes an optimal experimental strategy.

  14. Research Strategies in European Union Studies

    DEFF Research Database (Denmark)

    Manners, Ian James; Lynggaard, Kennet; Löfgren, Karl

    2015-01-01

    agenda for research on Europe. The crisis gripping the EU in the 21st century is not just an economic crisis, it is a crisis of belief in the EU. Research on the EU is deeply implicated in this crisis, not least because of the questions it does not ask, but also because of the pereceived weakness...... of demonstrating the methods and evidence used. A new agenda for research on Europe needs to acknowledge these weaknesses of the past and move beyond dichotomies towards greater awareness and openesss of the importance of research strategies, designs and methods....

  15. Synthetic strategies for studying embryonic development.

    Science.gov (United States)

    Ouyang, Xiaohu; Chen, James K

    2010-06-25

    Developmental biology has evolved from a descriptive science to one based on genetic principles and molecular mechanisms. Although molecular biology and genetic technologies have been the primary drivers of this transformation, synthetic strategies have been increasingly utilized to interrogate the mechanisms of embryonic patterning with spatial and temporal precision. In this review, we survey how chemical tools and engineered proteins have been used to perturb developmental processes at the DNA, RNA, protein, and cellular levels. We discuss the design principles, experimental capabilities, and limitations of each method, as well as future challenges for the chemical and developmental biology communities.

  16. Advances in study of molecular imaging reporte gene systems

    International Nuclear Information System (INIS)

    Wu Tao; An Rui

    2010-01-01

    The use of molecular imaging reporter gene systems has allowed gene therapy to move from the laboratory to the clinical application, which provides methodology to monitor the expression of therapeutic gene noninvasively and achieve quantitative outcome in vivo. Recently, the radionuclide reporter gene still is the focus many studies, but MRI and optical reporter gene have gradually played a important part in reporter gene systems. On the basis of combination of multi-subject, for example applied chemistry and molecular biology, more and more new modified reporter genes and molecular probes have spread out. This paper mainly introduces the advantages and disadvantages of reporter gene system and development trends. (authors)

  17. Strategy Escalation: An emerging paradigm for safe clinical development of T cell gene therapies

    Directory of Open Access Journals (Sweden)

    Junghans Richard

    2010-06-01

    Full Text Available Abstract Gene therapy techniques are being applied to modify T cells with chimeric antigen receptors (CARs for therapeutic ends. The versatility of this platform has spawned multiple options for their application with new permutations in strategies continually being invented, a testimony to the creative energies of many investigators. The field is rapidly expanding with immense potential for impact against diverse cancers. But this rapid expansion, like the Big Bang, comes with a somewhat chaotic evolution of its therapeutic universe that can also be dangerous, as seen by recently publicized deaths. Time-honored methods for new drug testing embodied in Dose Escalation that were suitable for traditional inert agents are now inadequate for these novel "living drugs". In the following, I propose an approach to escalating risk for patient exposures with these new immuno-gene therapy agents, termed Strategy Escalation, that accounts for the molecular and biological features of the modified cells and the methods of their administration. This proposal is offered not as a prescriptive but as a discussion framework that investigators may wish to consider in configuring their intended clinical applications.

  18. Study Strategy Predictors of Performance in Introductory Psychology

    Science.gov (United States)

    Marrs, Heath; Sigler, Ellen; Hayes, Kaira

    2009-01-01

    In this study, the relationship between student study strategies and performance in Introductory Psychology was examined. Eighty-eight students in three sections of Introductory Psychology at a Midwestern university in the United States completed a demographic questionnaire and the Learning and Study Strategies Inventory-2nd edition (LASSI-2)…

  19. Strategy knowledge and strategy change in skilled performance: a study of the game Othello.

    Science.gov (United States)

    Billman, D; Shaman, D

    1990-01-01

    Skill and skill development in playing the game Othello were investigated. In particular, we studied the role of strategies and strategy change, rather than focusing on knowledge of particular board patterns. The history of the development of the game suggests a shift from positional to mobility strategies, a change which also is reproduced in the development of individual players. The first two studies used historical analysis of tournament transcripts to study strategy change. The third study investigated one possible basis for the greater accessibility or ease of positional versus mobility strategy, namely differential encoding and memorability of typical board patterns. Study 3 demonstrated that completely naive as well as positional players remember positional games and moves more easily than mobility games and moves. The easier mastery of positional strategy may be caused in part by the greater ease of encoding typical positional patterns. We suggest that strategic change and conceptual reorganization may be particularly important for domains where the naive encoding of events is not the most apt. We also suggest that similarities exist between strategy change in Othello and other domains.

  20. Recreational music-making modulates the human stress response: a preliminary individualized gene expression strategy.

    Science.gov (United States)

    Bittman, Barry; Berk, Lee; Shannon, Mark; Sharaf, Muhammad; Westengard, Jim; Guegler, Karl J; Ruff, David W

    2005-02-01

    A central component of the complex human biological stress response is the modulation of the neuro-endocrine-immune system with its intricate feedback loops that support homeostatic regulation. Well-documented marked gene expression variability among human and animal subjects coupled with sample collection timing and delayed effects, as well as a host of molecular detection challenges renders the quest for deciphering the human biological stress response challenging from many perspectives. A novel Recreational Music-Making (RMM) program was used in combination with a new strategy for peripheral blood gene expression analysis to assess individualized genomic stress induction signatures. The expression of 45 immune response-related genes was determined using a multiplex preamplification step prior to conventional quantitative Real Time Polymerase Chain Reaction (qRT-PCR) mRNA analysis to characterize the multidimensional biological impact of a 2-phase controlled stress induction/amelioration experimental protocol in 32 randomly assigned individuals. In subjects performing the RMM activity following a 1-hour stress induction protocol, 19 out of 45 markers demonstrated reversal with significant (P = 0.05) Pearson correlations in contrast to 6 out of 45 markers in the resting control group and 0 out of 45 in the ongoing stressor group. The resultant amelioration of stress-induced genomic expression supports the underlying premise that RMM warrants additional consideration as a rational choice within our armamentarium of stress reduction strategies. Modulation of individualized genomic stress induction signatures in peripheral blood presents a new opportunity for elucidating the dynamics of the human stress response.

  1. Tropism-Modification Strategies for Targeted Gene Delivery Using Adenoviral Vectors

    Directory of Open Access Journals (Sweden)

    Andrew H. Baker

    2010-10-01

    Full Text Available Achieving high efficiency, targeted gene delivery with adenoviral vectors is a long-standing goal in the field of clinical gene therapy. To achieve this, platform vectors must combine efficient retargeting strategies with detargeting modifications to ablate native receptor binding (i.e. CAR/integrins/heparan sulfate proteoglycans and “bridging” interactions. “Bridging” interactions refer to coagulation factor binding, namely coagulation factor X (FX, which bridges hepatocyte transduction in vivo through engagement with surface expressed heparan sulfate proteoglycans (HSPGs. These interactions can contribute to the off-target sequestration of Ad5 in the liver and its characteristic dose-limiting hepatotoxicity, thereby significantly limiting the in vivo targeting efficiency and clinical potential of Ad5-based therapeutics. To date, various approaches to retargeting adenoviruses (Ad have been described. These include genetic modification strategies to incorporate peptide ligands (within fiber knob domain, fiber shaft, penton base, pIX or hexon, pseudotyping of capsid proteins to include whole fiber substitutions or fiber knob chimeras, pseudotyping with non-human Ad species or with capsid proteins derived from other viral families, hexon hypervariable region (HVR substitutions and adapter-based conjugation/crosslinking of scFv, growth factors or monoclonal antibodies directed against surface-expressed target antigens. In order to maximize retargeting, strategies which permit detargeting from undesirable interactions between the Ad capsid and components of the circulatory system (e.g. coagulation factors, erythrocytes, pre-existing neutralizing antibodies, can be employed simultaneously. Detargeting can be achieved by genetic ablation of native receptor-binding determinants, ablation of “bridging interactions” such as those which occur between the hexon of Ad5 and coagulation factor X (FX, or alternatively, through the use of polymer

  2. Aging, rule-violation checking strategies, and strategy combination: An EEG study in arithmetic.

    Science.gov (United States)

    Hinault, Thomas; Lemaire, Patrick

    2017-10-01

    In arithmetic, rule-violation checking strategies are used while participants solve problems that violate arithmetic rules, like the five rule (i.e., products of problems including five as an operand end with either five or zero; e.g., 5×14=70) or the parity rule (i.e., when at least one of the two operands is even, the product is also even; otherwise the product is odd; e.g., 4×13=52). When problems violate both rules, participants use strategy combination and have better performance on both-rule than on one-rule violation problems (i.e., five or parity rule). Aging studies found that older adults efficiently use one-rule violation checking strategies but have difficulties to combine two strategies. To better understand these aging effects, we used EEG and found important age-related changes while participants used rule-violation checking strategies. We compared participants' performance while they verified arithmetic problems that differ in number and type of violated rule. More specifically, both-rule violation problems elicited larger negativity than one-rule violation problems between 600 and 800ms. Five-rule violation problems differed from parity-rule violation problems between 1100 and 1200ms. Moreover, rule-violation checking strategies and strategy combination involved delta, theta, and lower alpha frequencies. Age-related changes in ERPs and frequency were associated with less efficient strategy combination. Moreover, efficient use of one-rule violation checking strategies in older adults was associated with changes in ERPs and frequency. These findings contribute to further our understanding of age-related changes and invariance in arithmetic strategies, and in combination of arithmetic strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Knock-in strategy at 3'-end of Crx gene by CRISPR/Cas9 system shows the gene expression profiles during human photoreceptor differentiation.

    Science.gov (United States)

    Homma, Kohei; Usui, Sumiko; Kaneda, Makoto

    2017-03-01

    Fluorescent reporter gene knock-in induced pluripotent stem cell (iPSC) lines have been used to evaluate the efficiency of differentiation into specific cell lineages. Here, we report a knock-in strategy for the generation of human iPSC reporter lines in which a 2A peptide sequence and a red fluorescent protein (E2-Crimson) gene were inserted at the termination codon of the cone-rod homeobox (Crx) gene, a photoreceptor-specific transcriptional factor gene. The knock-in iPSC lines were differentiated into fluorescence-expressing cells in 3D retinal differentiation culture, and the fluorescent cells also expressed Crx specifically in the nucleus. We found that the fluorescence intensity was positively correlated with the expression levels of Crx mRNA and that fluorescent cells expressed rod photoreceptor-specific genes in the later stage of differentiation. Finally, we treated the fluorescent cells with DAPT, a Notch inhibitor, and found that DAPT-enhanced retinal differentiation was associated with up-regulation of Crx, Otx2 and NeuroD1, and down-regulation of Hes5 and Ngn2. These suggest that this knock-in strategy at the 3'-end of the target gene, combined with the 2A peptide linked to fluorescent proteins, offers a useful tool for labeling specific cell lineages or monitoring expression of any marker genes without affecting the function of the target gene. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  4. Validation of reference genes for quantitative RT-PCR studies of gene expression in perennial ryegrass (Lolium perenne L.

    Directory of Open Access Journals (Sweden)

    Thrush Anthony

    2010-01-01

    Full Text Available Abstract Background Perennial ryegrass (Lolium perenne L. is an important pasture and turf crop. Biotechniques such as gene expression studies are being employed to improve traits in this temperate grass. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR is among the best methods available for determining changes in gene expression. Before analysis of target gene expression, it is essential to select an appropriate normalisation strategy to control for non-specific variation between samples. Reference genes that have stable expression at different biological and physiological states can be effectively used for normalisation; however, their expression stability must be validated before use. Results Existing Serial Analysis of Gene Expression data were queried to identify six moderately expressed genes that had relatively stable gene expression throughout the year. These six candidate reference genes (eukaryotic elongation factor 1 alpha, eEF1A; TAT-binding protein homolog 1, TBP-1; eukaryotic translation initiation factor 4 alpha, eIF4A; YT521-B-like protein family protein, YT521-B; histone 3, H3; ubiquitin-conjugating enzyme, E2 were validated for qRT-PCR normalisation in 442 diverse perennial ryegrass (Lolium perenne L. samples sourced from field- and laboratory-grown plants under a wide range of experimental conditions. Eukaryotic EF1A is encoded by members of a multigene family exhibiting differential expression and necessitated the expression analysis of different eEF1A encoding genes; a highly expressed eEF1A (h, a moderately, but stably expressed eEF1A (s, and combined expression of multigene eEF1A (m. NormFinder identified eEF1A (s and YT521-B as the best combination of two genes for normalisation of gene expression data in perennial ryegrass following different defoliation management in the field. Conclusions This study is unique in the magnitude of samples tested with the inclusion of numerous field-grown samples

  5. Incorporating Study Strategies in Developmental Mathematics/College Algebra

    Science.gov (United States)

    Mireles, Selina Vasquez; Offer, Joey; Ward, Debra P.; Dochen, Carol W.

    2011-01-01

    The purpose of this paper is to discuss the effectiveness of incorporating study strategies in a developmental mathematics/college algebra program. Both quantitative and qualitative data were collected through a quasiexperimental methodology. Results show that students reported increases on the Learning and Study Strategies Inventory (LASSI)…

  6. Test Review: Learning and Study Strategies Inventory (LASSI).

    Science.gov (United States)

    Mealey, Donna L.

    1988-01-01

    Reviews the Learning and Study Strategies Inventory (LASSI), a test designed to measure college students' learning and study strategies through self report. Advises that the test is still in experimental form, with a questionable norm group, and thus must be used with caution, especially in interpreting percentile ranks. (SKC)

  7. The Use of Learning and Study Strategies by College Freshmen.

    Science.gov (United States)

    Hulick, Chuck; Higginson, Bonnie

    This paper reports on an investigation of study strategies of 514 college freshmen at Murray State University (Kentucky) enrolled in a Freshman Orientation class. A demographic questionnaire and the Learning and Study Strategies Inventory (LASSI) were administered. Responses on the LASSI are categorized into ten subscales (attitude, motivation,…

  8. Discovery-based strategies for studying platelet function.

    Science.gov (United States)

    Flaumenhaft, R; Dilks, J R

    2008-04-01

    The platelet is an anucleate cell, complicating efforts to study platelet function by traditional genetic means. Discovery-based strategies have lead to the identification of pharmacological agents capable of targeting specific proteins critical for platelet activation. This review will address the evolution of discovery-based strategies to identify probes that are at once useful reagents for studying platelet activation and effective therapeutics.

  9. The CanOE strategy: integrating genomic and metabolic contexts across multiple prokaryote genomes to find candidate genes for orphan enzymes.

    Directory of Open Access Journals (Sweden)

    Adam Alexander Thil Smith

    2012-05-01

    Full Text Available Of all biochemically characterized metabolic reactions formalized by the IUBMB, over one out of four have yet to be associated with a nucleic or protein sequence, i.e. are sequence-orphan enzymatic activities. Few bioinformatics annotation tools are able to propose candidate genes for such activities by exploiting context-dependent rather than sequence-dependent data, and none are readily accessible and propose result integration across multiple genomes. Here, we present CanOE (Candidate genes for Orphan Enzymes, a four-step bioinformatics strategy that proposes ranked candidate genes for sequence-orphan enzymatic activities (or orphan enzymes for short. The first step locates "genomic metabolons", i.e. groups of co-localized genes coding proteins catalyzing reactions linked by shared metabolites, in one genome at a time. These metabolons can be particularly helpful for aiding bioanalysts to visualize relevant metabolic data. In the second step, they are used to generate candidate associations between un-annotated genes and gene-less reactions. The third step integrates these gene-reaction associations over several genomes using gene families, and summarizes the strength of family-reaction associations by several scores. In the final step, these scores are used to rank members of gene families which are proposed for metabolic reactions. These associations are of particular interest when the metabolic reaction is a sequence-orphan enzymatic activity. Our strategy found over 60,000 genomic metabolons in more than 1,000 prokaryote organisms from the MicroScope platform, generating candidate genes for many metabolic reactions, of which more than 70 distinct orphan reactions. A computational validation of the approach is discussed. Finally, we present a case study on the anaerobic allantoin degradation pathway in Escherichia coli K-12.

  10. Identification of Human HK Genes and Gene Expression Regulation Study in Cancer from Transcriptomics Data Analysis

    Science.gov (United States)

    Zhang, Zhang; Liu, Jingxing; Wu, Jiayan; Yu, Jun

    2013-01-01

    The regulation of gene expression is essential for eukaryotes, as it drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms. RNA-Sequencing (RNA-Seq) provides researchers with a powerful toolbox for characterization and quantification of transcriptome. Many different human tissue/cell transcriptome datasets coming from RNA-Seq technology are available on public data resource. The fundamental issue here is how to develop an effective analysis method to estimate expression pattern similarities between different tumor tissues and their corresponding normal tissues. We define the gene expression pattern from three directions: 1) expression breadth, which reflects gene expression on/off status, and mainly concerns ubiquitously expressed genes; 2) low/high or constant/variable expression genes, based on gene expression level and variation; and 3) the regulation of gene expression at the gene structure level. The cluster analysis indicates that gene expression pattern is higher related to physiological condition rather than tissue spatial distance. Two sets of human housekeeping (HK) genes are defined according to cell/tissue types, respectively. To characterize the gene expression pattern in gene expression level and variation, we firstly apply improved K-means algorithm and a gene expression variance model. We find that cancer-associated HK genes (a HK gene is specific in cancer group, while not in normal group) are expressed higher and more variable in cancer condition than in normal condition. Cancer-associated HK genes prefer to AT-rich genes, and they are enriched in cell cycle regulation related functions and constitute some cancer signatures. The expression of large genes is also avoided in cancer group. These studies will help us understand which cell type-specific patterns of gene expression differ among different cell types, and particularly for cancer. PMID:23382867

  11. Visualization strategies in tokamak fluid turbulence studies

    International Nuclear Information System (INIS)

    Kerbel, G.D.; Waltz, R.E.

    1993-01-01

    Computational model development represents an essential part of fusion research. The time and effort needed to assess and improve these models depends critically on the realism and complexity of the model and, in particular, on the capability of computing resource brought to bear on the problem. Not only must one ask open-quotes How much computation can one realistically expect to do with a particular resource?close quotes, but one must further assess open-quotes How much computation can one, in actuality, realize from this resource in a day?close quotes In this context, a day is the turn-around time, the psychological scope appropriate for running a simulation, reducing the results to palatable form and assessing the need for changes to the model. With more computer and communications resources, the complexity, the realism, and the resolution of the models one can hope to refine on a fixed psychological timescale increase only with a commensurate increase in ones ability to grasp and integrate the behavior produced by simulation. A successful strategy to help one to retrieve, understand and compare model behavior under the action of model development will likely need to use the increased power of the computing resource itself to create visual experience. The impact of the experience will depend strongly on the craft used in its creation. Trying to bring the analysis, model development and assessment, execution and improvement cycles into a realistic daily working schedule involves using more powerful computer supported collaborative work communications and analysis tools. A computer environment which supports generating and storing enormous quantities of data, but lacks the powerful data navigation and visualization tools necessary to determine quickly and effectively whether the data should be archived or destroyed soon becomes dysfunctional

  12. Pengaruh Strategi Bisnis Terhadap Sistem Pengendalian Manajemen – Studi pada BUMN Kategori Industri Strategis di Indonesia

    Directory of Open Access Journals (Sweden)

    Karsam Karsam

    2017-03-01

    Full Text Available The objective of this study is to investigate the influence of business strategy for management control system. The study was carried out on twelve state-owned enterprises strategic industries (BUMNIS in Indonesia between 2015 and 2016. The studied BUMNIS were selected based on criteria. The data was collected from questionaires that filled by top managements, the board of directors and internal control unit staff. In total, there were sixty respondents and 100% respondent rate. Structural Equation Modelling (SEM with PLS approach was used to analysis the survey results. This study demonstrates that business strategy has an impact on management control systems of studied BUMNIS.

  13. Data-processing strategies for metabolomics studies

    NARCIS (Netherlands)

    Hendriks, M.M.W.B.; Eeuwijk, van F.A.; Jellema, R.H.; Westerhuis, J.A.; Reijmers, T.H.; Hoefsloot, H.C.J.; Smilde, A.K.

    2011-01-01

    Metabolomics studies aim at a better understanding of biochemical processes by studying relations between metabolites and between metabolites and other types of information (e.g., sensory and phenotypic features). The objectives of these studies are diverse, but the types of data generated and the

  14. Non integrative strategy decreases chromosome instability and improves endogenous pluripotency genes reactivation in porcine induced pluripotent-like stem cells.

    Science.gov (United States)

    Congras, Annabelle; Barasc, Harmonie; Canale-Tabet, Kamila; Plisson-Petit, Florence; Delcros, Chantal; Feraud, Olivier; Oudrhiri, Noufissa; Hadadi, Eva; Griscelli, Franck; Bennaceur-Griscelli, Annelise; Turhan, Ali; Afanassieff, Marielle; Ferchaud, Stéphane; Pinton, Alain; Yerle-Bouissou, Martine; Acloque, Hervé

    2016-06-01

    The pig is an emerging animal model, complementary to rodents for basic research and for biomedical and agronomical purposes. However despite the progress made on mouse and rat models to produce genuine pluripotent cells, it remains impossible to produce porcine pluripotent cell lines with germline transmission. Reprogramming of pig somatic cells using conventional integrative strategies remains also unsatisfactory. In the present study, we compared the outcome of both integrative and non-integrative reprogramming strategies on pluripotency and chromosome stability during pig somatic cell reprogramming. The porcine cell lines produced with integrative strategies express several pluripotency genes but they do not silence the integrated exogenes and present a high genomic instability upon passaging. In contrast, pig induced pluripotent-like stem cells produced with non-integrative reprogramming system (NI-iPSLCs) exhibit a normal karyotype after more than 12 months in culture and reactivate endogenous pluripotency markers. Despite the persistent expression of exogenous OCT4 and MYC, these cells can differentiate into derivatives expressing markers of the three embryonic germ layers and we propose that these NI-iPSLCs can be used as a model to bring new insights into the molecular factors controlling and maintaining pluripotency in the pig and other non-rodent mammalians.

  15. Identification of Hematopoietic Stem Cell Engraftment Genes in Gene Therapy Studies.

    Science.gov (United States)

    Powers, John M; Trobridge, Grant D

    2013-09-01

    Hematopoietic stem cell (HSC) therapy using replication-incompetent retroviral vectors is a promising approach to provide life-long correction for genetic defects. HSC gene therapy clinical studies have resulted in functional cures for several diseases, but in some studies clonal expansion or leukemia has occurred. This is due to the dyregulation of endogenous host gene expression from vector provirus insertional mutagenesis. Insertional mutagenesis screens using replicating retroviruses have been used extensively to identify genes that influence oncogenesis. However, retroviral mutagenesis screens can also be used to determine the role of genes in biological processes such as stem cell engraftment. The aim of this review is to describe the potential for vector insertion site data from gene therapy studies to provide novel insights into mechanisms of HSC engraftment. In HSC gene therapy studies dysregulation of host genes by replication-incompetent vector proviruses may lead to enrichment of repopulating clones with vector integrants near genes that influence engraftment. Thus, data from HSC gene therapy studies can be used to identify novel candidate engraftment genes. As HSC gene therapy use continues to expand, the vector insertion site data collected will be of great interest to help identify novel engraftment genes and may ultimately lead to new therapies to improve engraftment.

  16. Gene Delivery Particle Engineering Strategies for Shape-dependent Targeting of Cells and Tissues.

    Science.gov (United States)

    Kozielski, Kristen L; Sitti, Metin

    2017-01-01

    Successful gene delivery requires overcoming both systemic and intracellular obstacles before the nucleic acid cargo can successfully reach its tissue and subcellular target location. Materials & Methods: Non-viral mechanisms to enable targeting while avoiding off-target delivery have arisen via biological, chemical, and physical engineering strategies. Herein we will discuss the physical parameters in particle design that promote tissue- and cell-targeted delivery of genetic cargo. We will discuss systemic concerns, such as circulation, tissue localization, and clearance, as well as cell-scale obstacles, such as cellular uptake and nucleic acid packaging. In particular, we will focus on engineering particle shape and size in order to enhance delivery and promote precise targeting. We will also address methods to program or change particle shape in situ using environmentally triggered cues. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Optimizing the 3R Study Strategy to Learn from Text

    NARCIS (Netherlands)

    Reijners, Pauline; Kester, Liesbeth; Wetzels, Sandra; Kirschner, Paul A.

    2014-01-01

    Learning from text is often very difficult for students. In this presentation the results of a study with the 3R study strategy are presented in which possible mechanisms for stimulating successful text learning are discussed.

  18. Evaluation of Gene Modification Strategies for the Development of Low-Alcohol-Wine Yeasts

    Science.gov (United States)

    Kutyna, D. R.; Solomon, M. R.; Black, C. A.; Borneman, A.; Henschke, P. A.; Pretorius, I. S.; Chambers, P. J.

    2012-01-01

    Saccharomyces cerevisiae has evolved a highly efficient strategy for energy generation which maximizes ATP energy production from sugar. This adaptation enables efficient energy generation under anaerobic conditions and limits competition from other microorganisms by producing toxic metabolites, such as ethanol and CO2. Yeast fermentative and flavor capacity forms the biotechnological basis of a wide range of alcohol-containing beverages. Largely as a result of consumer demand for improved flavor, the alcohol content of some beverages like wine has increased. However, a global trend has recently emerged toward lowering the ethanol content of alcoholic beverages. One option for decreasing ethanol concentration is to use yeast strains able to divert some carbon away from ethanol production. In the case of wine, we have generated and evaluated a large number of gene modifications that were predicted, or known, to impact ethanol formation. Using the same yeast genetic background, 41 modifications were assessed. Enhancing glycerol production by increasing expression of the glyceraldehyde-3-phosphate dehydrogenase gene, GPD1, was the most efficient strategy to lower ethanol concentration. However, additional modifications were needed to avoid negatively affecting wine quality. Two strains carrying several stable, chromosomally integrated modifications showed significantly lower ethanol production in fermenting grape juice. Strain AWRI2531 was able to decrease ethanol concentrations from 15.6% (vol/vol) to 13.2% (vol/vol), whereas AWRI2532 lowered ethanol content from 15.6% (vol/vol) to 12% (vol/vol) in both Chardonnay and Cabernet Sauvignon juices. Both strains, however, produced high concentrations of acetaldehyde and acetoin, which negatively affect wine flavor. Further modifications of these strains allowed reduction of these metabolites. PMID:22729542

  19. Evaluation of gene modification strategies for the development of low-alcohol-wine yeasts.

    Science.gov (United States)

    Varela, C; Kutyna, D R; Solomon, M R; Black, C A; Borneman, A; Henschke, P A; Pretorius, I S; Chambers, P J

    2012-09-01

    Saccharomyces cerevisiae has evolved a highly efficient strategy for energy generation which maximizes ATP energy production from sugar. This adaptation enables efficient energy generation under anaerobic conditions and limits competition from other microorganisms by producing toxic metabolites, such as ethanol and CO(2). Yeast fermentative and flavor capacity forms the biotechnological basis of a wide range of alcohol-containing beverages. Largely as a result of consumer demand for improved flavor, the alcohol content of some beverages like wine has increased. However, a global trend has recently emerged toward lowering the ethanol content of alcoholic beverages. One option for decreasing ethanol concentration is to use yeast strains able to divert some carbon away from ethanol production. In the case of wine, we have generated and evaluated a large number of gene modifications that were predicted, or known, to impact ethanol formation. Using the same yeast genetic background, 41 modifications were assessed. Enhancing glycerol production by increasing expression of the glyceraldehyde-3-phosphate dehydrogenase gene, GPD1, was the most efficient strategy to lower ethanol concentration. However, additional modifications were needed to avoid negatively affecting wine quality. Two strains carrying several stable, chromosomally integrated modifications showed significantly lower ethanol production in fermenting grape juice. Strain AWRI2531 was able to decrease ethanol concentrations from 15.6% (vol/vol) to 13.2% (vol/vol), whereas AWRI2532 lowered ethanol content from 15.6% (vol/vol) to 12% (vol/vol) in both Chardonnay and Cabernet Sauvignon juices. Both strains, however, produced high concentrations of acetaldehyde and acetoin, which negatively affect wine flavor. Further modifications of these strains allowed reduction of these metabolites.

  20. Integrating Comprehension Strategies into Social Studies Instruction

    Science.gov (United States)

    Hughes, Marie Tejero; Parker-Katz, Michelle

    2013-01-01

    The number of middle school students with learning disabilities (LD) taught social studies in general education classes continues to rise. Providing general education teachers with additional ways to support students with LD as they navigate social studies reading materials could help planning and teaching for all students. In middle school, when…

  1. Competitive Strategy of Banking Industry (Studies in Bengkulu Province

    Directory of Open Access Journals (Sweden)

    Syaiful Anwar AB

    2015-12-01

    Full Text Available The purpose of this study examines the competitive strategies tested the banking industry in the province of Bengkulu. Issues raised in this study is the extent the competitive strategy of banking and can ultimately increased customer. The aim to be achieved is to know what strategies can be applied. The analysis tool is to use qualitative paradigm mapping descriptive with banks in the province of Bengkulu with cluster analysis. Data collection method used in this study was secondary data collection and in-depth interviews. The results of this study conducted that the application of competitive strategy of Bank Rakyat Indonesia, Bank Mandiri, Bank Bengkulu and market penetration strategy was by opening a branch office network and cash office assistant sub-district area are yielded  positive results. From the aspect of services offered, the customer feels that the diversification of services has been able to meet customer needs. The aspect of competitive strategy, distribution aspects of a positive assessment, especially the ease of access, is felt more quickly. Customers feel that the branch offices is still lack, particularly for the Bank are classified as market followers. Customers feel that the promotion is still lacking, particularly those Bank whose branches or cash office in the area. The  strategy  that may be used is a segmentation strategy, developing target market, and positioning.

  2. Leisure negotiation strategies scale: a study of validity and reliability ...

    African Journals Online (AJOL)

    The aim of this study was to develop a Turkish version of the “Leisure Negotiation Strategies Scale” for university students and to examine its validity and reliability. The Leisure Negotiation Strategies Scale contains 31 items, which are expressed on a 5-point Likert scale. The scale was tested in two separate samples ...

  3. Strategies to bring about change: a longitudinal study on challenges ...

    African Journals Online (AJOL)

    The strategies they most used to get away from abusive home situations were to inform a relative about the mistreatment or to run away. Children's and adolescents' limitations concerning strategies for improving their adverse living situations are also discussed. Keywords: coping, family relationships, longitudinal study, ...

  4. Genes and gene expression: Localization, damage and control: A multilevel and inter-disciplinary study

    Energy Technology Data Exchange (ETDEWEB)

    Ts' o, P.O.P.

    1990-09-01

    The main objectives of this Program Project is to develop strategy and technology for the study of gene structure, organization and function in a multi-disciplinary, highly coordinated manner. In Project I, Molecular Cytology, the establishment of all instrumentation for the computerized microscopic imaging system (CMIS) has been completed with the software in place, including measurement of the third dimension (along the Z-axis). The technique is now at hand to measure single copy DNA in the nucleus, single copy mRNA in the cell, and finally, we are in the process of developing mathematical approaches for the analysis of the relative spatial 3-D relationship among the chromosomes and the individual genes in the interphasal nucleus. Also, we have a sensitive and reliable method for measuring single-stranded DNA breaks which will be useful for the determination of damage to DNA caused by ionizing radiation. In Project II, the mapping of restriction fragments by 2-D enzymatic and electrophoretic analysis has been perfected for application. In Project III, a major finding is that the binding constant and effectiveness of antisense oligonucleotide analogues, Matagen, can be significantly improved by substituting 2{prime}-O-methylribos methylphosphonate backbones for the current 2{prime}-deoxyribomethylphosphonate backbones. 15 refs., 10 figs., 2 tabs.

  5. Strategies for Integrated Analysis of Genetic, Epigenetic, and Gene Expression Variation in Cancer

    DEFF Research Database (Denmark)

    Thingholm, Louise B; Andersen, Lars; Makalic, Enes

    2016-01-01

    The development and progression of cancer, a collection of diseases with complex genetic architectures, is facilitated by the interplay of multiple etiological factors. This complexity challenges the traditional single-platform study design and calls for an integrated approach to data analysis...... to integration strategies used for analyzing genetic risk factors for cancer. We critically examine the ability of these strategies to handle the complexity of the human genome and also accommodate information about the biological and functional interactions between the elements that have been measured...

  6. Delivery strategies of the CRISPR-Cas9 gene-editing system for therapeutic applications.

    Science.gov (United States)

    Liu, Chang; Zhang, Li; Liu, Hao; Cheng, Kun

    2017-11-28

    The CRISPR-Cas9 genome-editing system is a part of the adaptive immune system in archaea and bacteria to defend against invasive nucleic acids from phages and plasmids. The single guide RNA (sgRNA) of the system recognizes its target sequence in the genome, and the Cas9 nuclease of the system acts as a pair of scissors to cleave the double strands of DNA. Since its discovery, CRISPR-Cas9 has become the most robust platform for genome engineering in eukaryotic cells. Recently, the CRISPR-Cas9 system has triggered enormous interest in therapeutic applications. CRISPR-Cas9 can be applied to correct disease-causing gene mutations or engineer T cells for cancer immunotherapy. The first clinical trial using the CRISPR-Cas9 technology was conducted in 2016. Despite the great promise of the CRISPR-Cas9 technology, several challenges remain to be tackled before its successful applications for human patients. The greatest challenge is the safe and efficient delivery of the CRISPR-Cas9 genome-editing system to target cells in human body. In this review, we will introduce the molecular mechanism and different strategies to edit genes using the CRISPR-Cas9 system. We will then highlight the current systems that have been developed to deliver CRISPR-Cas9 in vitro and in vivo for various therapeutic purposes. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Gene therapy strategy to reduced bone marrow aplasia: evaluation in cynomolgus macaque exposed to a gamma total body irradiation

    International Nuclear Information System (INIS)

    Becard, N.

    2003-01-01

    The aim of this work was to assess whether direct intra-marrow injection of an adeno-viral vector expressing human IL-1α gene stimulates hematopoiesis in healthy non-irradiated and gamma irradiated cynomolgus macaques. In the first hand, we have evaluated the feasibility of this gene therapy strategy in two healthy non-irradiated macaques. In this work, we have observed an increase of neutrophil, monocyte and platelets in the two animals treated with the therapeutic construct. This effect was associated with no abnormal clinical side effect. On the other hand, we have evaluated this strategy in non-human primate exposed to a sublethal gamma irradiation. Two of three animals treated by the therapeutic construct reduced significantly the neutropenia, thrombocytopenia and anemia radio-induced. In conclusion, this gene therapy strategy gave a similar clinical benefit comparatively to systemic administration of huIL-1α but without severe side effect. (author) [fr

  8. Sensemaking and strategy: A planned study

    DEFF Research Database (Denmark)

    Nielsen, Renate

    2000-01-01

    This study adopts a sensemaking perspective to uncover how an organisation improves its competitiveness. By looking at various levels in the organisation, from the individual organisation member via the departments to the management team, the idea is to map the elements involved in sensemaking...... on the various levels, and the influence these have on the organisation's performance and competitiveness. The study will be conducted in a selection of Danish food processing companies....

  9. Cracking the regulatory code of biosynthetic gene clusters as a strategy for natural product discovery.

    Science.gov (United States)

    Rigali, Sébastien; Anderssen, Sinaeda; Naômé, Aymeric; van Wezel, Gilles P

    2018-01-05

    The World Health Organization (WHO) describes antibiotic resistance as "one of the biggest threats to global health, food security, and development today", as the number of multi- and pan-resistant bacteria is rising dangerously. Acquired resistance phenomena also impair antifungals, antivirals, anti-cancer drug therapy, while herbicide resistance in weeds threatens the crop industry. On the positive side, it is likely that the chemical space of natural products goes far beyond what has currently been discovered. This idea is fueled by genome sequencing of microorganisms which unveiled numerous so-called cryptic biosynthetic gene clusters (BGCs), many of which are transcriptionally silent under laboratory culture conditions, and by the fact that most bacteria cannot yet be cultivated in the laboratory. However, brute force antibiotic discovery does not yield the same results as it did in the past, and researchers have had to develop creative strategies in order to unravel the hidden potential of microorganisms such as Streptomyces and other antibiotic-producing microorganisms. Identifying the cis elements and their corresponding transcription factors(s) involved in the control of BGCs through bioinformatic approaches is a promising strategy. Theoretically, we are a few 'clicks' away from unveiling the culturing conditions or genetic changes needed to activate the production of cryptic metabolites or increase the production yield of known compounds to make them economically viable. In this opinion article, we describe and illustrate the idea beyond 'cracking' the regulatory code for natural product discovery, by presenting a series of proofs of concept, and discuss what still should be achieved to increase the rate of success of this strategy. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Studying the Complex Expression Dependences between Sets of Coexpressed Genes

    Directory of Open Access Journals (Sweden)

    Mario Huerta

    2014-01-01

    Full Text Available Organisms simplify the orchestration of gene expression by coregulating genes whose products function together in the cell. The use of clustering methods to obtain sets of coexpressed genes from expression arrays is very common; nevertheless there are no appropriate tools to study the expression networks among these sets of coexpressed genes. The aim of the developed tools is to allow studying the complex expression dependences that exist between sets of coexpressed genes. For this purpose, we start detecting the nonlinear expression relationships between pairs of genes, plus the coexpressed genes. Next, we form networks among sets of coexpressed genes that maintain nonlinear expression dependences between all of them. The expression relationship between the sets of coexpressed genes is defined by the expression relationship between the skeletons of these sets, where this skeleton represents the coexpressed genes with a well-defined nonlinear expression relationship with the skeleton of the other sets. As a result, we can study the nonlinear expression relationships between a target gene and other sets of coexpressed genes, or start the study from the skeleton of the sets, to study the complex relationships of activation and deactivation between the sets of coexpressed genes that carry out the different cellular processes present in the expression experiments.

  11. Flexible Studies as Strategy for Lifelong Learning

    Science.gov (United States)

    Bugge, Liv Susanne; Wikan, Gerd

    2016-01-01

    Many countries face a challenge in recruiting teachers. At the same time, the labour market is changing and the demand for re-education is increasing. In this situation, lifelong learning is seen as relevant and higher education institutions are asked to offer flexible and decentralised study programmes in order to accommodate the need for formal…

  12. Liver steatosis study_PFAA treated mouse gene array data

    Data.gov (United States)

    U.S. Environmental Protection Agency — This file contains a link for Gene Expression Omnibus and the GSE designations for the publicly available gene expression data used in the study and reflected in...

  13. Identification and validation of suitable endogenous reference genes for gene expression studies in human peripheral blood.

    Science.gov (United States)

    Stamova, Boryana S; Apperson, Michelle; Walker, Wynn L; Tian, Yingfang; Xu, Huichun; Adamczy, Peter; Zhan, Xinhua; Liu, Da-Zhi; Ander, Bradley P; Liao, Isaac H; Gregg, Jeffrey P; Turner, Renee J; Jickling, Glen; Lit, Lisa; Sharp, Frank R

    2009-08-05

    Gene expression studies require appropriate normalization methods. One such method uses stably expressed reference genes. Since suitable reference genes appear to be unique for each tissue, we have identified an optimal set of the most stably expressed genes in human blood that can be used for normalization. Whole-genome Affymetrix Human 2.0 Plus arrays were examined from 526 samples of males and females ages 2 to 78, including control subjects and patients with Tourette syndrome, stroke, migraine, muscular dystrophy, and autism. The top 100 most stably expressed genes with a broad range of expression levels were identified. To validate the best candidate genes, we performed quantitative RT-PCR on a subset of 10 genes (TRAP1, DECR1, FPGS, FARP1, MAPRE2, PEX16, GINS2, CRY2, CSNK1G2 and A4GALT), 4 commonly employed reference genes (GAPDH, ACTB, B2M and HMBS) and PPIB, previously reported to be stably expressed in blood. Expression stability and ranking analysis were performed using GeNorm and NormFinder algorithms. Reference genes were ranked based on their expression stability and the minimum number of genes needed for nomalization as calculated using GeNorm showed that the fewest, most stably expressed genes needed for acurate normalization in RNA expression studies of human whole blood is a combination of TRAP1, FPGS, DECR1 and PPIB. We confirmed the ranking of the best candidate control genes by using an alternative algorithm (NormFinder). The reference genes identified in this study are stably expressed in whole blood of humans of both genders with multiple disease conditions and ages 2 to 78. Importantly, they also have different functions within cells and thus should be expressed independently of each other. These genes should be useful as normalization genes for microarray and RT-PCR whole blood studies of human physiology, metabolism and disease.

  14. Identification and validation of suitable endogenous reference genes for gene expression studies in human peripheral blood

    Directory of Open Access Journals (Sweden)

    Turner Renee J

    2009-08-01

    Full Text Available Abstract Background Gene expression studies require appropriate normalization methods. One such method uses stably expressed reference genes. Since suitable reference genes appear to be unique for each tissue, we have identified an optimal set of the most stably expressed genes in human blood that can be used for normalization. Methods Whole-genome Affymetrix Human 2.0 Plus arrays were examined from 526 samples of males and females ages 2 to 78, including control subjects and patients with Tourette syndrome, stroke, migraine, muscular dystrophy, and autism. The top 100 most stably expressed genes with a broad range of expression levels were identified. To validate the best candidate genes, we performed quantitative RT-PCR on a subset of 10 genes (TRAP1, DECR1, FPGS, FARP1, MAPRE2, PEX16, GINS2, CRY2, CSNK1G2 and A4GALT, 4 commonly employed reference genes (GAPDH, ACTB, B2M and HMBS and PPIB, previously reported to be stably expressed in blood. Expression stability and ranking analysis were performed using GeNorm and NormFinder algorithms. Results Reference genes were ranked based on their expression stability and the minimum number of genes needed for nomalization as calculated using GeNorm showed that the fewest, most stably expressed genes needed for acurate normalization in RNA expression studies of human whole blood is a combination of TRAP1, FPGS, DECR1 and PPIB. We confirmed the ranking of the best candidate control genes by using an alternative algorithm (NormFinder. Conclusion The reference genes identified in this study are stably expressed in whole blood of humans of both genders with multiple disease conditions and ages 2 to 78. Importantly, they also have different functions within cells and thus should be expressed independently of each other. These genes should be useful as normalization genes for microarray and RT-PCR whole blood studies of human physiology, metabolism and disease.

  15. Selection of housekeeping genes for gene expression studies in human reticulocytes using real-time PCR

    Science.gov (United States)

    Silver, Nicholas; Best, Steve; Jiang, Jie; Thein, Swee Lay

    2006-01-01

    Background Control genes, which are often referred to as housekeeping genes, are frequently used to normalise mRNA levels between different samples. However, the expression level of these genes may vary among tissues or cells and may change under certain circumstances. Thus, the selection of housekeeping genes is critical for gene expression studies. To address this issue, 7 candidate housekeeping genes including several commonly used ones were investigated in isolated human reticulocytes. For this, a simple ΔCt approach was employed by comparing relative expression of 'pairs of genes' within each sample. On this basis, stability of the candidate housekeeping genes was ranked according to repeatability of the gene expression differences among 31 samples. Results Initial screening of the expression pattern demonstrated that 1 of the 7 genes was expressed at very low levels in reticulocytes and was excluded from further analysis. The range of expression stability of the other 6 genes was (from most stable to least stable): GAPDH (glyceraldehyde 3-phosphate dehydrogenase), SDHA (succinate dehydrogenase), HPRT1 (hypoxanthine phosphoribosyl transferase 1), HBS1L (HBS1-like protein) and AHSP (alpha haemoglobin stabilising protein), followed by B2M (beta-2-microglobulin). Conclusion Using this simple approach, GAPDH was found to be the most suitable housekeeping gene for expression studies in reticulocytes while the commonly used B2M should be avoided. PMID:17026756

  16. Reference genes for gene expression studies in wheat flag leaves grown under different farming conditions

    Directory of Open Access Journals (Sweden)

    Cordeiro Raposo Fernando

    2011-09-01

    Full Text Available Abstract Background Internal control genes with highly uniform expression throughout the experimental conditions are required for accurate gene expression analysis as no universal reference genes exists. In this study, the expression stability of 24 candidate genes from Triticum aestivum cv. Cubus flag leaves grown under organic and conventional farming systems was evaluated in two locations in order to select suitable genes that can be used for normalization of real-time quantitative reverse-transcription PCR (RT-qPCR reactions. The genes were selected among the most common used reference genes as well as genes encoding proteins involved in several metabolic pathways. Findings Individual genes displayed different expression rates across all samples assayed. Applying geNorm, a set of three potential reference genes were suitable for normalization of RT-qPCR reactions in winter wheat flag leaves cv. Cubus: TaFNRII (ferredoxin-NADP(H oxidoreductase; AJ457980.1, ACT2 (actin 2; TC234027, and rrn26 (a putative homologue to RNA 26S gene; AL827977.1. In addition of these three genes that were also top-ranked by NormFinder, two extra genes: CYP18-2 (Cyclophilin A, AY456122.1 and TaWIN1 (14-3-3 like protein, AB042193 were most consistently stably expressed. Furthermore, we showed that TaFNRII, ACT2, and CYP18-2 are suitable for gene expression normalization in other two winter wheat varieties (Tommi and Centenaire grown under three treatments (organic, conventional and no nitrogen and a different environment than the one tested with cv. Cubus. Conclusions This study provides a new set of reference genes which should improve the accuracy of gene expression analyses when using wheat flag leaves as those related to the improvement of nitrogen use efficiency for cereal production.

  17. The Study of Frequency Self Care Strategies against Auditory Hallucinations

    Directory of Open Access Journals (Sweden)

    Mahin Nadem

    2012-03-01

    Full Text Available Background: In schizophrenic clients, self-care strategies against auditory hallucinations can decrease disturbances results in hallucination. This study was aimed to assess frequency of self-care strategies against auditory hallucinations in paranoid schizophrenic patients, hospitalized in Shafa Hospital.Materials and Method: This was a descriptive study on 201 patients with paranoid schizophrenia hospitalized in psychiatry unit with convenience sampling in Rasht. The gathered data consists of two parts, first unit demographic characteristic and the second part, self- report questionnaire include 38 items about self-care strategies.Results: There were statistically significant relationship between demographic variables and knowledg effect and self-care strategies against auditory hallucinaions. Sex with phisical domain p0.07, marriage status with cognitive domain (p>0.07 and life status with behavioural domain (p>0.01. 53.2% of reported type of our auditory hallucinations were command hallucinations, furtheremore the most effective self-care strategies against auditory hallucinations were from physical domain and substance abuse (82.1% was the most effective strategies in this domain.Conclusion: The client with paranoid schizophrenia used more than physical domain strategies against auditory hallucinaions and this result highlight need those to approprait nursing intervention. Instruction and leading about selection the effective self-care strategies against auditory ha

  18. A Generally Applicable Translational Strategy Identifies S100A4 as a Candidate Gene in Allergy

    DEFF Research Database (Denmark)

    Bruhn, Sören; Fang, Yu; Barrenäs, Fredrik

    2014-01-01

    The identification of diagnostic markers and therapeutic candidate genes in common diseases is complicated by the involvement of thousands of genes. We hypothesized that genes co-regulated with a key gene in allergy, IL13, would form a module that could help to identify candidate genes. We identi...

  19. Development and evaluation of a rapid strategy to determine enterotoxin gene content in Staphylococcus aureus.

    Science.gov (United States)

    Fischer, Adrien; Francois, Patrice; Holtfreter, Silva; Broeker, Barbara; Schrenzel, Jacques

    2009-05-01

    Enterotoxins of S. aureus are important molecules displaying superantigenic properties. To date no less than 18 enterotoxins have been identified in S. aureus and their role has been documented in very diverse diseases. Using available nucleotide sequence information, we developed a rapid and automated PCR-based approach to evaluate enterotoxin content in S aureus. We studied a collection of S. aureus strains previously analyzed for enterotoxins gene content and report a perfect correlation between simplex and multiplex PCR assays for the presence of all enterotoxin genes described so far. The determination of enterotoxin content relies on 4 multiplex PCR tubes whose amplification products are resolved by a rapid microcapillary electrophoresis. Automated analysis of the PCR profiles evaluates for the presence of the 18 enterotoxin genes in less than 3 h and at moderate cost. Finally, the use of enterotoxin gene content for genotyping purpose was compared to multi-locus variable number of tandem repeat assay and spa genotyping. Analysis revealed an important homogeneity of the genetic backgrounds for strains harboring the egc cluster as well as a large diversity for strains harboring other enterotoxins but lacking the egc cluster. A combined genotyping method that includes rapid enterotoxin content determination appears informative for various epidemiological survey purposes.

  20. Statistical Analysis of Cooperative Strategy Compared with Individualistic Strategy: An Application Study

    Science.gov (United States)

    Saleh, Tawfik A.

    2011-01-01

    The study investigates the effect of cooperative and individualistic learning strategies on the academic performance of students in the general chemistry laboratory. The samples of the study were divided into experimental and control groups. The hypotheses were first generated and, after collecting data, analyzed by an analysis of t-test at an a =…

  1. A new strategy for exploring the hierarchical structure of cancers by adaptively partitioning functional modules from gene expression network.

    Science.gov (United States)

    Xu, Junmei; Jing, Runyu; Liu, Yuan; Dong, Yongcheng; Wen, Zhining; Li, Menglong

    2016-06-28

    The interactions among the genes within a disease are helpful for better understanding the hierarchical structure of the complex biological system of it. Most of the current methodologies need the information of known interactions between genes or proteins to create the network connections. However, these methods meet the limitations in clinical cancer researches because different cancers not only share the common interactions among the genes but also own their specific interactions distinguished from each other. Moreover, it is still difficult to decide the boundaries of the sub-networks. Therefore, we proposed a strategy to construct a gene network by using the sparse inverse covariance matrix of gene expression data, and divide it into a series of functional modules by an adaptive partition algorithm. The strategy was validated by using the microarray data of three cancers and the RNA-sequencing data of glioblastoma. The different modules in the network exhibited specific functions in cancers progression. Moreover, based on the gene expression profiles in the modules, the risk of death was well predicted in the clustering analysis and the binary classification, indicating that our strategy can be benefit for investigating the cancer mechanisms and promoting the clinical applications of network-based methodologies in cancer researches.

  2. Selection of reliable reference genes for gene expression studies in peach using real-time PCR

    Directory of Open Access Journals (Sweden)

    Zhou Jun

    2009-07-01

    Full Text Available Abstract Background RT-qPCR is a preferred method for rapid and reliable quantification of gene expression studies. Appropriate application of RT-qPCR in such studies requires the use of reference gene(s as an internal control to normalize mRNA levels between different samples for an exact comparison of gene expression level. However, recent studies have shown that no single reference gene is universal for all experiments. Thus, the identification of high quality reference gene(s is of paramount importance for the interpretation of data generated by RT-qPCR. Only a few studies on reference genes have been done in plants and none in peach (Prunus persica L. Batsch. Therefore, the present study was conducted to identify suitable reference gene(s for normalization of gene expression in peach. Results In this work, eleven reference genes were investigated in different peach samples using RT-qPCR with SYBR green. These genes are: actin 2/7 (ACT, cyclophilin (CYP2, RNA polymerase II (RP II, phospholipase A2 (PLA2, ribosomal protein L13 (RPL13, glyceraldehyde-3-phosphate dehydrogenase (GAPDH, 18S ribosomal RNA (18S rRNA, tubblin beta (TUB, tubblin alpha (TUA, translation elongation factor 2 (TEF2 and ubiquitin 10 (UBQ10. All eleven reference genes displayed a wide range of Cq values in all samples, indicating that they expressed variably. The stability of these genes except for RPL13 was determined by three different descriptive statistics, geNorm, NormFinder and BestKeeper, which produced highly comparable results. Conclusion Our study demonstrates that expression stability varied greatly between genes studied in peach. Based on the results from geNorm, NormFinder and BestKeeper analyses, for all the sample pools analyzed, TEF2, UBQ10 and RP II were found to be the most suitable reference genes with a very high statistical reliability, and TEF2 and RP II for the other sample series, while 18S rRNA, RPL13 and PLA2 were unsuitable as internal controls

  3. Processes in arithmetic strategy selection: a fMRI study.

    Science.gov (United States)

    Taillan, Julien; Ardiale, Eléonore; Anton, Jean-Luc; Nazarian, Bruno; Félician, Olivier; Lemaire, Patrick

    2015-01-01

    This neuroimaging (functional magnetic resonance imaging) study investigated neural correlates of strategy selection. Young adults performed an arithmetic task in two different conditions. In both conditions, participants had to provide estimates of two-digit multiplication problems like 54 × 78. In the choice condition, participants had to select the better of two available rounding strategies, rounding-up (RU) strategy (i.e., doing 60 × 80 = 4,800) or rounding-down (RD) strategy (i.e., doing 50 × 70 = 3,500 to estimate product of 54 × 78). In the no-choice condition, participants did not have to select strategy on each problem but were told which strategy to use; they executed RU and RD strategies each on a series of problems. Participants also had a control task (i.e., providing correct products of multiplication problems like 40 × 50). Brain activations and performance were analyzed as a function of these conditions. Participants were able to frequently choose the better strategy in the choice condition; they were also slower when they executed the difficult RU than the easier RD. Neuroimaging data showed greater brain activations in right anterior cingulate cortex (ACC), dorso-lateral prefrontal cortex (DLPFC), and angular gyrus (ANG), when selecting (relative to executing) the better strategy on each problem. Moreover, RU was associated with more parietal cortex activation than RD. These results suggest an important role of fronto-parietal network in strategy selection and have important implications for our further understanding and modeling cognitive processes underlying strategy selection.

  4. Processes in arithmetic strategy selection: A fMRI study.

    Directory of Open Access Journals (Sweden)

    Julien eTaillan

    2015-02-01

    Full Text Available This neuroimaging (fMRI study investigated neural correlates of strategy selection. Young adults performed an arithmetic task in two different conditions. In both conditions, participants had to provide estimates of two-digit multiplication problems like 54 x 78. In the choice condition, participants had to select the better of two available rounding strategies, rounding-up strategy (RU (i.e., doing 60x80 = 4,800 or rounding-down strategy (RD (i.e., doing 50x70=3,500 to estimate product of 54x78. In the no-choice condition, participants did not have to select strategy on each problem but were told which strategy to use; they executed RU and RD strategies each on a series of problems. Participants also had a control task (i.e., providing correct products of multiplication problems like 40x50. Brain activations and performance were analyzed as a function of these conditions. Participants were able to frequently choose the better strategy in the choice condition; they were also slower when they executed the difficult RU than the easier RD. Neuroimaging data showed greater brain activations in right anterior cingulate cortex (ACC, dorso-lateral prefrontal cortex (DLPFC, and angular gyrus (ANG, when selecting (relative to executing the better strategy on each problem. Moreover, RU was associated with more parietal cortex activation than RD. These results suggest an important role of fronto-parietal network in strategy selection and have important implications for our further understanding and modelling cognitive processes underlying strategy selection.

  5. Optimizing the 3R study strategy to learn from text

    NARCIS (Netherlands)

    Reijners, Pauline; Kester, Liesbeth; Wetzels, Sandra; Kirschner, Paul A.

    2013-01-01

    Reijners, P. B. G., Kester, L., Wetzels, S. A. J., & Kirschner, P. A. (2013, 29 May). Optimizing the 3R study strategy to learn from text. Presentation at plenary meeting Learning & Cogntion, Heerlen, The Netherlands.

  6. Optimizing the 3R study strategy to learn from text

    NARCIS (Netherlands)

    Reijners, Pauline; Kester, Liesbeth; Wetzels, Sandra; Kirschner, Paul A.

    2013-01-01

    Reijners, P. B. G., Kester, L., Wetzels, S. A. J., & Kirschner, P. A. (2013, 7 November). Optimizing the 3R study strategy to learn from text. Paper presented at the ICO National Fall School, Maastricht, The Netherlands.

  7. Optimizing the 3R study strategy to learn from text

    NARCIS (Netherlands)

    Reijners, Pauline; Kester, Liesbeth; Wetzels, Sandra; Kirschner, Paul A.

    2012-01-01

    Reijners, P. B. G., Kester, L., Wetzels, S. A. J., & Kirschner, P. A. (2012, 21 November). Optimizing the 3R study strategy to learn from text. Presentation at research meeting Educational and Developmental Psychology, Erasmus University, Rotterdam, The Netherlands.

  8. Drug Induced Hearing Loss: Researchers Study Strategies to Preserve Hearing

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Drug-Induced Hearing Loss Researchers Study Strategies to Preserve ... brain there was a sound. What are ototoxic drugs and why are they important? Ototoxic drugs are ...

  9. Gene inactivation in the plant pathogen Glomerella cingulata: three strategies for the disruption of the pectin lyase gene pnlA.

    Science.gov (United States)

    Bowen, J K; Templeton, M D; Sharrock, K R; Crowhurst, R N; Rikkerink, E H

    1995-01-20

    The feasibility of performing routine transformation-mediated mutagenesis in Glomerella cingulata was analysed by adopting three one-step gene disruption strategies targeted at the pectin lyase gene pnlA. The efficiencies of disruption following transformation with gene replacement- or gene truncation-disruption vectors were compared. To effect replacement-disruption, G. cingulata was transformed with a vector carrying DNA from the pnlA locus in which the majority of the coding sequence had been replaced by the gene for hygromycin B resistance. Two of the five transformants investigated contained an inactivated pnlA gene (pnlA-); both also contained ectopically integrated vector sequences. The efficacy of gene disruption by transformation with two gene truncation-disruption vectors was also assessed. Both vectors carried at 5' and 3' truncated copy of the pnlA coding sequence, adjacent to the gene for hygromycin B resistance. The promoter sequences controlling the selectable marker differed in the two vectors. In one vector the homologous G. cingulata gpdA promoter controlled hygromycin B phosphotransferase expression (homologous truncation vector), whereas in the second vector promoter elements were from the Aspergillus nidulans gpdA gene (heterologous truncation vector). Following transformation with the homologous truncation vector, nine transformants were analysed by Southern hybridisation; no transformants contained a disrupted pnlA gene. Of nineteen heterologous truncation vector transformants, three contained a disrupted pnlA gene; Southern analysis revealed single integrations of vector sequence at pnlA in two of these transformants. pnlA mRNA was not detected by Northern hybridisation in pnlA- transformants. pnlA- transformants failed to produce a PNLA protein with a pI identical to one normally detected in wild-type isolates by silver and activity staining of isoelectric focussing gels. Pathogenesis on Capsicum and apple was unaffected by disruption of

  10. The Plasmodium falciparum var gene transcription strategy at the onset of blood stage infection in a human volunteer

    DEFF Research Database (Denmark)

    Wang, Christian W; Hermsen, Cornelus C; Sauerwein, Robert W

    2009-01-01

    transcript distribution of var genes in a P. falciparum-infected non-immune individual and show that the initial expression of PfEMP1 is based on a strategy that allows all or most variants of PfEMP1s to be expressed by the parasite population at the onset of the blood stage infection.......The var genes encode a family of adhesion receptor proteins, Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), which profoundly influence malaria pathogenesis. Only a single var gene is transcribed and one PfEMP1 expressed per P.falciparum parasite. Here we present the in vivo...

  11. Beyond Gene Delivery: Strategies to Engineer the Surfaces of Viral Vectors

    OpenAIRE

    Capasso, Cristian; Hirvinen, Mari; Cerullo, Vincenzo

    2013-01-01

    Viral vectors have been extensively studied due to their great transduction efficiency compared to non-viral vectors. These vectors have been used extensively in gene therapy, enabling the comprehension of, not only the advantages of these vectors, but also the limitations, such as the activation of the immune system after vector administration. Moreover, the need to control the target of the vector has led to the development of chemical and non-chemical modifications of the vector surface, a...

  12. Does fragmentation of wetlands affect gene flow in sympatric Acrocephalus warblers with different migration strategies?

    OpenAIRE

    Ceresa, Francesco; Belda, E.J.; Kvist, Laura; Rguibi-Idrissi, Hamid; Monrós González, Juan Salvador

    2015-01-01

    Wetlands are naturally patchy habitats, but patchiness has been accentuated by the extensive wetlands loss due to human activities. In such a fragmented habitat, dispersal ability is especially important to maintain gene flow between populations. Here we studied population structure, genetic diversity and demographic history of Iberian and North African populations of two wetland passerines, the Eurasian reed warbler Acrocephalus scirpaceus and the moustached warbler Acrocephalus melanopogon....

  13. Study Strategies Comparison and Self-Regulationin University Students

    Directory of Open Access Journals (Sweden)

    Irma Rosa Alvarado Guerrero

    2014-04-01

    Full Text Available The main factors associated with academic performance are study strategies and self-regulation in university students, thus the objective of this paper is to compare two sample groups: those in a regular status and others under certain academic lag. The Study Strategies Inventory and Self-Regulation (IEEA BY Castaneda was applied to 41 learners. It was observed that both groups need support to develop strategies for the four scales of the instrument: Information acquisition, memory resource management, information processing and self-regulation in all three dimensions: people, tasks and materials. In conclusion there is a need to develop programs to help the consolidation of study strategies and self-regulation and highlights the importance of analyzing the factors in teacher’s education and development of programs and curricula, to improve academic performance in higher educationinstitutions.

  14. Validation of housekeeping genes for studying differential gene expression in the bovine myometrium.

    Science.gov (United States)

    Rekawiecki, Robert; Kowalik, Magdalena K; Kotwica, Jan

    2013-12-01

    The aim of this study was to determine the steady-state expression of 13 selected housekeeping genes in the myometrium of cyclic and pregnant cows. Cells taken from bovine myometrium on days 1-5, 6-10, 11-16 and 17-20 of the oestrous cycle and in weeks 3-5, 6-8 and 9-12 of pregnancy were used. Reverse transcribed RNA was amplified in real-time PCR using designed primers. Reaction efficiency was determined with the Linreg programme. The geNorm and NormFinder programmes were used to select the best housekeeping genes. They calculate the expression stability factor for each used housekeeping gene with the smallest value for most stably expressed genes. According to geNorm, the most stable housekeeping genes in the myometrium were C2orf29, TPB and TUBB2B, while the least stably expressed genes were 18S RNA, HPRT1 and GAPDH. NormFinder identified the best genes in the myometrium as C2orf29, MRPL12 and TBP, while the worst genes were 18S RNA, B2M and SF3A1. Differences in stability factors between the two programmes may also indicate that the physiological status of the female, e.g. pregnancy, affects the stability of expression of housekeeping genes. The different expression stability of housekeeping genes did not affect progesterone receptor expression but it could be important if small differences in gene expression were measured between studies.

  15. Identification of reference genes in human myelomonocytic cells for gene expression studies in altered gravity.

    Science.gov (United States)

    Thiel, Cora S; Hauschild, Swantje; Tauber, Svantje; Paulsen, Katrin; Raig, Christiane; Raem, Arnold; Biskup, Josefine; Gutewort, Annett; Hürlimann, Eva; Unverdorben, Felix; Buttron, Isabell; Lauber, Beatrice; Philpot, Claudia; Lier, Hartwin; Engelmann, Frank; Layer, Liliana E; Ullrich, Oliver

    2015-01-01

    Gene expression studies are indispensable for investigation and elucidation of molecular mechanisms. For the process of normalization, reference genes ("housekeeping genes") are essential to verify gene expression analysis. Thus, it is assumed that these reference genes demonstrate similar expression levels over all experimental conditions. However, common recommendations about reference genes were established during 1 g conditions and therefore their applicability in studies with altered gravity has not been demonstrated yet. The microarray technology is frequently used to generate expression profiles under defined conditions and to determine the relative difference in expression levels between two or more different states. In our study, we searched for potential reference genes with stable expression during different gravitational conditions (microgravity, normogravity, and hypergravity) which are additionally not altered in different hardware systems. We were able to identify eight genes (ALB, B4GALT6, GAPDH, HMBS, YWHAZ, ABCA5, ABCA9, and ABCC1) which demonstrated no altered gene expression levels in all tested conditions and therefore represent good candidates for the standardization of gene expression studies in altered gravity.

  16. Relationships between strategy switching and strategy switch costs in young and older adults: a study in arithmetic problem solving.

    Science.gov (United States)

    Taillan, Julien; Ardiale, Eléonore; Lemaire, Patrick

    2015-01-01

    BACKGROUND/STUDY CONTEXT: This study investigated age-related differences in within-item strategy switching (i.e., revising initial strategy choices to select a better strategy while solving a given problem) and in strategy switch costs (i.e., longer latencies when participants switch strategies than when they do not switch strategy during strategy execution). In a computational estimation task, participants had to give approximate products to two-digit multiplication problems (e.g., 41×67) while rounding up (i.e., do 50×70 for 41×67) or rounding down (i.e., do 40×60 for 41×67) operands to their nearest decades. After executing a cued strategy during 1000 ms, participants had the possibility to switch to another strategy (or repeat the same strategy) in a selection condition. In an execution condition, participants were forced to repeat the same strategy or to switch to another strategy. It was found that (1) older adults were less able than young adults to switch strategy after starting to execute a cued strategy (36.1% vs. 45.8%); (2) older adults showed larger switch costs than young adults (422 vs. 223 ms); and (3) strategy switches and strategy switch costs correlated in older adults but not in young adults. These findings have important implications for our understanding of the mechanisms underlying within-item strategy switching and aging effects on these mechanisms as well as, more generally, of strategic variations during cognitive aging.

  17. Evaluation of suitable reference genes for gene expression studies in bovine muscular tissue

    Directory of Open Access Journals (Sweden)

    Dunner Susana

    2008-09-01

    Full Text Available Abstract Background Real-time reverse transcriptase quantitative polymerase chain reaction (real-time RTqPCR is a technique used to measure mRNA species copy number as a way to determine key genes involved in different biological processes. However, the expression level of these key genes may vary among tissues or cells not only as a consequence of differential expression but also due to different factors, including choice of reference genes to normalize the expression levels of the target genes; thus the selection of reference genes is critical for expression studies. For this purpose, ten candidate reference genes were investigated in bovine muscular tissue. Results The value of stability of ten candidate reference genes included in three groups was estimated: the so called 'classical housekeeping' genes (18S, GAPDH and ACTB, a second set of genes used in expression studies conducted on other tissues (B2M, RPII, UBC and HMBS and a third set of novel genes (SF3A1, EEF1A2 and CASC3. Three different statistical algorithms were used to rank the genes by their stability measures as produced by geNorm, NormFinder and Bestkeeper. The three methods tend to agree on the most stably expressed genes and the least in muscular tissue. EEF1A2 and HMBS followed by SF3A1, ACTB, and CASC3 can be considered as stable reference genes, and B2M, RPII, UBC and GAPDH would not be appropriate. Although the rRNA-18S stability measure seems to be within the range of acceptance, its use is not recommended because its synthesis regulation is not representative of mRNA levels. Conclusion Based on geNorm algorithm, we propose the use of three genes SF3A1, EEF1A2 and HMBS as references for normalization of real-time RTqPCR in muscle expression studies.

  18. Beyond Gene Delivery: Strategies to Engineer the Surfaces of Viral Vectors

    Directory of Open Access Journals (Sweden)

    Cristian Capasso

    2013-12-01

    Full Text Available Viral vectors have been extensively studied due to their great transduction efficiency compared to non-viral vectors. These vectors have been used extensively in gene therapy, enabling the comprehension of, not only the advantages of these vectors, but also the limitations, such as the activation of the immune system after vector administration. Moreover, the need to control the target of the vector has led to the development of chemical and non-chemical modifications of the vector surface, allowing researchers to modify the tropism and biodistribution profile of the vector, leading to the production of viral vectors able to target different tissues and organs. This review describes recent non-genetic modifications of the surfaces of viral vectors to decrease immune system activation and to control tissue targeting. The developments described herein provide opportunities for applications of gene therapy to treat acquired disorders and genetic diseases and to become useful tools in regenerative medicine.

  19. Strategie di rifuto in Italiano: uno studio etnografico (Refusal Strategies in Italian: An Ethnographic Study).

    Science.gov (United States)

    Frescura, Marina

    1997-01-01

    After reviewing previous research on speech acts, this article describes a study that analyzed the behavior of speakers of standard Italian in refusing an offer of food. The importance of "face" is explained, and the refusal strategies are classified into four categories: explicit, tactical, decisive, and conclusive. (CFM)

  20. Non-viral gene delivery strategies for gene therapy: a “ménage à trois” among nucleic acids, materials, and the biological environment

    International Nuclear Information System (INIS)

    Pezzoli, Daniele; Candiani, Gabriele

    2013-01-01

    Gene delivery is the science of transferring genetic material into cells by means of a vector to alter cellular function or structure at a molecular level. In this context, a number of nucleic acid-based drugs have been proposed and experimented so far and, as they act on distinct steps along the gene transcription–translation pathway, specific delivery strategies are required to elicit the desired outcome. Cationic lipids and polymers, collectively known as non-viral delivery systems, have thus made their breakthrough in basic and medical research. Albeit they are promising alternatives to viral vectors, their therapeutic application is still rather limited as high transfection efficiencies are normally associated to adverse cytotoxic side effects. In this scenario, drawing inspiration from processes naturally occurring in vivo, major strides forward have been made in the development of more effective materials for gene delivery applications. Specifically, smart vectors sensitive to a variety of physiological stimuli such as cell enzymes, redox status, and pH are substantially changing the landscape of gene delivery by helping to overcome some of the systemic and intracellular barriers that viral vectors naturally evade. Herein, after summarizing the state-of-the-art information regarding the use of nucleic acids as drugs, we review the main bottlenecks still limiting the overall effectiveness of non-viral gene delivery systems. Finally, we provide a critical outline of emerging stimuli-responsive strategies and discuss challenges still existing on the road toward conceiving more efficient and safer multifunctional vectors.

  1. A direct gene transfer strategy via brain internal capsule reverses the biochemical defect in Tay-Sachs disease.

    Science.gov (United States)

    Martino, S; Marconi, P; Tancini, B; Dolcetta, D; De Angelis, M G Cusella; Montanucci, P; Bregola, G; Sandhoff, K; Bordignon, C; Emiliani, C; Manservigi, R; Orlacchio, A

    2005-08-01

    Therapy for neurodegenerative lysosomal Tay-Sachs (TS) disease requires active hexosaminidase (Hex) A production in the central nervous system and an efficient therapeutic approach that can act faster than human disease progression. We combined the efficacy of a non-replicating Herpes simplex vector encoding for the Hex A alpha-subunit (HSV-T0alphaHex) and the anatomic structure of the brain internal capsule to distribute the missing enzyme optimally. With this gene transfer strategy, for the first time, we re-established the Hex A activity and totally removed the GM2 ganglioside storage in both injected and controlateral hemispheres, in the cerebellum and spinal cord of TS animal model in the span of one month's treatment. In our studies, no adverse effects were observed due to the viral vector, injection site or gene expression and on the basis of these results, we feel confident that the same approach could be applied to similar diseases involving an enzyme defect.

  2. Marketing strategies: Study in travel agencies and tourism sector

    OpenAIRE

    Aléssio Bessa Sarquis; Nádia Pizzinatto; Antônio Carlos Giuliani; Andréa Simone Machiavelli Pontes

    2015-01-01

    The tourism sector has an important economic and social role and marketing strategies can help improve the market performance of service organizations. Thus, the study analyzed the marketing strategies applied in the travel agency services sector in the state of Santa Catarina and, therefore, a quantitative, descriptive inconclusive and in the form of field survey (survey) was applied with self-administered questionnaires available in the Google Docs platform for a sample of 109 emissive agen...

  3. 3p22.1p21.31 microdeletion identifies CCK as Asperger syndrome candidate gene and shows the way for therapeutic strategies in chromosome imbalances.

    Science.gov (United States)

    Iourov, Ivan Y; Vorsanova, Svetlana G; Voinova, Victoria Y; Yurov, Yuri B

    2015-01-01

    In contrast to other autism spectrum disorders, chromosome abnormalities are rare in Asperger syndrome (AS) or high-functioning autism. Consequently, AS was occasionally subjected to classical positional cloning. Here, we report on a case of AS associated with a deletion of the short arm of chromosome 3. Further in silico analysis has identified a candidate gene for AS and has suggested a therapeutic strategy for manifestations of the chromosome rearrangement. Using array comparative genomic hybridization, an interstitial deletion of 3p22.1p21.31 (~2.5 Mb in size) in a child with Asperger's syndrome, seborrheic dermatitis and chronic pancreatitis was detected. Original bioinformatic approach to the prioritization of candidate genes/processes identified CCK (cholecystokinin) as a candidate gene for AS. In addition to processes associated with deleted genes, bioinformatic analysis of CCK gene interactome indicated that zinc deficiency might be a pathogenic mechanism in this case. This suggestion was supported by plasma zinc concentration measurements. The increase of zinc intake produced a rise in zinc plasma concentration and the improvement in the patient's condition. Our study supported previous linkage findings and had suggested a new candidate gene in AS. Moreover, bioinformatic analysis identified the pathogenic mechanism, which was used to propose a therapeutic strategy for manifestations of the deletion. The relative success of this strategy allows speculating that therapeutic or dietary normalization of metabolic processes altered by a chromosome imbalance or genomic copy number variations may be a way for treating at least a small proportion of cases of these presumably incurable genetic conditions.

  4. A search strategy for occupational health intervention studies

    NARCIS (Netherlands)

    Verbeek, J.; Salmi, J.; Pasternack, I.; Jauhiainen, M.; Laamanen, I.; Schaafsma, F.; Hulshof, C.; van Dijk, F.

    2005-01-01

    As a result of low numbers and diversity in study type, occupational health intervention studies are not easy to locate in electronic literature databases. To develop a search strategy that facilitates finding occupational health intervention studies in Medline, both for researchers and

  5. Opinions and Strategies in Mainstreaming Gender Studies in ...

    African Journals Online (AJOL)

    Nekky Umera

    institutions in mainstreaming gender education as a GST/GSS course. It also examines opinions and strategies in mainstreaming gender studies in our tertiary institutions. Research Questions. The following research questions are formulated to guide the study: 1. Does successful inclusion of Gender Studies in tertiary ...

  6. Distinct Gene Expression and Epigenetic Signatures in Hepatocyte-like Cells Produced by Different Strategies from the Same Donor

    Directory of Open Access Journals (Sweden)

    Yimeng Gao

    2017-12-01

    Full Text Available Summary: Hepatocyte-like cells (HLCs can be generated through directed differentiation or transdifferentiation. Employing two strategies, we generated induced pluripotent stem cell (iPSC-HLCs and hiHeps from the same donor cell line. Both types of HLCs clustered distinctly from each other during gene expression profiling. In particular, differences existed in gene expression for phase II drug metabolism and lipid accumulation, underpinned by H3K27 acetylation status in iPSC-HLCs and hiHeps. While distinct phenotypes were achieved in vitro, both types of HLCs demonstrated similar phenotypes following transplantation into Fah-deficient mice. In conclusion, functional HLCs can be obtained from the same donor using two strategies. Global gene expression defined the differences between those populations in vitro. Importantly, both HLCs displayed partial but markedly improved hepatic function following transplantation in vivo, demonstrating plasticity and the potential for cell-based modeling in the dish and cell-based therapy in the future. : In this article, Hui and colleagues show that hiHeps and iPSC-HLCs generated from the same donor display different gene expression patterns that correlate with their hepatic functions. Distinct H3K27ac modifications partially explain the functional differences between the two types of HLCs. Importantly, both HLCs show improved hepatic gene expression after repopulation in murine livers. Keywords: transdifferentiation, directed differentiation, hepatocyte-like cells, gene expression pattern

  7. A Comparative Study on Multifactor Dimensionality Reduction Methods for Detecting Gene-Gene Interactions with the Survival Phenotype.

    Science.gov (United States)

    Lee, Seungyeoun; Kim, Yongkang; Kwon, Min-Seok; Park, Taesung

    2015-01-01

    Genome-wide association studies (GWAS) have extensively analyzed single SNP effects on a wide variety of common and complex diseases and found many genetic variants associated with diseases. However, there is still a large portion of the genetic variants left unexplained. This missing heritability problem might be due to the analytical strategy that limits analyses to only single SNPs. One of possible approaches to the missing heritability problem is to consider identifying multi-SNP effects or gene-gene interactions. The multifactor dimensionality reduction method has been widely used to detect gene-gene interactions based on the constructive induction by classifying high-dimensional genotype combinations into one-dimensional variable with two attributes of high risk and low risk for the case-control study. Many modifications of MDR have been proposed and also extended to the survival phenotype. In this study, we propose several extensions of MDR for the survival phenotype and compare the proposed extensions with earlier MDR through comprehensive simulation studies.

  8. A Comparative Study on Multifactor Dimensionality Reduction Methods for Detecting Gene-Gene Interactions with the Survival Phenotype

    Directory of Open Access Journals (Sweden)

    Seungyeoun Lee

    2015-01-01

    Full Text Available Genome-wide association studies (GWAS have extensively analyzed single SNP effects on a wide variety of common and complex diseases and found many genetic variants associated with diseases. However, there is still a large portion of the genetic variants left unexplained. This missing heritability problem might be due to the analytical strategy that limits analyses to only single SNPs. One of possible approaches to the missing heritability problem is to consider identifying multi-SNP effects or gene-gene interactions. The multifactor dimensionality reduction method has been widely used to detect gene-gene interactions based on the constructive induction by classifying high-dimensional genotype combinations into one-dimensional variable with two attributes of high risk and low risk for the case-control study. Many modifications of MDR have been proposed and also extended to the survival phenotype. In this study, we propose several extensions of MDR for the survival phenotype and compare the proposed extensions with earlier MDR through comprehensive simulation studies.

  9. Recent studies on the ATM gene

    International Nuclear Information System (INIS)

    Lavin, M.F.; Khanna, K.K.; Waters, D.

    1996-01-01

    Full text: Radiosensitivity is a universal characteristic of ataxia-telangiectasia (A-T), observed after exposure of patients and of cells in culture to radiation. This sensitivity is manifested as higher levels of radiation-induced chromosomal aberrations and reduced survival compared to controls. The gene for A-T was mapped to chromosome 11q 22-23 seven years ago and more recently we have been involved in the cloning of a single gene, ATM (ataxia-telangiectasia mutated), mutated in this syndrome. ATM is a large gene, approximately 150 kb in size, composed of 66 exons and codes for a major mRNA of 13 kb with a predicted open reading frame of 9.135 kb. It is not yet known what activity the ATM gene product possesses, but the ralatedness of this gene sequence to the phosphatidylinositol 3-kinase gene family supports a role for ATM in intracellular signalling. Considerable information is already available on defective signalling through the p53 damage-inducible pathway in A-T. This includes failure to arrest at either the G1/S or G2/M checkpoints as well as radioresistant DNA synthesis. A reduced and/or delayed response in the induction of p53 after exposure of A-T cells to ionizing radiation can account for the defective G1/S checkpoint. More recently we have demonstrated that the ATM gene product is involved in the control of multiple cell cycle checkpoints. Antibodies prepared against ATM peptides demonstrate the presence of a protein 350 kDa in size, which is the predicted size for this protein based on open reading frame of 9 kb. This protein is present both in the nucleus and in the cytoplasm where it is present in vesicular structures. As expected from mutation data the ATM protein is absent in cells from some patients with A-T. The cloning of the ATM gene will allow for screening of radiosensitive patients for mutations in this gene and will provide a means of identifying interacting proteins and thus an understanding of how it functions

  10. Marketing strategies: Study in travel agencies and tourism sector

    Directory of Open Access Journals (Sweden)

    Aléssio Bessa Sarquis

    2015-08-01

    Full Text Available The tourism sector has an important economic and social role and marketing strategies can help improve the market performance of service organizations. Thus, the study analyzed the marketing strategies applied in the travel agency services sector in the state of Santa Catarina and, therefore, a quantitative, descriptive inconclusive and in the form of field survey (survey was applied with self-administered questionnaires available in the Google Docs platform for a sample of 109 emissive agencies of small and medium. Statistical analyzes were performed by means, frequency, stand-ard deviation and hypothesis testing as the measurement scales applied. The results show that the vast majority of the surveyed agencies use internal marketing strategies, external, interactive and relationship management with clients and midsize agencies use more often most measured marketing strategies.

  11. Are study strategies related to medical licensing exam performance?

    Science.gov (United States)

    West, Courtney; Kurz, Terri; Smith, Sherry; Graham, Lori

    2014-11-02

    To examine the relationship between study strategies and performance on a high stakes medical licensing exam entitled the United States Medical Licensing Examination Step 1. The action research project included seventy nine student participants at the Texas A & M Health Science Center College of Medicine during their pre-clinical education. Data collection included pre-matriculation and matriculation academic performance data, standardized exam data, and the Learning and Study Strategies Instrument. Multiple regression analyses were conducted. For both models, the dependent variable was the Step 1 score, and the independent variables included Medical College Admission Test, Undergraduate Grade Point Average, Year 1 Average, Year 2 Average, Customized National Board of Medical Examiners Average, Comprehensive Basic Science Exam score, and Learning and Study Strategy Instrument sub-scores. Model 2 added Comprehensive Basic Science Self-Assessment average. Concentration (Model 1 - β = .264; Model 2 - β = .254) was the only study strategy correlated with Step 1 performance. The other statistically significant predictors were Customized National Board of Medical Examiners Average (β = .315) and Year 2 Average (β = .280) in Model 1 and Comprehensive Basic Science Self-Assessment Average (β = .338) in Model 2. There does appear to be a relationship between the study strategy concentration and Step 1 licensing exam performance. Teaching students to practice and utilize certain techniques to improve concentration skills when preparing for and taking exams may help improve licensing exam scores.

  12. Strategies for integrated analysis of genetic, epigenetic and gene expression variation in cancer: addressing the challenges

    Directory of Open Access Journals (Sweden)

    Louise Bruun Thingholm

    2016-02-01

    Full Text Available The development and progression of cancer, a collection of diseases with complex genetic architectures, is facilitated by the interplay of multiple etiological factors. This complexity challenges the traditional single-platform study design and calls for an integrated approach to data analysis. However, integration of heterogeneous measurements of biological variation is a non-trivial exercise due to the diversity of the human genome and the variety of output data formats and genome coverage obtained from the commonly used molecular platforms. This review article will provide an introduction to integration strategies used for analyzing genetic risk factors for cancer. We critically examine the ability of these strategies to handle the complexity of the human genome and also accommodate information about the biological and functional interactions between the elements that have been measured – making the assessment of disease risk against a composite genomic factor possible. The focus of this review is to provide an overview and introduction to the main strategies and to discuss where there is a need for further development.

  13. A post hoc study on gene panel analysis for the diagnosis of dystonia.

    Science.gov (United States)

    van Egmond, Martje E; Lugtenberg, Coen H A; Brouwer, Oebele F; Contarino, Maria Fiorella; Fung, Victor S C; Heiner-Fokkema, M Rebecca; van Hilten, Jacobus J; van der Hout, Annemarie H; Peall, Kathryn J; Sinke, Richard J; Roze, Emmanuel; Verschuuren-Bemelmans, Corien C; Willemsen, Michel A; Wolf, Nicole I; Tijssen, Marina A; de Koning, Tom J

    2017-04-01

    Genetic disorders causing dystonia show great heterogeneity. Recent studies have suggested that next-generation sequencing techniques such as gene panel analysis can be effective in diagnosing heterogeneous conditions. The objective of this study was to investigate whether dystonia patients with a suspected genetic cause could benefit from the use of gene panel analysis. In this post hoc study, we describe gene panel analysis results of 61 dystonia patients (mean age, 31 years; 72% young onset) in our tertiary referral center. The panel covered 94 dystonia-associated genes. As comparison with a historic cohort was not possible because of the rapidly growing list of dystonia genes, we compared the diagnostic workup with and without gene panel analysis in the same patients. The workup without gene panel analysis (control group) included theoretical diagnostic strategies formulated by independent experts in the field, based on detailed case descriptions. The primary outcome measure was diagnostic yield; secondary measures were cost and duration of diagnostic workup. Workup with gene panel analysis led to a confirmed molecular diagnosis in 14.8%, versus 7.4% in the control group (P = 0.096). In the control group, on average 3 genes/case were requested. The mean costs were lower in the gene panel analysis group (€1822/case) than in the controls (€2660/case). The duration of the workup was considerably shorter with gene panel analysis (28 vs 102 days). Gene panel analysis facilitates molecular diagnosis in complex cases of dystonia, with a good diagnostic yield (14.8%), a quicker diagnostic workup, and lower costs, representing a major improvement for patients and their families. © 2016 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  14. Gene expression profile study on osteoinductive effect of natural hydroxyapatite.

    Science.gov (United States)

    Lü, Xiaoying; Wang, Jiandan; Li, Bin; Zhang, Zhiwei; Zhao, Lifeng

    2014-08-01

    The aim of this study was to investigate the osteoinductive effect of natural hydroxyapatite (NHA). NHA was extracted from pig bones and prepared into disk-like samples. Then, proliferation of mouse bone mesenchymal stem cells (MSCs) cultured on NHA was assessed by the methylthiazoltetrazolium (MTT) assay. Furthermore, microarray technology was applied to obtain the gene expression profiles of MSCs cultured on NHA at 24, 48, and 72 h. The gene expression profile was then comprehensively analyzed by clustering, Gene Ontology (GO), Gene Microarray Pathway Profiler (GenMAPP) and Ingenuity Pathway Analysis (IPA). According to the results of microarray experiment, 8992 differentially expressed genes were obtained. 90 differential expressed genes related to HA osteogenic differentiation were determined by GO analysis. These genes included not only 6 genes related to HA osteogenic differentiation as mentioned in the literatures but also newly discovered 84 genes. Some important signaling pathways (TGF-β, MAPK, Wnt, etc.) were influenced by these genes. Gene interaction networks were obtained by IPA software, in which the scoring values of two networks were highest, and their main functions were related to cell development. The comprehensive analysis of these results indicate that NHA regulate some crucial genes (e.g., Bmp2, Spp1) and then activate some pathways such as TGF-β signaling pathway, and ultimately osteogenic differentiation was induced. © 2013 Wiley Periodicals, Inc.

  15. Colocalization of coregulated genes: a steered molecular dynamics study of human chromosome 19.

    Directory of Open Access Journals (Sweden)

    Marco Di Stefano

    Full Text Available The connection between chromatin nuclear organization and gene activity is vividly illustrated by the observation that transcriptional coregulation of certain genes appears to be directly influenced by their spatial proximity. This fact poses the more general question of whether it is at all feasible that the numerous genes that are coregulated on a given chromosome, especially those at large genomic distances, might become proximate inside the nucleus. This problem is studied here using steered molecular dynamics simulations in order to enforce the colocalization of thousands of knowledge-based gene sequences on a model for the gene-rich human chromosome 19. Remarkably, it is found that most (≈ 88% gene pairs can be brought simultaneously into contact. This is made possible by the low degree of intra-chromosome entanglement and the large number of cliques in the gene coregulatory network. A clique is a set of genes coregulated all together as a group. The constrained conformations for the model chromosome 19 are further shown to be organized in spatial macrodomains that are similar to those inferred from recent HiC measurements. The findings indicate that gene coregulation and colocalization are largely compatible and that this relationship can be exploited to draft the overall spatial organization of the chromosome in vivo. The more general validity and implications of these findings could be investigated by applying to other eukaryotic chromosomes the general and transferable computational strategy introduced here.

  16. Paralogous Genes as a Tool to Study the Regulation of Gene Expression

    DEFF Research Database (Denmark)

    Hoffmann, Robert D

    their duplicate were found to be under less purifying selection. A gene ontology (GO) term enrichment analysis showed that paralogs with similar expression levels were enriched in GO terms related to macromolecular complexes, whereas paralogs with different expression levels were enriched in terms associated...... new functions, or their gene products are in a dosage balance. Regulatory DNA elements - some of which are conserved across species and hence called conserved non-coding sequences (CNSs) - that control expression of duplicated genes are thus under similar purifying selection. In the present study, I...... have performed in-depth analyses of paralogous genes in Arabidopsis thaliana, their expression profile, their sequence conservation, and their functions, in order to investigate the relationship between gene expression and retention of paralogous genes. Paralogs with lower expression than...

  17. Selection of reference genes for gene expression studies in heart failure for left and right ventricles.

    Science.gov (United States)

    Li, Mengmeng; Rao, Man; Chen, Kai; Zhou, Jianye; Song, Jiangping

    2017-07-15

    Real-time quantitative reverse transcriptase-PCR (qRT-PCR) is a feasible tool for determining gene expression profiles, but the accuracy and reliability of the results depends on the stable expression of selected housekeeping genes in different samples. By far, researches on stable housekeeping genes in human heart failure samples are rare. Moreover the effect of heart failure on the expression of housekeeping genes in right and left ventricles is yet to be studied. Therefore we aim to provide stable housekeeping genes for both ventricles in heart failure and normal heart samples. In this study, we selected seven commonly used housekeeping genes as candidates. By using the qRT-PCR, the expression levels of ACTB, RAB7A, GAPDH, REEP5, RPL5, PSMB4 and VCP in eight heart failure and four normal heart samples were assessed. The stability of candidate housekeeping genes was evaluated by geNorm and Normfinder softwares. GAPDH showed the least variation in all heart samples. Results also indicated the difference of gene expression existed in heart failure left and right ventricles. GAPDH had the highest expression stability in both heart failure and normal heart samples. We also propose using different sets of housekeeping genes for left and right ventricles respectively. The combination of RPL5, GAPDH and PSMB4 is suitable for the right ventricle and the combination of GAPDH, REEP5 and RAB7A is suitable for the left ventricle. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Global Obesity Study on Drivers for Weight Reduction Strategies

    Directory of Open Access Journals (Sweden)

    Carola Grebitus

    2015-01-01

    Full Text Available Objective: To assess factors determining the reaction of individuals to the threats of overweight and obesity and to examine the interdependencies between weight-reducing strategies. Methods: Cross-country survey covering 19 countries and 13,155 interviews. Data were analysed using a bivariate probit model that allows simultaneously analysing two weight-reducing strategies. Results: Results show that weight-reducing strategies chosen are not independent from each other. Findings also reveal that different strategies are chosen by different population segments. Women are more likely to change their dietary patterns and less likely to become physically active after surpassing a weight threshold. In addition, the probability of a dietary change in case of overweight differs considerably between countries. The study also reveals that attitudes are an important factor for the strategy choice. Conclusions: It is vital for public health policies to understand determinants of citizens' engagement in weight reduction strategies once a certain threshold is reached. Thus, results can support the design of public health campaigns and programmes that aim to change community or national health behaviour trends taking into account, e.g., national differences.

  19. Study of obesity associated proopiomelanocortin gene polymorphism

    African Journals Online (AJOL)

    ... fasting glucose, fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR) and fasting lipid profiles, and higher frequency of occurrence of non alcoholic fatty liver disease and BED. Allelic frequencies of POMC gene 9 bp insertional polymorphism were comparable in patients and controls (p= 0.956).

  20. A Comparative Study of School Based Violence and Strategies for ...

    African Journals Online (AJOL)

    Background: Violence is universal; it occurs in schools (both public and private). The study aim was to assess the rates of violence as well as existing violence prevention strategies in public and private schools in Osun state. Methodology: A cross sectional study was conducted among 800 secondary school students (599 in ...

  1. Strategies for Integrating Peace Education into Social Studies ...

    African Journals Online (AJOL)

    The findings also identified co-curricular and instructional strategies for use in teaching the identified peace education concepts. It was recommended that the identified peace education concepts could be added to the Social Studies curriculum and the thematic approach should be used in restructuring the Social Studies ...

  2. Reading Online in Foreign Languages: A Study of Strategy Use

    Science.gov (United States)

    Cheng, Richard Tsan-Jui

    2016-01-01

    Scores of studies have established that when learning online, students must be equipped with different sets of strategies and skills than in a physical classroom setting (Anderson, 2003; Broadbent & Poon, 2015; Coiro, 2007; Leu et al., 2007; Michinov, Brunot, Le Bohec, Juhel, & Delaval, 2011; Salmon, 2013). The present study, by virtue of…

  3. Heuristical Strategies on the Study Theme "The Unsaturated Hydrocarbons -- Alkenes"

    Science.gov (United States)

    Naumescu, Adrienne Kozan; Pasca, Roxana-Diana

    2011-01-01

    The influence of heuristical strategies upon the level of two experimental classes is studied in this paper. The didactic experiment took place at secondary school in Cluj-Napoca, in 2008-2009 school year. The study theme "The Unsaturated Hydrocarbons--Alkenes" has been efficiently learned by using the most active methods: laboratory…

  4. Achievement Goal Orientations and Self-Reported Study Strategies as Predictors of Online Studying Activities

    Science.gov (United States)

    Adesope, Olusola O.; Zhou, Mingming; Nesbit, John C.

    2015-01-01

    The purpose of this study was to investigate whether achievement motivations influence the adoption of learning strategies and learning strategies influence studying behavior in an online learning environment. The Goal Orientation Questionnaire was used to measure achievement motives, and the Motivated Strategies for Learning Questionnaire was…

  5. Imaging genetics studies on monoaminergic genes in major depressive disorder.

    Science.gov (United States)

    Won, Eunsoo; Ham, Byung-Joo

    2016-01-04

    Although depression is the leading cause of disability worldwide, current understanding of the neurobiology of depression has failed to be translated into clinical practice. Major depressive disorder (MDD) pathogenesis is considered to be significantly influenced by multiple risk genes, however genetic effects are not simply expressed at a behavioral level. Therefore the concept of endophenotype has been applied in psychiatric genetics. Imaging genetics applies anatomical or functional imaging technologies as phenotypic assays to evaluate genetic variation and their impact on behavior. This paper attempts to provide a comprehensive review of available imaging genetics studies, including reports on genetic variants that have most frequently been linked to MDD, such as the monoaminergic genes (serotonin transporter gene, monoamine oxidase A gene, tryptophan hydroxylase-2 gene, serotonin receptor 1A gene and catechol-O-methyl transferase gene), with regard to key structures involved in emotion processing, such as the hippocampus, amygdala, anterior cingulate cortex and orbitofrontal cortex. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Evidence for plasticity genotypes in a gene-gene-environment interaction : the TRAILS study

    NARCIS (Netherlands)

    Nederhof, E; Bouma, Esther; Riese, Harriette; Laceulle, Odilia; Ormel, J.; Oldehinkel, A.J.

    2010-01-01

    The purpose was to study how functional polymorphisms in the brain derived neurotrophic factor gene (BDNF val66met) and the serotonin transporter gene linked promotor region (5-HTTLPR) interact with childhood adversities in predicting Effortful Control. Effortful Control refers to the ability to

  7. Marketing strategy and product performance: a study of selected ...

    African Journals Online (AJOL)

    The results show that indeed marketing strategy impacts product performance of the observed firms. More so, of all the factors considered (promotion strategy, Product strategy, Distribution strategy, General marketing strategy and Pricing Strategy) promotional factors were found to be most important, then product strategy ...

  8. Study of candidate genes for dyslexia in Brazilian individuals.

    Science.gov (United States)

    Svidnicki, M C C M; Salgado, C A; Lima, R F; Ciasca, S M; Secolin, R; Pomilio, M C A; Junqueira, P A; Pinto, M S; Pereira, M M; Sartorato, E L

    2013-11-07

    Dyslexia or reading disability (RD) is the most common childhood learning disorder and a significantly heritable trait. Many recent studies have investigated the genetic basis of dyslexia, and several candidate genes have been proposed. Among these, DCDC2 and KIAA0319 have emerged as the strongest candidate genes for dyslexia; however studies have not provided uniformly supportive results. The aim of this study was to assess the contribution of proposed candidate genes to the molecular etiology of dyslexia in a Brazilian sample. Large deletions and duplications in the candidate genes DCDC2, KIAA0319, and ROBO1 were investigated in 51 dyslexic subjects. Furthermore, a family-based association study was performed to investigate whether associations observed in other populations with variants in the DCDC2 and KIAA0319 genes were reproducible in Brazilian dyslexic individuals. Our analysis did not detect any deletions or duplications in the genes studied, and we found no evidence that the allelic variants in the two candidate genes were significantly associated with RD in our sample. Our data do not support a role of the DCDC2/KIAA0319 locus in influencing dyslexia as a categorical trait. Given the genetic complexity of dyslexia, it is plausible that both genes contribute to an increased risk, but the relative influence of these 2 genes on RD varies in different study samples, and/or depends on analytical approaches.

  9. Strategies to optimize MEDLINE and EMBASE search strategies for anesthesiology systematic reviews. An experimental study.

    Science.gov (United States)

    Volpato, Enilze de Souza Nogueira; Betini, Marluci; Puga, Maria Eduarda; Agarwal, Arnav; Cataneo, Antônio José Maria; Oliveira, Luciane Dias de; Bazan, Rodrigo; Braz, Leandro Gobbo; Pereira, José Eduardo Guimarães; El Dib, Regina

    2018-01-15

    A high-quality electronic search is essential for ensuring accuracy and comprehensiveness among the records retrieved when conducting systematic reviews. Therefore, we aimed to identify the most efficient method for searching in both MEDLINE (through PubMed) and EMBASE, covering search terms with variant spellings, direct and indirect orders, and associations with MeSH and EMTREE terms (or lack thereof). Experimental study. UNESP, Brazil. We selected and analyzed 37 search strategies that had specifically been developed for the field of anesthesiology. These search strategies were adapted in order to cover all potentially relevant search terms, with regard to variant spellings and direct and indirect orders, in the most efficient manner. When the strategies included variant spellings and direct and indirect orders, these adapted versions of the search strategies selected retrieved the same number of search results in MEDLINE (mean of 61.3%) and a higher number in EMBASE (mean of 63.9%) in the sample analyzed. The numbers of results retrieved through the searches analyzed here were not identical with and without associated use of MeSH and EMTREE terms. However, association of these terms from both controlled vocabularies retrieved a larger number of records than did the use of either one of them. In view of these results, we recommend that the search terms used should include both preferred and non-preferred terms (i.e. variant spellings and direct/indirect order of the same term) and associated MeSH and EMTREE terms, in order to develop highly-sensitive search strategies for systematic reviews.

  10. High-speed biosensing strategy for non-invasive profiling of multiple cancer fusion genes in urine.

    Science.gov (United States)

    Koo, Kevin M; Wee, Eugene J H; Trau, Matt

    2017-03-15

    Aberrant chromosal rearrangements, such as the multiple variants of TMPRSS2:ERG fusion gene mutations in prostate cancer (PCa), are promising diagnostic and prognostic biomarkers due to their specific expression in cancerous tissue only. Additionally, TMPRSS2:ERG variants are detectable in urine to provide non-invasive PCa diagnostic sampling as an attractive surrogate for needle biopsies. Therefore, rapid and simplistic assays for identifying multiple urinary TMPRSS2:ERG variants are potentially useful to aid in early cancer detection, immediate patient risk stratification, and prompt personalized treatment. However, current strategies for simultaneous detection of multiple gene fusions are limited by tedious and prolonged experimental protocols, thus limiting their use as rapid clinical screening tools. Herein, we report a simple and rapid gene fusion strategy which expliots the specificity of DNA ligase and the speed of isothermal amplification to simultaneously detect multiple fusion gene RNAs within a short sample-to-answer timeframe of 60min. The method has a low detection limit of 2 amol (1000 copies), and was successfully applied for non-invasive fusion gene profiling in patient urine samples with subsequent validation by a PCR-based gold standard approach. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Understanding the molecular biology of intervertebral disc degeneration and potential gene therapy strategies for regeneration: a review.

    Science.gov (United States)

    Sampara, Prasanthi; Banala, Rajkiran Reddy; Vemuri, Satish Kumar; Av, Gurava Reddy; Gpv, Subbaiah

    2018-03-22

    Intervertebral disc degeneration (IVDD) is a multi-factorial process characterized by phenotypic and genotypic changes, which leads to low back pain and disability. Prolonged imbalance between anabolism and catabolism in discs alters their composition resulting in progressive loss of proteoglycans and hydration leading to IVDD. The current managements for IVDD are only able to relieve the symptoms but do not address the underlying pathology of degeneration. Researchers have tried to find out differences between the aging and degeneration of the disc. Intense attempts are in progress for identifying the various factors responsible for disc degeneration, as well as strategies for regeneration. Recently biological approaches have gained thrust in the field of IVDD. The present review illustrates the current understanding of intervertebral disc degeneration and aims to put forth recent advancements in regeneration strategies involving different biological therapies such as growth factor, cell, and gene therapy. The potentials and consequences of these therapies are also extensively discussed along with citing the most suitable method, that is, the gene therapy in detail. Initially, gene therapy was mediated by viral vectors but recent progress has enabled researchers to opt for non-virus-mediated gene therapy methods, which ensure that there are no risks of mutagenicity and infection in target cells. With constant efforts, non-virus-mediated gene therapy may prove to be an extremely powerful tool in treatment of IVDD in future.

  12. Do study strategies predict academic performance in medical school?

    Science.gov (United States)

    West, Courtney; Sadoski, Mark

    2011-07-01

    Study strategies, such as time and study management techniques, seem to be consistently related to achievement even when aptitude is controlled for, but the picture is not entirely clear. As there is limited research in this area, we explored the relative strengths of academic aptitude, as measured by the Medical College Admission Test (MCAT), undergraduate grade point average (UGPA) and study strategies, as measured by the Learning and Study Strategies Inventory (LASSI), in predicting academic performance in 106 students in the first semester of an integrated curriculum.  Our purpose was to determine whether relationships could be identified between academic aptitude, study strategies and academic performance which would enable us to provide students with feedback in certain skill areas in order to maximise achievement. Data analysis consisted of four multiple regression analyses. The criterion variables were: semester overall final average, semester written examination average, semester practical examination average, and percentage correct on a customised National Board of Medical Examiners (NBME) examination. The predictor variables in each regression were: MCAT score; UGPA; and subscores on the 10 LASSI subscales for Anxiety, Attitude, Motivation, Concentration, Information Processing, Self-Testing, Selecting Main Idea, Study Aids, Time Management and Test-Taking Strategies. The results of three regressions indicated that two study skills, time management and self-testing, were generally stronger predictors of first-semester academic performance than aptitude. Improving the prioritisation and organisation of study time and teaching students to predict, compose and answer their own questions when studying may help to advance student performance regardless of student aptitude, especially on course-specific examinations. © Blackwell Publishing Ltd 2011.

  13. An albumin-mediated cholesterol design-based strategy for tuning siRNA pharmacokinetics and gene silencing

    DEFF Research Database (Denmark)

    Bienk, Konrad; Hvam, Michael Lykke; Pakula, Malgorzata Maria

    2016-01-01

    Major challenges for the clinical translation of small interfering RNA (siRNA) include overcoming the poor plasma half-life, site-specific delivery and modulation of gene silencing. In this work, we exploit the intrinsic transport properties of human serum albumin to tune the blood circulatory ha...... of 28% (rHSA/siRNA) compared to 4% (naked siRNA) 6 days post-injection. This work presents a novel albumin-mediated cholesteryl design-based strategy for tuning pharmacokinetics and systemic gene silencing....

  14. Optimal design strategies for sibling studies with binary exposures.

    Science.gov (United States)

    Li, Zhigang; McKeague, Ian W; Lumey, Lambert H

    2014-01-01

    Sibling studies have become increasingly popular because they provide better control over confounding by unmeasured family-level risk factors than can be obtained in standard cohort studies. However, little attention has been devoted to the development of efficient design strategies for sibling studies in terms of optimizing power. We here address this issue in commonly encountered types of sibling studies, allowing for continuous and binary outcomes and varying numbers of exposed and unexposed siblings. For continuous outcomes, we show that in families with sibling pairs, optimal study power is obtained by recruiting discordant (exposed-control) pairs of siblings. More generally, balancing the exposure status within each family as evenly as possible is shown to be optimal. For binary outcomes, we elucidate how the optimal strategy depends on the variation of the binary response; as the within-family correlation increases, the optimal strategy tends toward only recruiting discordant sibling pairs (as in the case of continuous outcomes). R code for obtaining the optimal strategies is included.

  15. Insights into the molecular pathogenesis of atherosclerosis and therapeutic strategies using gene transfer.

    Science.gov (United States)

    Hiltunen, M O; Turunen, M P; Laitinen, M; Ylä-Herttuala, S

    2000-01-01

    Gene therapy for the treatment of atherosclerosis and related diseases has shown its potential in animal models and in the first human trials. Gene transfer to the vascular system can be performed both via intravascular and extravascular periadventitial routes. Intravascular gene transfer can be done with several types of catheters under fluoroscopic control. Extravascular gene transfer, on the other hand, provides a well-targeted gene delivery route available during vascular surgery. It can be done with direct injection or by using perivascular cuffs or surgical collagen sheets. Ex vivo gene delivery via transfected smooth muscle cells or endothelial cells might be useful for the production of secreted therapeutic compounds. Gene transfer to the liver has been used for the treatment of hyperlipidemia. The first clinical trials for the induction of therapeutic angiogenesis in ischemic myocardium or peripheral muscles with VEGF or FGF gene transfer are under way and preliminary results are promising. VEGF has also been used for the prevention of postangioplasty restenosis because of its capability to induce endothelial repair and production of NO and prostacyclin. However, further basic research is needed to fully understand the pathophysiological mechanisms involved in conditions related to atherosclerosis. Also, further development of gene transfer vectors and gene delivery techniques will improve the efficacy and safety of human gene therapy.

  16. Human reporter genes: potential use in clinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Serganova, Inna [Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Ponomarev, Vladimir [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Blasberg, Ronald [Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States)], E-mail: blasberg@neuro1.mskcc.org

    2007-10-15

    The clinical application of positron-emission-tomography-based reporter gene imaging will expand over the next several years. The translation of reporter gene imaging technology into clinical applications is the focus of this review, with emphasis on the development and use of human reporter genes. Human reporter genes will play an increasingly more important role in this development, and it is likely that one or more reporter systems (human gene and complimentary radiopharmaceutical) will take leading roles. Three classes of human reporter genes are discussed and compared: receptors, transporters and enzymes. Examples of highly expressed cell membrane receptors include specific membrane somatostatin receptors (hSSTrs). The transporter group includes the sodium iodide symporter (hNIS) and the norepinephrine transporter (hNET). The endogenous enzyme classification includes human mitochondrial thymidine kinase 2 (hTK2). In addition, we also discuss the nonhuman dopamine 2 receptor and two viral reporter genes, the wild-type herpes simplex virus 1 thymidine kinase (HSV1-tk) gene and the HSV1-tk mutant (HSV1-sr39tk). Initial applications of reporter gene imaging in patients will be developed within two different clinical disciplines: (a) gene therapy and (b) adoptive cell-based therapies. These studies will benefit from the availability of efficient human reporter systems that can provide critical monitoring information for adenoviral-based, retroviral-based and lenteviral-based gene therapies, oncolytic bacterial and viral therapies, and adoptive cell-based therapies. Translational applications of noninvasive in vivo reporter gene imaging are likely to include: (a) quantitative monitoring of gene therapy vectors for targeting and transduction efficacy in clinical protocols by imaging the location, extent and duration of transgene expression; (b) monitoring of cell trafficking, targeting, replication and activation in adoptive T-cell and stem/progenitor cell therapies

  17. Human reporter genes: potential use in clinical studies

    International Nuclear Information System (INIS)

    Serganova, Inna; Ponomarev, Vladimir; Blasberg, Ronald

    2007-01-01

    The clinical application of positron-emission-tomography-based reporter gene imaging will expand over the next several years. The translation of reporter gene imaging technology into clinical applications is the focus of this review, with emphasis on the development and use of human reporter genes. Human reporter genes will play an increasingly more important role in this development, and it is likely that one or more reporter systems (human gene and complimentary radiopharmaceutical) will take leading roles. Three classes of human reporter genes are discussed and compared: receptors, transporters and enzymes. Examples of highly expressed cell membrane receptors include specific membrane somatostatin receptors (hSSTrs). The transporter group includes the sodium iodide symporter (hNIS) and the norepinephrine transporter (hNET). The endogenous enzyme classification includes human mitochondrial thymidine kinase 2 (hTK2). In addition, we also discuss the nonhuman dopamine 2 receptor and two viral reporter genes, the wild-type herpes simplex virus 1 thymidine kinase (HSV1-tk) gene and the HSV1-tk mutant (HSV1-sr39tk). Initial applications of reporter gene imaging in patients will be developed within two different clinical disciplines: (a) gene therapy and (b) adoptive cell-based therapies. These studies will benefit from the availability of efficient human reporter systems that can provide critical monitoring information for adenoviral-based, retroviral-based and lenteviral-based gene therapies, oncolytic bacterial and viral therapies, and adoptive cell-based therapies. Translational applications of noninvasive in vivo reporter gene imaging are likely to include: (a) quantitative monitoring of gene therapy vectors for targeting and transduction efficacy in clinical protocols by imaging the location, extent and duration of transgene expression; (b) monitoring of cell trafficking, targeting, replication and activation in adoptive T-cell and stem/progenitor cell therapies

  18. Screening for the Most Suitable Reference Genes for Gene Expression Studies in Equine Milk Somatic Cells.

    Directory of Open Access Journals (Sweden)

    Jakub Cieslak

    Full Text Available Apart from the well-known role of somatic cell count as a parameter reflecting the inflammatory status of the mammary gland, the composition of cells isolated from milk is considered as a valuable material for gene expression studies in mammals. Due to its unique composition, in recent years an increasing interest in mare's milk consumption has been observed. Thus, investigating the genetic background of horse's milk variability presents and interesting study model. Relying on 39 milk samples collected from mares representing three breeds (Polish Primitive Horse, Polish Cold-blooded Horse, Polish Warmblood Horse we aimed to investigate the utility of equine milk somatic cells as a source of mRNA and to screen the best reference genes for RT-qPCR using geNorm and NormFinder algorithms. The results showed that despite relatively low somatic cell counts in mare's milk, the amount and the quality of the extracted RNA are sufficient for gene expression studies. The analysis of the utility of 7 potential reference genes for RT-qPCR experiments for the normalization of equine milk somatic cells revealed some differences between the outcomes of the applied algorithms, although in both cases the KRT8 and TOP2B genes were pointed as the most stable. Analysis by geNorm showed that the combination of 4 reference genes (ACTB, GAPDH, TOP2B and KRT8 is required for apropriate RT-qPCR experiments normalization, whereas NormFinder algorithm pointed the combination of KRT8 and RPS9 genes as the most suitable. The trial study of the relative transcript abundance of the beta-casein gene with the use of various types and numbers of internal control genes confirmed once again that the selection of proper reference gene combinations is crucial for the final results of each real-time PCR experiment.

  19. Studies on the strategies of minimizing radiation damage

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Hee Yong; Sohn, Young Sook

    1998-04-01

    We studied on the strategies of minimizing radiation damage in animal system. To this end we studied following areas of research (1) mechanisms involved in bone marrow damage after total body irradiation, (2) extraction of components that are useful in protecting hematopoietic system from radiation damage, (3) cell therapy approach in restoring the damaged tissue, (4) development of radioprotective chemical reagent, and (5) epidemiological study on the population that had been exposed to radiation.

  20. Studies on the strategies of minimizing radiation damage

    International Nuclear Information System (INIS)

    Chung, Hee Yong; Sohn, Young Sook

    1998-04-01

    We studied on the strategies of minimizing radiation damage in animal system. To this end we studied following areas of research 1) mechanisms involved in bone marrow damage after total body irradiation, 2) extraction of components that are useful in protecting hematopoietic system from radiation damage, 3) cell therapy approach in restoring the damaged tissue, 4) development of radioprotective chemical reagent, and 5) epidemiological study on the population that had been exposed to radiation

  1. Investigating Young Children's Use of Reading Strategies: A Longitudinal Study

    Science.gov (United States)

    Kragler, Sherry; Martin, Linda; Schreier, Virginia

    2015-01-01

    In this three-year study, the authors examined the reading strategy use of 16 primary-grade students as they read fiction and expository text. The students (9 boys and 7 girls) represented low, average, and above-average readers. Structured interviews and observational data were collected each year as they progressed from first to third grade.…

  2. Aligning IT and Business Strategy: An Australian University Case Study

    Science.gov (United States)

    Dent, Alan

    2015-01-01

    Alignment with business objectives is considered to be an essential outcome of information technology (IT) strategic planning. This case study examines the process of creating an IT strategy for an Australian university using an industry standard methodology. The degree of alignment is determined by comparing the strategic priorities supported by…

  3. Understanding Foreign Language Learning Strategies: A Validation Study

    Science.gov (United States)

    Tragant, Elsa; Thompson, Marilyn S.; Victori, Mia

    2013-01-01

    The present work aims to contribute to our understanding of the underlying dimensions of language learning strategies in foreign language contexts. The study analyzes alternative factor structures underlying a recently developed instrument (Tragant and Victori, 2012) and it includes the age factor in the examination of its construct validity. The…

  4. An empirical study of university student-athletes' strategies for ...

    African Journals Online (AJOL)

    Because of the increased demand for sport as a product, university studentathletes are subjected to higher levels of pressure which ultimately results in stress. Hence it is a common feature that athletes in competitive sports have to perform in stressful situations. This study was conducted to assess the coping strategies ...

  5. A Study on Developing Learning Strategies in Violin Education

    Science.gov (United States)

    Afacan, Senol; Cilden, Seyda

    2018-01-01

    This study was conducted for the purpose of developing a valid and reliable learning strategies scale for students receiving violin education in Departments of Music at Fine Arts High Schools. The scale was applied to 391 violin students receiving education in the 11th and 12th grades in Departments of Music at Fine Arts High Schools in the…

  6. Mothers' Teaching Strategies and Children's Effortful Control: A Longitudinal Study

    Science.gov (United States)

    Eisenberg, Nancy; Vidmar, Masa; Spinrad, Tracy L.; Eggum, Natalie D.; Edwards, Alison; Gaertner, Bridget; Kupfer, Anne

    2010-01-01

    Findings on the relation of maternal verbal teaching strategies to children's effortful control (EC; i.e., self-regulation) are limited in quantity and somewhat inconsistent. In this study, children's EC was assessed at 18, 30, and 42 months (ns = 255, 229, and 209, respectively) with adults' reports and a behavioral measure. Mothers' verbal…

  7. Study of selected phenotype switching strategies in time varying environment

    Energy Technology Data Exchange (ETDEWEB)

    Horvath, Denis, E-mail: horvath.denis@gmail.com [Centre of Interdisciplinary Biosciences, Institute of Physics, Faculty of Science, P.J. Šafárik University in Košice, Jesenná 5, 040 01 Košice (Slovakia); Brutovsky, Branislav, E-mail: branislav.brutovsky@upjs.sk [Department of Biophysics, Institute of Physics, P.J. Šafárik University in Košice, Jesenná 5, 040 01 Košice (Slovakia)

    2016-03-22

    Population heterogeneity plays an important role across many research, as well as the real-world, problems. The population heterogeneity relates to the ability of a population to cope with an environment change (or uncertainty) preventing its extinction. However, this ability is not always desirable as can be exemplified by an intratumor heterogeneity which positively correlates with the development of resistance to therapy. Causation of population heterogeneity is therefore in biology and medicine an intensively studied topic. In this paper the evolution of a specific strategy of population diversification, the phenotype switching, is studied at a conceptual level. The presented simulation model studies evolution of a large population of asexual organisms in a time-varying environment represented by a stochastic Markov process. Each organism disposes with a stochastic or nonlinear deterministic switching strategy realized by discrete-time models with evolvable parameters. We demonstrate that under rapidly varying exogenous conditions organisms operate in the vicinity of the bet-hedging strategy, while the deterministic patterns become relevant as the environmental variations are less frequent. Statistical characterization of the steady state regimes of the populations is done using the Hellinger and Kullback–Leibler functional distances and the Hamming distance. - Highlights: • Relation between phenotype switching and environment is studied. • The Markov chain Monte Carlo based model is developed. • Stochastic and deterministic strategies of phenotype switching are utilized. • Statistical measures of the dynamic heterogeneity reveal universal properties. • The results extend to higher lattice dimensions.

  8. Strategies for Integrating Peace Education into Social Studies ...

    African Journals Online (AJOL)

    gold

    2012-07-26

    Jul 26, 2012 ... resources and resource problems in Nigeria and religion concepts into the social studies curriculum. The findings also identified co-curricular and instructional strategies for use in teaching the identified peace education concepts. It was recommended that the identified peace education concepts could be ...

  9. A study of optimal abstract jamming strategies vs. noncoherent MFSK

    Science.gov (United States)

    Mceliece, R. J.; Rodemich, E. R.

    1983-01-01

    The present investigation is concerned with the performance of uncoded MFSK modulation in the presence of arbitrary additive jamming, taking into account the objective to devise robust antijamming strategies. An abstract model is considered, giving attention to the signal strength as a nonnegative real number X, the employment of X as a random variable, its distribution function G(x), the transmitter's strategy G, the jamming noise as an M-dimensional random vector Z, and the error probability. A summary of previous work on the considered problem is provided, and the results of the current study are presented.

  10. Selection of Reliable Reference Genes for Gene Expression Studies on Rhododendron molle G. Don

    Directory of Open Access Journals (Sweden)

    Zheng Xiao

    2016-10-01

    Full Text Available The quantitative real-time polymerase chain reaction (qRT-PCR approach has become a widely used method to analyze expression patterns of target genes. The selection of an optimal reference gene is a prerequisite for the accurate normalization of gene expression in qRT-PCR. The present study constitutes the first systematic evaluation of potential reference genes in Rhododendron molle G. Don. Eleven candidate reference genes in different tissues and flowers at different developmental stages of R. molle were assessed using the following three software packages: GeNorm, NormFinder and BestKeeper. The results showed that EF1-α (elongation factor 1-alpha, 18S (18s ribosomal RNA and RPL3 (ribosomal protein L3 were the most stable reference genes in developing rhododendron flowers and, thus, in all of the tested samples, while tublin (TUB was the least stable. ACT5 (actin, RPL3, 18S and EF1-α were found to be the top four choices for different tissues, whereas TUB was not found to favor qRT-PCR normalization in these tissues. Three stable reference genes are recommended for the normalization of qRT-PCR data in R. molle. Furthermore, the expression profiles of RmPSY (phytoene synthase and RmPDS (phytoene dehydrogenase were assessed using EF1-α, 18S, ACT5, and RPL3 and their combination as internals. Similar trends were found, but these trends varied when the least stable reference gene TUB was used. The results further prove that it is necessary to validate the stability of reference genes prior to their use for normalization under different experimental conditions. This study provides useful information for reliable qRT-PCR data normalization in gene studies of R. molle.

  11. Marine Microbiological Enzymes: Studies with Multiple Strategies and Prospects

    Directory of Open Access Journals (Sweden)

    Yan Wang

    2016-09-01

    Full Text Available Marine microorganisms produce a series of promising enzymes that have been widely used or are potentially valuable for our daily life. Both classic and newly developed biochemistry technologies have been broadly used to study marine and terrestrial microbiological enzymes. In this brief review, we provide a research update and prospects regarding regulatory mechanisms and related strategies of acyl-homoserine lactones (AHL lactonase, which is an important but largely unexplored enzyme. We also detail the status and catalytic mechanism of the main types of polysaccharide-degrading enzymes that broadly exist among marine microorganisms but have been poorly explored. In order to facilitate understanding, the regulatory and synthetic biology strategies of terrestrial microorganisms are also mentioned in comparison. We anticipate that this review will provide an outline of multiple strategies for promising marine microbial enzymes and open new avenues for the exploration, engineering and application of various enzymes.

  12. A general strategy to achieve ultra-high gene transfection efficiency using lipid-nanoparticle composites.

    Science.gov (United States)

    Vankayala, Raviraj; Chiang, Chi-Shiun; Chao, Jui-I; Yuan, Chiun-Jye; Lin, Shyr-Yeu; Hwang, Kuo Chu

    2014-09-01

    Gene therapy provides a new hope for previously "incurable" diseases. Low gene transfection efficiency, however, is the bottle-neck to the success of gene therapy. It is very challenging to develop non-viral nanocarriers to achieve ultra-high gene transfection efficiencies. Herein, we report a novel design of "tight binding-but-detachable" lipid-nanoparticle composite to achieve ultrahigh gene transfection efficiencies of 60∼82%, approaching the best value (∼90%) obtained using viral vectors. We show that Fe@CNPs nanoparticles coated with LP-2000 lipid molecules can be used as gene carriers to achieve ultra-high (60-80%) gene transfection efficiencies in HeLa, U-87MG, and TRAMP-C1 cells. In contrast, Fe@CNPs having surface-covalently bound N,N,N-trimethyl-N-2-methacryloxyethyl ammonium chloride (TMAEA) oligomers can only achieve low (23-28%) gene transfection efficiencies. Similarly ultrahigh gene transfection/expression was also observed in zebrafish model using lipid-coated Fe@CNPs as gene carriers. Evidences for tight binding and detachability of DNA from lipid-nanoparticle nanocarriers will be presented. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. In silico analysis and DHPLC screening strategy identifies novel apoptotic gene targets of aberrant promoter hypermethylation in prostate cancer.

    LENUS (Irish Health Repository)

    Murphy, Therese M

    2011-01-01

    Aberrant DNA methylation has been implicated as a key survival mechanism in cancer, whereby promoter hypermethylation silences genes essential for many cellular processes including apoptosis. Limited data is available on the methylation profile of apoptotic genes in prostate cancer (CaP). The aim of this study was to profile methylation of apoptotic-related genes in CaP using denaturing high performance liquid chromatography (DHPLC).

  14. Genes and gene expression: Localization, damage and control -- A multilevel and inter-disciplinary study

    Energy Technology Data Exchange (ETDEWEB)

    Ts' o, P.O.P.

    1990-09-01

    All projects are working toward a goal for describing the three dimensional nuclear topography in terms of relative spatial relationships among genes (specific DNA sequence). Methods are now being perfected to detect these genes, quantitatively and spatially, to perturb these genes specifically, and to measure the perturbation in order to assure specificity. We are developing methods to assay, after perturbation of the target DNA within living cells, whether or not only the target sequence are attacked while other sequences remain unharmed. We are now at the stage to do chemical gene modification or masking within living cells in a strictly sequence-specific manner. Soon, we will be able to study the function and the physical location of each gene in living cells with exquisite specificity. 25 refs., 15 figs.

  15. Genes and gene expression: Localization, damage and control -- A multilevel and inter-disciplinary study

    International Nuclear Information System (INIS)

    Ts'o, P.O.P.

    1990-09-01

    All projects are working toward a goal for describing the three dimensional nuclear topography in terms of relative spatial relationships among genes (specific DNA sequence). Methods are now being perfected to detect these genes, quantitatively and spatially, to perturb these genes specifically, and to measure the perturbation in order to assure specificity. We are developing methods to assay, after perturbation of the target DNA within living cells, whether or not only the target sequence are attacked while other sequences remain unharmed. We are now at the stage to do chemical gene modification or masking within living cells in a strictly sequence-specific manner. Soon, we will be able to study the function and the physical location of each gene in living cells with exquisite specificity. 25 refs., 15 figs

  16. Effects of strategy sequences and response-stimulus intervals on children's strategy selection and strategy execution: a study in computational estimation.

    Science.gov (United States)

    Lemaire, Patrick; Brun, Fleur

    2014-07-01

    The present study investigates how children's better strategy selection and strategy execution on a given problem are influenced by which strategy was used on the immediately preceding problem and by the duration between their answer to the previous problem and current problem display. These goals are pursued in the context of an arithmetic problem solving task. Third and fifth graders were asked to select the better strategy to find estimates to two-digit addition problems like 36 + 78. On each problem, children could choose rounding-down (i.e., rounding both operands down to the closest smaller decades, like doing 40 + 60 to solve 42 + 67) or rounding-up strategies (i.e., rounding both operands up to the closest larger decades, like doing 50 + 70 to solve 42 + 67). Children were tested under a short RSI condition (i.e., the next problem was displayed 900 ms after participants' answer) or under a long RSI condition (i.e., the next problem was displayed 1,900 ms after participants' answer). Results showed that both strategy selection (e.g., children selected the better strategy more often under long RSI condition and after selecting the poorer strategy on the immediately preceding problem) and strategy execution (e.g., children executed strategy more efficiently under long RSI condition and were slower when switching strategy over two consecutive problems) were influenced by RSI and which strategy was used on the immediately preceding problem. Moreover, data showed age-related changes in effects of RSI and strategy sequence on mean percent better strategy selection and on strategy performance. The present findings have important theoretical and empirical implications for our understanding of general and specific processes involved in strategy selection, strategy execution, and strategic development.

  17. Application of radiation chemistry in studies of gene

    International Nuclear Information System (INIS)

    Yao, S.D.

    2000-01-01

    The explosive growth in gene has opened doors through which scientists from many different disciplines have passed in recent years. Along the way we have applied the radiation chemical tools and knowledge of our respective fields to address questions of fundamental and applied gene's importance. It should be believed that radiation chemical scientists could make much contribution to the studies of gene and life science in 21st century. In this paper it is shown what we have done and what we will do with gene by use of radiation chemical methods. 1. The damage mechanism of DNA under ionized radiation and UV light. 2. The protection mechanism of DNA damage involved irradiation and active oxygen radicals. 3. Radiation sensitization of DNA. 4. Photo-sensitization damage of DNA. 5. The identification, signal transfer and control of telomer of gene by radicals. 6. Gene mapping by use of special fluorescent agents and single-molecular operation. (J.P.N.)

  18. Reliable reference gene selection for Cordyceps militaris gene expression studies under different developmental stages and media.

    Science.gov (United States)

    Lian, Tiantian; Yang, Tao; Liu, Guijun; Sun, Junde; Dong, Caihong

    2014-07-01

    Cordyceps militaris is considered a model organism for the study of Cordyceps species, which are highly prized in traditional Chinese medicine. Gene expression analysis has become more popular and important in studies of this fungus. Reference gene validation under different experimental conditions is crucial for RT-qPCR analysis. In this study, eight candidate reference genes, actin, cox5, gpd, rpb1, tef1, try, tub, and ubi, were selected and their expression stability was evaluated in C. militaris samples using four algorithms, genorm, normfinder, bestkeeper, and the comparative ∆Ct method. Three sets of samples, five different developmental stages cultured in wheat medium and pupae, and all the samples pool were included. The results showed that rpb1 was the best reference gene during all developmental stages examined, while the most common reference genes, actin and tub, were not suitable internal controls. Cox5 also performed poorly and was less stable in our analysis. The ranks of ubi and gpd were inconsistent in different sample sets by different methods. Our results provide guidelines for reference gene selection at different developmental stages and also represent a foundation for more accurate and widespread use of RT-qPCR in C. militaris gene expression analysis. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  19. Superior cross-species reference genes: a blueberry case study.

    Directory of Open Access Journals (Sweden)

    Jose V Die

    Full Text Available The advent of affordable Next Generation Sequencing technologies has had major impact on studies of many crop species, where access to genomic technologies and genome-scale data sets has been extremely limited until now. The recent development of genomic resources in blueberry will enable the application of high throughput gene expression approaches that should relatively quickly increase our understanding of blueberry physiology. These studies, however, require a highly accurate and robust workflow and make necessary the identification of reference genes with high expression stability for correct target gene normalization. To create a set of superior reference genes for blueberry expression analyses, we mined a publicly available transcriptome data set from blueberry for orthologs to a set of Arabidopsis genes that showed the most stable expression in a developmental series. In total, the expression stability of 13 putative reference genes was evaluated by qPCR and a set of new references with high stability values across a developmental series in fruits and floral buds of blueberry were identified. We also demonstrated the need to use at least two, preferably three, reference genes to avoid inconsistencies in results, even when superior reference genes are used. The new references identified here provide a valuable resource for accurate normalization of gene expression in Vaccinium spp. and may be useful for other members of the Ericaceae family as well.

  20. Superior Cross-Species Reference Genes: A Blueberry Case Study

    Science.gov (United States)

    Die, Jose V.; Rowland, Lisa J.

    2013-01-01

    The advent of affordable Next Generation Sequencing technologies has had major impact on studies of many crop species, where access to genomic technologies and genome-scale data sets has been extremely limited until now. The recent development of genomic resources in blueberry will enable the application of high throughput gene expression approaches that should relatively quickly increase our understanding of blueberry physiology. These studies, however, require a highly accurate and robust workflow and make necessary the identification of reference genes with high expression stability for correct target gene normalization. To create a set of superior reference genes for blueberry expression analyses, we mined a publicly available transcriptome data set from blueberry for orthologs to a set of Arabidopsis genes that showed the most stable expression in a developmental series. In total, the expression stability of 13 putative reference genes was evaluated by qPCR and a set of new references with high stability values across a developmental series in fruits and floral buds of blueberry were identified. We also demonstrated the need to use at least two, preferably three, reference genes to avoid inconsistencies in results, even when superior reference genes are used. The new references identified here provide a valuable resource for accurate normalization of gene expression in Vaccinium spp. and may be useful for other members of the Ericaceae family as well. PMID:24058469

  1. Search strategies for identifying qualitative studies in CINAHL.

    Science.gov (United States)

    Wilczynski, Nancy L; Marks, Susan; Haynes, R Brian

    2007-05-01

    Nurses, allied health professionals, clinicians, and researchers increasingly use online access to evidence in the course of patient care or when conducting reviews on a particular topic. Qualitative research has an important role in evidence-based health care. Online searching for qualitative studies can be difficult, however, resulting in the need to develop search filters. The objective of this study was to develop optimal search strategies to retrieve qualitative studies in CINAHL for the 2000 publishing year. The authors conducted an analytic survey comparing hand searches of journals with retrievals from CINAHL for candidate search terms and combinations. Combinations of search terms reached peak sensitivities of 98.9% and peak specificities of 99.5%. Combining search terms optimized both sensitivity and specificity at 94.2%. Empirically derived search strategies combining indexing terms and textwords can achieve high sensitivity and high specificity for retrieving qualitative studies from CINAHL.

  2. QUALITATIVE STUDIES IN ACCOUNTING: THE ABDUCTIVE. RESEARCH STRATEGY.

    Directory of Open Access Journals (Sweden)

    Claudia URDARI

    2014-11-01

    Full Text Available This paper addresses to accounting researchers and proposes the use of abductive research strategy to improve the quality of accounting research outcomes. We argue that abductive reasoning has developed as a typical research method in all fields of interpretive studies but is still unrecognized by accounting researchers and practitioners. Therefore, this study aims to raise awareness on the benefits obtained through the implementation of abduction as a research strategy. Starting from Peirce (1903 and Blaikie (1993, we explore two types of abduction designs and discuss the advantages of building accounting research on grounded concepts. While this is a conceptual paper that only describes the bridge abduction reasoning can build between studying the reality and new theory emergence, we do not tackle any ethnographical case studies, social survey, or other exploratory field analyses.

  3. The Study of Teaching Effective Strategies on Student's Math Achievements

    Directory of Open Access Journals (Sweden)

    Mohammad-Hassan Behzadi

    2014-01-01

    Full Text Available One of the most important factors in student's learning weakness and academic failure, is their unfamilarity or low awareness of the learning strategies and studying in mathematics. This study is performed to examine the students' math and reading skills and their study skills that impact on their academic progress. The main objective of the research is to study with emphasis on training study strategies versus ususal method (teaching without emphasis on training study strategies to increase the learning of mathematical concepts. The present method is quasi-experimental that via quasi-cluster sampling to adopt 17 guidance girly schools in grade 3th, to gauge effects of teaching reading skills on math learning of the students.The results of T-test showed that students who were taught with emphasis on study skills versus students who have been traditionally trained, had better math performance and higher academic achievement.Therefore it seems that teaching reading stratefies such as cognitive and meta-cognitive will ease mathematical learning process.

  4. Functionally enigmatic genes: a case study of the brain ignorome.

    Directory of Open Access Journals (Sweden)

    Ashutosh K Pandey

    Full Text Available What proportion of genes with intense and selective expression in specific tissues, cells, or systems are still almost completely uncharacterized with respect to biological function? In what ways do these functionally enigmatic genes differ from well-studied genes? To address these two questions, we devised a computational approach that defines so-called ignoromes. As proof of principle, we extracted and analyzed a large subset of genes with intense and selective expression in brain. We find that publications associated with this set are highly skewed--the top 5% of genes absorb 70% of the relevant literature. In contrast, approximately 20% of genes have essentially no neuroscience literature. Analysis of the ignorome over the past decade demonstrates that it is stubbornly persistent, and the rapid expansion of the neuroscience literature has not had the expected effect on numbers of these genes. Surprisingly, ignorome genes do not differ from well-studied genes in terms of connectivity in coexpression networks. Nor do they differ with respect to numbers of orthologs, paralogs, or protein domains. The major distinguishing characteristic between these sets of genes is date of discovery, early discovery being associated with greater research momentum--a genomic bandwagon effect. Finally we ask to what extent massive genomic, imaging, and phenotype data sets can be used to provide high-throughput functional annotation for an entire ignorome. In a majority of cases we have been able to extract and add significant information for these neglected genes. In several cases--ELMOD1, TMEM88B, and DZANK1--we have exploited sequence polymorphisms, large phenome data sets, and reverse genetic methods to evaluate the function of ignorome genes.

  5. Functionally Enigmatic Genes: A Case Study of the Brain Ignorome

    Science.gov (United States)

    Pandey, Ashutosh K.; Lu, Lu; Wang, Xusheng; Homayouni, Ramin; Williams, Robert W.

    2014-01-01

    What proportion of genes with intense and selective expression in specific tissues, cells, or systems are still almost completely uncharacterized with respect to biological function? In what ways do these functionally enigmatic genes differ from well-studied genes? To address these two questions, we devised a computational approach that defines so-called ignoromes. As proof of principle, we extracted and analyzed a large subset of genes with intense and selective expression in brain. We find that publications associated with this set are highly skewed—the top 5% of genes absorb 70% of the relevant literature. In contrast, approximately 20% of genes have essentially no neuroscience literature. Analysis of the ignorome over the past decade demonstrates that it is stubbornly persistent, and the rapid expansion of the neuroscience literature has not had the expected effect on numbers of these genes. Surprisingly, ignorome genes do not differ from well-studied genes in terms of connectivity in coexpression networks. Nor do they differ with respect to numbers of orthologs, paralogs, or protein domains. The major distinguishing characteristic between these sets of genes is date of discovery, early discovery being associated with greater research momentum—a genomic bandwagon effect. Finally we ask to what extent massive genomic, imaging, and phenotype data sets can be used to provide high-throughput functional annotation for an entire ignorome. In a majority of cases we have been able to extract and add significant information for these neglected genes. In several cases—ELMOD1, TMEM88B, and DZANK1—we have exploited sequence polymorphisms, large phenome data sets, and reverse genetic methods to evaluate the function of ignorome genes. PMID:24523945

  6. How developments in cryobiology, reproductive technologies and conservation genomics could shape gene banking strategies for (farm) animals.

    Science.gov (United States)

    Woelders, H; Windig, J; Hiemstra, S J

    2012-08-01

    Many local breeds are currently at risk because of replacement by a limited number of specialized commercial breeds. Concurrently, for many breeds, allelic diversity within breeds declines because of inbreeding. Gene banking of germplasm may serve to secure the breeds and the alleles for any future use, for instance to recover a lost breed, to address new breeding goals, to support breeding schemes in small populations to minimize inbreeding, and for conservation genetics and genomics research. Developments in cryobiology and reproductive technology have generated several possibilities for preserving germplasm in farm animals. Furthermore, in some mammalian and bird species, gene banking of material is difficult or impossible, requiring development of new alternative methods or improvement of existing methods. Depending on the species, there are interesting possibilities or research developments in the use of epididymal spermatozoa, oocytes and embryos, ovarian and testicular tissue, primordial germ cells, and somatic cells for the conservation of genetic diversity in farm- and other animal species. Rapid developments in genomics research also provide new opportunities to optimize conservation and sampling strategies and to characterize genome-wide genetic variation. With regard to gene banks for farm animals, collaboration between European countries is being developed through a number of organizations, aimed at sharing knowledge and expertise between national programmes. It would be useful to explore further collaboration between countries, within the framework of a European gene banking strategy that should minimize costs of conservation and maximize opportunities for exploitation and sustainable use of genetic diversity. © 2012 Blackwell Verlag GmbH.

  7. A strategy analysis for genetic association studies with known inbreeding

    Directory of Open Access Journals (Sweden)

    del Giacco Stefano

    2011-07-01

    Full Text Available Abstract Background Association studies consist in identifying the genetic variants which are related to a specific disease through the use of statistical multiple hypothesis testing or segregation analysis in pedigrees. This type of studies has been very successful in the case of Mendelian monogenic disorders while it has been less successful in identifying genetic variants related to complex diseases where the insurgence depends on the interactions between different genes and the environment. The current technology allows to genotype more than a million of markers and this number has been rapidly increasing in the last years with the imputation based on templates sets and whole genome sequencing. This type of data introduces a great amount of noise in the statistical analysis and usually requires a great number of samples. Current methods seldom take into account gene-gene and gene-environment interactions which are fundamental especially in complex diseases. In this paper we propose to use a non-parametric additive model to detect the genetic variants related to diseases which accounts for interactions of unknown order. Although this is not new to the current literature, we show that in an isolated population, where the most related subjects share also most of their genetic code, the use of additive models may be improved if the available genealogical tree is taken into account. Specifically, we form a sample of cases and controls with the highest inbreeding by means of the Hungarian method, and estimate the set of genes/environmental variables, associated with the disease, by means of Random Forest. Results We have evidence, from statistical theory, simulations and two applications, that we build a suitable procedure to eliminate stratification between cases and controls and that it also has enough precision in identifying genetic variants responsible for a disease. This procedure has been successfully used for the beta-thalassemia, which is

  8. In search of suitable reference genes for gene expression studies of human renal cell carcinoma by real-time PCR

    Directory of Open Access Journals (Sweden)

    Kristiansen Glen

    2007-06-01

    Full Text Available Abstract Background Housekeeping genes are commonly used as endogenous reference genes for the relative quantification of target genes in gene expression studies. No conclusive systematic study comparing the suitability of different candidate reference genes in clear cell renal cell carcinoma has been published to date. To remedy this situation, 10 housekeeping genes for normalizing purposes of RT-PCR measurements already recommended in various studies were examined with regard to their usefulness as reference genes. Results The expression of the potential reference genes was examined in matched malignant and non-malignant tissue specimens from 25 patients with clear cell renal cell carcinoma. Quality assessment of isolated RNA performed with a 2100 Agilent Bioanalyzer showed a mean RNA integrity number of 8.7 for all samples. The between-run variations related to the crossing points of PCR reactions of a control material ranged from 0.17% to 0.38%. The expression of all genes did not depend on age, sex, and tumour stage. Except the genes TATA box binding protein (TBP and peptidylprolyl isomerase A (PPIA, all genes showed significant differences in expression between malignant and non-malignant pairs. The expression stability of the candidate reference genes was additionally controlled using the software programs geNorm and NormFinder. TBP and PPIA were validated as suitable reference genes by normalizing the target gene ADAM9 using these two most stably expressed genes in comparison with up- and down-regulated housekeeping genes of the panel. Conclusion Our study demonstrated the suitability of the two housekeeping genes PPIA and TBP as endogenous reference genes when comparing malignant tissue samples with adjacent normal tissue samples from clear cell renal cell carcinoma. Both genes are recommended as reference genes for relative gene quantification in gene profiling studies either as single gene or preferably in combination.

  9. A strategy to search for common obesity and type 2 diabetes genes.

    Science.gov (United States)

    Elbers, Clara C; Onland-Moret, N Charlotte; Franke, Lude; Niehoff, Anne G; van der Schouw, Yvonne T; Wijmenga, Cisca

    2007-01-01

    Worldwide, the incidence of type 2 diabetes is rising rapidly, mainly because of the increase in the incidence of obesity, which is an important risk factor for this condition. Both obesity and type 2 diabetes are complex genetic traits but they also share some nongenetic risk factors. Hence, it is tempting to speculate that the susceptibility to type 2 diabetes and obesity might also partly be due to shared genes. By comparing all of the published genome scans for type 2 diabetes and obesity, five overlapping chromosomal regions for both diseases (encompassing 612 candidate genes) have been identified. By analysing these five susceptibility loci for type 2 diabetes and obesity, using six freely available bioinformatics tools for disease gene identification, 27 functional candidate genes have been pinpointed that are involved in eating behaviour, metabolism and inflammation. These genes might reveal a molecular link between the two disorders.

  10. Reference gene selection for head and neck squamous cell carcinoma gene expression studies

    Directory of Open Access Journals (Sweden)

    Raynal Caroline

    2009-08-01

    Full Text Available Abstract Background It is no longer adequate to choose reference genes blindly. We present the first study that defines the suitability of 12 reference genes commonly used in cancer studies (ACT, ALAS, B2M, GAPDH, HMBS, HPRT, KALPHA, RPS18, RPL27, RPS29, SHAD and TBP for the normalization of quantitative expression data in the field of head and neck squamous cell carcinoma (HNSCC. Results Raw expression levels were measured by RT-qPCR in HNSCC and normal matched mucosa of 46 patients. We analyzed the expression stability using geNorm and NormFinder and compared the expression levels between subgroups. In HNSCC and/or normal mucosa, the four best normalization genes were ALAS, GAPDH, RPS18 and SHAD and the most stable combination of two genes was GAPDH-SHAD. We recommend using KALPHA-TBP for the study of T1-T2 tumors, RPL27-SHAD for T3-T4 tumors, KALPHA-SHAD for N0 tumors, and ALAS-TBP for N+ tumors. ACT, B2M, GAPDH, HMBS, HPRT, KALPHA, RPS18, RPS29, SHAD and TBP were slightly misregulated ( Conclusion In the field of HNSCC, this study will guide researchers in selecting the most appropriate reference genes from among 12 potentially suitable reference genes, depending on the specific setting of their experiments.

  11. Skills and compensation strategies in adult ADHD - A qualitative study.

    Science.gov (United States)

    Canela, Carlos; Buadze, Anna; Dube, Anish; Eich, Dominique; Liebrenz, Michael

    2017-01-01

    The primary objectives of this study were to investigate how adult patients with ADHD coped with their symptoms prior to diagnosis and treatment, what skills and compensation strategies they had developed and what their self-perceptions of these strategies were. We used a qualitative approach to analyze interviews with 32 outpatients of a specialty care unit at a university hospital. Patients reported frequent use of diverse compensatory strategies with varying degrees of effectiveness. These were classified into five categories (organizational, motoric, attentional, social, psychopharmacological). In certain circumstances, ADHD symptoms were even perceived as useful. Before diagnosis and treatment, patients with ADHD may develop a variety of skills to cope with their symptoms. Several of these skills are perceived as helpful. Knowledge of self-generated coping strategies may help better understand patients and their histories and thus facilitate patient cooperation. Moreover, knowing ways in which such patients cope with their symptoms may help elucidate reasons for late or under-diagnosing of the disorder.

  12. Variable-length haplotype construction for gene-gene interaction studies

    OpenAIRE

    Assawamakin, Anunchai; Chaiyaratana, Nachol; Limwongse, Chanin; Sinsomros, Saravudh; Yenchitsomanus, Pa-thai; Youngkong, Prakarnkiat

    2013-01-01

    This paper presents a non-parametric classification technique for identifying a candidate bi-allelic genetic marker set that best describes disease susceptibility in gene-gene interaction studies. The developed technique functions by creating a mapping between inferred haplotypes and case/control status. The technique cycles through all possible marker combination models generated from the available marker set where the best interaction model is determined from prediction accuracy and two aux...

  13. Unintentional miRNA ablation is a risk factor in gene knockout studies: a short report.

    Directory of Open Access Journals (Sweden)

    Ivan Osokine

    2008-02-01

    Full Text Available One of the most powerful techniques for studying the function of a gene is to disrupt the expression of that gene using genetic engineering strategies such as targeted recombination or viral integration of gene trap cassettes. The tremendous utility of these tools was recognized this year with the awarding of the Nobel Prize in Physiology or Medicine to Capecchi, Evans, and Smithies for their pioneering work in targeted recombination mutagenesis in mammals. Another noteworthy discovery made nearly a decade ago was the identification of a novel class of non-coding genes called microRNAs. MicroRNAs are among the largest known classes of regulatory elements with more than 1000 predicted to exist in the mouse genome. Over 50% of known microRNAs are located within introns of coding genes. Given that currently about half of the genes in mouse have been knocked out, we investigated the possibility that intronic microRNAs may have been coincidentally deleted or disrupted in some of these mouse models. We searched published murine knockout studies and gene trap embryonic stem cell line databases for cases where a microRNA was located within or near the manipulated genomic loci, finding almost 200 cases where microRNA expression may have been disrupted along with another gene. Our results draw attention to the need for careful planning in future knockout studies to minimize the unintentional disruption of microRNAs. These data also raise the possibility that many knockout studies may need to be reexamined to determine if loss of a microRNA contributes to the phenotypic consequences attributed to loss of a protein-encoding gene.

  14. The relationship between study strategies and academic performance.

    Science.gov (United States)

    Zhou, Yuanyuan; Graham, Lori; West, Courtney

    2016-10-07

    To investigate if and to what extent the Learning and Study Strategy Inventory (LASSI) and the Self-Directed Learning Readiness Scale (SDLRS) yield academic performance predictors; To examine if LASSI findings are consistent with previous research. Medical school students completed the LASSI and SDLRS before their first and second years (n = 168). Correlational and regression analyses were used to determine the predictive value of the LASSI and the SDLRS. Paired t-tests were used to test if the two measurement points differed. Bivariate correlations and R 2 s were compared with five other relevant studies. The SDLRS was moderately correlated with all LASSI subscales in both measures (r (152) =.255, p=.001) to (r (152) =.592, p =.000). The first SDLRS, nor the first LASSI, were predictive of academic performance. The second LASSI measure was a significant predictor of academic performance (R 2 (138) = 0.188, p = .003). Six prior LASSI studies yielded a range of R 2 s from 10-49%. The SDLRS is moderately correlated with all LASSI subscales. However, the predictive value of the SDLRS and LASSI differ. The SDLRS does not appear to be directly related to academic performance, but LASSI subscales: Concentration, Motivation, Time Management, and Test Strategies tend to be correlated. The explained LASSI variance ranges from 10% to 49%, indicating a small to substantial effect. Utilizing the LASSI to provide medical school students with information about their strengths and weaknesses and implementing targeted support in specific study strategies may yield positive academic performance outcomes.

  15. Environmental confounding in gene-environment interaction studies.

    Science.gov (United States)

    Vanderweele, Tyler J; Ko, Yi-An; Mukherjee, Bhramar

    2013-07-01

    We show that, in the presence of uncontrolled environmental confounding, joint tests for the presence of a main genetic effect and gene-environment interaction will be biased if the genetic and environmental factors are correlated, even if there is no effect of either the genetic factor or the environmental factor on the disease. When environmental confounding is ignored, such tests will in fact reject the joint null of no genetic effect with a probability that tends to 1 as the sample size increases. This problem with the joint test vanishes under gene-environment independence, but it still persists if estimating the gene-environment interaction parameter itself is of interest. Uncontrolled environmental confounding will bias estimates of gene-environment interaction parameters even under gene-environment independence, but it will not do so if the unmeasured confounding variable itself does not interact with the genetic factor. Under gene-environment independence, if the interaction parameter without controlling for the environmental confounder is nonzero, then there is gene-environment interaction either between the genetic factor and the environmental factor of interest or between the genetic factor and the unmeasured environmental confounder. We evaluate several recently proposed joint tests in a simulation study and discuss the implications of these results for the conduct of gene-environment interaction studies.

  16. A lentiviral gene therapy strategy for the in vitro production of feline erythropoietin.

    Directory of Open Access Journals (Sweden)

    Natalia Vapniarsky

    Full Text Available Nonregenerative anemia due to chronic renal failure is a common problem in domestic cats. Unfortunately, administration of recombinant human erythropoietin often only improves anemia temporarily due to antibody development. In this in vitro study, feline erythropoietin cDNA was cloned from feline renal tissue and utilized in the construction of a replication-defective lentiviral vector. The native recombinant feline erythropoietin (rfEPO sequence was confirmed by sequencing. Upon viral vector infection of human 293H cells, Crandall Renal Feline Kidney cell line and primary feline peripheral blood mononuclear cells, bioactive rfEPO protein was produced. The presence of cellular rfEPO cDNA was confirmed by standard PCR, production of abundant rfEPO mRNA was confirmed by real-time PCR, and secretion of rfEPO protein was demonstrated by Western blot analyses, while rfEPO protein bioactivity was confirmed via an MTT proliferation bioassay. This in vitro study demonstrates the feasibility of a replication-defective lentiviral vector delivery system for the in vitro production of biologically active feline erythropoietin. Anemic cats with chronic renal failure represent a potential in vivo application of a lentiviral gene therapy system.

  17. Generic strategies: an evolutionary and comparative study of three views

    Directory of Open Access Journals (Sweden)

    Sidney Chaves

    2010-04-01

    Full Text Available This study analyses visions of three of the most renowned authors regarding generic strategies, making a comparison among those visions along the time. To perform such comparison, two distinct works of each author were selected and then it is pointed out how changes showed up from one moment to another. The selected authors are Ansoff, Miles et al. and Porter, all responsible for three of the most spread typologies for generic strategies. From a chronological point of view, these typologies have been originally proposed between 1965 and 1980 and revisited between 1985 and 1988. Despite time passed from then until today, these typologies are still fully adequate and completely applicable to organizations' present reality. Contributions of this study reside on detailed presentation of each typology's major characteristics, due to detailed and judicious bibliography revision.

  18. A longitudinal study of gene expression in healthy individuals

    Directory of Open Access Journals (Sweden)

    Tessier Michel

    2009-06-01

    Full Text Available Abstract Background The use of gene expression in venous blood either as a pharmacodynamic marker in clinical trials of drugs or as a diagnostic test requires knowledge of the variability in expression over time in healthy volunteers. Here we defined a normal range of gene expression over 6 months in the blood of four cohorts of healthy men and women who were stratified by age (22–55 years and > 55 years and gender. Methods Eleven immunomodulatory genes likely to play important roles in inflammatory conditions such as rheumatoid arthritis and infection in addition to four genes typically used as reference genes were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR, as well as the full genome as represented by Affymetrix HG U133 Plus 2.0 microarrays. Results Gene expression levels as assessed by qRT-PCR and microarray were relatively stable over time with ~2% of genes as measured by microarray showing intra-subject differences over time periods longer than one month. Fifteen genes varied by gender. The eleven genes examined by qRT-PCR remained within a limited dynamic range for all individuals. Specifically, for the seven most stably expressed genes (CXCL1, HMOX1, IL1RN, IL1B, IL6R, PTGS2, and TNF, 95% of all samples profiled fell within 1.5–2.5 Ct, the equivalent of a 4- to 6-fold dynamic range. Two subjects who experienced severe adverse events of cancer and anemia, had microarray gene expression profiles that were distinct from normal while subjects who experienced an infection had only slightly elevated levels of inflammatory markers. Conclusion This study defines the range and variability of gene expression in healthy men and women over a six-month period. These parameters can be used to estimate the number of subjects needed to observe significant differences from normal gene expression in clinical studies. A set of genes that varied by gender was also identified as were a set of genes with elevated

  19. The relationship between study strategies and academic performance

    OpenAIRE

    Zhou, Yuanyuan; Graham, Lori; West, Courtney

    2016-01-01

    Objectives To investigate if and to what extent the Learning and Study Strategy Inventory (LASSI) and the Self-Directed Learning Readiness Scale (SDLRS) yield academic performance predictors; To examine if LASSI findings are consistent with previous research. Methods Medical school students completed the LASSI and SDLRS before their first and second years (n = 168). Correlational and regression analyses were used to determine the predictive value of the LASSI and the SDLRS. Paired t-tests wer...

  20. Study of selected phenotype switching strategies in time varying environment

    Science.gov (United States)

    Horvath, Denis; Brutovsky, Branislav

    2016-03-01

    Population heterogeneity plays an important role across many research, as well as the real-world, problems. The population heterogeneity relates to the ability of a population to cope with an environment change (or uncertainty) preventing its extinction. However, this ability is not always desirable as can be exemplified by an intratumor heterogeneity which positively correlates with the development of resistance to therapy. Causation of population heterogeneity is therefore in biology and medicine an intensively studied topic. In this paper the evolution of a specific strategy of population diversification, the phenotype switching, is studied at a conceptual level. The presented simulation model studies evolution of a large population of asexual organisms in a time-varying environment represented by a stochastic Markov process. Each organism disposes with a stochastic or nonlinear deterministic switching strategy realized by discrete-time models with evolvable parameters. We demonstrate that under rapidly varying exogenous conditions organisms operate in the vicinity of the bet-hedging strategy, while the deterministic patterns become relevant as the environmental variations are less frequent. Statistical characterization of the steady state regimes of the populations is done using the Hellinger and Kullback-Leibler functional distances and the Hamming distance.

  1. Strategies for Integrated Analysis of Genetic, Epigenetic, and Gene Expression Variation in Cancer: Addressing the Challenges

    DEFF Research Database (Denmark)

    Thingholm, Louise Bruun; Andersen, Lars; Makalic, Enes

    2016-01-01

    The development and progression of cancer, a collection of diseases with complex genetic architectures, is facilitated by the interplay of multiple etiological factors. This complexity challenges the traditional single-platform study design and calls for an integrated approach to data analysis. H......—making the assessment of disease risk against a composite genomic factor possible. The focus of this review is to provide an overview and introduction to the main strategies and to discuss where there is a need for further development.......The development and progression of cancer, a collection of diseases with complex genetic architectures, is facilitated by the interplay of multiple etiological factors. This complexity challenges the traditional single-platform study design and calls for an integrated approach to data analysis....... However, integration of heterogeneous measurements of biological variation is a non-trivial exercise due to the diversity of the human genome and the variety of output data formats and genome coverage obtained from the commonly used molecular platforms. This review article will provide an introduction...

  2. Validation of Reference Genes for Relative Quantitative Gene Expression Studies in Cassava (Manihot esculenta Crantz) by Using Quantitative Real-Time PCR.

    Science.gov (United States)

    Hu, Meizhen; Hu, Wenbin; Xia, Zhiqiang; Zhou, Xincheng; Wang, Wenquan

    2016-01-01

    Reverse transcription quantitative real-time polymerase chain reaction (real-time PCR, also referred to as quantitative RT-PCR or RT-qPCR) is a highly sensitive and high-throughput method used to study gene expression. Despite the numerous advantages of RT-qPCR, its accuracy is strongly influenced by the stability of internal reference genes used for normalizations. To date, few studies on the identification of reference genes have been performed on cassava (Manihot esculenta Crantz). Therefore, we selected 26 candidate reference genes mainly via the three following channels: reference genes used in previous studies on cassava, the orthologs of the most stable Arabidopsis genes, and the sequences obtained from 32 cassava transcriptome sequence data. Then, we employed ABI 7900 HT and SYBR Green PCR mix to assess the expression of these genes in 21 materials obtained from various cassava samples under different developmental and environmental conditions. The stability of gene expression was analyzed using two statistical algorithms, namely geNorm and NormFinder. geNorm software suggests the combination of cassava4.1_017977 and cassava4.1_006391 as sufficient reference genes for major cassava samples, the union of cassava4.1_014335 and cassava4.1_006884 as best choice for drought stressed samples, and the association of cassava4.1_012496 and cassava4.1_006391 as optimal choice for normally grown samples. NormFinder software recommends cassava4.1_006884 or cassava4.1_006776 as superior reference for qPCR analysis of different materials and organs of drought stressed or normally grown cassava, respectively. Results provide an important resource for cassava reference genes under specific conditions. The limitations of these findings were also discussed. Furthermore, we suggested some strategies that may be used to select candidate reference genes.

  3. Gene set-based analysis of polymorphisms: finding pathways or biological processes associated to traits in genome-wide association studies

    Science.gov (United States)

    Medina, Ignacio; Montaner, David; Bonifaci, Nuria; Pujana, Miguel Angel; Carbonell, José; Tarraga, Joaquin; Al-Shahrour, Fatima; Dopazo, Joaquin

    2009-01-01

    Genome-wide association studies have become a popular strategy to find associations of genes to traits of interest. Despite the high-resolution available today to carry out genotyping studies, the success of its application in real studies has been limited by the testing strategy used. As an alternative to brute force solutions involving the use of very large cohorts, we propose the use of the Gene Set Analysis (GSA), a different analysis strategy based on testing the association of modules of functionally related genes. We show here how the Gene Set-based Analysis of Polymorphisms (GeSBAP), which is a simple implementation of the GSA strategy for the analysis of genome-wide association studies, provides a significant increase in the power testing for this type of studies. GeSBAP is freely available at http://bioinfo.cipf.es/gesbap/ PMID:19502494

  4. Faculty and student perceptions of effective study strategies and materials.

    Science.gov (United States)

    Suda, Katie J; Bell, Gillian C; Franks, Andrea S

    2011-12-15

    To evaluate faculty members' and students' perceptions of study strategies and materials. Focus groups were conducted with course directors and first- and second-year students to generate ideas relating to use of course materials, technology, class attendance, and study strategies for mastering class concepts. Students and faculty members differed in their opinions about the utility of textbooks and supplemental resources. The main learning method recommended by students and faculty members was repeated review of course material. Students recommended viewing classroom lectures again online, if possible. Course directors reported believing that class attendance is important, but students based their opinions regarding the importance of attendance on their perceptions of lecture and handout quality. Results did not differ by campus or by student group (first-year vs. second-year students). Students and faculty members have differing opinions on the process that could influence learning and course design. Faculty members should understand the strategies students are using to learn course material and consider additional or alternative course design and delivery techniques based on student feedback.

  5. The what, how much, and when of study strategies: comparing intended versus actual study behaviour.

    Science.gov (United States)

    Blasiman, Rachael N; Dunlosky, John; Rawson, Katherine A

    2017-07-01

    The study behaviours of students can be assessed from several perspectives, such as what study strategies are used, the total number of hours of study, and the distribution of studying over time. Here, we present the results of a survey study that considered each of these perspectives by asking students to report the what, how much, and when of their study behaviours over the course of a semester. As important, to better understand students' use of study strategies, we also had students report at the beginning of the semester how they intended to study and their beliefs about the effectiveness of a variety of common strategies. Our results indicate that during the semester, students rely on relatively ineffective strategies and mass their studying the day or two before an exam. However, students intended to begin studying earlier and to use a mix of effective and ineffective study habits. Despite their use of some ineffective strategies, they did have a relatively accurate assessment of which strategies were less versus more effective. Taken together, our results suggest that students have some excellent intentions but may falter because massing study the evening before an exam limits their use of more effective study strategies.

  6. Stem cell gene therapy for HIV: strategies to inhibit viral entry and replication.

    Science.gov (United States)

    DiGiusto, David L

    2015-03-01

    Since the demonstration of a cure of an HIV+ patient with an allogeneic stem cell transplant using naturally HIV-resistant cells, significant interest in creating similar autologous products has fueled the development of a variety of "cell engineering" approaches to stem cell therapy for HIV. Among the more well-studied strategies is the inhibition of viral entry through disruption of expression of viral co-receptors or through competitive inhibitors of viral fusion with the cell membrane. Preclinical evaluation of these approaches often starts in vitro but ultimately is tested in animal models prior to clinical implementation. In this review, we trace the development of several key approaches (meganucleases, short hairpin RNA (shRNA), and fusion inhibitors) to modification of hematopoietic stem cells designed to impart resistance to HIV to their T-cell and monocytic progeny. The basic evolution of technologies through in vitro and in vivo testing is discussed as well as the pros and cons of each approach and how the addition of postentry inhibitors may enhance the overall antiviral efficacy of these approaches.

  7. Social Strategies during University Studies Predict Early Career Work Burnout and Engagement: 18-Year Longitudinal Study

    Science.gov (United States)

    Salmela-Aro, Katariina; Tolvanen, Asko; Nurmi, Jari-Erik

    2011-01-01

    This longitudinal study spanning 18 years examined the role of social strategies in early career adaptation. The aim was to find out whether individuals' social strategies measured during their university studies had an impact on work burnout and work engagement measured 10-18 years later. A sample of 292 university students completed the SAQ…

  8. mRNA expression in rabbit experimental aneurysms: a study using gene chip microarrays.

    Science.gov (United States)

    Mangrum, W I; Farassati, F; Kadirvel, R; Kolbert, C P; Raghavakaimal, S; Dai, D; Ding, Y H; Grill, D; Khurana, V G; Kallmes, D F

    2007-05-01

    The molecular characteristics of intracranial aneurysms are still poorly documented. A rabbit elastase aneurysm model has been helpful in the evaluation of devices and strategies involved in endovascular treatment of aneurysms. The goal of this project was to document the molecular changes, assessed by gene chip microarrays, associated with the creation of aneurysms in this model compared with the contralateral carotid artery. A microarray of rabbit genes of interest was constructed using rabbit nucleotide sequences from GenBank. Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery in 4 rabbits. Twelve weeks after aneurysm creation, RNA was isolated from the aneurysm as well as the contralateral common carotid artery and used for microarray experiments. Reverse transcription-polymerase chain reaction (RT-PCR) was performed on 1 animal as a confirmatory test. Ninety-six (46%) of 209 genes in the microarray were differentially expressed in the rabbit aneurysm compared with the contralateral common carotid artery. In general, differential gene expression followed specific molecular pathways. Similarities were found between rabbit aneurysms and human intracranial aneurysms, including increased metalloproteinase activity and decreased production of the extracellular matrix. RT-PCR results confirmed the differential expression found by the gene chip microarray. The molecular characteristics of the rabbit elastase-induced saccular aneurysm are described. The rabbit aneurysm model shares some molecular features with human intracranial aneurysms. Future studies can use the rabbit model and the new rabbit gene chip microarray to study the molecular aspects of saccular aneurysms.

  9. A comparative study of three different gene expression analysis methods.

    Science.gov (United States)

    Choe, Jae Young; Han, Hyung Soo; Lee, Seon Duk; Lee, Hanna; Lee, Dong Eun; Ahn, Jae Yun; Ryoo, Hyun Wook; Seo, Kang Suk; Kim, Jong Kun

    2017-12-04

    TNF-α regulates immune cells and acts as an endogenous pyrogen. Reverse transcription polymerase chain reaction (RT-PCR) is one of the most commonly used methods for gene expression analysis. Among the alternatives to PCR, loop-mediated isothermal amplification (LAMP) shows good potential in terms of specificity and sensitivity. However, few studies have compared RT-PCR and LAMP for human gene expression analysis. Therefore, in the present study, we compared one-step RT-PCR, two-step RT-LAMP and one-step RT-LAMP for human gene expression analysis. We compared three gene expression analysis methods using the human TNF-α gene as a biomarker from peripheral blood cells. Total RNA from the three selected febrile patients were subjected to the three different methods of gene expression analysis. In the comparison of three gene expression analysis methods, the detection limit of both one-step RT-PCR and one-step RT-LAMP were the same, while that of two-step RT-LAMP was inferior. One-step RT-LAMP takes less time, and the experimental result is easy to determine. One-step RT-LAMP is a potentially useful and complementary tool that is fast and reasonably sensitive. In addition, one-step RT-LAMP could be useful in environments lacking specialized equipment or expertise.

  10. Strategy for standardization of preeclampsia research study design.

    Science.gov (United States)

    Myatt, Leslie; Redman, Christopher W; Staff, Anne Cathrine; Hansson, Stefan; Wilson, Melissa L; Laivuori, Hannele; Poston, Lucilla; Roberts, James M

    2014-06-01

    Preeclampsia remains a major problem worldwide for mothers and babies. Despite intensive study, we have not been able to improve the management or early recognition of preeclampsia. At least part of this is because of failure to standardize the approach to studying this complex syndrome. It is possible that within the syndrome there may be different phenotypes with pathogenic pathways that differ between the subtypes. The capacity to recognize and to exploit different subtypes is of obvious importance for prediction, prevention, and treatment. We present a strategy for research to study preeclampsia, which will allow discrimination of such possible subtypes and also allow comparison and perhaps combinations of findings in different studies by standardized data and biosample collection. To make studies relevant to current clinical practice, the definition of preeclampsia can be that currently used and accepted. However, more importantly, sufficient data should be collected to allow other diagnostic criteria to be used and applied retrospectively. To that end, we present what we consider to be the minimum requirements for a data set in a study of preeclampsia that will facilitate comparisons. We also present a comprehensive or optimal data set for in-depth investigation of pathophysiology. As we approach the definition of phenotypes of preeclampsia by clinical and biochemical criteria, adherence to standardized protocols will hasten our understanding of the causes of preeclampsia and development of targeted treatment strategies.

  11. A strategy for the analysis of gene expression during neural development.

    Science.gov (United States)

    Arnold, D; Feng, L; Kim, J; Heintz, N

    1994-10-11

    The delineation of cis-acting elements regulating stage-specific gene expression has played a critical role in the definition of the transcriptional circuitry regulating differentiation. In complex tissues such as the central nervous system, differentiation often requires temporally and spatially dynamic epigenetic cues that cannot be reproduced in cell culture. In these cases, identification of critical regulatory sequences and subsequent characterization of cognate transcription factors have been limited by lack of a rapid and efficient assay system for gene expression. We report a methodology that combines particle-bombardment transfection procedures and organotypic slice culture techniques to provide an acute assay system for transcriptional control in the developing central nervous system. Using this system, we demonstrate that cell-specific regulation of the brain lipid-binding protein (BLBP) gene in Bergmann glia, astrocytes, and migrating granule cells is conferred by 1.7 kb of 5' flanking sequences and that Purkinje cell-specific expression of the calbindin D28k gene in cerebellar cortex can be achieved with 1.1 kb of flanking DNA. Nearly 100% cotransfection of multiple DNAs can be achieved, allowing the design of precisely internally controlled experiments and providing the potential for rapid and efficient genetic analysis of gene function in single cells in a wild-type environment.

  12. Supply strategy configuration in fragmented production systems: An empirical study

    Directory of Open Access Journals (Sweden)

    Claudia Chackelson

    2013-07-01

    Full Text Available Purpose: Companies survive in saturated markets trying to be more productive and more efficient. In this context, it becomes critical for companies to manage the entire supply network to optimize overall performance.  Hence, the supply strategy plays an important role because it influences the way in which production and logistics network has to be configured and managed. This paper explores the benefits obtained configuring different supply strategies adapted to customer needs.Design/methodology/approach: For this purpose a case research from a Tier 2 point of view of the supply chain has been conducted. Findings and Originality/value: The case research demonstrates that a higher service level, less holding costs and increase turnovers can be obtained implementing the adequate supply strategy. Originality/value: There is a scarcity of research specifically focused on applied Supply Chain Principles within network configuration processes. Moreover, there are few empirical studies of global Tier 2 with multiple decoupling points into its supply chain network.

  13. Design and analysis issues in gene and environment studies

    Directory of Open Access Journals (Sweden)

    Liu Chen-yu

    2012-12-01

    Full Text Available Abstract Both nurture (environmental and nature (genetic factors play an important role in human disease etiology. Traditionally, these effects have been thought of as independent. This perspective is ill informed for non-mendelian complex disorders which result as an interaction between genetics and environment. To understand health and disease we must study how nature and nurture interact. Recent advances in human genomics and high-throughput biotechnology make it possible to study large numbers of genetic markers and gene products simultaneously to explore their interactions with environment. The purpose of this review is to discuss design and analytic issues for gene-environment interaction studies in the “-omics” era, with a focus on environmental and genetic epidemiological studies. We present an expanded environmental genomic disease paradigm. We discuss several study design issues for gene-environmental interaction studies, including confounding and selection bias, measurement of exposures and genotypes. We discuss statistical issues in studying gene-environment interactions in different study designs, such as choices of statistical models, assumptions regarding biological factors, and power and sample size considerations, especially in genome-wide gene-environment studies. Future research directions are also discussed.

  14. The Effect of Self-Regulated Learning Strategies on Academic Achievement: A Meta-Analysis Study

    Science.gov (United States)

    Ergen, Binnur; Kanadli, Sedat

    2017-01-01

    Problem Statement: Self-regulated learning strategies (cognitive, metacognitive, resource management, and motivational strategies) influence students' academic achievement, conceptual understanding, and motivation. Reviewing the national literature about self-regulated learning strategies, studies have indicated both significant and insignificant…

  15. The relationship between study strategies and academic performance

    Science.gov (United States)

    Graham, Lori; West, Courtney

    2016-01-01

    Objectives To investigate if and to what extent the Learning and Study Strategy Inventory (LASSI) and the Self-Directed Learning Readiness Scale (SDLRS) yield academic performance predictors; To examine if LASSI findings are consistent with previous research. Methods Medical school students completed the LASSI and SDLRS before their first and second years (n = 168). Correlational and regression analyses were used to determine the predictive value of the LASSI and the SDLRS. Paired t-tests were used to test if the two measurement points differed. Bivariate correlations and R2s were compared with five other relevant studies. Results The SDLRS was moderately correlated with all LASSI subscales in both measures (r(152) =.255, p=.001) to (r(152) =.592, p =.000). The first SDLRS, nor the first LASSI, were predictive of academic performance. The second LASSI measure was a significant predictor of academic performance (R2(138) = 0.188, p = .003). Six prior LASSI studies yielded a range of R2s from 10-49%. Conclusions The SDLRS is moderately correlated with all LASSI subscales. However, the predictive value of the SDLRS and LASSI differ. The SDLRS does not appear to be directly related to academic performance, but LASSI subscales: Concentration, Motivation, Time Management, and Test Strategies tend to be correlated. The explained LASSI variance ranges from 10% to 49%, indicating a small to substantial effect. Utilizing the LASSI to provide medical school students with information about their strengths and weaknesses and implementing targeted support in specific study strategies may yield positive academic performance outcomes. PMID:27718497

  16. A Comparative Study of Feature Selection and Classification Methods for Gene Expression Data

    KAUST Repository

    Abusamra, Heba

    2013-05-01

    Microarray technology has enriched the study of gene expression in such a way that scientists are now able to measure the expression levels of thousands of genes in a single experiment. Microarray gene expression data gained great importance in recent years due to its role in disease diagnoses and prognoses which help to choose the appropriate treatment plan for patients. This technology has shifted a new era in molecular classification, interpreting gene expression data remains a difficult problem and an active research area due to their native nature of “high dimensional low sample size”. Such problems pose great challenges to existing classification methods. Thus, effective feature selection techniques are often needed in this case to aid to correctly classify different tumor types and consequently lead to a better understanding of genetic signatures as well as improve treatment strategies. This thesis aims on a comparative study of state-of-the-art feature selection methods, classification methods, and the combination of them, based on gene expression data. We compared the efficiency of three different classification methods including: support vector machines, k- nearest neighbor and random forest, and eight different feature selection methods, including: information gain, twoing rule, sum minority, max minority, gini index, sum of variances, t- statistics, and one-dimension support vector machine. Five-fold cross validation was used to evaluate the classification performance. Two publicly available gene expression data sets of glioma were used for this study. Different experiments have been applied to compare the performance of the classification methods with and without performing feature selection. Results revealed the important role of feature selection in classifying gene expression data. By performing feature selection, the classification accuracy can be significantly boosted by using a small number of genes. The relationship of features selected in

  17. Robust Gene-Gene Interaction Analysis in Genome Wide Association Studies.

    Directory of Open Access Journals (Sweden)

    Yongkang Kim

    Full Text Available Genome-wide association studies (GWAS have successfully discovered hundreds of associations between genetic variants and complex traits. Most GWAS have focused on the identification of single variants. It has been shown that most of the variants that were discovered by GWAS could only partially explain disease heritability. The explanation for this missing heritability is generally believed to be gene-gene (GG or gene-environment (GE interactions and other structural variants. Generalized multifactor dimensionality reduction (GMDR has been proven to be reasonably powerful in detecting GG and GE interactions; however, its performance has been found to decline when outlying quantitative traits are present. This paper proposes a robust GMDR estimation method (based on the L-estimator and M-estimator estimation methods in an attempt to reduce the effects caused by outlying traits. A comparison of robust GMDR with the original MDR based on simulation studies showed the former method to outperform the latter. The performance of robust GMDR is illustrated through a real GWA example consisting of 8,577 samples from the Korean population using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR level as a phenotype. Robust GMDR identified the KCNH1 gene to have strong interaction effects with other genes on the function of insulin secretion.

  18. Comparison of Value Generation Strategies Between Planned and Emerging Strategies: A Study Based on Games of Companies

    Directory of Open Access Journals (Sweden)

    Marcos Paixão Garcez

    2012-06-01

    Full Text Available This study aims to analyze the economic results of the planned strategies compared to the emergent strategies in decision-making. The theoretical background emphasizes some aspects, like the strategy concept evolution throughout the time, the typology of strategies proposed by Mintzberg, the comparison between competition and cooperation, and the use of a business simulator as a tool for business research purposes. As a controlled experiment, the EGS simulator (Management Exercise Simulated allowed comparison of the economic results of the two decision-making situations. The findings show that when planned strategies were implemented without corrections, the value generated (expressed by the internal rate of return IRR = 1.51% was greater than in the case of adjusted emerging strategies in three periods (IRR= 1.40%. Comparing the two situations, it is possible to find a value added advantage of 7.86% in favor of the planned strategies, indicating the competition might be responsible for the value decreasing in real environment. Analyzing the performance degrees reached by the competitors, the ranking results show that there is no association between planned strategy and emerging strategies. Although the business simulators can be considered weak approximations for the business environment, the experiment contributed new evidence of the competition rise in oligopoly industries and a new methodological approach for studying this phenomenon.

  19. The Risk-Stratified Osteoporosis Strategy Evaluation study (ROSE)

    DEFF Research Database (Denmark)

    Rubin, Katrine Hass; Holmberg, Teresa; Rothmann, Mette Juel

    2015-01-01

    The risk-stratified osteoporosis strategy evaluation study (ROSE) is a randomized prospective population-based study investigating the effectiveness of a two-step screening program for osteoporosis in women. This paper reports the study design and baseline characteristics of the study population....... 35,000 women aged 65-80 years were selected at random from the population in the Region of Southern Denmark and-before inclusion-randomized to either a screening group or a control group. As first step, a self-administered questionnaire regarding risk factors for osteoporosis based on FRAX......(®) was issued to both groups. As second step, subjects in the screening group with a 10-year probability of major osteoporotic fractures ≥15 % were offered a DXA scan. Patients diagnosed with osteoporosis from the DXA scan were advised to see their GP and discuss pharmaceutical treatment according to Danish...

  20. Cell- and gene-based therapeutic strategies for periodontal regenerative medicine.

    Science.gov (United States)

    Rios, Hector F; Lin, Zhao; Oh, Bina; Park, Chan Ho; Giannobile, William V

    2011-09-01

    Inflammatory periodontal diseases are a leading cause of tooth loss and are linked to multiple systemic conditions, such as cardiovascular disease and stroke. Reconstruction of the support and function of affected tooth-supporting tissues represents an important therapeutic endpoint for periodontal regenerative medicine. An improved understanding of periodontal biology coupled with current advances in scaffolding matrices has introduced novel treatments that use cell and gene therapy to enhance periodontal tissue reconstruction and its biomechanical integration. Cell and gene delivery technologies have the potential to overcome limitations associated with existing periodontal therapies, and may provide a new direction in sustainable inflammation control and more predictable tissue regeneration of supporting alveolar bone, periodontal ligament, and cementum. This review provides clinicians with the current status of these early-stage and emerging cell- and gene-based therapeutics in periodontal regenerative medicine, and introduces their future application in clinical periodontal treatment. The paper concludes with prospects on the application of cell and gene tissue engineering technologies for reconstructive periodontology.

  1. Learning histology - dental and medical students' study strategies.

    Science.gov (United States)

    Johnson, S; Purkiss, J; Holaday, L; Selvig, D; Hortsch, M

    2015-05-01

    Histology, the science of cells and tissues at the microscopic level, is an integral component of most dental and medical curricula and is often taught using both traditional and novel computer-based didactic approaches. The purpose of this study was to analyse the strategies used by dental and medical students when studying this very visual and challenging subject. Data were collected from 75 dental and 143 medical students, who had almost identical histology learning resources at their disposal. When compared with their medical counterparts, dental students view histology as a more difficult subject and as less relevant for their future career. Whereas dental students, who are required to attend class unlike medical students, made more use of in-classroom learning opportunities, they did not take as much advantage of out-of-classroom resources. In addition, dental students reported a significantly higher tendency than medical students to work together, rather than to study alone. Small differences in the dental versus the medical learning environment associate with several observed differences in learning strategies that are adopted by dental and medical students. These differences should be considered when teaching the subject of histology to dental or to medical students. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Oscillatory EEG correlates of arithmetic strategies: A training study

    Directory of Open Access Journals (Sweden)

    Roland H. Grabner

    2012-10-01

    Full Text Available There has been a long tradition of research on mathematics education showing that children and adults use different strategies to solve arithmetic problems. Neurophysiological studies have recently begun to investigate the brain correlates of these strategies. The existing body of data, however, reflect static end points of the learning process and do not provide information on how brain activity changes in response to training or intervention. In this study, we explicitly address this issue by training participants in using fact retrieval strategies. We also investigate whether brain activity related to arithmetic fact learning is domain-specific or whether this generalizes to other learning materials, such as the solution of figural-spatial problems. Twenty adult students were trained on sets of two-digit multiplication problems and figural-spatial problems. After the training, they were presented with the trained and untrained problems while their brain activity was recorded by means of electroencephalography (EEG . In both problem types, the training resulted in accuracies over 90 % and significant decreases in solution times. Analyses of the oscillatory EEG data also revealed training effects across both problem types. Specifically, we observed training-related activity increases in the theta band (3-6 Hz and decreases in the lower alpha band (8-10 Hz, especially over parieto-occipital and parietal brain regions. These results provide the first evidence that a short term fact retrieval training results in significant changes in oscillatory EEG activity. These findings further corroborate the role of the theta band in the retrieval of semantic information from memory and suggest that theta activity is not only sensitive to fact retrieval in mental arithmetic but also in other domains.

  3. Oscillatory EEG Correlates of Arithmetic Strategies: A Training Study

    Science.gov (United States)

    Grabner, Roland H.; De Smedt, Bert

    2012-01-01

    There has been a long tradition of research on mathematics education showing that children and adults use different strategies to solve arithmetic problems. Neurophysiological studies have recently begun to investigate the brain correlates of these strategies. The existing body of data, however, reflect static end points of the learning process and do not provide information on how brain activity changes in response to training or intervention. In this study, we explicitly address this issue by training participants in using fact retrieval strategies. We also investigate whether brain activity related to arithmetic fact learning is domain-specific or whether this generalizes to other learning materials, such as the solution of figural-spatial problems. Twenty adult students were trained on sets of two-digit multiplication problems and figural-spatial problems. After the training, they were presented with the trained and untrained problems while their brain activity was recorded by means of electroencephalography (EEG). In both problem types, the training resulted in accuracies over 90% and significant decreases in solution times. Analyses of the oscillatory EEG data also revealed training effects across both problem types. Specifically, we observed training-related activity increases in the theta band (3–6 Hz) and decreases in the lower alpha band (8–10 Hz), especially over parietooccipital and parietal brain regions. These results provide the first evidence that a short-term fact retrieval training results in significant changes in oscillatory EEG activity. These findings further corroborate the role of the theta band in the retrieval of semantic information from memory and suggest that theta activity is sensitive to fact retrieval not only in mental arithmetic but also in other domains. PMID:23162495

  4. Evaluation and validation of housekeeping genes as reference for gene expression studies in pigeonpea (Cajanus cajan) under drought stress conditions.

    Science.gov (United States)

    Sinha, Pallavi; Singh, Vikas K; Suryanarayana, V; Krishnamurthy, L; Saxena, Rachit K; Varshney, Rajeev K

    2015-01-01

    Gene expression analysis using quantitative real-time PCR (qRT-PCR) is a very sensitive technique and its sensitivity depends on the stable performance of reference gene(s) used in the study. A number of housekeeping genes have been used in various expression studies in many crops however, their expression were found to be inconsistent under different stress conditions. As a result, species specific housekeeping genes have been recommended for different expression studies in several crop species. However, such specific housekeeping genes have not been reported in the case of pigeonpea (Cajanus cajan) despite the fact that genome sequence has become available for the crop. To identify the stable housekeeping genes in pigeonpea for expression analysis under drought stress conditions, the relative expression variations of 10 commonly used housekeeping genes (EF1α, UBQ10, GAPDH, 18SrRNA, 25SrRNA, TUB6, ACT1, IF4α, UBC and HSP90) were studied on root, stem and leaves tissues of Asha (ICPL 87119). Three statistical algorithms geNorm, NormFinder and BestKeeper were used to define the stability of candidate genes. geNorm analysis identified IF4α and TUB6 as the most stable housekeeping genes however, NormFinder analysis determined IF4α and HSP90 as the most stable housekeeping genes under drought stress conditions. Subsequently validation of the identified candidate genes was undertaken in qRT-PCR based gene expression analysis of uspA gene which plays an important role for drought stress conditions in pigeonpea. The relative quantification of the uspA gene varied according to the internal controls (stable and least stable genes), thus highlighting the importance of the choice of as well as validation of internal controls in such experiments. The identified stable and validated housekeeping genes will facilitate gene expression studies in pigeonpea especially under drought stress conditions.

  5. A combination test for detection of gene-environment interaction in cohort studies.

    Science.gov (United States)

    Coombes, Brandon; Basu, Saonli; McGue, Matt

    2017-07-01

    Identifying gene-environment (G-E) interactions can contribute to a better understanding of disease etiology, which may help researchers develop disease prevention strategies and interventions. One big criticism of studying G-E interaction is the lack of power due to sample size. Studies often restrict the interaction search to the top few hundred hits from a genome-wide association study or focus on potential candidate genes. In this paper, we test interactions between a candidate gene and an environmental factor to improve power by analyzing multiple variants within a gene. We extend recently developed score statistic based genetic association testing approaches to the G-E interaction testing problem. We also propose tests for interaction using gene-based summary measures that pool variants together. Although it has recently been shown that these summary measures can be biased and may lead to inflated type I error, we show that under several realistic scenarios, we can still provide valid tests of interaction. These tests use significantly less degrees of freedom and thus can have much higher power to detect interaction. Additionally, we demonstrate that the iSeq-aSum-min test, which combines a gene-based summary measure test, iSeq-aSum-G, and an interaction-based summary measure test, iSeq-aSum-I, provides a powerful alternative to test G-E interaction. We demonstrate the performance of these approaches using simulation studies and illustrate their performance to study interaction between the SNPs in several candidate genes and family climate environment on alcohol consumption using the Minnesota Center for Twin and Family Research dataset. © 2017 WILEY PERIODICALS, INC.

  6. Statistical power of model selection strategies for genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Zheyang Wu

    2009-07-01

    Full Text Available Genome-wide association studies (GWAS aim to identify genetic variants related to diseases by examining the associations between phenotypes and hundreds of thousands of genotyped markers. Because many genes are potentially involved in common diseases and a large number of markers are analyzed, it is crucial to devise an effective strategy to identify truly associated variants that have individual and/or interactive effects, while controlling false positives at the desired level. Although a number of model selection methods have been proposed in the literature, including marginal search, exhaustive search, and forward search, their relative performance has only been evaluated through limited simulations due to the lack of an analytical approach to calculating the power of these methods. This article develops a novel statistical approach for power calculation, derives accurate formulas for the power of different model selection strategies, and then uses the formulas to evaluate and compare these strategies in genetic model spaces. In contrast to previous studies, our theoretical framework allows for random genotypes, correlations among test statistics, and a false-positive control based on GWAS practice. After the accuracy of our analytical results is validated through simulations, they are utilized to systematically evaluate and compare the performance of these strategies in a wide class of genetic models. For a specific genetic model, our results clearly reveal how different factors, such as effect size, allele frequency, and interaction, jointly affect the statistical power of each strategy. An example is provided for the application of our approach to empirical research. The statistical approach used in our derivations is general and can be employed to address the model selection problems in other random predictor settings. We have developed an R package markerSearchPower to implement our formulas, which can be downloaded from the

  7. Validation of reference housekeeping genes for gene expression studies in western corn rootworm (Diabrotica virgifera virgifera.

    Directory of Open Access Journals (Sweden)

    Thaís Barros Rodrigues

    Full Text Available Quantitative Real-time PCR (qRT-PCR is a powerful technique to investigate comparative gene expression. In general, normalization of results using a highly stable housekeeping gene (HKG as an internal control is recommended and necessary. However, there are several reports suggesting that regulation of some HKGs is affected by different conditions. The western corn rootworm (WCR, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae, is a serious pest of corn in the United States and Europe. The expression profile of target genes related to insecticide exposure, resistance, and RNA interference has become an important experimental technique for study of western corn rootworms; however, lack of information on reliable HKGs under different conditions makes the interpretation of qRT-PCR results difficult. In this study, four distinct algorithms (Genorm, NormFinder, BestKeeper and delta-CT and five candidate HKGs to genes of reference (β-actin; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; β-tubulin; RPS9, ribosomal protein S9; EF1a, elongation factor-1α were evaluated to determine the most reliable HKG under different experimental conditions including exposure to dsRNA and Bt toxins and among different tissues and developmental stages. Although all the HKGs tested exhibited relatively stable expression among the different treatments, some differences were noted. Among the five candidate reference genes evaluated, β-actin exhibited highly stable expression among different life stages. RPS9 exhibited the most similar pattern of expression among dsRNA treatments, and both experiments indicated that EF1a was the second most stable gene. EF1a was also the most stable for Bt exposure and among different tissues. These results will enable researchers to use more accurate and reliable normalization of qRT-PCR data in WCR experiments.

  8. 'Smoking genes': a genetic association study.

    Directory of Open Access Journals (Sweden)

    Zoraida Verde

    Full Text Available Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A [rs1801272], CYP2A6*9 (-48T>G [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T [rs8192789], CYP2A13*3 (7520C>G, CYP2A13*4 (579G>A, CYP2A13*7 (578C>T [rs72552266], CYP2B6*4 (785A>G, CYP2B6*9 (516G>T, CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A [rs1800497], 5HTT LPR, HTR2A -1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126 and ethnically matched never smokers (controls, N = 80. The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both PA (Taq1A polymorphisms was 3.60 (95%CI: 1.75, 7.44 and 2.63 (95%CI: 1.41, 4.89 respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65. We found a significant genotype effect (all P≤0.017 for the following smoking-related phenotypes: (i cigarettes smoked per day and CYP2A13*3; (ii pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A; (iii nicotine dependence (assessed with the Fagestrom test and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5, serotoninergic (HTR2A, opioid (OPRM1 or cannabinoid receptors (CNR1.

  9. The Effect of Strategy on Problem Solving: An FMRI Study

    Science.gov (United States)

    Newman, Sharlene D.; Pruce, Benjamin; Rusia, Akash; Burns, Thomas, Jr.

    2010-01-01

    fMRI was used to examine the differential effect of two problem-solving strategies. Participants were trained to use both a pictorial/spatial and a symbolic/algebraic strategy to solve word problems. While these two strategies activated similar cortical regions, a number of differences were noted in the level of activation. These differences…

  10. Green supply chain management strategy selection using analytic network process: case study at PT XYZ

    Science.gov (United States)

    Adelina, W.; Kusumastuti, R. D.

    2017-01-01

    This study is about business strategy selection for green supply chain management (GSCM) for PT XYZ by using Analytic Network Process (ANP). GSCM is initiated as a response to reduce environmental impacts from industrial activities. The purposes of this study are identifying criteria and sub criteria in selecting GSCM Strategy, and analysing a suitable GSCM strategy for PT XYZ. This study proposes ANP network with 6 criteria and 29 sub criteria, which are obtained from the literature and experts’ judgements. One of the six criteria contains GSCM strategy options, namely risk-based strategy, efficiency-based strategy, innovation-based strategy, and closed loop strategy. ANP solves complex GSCM strategy-selection by using a more structured process and considering green perspectives from experts. The result indicates that innovation-based strategy is the most suitable green supply chain management strategy for PT XYZ.

  11. Study on Fusion Protein and Its gene in Baculovirus Specificity

    International Nuclear Information System (INIS)

    Nemr, W.A.H.

    2012-01-01

    Baculoviruses are subdivided into two groups depending on the type of budded virus envelop fusion protein; group I utilized gp64 which include the most of nucleopolyhedroviruses (NPVs), group II utilized F protein which include the remnants of NPVs and all Granuloviruses (GVs). Recent studies reported the viral F protein coding gene as a host cellular sourced gene and may evolutionary acquired from the host genome referring to phylogeny analysis of fusion proteins. Thus, it was deduced that F protein coding gene is species- specific nucleotide sequence related to the type of the specific host and if virus could infect an unexpected host, the resulted virus may encode a vary F gene. In this regard, the present study utilized the mentioned properties of F gene in an attempt to produce a model of specific and more economic wider range granulovirus bio- pesticide able to infect both Spodoptera littoralis and Phthorimaea operculella larvae. Multiple sequence alignment and phylogeny analysis were performed on six members of group II baculovirus, novel universal PCR primers were manually designed from the conserved regions in the alignment graph, targeted to amplify species- specific sequence entire F gene open reading frame (ORF) which is useful in molecular identification of baculovirus in unknown samples. So, the PCR product of SpliGV used to prepare a specific probe for the F gene of this type of virus. Results reflected that it is possible to infect S. littoralis larvae by PhopGV if injected into larval haemocoel, the resulted virus of this infection showed by using DNA hybridization technique to be encode to F gene homologous with the F gene of Spli GV, which is revealed that the resulted virus acquired this F gene sequence from the host genome after infection. Consequently, these results may infer that if genetic aberrations occur in the host genome, this may affect in baculoviral infectivity. So, this study aimed to investigate the effect of gamma radiation at

  12. Evaluating the ovarian cancer gonadotropin hypothesis: A candidate gene study

    Science.gov (United States)

    Lee, Alice W.; Tyrer, Jonathan P.; Doherty, Jennifer A.; Stram, Douglas A.; Kupryjanczyk, Jolanta; Dansonka-Mieszkowska, Agnieszka; Plisiecka-Halasa, Joanna; Spiewankiewicz, Beata; Myers, Emily J.; Chenevix-Trench, Georgia; Fasching, Peter A.; Beckmann, Matthias W.; Ekici, Arif B.; Hein, Alexander; Vergote, Ignace; Van Nieuwenhuysen, Els; Lambrechts, Diether; Wicklund, Kristine G.; Eilber, Ursula; Wang-Gohrke, Shan; Chang-Claude, Jenny; Rudolph, Anja; Sucheston-Campbell, Lara; Odunsi, Kunle; Moysich, Kirsten B.; Shvetsov, Yurii B.; Thompson, Pamela J.; Goodman, Marc T.; Wilkens, Lynne R.; Dörk, Thilo; Hillemanns, Peter; Dürst, Matthias; Runnebaum, Ingo B.; Bogdanova, Natalia; Pelttari, Liisa M.; Nevanlinna, Heli; Leminen, Arto; Edwards, Robert P.; Kelley, Joseph L.; Harter, Philipp; Schwaab, Ira; Heitz, Florian; du Bois, Andreas; Orsulic, Sandra; Lester, Jenny; Walsh, Christine; Karlan, Beth Y.; Hogdall, Estrid; Kjaer, Susanne K.; Jensen, Allan; Vierkant, Robert A.; Cunningham, Julie M.; Goode, Ellen L.; Fridley, Brooke L.; Southey, Melissa C.; Giles, Graham G.; Bruinsma, Fiona; Wu, Xifeng; Hildebrandt, Michelle A.T.; Lu, Karen; Liang, Dong; Bisogna, Maria; Levine, Douglas A.; Weber, Rachel Palmieri; Schildkraut, Joellen M.; Iversen, Edwin S.; Berchuck, Andrew; Terry, Kathryn L.; Cramer, Daniel W.; Tworoger, Shelley S.; Poole, Elizabeth M.; Olson, Sara H.; Orlow, Irene; Bandera, Elisa V.; Bjorge, Line; Tangen, Ingvild L.; Salvesen, Helga B.; Krakstad, Camilla; Massuger, Leon F.A.G.; Kiemeney, Lambertus A.; Aben, Katja K.H.; van Altena, Anne M.; Bean, Yukie; Pejovic, Tanja; Kellar, Melissa; Le, Nhu D.; Cook, Linda S.; Kelemen, Linda E.; Brooks-Wilson, Angela; Lubinski, Jan; Gronwald, Jacek; Cybulski, Cezary; Jakubowska, Anna; Wentzensen, Nicolas; Brinton, Louise A.; Lissowska, Jolanta; Yang, Hannah; Nedergaard, Lotte; Lundvall, Lene; Hogdall, Claus; Song, Honglin; Campbell, Ian G.; Eccles, Diana; Glasspool, Rosalind; Siddiqui, Nadeem; Carty, Karen; Paul, James; McNeish, Iain A.; Sieh, Weiva; McGuire, Valerie; Rothstein, Joseph H.; Whittemore, Alice S.; McLaughlin, John R.; Risch, Harvey A.; Phelan, Catherine M.; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Harrington, Patricia; Pike, Malcolm C.; Modugno, Francesmary; Rossing, Mary Anne; Ness, Roberta B.; Pharoah, Paul D.P.; Stram, Daniel O.; Wu, Anna H.; Pearce, Celeste Leigh

    2016-01-01

    Objective Ovarian cancer is a hormone-related disease with a strong genetic basis. However, none of its high-penetrance susceptibility genes and GWAS-identified variants to date are known to be involved in hormonal pathways. Given the hypothesized etiologic role of gonadotropins, an assessment of how variability in genes involved in the gonadotropin signaling pathway impacts disease risk is warranted. Methods Genetic data from 41 ovarian cancer study sites were pooled and unconditional logistic regression was used to evaluate whether any of the 2185 SNPs from 11 gonadotropin signaling pathway genes was associated with ovarian cancer risk. A burden test using the admixture likelihood (AML) method was also used to evaluate gene-level associations. Results We did not find any genome-wide significant associations between individual SNPs and ovarian cancer risk. However, there was some suggestion of gene-level associations for four gonadotropin signaling pathway genes: INHBB (p = 0.045, mucinous), LHCGR (p = 0.046, high-grade serous), GNRH (p = 0.041, high-grade serous), and FSHB (p = 0.036, overall invasive). There was also suggestive evidence for INHA (p = 0.060, overall invasive). Conclusions Ovarian cancer studies have limited sample numbers, thus fewer genome-wide susceptibility alleles, with only modest associations, have been identified relative to breast and prostate cancers. We have evaluated the majority of ovarian cancer studies with biological samples, to our knowledge, leaving no opportunity for replication. Using both our understanding of biology and powerful gene-level tests, we have identified four putative ovarian cancer loci near INHBB, LHCGR, GNRH, and FSHB that warrant a second look if larger sample sizes and denser genotype chips become available. PMID:25528498

  13. A study of structural properties of gene network graphs for mathematical modeling of integrated mosaic gene networks.

    Science.gov (United States)

    Petrovskaya, Olga V; Petrovskiy, Evgeny D; Lavrik, Inna N; Ivanisenko, Vladimir A

    2017-04-01

    Gene network modeling is one of the widely used approaches in systems biology. It allows for the study of complex genetic systems function, including so-called mosaic gene networks, which consist of functionally interacting subnetworks. We conducted a study of a mosaic gene networks modeling method based on integration of models of gene subnetworks by linear control functionals. An automatic modeling of 10,000 synthetic mosaic gene regulatory networks was carried out using computer experiments on gene knockdowns/knockouts. Structural analysis of graphs of generated mosaic gene regulatory networks has revealed that the most important factor for building accurate integrated mathematical models, among those analyzed in the study, is data on expression of genes corresponding to the vertices with high properties of centrality.

  14. Strategy of water resource protection and indicators: a pilot study

    International Nuclear Information System (INIS)

    Mancini, L.; Pace, G.

    2008-01-01

    Environmental integrated assessment of territorial areas allows to describe the actual status of pollution and ecosystem quality. This information can be considered as a starting point for an appropriate planning of territorial management. Integrated approach strategies will provide the possibility to obtain a sustainable balance among human social and economical needs and natural ecosystem conservation actions, extremely important for people wellness. Despite the national and regional value of these considerations, the Tiber river basin has been chosen as a case study, due to the presence of a complete spectrum of conditions and human pressures in its area. This research can be considered as one of the first studies correlating functional and structural degradation of ecosystems with human health in Italy [it

  15. Genes and Longevity: Lessons from Studies of Centenarians

    DEFF Research Database (Denmark)

    Yashin, AI; De Benedictis, G; Vaupel, JW

    2000-01-01

    In population studies of aging, the data on genetic markers are often collected for individuals from different age groups. The idea of such studies is to identify "longevity" or "frailty" genes by comparing the frequencies of genotypes in the oldest and in the younger groups of individuals. In th...

  16. Bone marrow transplantations to study gene function in hematopoietic cells

    NARCIS (Netherlands)

    de Winther, Menno P. J.; Heeringa, Peter

    2011-01-01

    Immune cells are derived from hematopoietic stem cells in the bone marrow. Experimental replacement of bone marrow offers the unique possibility to replace immune cells, to study gene function in mouse models of disease. Over the past decades, this technique has been used extensively to study, for

  17. Immunogenetic study in Chinese population with ankylosing spondylitis: are there specific genes recently disclosed?

    Science.gov (United States)

    Zhai, Jiayu; Rong, Ju; Li, Qiuxia; Gu, Jieruo

    2013-01-01

    Ankylosing spondylitis (AS) is a systemic, autoimmune disease resulting in the destruction of the affected joints. Over the past 5 years, several new genes or genetic regions associated with AS have been identified in the Chinese population. This paper aims to discuss the major findings and related potential mechanisms of these studies in our population. In recent years, due to the rapid advances in computational genetics and technology, there has been an increasing list of well-validated genes or genetic regions associated with AS susceptibility. So far, several genes or genetic regions have now been reported in the Han ethnic Chinese population, containing the major histocompatibility complex (MHC), ERAP1, IL-23R, 12q12, 2p15, 5q14.3, and so on. Different hypotheses for disease mechanisms have been investigated on the basis of the functional studies of these genes or genetic regions. This paper tries to summarize the association of several candidate genes with risk for AS in the Han ethnic Chinese population and aims to identify the novel inflammatory pathways and provide potential strategies for better therapies.

  18. Immunogenetic Study in Chinese Population with Ankylosing Spondylitis: Are There Specific Genes Recently Disclosed?

    Directory of Open Access Journals (Sweden)

    Jiayu Zhai

    2013-01-01

    Full Text Available Purpose. Ankylosing spondylitis (AS is a systemic, autoimmune disease resulting in the destruction of the affected joints. Over the past 5 years, several new genes or genetic regions associated with AS have been identified in the Chinese population. This paper aims to discuss the major findings and related potential mechanisms of these studies in our population. Recent Findings. In recent years, due to the rapid advances in computational genetics and technology, there has been an increasing list of well-validated genes or genetic regions associated with AS susceptibility. So far, several genes or genetic regions have now been reported in the Han ethnic Chinese population, containing the major histocompatibility complex (MHC, ERAP1, IL-23R, 12q12, 2p15, 5q14.3, and so on. Different hypotheses for disease mechanisms have been investigated on the basis of the functional studies of these genes or genetic regions. Summary. This paper tries to summarize the association of several candidate genes with risk for AS in the Han ethnic Chinese population and aims to identify the novel inflammatory pathways and provide potential strategies for better therapies.

  19. Antibiotic discovery throughout the Small World Initiative: A molecular strategy to identify biosynthetic gene clusters involved in antagonistic activity.

    Science.gov (United States)

    Davis, Elizabeth; Sloan, Tyler; Aurelius, Krista; Barbour, Angela; Bodey, Elijah; Clark, Brigette; Dennis, Celeste; Drown, Rachel; Fleming, Megan; Humbert, Allison; Glasgo, Elizabeth; Kerns, Trent; Lingro, Kelly; McMillin, MacKenzie; Meyer, Aaron; Pope, Breanna; Stalevicz, April; Steffen, Brittney; Steindl, Austin; Williams, Carolyn; Wimberley, Carmen; Zenas, Robert; Butela, Kristen; Wildschutte, Hans

    2017-06-01

    The emergence of bacterial pathogens resistant to all known antibiotics is a global health crisis. Adding to this problem is that major pharmaceutical companies have shifted away from antibiotic discovery due to low profitability. As a result, the pipeline of new antibiotics is essentially dry and many bacteria now resist the effects of most commonly used drugs. To address this global health concern, citizen science through the Small World Initiative (SWI) was formed in 2012. As part of SWI, students isolate bacteria from their local environments, characterize the strains, and assay for antibiotic production. During the 2015 fall semester at Bowling Green State University, students isolated 77 soil-derived bacteria and genetically characterized strains using the 16S rRNA gene, identified strains exhibiting antagonistic activity, and performed an expanded SWI workflow using transposon mutagenesis to identify a biosynthetic gene cluster involved in toxigenic compound production. We identified one mutant with loss of antagonistic activity and through subsequent whole-genome sequencing and linker-mediated PCR identified a 24.9 kb biosynthetic gene locus likely involved in inhibitory activity in that mutant. Further assessment against human pathogens demonstrated the inhibition of Bacillus cereus, Listeria monocytogenes, and methicillin-resistant Staphylococcus aureus in the presence of this compound, thus supporting our molecular strategy as an effective research pipeline for SWI antibiotic discovery and genetic characterization. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  20. rpoB Gene Analysis as a Novel Strategy for Identification of Spirochetes from the Genera Borrelia, Treponema, and Leptospira

    Science.gov (United States)

    Renesto, Patricia; Lorvellec-Guillon, Katell; Drancourt, Michel; Raoult, Didier

    2000-01-01

    Spirochetes are emerging pathogens for which culture and identification are partly unresolved. In fact, 16S rRNA-based sequencing is by far the most widely used PCR methodology that is able to detect such uncultivable pathogens. However, this assay actually has some limitations linked to potential problems of contamination, which hampers diagnosis. To circumvent this, we have devised a simple PCR strategy involving targeting of the gene encoding the RNA polymerase beta subunit (rpoB), a highly conserved enzyme. The complete sequence of the Leptospira biflexa (serovar patoc) rpoB gene was determined and compared with the published sequences for Borrelia burgdorferi and Treponema pallidum. From the resulting analysis, degenerate nucleotide primers were designed and tested for their ability to amplify a portion of the rpoB gene from various spirochetes. Using two different pairs of these primers, we succeeded in obtaining specific rpoB-amplified fragments for all members of the genera Leptospira, Treponema, and Borrelia tested and no other bacteria. Our findings may have significant implications for the development of a new tool for the identification of spirochetes, especially if clinical samples are contaminated or when the infecting strain is uncultivable. PMID:10834976

  1. EXPOSING LEARNERS WITH LEARNING STRATEGIES IN STRATEGY TRAING: ONE OF THE WAYS FOR IMPROVING THEIR STUDY SKILL

    Directory of Open Access Journals (Sweden)

    Kartika Nuswantara

    2009-06-01

    Full Text Available Recognizing our own learning strategies is an effective way to help ourselves to self evaluate for what we have done in our own learning. One among other factors leading to a successful learning is due to the effective learning strategies. However, not all learners are aware of what they have been doing in learning, or they even sometimes do not know how to learn. If this is the problem, learning strategy training can be very beneficial for the learners with this problem. Why should be through strategy training? The answer might lie on the fact that strategy is quite amenable to change, and by nature, teachable as well as learneable (Oxford, 1990. In addition, Nuswantara (2008 also found out that the successful learners (i.e. in learning English were triggered by the courage of using various learning strategies, the more varied the learners are willing to try out, the broader the chance for success. Training is the way that can be selected to present to the learners’ various strategies that they can choose and at the same time employ when learning is taken place. Moreover, by means of training, learners are made aware of the strategy, and they can mend their own strategy, as a result, they become more self - directed rather than dependent. This article attempts to frame out from the perspective of how to bring reading strategies that are applicable for handling various reading content texts to the learners, and present the result of a one-group experimental study. Thus, training is prepared for college learners who are inevitably deal with various English content textbooks and the final aim of the training is to improve learners’ study skills. Then, one group experimental study using correlated sample provides some evidences supporting the effectiveness of the training. Specifying on reading strategies, SQ3R that is joined with other learning strategies involving writing activity, annotating a text and paraphrasing/summarizing is exposed to

  2. Aging and List-Wide Modulations of Strategy Execution:A Study in Arithmetic.

    Science.gov (United States)

    Hinault, Thomas; Lemaire, Patrick

    2017-01-01

    Background/Study Context: This study aimed at further our understanding of the cognitive processes involved during strategy execution, and how the processes involved change with age. More specifically, the main goal was to investigate whether poorer-strategy effects (i.e., poorer performance when a cued strategy is not the best) and sequential modulations of poorer-strategy effects (i.e., decreased poorer-strategy effects on current problems following poorer-strategy problems compared with after better-strategy problems) are influenced by proportions of poorer-strategy problems. We used a computational estimation task (i.e., providing approximate products to two-digit multiplication problems such as 38 × 74) with problems sets including 75%, 50%, or 25% of poorer-strategy problems (i.e., participants have to estimate products with another strategy than the better strategy). The remaining problems were cued with the better strategy. Age-related differences were also investigated. We found that proportions of poorer-strategy problems influenced sequential modulations of poorer-strategy effects. Indeed, sequential modulations of poorer-strategy effects were larger when proportions of poorer-strategy problems were equal than unequal. Moreover, proportion effects were different for young and older adults, as older adults benefited more from low proportions of poorer-strategy problems compared with young adults. These findings have important implications regarding cognitive control mechanisms underlying both list-wide and trial-to-trial modulations of strategy execution, and how these processes change during aging.

  3. A study of palm biomass processing strategy in Sarawak

    Science.gov (United States)

    Lee, S. J. Y.; Ng, W. P. Q.; Law, K. H.

    2017-06-01

    In the past decades, palm industry is booming due to its profitable nature. An environmental concern regarding on the palm industry is the enormous amount of waste produced from palm industry. The waste produced or palm biomass is one significant renewable energy source and raw material for value-added products like fiber mats, activated carbon, dried fiber, bio-fertilizer and et cetera in Malaysia. There is a need to establish the palm biomass industry for the recovery of palm biomass for efficient utilization and waste reduction. The development of the industry is strongly depending on the two reasons, the availability and supply consistency of palm biomass as well as the availability of palm biomass processing facilities. In Malaysia, the development of palm biomass industry is lagging due to the lack of mature commercial technology and difficult logistic planning as a result of scattered locality of palm oil mill, where palm biomass is generated. Two main studies have been carried out in this research work: i) industrial study of the feasibility of decentralized and centralized palm biomass processing in Sarawak and ii) development of a systematic and optimized palm biomass processing planning for the development of palm biomass industry in Sarawak, Malaysia. Mathematical optimization technique is used in this work to model the above case scenario for biomass processing to achieve maximum economic potential and resource feasibility. An industrial study of palm biomass processing strategy in Sarawak has been carried out to evaluate the optimality of centralized processing and decentralize processing of the local biomass industry. An optimal biomass processing strategy is achieved.

  4. Baculovirus as an ideal radionuclide reporter gene vector: a new strategy for monitoring the fate of human stem cells in vivo.

    Science.gov (United States)

    Pan, Yu; Liu, Shuai; Wu, Haifei; Lv, Jing; Xu, Xiaoqian; Zhang, Yifan

    2013-01-01

    Radionuclide reporter gene imaging holds promise for non-invasive monitoring of transplanted stem cells. Thus, the feasibility of utilizing recombinant baculoviruses carrying the sodium iodide symporter (NIS) reporter gene in monitoring stem cell therapy by radionuclide imaging was explored in this study. Recombinant baculoviruses carrying NIS and green fluorescent protein (GFP) reporter genes (Bac-NIS and Bac-GFP) were constructed and used to infect human induced pluripotent stem cells (hiPSCs), human embryonic stem cells (hESCs) and human umbilical cord blood mesenchymal stem cells (hUCB-MSCs). Infection efficiency, total fluorescence intensity and duration of transgene expression were determined by flow cytometry. Cytotoxicity/proliferative effects of baculovirus on hUCB-MSCs were assessed using CCK-8 assays. ¹²⁵I uptake and perchlorate inhibition assays were performed on Bac-NIS-infected hUCB-MSCs. Radionuclide imaging of mice transplanted with Bac-NIS-infected hUCB-MSCs was performed by NanoSPECT/CT imaging. Infection efficiencies of recombinant baculovirus in hESCs, hiPSCs and hUCB-MSCs increased with increasing MOIs (27.3%, 35.8% and 95.6%, respectively, at MOI = 800). Almost no cytotoxicity and only slight effects on hUCB-MSCs proliferation were observed. Obvious GFP expression (40.6%) remained at 8 days post-infection. The radioiodide was functionally accumulated by NIS gene products and specifically inhibited by perchlorate (ClO₄⁻). Radioiodide uptake, peaking at 30 min and gradually decreasing over time, significantly correlated with hUCB-MSCs cell number (R² = 0.994). Finally, radionuclide imaging showed Bac-NIS-infected hUCB-MSCs effectively accumulated radioiodide in vivo, which gradually weakened over time. Baculovirus as transgenic vector of radionuclide reporter gene imaging technology is a promising strategy for monitoring stem cell transplantation therapy.

  5. Identification and Validation of Reference Genes for qRT-PCR Studies of Gene Expression in Dioscorea opposita.

    Science.gov (United States)

    Zhao, Xiting; Zhang, Xiaoli; Guo, Xiaobo; Li, Shujie; Han, Linlin; Song, Zhihui; Wang, Yunying; Li, Junhua; Li, Mingjun

    2016-01-01

    Quantitative real-time polymerase chain reaction (qRT-PCR) is one of the most common methods for gene expression studies. Data normalization based on reference genes is essential for obtaining reliable results for qRT-PCR assays. This study evaluated potential reference genes of Chinese yam (Dioscorea opposita Thunb.), which is an important tuber crop and medicinal plant in East Asia. The expression of ten candidate reference genes across 20 samples from different organs and development stages was assessed. We identified the most stable genes for qRT-PCR studies using combined samples from different organs. Our results also suggest that different suitable reference genes or combinations of reference genes for normalization should be applied according to different organs and developmental stages. To validate the suitability of the reference genes, we evaluated the relative expression of PE2.1 and PE53, which are two genes that may be associated with microtuber formation. Our results provide the foundation for reference gene(s) selection in D. opposita and will contribute toward more accurate gene analysis studies of the genus Dioscorea.

  6. Synthetic strategies for plant signalling studies: molecular toolbox and orthogonal platforms.

    Science.gov (United States)

    Braguy, Justine; Zurbriggen, Matias D

    2016-07-01

    Plants deploy a wide array of signalling networks integrating environmental cues with growth, defence and developmental responses. The high level of complexity, redundancy and connection between several pathways hampers a comprehensive understanding of involved functional and regulatory mechanisms. The implementation of synthetic biology approaches is revolutionizing experimental biology in prokaryotes, yeasts and animal systems and can likewise contribute to a new era in plant biology. This review gives an overview on synthetic biology approaches for the development and implementation of synthetic molecular tools and techniques to interrogate, understand and control signalling events in plants, ranging from strategies for the targeted manipulation of plant genomes up to the spatiotemporally resolved control of gene expression using optogenetic approaches. We also describe strategies based on the partial reconstruction of signalling pathways in orthogonal platforms, like yeast, animal and in vitro systems. This allows a targeted analysis of individual signalling hubs devoid of interconnectivity with endogenous interacting components. Implementation of the interdisciplinary synthetic biology tools and strategies is not exempt of challenges and hardships but simultaneously most rewarding in terms of the advances in basic and applied research. As witnessed in other areas, these original theoretical-experimental avenues will lead to a breakthrough in the ability to study and comprehend plant signalling networks. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  7. Synthetic strategies for plant signalling studies: molecular toolbox and orthogonal platforms

    KAUST Repository

    Braguy, Justine

    2016-05-26

    Plants deploy a wide array of signalling networks integrating environmental cues with growth, defence and developmental responses. The high level of complexity, redundancy and connection between several pathways hampers a comprehensive understanding of involved functional and regulatory mechanisms. The implementation of synthetic biology approaches is revolutionizing experimental biology in prokaryotes, yeasts and animal systems and can likewise contribute to a new era in plant biology. This review gives an overview on synthetic biology approaches for the development and implementation of synthetic molecular tools and techniques to interrogate, understand and control signalling events in plants, ranging from strategies for the targeted manipulation of plant genomes up to the spatiotemporally resolved control of gene expression using optogenetic approaches. We also describe strategies based on the partial reconstruction of signalling pathways in orthogonal platforms, like yeast, animal and in vitro systems. This allows a targeted analysis of individual signalling hubs devoid of inter-connectivity with endogenous interacting components. Implementation of the interdisciplinary synthetic biology tools and strategies is not exempt of challenges and hardships but simultaneously most rewarding in terms of the advances in basic and applied research. As witnessed in other areas, these original theoretical-experimental avenues will lead to a breakthrough in the ability to study and comprehend plant signalling networks. This article is protected by copyright. All rights reserved.

  8. Strategies for Studying the Sources of Gamma Ray Bursts

    Science.gov (United States)

    Cline, T. L.; Norris, J. P.; Hurley, K. C.

    2003-01-01

    The study of gamma ray bursts (GRBs) has rapidly evolved in recent years with the discovery of their cosmological nature and with BATSE, BeppoSAX, HETE and the IPN enabling a wide variety of associated . afterglow measurements. Multiwavelength observations ranging through the radio, optical, soft and hard x-ray, and gamma-ray regimes have exploded the field of GRB interpretation. Also, the Amanda, Milagro and LIGO experiments can search for related neutrino, cosmic-ray photon, and gravitational radiation events, even with the delayed alerts, such as from the IPN. The infrared region, where the optical emissions from sources at the extreme distances may be shifted, will become important but is undersubscribed. The soon-to-be launched Swift mission will greatly broaden the GRB discipline, and a strategy for associated ground-based measurements is outlined. The need for the improved global distribution of all instruments, in particular, robotic infrared detectors, is cited.

  9. Vaccination Strategies: a comparative study in an epidemic scenario

    Science.gov (United States)

    Prates, D. B.; Jardim, C. L. T. F.; Ferreira, L. A. F.; da Silva, J. M.; Kritz, M. V.

    2016-08-01

    Epidemics are an extremely important matter of study within the Mathematical Modeling area and can be widely found in the literature. Some epidemiological models use differential equations, which are very sensible to parameters, to represent and describe the diseases mathematically. For this work, a variation of the SIR model is discussed and applied to a certain epidemic scenario, wherein vaccination is introduced through two different strategies: constant vaccination and vaccination in pulses. Other epidemiological and population aspects are also considered, such as mortality/natality and infection rates. The analysis and results are performed through numerical solutions of the model and a special attention is given to the discussion generated by the paramenters variation.

  10. Study on Formulating Policy and Strategies for IAEA TC Program

    International Nuclear Information System (INIS)

    Min, B. J.; Lee, M. K.; Shin, J. Y.

    2010-10-01

    The objectives of this study is to provide recommendations for formulating adequate policy and strategies for IAEA-TC programme as being of a donor Member State and to guide directions to facing the challenges of changing the status from IAEA-TC recipient to donor country. In addition, this study gives recommendations and feedbacks to the IAEA-TC programmer: how it has contributed to nation's nuclear technology development in the past on one hand and how the country has contributed to it on the other. Besides, this study also conducted to identify the following impacts expected: termination of on-going National TC projects, discontinuation of TC-based technical advices, sponsored fellowship and scientific visits for capacity building opportunities, and limitation in participations of various regional projects due to termination of IAEA financial support. In terms of financial aspect, this study has also performed to assess the nation's annual financial contribution (Technical Cooperation (TC) Fund: 1,67 million dollars in 2008) by comparing the experiences of other OECD countries cases. In conclusion, it is expected that the results of this study will contribute to develop appropriate measures in order to maximize the benefits for future national nuclear technology development and in addition, to explore the possibilities to extend the nuclear technology export market potentials

  11. A review of the influence of treatment strategies on antibiotic resistant bacteria and antibiotic resistance genes.

    Science.gov (United States)

    Sharma, Virender K; Johnson, Natalie; Cizmas, Leslie; McDonald, Thomas J; Kim, Hyunook

    2016-05-01

    Antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARG) in the aquatic environment have become an emerging contaminant issue, which has implications for human and ecological health. This review begins with an introduction to the occurrence of ARB and ARG in different environmental systems such as natural environments and drinking water resources. For example, ARG or ARB with resistance to ciprofloxacin, sulfamethoxazole, trimethoprim, quinolone, vancomycin, or tetracycline (e.g., tet(A), tet(B), tet(C), tet(G), tet(O), tet(M), tet(W), sul I, and sul II) have been detected in the environment. The development of resistance may be intrinsic, may be acquired through spontaneous mutations (de novo), or may occur due to horizontal gene transfer from donor bacteria, phages, or free DNA to recipient bacteria. An overview is also provided of the current knowledge regarding inactivation of ARB and ARG, and the mechanism of the effects of different disinfection processes in water and wastewater (chlorination, UV irradiation, Fenton reaction, ozonation, and photocatalytic oxidation). The effects of constructed wetlands and nanotechnology on ARB and ARG are also summarized. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Network graph analysis of gene-gene interactions in genome-wide association study data.

    Science.gov (United States)

    Lee, Sungyoung; Kwon, Min-Seok; Park, Taesung

    2012-12-01

    Most common complex traits, such as obesity, hypertension, diabetes, and cancers, are known to be associated with multiple genes, environmental factors, and their epistasis. Recently, the development of advanced genotyping technologies has allowed us to perform genome-wide association studies (GWASs). For detecting the effects of multiple genes on complex traits, many approaches have been proposed for GWASs. Multifactor dimensionality reduction (MDR) is one of the powerful and efficient methods for detecting high-order gene-gene (GxG) interactions. However, the biological interpretation of GxG interactions identified by MDR analysis is not easy. In order to aid the interpretation of MDR results, we propose a network graph analysis to elucidate the meaning of identified GxG interactions. The proposed network graph analysis consists of three steps. The first step is for performing GxG interaction analysis using MDR analysis. The second step is to draw the network graph using the MDR result. The third step is to provide biological evidence of the identified GxG interaction using external biological databases. The proposed method was applied to Korean Association Resource (KARE) data, containing 8838 individuals with 327,632 single-nucleotide polymorphisms, in order to perform GxG interaction analysis of body mass index (BMI). Our network graph analysis successfully showed that many identified GxG interactions have known biological evidence related to BMI. We expect that our network graph analysis will be helpful to interpret the biological meaning of GxG interactions.

  13. Study of Deafness Associated with DFNB59 Gene (pejvakin Mutation in Fars Province

    Directory of Open Access Journals (Sweden)

    S Raeisi

    2012-05-01

    Full Text Available

    Background and Objectives: Hearing loss is the most frequent sensory disorder affecting 1 in 500 neonates with more than 50% of inherited cases. This trait is a very heterogeneous disorder and happens due to genetic or environmental causes or both. More than 46 genes may be involved in non-syndromic hearing loss. Recently, DFNB59 gene has been shown to cause deafness in some Iranian populations. The aim of this study was to determine the role of DFNB59 gene mutations causing deafness in a group of 130 deaf pupils in Fars province. Methods: This descriptive-laboratory based study investigated the frequency of DFNB59 gene mutations using PCR-SSCP/HA strategy. Results: Two different DFNB59 polymorphism including 874G>A and 793C>G were found in 1 and 9 of 130 patients studied respectively. However, no DFNB59 mutation was identified. Conclusion: The results of this study shows that the association of DFNB59 mutations with deafness in Fars province is very low.

  14. Saudi English Major Freshmen Students’ Vocabulary Learning Strategies: An Exploratory Study

    Directory of Open Access Journals (Sweden)

    Ibrahim R. Alqarni

    2017-12-01

    Full Text Available This study aims at exploring the vocabulary learning strategies (VLSs employed by Saudi Freshmen students majoring in English as a foreign language (EFL. The participants are 81 Saudi male students in their first semester in the English Department and Translation in the College of Language and Translation at King Saud University. Data was collected using a questionnaire which was adapted from the study of Rabadi (2016 and was analyzed using the SPSS program. The overall results of this study show that participants use all of the different vocabulary learning strategies: Determination strategies, Memory strategies, Cognitive strategies, Metacognitive strategies, and Social strategies, with different degrees of frequency. By looking at the sub-categories of the strategies the results indicate that Metacognitive strategies (mean score: 1.98/4 are the most used and/or preferred strategies by all participants, followed by Social strategies (MS: 1.91, Determination strategies (MS: 1.62, Cognitive strategies (MS: 1.39 and Memory strategies (MS: 1.26 respectively. However, the overall mean score of (1.63 for the use of the strategies indicates that the participants of this study are low/poor users of vocabulary learning strategies in general.

  15. Strategy selection in Alzheimer patients: a study in arithmetic.

    Science.gov (United States)

    Lemaire, Patrick; Leclère, Mariel

    2014-01-01

    We compared Alzheimer's disease (AD) patients' and elderly controls' abilities to select the best strategy on each item and determined whether AD patients tended to repeat the same strategy across consecutive items more often than controls. A total of 60 participants (30 healthy older adults, HOA; 30 AD patients) were asked to select the best rounding strategy to estimate products of multiplication problems (e.g., estimating 42 × 76 by rounding operands down or up, like doing 40 × 70 = 2800 or 50 × 80 = 3200). We identified strategies used on each problem and measured solution latencies and percentage errors with each strategy as a function of problem characteristics. Older adults and AD patients were able to use both available strategies. However, AD patients were less able to select the best strategy than HOA, especially on problems for which selecting the best strategy was most difficult. Moreover, AD patients significantly repeated the preceding strategies across successive problems more often than HOA. Our findings have important implications for further our understanding of dementia-related differences in strategic aspects of cognitive performance.

  16. Actin gene identification from selected medicinal plants for their use as internal controls for gene expression studies

    International Nuclear Information System (INIS)

    Mufti, F.U.D.; Banaras, S.

    2015-01-01

    Internal control genes are the constitutive genes which maintain the basic cellular functions and regularly express in both normal and stressed conditions in living organisms. They are used in normalization of gene expression studies in comparative analysis of target genes, as their expression remains comparatively unchanged in all varied conditions. Among internal control genes, actin is considered as a candidate gene for expression studies due to its vital role in shaping cytoskeleton and plant physiology. Unfortunately most of such knowledge is limited to only model plants or crops, not much is known about important medicinal plants. Therefore, we selected seven important medicinal wild plants for molecular identification of actin gene. We used gene specific primers designed from the conserved regions of several known orthologues or homologues of actin genes from other plants. The amplified products of 370-380 bp were sequenced and submitted to GeneBank after their confirmation using different bioinformatics tools. All the novel partial sequences of putative actin genes were submitted to GeneBank (Parthenium hysterophorus (KJ774023), Fagonia indica (KJ774024), Rhazya stricta (KJ774025), Whithania coagulans (KJ774026), Capparis decidua (KJ774027), Verbena officinalis (KJ774028) and Aerva javanica (KJ774029)). The comparisons of these partial sequences by Basic Local Alignment Search Tool (BLAST) and phylogenetic trees demonstrated high similarity with known actin genes of other plants. Our findings illustrated highly conserved nature of actin gene among these selected plants. These novel partial fragments of actin genes from these wild medicinal plants can be used as internal controls for future gene expression studies of these important plants after precise validations of their stable expression in such plants. (author)

  17. Nevada potential repository preliminary transportation strategy Study 2. Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-02-01

    The objectives of this study were to build on the findings of the Nevada Potential Repository Preliminary Transportation Strategy Study 1 (CRWMS M&O 1995b), and to provide additional information for input to the repository environmental impact statement (EIS) process. In addition, this study supported the future selection of a preferred rail corridor and/or heavy haul route based on defensible data, methods, and analyses. Study research did not consider proposed legislation. Planning was conducted according to the Civilian Radioactive Waste Management Program Plan (DOE 1994a). The specific objectives of Study 2 were to: eliminate or reduce data gaps, inconsistencies, and uncertainties, and strengthen the analysis performed in Study 1; develop a preliminary list of rail route evaluation criteria that could be used to solicit input from stakeholders during scoping meetings. The evaluation criteria will be revised based on comments received during scoping; restrict and refine the width of the four rail corridors identified in Study 1 to five miles or less, based on land use constraints and engineering criteria identified and established in Study 2; evaluate national-level effects of routing spent nuclear fuel and high-level waste to the four identified branch lines, including the effects of routing through or avoiding Las Vegas; continue to gather published land use information and environmental data to support the repository EIS; continue to evaluate heavy haul truck transport over three existing routes as an alternative to rail and provide sufficient information to support the repository EIS process; and evaluate secondary uses for rail (passenger use, repository construction, shared use).

  18. Nevada potential repository preliminary transportation strategy Study 2. Volume 1

    International Nuclear Information System (INIS)

    1996-02-01

    The objectives of this study were to build on the findings of the Nevada Potential Repository Preliminary Transportation Strategy Study 1 (CRWMS M ampersand O 1995b), and to provide additional information for input to the repository environmental impact statement (EIS) process. In addition, this study supported the future selection of a preferred rail corridor and/or heavy haul route based on defensible data, methods, and analyses. Study research did not consider proposed legislation. Planning was conducted according to the Civilian Radioactive Waste Management Program Plan (DOE 1994a). The specific objectives of Study 2 were to: eliminate or reduce data gaps, inconsistencies, and uncertainties, and strengthen the analysis performed in Study 1; develop a preliminary list of rail route evaluation criteria that could be used to solicit input from stakeholders during scoping meetings. The evaluation criteria will be revised based on comments received during scoping; restrict and refine the width of the four rail corridors identified in Study 1 to five miles or less, based on land use constraints and engineering criteria identified and established in Study 2; evaluate national-level effects of routing spent nuclear fuel and high-level waste to the four identified branch lines, including the effects of routing through or avoiding Las Vegas; continue to gather published land use information and environmental data to support the repository EIS; continue to evaluate heavy haul truck transport over three existing routes as an alternative to rail and provide sufficient information to support the repository EIS process; and evaluate secondary uses for rail (passenger use, repository construction, shared use)

  19. Genetics of wide compatible gene and variability studies in rice ...

    Indian Academy of Sciences (India)

    ... Refresher Courses · Symposia · Live Streaming. Home; Journals; Journal of Genetics; Volume 95; Issue 2. Genetics of wide compatible gene and variability studies in rice (Oryza sativa L.) S. REVATHI K. SAKTHIVEL S. MANONMANI M. UMADEVI R. USHAKUMARI S. ROBIN. RESEARCH NOTE Volume 95 Issue 2 June ...

  20. Association study of the oestrogen signalling pathway genes in ...

    Indian Academy of Sciences (India)

    Association study of the oestrogen signalling pathway genes in relation to age at natural menopause. Li-Na He ... The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China ...

  1. Association study of the oestrogen signalling pathway genes in ...

    Indian Academy of Sciences (India)

    [He Li-Na, Xiong D.-H., Liu Y.-J., Zhang F., Recker R. R. and Deng H.-W. 2007 Association study of the oestrogen signalling pathway genes in relation to age at natural menopause. J. Genet. 86, 269–276]. Introduction. Age at natural menopause (AANM) is closely related to women's psychological and physical well being. It.

  2. Recent advances in human gene-longevity association studies

    DEFF Research Database (Denmark)

    De Benedictis, G; Tan, Q; Jeune, B

    2001-01-01

    % of the variation in life span is genetically determined. Taking advantage of recent developments in molecular biology, researchers are now searching for candidate genes that might have an influence on life span. The data on unrelated individuals emerging from an ever-increasing number of centenarian studies makes...

  3. The time course of strategy sequential difficulty effects: an ERP study in arithmetic.

    Science.gov (United States)

    Uittenhove, Kim; Poletti, Celine; Dufau, Stephane; Lemaire, Patrick

    2013-05-01

    Uittenhove and Lemaire (Exp Psychol 59(5):295-301, 2012) found that we are slower when executing a strategy following a difficult strategy than when executing the same strategy following an easier strategy (i.e., strategy sequential difficulty effects). Uittenhove and Lemaire suggested that difficult strategies temporarily reduce available executive capacities, interfering with the next strategy execution. In this study, we used ERP to determine the time course of these effects. In a computational estimation task, we found greater cerebral activities during strategy execution following a more difficult compared to an easier strategy. Interestingly, greater cerebral activities were most apparent immediately after the encoding of the problem and not during encoding or in later stages of processing. This suggests that strategy sequential difficulty effects interfere most with the retrieval of procedures in contrast to execution of these procedures. We discuss implications of these findings for further understanding of execution of cognitive strategies.

  4. Blood lead levels, iron metabolism gene polymorphisms and homocysteine: a gene-environment interaction study.

    Science.gov (United States)

    Kim, Kyoung-Nam; Lee, Mee-Ri; Lim, Youn-Hee; Hong, Yun-Chul

    2017-12-01

    Homocysteine has been causally associated with various adverse health outcomes. Evidence supporting the relationship between lead and homocysteine levels has been accumulating, but most prior studies have not focused on the interaction with genetic polymorphisms. From a community-based prospective cohort, we analysed 386 participants (aged 41-71 years) with information regarding blood lead and plasma homocysteine levels. Blood lead levels were measured between 2001 and 2003, and plasma homocysteine levels were measured in 2007. Interactions of lead levels with 42 genotyped single-nucleotide polymorphisms (SNPs) in five genes ( TF , HFE , CBS , BHMT and MTR ) were assessed via a 2-degree of freedom (df) joint test and a 1-df interaction test. In secondary analyses using imputation, we further assessed 58 imputed SNPs in the TF and MTHFR genes. Blood lead concentrations were positively associated with plasma homocysteine levels (p=0.0276). Six SNPs in the TF and MTR genes were screened using the 2-df joint test, and among them, three SNPs in the TF gene showed interactions with lead with respect to homocysteine levels through the 1-df interaction test (phomocysteine levels at an α-level of 0.05, but the associations did not persist after Bonferroni correction. These SNPs did not show interactions with lead levels. Blood lead levels were positively associated with plasma homocysteine levels measured 4-6 years later, and three SNPs in the TF gene modified the association. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Diagnostic Strategy for Identifying Avian Pathogenic Escherichia coli Based on Four Patterns of Virulence Genes

    Science.gov (United States)

    Schaeffer, Brigitte; Brée, Annie; Mora, Azucena; Dahbi, Ghizlane; Biet, François; Oswald, Eric; Mainil, Jacques; Blanco, Jorge; Moulin-Schouleur, Maryvonne

    2012-01-01

    In order to improve the identification of avian pathogenic Escherichia coli (APEC) strains, an extensive characterization of 1,491 E. coli isolates was conducted, based on serotyping, virulence genotyping, and experimental pathogenicity for chickens. The isolates originated from lesions of avian colibacillosis (n = 1,307) or from the intestines of healthy animals (n = 184) from France, Spain, and Belgium. A subset (460 isolates) of this collection was defined according to their virulence for chicks. Six serogroups (O1, O2, O5, O8, O18, and O78) accounted for 56.5% of the APEC isolates and 22.5% of the nonpathogenic isolates. Thirteen virulence genes were more frequently present in APEC isolates than in nonpathogenic isolates but, individually, none of them could allow the identification of an isolate as an APEC strain. In order to take into account the diversity of APEC strains, a statistical analysis based on a tree-modeling method was therefore conducted on the sample of 460 pathogenic and nonpathogenic isolates. This resulted in the identification of four different associations of virulence genes that enables the identification of 70.2% of the pathogenic strains. Pathogenic strains were identified with an error margin of 4.3%. The reliability of the link between these four virulence patterns and pathogenicity for chickens was validated on a sample of 395 E. coli isolates from the collection. The genotyping method described here allowed the identification of more APEC isolates with greater reliability than the classical serotyping methods currently used in veterinary laboratories. PMID:22378905

  6. Early diagnosis of and surgical strategy for adrenal medullary disease in MEN II gene carriers

    Energy Technology Data Exchange (ETDEWEB)

    Jansson, S.; Tisell, L.E.; Fjaelling, M.L.; Lindberg, S.; Jacobsson, L.; Zachrisson, B.F.

    1988-01-01

    Sixteen multiple endocrine neoplasia type II (MEN II) gene carriers--12 who had undergone thyroidectomy because of medullary carcinoma of the thyroid and 4 whose thyroid glands had been removed because of C cell hyperplasia--were examined for the presence of pheochromocytomas. No patient had sought medical advice for pheochromocytoma symptoms. Fourteen patients had MEN IIa syndromes, one patient had a MEN IIb and another patient had a mixed syndrome of von Recklinghausen's neurofibromatosis and MEN II. Eight patients had undergone unilateral adrenalectomy for pheochromocytoma 11 +/- 4 years before. The patients underwent clinical examination, determination of the urinary excretion of catecholamines and metabolites, and /sup 131/I-metaiodobenzylguanidine (/sup 131/I-MIBG) and CAT scans. /sup 131/I-MIBG scanning was performed with images 1, 4, and 7 days after the radionuclide injection. In seven of eight patients who had undergone unilateral adrenalectomies, the /sup 131/I-MIBG scans showed accumulation of the radionuclide in the remaining adrenal gland. Bilateral adrenal accumulation of the radionuclide was demonstrated in seven of eight MEN IIa gene carriers who had not undergone adrenalectomy. Five patients, two of whom had undergone adrenalectomy, were found to have unilateral pheochromocytomas less than 2 cm in diameter. Only one of these five patients had an elevated excretion of urinary catecholamines. Between day 4 and day 7 after /sup 131/I-MIBG injection, adrenal glands with pheochromocytomas increased their relative accumulation of the radionuclide significantly more (p less than 0.02) than did adrenal glands without any demonstrable pheochromocytomas. All the pheochromocytomas were viewed by means of CAT scans.

  7. A flexible Bayesian model for studying gene-environment interaction.

    Directory of Open Access Journals (Sweden)

    Kai Yu

    2012-01-01

    Full Text Available An important follow-up step after genetic markers are found to be associated with a disease outcome is a more detailed analysis investigating how the implicated gene or chromosomal region and an established environment risk factor interact to influence the disease risk. The standard approach to this study of gene-environment interaction considers one genetic marker at a time and therefore could misrepresent and underestimate the genetic contribution to the joint effect when one or more functional loci, some of which might not be genotyped, exist in the region and interact with the environment risk factor in a complex way. We develop a more global approach based on a Bayesian model that uses a latent genetic profile variable to capture all of the genetic variation in the entire targeted region and allows the environment effect to vary across different genetic profile categories. We also propose a resampling-based test derived from the developed Bayesian model for the detection of gene-environment interaction. Using data collected in the Environment and Genetics in Lung Cancer Etiology (EAGLE study, we apply the Bayesian model to evaluate the joint effect of smoking intensity and genetic variants in the 15q25.1 region, which contains a cluster of nicotinic acetylcholine receptor genes and has been shown to be associated with both lung cancer and smoking behavior. We find evidence for gene-environment interaction (P-value = 0.016, with the smoking effect appearing to be stronger in subjects with a genetic profile associated with a higher lung cancer risk; the conventional test of gene-environment interaction based on the single-marker approach is far from significant.

  8. 5'/ 3' imbalance strategy to detect ALK fusion genes in circulating tumor RNA from patients with non-small cell lung cancer.

    Science.gov (United States)

    Tong, Yongqing; Zhao, Zhijun; Liu, Bei; Bao, Anyu; Zheng, Hongyun; Gu, Jian; McGrath, Mary; Xia, Ying; Tan, Bihua; Song, Chunhua; Li, Yan

    2018-03-27

    Detecting an ALK fusion gene in patients with non-small cell lung cancer (NSCLC) could provide evidence to guide individualized therapy. The 5'/3' imbalance strategy for quantitative reverse transcription-PCR (RT-qPCR) was developed to detect ALK fusion genes in circulating tumor RNA (ctRNA) of NSCLC patients. This method was validated in patients with the ALK fusion gene confirmed by next generation sequencing (NGS). The amount of the ALK fusion gene detected by the new method ranged from 33.2 to 987.4, (mean 315.2), in the patients confirmed to have the ALK fusion gene (+). This is much higher than the amount of fusion gene detected in the patients who are negative for the ALK fusion gene (-). The amount detected in the ALK fusion gene (-) samples ranged from 0.36 to 13.04, (mean 4.58). In 188 NSCLC patients, the specificity and sensitivity of the method was compared to that of the FISH method. About 10.64% of the patients showed higher ALK fusion gene expression, and were classified as ALK fusion gene (+). This is identical to the percentage of patients detected by the FISH method to be ALK fusion gene (+). The cutoff value for diagnosis of ALK fusion (+) is 32.9 as determined by this method. A new RT-PCR method using a 5'/3' imbalance strategy was developed, with high specificity and sensitivity, for detection of the ALK fusion gene in ctRNA of NSCLC patients. This method can rapidly detect ALK fusion genes in patients, which will be helpful for guiding targeted therapy, particularly the individualized usage of TKIs in these patients.

  9. Ventilation strategies in burn intensive care: A retrospective observational study

    Directory of Open Access Journals (Sweden)

    Stefano Palazzo

    2014-01-01

    Full Text Available Consensus regarding optimal burns intensive care (BICU patient management is lacking. This study aimed to assess whether ventilation strategies, cardiovascular support and sedation in BICU patients have changed over time, and whether this affects outcome. A retrospective observational study comparing two 12-patient BICU cohorts (2005/06 and 2010/11 was undertaken. Demographic and admission characteristics, ventilation parameters, sedation, fluid resuscitation, cardiovascular support and outcome (length of stay, mortality data were collected from patient notes. Data was analysed using T-tests, Fisher's exact and Mann-Whitney U tests. In our study cohort groups were equivalent in demographic and admission parameters. There were equal ventilator-free days in the two cohorts 10 ± 12.7 vs. 13.3 ± 12.2 ventilator free days; P = 0.447. The 2005/06 cohort were mechanically ventilated more often than in 2010/11 cohort (568 ventilator days/1000 patient BICU days vs. 206 ventilator days/1000 patient BICU days; P = 0.001. The 2005/06 cohort were ventilated less commonly in tracheostomy group/endotracheal tube spontaneous (17.8% vs. 26%; P = 0.001 and volume-controlled modes (34.4% vs. 40.8%; P = 0.001. Patients in 2010/11 cohort were more heavily sedated (P = 0.001 with more long-acting sedative drug use (P = 0.001 than the 2005/06 cohort, fluid administration was equivalent. Patient outcome did not vary. Inhalational injury patients were ventilated in volume-controlled (44.5% vs. 28.1%; P = 0.001 and pressure-controlled modes (18.2% vs. 9.5%; P = 0.001 more frequently than those without. Outcome did not vary. This study showed there has been shift away from mechanical ventilation, with increased use of tracheostomy/tracheal tube airway spontaneous ventilation. Inhalation injury patients require more ventilatory support though patient outcomes do not differ. Prospective trials are required to establish which strategies confer benefit.

  10. Stress and coping strategies among nursing students: an international study.

    Science.gov (United States)

    Labrague, Leodoro J; McEnroe-Petitte, Denise M; Papathanasiou, Ioanna V; Edet, Olaide B; Tsaras, Konstantinos; Leocadio, Michael C; Colet, Paolo; Kleisiaris, Christos F; Fradelos, Evangelos C; Rosales, Rheajane A; Vera Santos-Lucas, Katherine; Velacaria, Pearl Irish T

    2017-12-20

    Mounting literature on stress and coping in nursing students are available; however, most of the findings are confined to a single cultural group. This study was conducted to determine the level of stress, its sources and coping strategies among nursing students from three countries: Greece, the Philippines and Nigeria. Using a descriptive, comparative research design, 547 nursing students (161 Greek nursing students, 153 Filipino nursing students, 233 Nigerian nursing students) participated in the study from August 2015 to April 2016. Two standardized instruments were used, the Perceived Stress Scale (PSS) and the Coping Behavior Inventory (CBI). Findings revealed that the degree of stress and the type of stressors and coping styles utilized by nursing students differ according to the country of origin. The year of study predicted overall stress (β = -0.149, p students. Strengthening nursing students' positive coping skills may be helpful for them to effectively deal with various stressors during their educational experiences while maximizing learning. Implementing empirically tested approaches maybe useful to prevent the recurrence of stress and lessen its impact such as stress management counseling, counseling programs, establishing peer and family support systems, and formulating hospital policies that will support nursing students.

  11. Comparative study of maternal and paternal disciplinary strategies.

    Science.gov (United States)

    Hart, C H; Robinson, C C

    1994-04-01

    Parents (109 mothers, 109 fathers) of 109 middle-class preschool-age children were interviewed separately in individual taperecorded home interviews to assess whether either parent was prone to use assertion of power or inductive reasoning as disciplinary strategies. Fathers reported using more power-assertive disciplining strategies with their preschool-age children than mothers.

  12. Winning Strategies: A Case Study of Oyo State Lottery, Nigeria

    African Journals Online (AJOL)

    PROF. OLIVER OSUAGWA

    2014-06-01

    Jun 1, 2014 ... 3.1 Simulation of Lottery Strategies. The data used for this research work consisted of the year 2011 lottery winning numbers of the Daily draw type of game as collected from the Oyo State Lottery. Commission. The data was used to simulate the random, low frequency and high frequency game strategies.

  13. Development of a qPCR strategy to select bean genes involved in plant defence response and regulated by the Trichoderma velutinum - Rhizoctonia solani interaction

    Directory of Open Access Journals (Sweden)

    Sara Mayo

    2016-08-01

    Full Text Available Bean production is affected by a wide diversity of fungal pathogens, among them Rhizoctonia solani is one of the most important. A strategy to control bean infectious diseases, mainly those caused by fungi, is based on the use of biocontrol agents that can reduce the negative effects of plant pathogens and also can promote positive responses in the plant. Trichoderma is a fungal genus that is able to induce the expression of genes involved in plant defence response and also to promote plant growth, root development and nutrient uptake. In this article, a strategy that combines in silico analysis and real time PCR to detect additional bean defence-related genes, regulated by the presence of Trichoderma velutinum and/or R. solani has been applied. Based in this strategy, from From the 48 bean genes initially analysed, 14 were selected, and only WRKY33, CH5b and hGS showed an up-regulatory response in the presence of T. velutinum. The other genes were or not affected (OSM34 or down-regulated by the presence of this fungus. R. solani infection resulted in a down-regulation of most of the genes analyzed, except PR1, OSM34 and CNGC2 that were not affected, and the presence of both, T. velutinum and R. solani, up-regulates hGS and down-regulates all the other genes analyzed, except CH5b which was not significantly affected.As conclusion, the strategy described in the present work has been shown to be effective to detect genes involved in plant defence, which respond to the presence of a biocontrol agent or to a pathogen and also to the presence of both. The selected genes show significant homology with previously described plant defence genes and they are expressed in bean leaves of plants treated with T. velutinum and/or infected with R. solani.

  14. Gene expression profiling in cluster headache: a pilot microarray study.

    Science.gov (United States)

    Sjöstrand, Christina; Duvefelt, Kristina; Steinberg, Anna; Remahl, Ingela Nilsson; Waldenlind, Elisabet; Hillert, Jan

    2006-01-01

    Cluster headache (CH) is a primary neurovascular headache disorder characterized by attacks of excruciating pain accompanied by ipsilateral autonomic symptoms. CH pathophysiology is presumed to involve an activation of hypothalamic and trigeminovascular systems, but inflammation and immunological mechanisms have also been hypothesized to be of importance. To identify differentially expressed genes during different clinical phases of CH, assuming that changes of pathophysiological importance would also be seen in peripheral venous blood. Blood samples were drawn at 3 consecutive occasions from 3 episodic CH patients: during attacks, between attacks and in remission, and at 1 occasion from 3 matched controls. Global gene expression was analyzed with microarray tehnology using the Affymetrix Human Genome U133 2.0 Plus GeneChip Set, covering more than 54,000 gene transcripts, corresponding to almost 22,000 genes. Quantitative RT-PCR on S100P gene expression was analyzed in 6 patients and 14 controls. Overall, quite small differences were seen intraindividually and large differences interindividually. However, pairwise comparisons of signal values showed upregulation of several S100 calcium binding proteins; S100A8 (calgranulin A), S100A12 (calgranulin C), and S100P during active phase of the disease compared to remission. Also, annexin A3 (calcium-binding) and ICAM3 showed upregulation. BIRC1 (neuronal apoptosis inhibitory protein), CREB5, HLA-DQA1, and HLA-DQB1 were upregulated in patients compared to controls. The upregulation of S100P during attack versus remission was confirmed by quantitative RT-PCR analysis. The S100A8 and S100A12 proteins are considered markers of non-infectious inflammatory disease, while the function of S100P is still largely unknown. Furthermore, upregulation of HLA-DQ genes in CH patients may also indicate an inflammatory response. Upregulation of these pro-inflammatory genes during the active phase of CH has not formerly been reported. Data

  15. Exploring factors affecting undergraduate medical students' study strategies in the clinical years: a qualitative study.

    NARCIS (Netherlands)

    Al Kadri, H.M.; Al-Moamary, M.S.; Elzubair, M.; Magzoub, M.E.; AlMutairi, A.; Roberts, C.; Vleuten, C.P.M. van der

    2011-01-01

    The aim of this study is to explore the effects of clinical supervision, and assessment characteristics on the study strategies used by undergraduate medical students during their clinical rotations. We conducted a qualitative phenomenological study at King Saud Bin Abdulaziz University for Health

  16. Exploring Factors Affecting Undergraduate Medical Students' Study Strategies in the Clinical Years: A Qualitative Study

    Science.gov (United States)

    Al Kadri, Hanan M. F.; Al-Moamary, Mohamed S.; Elzubair, Margaret; Magzoub, Mohi Eldien; AlMutairi, Abdulrahman; Roberts, Christopher; van der Vleuten, Cees

    2011-01-01

    The aim of this study is to explore the effects of clinical supervision, and assessment characteristics on the study strategies used by undergraduate medical students during their clinical rotations. We conducted a qualitative phenomenological study at King Saud Bin Abdulaziz University for Health Sciences, College of Medicine, Riyadh, Saudi…

  17. [Detection of Staphylococcus aureus resistant to methicillin (MRSA) by molecular biology (Cepheid GeneXpert IL, GeneOhm BD, Roche LightCycler, Hyplex Evigene I2A) versus screening by culture: Economic and practical strategy for the laboratory].

    Science.gov (United States)

    Laudat, P; Demondion, E; Jouannet, C; Charron, J; Chillou, C; Salaun, V; Mankikian, B

    2012-06-01

    Patients admitted in cardiac surgery and cardiac ICU at the Clinic Saint-Gatien (Tours) are screened for MRSA at the entrance by nasal swab and culture on blood agar and selective chromogenic medium made by addition of cefoxitin: BBL CHROMagar MRSA-II BD (result obtained at Day +1). We wanted to assess the molecular biology techniques available to obtain a result at day 0 for the majority of patients and to define an economic and practical strategy for the laboratory. We studied four molecular biology techniques: Cepheid GeneXpert (Cepheid) GeneOhm (BD), LightCycler (Roche) and Hyplex (I2A). Upon reception, nasal swabs were treated by culture, considered as reference, and one of the techniques of molecular biology, according to the manufacturer's notice. We conducted four studies between April 2008 and February 2009 to obtain a significant sample for each of them. By screening we mean a method that allows us to exclude MRSA carriage for patients waiting for surgery, and not to change patient management: for example, lack of isolation measures specific to entrance, no modification of antibiotic prophylaxis during surgery and no isolation measures in the immediate postoperative period. The criteria we considered for this evaluation were: (1) technician time: time to perform one or a series of sample(s) n=10 or more (about 2h for all techniques except GeneXpert 75min), level of skilled competences (no specific training for GeneXpert); (2) results: turnaround time (all molecular biology techniques), ease of reading and results interpretations (no specialized training required for GeneXpert), failure or not (12% of failure of internal controls for GeneOhm); (3) economic: cost for one or a series of sample(s) (n=10 or more), if we considered X as the reference culture cost (10 X Hyplex and LightCycler, 20 X and 40 X for GeneXpert GeneOhm); (4) NPV: 100% for GeneXpert and LightCycler. At same sensitivity, no technique, including culture, can solve alone our problem, which

  18. Reverse Engineering of Gene Regulatory Networks: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Hendrik Hache

    2009-01-01

    Full Text Available Reverse engineering of gene regulatory networks has been an intensively studied topic in bioinformatics since it constitutes an intermediate step from explorative to causative gene expression analysis. Many methods have been proposed through recent years leading to a wide range of mathematical approaches. In practice, different mathematical approaches will generate different resulting network structures, thus, it is very important for users to assess the performance of these algorithms. We have conducted a comparative study with six different reverse engineering methods, including relevance networks, neural networks, and Bayesian networks. Our approach consists of the generation of defined benchmark data, the analysis of these data with the different methods, and the assessment of algorithmic performances by statistical analyses. Performance was judged by network size and noise levels. The results of the comparative study highlight the neural network approach as best performing method among those under study.

  19. Did Not Wait Patient Management Strategy (DNW PMS) Study.

    LENUS (Irish Health Repository)

    O'Keeffe, Fran

    2011-06-14

    Objectives This study was undertaken to assess the usefulness of senior emergency medicine specialists\\' review of all \\'did not wait\\' (DNW) patients\\' triage notes and the recall of at-risk patients. Methods A prospective study of all DNW patients was performed from 1 January to 31 December 2008. Following a daily review of charts of those who failed to wait to be seen, those patients considered to be at risk of adverse outcome were contacted by the liaison team and advised to return. Data were gathered on all DNW patients on the Oracle database and interrogated using the Diver solution. Results 2872 (6.3%) of 45 959 patients did not wait to be seen. 107 (3.7%) were recalled on the basis of senior emergency medicine doctor review of the patients\\' triage notes. Variables found to be associated with increased likelihood of being recalled included triage category (p<0.001), male sex (p<0.004) and certain clinical presentations. The presenting complaints associated with being recalled were chest pain (p<0.001) and alcohol\\/drug overdose (p=0.001). 9.4% of DNW patients required admission following recall. Conclusion The systematic senior doctor review of triage notes led to 3.7% of patients who failed to wait being recalled. 9.4% of those recalled required acute admission. The daily review of DNW patients\\' triage notes and the recalling of at-risk patients is a valuable addition to our risk management strategy.

  20. Nattokinase production: Medium components and feeding strategy studies

    Directory of Open Access Journals (Sweden)

    Berenjian Aydin

    2014-01-01

    Full Text Available In the present study, the effect of nutrients on nattokinase activity during the fermentation of Bacillus subtilis natto was investigated. The highest nattokinase activity of 587 U/mL was obtained in fermenter for a media consisting of yeast extract (6%, w/v, soy peptone (1.2%, w/v and glycerol (6%, w/v. The second order polynomial equation was fitted to the results by using central composite face design. The polynomial model fitted the experimental data well with R2 = 0.939 and R2(Adj = 0.861. In addition, contribution of fed-batch glycerol addition on the nattokinase production pathway was further investigated. Maximum nattokinase activity was resulted when 3% (w/v glycerol was added to the fermentation media during the cell growth phase. Results demonstrate 25 fold increase of nattokinase activity compared to the batch and not optimized culture. This study provides valuable data on the key nutrients and feeding strategy for further investigations and scale up of nattokinase production process.

  1. Did Not Wait Patient Management Strategy (DNW PMS) Study.

    LENUS (Irish Health Repository)

    2012-02-01

    Objectives This study was undertaken to assess the usefulness of senior emergency medicine specialists\\' review of all \\'did not wait\\' (DNW) patients\\' triage notes and the recall of at-risk patients. Methods A prospective study of all DNW patients was performed from 1 January to 31 December 2008. Following a daily review of charts of those who failed to wait to be seen, those patients considered to be at risk of adverse outcome were contacted by the liaison team and advised to return. Data were gathered on all DNW patients on the Oracle database and interrogated using the Diver solution. Results 2872 (6.3%) of 45 959 patients did not wait to be seen. 107 (3.7%) were recalled on the basis of senior emergency medicine doctor review of the patients\\' triage notes. Variables found to be associated with increased likelihood of being recalled included triage category (p<0.001), male sex (p<0.004) and certain clinical presentations. The presenting complaints associated with being recalled were chest pain (p<0.001) and alcohol\\/drug overdose (p=0.001). 9.4% of DNW patients required admission following recall. Conclusion The systematic senior doctor review of triage notes led to 3.7% of patients who failed to wait being recalled. 9.4% of those recalled required acute admission. The daily review of DNW patients\\' triage notes and the recalling of at-risk patients is a valuable addition to our risk management strategy.

  2. Efficient two-step testing of gene-gene interactions in genome-wide association studies.

    Science.gov (United States)

    Lewinger, Juan Pablo; Morrison, John L; Thomas, Duncan C; Murcray, Cassandra E; Conti, David V; Li, Dalin; Gauderman, W James

    2013-07-01

    Exhaustive testing of all possible SNP pairs in a genome-wide association study (GWAS) generally yields low power to detect gene-gene (G × G) interactions because of small effect sizes and stringent requirements for multiple-testing correction. We introduce a new two-step procedure for testing G × G interactions in case-control GWAS to detect interacting single nucleotide polymorphisms (SNPs) regardless of their marginal effects. In an initial screening step, all SNP pairs are tested for gene-gene association in the combined sample of cases and controls. In the second step, the pairs that pass the screening are followed up with a traditional test for G × G interaction. We show that the two-step method is substantially more powerful to detect G × G interactions than the exhaustive testing approach. For example, with 2,000 cases and 2,000 controls, the two-step method can have more than 90% power to detect an interaction odds ratio of 2.0 compared to less than 50% power for the exhaustive testing approach. Moreover, we show that a hybrid two-step approach that combines our newly proposed two-step test and the two-step test that screens for marginal effects retains the best power properties of both. The two-step procedures we introduce have the potential to uncover genetic signals that have not been previously identified in an initial single-SNP GWAS. We demonstrate the computational feasibility of the two-step G × G procedure by performing a G × G scan in the asthma GWAS of the University of Southern California Children's Health Study. © 2013 WILEY PERIODICALS, INC.

  3. The Relative Effectiveness of Integrated Reading Study Strategy and Conceptual Physics Approach

    Science.gov (United States)

    Taslidere, Erdal; Eryilmaz, Ali

    2012-01-01

    The primary purpose of this study was to investigate the combined and partial effects of the Integrated Reading/Study Strategy and Conceptual Physics Approach on ninth grade private high school students' achievement in and attitudes toward optics. The Integrated Reading/Study Strategy is a new strategy which was developed by integrating previously…

  4. Genomic Approach to Study Floral Development Genes in Rosa sp.

    Science.gov (United States)

    Chauvet, Aurélie; Maene, Marion; Pécrix, Yann; Yang, Shu-Hua; Jeauffre, Julien; Thouroude, Tatiana; Boltz, Véronique; Martin-Magniette, Marie-Laure; Janczarski, Stéphane; Legeai, Fabrice; Renou, Jean-Pierre; Vergne, Philippe; Le Bris, Manuel; Foucher, Fabrice; Bendahmane, Mohammed

    2011-01-01

    Cultivated for centuries, the varieties of rose have been selected based on a number of flower traits. Understanding the genetic and molecular basis that contributes to these traits will impact on future improvements for this economically important ornamental plant. In this study, we used scanning electron microscopy and sections of meristems and flowers to establish a precise morphological calendar from early rose flower development stages to senescing flowers. Global gene expression was investigated from floral meristem initiation up to flower senescence in three rose genotypes exhibiting contrasted floral traits including continuous versus once flowering and simple versus double flower architecture, using a newly developed Affymetrix microarray (Rosa1_Affyarray) tool containing sequences representing 4765 unigenes expressed during flower development. Data analyses permitted the identification of genes associated with floral transition, floral organs initiation up to flower senescence. Quantitative real time PCR analyses validated the mRNA accumulation changes observed in microarray hybridizations for a selection of 24 genes expressed at either high or low levels. Our data describe the early flower development stages in Rosa sp, the production of a rose microarray and demonstrate its usefulness and reliability to study gene expression during extensive development phases, from the vegetative meristem to the senescent flower. PMID:22194838

  5. Evaluation of gene delivery strategies to efficiently overexpress functional HLA-G on human bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    Joana S Boura

    2014-01-01

    Full Text Available Mesenchymal stromal cells (MSC constitutively express low levels of human leukocyte antigen-G (HLA-G, which has been shown to contribute to their immunomodulatory and anti-inflammatory properties. Here, we hypothesized that overexpression of HLA-G on bone marrow-derived MSC would improve their immunomodulatory function, thus increasing their therapeutic potential. Therefore, we investigated which gene transfer system is best suited for delivering this molecule while maintaining its immunomodulatory effects. We performed a side-by-side comparison between three nonviral plasmid-based platforms (pmax-HLA-G1; MC-HLA-G1; pEP-HLA-G1 and a viral system (Lv-HLA-G1 using gene transfer parameters that yielded similar levels of HLA-G1-expressing MSC. Natural killer (NK cell–mediated lysis assays and T cell proliferation assays showed that MSC modified with the HLA-G1 expressing viral vector had significantly lower susceptibility to NK-lysis and significantly reduced T cell proliferation when compared to nonmodified cells or MSC modified with plasmid. We also show that, in plasmid-modified MSC, an increase in Toll-like receptor (TLR9 expression is the mechanism responsible for the abrogation of HLA-G1's immunomodulatory effect. Although MSC can be efficiently modified to overexpress HLA-G1 using viral and nonviral strategies, only viral-based delivery of HLA-G1 is suitable for improvement of MSC's immunomodulatory properties.

  6. Application of the differential display RT-PCR strategy for the identification of inflammation-related mouse genes

    Directory of Open Access Journals (Sweden)

    Silva A.M.

    1999-01-01

    Full Text Available The inflammatory response elicited by various stimuli such as microbial products or cytokines is determined by differences in the pattern of cellular gene expression. We have used the differential display RT-PCR (DDRT-PCR strategy to identify mRNAs that are differentially expressed in various murine cell types stimulated with pro-inflammatory cytokines, microbial products or anti-inflammatory drugs. Mouse embryonic fibroblasts (MEFs were treated with IFNs, TNF, or sodium salicylate. Also, peritoneal macrophages from C3H/Hej mice were stimulated with T. cruzi-derived GPI-mucin and/or IFN-g. After DDRT-PCR, various cDNA fragments that were differentially represented on the sequencing gel were recovered, cloned and sequenced. Here, we describe a summary of several experiments and show that, when 16 of a total of 28 recovered fragments were tested for differential expression, 5 (31% were found to represent mRNAs whose steady-state levels are indeed modulated by the original stimuli. Some of the identified cDNAs encode for known proteins that were not previously associated with the inflammatory process triggered by the original stimuli. Other cDNA fragments (8 of 21 sequences, or 38% showed no significant homology with known sequences and represent new mouse genes whose characterization might contribute to our understanding of inflammation. In conclusion, DDRT-PCR has proven to be a potent technology that will allow us to identify genes that are differentially expressed when cells are subjected to changes in culture conditions or isolated from different organs.

  7. Herpesvirus microRNAs for use in gene therapy immune-evasion strategies.

    Science.gov (United States)

    Bots, S T F; Hoeben, R C

    2017-07-01

    Transplantation of allogeneic cells as well as of genetically corrected autologous cells are potent approaches to restore cellular functions in patients suffering from genetic diseases. The recipient's immune responses against non-self-antigens may compromise the survival of the grafted cells. Recipients of the graft may therefore require lifelong treatment with immunosuppressive drugs. An alternative approach to reduce graft rejection could involve the use of immune-evasion molecules. Expression of such molecules in cells of the graft may subvert recognition by the host's immune system. Viruses in particular are masters of exploitation and modulation of their hosts immune response. The Herpesviridae family provides a proof of concept for this as these viruses are capable to establish latency and a lifelong persistence in the infected hosts. While several viral proteins involved in immune evasion have been characterized, the Herpesviridae also encode a multitude of viral microRNA (miRNAs). Several of these miRNAs have been demonstrated to reduce the sensitivity of the infected cells to the destructive action of the host's immune cells. In this review, the miRNAs of some common herpesviruses that are associated with immune modulation will be discussed with a focus on their potential use in strategies aiming at generating non-immunogenic cells for transplantation.

  8. Simple, Efficient CRISPR-Cas9-Mediated Gene Editing in Mice: Strategies and Methods.

    Science.gov (United States)

    Low, Benjamin E; Kutny, Peter M; Wiles, Michael V

    2016-01-01

    Genetic modification of almost any species is now possible using approaches based on targeted nucleases. These novel tools now bypass previous limited species windows, allowing precision nucleotide modification of the genome at high efficiency, rapidly and economically. Here we focus on the modification of the mouse genome; the mouse, with its short generation time and comparatively low maintenance/production costs is the perfect mammal with which to probe the genome to understand its functions and complexities. Further, using targeted nucleases combined with homologous recombination, it is now possible to precisely tailor the genome, creating models of human diseases and conditions directly and efficiently in zygotes derived from any mouse strain. Combined these approaches make it possible to sequentially and progressively refine mouse models to better reflect human disease, test and develop therapeutics. Here, we briefly review the strategies involved in designing targeted nucleases (sgRNAs) providing solutions and outlining in detail the practical processes involved in precision targeting and modification of the mouse genome and the establishing of new precision genetically modified mouse lines.

  9. Within-item strategy switching in arithmetic: a comparative study in children.

    Science.gov (United States)

    Ardiale, Eléonore; Lemaire, Patrick

    2013-01-01

    The present study aimed at determining whether (1) children were able to interrupt a strategy execution to switch and choose another better strategy, and (2) their ability to switch strategy within-item improved with age. Third, fifth, and seventh graders performed a computational estimation task in which they had to provide the better estimates to two-digit addition problems (e.g., 32 + 54) while using the rounding-down (e.g., 30 + 50) or the rounding-up strategy (e.g., 40 + 60). After having executing the cued strategy (e.g., 30 + 50) during 1,000 ms, participants were given the opportunity to switch to another better strategy (e.g., 40 + 60) or to repeat the same strategy (e.g., 30 + 50). The results showed that children switched strategies within items, and were able to switch more often when the addition problems were cued with the poorer strategy (e.g., 40 + 60 for 32 + 54) than when cued with the better strategy (e.g., 30 + 50). As they grew up, children based their decisions to switch strategies more often on whether the 1,000-ms strategy execution concerned the better strategy or strategy difficulty (i.e., the rounding-up strategy). These findings have important implications to further understand mechanisms underlying within-item strategy switching as well as strategic variations in children.

  10. Within-item strategy switching in arithmetic: a comparative study in children

    Science.gov (United States)

    Ardiale, Eléonore; Lemaire, Patrick

    2013-01-01

    The present study aimed at determining whether (1) children were able to interrupt a strategy execution to switch and choose another better strategy, and (2) their ability to switch strategy within-item improved with age. Third, fifth, and seventh graders performed a computational estimation task in which they had to provide the better estimates to two-digit addition problems (e.g., 32 + 54) while using the rounding-down (e.g., 30 + 50) or the rounding-up strategy (e.g., 40 + 60). After having executing the cued strategy (e.g., 30 + 50) during 1,000 ms, participants were given the opportunity to switch to another better strategy (e.g., 40 + 60) or to repeat the same strategy (e.g., 30 + 50). The results showed that children switched strategies within items, and were able to switch more often when the addition problems were cued with the poorer strategy (e.g., 40 + 60 for 32 + 54) than when cued with the better strategy (e.g., 30 + 50). As they grew up, children based their decisions to switch strategies more often on whether the 1,000-ms strategy execution concerned the better strategy or strategy difficulty (i.e., the rounding-up strategy). These findings have important implications to further understand mechanisms underlying within-item strategy switching as well as strategic variations in children. PMID:24368906

  11. Defining a data management strategy for USGS Chesapeake Bay studies

    Science.gov (United States)

    Ladino, Cassandra

    2013-01-01

    The mission of U.S. Geological Survey’s (USGS) Chesapeake Bay studies is to provide integrated science for improved understanding and management of the Chesapeake Bay ecosystem. Collective USGS efforts in the Chesapeake Bay watershed began in the 1980s, and by the mid-1990s the USGS adopted the watershed as one of its national place-based study areas. Great focus and effort by the USGS have been directed toward Chesapeake Bay studies for almost three decades. The USGS plays a key role in using “ecosystem-based adaptive management, which will provide science to improve the efficiency and accountability of Chesapeake Bay Program activities” (Phillips, 2011). Each year USGS Chesapeake Bay studies produce published research, monitoring data, and models addressing aspects of bay restoration such as, but not limited to, fish health, water quality, land-cover change, and habitat loss. The USGS is responsible for collaborating and sharing this information with other Federal agencies and partners as described under the President’s Executive Order 13508—Strategy for Protecting and Restoring the Chesapeake Bay Watershed signed by President Obama in 2009. Historically, the USGS Chesapeake Bay studies have relied on national USGS databases to store only major nationally available sources of data such as streamflow and water-quality data collected through local monitoring programs and projects, leaving a multitude of other important project data out of the data management process. This practice has led to inefficient methods of finding Chesapeake Bay studies data and underutilization of data resources. Data management by definition is “the business functions that develop and execute plans, policies, practices and projects that acquire, control, protect, deliver and enhance the value of data and information.” (Mosley, 2008a). In other words, data management is a way to preserve, integrate, and share data to address the needs of the Chesapeake Bay studies to better

  12. The 3R study strategy. Optimizing the effectiveness of the ‘Read-Recite-Review’ study strategy in learning from text

    NARCIS (Netherlands)

    Reijners, Pauline; Kester, Liesbeth; Wetzels, Sandra; Kirschner, Paul A.

    2011-01-01

    Reijners, P. B. G., Kester, L., Wetzels, S. A. J., & Kirschner, P. A. (2011, 14 October). The 3R study strategy. Optimizing the effectiveness of the ‘Read-Recite-Review’ study strategy in learning from text. Presentation at ICO Introductory Course, Utrecht.

  13. The 3R Study Strategy - Optimizing the effectiveness of the ‘Read-Recite-Review’ study strategy in learning from text

    NARCIS (Netherlands)

    Reijners, Pauline; Kester, Liesbeth; Wetzels, Sandra; Kirschner, Paul A.

    2012-01-01

    Reijners, P. B. G., Kester, L., Wetzels, S. A. J., & Kirschner, P. A. (2012, 16 February). The 3R Study Strategy - Optimizing the effectiveness of the ‘Read-Recite-Review’ study strategy in learning from text. Presentation at plenary meeting Learning & Cogntion, Heerlen, The Netherlands.

  14. Mutations in the PAH gene: A Tool for population genetics study

    Directory of Open Access Journals (Sweden)

    Stojiljković Maja

    2007-01-01

    Full Text Available Phenylketonuria (PKU, an inborn error of metabolism, is caused by mutations in the phenylalanine hydroxylase (PAH gene. In the Serbian population, 19 different PAH mutations have been identified. We used PAH mutations as molecular markers for population genetics study. The low homozygosity value of the PAH gene (0.10 indicates that PKU in Serbia is heterogeneous, reflecting numerous migrations throughout Southeast Europe. The strategy for molecular diagnostics of PKU was designed accordingly. To elucidate the origin of the most common (L48S PKU mutation in Serbia, we performed haplotype analysis by PCR-RFLP. Our results suggest that the L48S mutation was imported into Serbia from populations with different genetic backgrounds.

  15. Network Graph Analysis of Gene-Gene Interactions in Genome-Wide Association Study Data

    Directory of Open Access Journals (Sweden)

    Sungyoung Lee

    2012-12-01

    Full Text Available Most common complex traits, such as obesity, hypertension, diabetes, and cancers, are known to be associated with multiple genes, environmental factors, and their epistasis. Recently, the development of advanced genotyping technologies has allowed us to perform genome-wide association studies (GWASs. For detecting the effects of multiple genes on complex traits, many approaches have been proposed for GWASs. Multifactor dimensionality reduction (MDR is one of the powerful and efficient methods for detecting high-order gene-gene (GxG interactions. However, the biological interpretation of GxG interactions identified by MDR analysis is not easy. In order to aid the interpretation of MDR results, we propose a network graph analysis to elucidate the meaning of identified GxG interactions. The proposed network graph analysis consists of three steps. The first step is for performing GxG interaction analysis using MDR analysis. The second step is to draw the network graph using the MDR result. The third step is to provide biological evidence of the identified GxG interaction using external biological databases. The proposed method was applied to Korean Association Resource (KARE data, containing 8838 individuals with 327,632 single-nucleotide polymorphisms, in order to perform GxG interaction analysis of body mass index (BMI. Our network graph analysis successfully showed that many identified GxG interactions have known biological evidence related to BMI. We expect that our network graph analysis will be helpful to interpret the biological meaning of GxG interactions.

  16. Knowledge Management Strategy Adopted by PNRA: A Case Study

    International Nuclear Information System (INIS)

    Baig, Zaheer Ayub; Ansari, Fauzia; Awan, Ali

    2014-01-01

    PNRA’s objectives of the KM strategy: • Identification of critical knowledge domains; • Identification of explicit and tacit knowledge resources; • Conversion of tacit knowledge into explicit; • Preservation of the knowledge capital; • Efficient and simple access

  17. Afghanistan Study Group Report: Revitalizing Our Efforts, Rethinking Our Strategies

    National Research Council Canada - National Science Library

    Jones, James L; Pickering, Thomas R

    2008-01-01

    ... comprehensive strategy to fill the power vacuum outside Kabul and to counter the combined challenges of reconstituted Taliban and al-Qaeda forces in Afghanistan and Pakistan, a runaway opium economy...

  18. Changes in gene expression linked with adult reproductive diapause in a northern malt fly species: a candidate gene microarray study

    Directory of Open Access Journals (Sweden)

    Hoikkala Anneli

    2010-02-01

    Full Text Available Abstract Background Insect diapause is an important biological process which involves many life-history parameters important for survival and reproductive fitness at both individual and population level. Drosophila montana, a species of D. virilis group, has a profound photoperiodic reproductive diapause that enables the adult flies to survive through the harsh winter conditions of high latitudes and altitudes. We created a custom-made microarray for D. montana with 101 genes known to affect traits important in diapause, photoperiodism, reproductive behaviour, circadian clock and stress tolerance in model Drosophila species. This array gave us a chance to filter out genes showing expression changes during photoperiodic reproductive diapause in a species adapted to live in northern latitudes with high seasonal changes in environmental conditions. Results Comparisons among diapausing, reproducing and young D. montana females revealed expression changes in 24 genes on microarray; for example in comparison between diapausing and reproducing females one gene (Drosophila cold acclimation gene, Dca showed up-regulation and 15 genes showed down-regulation in diapausing females. Down-regulation of seven of these genes was specific to diapause state while in five genes the expression changes were linked with the age of the females rather than with their reproductive status. Also, qRT-PCR experiments confirmed couch potato (cpo gene to be involved in diapause of D. montana. Conclusions A candidate gene microarray proved to offer a practical and cost-effective way to trace genes that are likely to play an important role in photoperiodic reproductive diapause and further in adaptation to seasonally varying environmental conditions. The present study revealed two genes, Dca and cpo, whose role in photoperiodic diapause in D. montana is worth of studying in more details. Also, further studies using the candidate gene microarray with more specific experimental

  19. A novel extremophile strategy studied by Raman spectroscopy

    Science.gov (United States)

    Edwards, Howell G. M.

    2007-12-01

    A case is made for the classification of the colonisation by Dirina massiliensis forma sorediata of pigments on ancient wall-paintings as extremophilic behaviour. The lichen encrustations studied using FT-Raman spectroscopy have yielded important molecular information which has assisted in the identification of the survival strategy of the organism in the presence of significant levels of heavy metal toxins. The production of a carotenoid, probably astaxanthin, at the surface of the lichen thalli is identified from its characteristic biomolecular signatures in the Raman spectrum, whereas the presence of calcium oxalate dihydrate (weddellite) has been identified at both the upper and lower surfaces of the thalli and in core samples taken from depths of up to 10 mm through the encrustation into the rock substrate. The latter observation explains the significant disintegrative biodeteriorative effect of the colonisation upon the integrity of the wall-paintings and can be used to direct conservatorial and preservation efforts of the art work. A surprising result proved to be the absence of Raman spectroscopic evidence for the complexation of the metal pigments by the oxalic acid produced by the metabolic action of the organisms, unlike several cases that have been reported in the literature.

  20. Strategies for Growing User Popularity through Retweet: An Empirical Study

    Directory of Open Access Journals (Sweden)

    Yecely Aridaí Díaz-Beristain

    2017-01-01

    Full Text Available Web-based Social Networks (W-bSNs have recently experienced a significant rise regarding users and the number of relations among them. Twitter is a case of W-bSN in which the relevance of the commentaries posted influences how users create new relations. The reputation of a user has a direct effect on the perception and opinions of other people and can be appropriately used to obtain advantages. The thought expressed by an influential user can produce, as an effect, which other users changed an idea about a topic. In this work, we present the design and results of the empirical study to analyze the cross influence among users, for their interest, and the messages they post and how relevant these messages are in how we create new relations. One of the main contributions of this approach is to analyze the behavior of users and the impact of the diversification of topics and the inclusion of additional resources to the tweet such as videos, images, or URLs. Finally, the experimental results show that the proposed strategies are efficient for all accounts.

  1. The Role of Metacognitive Reading Strategies, Metacognitive Study and Learning Strategies, and Behavioral Study and Learning Strategies in Predicting Academic Success in Students with and without a History of Reading Difficulties

    Science.gov (United States)

    Chevalier, Thérèse M.; Parrila, Rauno; Ritchie, Krista C.; Deacon, S. Hélène

    2017-01-01

    We examined the self-reported use of reading, study, and learning strategies in university students with a history of reading difficulties (HRD; n = 77) and with no history of reading difficulties (NRD; n = 295). We examined both between-groups differences in strategy use and strategy use as a predictive measure of academic success. Participants…

  2. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  3. Language Learning Strategies of Turkish and Arabic Students: A Cross-Cultural Study

    Science.gov (United States)

    Köksal, Dinçay; Ulum, Ömer Gökhan

    2016-01-01

    This study investigates the language learning strategy use of Turkish and Arabic students enrolled in middle schools and having different cultural and linguistic backgrounds. Using a strategy inventory for language learning, the study examines the cross-cultural differences in strategy use of the mentioned students while learning English as a…

  4. Echinoderm systems for gene regulatory studies in evolution and development.

    Science.gov (United States)

    Arnone, Maria Ina; Andrikou, Carmen; Annunziata, Rossella

    2016-08-01

    One of the main challenges in Evolutionary Developmental Biology is to understand to which extent developmental changes are driven by regulatory alterations in the genomic sequence. In the recent years, the focus of comparative developmental studies has moved towards a systems biology approach providing a better understanding of the evolution of gene interactions that form the so called Gene Regulatory Networks (GRN). Echinoderms provide a powerful system to reveal regulatory mechanisms and within the past decade, due to the latest technological innovations, a great number of studies have provided valuable information for comparative GRN analyses. In this review we describe recent advances in evolution of GRNs arising from echinoderm systems, focusing on the properties of conserved regulatory kernels, circuit co-option events and GRN topological rearrangements. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Molecular genetic gene-environment studies using candidate genes in schizophrenia: a systematic review.

    Science.gov (United States)

    Modinos, Gemma; Iyegbe, Conrad; Prata, Diana; Rivera, Margarita; Kempton, Matthew J; Valmaggia, Lucia R; Sham, Pak C; van Os, Jim; McGuire, Philip

    2013-11-01

    The relatively high heritability of schizophrenia suggests that genetic factors play an important role in the etiology of the disorder. On the other hand, a number of environmental factors significantly influence its incidence. As few direct genetic effects have been demonstrated, and there is considerable inter-individual heterogeneity in the response to the known environmental factors, interactions between genetic and environmental factors may be important in determining whether an individual develops the disorder. To date, a considerable number of studies of gene-environment interactions (G×E) in schizophrenia have employed a hypothesis-based molecular genetic approach using candidate genes, which have led to a range of different findings. This systematic review aims to summarize the results from molecular genetic candidate studies and to review challenges and opportunities of this approach in psychosis research. Finally, we discuss the potential of future prospects, such as new studies that combine hypothesis-based molecular genetic candidate approaches with agnostic genome-wide association studies in determining schizophrenia risk. © 2013 Elsevier B.V. All rights reserved.

  6. Effects of emotion regulation strategies on music-elicited emotions: An experimental study explaining individual differences

    NARCIS (Netherlands)

    Karreman, A.; Laceulle, O.M.; Hanser, Waldie; Vingerhoets, Ad

    This experimental study examined if emotional experience can be manipulated by applying an emotion regulation strategy during music listening and if individual differences in effects of strategies can be explained by person characteristics. Adults (N = 466) completed questionnaires and rated

  7. Effects of emotion regulation strategies on music elicited emotions : An experimental study explaining individual differences

    NARCIS (Netherlands)

    Karreman, A.; Laceulle, O.M.; Hanser, W.E.; Vingerhoets, A.J.J.M.

    2017-01-01

    This experimental study examined if emotional experience can be manipulated by applying an emotion regulation strategy during music listening and if individual differences in effects of strategies can be explained by person characteristics. Adults (N = 466) completed questionnaires and rated

  8. A Simple and Rapid Gene Disruption Strategy in Mycobacterium abscessus: On the Design and Application of Glycopeptidolipid Mutants

    Directory of Open Access Journals (Sweden)

    Albertus Viljoen

    2018-03-01

    Full Text Available Little is known about the disease-causing genetic determinants that are used by Mycobacterium abscessus, increasingly acknowledged as an important emerging pathogen, notably in cystic fibrosis. The presence or absence of surface exposed glycopeptidolipids (GPL conditions the smooth (S or rough (R M. abscessus subsp. abscessus (M. abscessus variants, respectively, which are characterized by distinct infective programs. However, only a handful of successful gene knock-out and conditional mutants have been reported in M. abscessus, testifying that genetic manipulation of this mycobacterium is difficult. To facilitate gene disruption and generation of conditional mutants in M. abscessus, we have designed a one-step single cross-over system that allows the rapid and simple generation of such mutants. Cloning of as small as 300 bp of the target gene allows for efficient homologous recombination to occur without additional exogenous recombination-promoting factors. The presence of tdTomato on the plasmids allows easily sifting out the large background of mutants spontaneously resistant to antibiotics. Using this strategy in the S genetic background and the target gene mmpL4a, necessary for GPL synthesis and transport, nearly 100% of red fluorescent clones exhibited a rough morphotype and lost GPL on the surface, suggesting that most red fluorescent colonies obtained after transformation incorporated the plasmid through homologous recombination into the chromosome. This system was further exploited to generate another strain with reduced GPL levels to explore how the presence of these cell wall-associated glycolipids influences M. abscessus hydrophobicity as well as virulence in the zebrafish model of infection. This mutant exhibited a more pronounced killing phenotype in zebrafish embryos compared to its S progenitor and this effect correlated with the production of abscesses in the central nervous system. Overall, these results suggest that the near

  9. Validation of suitable reference genes for expression studies in different pilocarpine-induced models of mesial temporal lobe epilepsy.

    Directory of Open Access Journals (Sweden)

    Thalita Ewellyn Batista Sales Marques

    Full Text Available It is well recognized that the reference gene in a RT-qPCR should be properly validated to ensure that gene expression is unaffected by the experimental condition. We investigated eight potential reference genes in two different pilocarpine PILO-models of mesial temporal lobe epilepsy (MTLE performing a stability expression analysis using geNorm, NormFinder and BestKepeer softwares. Then, as a validation strategy, we conducted a relative expression analysis of the Gfap gene. Our results indicate that in the systemic PILO-model Actb, Gapdh, Rplp1, Tubb2a and Polr1a mRNAs were highly stable in hippocampus of rats from all experimental and control groups, whereas Gusb revealed to be the most variable one. In fact, we observed that using Gusb for normalization, the relative mRNA levels of the Gfap gene differed from those obtained with stable genes. On the contrary, in the intrahippocampal PILO-model, all softwares included Gusb as a stable gene, whereas B2m was indicated as the worst candidate gene. The results obtained for the other reference genes were comparable to those observed for the systemic Pilo-model. The validation of these data by the analysis of the relative expression of Gfap showed that the upregulation of the Gfap gene in the hippocampus of rats sacrificed 24 hours after status epilepticus (SE was undetected only when B2m was used as the normalizer. These findings emphasize that a gene that is stable in one pathology model may not be stable in a different experimental condition related to the same pathology and therefore, the choice of reference genes depends on study design.

  10. Developing Gene Silencing for the Study and Treatment of Dystonia

    Science.gov (United States)

    2017-12-01

    that this is possible but using cells growing in a dish in the laboratory, not in living animals. In this project, we aim to answer several specific... important therapeutic implication of these experiments is that either the striatum is not the primary site of dysfunction in DYT1, or that the molecular...1 AWARD NUMBER: W81XWH-14-1-0282 TITLE: Developing Gene Silencing for the Study and Treatment of Dystonia PRINCIPAL INVESTIGATOR: Pedro

  11. A double-mutant collection targeting MAP kinase related genes in Arabidopsis for studying genetic interactions.

    Science.gov (United States)

    Su, Shih-Heng; Krysan, Patrick J

    2016-12-01

    Mitogen-activated protein kinase cascades are conserved in all eukaryotes. In Arabidopsis thaliana there are approximately 80 genes encoding MAP kinase kinase kinases (MAP3K), 10 genes encoding MAP kinase kinases (MAP2K), and 20 genes encoding MAP kinases (MAPK). Reverse genetic analysis has failed to reveal abnormal phenotypes for a majority of these genes. One strategy for uncovering gene function when single-mutant lines do not produce an informative phenotype is to perform a systematic genetic interaction screen whereby double-mutants are created from a large library of single-mutant lines. Here we describe a new collection of 275 double-mutant lines derived from a library of single-mutants targeting genes related to MAP kinase signaling. To facilitate this study, we developed a high-throughput double-mutant generating pipeline using a system for growing Arabidopsis seedlings in 96-well plates. A quantitative root growth assay was used to screen for evidence of genetic interactions in this double-mutant collection. Our screen revealed four genetic interactions, all of which caused synthetic enhancement of the root growth defects observed in a MAP kinase 4 (MPK4) single-mutant line. Seeds for this double-mutant collection are publicly available through the Arabidopsis Biological Resource Center. Scientists interested in diverse biological processes can now screen this double-mutant collection under a wide range of growth conditions in order to search for additional genetic interactions that may provide new insights into MAP kinase signaling. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  12. A Comparative Study of Feature Selection and Classification Methods for Gene Expression Data of Glioma

    KAUST Repository

    Abusamra, Heba

    2013-11-01

    Microarray gene expression data gained great importance in recent years due to its role in disease diagnoses and prognoses which help to choose the appropriate treatment plan for patients. This technology has shifted a new era in molecular classification. Interpreting gene expression data remains a difficult problem and an active research area due to their native nature of “high dimensional low sample size”. Such problems pose great challenges to existing classification methods. Thus, effective feature selection techniques are often needed in this case to aid to correctly classify different tumor types and consequently lead to a better understanding of genetic signatures as well as improve treatment strategies. This paper aims on a comparative study of state-of-the- art feature selection methods, classification methods, and the combination of them, based on gene expression data. We compared the efficiency of three different classification methods including: support vector machines, k-nearest neighbor and random forest, and eight different feature selection methods, including: information gain, twoing rule, sum minority, max minority, gini index, sum of variances, t-statistics, and one-dimension support vector machine. Five-fold cross validation was used to evaluate the classification performance. Two publicly available gene expression data sets of glioma were used in the experiments. Results revealed the important role of feature selection in classifying gene expression data. By performing feature selection, the classification accuracy can be significantly boosted by using a small number of genes. The relationship of features selected in different feature selection methods is investigated and the most frequent features selected in each fold among all methods for both datasets are evaluated.

  13. Investigating Learning Strategies for Vocabulary Development: A Comparative Study of Two Universities of Quetta, Pakistan

    Directory of Open Access Journals (Sweden)

    Irum Fatima

    2016-04-01

    Full Text Available The primary purpose of this research is to investigate the vocabulary learning strategies employed by the undergraduate students of Sardar Bahadur Khan Women’s University (SBKWU and University of Balochistan (UOB, Quetta, Pakistan. A quantitative design was employed in this study to answer the two research questions of the present study. The quantitative data was obtained from the responses of 180 undergraduates in a questionnaire adapted from the study by Noor and Amir (2009 on vocabulary learning strategies proposed by Gu and Johnson (1996. The questionnaire comprised of 45 close-ended items on four broad vocabulary learning strategies, metacognitive regulation strategy, cognitive strategy, memory strategy, and activation strategy. Descriptive statistics was run in SPSS to obtain the results. The independent-samples t-test was run to test for statistically significant differences if any in the use of vocabulary learning strategies across the undergraduates of two universities. However, cognitive regulation strategy, and activation strategy emerged as the most influential source of learning new English words. The findings also revealed that there were no statistically significant differences found in practicing vocabulary learning strategies between undergraduates of SBKWU and UOB. The findings of the study have implications on enhancing teaching and learning by acquainting students with vocabulary learning strategies that can enhance their vocabulary in English language and can result to boost up their proficiency in this language. Keywords: Vocabulary development, learning strategies, gender difference

  14. An Integrated Strategy to Identify Key Genes in Almond Adventitious Shoot Regeneration

    Science.gov (United States)

    Plant genetic transformation usually depends on efficient adventitious regeneration systems. In almond (Prunus dulcis Mill.), regeneration of transgenic adventitious shoots was achieved but with low efficiency. Histological studies identified two main stages of organogenesis in almond explants that ...

  15. Comparison of Two Output-Coding Strategies for Multi-Class Tumor Classification Using Gene Expression Data and Latent Variable Model as Binary Classifier

    Directory of Open Access Journals (Sweden)

    Sandeep J. Joseph

    2010-03-01

    Full Text Available Multi-class cancer classification based on microarray data is described. A generalized output-coding scheme based on One Versus One (OVO combined with Latent Variable Model (LVM is used. Results from the proposed One Versus One (OVO output- coding strategy is compared with the results obtained from the generalized One Versus All (OVA method and their efficiencies of using them for multi-class tumor classification have been studied. This comparative study was done using two microarray gene expression data: Global Cancer Map (GCM dataset and brain cancer (BC dataset. Primary feature selection was based on fold change and penalized t-statistics. Evaluation was conducted with varying feature numbers. The OVO coding strategy worked quite well with the BC data, while both OVO and OVA results seemed to be similar for the GCM data. The selection of output coding methods for combining binary classifiers for multi-class tumor classification depends on the number of tumor types considered, the discrepancies between the tumor samples used for training as well as the heterogeneity of expression within the cancer subtypes used as training data.

  16. Comparison of two output-coding strategies for multi-class tumor classification using gene expression data and Latent Variable Model as binary classifier.

    Science.gov (United States)

    Joseph, Sandeep J; Robbins, Kelly R; Zhang, Wensheng; Rekaya, Romdhane

    2010-03-10

    Multi-class cancer classification based on microarray data is described. A generalized output-coding scheme based on One Versus One (OVO) combined with Latent Variable Model (LVM) is used. Results from the proposed One Versus One (OVO) outputcoding strategy is compared with the results obtained from the generalized One Versus All (OVA) method and their efficiencies of using them for multi-class tumor classification have been studied. This comparative study was done using two microarray gene expression data: Global Cancer Map (GCM) dataset and brain cancer (BC) dataset. Primary feature selection was based on fold change and penalized t-statistics. Evaluation was conducted with varying feature numbers. The OVO coding strategy worked quite well with the BC data, while both OVO and OVA results seemed to be similar for the GCM data. The selection of output coding methods for combining binary classifiers for multi-class tumor classification depends on the number of tumor types considered, the discrepancies between the tumor samples used for training as well as the heterogeneity of expression within the cancer subtypes used as training data.

  17. Not all coping strategies are created equal: a mixed methods study exploring physicians' self reported coping strategies

    Directory of Open Access Journals (Sweden)

    Wallace Jean E

    2010-07-01

    Full Text Available Abstract Background Physicians experience workplace stress and draw on different coping strategies. The primary goal of this paper is to use interview data to explore physicians' self reported coping strategies. In addition, questionnaire data is utilized to explore the degree to which the coping strategies are used and are associated with feelings of emotional exhaustion, a key symptom of burnout. Methods This mixed methods study explores factors related to physician wellness within a large health region in Western Canada. This paper focuses on the coping strategies that physicians use in response to work-related stress. The qualitative component explores physicians' self reported coping strategies through open ended interviews of 42 physicians representing diverse medical specialties and settings (91% response rate. The major themes extracted from the qualitative interviews were used to construct 12 survey items that were included in the comprehensive quantitative questionnaire. Questionnaires were sent to all eligible physicians in the health region with 1178 completed surveys (40% response rate. Questionnaire items were used to measure how often physicians draw on the various coping strategies. Feelings of burnout were also measured in the survey by 5 items from the Emotional Exhaustion subscale of the revised Maslach Burnout Inventory. Results Major themes identified from the interviews include coping strategies used at work (e.g., working through stress, talking with co-workers, taking a time out, using humor and after work (e.g., exercise, quiet time, spending time with family. Analysis of the questionnaire data showed three often used workplace coping strategies were positively correlated with feeling emotionally exhausted (i.e., keeping stress to oneself (r = .23, concentrating on what to do next (r = .16, and going on as if nothing happened (r = .07. Some less often used workplace coping strategies (e.g., taking a time out and all

  18. Counterfeit analysis strategy illustrated by a case study.

    Science.gov (United States)

    Dégardin, Klara; Roggo, Yves

    2016-01-01

    Medicine counterfeiting is a current problem that the whole pharmaceutical field has to deal with. In 2014, counterfeits entered the legitimate supply chain in Europe. Quick and efficient action had to be taken. The aim of this paper is to explain which analytical strategy was chosen to deal with six of the cases concerned and which criteria have to be considered to provide quick and thorough information about the counterfeits. The evaluation of the packaging was performed in a first step, based on a comparison with genuine samples and evaluation of manipulation signs. Chemical methods were then used, consisting of near infrared and infrared spectroscopy, capillary zone electrophoresis and ultraviolet-visible spectrophotometry, in order to authenticate the samples and provide the chemical composition of the confirmed counterfeits. Among the 20 samples analyzed, 17 were confirmed as counterfeits. The counterfeits were the results of the manipulation of genuine samples, and one contained totally counterfeited parts. Several manipulation signs were asserted, like the addition of glue on the boxes and the vials. Genuine stolen goods had been diluted with water, while for an isolated case, a different active ingredient had been introduced in a vial. The analytical data generated were further investigated from a forensic intelligence perspective. Links could be revealed between the analyzed counterfeits, together with some interesting information about the modus operandi of the counterfeiters. The study was performed on a limited number of cases, and therefore encourages chemical and packaging profiling of counterfeits at a bigger scale. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  19. Permasalahan dan Strategi Pembangunan Lingkungan Berkelanjutan Studi Kasus: Cekungan Bandung

    Directory of Open Access Journals (Sweden)

    Setiawan Wangsaatmaja

    2014-06-01

    Full Text Available http://dx.doi.org/10.17014/ijog.vol1no3.20065Environmental problems occurring in the Bandung Basin are resulted from improper management pertaining to land and spatial planning, including landuse policy and control. Arising environmental problems are covering disturbance of watershed hydrological function, surface and groundwater quality and quantity, solid waste, and air quality. Environmental studies in the Bandung Basin have been implemented by landuse change interpretation, surface water regime measurements, water quality, solid waste management, and air quality. Landuse change has occurred where some vegetation areas, such as forests and paddy fi elds, have decreased for 54% in one hand, and developed area has increased into 223% in the other hand. Watershed degradation is indicated by run off coeffi cient increasing from 0.3 in 1950 to 0.55 in 1998. Flow regime has also changed by presence of a maximum extreme discharge increasing tendency from 217.9 m3/sec in 1951 to 285.8 m3/sec in 1998, and minimum extreme discharge decreasing tendency from 6.35 m3/sec in 1951 to 5.7 m3/sec in 1998. Groundwater productivity index continued decreasing from 0.1 million m3/unit in 1900 to 0.0188 million m3/unit in 2002. Environmental problem has also occurred in a solid waste management sector where an average level of service is only 43.7%, and air pollution by motor vehicle and industrial emission, such as PM10, NOx, CO2, SO2, Pb, and acid rain phenomena have also occurred. Fresh water supply level of service in the Bandung Basin only covers 43% of the total needs. Watershed degradation occurring in the Basin needs a management system recovery, administrative based-management that shifted to ecological based integrated watershed management. Effort and strategy required include the policy and institutional reassembling, pollution control, land rehabilitation and conservation, and community empowerment.  

  20. Study on coolability of melt pool with different strategies

    International Nuclear Information System (INIS)

    Kulkarni, P.P.; Nayak, A.K.

    2014-01-01

    Highlights: • Experiments have been performed to test quenching of molten pool with different schemes. • Top flooding, bottom flooding and indirect cooling schemes were used. • A single simulant material with same mass and initial temperature was used. • Bottom flooding technique is found to be the most effective technique. • A comparison of all the three techniques has been presented. - Abstract: After the Fukushima accident, there have been a lot of concerns regarding long term core melt stabilization following a severe accident in nuclear reactors. Several strategies have been contemplated for quenching and stabilization of core melt like top flooding, bottom flooding, indirect cooling, etc. However, the effectiveness of these schemes is yet to be determined properly, for which, lot of experiments are needed. Several experiments have been performed for coolability of molten pool under top flooding condition. A few experiments have been performed for study of coolability of melt pool under bottom flooding as well as for indirect cooling. Besides, these tests are very scattered because they involve different simulant materials, initial temperatures and masses of melt, which makes it very difficult to judge the effectiveness of a particular technique and advantage over the other. In the present paper we have carried out different experiments wherein a single simulant material with same mass was cooled with different techniques starting from the same initial temperature. The result showed that, while top flooding and indirect cooling took several hours to cool, bottom flooding took a few minutes to cool the melt which makes it the most effective technique

  1. An empirical study to analyze CRM strategy using BSC

    Directory of Open Access Journals (Sweden)

    Zahra Safari Kahreh

    2012-08-01

    Full Text Available In the new marketing paradigm that is based on the relationship marketing, corporations and organizations look for retaining and enhancing the long run relationships with their customers. Customer relationship management (CRM as a heart of the new marketing paradigm includes numbers of mechanisms that endeavor to manage sustainable and profitable long-term relations with valuable customers. Every year, there are many programs and resources dedicated for marketing strategy and planning. Evaluation of these endeavors especially the CRM strategy is much important. Hence, the primary purpose of this research is to analyze CRM using balanced scorecard as a valuable strategic tool. Required data was gathered from one of the biggest commercial banks of Iran and they were analyzed using BSC and statistical software packages. Results indicate that there is a meaningful relationship between 3 main aspects of CRM strategy and 4 main aspects of BSC.

  2. Memory Training and Strategy Use in Older Adults: Results from the ACTIVE Study

    Science.gov (United States)

    Gross, Alden L.; Rebok, George W.

    2013-01-01

    Little is known about the long-term effects of memory training in later life on strategy use. Data from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study (n = 1,401) were used to describe strategy use in a community-dwelling sample of older adults. Strategy clustering scores on verbal list learning tasks of episodic memory were used to test the impact of memory training on strategy use and study longitudinal associations between strategy clustering, memory performance, and everyday functioning. Results suggested that younger, female, white, healthier, and more educated participants show higher strategy clustering scores initially but no characteristics were consistently associated with different trajectories in strategy clustering across all strategy clustering measures together. Memory training had significant immediate effects on all measures of strategy use that were maintained through five years of follow-up. With respect to longitudinal mediation, pre-post training changes in most strategy clustering scores mediate changes in objective memory performance and everyday functioning, implying that strategies can be modified and are closely related to both memory ability and the ability to function independently. This study provides evidence that older adults can be trained to use cognitive strategies, the effects are durable, and strategies are associated with memory and everyday functioning. PMID:21443356

  3. Systematic targeted integration to study Albumin gene control elements.

    Directory of Open Access Journals (Sweden)

    Sanchari Bhattacharyya

    Full Text Available To study transcriptional regulation by distant enhancers, we devised a system of easily modified reporter plasmids for integration into single-copy targeting cassettes in clones of HuH7, a human hepatocellular carcinoma. The plasmid constructs tested transcriptional function of a 35-kb region that contained the rat albumin gene and its upstream flanking region. Expression of integrants was analyzed in two orientations, and compared to transient expression of non-integrated plasmids. Enhancers were studied in their natural positions relative to the promoter and localized by deletion. All constructs were also analyzed by transient transfection assays. In addition to the known albumin gene enhancer (E1 at -10 kb, we demonstrated two new enhancers, E2 at -13, and E4 at +1.2 kb. All three enhancers functioned in both transient assays and integrated constructs. However, chromosomal integration demonstrated several differences from transient expression. For example, analysis of E2 showed that enhancer function within the chromosome required a larger gene region than in transient assays. Another conserved region, E3 at -0.7 kb, functioned as an enhancer in transient assays but inhibited the function of E1 and E2 when chromosomally integrated. The enhancers did not show additive or synergistic behavior,an effect consistent with competition for the promoter or inhibitory interactions among enhancers. Growth arrest by serum starvation strongly stimulated the function of some integrated enhancers, consistent with the expected disruption of enhancer-promoter looping during the cell cycle.

  4. SVM-based generalized multifactor dimensionality reduction approaches for detecting gene-gene interactions in family studies.

    Science.gov (United States)

    Fang, Yao-Hwei; Chiu, Yen-Feng

    2012-02-01

    Gene-gene interaction plays an important role in the etiology of complex diseases, which may exist without a genetic main effect. Most current statistical approaches, however, focus on assessing an interaction effect in the presence of the gene's main effects. It would be very helpful to develop methods that can detect not only the gene's main effects but also gene-gene interaction effects regardless of the existence of the gene's main effects while adjusting for confounding factors. In addition, when a disease variant is rare or when the sample size is quite limited, the statistical asymptotic properties are not applicable; therefore, approaches based on a reasonable and applicable computational framework would be practical and frequently applied. In this study, we have developed an extended support vector machine (SVM) method and an SVM-based pedigree-based generalized multifactor dimensionality reduction (PGMDR) method to study interactions in the presence or absence of main effects of genes with an adjustment for covariates using limited samples of families. A new test statistic is proposed for classifying the affected and the unaffected in the SVM-based PGMDR approach to improve performance in detecting gene-gene interactions. Simulation studies under various scenarios have been performed to compare the performances of the proposed and the original methods. The proposed and original approaches have been applied to a real data example for illustration and comparison. Both the simulation and real data studies show that the proposed SVM and SVM-based PGMDR methods have great prediction accuracies, consistencies, and power in detecting gene-gene interactions. © 2012 Wiley Periodicals, Inc.

  5. Suiformes conservation: a study case of strategies for DNA utilization

    Indian Academy of Sciences (India)

    applied to the DNA extracted from faeces using GenomiPhi. V2 DNA Amplification kit (GE Healthcare, Canada) and. REPLI-gR Mini Kit (Qiagen, Hilden, Germany), following manufacturer's instructions. The WGA DNA was further compared with genomic DNA. PCR amplification of a nuclear histone H4 gene fragment and a.

  6. Gene expression profiling to study racial differences after heart transplantation.

    Science.gov (United States)

    Khush, Kiran K; Pham, Michael X; Teuteberg, Jeffrey J; Kfoury, Abdallah G; Deng, Mario C; Kao, Andrew; Anderson, Allen S; Cotts, William G; Ewald, Gregory A; Baran, David A; Hiller, David; Yee, James; Valantine, Hannah A

    2015-07-01

    The basis for increased mortality after heart transplantation in African Americans and other non-Caucasian racial groups is poorly defined. We hypothesized that increased risk of adverse events is driven by biologic factors. To test this hypothesis in the Invasive Monitoring Attenuation through Gene Expression (IMAGE) study, we determined whether the event rate of the primary outcome of acute rejection, graft dysfunction, death, or retransplantation varied by race as a function of calcineurin inhibitor (CNI) levels and gene expression profile (GEP) scores. We determined the event rate of the primary outcome, comparing racial groups, stratified by time after transplant. Logistic regression was used to compute the relative risk across racial groups, and linear modeling was used to measure the dependence of CNI levels and GEP score on race. In 580 patients monitored for a median of 19 months, the incidence of the primary end point was 18.3% in African Americans, 22.2% in other non-Caucasians, and 8.5% in Caucasians (p racial groups. African American recipients demonstrated a unique decrease in expression of the FLT3 gene in response to higher tacrolimus levels. African Americans and other non-Caucasian heart transplant recipients were 2.5-times to 3-times more likely than Caucasians to experience outcome events in the Invasive Monitoring Attenuation through Gene Expression study. The increased risk of adverse outcomes may be partly due to the biology of the alloimmune response, which is less effectively inhibited at similar tacrolimus levels in minority racial groups. Copyright © 2015 International Society for Heart and Lung Transplantation. All rights reserved.

  7. The Role of Metacognitive Reading Strategies, Metacognitive Study and Learning Strategies, and Behavioral Study and Learning Strategies in Predicting Academic Success in Students With and Without a History of Reading Difficulties.

    Science.gov (United States)

    Chevalier, Thérèse M; Parrila, Rauno; Ritchie, Krista C; Deacon, S Hélène

    2017-01-01

    We examined the self-reported use of reading, study, and learning strategies in university students with a history of reading difficulties (HRD; n = 77) and with no history of reading difficulties (NRD; n = 295). We examined both between-groups differences in strategy use and strategy use as a predictive measure of academic success. Participants completed online questionnaires regarding reading history and strategy use. GPA and frequency of use of academic support services were also obtained for all students. University students with HRD reported a different profile of strategy use than their NRD peers, and self-reported strategy use was differentially predictive of GPA for students with HRD and NRD. For students with HRD, the use of metacognitive reading strategies and the use of study aids predicted academic success. Implications for university student services providers are discussed. © Hammill Institute on Disabilities 2015.

  8. A salmonid EST genomic study: genes, duplications, phylogeny and microarrays

    Directory of Open Access Journals (Sweden)

    Brahmbhatt Sonal

    2008-11-01

    Full Text Available Abstract Background Salmonids are of interest because of their relatively recent genome duplication, and their extensive use in wild fisheries and aquaculture. A comprehensive gene list and a comparison of genes in some of the different species provide valuable genomic information for one of the most widely studied groups of fish. Results 298,304 expressed sequence tags (ESTs from Atlantic salmon (69% of the total, 11,664 chinook, 10,813 sockeye, 10,051 brook trout, 10,975 grayling, 8,630 lake whitefish, and 3,624 northern pike ESTs were obtained in this study and have been deposited into the public databases. Contigs were built and putative full-length Atlantic salmon clones have been identified. A database containing ESTs, assemblies, consensus sequences, open reading frames, gene predictions and putative annotation is available. The overall similarity between Atlantic salmon ESTs and those of rainbow trout, chinook, sockeye, brook trout, grayling, lake whitefish, northern pike and rainbow smelt is 93.4, 94.2, 94.6, 94.4, 92.5, 91.7, 89.6, and 86.2% respectively. An analysis of 78 transcript sets show Salmo as a sister group to Oncorhynchus and Salvelinus within Salmoninae, and Thymallinae as a sister group to Salmoninae and Coregoninae within Salmonidae. Extensive gene duplication is consistent with a genome duplication in the common ancestor of salmonids. Using all of the available EST data, a new expanded salmonid cDNA microarray of 32,000 features was created. Cross-species hybridizations to this cDNA microarray indicate that this resource will be useful for studies of all 68 salmonid species. Conclusion An extensive collection and analysis of salmonid RNA putative transcripts indicate that Pacific salmon, Atlantic salmon and charr are 94–96% similar while the more distant whitefish, grayling, pike and smelt are 93, 92, 89 and 86% similar to salmon. The salmonid transcriptome reveals a complex history of gene duplication that is

  9. Elaboration and Organization Strategies Used by Prospective Class Teachers While Studying Social Studies Education Textbooks

    Science.gov (United States)

    Tay, Bayram

    2013-01-01

    Problem Statement: Students spend a considerable amount of their time studying from textbooks, which play an important role in their learning activities. The strategies students use to learn work as guides, requiring them to mentally process, make sense of and internalize information offered to them during the instructional process. Of these,…

  10. A systematic study on drug-response associated genes using baseline gene expressions of the Cancer Cell Line Encyclopedia

    Science.gov (United States)

    Liu, Xiaoming; Yang, Jiasheng; Zhang, Yi; Fang, Yun; Wang, Fayou; Wang, Jun; Zheng, Xiaoqi; Yang, Jialiang

    2016-03-01

    We have studied drug-response associated (DRA) gene expressions by applying a systems biology framework to the Cancer Cell Line Encyclopedia data. More than 4,000 genes are inferred to be DRA for at least one drug, while the number of DRA genes for each drug varies dramatically from almost 0 to 1,226. Functional enrichment analysis shows that the DRA genes are significantly enriched in genes associated with cell cycle and plasma membrane. Moreover, there might be two patterns of DRA genes between genders. There are significantly shared DRA genes between male and female for most drugs, while very little DRA genes tend to be shared between the two genders for a few drugs targeting sex-specific cancers (e.g., PD-0332991 for breast cancer and ovarian cancer). Our analyses also show substantial difference for DRA genes between young and old samples, suggesting the necessity of considering the age effects for personalized medicine in cancers. Lastly, differential module and key driver analyses confirm cell cycle related modules as top differential ones for drug sensitivity. The analyses also reveal the role of TSPO, TP53, and many other immune or cell cycle related genes as important key drivers for DRA network modules. These key drivers provide new drug targets to improve the sensitivity of cancer therapy.

  11. A systematic study on drug-response associated genes using baseline gene expressions of the Cancer Cell Line Encyclopedia.

    Science.gov (United States)

    Liu, Xiaoming; Yang, Jiasheng; Zhang, Yi; Fang, Yun; Wang, Fayou; Wang, Jun; Zheng, Xiaoqi; Yang, Jialiang

    2016-03-10

    We have studied drug-response associated (DRA) gene expressions by applying a systems biology framework to the Cancer Cell Line Encyclopedia data. More than 4,000 genes are inferred to be DRA for at least one drug, while the number of DRA genes for each drug varies dramatically from almost 0 to 1,226. Functional enrichment analysis shows that the DRA genes are significantly enriched in genes associated with cell cycle and plasma membrane. Moreover, there might be two patterns of DRA genes between genders. There are significantly shared DRA genes between male and female for most drugs, while very little DRA genes tend to be shared between the two genders for a few drugs targeting sex-specific cancers (e.g., PD-0332991 for breast cancer and ovarian cancer). Our analyses also show substantial difference for DRA genes between young and old samples, suggesting the necessity of considering the age effects for personalized medicine in cancers. Lastly, differential module and key driver analyses confirm cell cycle related modules as top differential ones for drug sensitivity. The analyses also reveal the role of TSPO, TP53, and many other immune or cell cycle related genes as important key drivers for DRA network modules. These key drivers provide new drug targets to improve the sensitivity of cancer therapy.

  12. Self-assessment and students’ study strategies in a community of clinical practice: A qualitative study

    Science.gov (United States)

    Al-Kadri, Hanan M.; Al-Moamary, Mohamed S.; Al-Takroni, Habib; Roberts, Chris; van der Vleuten, Cees P. M.

    2012-01-01

    Background Self-assessment is recognized as a necessary skill for lifelong learning. It is widely reported to offer numerous advantages to the learner. The research evaluated the impact of students’ and supervisors’ self-assessment and feedback training on students’ perceptions and practices of self-assessment. Moreover, it evaluated the effect of self-assessment process on students’ study strategies within a community of clinical practice. Methods We conducted a qualitative phenomenological study from May 2008 to December 2009. We held 37 semi-structured individual interviews with three different cohorts of undergraduate medical students until we reached data saturation. The cohorts were exposed to different contexts while experiencing their clinical years’ assessment program. In the interviews, students’ perceptions and interpretations of ‘self-assessment practice’ and ‘supervisor-provided feedback’ within different contexts and the resulting study strategies were explored. Results The analysis of interview data with the three cohorts of students yielded three major themes: strategic practice of self-assessment, self-assessment and study strategies, and feedback and study strategies. It appears that self-assessment is not appropriate within a summative context, and its implementation requires cultural preparation. Despite education and orientation on the two major components of the self-assessment process, feedback was more effective in enhancing deeper study strategies. Conclusion This research suggests that the theoretical advantages linked to the self-assessment process are a result of its feedback component rather than the practice of self-assessment isolated from feedback. Further research exploring the effects of different contextual and personal factors on students’ self-assessment is needed. PMID:22355241

  13. Suiformes conservation: a study case of strategies for DNA utilization

    Indian Academy of Sciences (India)

    are more often used to obtain samples like hair, faeces and old museum collections .... agarose gel electrophoresis. Whole genome ... 2001) were used to confirm that the DNA was amplifiable after the extrac- tion (muscular tissue) and WGA and extraction strategy (in the faecal samples) (table 1). To obtain the histone H4 ...

  14. Cybersecurity Strategy in Developing Nations: A Jamaica Case Study

    Science.gov (United States)

    Newmeyer, Kevin Patrick

    2014-01-01

    Developing nations have been slow to develop and implement cybersecurity strategies despite a growing threat to governance and public security arising from an increased dependency on Internet-connected systems in the developing world and rising cybercrime. Using a neorealist theoretical framework that draws from Gilpin and Waltz, this qualitative…

  15. Multi-Stepped Optogenetics: A Novel Strategy to Analyze Neural Network Formation and Animal Behaviors by Photo-Regulation of Local Gene Expression, Fluorescent Color and Neural Excitation

    Science.gov (United States)

    Hatta, Kohei; Nakajima, Yohei; Isoda, Erika; Itoh, Mariko; Yamamoto, Tamami

    The brain is one of the most complicated structures in nature. Zebrafish is a useful model to study development of vertebrate brain, because it is transparent at early embryonic stage and it develops rapidly outside of the body. We made a series of transgenic zebrafish expressing green-fluorescent protein related molecules, for example, Kaede and KikGR, whose green fluorescence can be irreversibly converted to red upon irradiation with ultra-violet (UV) or violet light, and Dronpa, whose green fluorescence is eliminated with strong blue light but can be reactivated upon irradiation with UV or violet-light. We have recently shown that infrared laser evoked gene operator (IR-LEGO) which causes a focused heat shock could locally induce these fluorescent proteins and the other genes. Neural cell migration and axonal pattern formation in living brain could be visualized by this technique. We also can express channel rhodopsine 2 (ChR2), a photoactivatable cation channel, or Natronomonas pharaonis halorhodopsin (NpHR), a photoactivatable chloride ion pump, locally in the nervous system by IR. Then, behaviors of these animals can be controlled by activating or silencing the local neurons by light. This novel strategy is useful in discovering neurons and circuits responsible for a wide variety of animal behaviors. We proposed to call this method ‘multi-stepped optogenetics’.

  16. EFL Teachers' Perceptions of Strategy Deficiency Syndrome: A Grounded Theory Study

    Science.gov (United States)

    Ostovar-Namaghi, Seyyed Ali; Ahmadabadi-Tak, Bahareh

    2017-01-01

    Strategy-deficient language learners struggle to develop their language proficiency through limiting and inappropriate strategies. This study aims at exploring experienced teachers' perceptions of strategy deficiency syndrome among EFL learners. To this end, the perspectives of a purposive sample of experienced teachers teaching in private…

  17. The Relationship between Reading Proficiency and Reading Strategy Use: A Study of Adult ESL Learners

    Science.gov (United States)

    Huang, Jiuhan; Nisbet, Deanna

    2014-01-01

    This article explores the relationship between reading strategy use and reading proficiency among 121 adult ESL learners. Reading strategy use was measured by the SORS, and reading proficiency was determined by the CASAS Reading Test and BEST Literacy Test. Findings of the study reveal that (a) adult ESL learners are active strategies users; (b)…

  18. Multifunctionalized polyethyleneimine-based nanocarriers for gene and chemotherapeutic drug combination therapy through one-step assembly strategy

    Directory of Open Access Journals (Sweden)

    Jiang D

    2017-12-01

    Dox group (P<0.05 and the murine PCT group (P<0.05. These results indicated that the TRAIL + Dox synergistic antitumor effect could be achieved by PDT, which paves the way to gene–drug combination therapy for cancer. Keywords: multifunctional, gene therapy, chemotherapy, TRAIL, one-step assembly strategy, CAIR theory

  19. Selection of reference genes for gene expression studies in pig tissues using SYBR green qPCR

    DEFF Research Database (Denmark)

    Hillig, Ann-Britt Nygaard; Jørgensen, Claus Bøttcher; Cirera, Susanna

    2007-01-01

    Background: Real-time quantitative PCR (qPCR) is a method for rapid and reliable quantification of mRNA transcription. Internal standards such as reference genes are used to normalise mRNA levels between different samples for an exact comparison of mRNA transcription level. Selection of high...... quality reference genes is of crucial importance for the interpretation of data generated by real-time qPCR. Results: In this study nine commonly used reference genes were investigated in 17 different pig tissues using real-time qPCR with SYBR green. The genes included beta-actin (ACTB), beta-2...

  20. Identification of valid reference genes for gene expression studies of human stomach cancer by reverse transcription-qPCR

    International Nuclear Information System (INIS)

    Rho, Hyun-Wook; Lee, Byoung-Chan; Choi, Eun-Seok; Choi, Il-Ju; Lee, Yeon-Su; Goh, Sung-Ho

    2010-01-01

    Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) is a powerful method for the analysis of gene expression. Target gene expression levels are usually normalized to a consistently expressed reference gene also known as internal standard, in the same sample. However, much effort has not been expended thus far in the search for reference genes suitable for the study of stomach cancer using RT-qPCR, although selection of optimal reference genes is critical for interpretation of results. We assessed the suitability of six possible reference genes, beta-actin (ACTB), glyceraldehydes-3-phosphate dehydrogenase (GAPDH), hypoxanthine phosphoribosyl transferase 1 (HPRT1), beta-2-microglobulin (B2M), ribosomal subunit L29 (RPL29) and 18S ribosomal RNA (18S rRNA) in 20 normal and tumor stomach tissue pairs of stomach cancer patients and 6 stomach cancer cell lines, by RT-qPCR. Employing expression stability analyses using NormFinder and geNorm algorithms we determined the order of performance of these reference genes and their variation values. This RT-qPCR study showed that there are statistically significant (p < 0.05) differences in the expression levels of HPRT1 and 18S rRNA in 'normal-' versus 'tumor stomach tissues'. The stability analyses by geNorm suggest B2M-GAPDH, as best reference gene combination for 'stomach cancer cell lines'; RPL29-HPRT1, for 'all stomach tissues'; and ACTB-18S rRNA, for 'all stomach cell lines and tissues'. NormFinder also identified B2M as the best reference gene for 'stomach cancer cell lines', RPL29-B2M for 'all stomach tissues', and 18S rRNA-ACTB for 'all stomach cell lines and tissues'. The comparisons of normalized expression of the target gene, GPNMB, showed different interpretation of target gene expression depend on best single reference gene or combination. This study validated RPL29 and RPL29-B2M as the best single reference

  1. DNA microarray-based experimental strategy for trustworthy expression profiling of the hippocampal genes by astaxanthin supplementation in adult mouse.

    Science.gov (United States)

    Yook, Jang Soo; Shibato, Junko; Rakwal, Randeep; Soya, Hideaki

    2016-03-01

    Naturally occurring astaxantin (ASX) is one of the noticeable carotenoid and dietary supplement, which has strong antioxidant and anti-inflammatory properties, and neuroprotective effects in the brain through crossing the blood-brain barrier. Specially, we are interested in the role of ASX as a brain food. Although ASX has been suggested to have potential benefit to the brain function, the underlying molecular mechanisms and events mediating such effect remain unknown. Here we examined molecular factors in the hippocampus of adult mouse fed ASX diets (0.1% and 0.5% doses) using DNA microarray (Agilent 4 × 44 K whole mouse genome chip) analysis. In this study, we described in detail our experimental workflow and protocol, and validated quality controls with the housekeeping gene expression (Gapdh and Beta-actin) on the dye-swap based approach to advocate our microarray data, which have been uploaded to Gene Expression Omnibus (accession number GSE62197) as a gene resource for the scientific community. This data will also form an important basis for further detailed experiments and bioinformatics analysis with an aim to unravel the potential molecular pathways or mechanisms underlying the positive effects of ASX supplementation on the brain, in particular the hippocampus.

  2. DNA microarray-based experimental strategy for trustworthy expression profiling of the hippocampal genes by astaxanthin supplementation in adult mouse

    Directory of Open Access Journals (Sweden)

    Jang Soo Yook

    2016-03-01

    Full Text Available Naturally occurring astaxantin (ASX is one of the noticeable carotenoid and dietary supplement, which has strong antioxidant and anti-inflammatory properties, and neuroprotective effects in the brain through crossing the blood–brain barrier. Specially, we are interested in the role of ASX as a brain food. Although ASX has been suggested to have potential benefit to the brain function, the underlying molecular mechanisms and events mediating such effect remain unknown. Here we examined molecular factors in the hippocampus of adult mouse fed ASX diets (0.1% and 0.5% doses using DNA microarray (Agilent 4 × 44 K whole mouse genome chip analysis. In this study, we described in detail our experimental workflow and protocol, and validated quality controls with the housekeeping gene expression (Gapdh and Beta-actin on the dye-swap based approach to advocate our microarray data, which have been uploaded to Gene Expression Omnibus (accession number GSE62197 as a gene resource for the scientific community. This data will also form an important basis for further detailed experiments and bioinformatics analysis with an aim to unravel the potential molecular pathways or mechanisms underlying the positive effects of ASX supplementation on the brain, in particular the hippocampus.

  3. Gene and DNA concepts by UNIFAL-MG entering students and the effectiveness of drama as a Molecular Biology teaching strategy

    Directory of Open Access Journals (Sweden)

    Marina Isidoro Silva

    2014-10-01

    Full Text Available The Molecular Biology concepts comprehension is important for understanding several Biological processes as well as to establish correlations and interrelations among cell processes and its interaction with the environment. The aim of this work was to evaluate the undergraduate students from the Universidade Federal de Alfenas-MG (UNIFAL-MG knowledge about gene and DNA concepts as well as to evaluate the effectiveness of drama as an innovative teaching strategy. This strategy was evaluated by the students` knowledge gain and scholar performance. The results showed the UNIFAL-MG beginners’ students presented defective concepts about gene and DNA composition and structure, probably due to deficient teaching-learning process before the University entrance. Drama was an efficient strategy to induce learning gain and to improve scholar performance of classes with a good initial level of knowledge.

  4. Evaluation of endogenous control gene(s) for gene expression studies in human blood exposed to 60Co γ-rays ex vivo

    International Nuclear Information System (INIS)

    Vaiphei, S. Thangminlal; Keppen, Joshua; Nongrum, Saibadaiahun; Sharan, R.N.; Chaubey, R.C.; Kma, L.

    2015-01-01

    In gene expression studies, it is critical to normalize data using a stably expressed endogenous control gene in order to obtain accurate and reliable results. However, we currently do not have a universally applied endogenous control gene for normalization of data for gene expression studies, particularly those involving 60 Co γ-ray-exposed human blood samples. In this study, a comparative assessment of the gene expression of six widely used housekeeping endogenous control genes, namely 18S, ACTB, B2M, GAPDH, MT-ATP6 and CDKN1A, was undertaken for a range of 60 Co γ-ray doses (0.5, 1.0, 2.0 and 4.0 Gy) at 8.4 Gy min -1 at 0 and 24 h post-irradiation time intervals. Using the NormFinder algorithm, real-time PCR data obtained from six individuals (three males and three females) were analyzed with respect to the threshold cycle (Ct) value and abundance, ΔCt pair-wise comparison, intra- and inter-group variability assessments, etc. GAPDH, either alone or in combination with 18S, was found to be the most suitable endogenous control gene and should be used in gene expression studies, especially those involving qPCR of γ-ray-exposed human blood samples. (author)

  5. Evaluation of endogenous control gene(s) for gene expression studies in human blood exposed to 60Co γ-rays ex vivo.

    Science.gov (United States)

    Vaiphei, S Thangminlal; Keppen, Joshua; Nongrum, Saibadaiahun; Chaubey, R C; Kma, L; Sharan, R N

    2015-01-01

    In gene expression studies, it is critical to normalize data using a stably expressed endogenous control gene in order to obtain accurate and reliable results. However, we currently do not have a universally applied endogenous control gene for normalization of data for gene expression studies, particularly those involving (60)Co γ-ray-exposed human blood samples. In this study, a comparative assessment of the gene expression of six widely used housekeeping endogenous control genes, namely 18S, ACTB, B2M, GAPDH, MT-ATP6 and CDKN1A, was undertaken for a range of (60)Co γ-ray doses (0.5, 1.0, 2.0 and 4.0 Gy) at 8.4 Gy min(-1) at 0 and 24 h post-irradiation time intervals. Using the NormFinder algorithm, real-time PCR data obtained from six individuals (three males and three females) were analyzed with respect to the threshold cycle (Ct) value and abundance, ΔCt pair-wise comparison, intra- and inter-group variability assessments, etc. GAPDH, either alone or in combination with 18S, was found to be the most suitable endogenous control gene and should be used in gene expression studies, especially those involving qPCR of γ-ray-exposed human blood samples. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  6. A case study on primary school students' perceptions about their use of language learning and reading strategies and strategy training

    OpenAIRE

    Wilkes, Jane Crawford

    2011-01-01

    Ankara : The Program of Curriculum and Instruction, Bilkent University, 2011. Thesis (Master's) -- Bilkent University, 2011. Includes bibliographical references leaves 59-60. This study looks at the language learning and reading comprehension strategies of students in 3rd – 8 th grades. The study takes place at Bilkent Laboratory and International School, which is a bilingual school in Ankara, Turkey that combines curricula from the Primary Years Program (PYP), Intern...

  7. Assessment of learning and study strategies of university students in Qatar using an Arabic translation of the Learning and Study Strategies Inventory.

    Science.gov (United States)

    Alkhateeb, Haitham M; Nasser, Ramzi

    2014-06-01

    413 (119 men, 294 women) undergraduate university students in Qatar completed an Arabic version of the Learning and Study Strategies Inventory (LASSI) measuring Anxiety, Attitude, Concentration, Information Processing, Motivation, Self-testing, Selecting Main Ideas, Study Aids, Time Management, and Test Strategies. The students' learning and study strategies scores were similar to those reported in the literature. Factor analysis indicated the same general factors as in the original study. Internal consistency estimates ranged from .62 to .88. Nine of the 10 scales (i.e., all with the exception of the Study Aids) significantly correlated with students' GPAs. Scores obtained from these scales provide valid assessments of Qatar University students' use of learning and study strategies related to skill, will, and self-regulation components of strategic learning and also academic achievement. There also were statistically significant differences between higher and lower achieving students in their learning and study strategies. This study also explored the use of the LASSI as a predictive measure of academic achievement. Anxiety and test strategies were significant predictors of academic achievement as measured by students' GPA.

  8. Case Study: SEO Strategy and Implementation for Industrial Pump Company

    OpenAIRE

    Kivistö, Miika

    2016-01-01

    The goal of this Master Thesis was to define the search engine visibility requirements for an industrial pump company in Finland, create a search engine optimization strategy and implement changes to the company´s website and analyse their effect. The company´s website was transferred from Wordpress to the Joomla! content management system. Google Webmaster Tools and Tag Manager collected the data. Keyword research, Technical optimization, Semantic content optimization (On-page optimizat...

  9. Identification of valid reference genes for gene expression studies of human stomach cancer by reverse transcription-qPCR

    Directory of Open Access Journals (Sweden)

    Lee Yeon-Su

    2010-05-01

    Full Text Available Abstract Background Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR is a powerful method for the analysis of gene expression. Target gene expression levels are usually normalized to a consistently expressed reference gene also known as internal standard, in the same sample. However, much effort has not been expended thus far in the search for reference genes suitable for the study of stomach cancer using RT-qPCR, although selection of optimal reference genes is critical for interpretation of results. Methods We assessed the suitability of six possible reference genes, beta-actin (ACTB, glyceraldehydes-3-phosphate dehydrogenase (GAPDH, hypoxanthine phosphoribosyl transferase 1 (HPRT1, beta-2-microglobulin (B2M, ribosomal subunit L29 (RPL29 and 18S ribosomal RNA (18S rRNA in 20 normal and tumor stomach tissue pairs of stomach cancer patients and 6 stomach cancer cell lines, by RT-qPCR. Employing expression stability analyses using NormFinder and geNorm algorithms we determined the order of performance of these reference genes and their variation values. Results This RT-qPCR study showed that there are statistically significant (p Conclusion This study validated RPL29 and RPL29-B2M as the best single reference genes and combination, for RT-qPCR analysis of 'all stomach tissues', and B2M and B2M-GAPDH as the best single reference gene and combination, for 'stomach cancer cell lines'. Use of these validated reference genes should provide more exact interpretation of differential gene expressions at transcription level in stomach cancer.

  10. Direct introduction of gene constructs into the pronucleus-like structure of cloned embryos: a new strategy for the generation of genetically modified pigs.

    Science.gov (United States)

    Kurome, Mayuko; Leuchs, Simon; Kessler, Barbara; Kemter, Elisabeth; Jemiller, Eva-Maria; Foerster, Beatrix; Klymiuk, Nikolai; Zakhartchenko, Valeri; Wolf, Eckhard

    2017-04-01

    Due to a rising demand of porcine models with complex genetic modifications for biomedical research, the approaches for their generation need to be adapted. In this study we describe the direct introduction of a gene construct into the pronucleus (PN)-like structure of cloned embryos as a novel strategy for the generation of genetically modified pigs, termed "nuclear injection". To evaluate the reliability of this new strategy, the developmental ability of embryos in vitro and in vivo as well as the integration and expression efficiency of a transgene carrying green fluorescence protein (GFP) were examined. Eighty percent of the cloned pig embryos (633/787) exhibited a PN-like structure, which met the prerequisite to technically perform the new method. GFP fluorescence was observed in about half of the total blastocysts (21/40, 52.5%), which was comparable to classical zygote PN injection (28/41, 68.3%). In total, 478 cloned embryos injected with the GFP construct were transferred into 4 recipients and from one recipient 4 fetuses (day 68) were collected. In one of the fetuses which showed normal development, the integration of the transgene was confirmed by PCR in different tissues and organs from all three primary germ layers and placenta. The integration pattern of the transgene was mosaic (48 out of 84 single-cell colonies established from a kidney were positive for GFP DNA by PCR). Direct GFP fluorescence was observed macro- and microscopically in the fetus. Our novel strategy could be useful particularly for the generation of pigs with complex genetic modifications.

  11. An Improved Single-Step Cloning Strategy Simplifies the Agrobacterium tumefaciens-Mediated Transformation (ATMT)-Based Gene-Disruption Method for Verticillium dahliae.

    Science.gov (United States)

    Wang, Sheng; Xing, Haiying; Hua, Chenlei; Guo, Hui-Shan; Zhang, Jie

    2016-06-01

    The soilborne fungal pathogen Verticillium dahliae infects a broad range of plant species to cause severe diseases. The availability of Verticillium genome sequences has provided opportunities for large-scale investigations of individual gene function in Verticillium strains using Agrobacterium tumefaciens-mediated transformation (ATMT)-based gene-disruption strategies. Traditional ATMT vectors require multiple cloning steps and elaborate characterization procedures to achieve successful gene replacement; thus, these vectors are not suitable for high-throughput ATMT-based gene deletion. Several advancements have been made that either involve simplification of the steps required for gene-deletion vector construction or increase the efficiency of the technique for rapid recombinant characterization. However, an ATMT binary vector that is both simple and efficient is still lacking. Here, we generated a USER-ATMT dual-selection (DS) binary vector, which combines both the advantages of the USER single-step cloning technique and the efficiency of the herpes simplex virus thymidine kinase negative-selection marker. Highly efficient deletion of three different genes in V. dahliae using the USER-ATMT-DS vector enabled verification that this newly-generated vector not only facilitates the cloning process but also simplifies the subsequent identification of fungal homologous recombinants. The results suggest that the USER-ATMT-DS vector is applicable for efficient gene deletion and suitable for large-scale gene deletion in V. dahliae.

  12. Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study

    Directory of Open Access Journals (Sweden)

    Cribbs David H

    2012-07-01

    Full Text Available Abstract Background This study undertakes a systematic and comprehensive analysis of brain gene expression profiles of immune/inflammation-related genes in aging and Alzheimer’s disease (AD. Methods In a well-powered microarray study of young (20 to 59 years, aged (60 to 99 years, and AD (74 to 95 years cases, gene responses were assessed in the hippocampus, entorhinal cortex, superior frontal gyrus, and post-central gyrus. Results Several novel concepts emerge. First, immune/inflammation-related genes showed major changes in gene expression over the course of cognitively normal aging, with the extent of gene response far greater in aging than in AD. Of the 759 immune-related probesets interrogated on the microarray, approximately 40% were significantly altered in the SFG, PCG and HC with increasing age, with the majority upregulated (64 to 86%. In contrast, far fewer immune/inflammation genes were significantly changed in the transition to AD (approximately 6% of immune-related probesets, with gene responses primarily restricted to the SFG and HC. Second, relatively few significant changes in immune/inflammation genes were detected in the EC either in aging or AD, although many genes in the EC showed similar trends in responses as in the other brain regions. Third, immune/inflammation genes undergo gender-specific patterns of response in aging and AD, with the most pronounced differences emerging in aging. Finally, there was widespread upregulation of genes reflecting activation of microglia and perivascular macrophages in the aging brain, coupled with a downregulation of select factors (TOLLIP, fractalkine that when present curtail microglial/macrophage activation. Notably, essentially all pathways of the innate immune system were upregulated in aging, including numerous complement components, genes involved in toll-like receptor signaling and inflammasome signaling, as well as genes coding for immunoglobulin (Fc receptors and human

  13. Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study

    Science.gov (United States)

    2012-01-01

    Background This study undertakes a systematic and comprehensive analysis of brain gene expression profiles of immune/inflammation-related genes in aging and Alzheimer’s disease (AD). Methods In a well-powered microarray study of young (20 to 59 years), aged (60 to 99 years), and AD (74 to 95 years) cases, gene responses were assessed in the hippocampus, entorhinal cortex, superior frontal gyrus, and post-central gyrus. Results Several novel concepts emerge. First, immune/inflammation-related genes showed major changes in gene expression over the course of cognitively normal aging, with the extent of gene response far greater in aging than in AD. Of the 759 immune-related probesets interrogated on the microarray, approximately 40% were significantly altered in the SFG, PCG and HC with increasing age, with the majority upregulated (64 to 86%). In contrast, far fewer immune/inflammation genes were significantly changed in the transition to AD (approximately 6% of immune-related probesets), with gene responses primarily restricted to the SFG and HC. Second, relatively few significant changes in immune/inflammation genes were detected in the EC either in aging or AD, although many genes in the EC showed similar trends in responses as in the other brain regions. Third, immune/inflammation genes undergo gender-specific patterns of response in aging and AD, with the most pronounced differences emerging in aging. Finally, there was widespread upregulation of genes reflecting activation of microglia and perivascular macrophages in the aging brain, coupled with a downregulation of select factors (TOLLIP, fractalkine) that when present curtail microglial/macrophage activation. Notably, essentially all pathways of the innate immune system were upregulated in aging, including numerous complement components, genes involved in toll-like receptor signaling and inflammasome signaling, as well as genes coding for immunoglobulin (Fc) receptors and human leukocyte antigens I

  14. A comparative study of ATPase subunit 9 (Atp9) gene between ...

    African Journals Online (AJOL)

    ATPase subunit 9 gene (Atp9) is an important functional gene in mitochondria, and is closely related with energy supply. RNA editing of atp9 gene was associated with male sterility in plants. In this study, the atp9 gene in soybeans was cloned from a soybean cytoplasmic male sterile line NJCMS2A and its maintainer line ...

  15. Behavioral science and the study of gene-nutrition and gene-physical activity interactions in obesity research.

    Science.gov (United States)

    Faith, Myles S

    2008-12-01

    This report summarizes emerging opportunities for behavioral science to help advance the field of gene-environment and gene-behavior interactions, based on presentations at The National Cancer Institute (NCI) Workshop, "Gene-Nutrition and Gene-Physical Activity Interactions in the Etiology of Obesity." Three opportunities are highlighted: (i) designing potent behavioral "challenges" in experiments, (ii) determining viable behavioral phenotypes for genetics studies, and (iii) identifying specific measures of the environment or environmental exposures. Additional points are underscored, including the need to incorporate novel findings from neuroimaging studies regarding motivation and drive for eating and physical activity. Advances in behavioral science theory and methods can play an important role in advancing understanding of gene-brain-behavior relationships in obesity onset.

  16. Investigating Self-Regulated Study Strategies among Postsecondary Students with and without Dyslexia: A Diary Method Study

    Science.gov (United States)

    Andreassen, Rune; Jensen, Magne S.; Bråten, Ivar

    2017-01-01

    We investigated the use of self-regulated study strategies among undergraduates with dyslexia by means of extensive web-based diary data, comparing their strategy use to that of matched students without dyslexia who completed the diary in the same period. Additionally, we examined the perceived benefits of using the recorded strategies in both…

  17. A comprehensive family-based replication study of schizophrenia genes

    DEFF Research Database (Denmark)

    Aberg, Karolina A; Liu, Youfang; Bukszár, Jozsef

    2013-01-01

    (P = 9.01 × 10-7), CNNM2 (P = 6.07 × 10-7), and NT5C2 (P = 4.09 × 10-7). To explore the many small effects, we performed pathway analyses. The most significant pathways involved neuronal function (axonal guidance, neuronal systems, and L1 cell adhesion molecule interaction) and the immune system...... genes. DESIGN We integrated results from a meta-analysis of 18 genome-wide association studies (GWAS) involving 1 085 772 single-nucleotide polymorphisms (SNPs) and 6 databases that showed significant informativeness for SCZ. The 9380 most promising SNPs were then specifically genotyped...... in an independent family-based replication study that, after quality control, consisted of 8107 SNPs. SETTING Linkage meta-analysis, brain transcriptome meta-analysis, candidate gene database, OMIM, relevant mouse studies, and expression quantitative trait locus databases. PATIENTS We included 11 185 cases and 10...

  18. Customer driven marketing strategy of LIC international in Bahrain: a product specific study

    OpenAIRE

    Pillai, Rajasekharan; Rao, M S; Thampy, Jaik; Peter, Jerrin

    2011-01-01

    Abstract Marketing of service product requires a slightly different strategy owing to the idiosyncratic nature of service items. The present study explores the customer oriented marketing strategy of LIC International in the Kingdom of Bahrain. The approach of the study was exploratory and personal interview was conducted to contribute major input source to the research. The company has been following a different marketing strategy in the study area different from the conventional approach...

  19. A Growth Curve Model with Fractional Polynomials for Analysing Incomplete Time-Course Data in Microarray Gene Expression Studies

    Science.gov (United States)

    Tan, Qihua; Thomassen, Mads; Hjelmborg, Jacob v. B.; Clemmensen, Anders; Andersen, Klaus Ejner; Petersen, Thomas K.; McGue, Matthew; Christensen, Kaare; Kruse, Torben A.

    2011-01-01

    Identifying the various gene expression response patterns is a challenging issue in expression microarray time-course experiments. Due to heterogeneity in the regulatory reaction among thousands of genes tested, it is impossible to manually characterize a parametric form for each of the time-course pattern in a gene by gene manner. We introduce a growth curve model with fractional polynomials to automatically capture the various time-dependent expression patterns and meanwhile efficiently handle missing values due to incomplete observations. For each gene, our procedure compares the performances among fractional polynomial models with power terms from a set of fixed values that offer a wide range of curve shapes and suggests a best fitting model. After a limited simulation study, the model has been applied to our human in vivo irritated epidermis data with missing observations to investigate time-dependent transcriptional responses to a chemical irritant. Our method was able to identify the various nonlinear time-course expression trajectories. The integration of growth curves with fractional polynomials provides a flexible way to model different time-course patterns together with model selection and significant gene identification strategies that can be applied in microarray-based time-course gene expression experiments with missing observations. PMID:21966290

  20. Strategy; Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2005-07-15

    Francois Loos, Minister of Industry, explains the French energy policy in the frame of Europe. ONERC is a French public body in charge of defining a national strategy against climate changes. It submits its first strategic elements to the Government. (authors)

  1. Metacognitive Language Learning Strategies Use, Gender, and Learning Achievement: a Correlation Study

    Directory of Open Access Journals (Sweden)

    Ahlam Bouirane

    2015-06-01

    Full Text Available This study investigates the relationship between metacognitive language learning strategies (MLLS and gender and achievement of EFL students. Metacognitive language learning strategies are crucial for students of English as a foreign language to learn effectively. The theoretical issues discuss metacognitive language learning strategies in particular, and language learning strategies (LLS in general. The practical research took place at the English language department at Farhat Abbes University, Sétif, Algeria, with third year students learning English as a foreign language. The study hypothesized that there is a positive correlation between metacognitive language learning strategies use and achievement. Two main parts following a qualitative design constitute the body of the present research. The first part uses the Metacognitive Language Learning Strategies Questionnaire (MLLSQ to account for differences in the reported frequency of metacognitive strategies use across all the students, and across gender differences. The second part uses interviews to account for the use of these strategies at the individual level, in their relation to the students’ gender and achievement in language learning. The results of the first part revealed a significant use of metacognitive strategies among all the students and significant differences between male students and female students in the frequency of use of these strategies. Moreover, the results of the second part reflected more significant differences in the use of Metacognitive strategies at the level of gender and learning achievement. The study concludes by bringing together key findings and some suggestions for further research.

  2. Towards a rAAV-based gene therapy for ADA-SCID: from ADA deficiency to current and future treatment strategies.

    Science.gov (United States)

    Silver, Jared N; Flotte, Terence R

    2008-07-01

    Adenosine deaminase deficiency fosters a rare, devastating pediatric immune deficiency with concomitant opportunistic infections, metabolic anomalies and multiple organ system pathology. The standard of care for adenosine deaminase deficient severe combined immune deficiency (ADA-SCID) includes enzyme replacement therapy or bone marrow transplantation. Gene therapies for ADA-SCID over nearly two decades have exclusively involved retroviral vectors targeted to lymphocytes and hematopoetic progenitors. These groundbreaking gene therapies represent a revolution in clinical medicine, but come with several challenges, including the risk of insertional mutagenesis. An alternative gene therapy for ADA-SCID may utilize recombinant adeno-associated virus vectors in vivo, with numerous target tissues, to foster ectopic expression and secretion of adenosine deaminase. This review endeavors to describe ADA-SCID, the traditional treatments, previous retroviral gene therapies, and primarily, alternative recombinant adeno-associated virus-based strategies to remedy this potentially fatal genetic disease.

  3. An intron capture strategy used to identify and map a lysyl oxidase-like gene on chromosome 9 in the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Wydner, K.S.; Passmore, H.C. [Rutgers Univ., Piscataway, NJ (United States); Kim, Houngho; Csiszar, K.; Boyd, C.D. [UMDNJ, New Brunswick, NJ (United States)

    1997-03-01

    An intron capture strategy involving use of polymerase chain reaction was used to identify and map the mouse homologue of a human lysyl oxidase-like gene (LOXL). Oligonucleotides complementary to conserved domains within exons 4 and 5 of the human lysyl oxidase-like gene were used to amplify the corresponding segment from mouse genomic DNA. Sequencing of the resulting mouse DNA fragment of approximately 1 kb revealed that the exon sequences at the ends of the amplified fragment are highly homologous (90% nucleotide identity) to exons 4 and 5 of the human lysyl oxidase-like gene. An AluI restriction site polymorphism within intron 4 was used to map the mouse lysyl oxidase-like gene (Loxl) to mouse Chromosome 9 in a region that shares linkage conservation with human chromosome 15q24, to which the LOXL was recently mapped. 22 refs., 3 figs.

  4. Kajian Strategi Pengamanan Infrastruktur Sumber Daya Informasi Kritis [Study of Critical Information Resources Infrastructure Security Strategy

    Directory of Open Access Journals (Sweden)

    Ahmad Budi Setiawan

    2015-06-01

    Full Text Available Infrastruktur informasi kritis merupakan salah satu infrastruktur kritis yang menggabungkan antara infrastruktur telekomunikasi serta jaringan internet yang digunakan dalam pelayanan publik. Dengan demikian, infrastruktur informasi kritis  harus beroperasi dengan aman dan memenuhi aspek keamanan informasi. Kajian ini adalah studi kasus pada infrastruktur informasi kritis sebagai salah satu infrastruktur kritis Nasional yang digunakan dalam pelayanan publik. Adapun infrastruktur informasi kritis yang dijadikan studi kasus adalah pada bidang energi ketenagalistrikan. Tujuan kajian ini adalah memberikan masukan pada kebijakan pengamanan infrastruktur kritis berdasarkan studi kasus yang dilakukan. Kajian ini dilakukan dengan metode gabungan kuantitatif dan kualitatif yang mengkombinasikan hasil penilaian risiko pada obyek riset dengan pendapat pengambil kebijakan, akademisi, pakar dan praktisi. Hasil kajian ini adalah masukan untuk kebijakan dan kerangka kerja pengamanan infrastruktur kritis khususnya sector TIK. *****Critical information infrastructure is one of the critical infrastructure that combines telecommunications infrastructure and Internet networks used in the public service. Thus, the critical information infrastructure must operate safely and meet the aspects of information security. This study is a case study on critical information infrastructure as one of the critical national infrastructure used in public service. The critical information infrastructure which is used as a case study is in the field of electricity energy. The purpose of this sudy is to provide input on critical infrastructure security policy based on case studies conducted. This study was conducted with the combined quantitative and qualitative method that combines the results of the risk assessment on the research object with the opinion of policy makers, academics, experts and practitioners. These results are input to the policy framework and securing critical

  5. Selection of housekeeping genes for gene expression studies in a rat model of irinotecan-induced mucositis.

    Science.gov (United States)

    Al-Dasooqi, Noor; Bowen, Joanne M; Gibson, Rachel J; Logan, Richard M; Stringer, Andrea M; Keefe, Dorothy M

    2011-01-01

    Mucositis is the term used to describe damage caused by chemotherapy to mucous membranes of the alimentary tract. RT-PCR has recently been utilised to determine the molecular events that occur in mucositis. As this method relies on the use of a validated endogenous control, this study aims to validate commonly used housekeeping genes in an irinotecan-induced mucositis model. Rats were administered irinotecan and sacrificed at different time points, in particular 1, 24, 72 and 144 h following treatment. Histopathological damage was assessed by haematoxylin and eosin staining. RT-PCR was used to evaluate the expression of 11 housekeeping genes. Expression stability was determined by the Normfinder program. Matrix metalloproteinase 2 was used as a target gene to validate the appropriateness of the top-ranking housekeeping gene. For normalisation to multiple housekeeping genes, the most stable combination across all time points in the jejunum was Ywhaz/UBC and in the colon UBC/β-actin. SDHA and GAPDH were the most variable genes in the jejunum and colon where they were 4.4 and 3.2 fold upregulated following irinotecan, respectively. For normalisation of irinotecan-induced mucositis gene expression studies, a combination of Ywhaz/UBC and UBC/β-actin should be used in the jejunum and colon, respectively. UBC is the most favourable if restricted to a single housekeeping gene across all time points. Copyright © 2011 S. Karger AG, Basel.

  6. Study on status quo of shipbreaking sector and strategies

    Science.gov (United States)

    Shen, Wei; Xing, Guojing

    2017-11-01

    In recent years, the quantity of broken obsolete vessels tends to rise year by year in the shipbreaking sector, but breaking down obsolete vessels is one of vessel operations with high pollution and high risk, involving proper disposal of hazardous substances, bulge discarded oils and other materials, and thus causing great danger and harm. In this paper the author investigates mainly the status quo of the shipbreaking sector, comes up with the “green-shipbreaking” concept, analyzes main problems currently present in the shipbreaking sector and presents proper strategies and recommendations to deal with them.

  7. A comparative study of mutation screening of sarcomeric genes ...

    African Journals Online (AJOL)

    , TNNT2) using single gene approach versus targeted gene panel next generation sequencing in a cohort of HCM patients in Egypt. Heba Sh. Kassem, Roddy Walsh, Paul J. Barton, Besra S. Abdelghany, Remon S. Azer, Rachel Buchan, ...

  8. Validation of housekeeping genes for the normalization of RT-qPCR expression studies in oral squamous cell carcinoma cell line treated by 5 kinds of chemotherapy drugs.

    Science.gov (United States)

    Song, W; Zhang, W H; Zhang, H; Li, Y; Zhang, Y; Yin, W; Yang, Q

    2016-11-30

    Reverse transcription quantitative polymerase chain reaction (RT-qPCR) has become a frequently used strategy in gene expression studies. The relative quantification method is an important and commonly used method for the evaluation of RT-qPCR data. The key of this method is to identify an applicable internal control gene because the usage of different internal control genes may lead to distinct conclusions. Herein, we report the validation of 12 common housekeeping genes for RT-qPCR for gene expression analysis in the Oral squamous cell carcinoma (OSCC) cell line (KB and Tca-8113) treated by 5 kinds of Chemotherapy Drugs. The gene expression stability and applicability of the 12 housekeeping gene candidates were determined using the geNorm, NormFinder, and BestKeeper software programs. Comprehensive analyzing the results of the three software, ALAS1/GAPDH, ALAS1 and GUSB were suggested to be the most stable candidate genes for the study of both KB and Tca-8113 cell line together, KB cell line, and Tca-8113 cell line, respectively. This study provides useful information to normalize gene expression accurately for the investigation of target gene profiling in cell lines of OSCC. Further clarification of tumor molecular expression markers with our recommended housekeeping genes may improve the accuracy of diagnosis and estimation of prognostic factors as well as provide novel personalized treatments for OSCC patients.

  9. Gene cuisine or Frankenfood? The theory of reasoned action as an audience segmentation strategy for messages about genetically modified foods.

    Science.gov (United States)

    Silk, Kami J; Weiner, Judith; Parrott, Roxanne L

    2005-12-01

    Genetically modified (GM) foods are currently a controversial topic about which the lay public in the United States knows little. Formative research has demonstrated that the lay public is uncertain and concerned about GM foods. This study (N = 858) extends focus group research by using the Theory of Reasoned Action (TRA) to examine attitudes and subjective norms related to GM foods as a theoretical strategy for audience segmentation. A hierarchical cluster analysis revealed four unique audiences based on their attitude and subjective norm toward GM foods (ambivalent-biotech, antibiotech, biotech-normer, and biotech individual). Results are discussed in terms of the theoretical and practical significance for audience segmentation.

  10. An event-driven approach for studying gene block evolution in bacteria.

    Science.gov (United States)

    Ream, David C; Bankapur, Asma R; Friedberg, Iddo

    2015-07-01

    Gene blocks are genes co-located on the chromosome. In many cases, gene blocks are conserved between bacterial species, sometimes as operons, when genes are co-transcribed. The conservation is rarely absolute: gene loss, gain, duplication, block splitting and block fusion are frequently observed. An open question in bacterial molecular evolution is that of the formation and breakup of gene blocks, for which several models have been proposed. These models, however, are not generally applicable to all types of gene blocks, and consequently cannot be used to broadly compare and study gene block evolution. To address this problem, we introduce an event-based method for tracking gene block evolution in bacteria. We show here that the evolution of gene blocks in proteobacteria can be described by a small set of events. Those include the insertion of genes into, or the splitting of genes out of a gene block, gene loss, and gene duplication. We show how the event-based method of gene block evolution allows us to determine the evolutionary rateand may be used to trace the ancestral states of their formation. We conclude that the event-based method can be used to help us understand the formation of these important bacterial genomic structures. The software is available under GPLv3 license on http://github.com/reamdc1/gene_block_evolution.git. Supplementary online material: http://iddo-friedberg.net/operon-evolution © The Author 2015. Published by Oxford University Press.

  11. Plant reference genes for development and stress response studies

    Indian Academy of Sciences (India)

    Many reference genes are used by different laboratories for gene expression analyses to indicate the relative amount of inputRNA/DNA in the experiment. These reference genes are supposed to show least variation among the treatments and withthe control sets in a given experiment. However, expression of reference ...

  12. Study of BMP-15 gene polymorphism in Iranian goats | Deldar ...

    African Journals Online (AJOL)

    Different mutations in the bone morphogenetic protein-15 (BMP-15) and the Growth Differentiation Factor-9 (GDF-9) genes have increased ovulation rate and infertility in a dosage-sensitive manner in sheep. To test the polymorphisms of genes in goat, which have been demonstrated as major genes of fecundity in sheep, ...

  13. Student Teachers' Proactive Strategies and Experienced Learning Environment for Reducing Study-Related Burnout

    Science.gov (United States)

    Väisänen, Sanna; Pietarinen, Janne; Pyhältö, Kirsi; Toom, Auli; Soini, Tiina

    2018-01-01

    The study aims to gain a better understanding of the interrelation and the development of student teachers' proactive coping strategies, i.e., self-regulative and co-regulative strategies, perceived learning environment and study-related burnout. Longitudinal data were utilized with three annual measurements during bachelor studies. Altogether,…

  14. Gene study within the 5' flanking regions of growth hormone gene of ...

    African Journals Online (AJOL)

    Growth hormone (GH) is a main regulatory protein secreted by pituitary gland and placenta, involved in most anabolic processes in mammals. Expression of more than one gene for GH has been reported, indicating polymorphism at gene and protein level; apart from this, silent mutations has also been reported, relating to ...

  15. Gene study within the 5' flanking regions of growth hormone gene of ...

    African Journals Online (AJOL)

    user

    2011-01-17

    Jan 17, 2011 ... replacements and one addition, for GH 2.3 allele, as compared to Bos taurus Genome (Btau_4.0 ) and two earlier ... Key words: Bos indicus, growth hormone gene, silent mutation, growth hormone (GH) gene, allele. INTRODUCTION ..... Sami AJ (2007). Structure-function relation of somatotropin with.

  16. Gene study within the 5' flanking regions of growth hormone gene of ...

    African Journals Online (AJOL)

    user

    2011-01-17

    Jan 17, 2011 ... production, growth regulation, carcass and immune response traits in livestock, these changes could be used as a ... Key words: Bos indicus, growth hormone gene, silent mutation, growth hormone (GH) gene, allele. INTRODUCTION ..... sequence on level of expression of ovine growth hormones cDA.

  17. RNA-seq reveals more consistent reference genes for gene expression studies in human non-melanoma skin cancers

    Directory of Open Access Journals (Sweden)

    Van L.T. Hoang

    2017-08-01

    Full Text Available Identification of appropriate reference genes (RGs is critical to accurate data interpretation in quantitative real-time PCR (qPCR experiments. In this study, we have utilised next generation RNA sequencing (RNA-seq to analyse the transcriptome of a panel of non-melanoma skin cancer lesions, identifying genes that are consistently expressed across all samples. Genes encoding ribosomal proteins were amongst the most stable in this dataset. Validation of this RNA-seq data was examined using qPCR to confirm the suitability of a set of highly stable genes for use as qPCR RGs. These genes will provide a valuable resource for the normalisation of qPCR data for the analysis of non-melanoma skin cancer.

  18. mRNA-Mediated Gene Supplementation of Toll-Like Receptors as Treatment Strategy for Asthma In Vivo.

    Directory of Open Access Journals (Sweden)

    Franziska Zeyer

    Full Text Available Asthma is the most common chronic disease in childhood. Although several therapeutic options are currently available to control the symptoms, many drugs have significant side effects and asthma remains an incurable disease. Microbial exposure in early life reduces the risk of asthma and several studies have suggested protective effects of Toll-like receptor (TLR activation. We showed previously that modified mRNA provides a safe and efficient therapeutic tool for in vivo gene supplementation. Since current asthma drugs do not take patient specific immune and TLR backgrounds into consideration, treatment with tailored mRNA could be an attractive approach to account for the patient's individual asthma phenotype. Therefore, we investigated the effect of a preventative treatment with combinations of Tlr1, Tlr2 and Tlr6 mRNA in a House Dust Mite-induced mouse model of asthma. We used chemically modified mRNA which is-in contrast to conventional viral vectors-non-integrating and highly efficient in gene transfer. In our study, we found that treatment with either Tlr1/2 mRNA or Tlr2/6 mRNA, but not Tlr2 mRNA alone, resulted in better lung function as well as reduced airway inflammation in vivo. The present results point to a potentially protective effect of TLR heterodimers in asthma pathogenesis.

  19. Crisis strategies in BP's Deepwater Horizon response : An image repair and situational crisis communication study

    OpenAIRE

    Johansson, Mikael

    2017-01-01

    The BP Deepwater Horizon crisis in 2010 was one the largest catastrophes in the history of the oil industry. BP was sued over the disaster, and lost several billion dollars. This study examines the crisis response strategies and/or image repair strategies, which can be found in BP's press releases following the Deepwater Horizon crisis. In particular, the study looks closer at what established crisis communication strategies could be discerned in the material, and how they are used discursive...

  20. Empirical Studies on Legitimation Strategies: A Case for International Business Research Extension

    DEFF Research Database (Denmark)

    Turcan, Romeo V.; Marinova, Svetla Trifonova; Rana, Mohammad Bakhtiar

    2012-01-01

    The paper focuses on legitimation and legitimation strategies applied by companies. Following the process of systematic review, we analyze empirical studies exploring legitimation and legitimation strategies from different theoretical perspectives. Using the key findings by reconnoitering and com...... and comparing the theoretical background, approaches, methodologies, and findings of these empirical studies, we outline potential directions for research in the legitimation strategies of firms engaged in international business operations....

  1. Retail private label’s strategies: A case study in a large brazilian Supermarket chain.

    Directory of Open Access Journals (Sweden)

    Paula Bulamah Spineli

    2006-12-01

    Full Text Available The present study approaches the advantages and risks related to private labels under a retailers’ perspective, as well as the private label strategies and its growth in the Brazilian market. The paper analyses the strategies used by a large Brazilian supermarket chain with regards to its private labels’ management, using the case study method. The results showed the existence of two private label lines of products, with different strategies: one line of light products (proprietary brand and another line of products that carry the name of the supermarket under study (retail brand endorsement, both classified as using the fantasy positioning strategy.

  2. Embedding Literacy Strategies in Social Studies for Eighth-Grade Students

    Directory of Open Access Journals (Sweden)

    Alishia Gaston

    2016-05-01

    Full Text Available This action research study evaluated the effects of literacy strategies on academic achievement, motivation, and engagement of eighth-grade social studies students. Incorporating literacy strategies included teaching students to construct meaning, think critically, and build content knowledge, while stimulating their interests, using multiple texts and technology, and providing collaborative opportunities and high engagement during instructional activities. Students were divided into a literacy group and a direct instruction group with each class being taught the same content. Literacy strategies were incorporated in one class, and direct instruction activities were used in the other class. Results were determined using pre and posttest scores, a student motivation questionnaire, and a student engagement checklist. Results indicated significantly higher student achievement and engagement when literacy strategies were a part of the social studies instruction. Motivation also increased when literacy strategies were used. Literacy instruction was a beneficial strategy to improve student achievement, motivation, and engagement.

  3. A qualitative study of rural black adolescents' perspectives on primary STD prevention strategies.

    Science.gov (United States)

    Akers, Aletha Y; Gold, Melanie A; Coyne-Beasley, Tamera; Corbie-Smith, Giselle

    2012-06-01

    Primary STD prevention relies on five key strategies: practicing abstinence, choosing low-risk partners, discussing partners' sexual history, using condoms consistently and not having multiple partners. Few studies have examined all of these strategies simultaneously, and few have focused on rural black adolescents, whose rates of early sexual initiation and STDs are among the highest in the nation. In 2006, a sample of 37 black adolescents (20 female, 17 male) from two rural North Carolina counties participated in focus groups that explored their understanding of how primary prevention strategies reduce STD transmission, the common barriers they encounter in trying to adopt these strategies and the risk reduction strategies that they employ. Transcripts were analyzed using a grounded theory approach. Adolescents understood how primary prevention strategies reduce STD transmission. However, they perceived sex as normal and abstinence as unlikely during adolescence. Furthermore, they considered the remaining primary prevention strategies difficult to implement because these strategies depend on partner cooperation and incorrectly assume that STD prevention is paramount when adolescents make sexual decisions. Adolescents reported using alternative strategies to reduce their STD risk; the most commonly used approaches were indirect assessments of partner characteristics (e.g., evaluating partners' physical appearance and sexual history) and STD testing (to identify and treat infections). Adolescents try to reduce their STD risk, but do so by using ineffective practices. Promoting primary prevention strategies requires helping adolescents to identify opportunities to successfully employ these strategies. Copyright © 2012 by the Guttmacher Institute.

  4. ss-siRNAs allele selectively inhibit ataxin-3 expression: multiple mechanisms for an alternative gene silencing strategy.

    Science.gov (United States)

    Liu, Jing; Yu, Dongbo; Aiba, Yuichiro; Pendergraff, Hannah; Swayze, Eric E; Lima, Walt F; Hu, Jiaxin; Prakash, Thazha P; Corey, David R

    2013-11-01

    Single-stranded silencing RNAs (ss-siRNAs) provide an alternative approach to gene silencing. ss-siRNAs combine the simplicity and favorable biodistribution of antisense oligonucleotides with robust silencing through RNA interference (RNAi). Previous studies reported potent and allele-selective inhibition of human huntingtin expression by ss-siRNAs that target the expanded CAG repeats within the mutant allele. Mutant ataxin-3, the genetic cause of Machado-Joseph Disease, also contains an expanded CAG repeat. We demonstrate here that ss-siRNAs are allele-selective inhibitors of ataxin-3 expression and then redesign ss-siRNAs to optimize their selectivity. We find that both RNAi-related and non-RNAi-related mechanisms affect gene expression by either blocking translation or affecting alternative splicing. These results have four broad implications: (i) ss-siRNAs will not always behave similarly to analogous RNA duplexes; (ii) the sequences surrounding CAG repeats affect allele-selectivity of anti-CAG oligonucleotides; (iii) ss-siRNAs can function through multiple mechanisms and; and (iv) it is possible to use chemical modification to optimize ss-siRNA properties and improve their potential for drug discovery.

  5. Selective testing for calreticulin gene mutations in patients with splanchnic vein thrombosis: A prospective cohort study.

    Science.gov (United States)

    Poisson, Johanne; Plessier, Aurélie; Kiladjian, Jean-Jacques; Turon, Fanny; Cassinat, Bruno; Andreoli, Annalisa; De Raucourt, Emmanuelle; Goria, Odile; Zekrini, Kamal; Bureau, Christophe; Lorre, Florence; Cervantes, Francisco; Colomer, Dolors; Durand, François; Garcia-Pagan, Juan-Carlos; Casadevall, Nicole; Valla, Dominique-Charles; Rautou, Pierre-Emmanuel; Marzac, Christophe

    2017-09-01

    Myeloproliferative neoplasms (MPN) are the leading cause of splanchnic vein thrombosis (SVT). Janus kinase 2 gene (JAK2) V617F mutations are found in 80 to 90% of patients with SVT and MPN. Mutations of the calreticulin (CALR) gene have also been reported. However, as their prevalence ranges from 0 to 2%, the utility of routine testing is questionable. This study aimed to identify a group of patients with SVT at high risk of harboring CALR mutations and thus requiring this genetic testing. CALR, JAK2 V617F and thrombopoietin receptor gene (MPL) mutations were analysed in a test cohort that included 312 patients with SVT. Criteria to identify patients at high risk of CALR mutations in this test cohort was used and evaluated in a validation cohort that included 209 patients with SVT. In the test cohort, 59 patients had JAK2 V617F , five had CALR and none had MPL mutations. Patients with CALR mutations had higher spleen height and platelet count than patients without these mutations. All patients with CALR mutations had a spleen height ⩾16cm and platelet count >200×10 9 /L. These criteria had a positive predictive value of 56% (5/9) and a negative predictive value of 100% (0/233) for the identification of CALR mutations. In the validation cohort, these criteria had a positive predictive value of 33% (2/6) and a negative predictive value of 99% (1/96). CALR mutations should be tested in patients with SVT, a spleen height ⩾16cm, platelet count >200×10 9 /L, and no JAK2 V617F . This strategy avoids 96% of unnecessary CALR mutations testing. Lay summary: Mutations of the CALR gene are detected in 0 to 2% of patients with SVT, thus the utility of systematic CALR mutation testing to diagnose MPN is questionable. This study demonstrates that CALR mutations testing can be restricted to patients with SVT, a spleen height ⩾16cm, a platelet count >200×10 9 /L, and no JAK2 V617F . This strategy avoids 96% of unnecessary CALR mutations testing. Copyright © 2017 European

  6. A strategy for full interrogation of prognostic gene expression patterns: exploring the biology of diffuse large B cell lymphoma.

    Science.gov (United States)

    Rimsza, Lisa M; Unger, Joseph M; Tome, Margaret E; Leblanc, Michael L

    2011-01-01

    Gene expression profiling yields quantitative data on gene expression used to create prognostic models that accurately predict patient outcome in diffuse large B cell lymphoma (DLBCL). Often, data are analyzed with genes classified by whether they fall above or below the median expression level. We sought to determine whether examining multiple cut-points might be a more powerful technique to investigate the association of gene expression with outcome. We explored gene expression profiling data using variable cut-point analysis for 36 genes with reported prognostic value in DLBCL. We plotted two-group survival logrank test statistics against corresponding cut-points of the gene expression levels and smooth estimates of the hazard ratio of death versus gene expression levels. To facilitate comparisons we also standardized the expression of each of the genes by the fraction of patients that would be identified by any cut-point. A multiple comparison adjusted permutation p-value identified 3 different patterns of significance: 1) genes with significant cut-point points below the median, whose loss is associated with poor outcome (e.g. HLA-DR); 2) genes with significant cut-points above the median, whose over-expression is associated with poor outcome (e.g. CCND2); and 3) genes with significant cut-points on either side of the median, (e.g. extracellular molecules such as FN1). Variable cut-point analysis with permutation p-value calculation can be used to identify significant genes that would not otherwise be identified with median cut-points and may suggest biological patterns of gene effects.

  7. A strategy for full interrogation of prognostic gene expression patterns: exploring the biology of diffuse large B cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Lisa M Rimsza

    Full Text Available Gene expression profiling yields quantitative data on gene expression used to create prognostic models that accurately predict patient outcome in diffuse large B cell lymphoma (DLBCL. Often, data are analyzed with genes classified by whether they fall above or below the median expression level. We sought to determine whether examining multiple cut-points might be a more powerful technique to investigate the association of gene expression with outcome.We explored gene expression profiling data using variable cut-point analysis for 36 genes with reported prognostic value in DLBCL. We plotted two-group survival logrank test statistics against corresponding cut-points of the gene expression levels and smooth estimates of the hazard ratio of death versus gene expression levels. To facilitate comparisons we also standardized the expression of each of the genes by the fraction of patients that would be identified by any cut-point. A multiple comparison adjusted permutation p-value identified 3 different patterns of significance: 1 genes with significant cut-point points below the median, whose loss is associated with poor outcome (e.g. HLA-DR; 2 genes with significant cut-points above the median, whose over-expression is associated with poor outcome (e.g. CCND2; and 3 genes with significant cut-points on either side of the median, (e.g. extracellular molecules such as FN1.Variable cut-point analysis with permutation p-value calculation can be used to identify significant genes that would not otherwise be identified with median cut-points and may suggest biological patterns of gene effects.

  8. Embedding Literacy Strategies in Social Studies for Eighth-Grade Students

    Science.gov (United States)

    Gaston, Alishia; Martinez, James; Martin, Ellice P.

    2016-01-01

    This action research study evaluated the effects of literacy strategies on academic achievement, motivation, and engagement of eighth-grade social studies students. Incorporating literacy strategies included teaching students to construct meaning, think critically, and build content knowledge, while stimulating their interests, using multiple…

  9. Turkish EFL Instructors' Perceived Importance of Motivational Strategies: A Descriptive Study

    Science.gov (United States)

    Ustuk, Özgehan

    2018-01-01

    This study investigated how important Turkish EFL teachers perceive the ELT motivational strategies that are implemented in adult EFL teaching. 52 EFL instructors working in preparatory schools of foreign languages in four state universities in Turkey participated in the current study. The perceived importance of ELT motivational strategies was…

  10. Improved Learning and Study Strategies Inventory (LASSI) and Academic Performance: The Impact of Feedback on Freshmen.

    Science.gov (United States)

    Haught, Patricia A.; Hill, Lee Ann; Walls, Richard T.; Nardi, Anne H.

    1998-01-01

    In a study strategies course, 69 college freshmen were given individual profiles from the Learning and Study Strategies Inventory (LASSI) and general feedback in a group setting; half also received individualized feedback, including specific suggestions for improving LASSI performance. Students receiving the individualized feedback had higher…

  11. Investigation of the Latent Structure for the Learning and Study Strategies Inventory

    Science.gov (United States)

    Finch, W. Holmes; Cassady, Jerrell C.; Jones, James A.

    2016-01-01

    The Learning and Study Strategies Inventory (LASSI) is a very popular tool for measuring the learning and study strategies of high school and college students. Prior research with the LASSI has supported the originally proposed model with three latent traits, with minor variations among the contributing subtests contributing to those traits.…

  12. Strategies for Promoting Autonomous Reading Motivation: A Multiple Case Study Research in Primary Education

    Science.gov (United States)

    De Naeghel, Jessie; Van Keer, Hilde; Vanderlinde, Ruben

    2014-01-01

    It is important to reveal strategies which foster students' reading motivation in order to break through the declining trend in reading motivation throughout children's educational careers. Consequently, the present study advances an underexposed field in reading motivation research by studying and identifying the strategies of teachers excellent…

  13. Embedding Literacy Strategies in Social Studies for Eighth-Grade Students

    OpenAIRE

    Martinez, James; Gaston, Alishia; Martin, Ellice P.

    2016-01-01

    This action research study evaluated the effects of literacy strategies on academic achievement, motivation, and engagement of eighth-grade social studies students. Incorporating literacy strategies included teaching students to construct meaning, think critically, and build content knowledge, while stimulating their interests, using multiple texts and technology, and providing collaborative opportunities and high engagement during instructional activities. Students were divided i...

  14. Gene Therapy for Bone Defects in Oral and Maxillofacial Surgery: A Systematic Review and Meta-Analysis of Animal Studies.

    Science.gov (United States)

    Fliefel, Riham; Kühnisch, Jan; Ehrenfeld, Michael; Otto, Sven

    2017-02-15

    Craniofacial bone defects are challenging problems for maxillofacial surgeons over the years. With the development of cell and molecular biology, gene therapy is a breaking new technology with the aim of regenerating tissues by acting as a delivery system for therapeutic genes in the craniofacial region rather than treating genetic disorders. A systematic review was conducted summarizing the articles reporting gene therapy in maxillofacial surgery to answer the question: Was gene therapy successfully applied to regenerate bone in the maxillofacial region? Electronic searching of online databases was performed in addition to hand searching of the references of included articles. No language or time restrictions were enforced. Meta-analysis was done to assess significant bone formation after delivery of gene material in the surgically induced maxillofacial defects. The search identified 2081 articles, of which 57 were included with 1726 animals. Bone morphogenetic proteins were commonly used proteins for gene therapy. Viral vectors were the universally used vectors. Sprague-Dawley rats were the frequently used animal model in experimental studies. The quality of the articles ranged from excellent to average. Meta-analysis results performed on 21 articles showed that defects favored bone formation by gene therapy. Funnel plot showed symmetry with the absence of publication bias. Gene therapy is on the top list of innovative strategies that developed in the last 10 years with the hope of developing a simple chair-side protocol in the near future, combining improvement of gene delivery as well as knowledge of the molecular basis of oral and maxillofacial structures.

  15. Organizational performance, Marketing strategy, and Financial strategic alignment: an empirical study on Iranian pharmaceutical firms.

    Science.gov (United States)

    Mohammadzadeh, Mehdi; Aarabi, Sied Mohammad; Salamzadeh, Jamshid

    2013-08-02

    Strategic Functional-level planning should be aligned with business level and other functional strategies of a company. It is presumed that assimilating the strategies could have positive contribution to business performance, in this regard alignment between marketing strategy and financial strategy seems to be the most important strategies being studied. An empirical work in generic pharmaceutical manufacturing companies for evaluating effect of alignment between these two functions on organizational performance was developed in this paper. All Iranian pharmaceutical generic manufactures listed in Tehran stock market have been tested for period of five years between 2006-2010 and their marketing strategies were determined by using Slater and Olson taxonomy and their financial strategies have been developed by calculating total risk and total return of sample companies for five years based on rate of risk and return in the frame of a 2 × 2 matrix. For the business performance three profitability indices including Q-Tubin (Rate of market value to net asset value), ROA (Return on Asset), ROE (Return on Equity) have been tested. For analysis, a series of one-way ANOVAs as a collection of statistical models within marketing strategies considering financial strategy as independent variable and the three performance measures as dependent variables was used. Results show strategic alignment between financial and marketing has significant impact on profitability of company resulting in arise of all three profitability indices. Q tubing's rate were 2.33,2.09,2.29,2.58 and rate of ROA were 0.21,0.194,0.25,0.22 and rate of ROE were 0.44,0.46,0.45,0.42 for matched strategy types, respectively the rates shown here are more than average meaning that specific type of marketing strategy is fitted with specific type of financial strategy. Managers should not consider decisions regarding marketing strategy independently of their financial strategy.

  16. Organizational Performance, Marketing Strategy, and Financial Strategic Alignment: an Empirical Study on Iranian Pharmaceutical Firms

    Directory of Open Access Journals (Sweden)

    Mehdi Mohammadzadeh

    2013-08-01

    Full Text Available Background:Strategic Functional-level planning should be aligned with business level and other functional strategies of a company. It is presumed that assimilating the strategies could have positive contribution to business performance, in this regard alignment between marketing strategy and financial strategy seems to be the most important strategies being studied. An empirical work in generic pharmaceutical manufacturing companies for evaluating effect of alignment between these two functions on organizational performance was developed in this paper.Methods:All Iranian pharmaceutical generic manufactures listed in Tehran stock market have been tested for period of five years between 2006--2010 and their marketing strategies were determined by using Slater and Olson taxonomy and their financial strategies have been developed by calculating total risk and total return of sample companies for five years based on rate of risk and return in the frame of a 2 x 2 matrix. For the business performance three profitability indices including Q-Tubin (Rate of market value to net asset value, ROA (Return on Asset, ROE (Return on Equity have been tested. For analysis, a series of one-way ANOVAs as a collection of statistical models within marketing strategies considering financial strategy as independent variable and the three performance measures as dependent variables was used.Results:Results show strategic alignment between financial and marketing has significant impact on profitability of company resulting in arise of all three profitability indices. Q tubing's rate were 2.33,2.09,2.29,2.58 and rate of ROA were 0.21,0.194,0.25,0.22 and rate of ROE were 0.44,0.46,0.45,0.42 for matched strategy types, respectively the rates shown here are more than average meaning that specific type of marketing strategy is fitted with specific type of financial strategy.Conclusion:Managers should not consider decisions regarding marketing strategy independently of their

  17. Organizational performance, Marketing strategy, and Financial strategic alignment: an empirical study on Iranian pharmaceutical firms

    Science.gov (United States)

    2013-01-01

    Background Strategic Functional-level planning should be aligned with business level and other functional strategies of a company. It is presumed that assimilating the strategies could have positive contribution to business performance, in this regard alignment between marketing strategy and financial strategy seems to be the most important strategies being studied. An empirical work in generic pharmaceutical manufacturing companies for evaluating effect of alignment between these two functions on organizational performance was developed in this paper. Methods All Iranian pharmaceutical generic manufactures listed in Tehran stock market have been tested for period of five years between 2006–2010 and their marketing strategies were determined by using Slater and Olson taxonomy and their financial strategies have been developed by calculating total risk and total return of sample companies for five years based on rate of risk and return in the frame of a 2 × 2 matrix. For the business performance three profitability indices including Q-Tubin (Rate of market value to net asset value), ROA (Return on Asset), ROE (Return on Equity) have been tested. For analysis, a series of one-way ANOVAs as a collection of statistical models within marketing strategies considering financial strategy as independent variable and the three performance measures as dependent variables was used. Results Results show strategic alignment between financial and marketing has significant impact on profitability of company resulting in arise of all three profitability indices. Q tubing’s rate were 2.33,2.09,2.29,2.58 and rate of ROA were 0.21,0.194,0.25,0.22 and rate of ROE were 0.44,0.46,0.45,0.42 for matched strategy types, respectively the rates shown here are more than average meaning that specific type of marketing strategy is fitted with specific type of financial strategy. Conclusion Managers should not consider decisions regarding marketing strategy independently of their financial

  18. Molecular Signature of Cancer at Gene Level or Pathway Level? Case Studies of Colorectal Cancer and Prostate Cancer Microarray Data

    Directory of Open Access Journals (Sweden)

    Jiajia Chen

    2013-01-01

    Full Text Available With recent advances in microarray technology, there has been a flourish in genome-scale identification of molecular signatures for cancer. However, the differentially expressed genes obtained by different laboratories are highly divergent. The present discrepancy at gene level indicates a need for a novel strategy to obtain more robust signatures for cancer. In this paper we hypothesize that (1 the expression signatures of different cancer microarray datasets are more similar at pathway level than at gene level; (2 the comparability of the cancer molecular mechanisms of different individuals is related to their genetic similarities. In support of the hypotheses, we summarized theoretical and experimental evidences, and conducted case studies on colorectal and prostate cancer microarray datasets. Based on the above assumption, we propose that reliable cancer signatures should be investigated in the context of biological pathways, within a cohort of genetically homogeneous population. It is hoped that the hypotheses can guide future research in cancer mechanism and signature discovery.

  19. Developmental prosopagnosia and adaptative compensatory strategies: Case study

    Directory of Open Access Journals (Sweden)

    Anair Rodrigues

    Full Text Available Abstract Prosopagnosia is a type of visual agnosia with inability to identify faces, usually secondary to brain lesion in associative cortex areas, but there is also a congenital form known as developmental prosopagnosia. Objectives: To describe a case of developmental prosopagnosia that illustrates the specificity of the pathways for perception of faces in the visual system. Also, we will describe possible mechanisms of recognition used by this patient. Methods: R.S., a 50 year-old woman, was referred for neuropsychological assessment due to difficulties in perception of familiar faces since childhood, unexplained by any loss of visual acuity. Results: The exam showed good performance for comprehension, reasoning, concept formation, constructional abilities, criticism, judgment, mental control, memory and visual perception for other kinds of stimuli. No difficulties were seen regarding identification of ethnicity, age and types of animals. The patient was able to match celebrities' faces in different positions, but could not identify the matching pictures for unknown people. Conclusions: These findings indicate the patient had developed strategies, throughout life, to recognize familiar faces (relatives, celebrities from memorized fragments, but still had difficulties in identifying non-familiar faces holistically.

  20. Robust Tests for Additive Gene-Environment Interaction in Case-Control Studies Using Gene-Environment Independence

    DEFF Research Database (Denmark)

    Liu, Gang; Lee, Seunggeun; Lee, Alice W

    2018-01-01

    There have been recent proposals advocating the use of additive gene-environment interaction instead of the widely used multiplicative scale, as a more relevant public health measure. Using gene-environment independence enhances the power for testing multiplicative interaction in case...... in a data-adaptive way, to the additive scale. An EB estimator of Relative Excess Risk due to Interaction is derived and the corresponding Wald test is proposed with general regression setting under a retrospective likelihood framework. We study the impact of gene-environment association on the resultant...... test with case-control data. Our simulation studies suggest that the EB approach uses the gene-environment independence assumption in a data-adaptive way and provides power gain compared to the standard logistic regression analysis and better control of Type I error when compared to the analysis...

  1. Reference genes for normalization: A study of rat brain tissue

    DEFF Research Database (Denmark)

    Bonefeld, Birgit; Elfving, Betina; Wegener, Gregers

    2008-01-01

    Norm software applets. Additionally, we have applied four different normalization approaches for normalization of the three target genes. We found using the NormFinder software that Ywhaz is the most stably expressed gene among the eight tested HKGs. However, the results of the analysis of the target genes...... are warranted. With the overall aim to inspect the gene expression of three target genes, NMDAR1, SORT, and CREB, in rat hippocampus, we tested a panel of eight HKGs, 18s rRNA, ActB, CycA, Gapd, Hmbs, Hprt1, Rpl13A, and Ywhaz in order to select the most stably expressed gene, using the NormFinder and ge...

  2. A Study on Motivation and Strategy Use of Bangladeshi University Students to Learn Spoken English

    OpenAIRE

    Mst. Moriam, Quadir

    2008-01-01

    This study discusses motivation and strategy use of university students to learn spoken English in Bangladesh. A group of 355 (187 males and 168 females) university students participated in this investigation. To measure learners' degree of motivation a modified version of questionnaire used by Schmidt et al. (1996) was administered. Participants reported their strategy use on a modified version of SILL, the Strategy Inventory for Language Learning, version 7.0 (Oxford, 1990). In order to fin...

  3. Neurogenesis in Huntington's disease: can studying adult neurogenesis lead to the development of new therapeutic strategies?

    Science.gov (United States)

    Gil-Mohapel, Joana; Simpson, Jessica M; Ghilan, Mohamed; Christie, Brian R

    2011-08-11

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an unstable expansion of CAG repeats in the HD gene. The symptoms include cognitive dysfunction and severe motor impairments. The neuropathology is characterized by neuronal loss mainly in the striatum and cortex, although other regions including the hippocampus are also affected. In this review we discuss the different mouse models of HD, and how the process of neurogenesis in the dentate gyrus (DG) of the hippocampus and the subventricular zone (SVZ) is affected in each. Deficits in adult hippocampal neurogenesis have been repeatedly shown in different genetic models of HD, raising the possibility that an impairment of the neurogenic process might underlie some of the cognitive deficits associated with this neurodegenerative disorder. On the other hand, an increase in SVZ neurogenesis has been observed in human HD brains while no differences in SVZ cell proliferation have been detected in the mouse models. In this review we will discuss the discrepancies between these findings as well as the several mechanisms that might contribute to a dysregulation of adult neurogenesis in HD. Finally, we will provide an overview of the various therapeutic strategies aimed at stimulating the endogenous neurogenic capacity that have been tested in HD genetic models. Ultimately, the insights obtained from these and future studies will greatly improve our understanding of the cognitive impairment characteristic of HD. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Identification of suitable reference genes for gene expression studies in tendons from patients with rotator cuff tear.

    Directory of Open Access Journals (Sweden)

    Mariana Ferreira Leal

    Full Text Available Rotator cuff tear is one of the most common causes of shoulder dysfunction. Gene expression analysis may be a useful tool for understanding tendon tears and the failure of cuff healing, and reverse-transcription quantitative polymerase chain reaction (RT-qPCR has become an effective method for such studies. However, this technique requires the use of suitable reference genes for data normalization. Here, we evaluate the suitability of six reference genes (18S, ACTB, B2M, GAPDH, HPRT1 and TBP using samples from the rotator cuff tendons of 28 individuals with tendon tears (3 tendons regions and 8 controls (2 tendon regions; for the tear patients, we evaluated ruptured and non-ruptured tendon samples. The stability of the candidate reference genes was determined using the NormFinder, geNorm, BestKeeper and DataAssist software packages. Overall, HPRT1 was the best single reference gene, and HPRT1+TBP composed the best pair and HPRT1+TBP+ACTB composed the best trio of reference genes from the analysis of different groups, including the simultaneous analysis of all tissue samples. To identify the optimal combination of reference genes, we evaluated the expression of COL1A1 and COL3A1, and no obvious differences were observed when using 2, 3 or 4 reference genes for most of the analyses. However, COL3A1 expression differed between ruptured and non-ruptured (posterior superior region tendons of patients only when normalized by HPRT1+TBP+B2M and HPRT1+TBP. On the other hand, the comparison between these two groups using the best trio of reference genes (HPRT1+TBP+ACTB and 4 reference genes did not revealed a significant difference in COL3A1 expression. Consequently, the use of suitable reference genes for a reliable gene expression evaluation by RT-qPCR should consider the type of tendon samples investigated. HPRT1+TBP+ACTB seems to be the best combination of reference genes for the analysis of involving different tendon samples of individuals with

  5. A Bayesian model for pooling gene expression studies that incorporates co-regulation information.

    Directory of Open Access Journals (Sweden)

    Erin M Conlon

    Full Text Available Current Bayesian microarray models that pool multiple studies assume gene expression is independent of other genes. However, in prokaryotic organisms, genes are arranged in units that are co-regulated (called operons. Here, we introduce a new Bayesian model for pooling gene expression studies that incorporates operon information into the model. Our Bayesian model borrows information from other genes within the same operon to improve estimation of gene expression. The model produces the gene-specific posterior probability of differential expression, which is the basis for inference. We found in simulations and in biological studies that incorporating co-regulation information improves upon the independence model. We assume that each study contains two experimental conditions: a treatment and control. We note that there exist environmental conditions for which genes that are supposed to be transcribed together lose their operon structure, and that our model is best carried out for known operon structures.

  6. A study of variability of capsid protein genes of Radish mosaic virus

    OpenAIRE

    HOLÁ, Marcela

    2008-01-01

    The part of RNA2 genome segment of several isolates of Radish mosaic virus (RaMV) including capsid protein genes was sequenced. Variability of capsid protein genes among the isolates of Radish mosaic virus was studied.

  7. A comparative study of mutation screening of sarcomeric genes (MYBPC3, MYH7, TNNT2 using single gene approach versus targeted gene panel next generation sequencing in a cohort of HCM patients in Egypt

    Directory of Open Access Journals (Sweden)

    Heba Sh. Kassem

    2017-10-01

    Full Text Available Background: NGS enables simultaneous sequencing of large numbers of associated genes in genetic heterogeneous disorders, in a more rapid and cost-effective manner than traditional technologies. However there have been limited direct comparisons between NGS and more established technologies to assess the sensitivity and false negative rates of this new approach. The scope of the present manuscript is to compare variants detected in MYBPC3, MYH7 and TNNT2 genes using the stepwise dHPLC/Sanger versus targeted NGS. Methods: In this study, we have analysed a group of 150 samples of patients from the Bibliotheca Alexandrina-Aswan Heart Centre National HCM program. The genetic testing was simultaneously undertaken by high throughput denaturing high-performance liquid chromatography (dHPLC followed by Sanger based sequencing and targeted next generation deep sequencing using panel of inherited cardiac genes (ICC. The panel included over 100 genes including the 3 sarcomeric genes. Analysis of the sequencing data of the 3 genes was undertaken in a double blinded strategy. Results: NGS analysis detected all pathogenic and likely pathogenic variants identified by dHPLC (50 in total, some samples had double hits. There was a 0% false negative rate for NGS based analysis. Nineteen variants were missed by dHPLC and detected by NGS, thus increasing the diagnostic yield in this co- analysed cohort from 22.0% (33/150 to 31.3% (47/150.Of interest to note that the mutation spectrum in this Egyptian HCM population revealed a high rate of homozygosity in MYBPC3 and MYH7 genes in comparison to other population studies (6/150, 4%. None of the homozygous samples were detected by dHPLC analysis. Conclusion: NGS provides a useful and rapid tool to allow panoramic screening of several genes simultaneously with a high sensitivity rate amongst genes of known etiologic role allowing high throughput analysis of HCM patients and relevant control series in a less characterised

  8. Aging and sequential modulations of poorer strategy effects: An EEG study in arithmetic problem solving.

    Science.gov (United States)

    Hinault, Thomas; Lemaire, Patrick; Phillips, Natalie

    2016-01-01

    This study investigated age-related differences in electrophysiological signatures of sequential modulations of poorer strategy effects. Sequential modulations of poorer strategy effects refer to decreased poorer strategy effects (i.e., poorer performance when the cued strategy is not the best) on current problem following poorer strategy problems compared to after better strategy problems. Analyses on electrophysiological (EEG) data revealed important age-related changes in time, frequency, and coherence of brain activities underlying sequential modulations of poorer strategy effects. More specifically, sequential modulations of poorer strategy effects were associated with earlier and later time windows (i.e., between 200- and 550 ms and between 850- and 1250 ms). Event-related potentials (ERPs) also revealed an earlier onset in older adults, together with more anterior and less lateralized activations. Furthermore, sequential modulations of poorer strategy effects were associated with theta and alpha frequencies in young adults while these modulations were found in delta frequency and theta inter-hemispheric coherence in older adults, consistent with qualitatively distinct patterns of brain activity. These findings have important implications to further our understanding of age-related differences and similarities in sequential modulations of cognitive control processes during arithmetic strategy execution. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Study Habits, Motives, and Strategies of College Students With Symptoms of ADHD.

    Science.gov (United States)

    Simon-Dack, Stephanie L; Rodriguez, P Dennis; Marcum, Geoff D

    2016-09-01

    Studies on ADHD in educational settings indicate that a student's motivation for learning is significantly related with the student's grade point average. The present study examined the relationship between ADHD symptoms and student academic achievement by considering the student's approach to and motivation for learning. Participants completed a questionnaire that breaks down learning strategies into a surface or deep approach. Each approach is then divided into a deep or surface motivation and strategy. A multivariate analysis of variance determined that those in the control group were using the deep approach, whereas those in the ADHD group strongly favored the surface approach. Furthermore, ADHD participants preferred surface motive and surface strategy. A factor analysis of a study-habits questionnaire identified five categories, with collaborative learning approaching significant levels. Implications for guiding ADHD college students toward effective study strategies are discussed in light of their preference for surface approach, motive, and strategy. © The Author(s) 2014.

  10. Recruitment strategies in a prospective longitudinal family study on parents with obesity and their toddlers

    Directory of Open Access Journals (Sweden)

    Sarah Bergmann

    2017-02-01

    Full Text Available Abstract Background Recruitment of participants with obesity is a real challenge. To reduce time and costs in similar projects, we investigated various recruiting strategies used in a longitudinal family study with respect to their enrolment yield and cost effectiveness. Results may help other research groups to optimize their recruitment strategies. Methods We applied different recruitment strategies to acquire families with children aged 6 to 47 months and at least one parent with obesity (risk group or two parents of normal weight (control group for a longitudinal non-interventional study. Based on four main strategies-via media, kindergartens, health professionals and focusing on the community-we examined 15 different subcategories of strategies. Based on enrolment yield and relative costs (e.g., material expenses, staff time we analyzed the effectiveness of each recruitment strategy. Results Following different recruitment approaches, 685 families contacted us; 26% (n = 178 of these met the inclusion criteria. Of the four main strategies, the community-focused strategy was the most successful one (accounting for 36.5% of the sample followed by contacts with kindergartens (accounting for 28.1% of the sample. Of the subcategories, two strategies were outstanding: Posters (community-focused strategies, and recruitment via kindergartens using phone contacts rather than emailing. Only a small number of participants were recruited via announcements in newspapers (lower cost strategy, advertisements on public transport or face-to-face recruitment at various places (higher cost strategies. Conclusions Results revealed that only a combination of different active and passive methods and approaches led to a sufficient sample size. In this study, recruitment via posters and contacting kindergartens on the phone produced the highest numbers of participants (high enrolment yield at moderate costs.

  11. Identification of Reference Genes for Quantitative Gene Expression Studies in a Non-Model Tree Pistachio (Pistacia vera L..

    Directory of Open Access Journals (Sweden)

    Maryam Moazzam Jazi

    Full Text Available The tree species, Pistacia vera (P. vera is an important commercial product that is salt-tolerant and long-lived, with a possible lifespan of over one thousand years. Gene expression analysis is an efficient method to explore the possible regulatory mechanisms underlying these characteristics. Therefore, having the most suitable set of reference genes is required for transcript level normalization under different conditions in P. vera. In the present study, we selected eight widely used reference genes, ACT, EF1α, α-TUB, β-TUB, GAPDH, CYP2, UBQ10, and 18S rRNA. Using qRT-PCR their expression was assessed in 54 different samples of three cultivars of P. vera. The samples were collected from different organs under various abiotic treatments (cold, drought, and salt across three time points. Several statistical programs (geNorm, NormFinder, and BestKeeper were applied to estimate the expression stability of candidate reference genes. Results obtained from the statistical analysis were then exposed to Rank aggregation package to generate a consensus gene rank. Based on our results, EF1α was found to be the superior reference gene in all samples under all abiotic treatments. In addition to EF1α, ACT and β-TUB were the second best reference genes for gene expression analysis in leaf and root. We recommended β-TUB as the second most stable gene for samples under the cold and drought treatments, while ACT holds the same position in samples analyzed under salt treatment. This report will benefit future research on the expression profiling of P. vera and other members of the Anacardiaceae family.

  12. Strategy to sequence the 89 exons of the human LRP1 gene coding for the lipoprotein receptor related protein: identification of one expressed mutation among 48 polymorphisms.

    Science.gov (United States)

    Van Leuven, F; Stas, L; Thiry, E; Nelissen, B; Miyake, Y

    1998-09-01

    The human lipoprotein receptor related protein (LRP) binds and internalizes a diverse set of ligands, making LRP the most multifunctional endocytic receptor known. This is possible due to the large size, i.e., 600 kDa, of the receptor protein containing three clusters of putative ligand binding domains, each structurally comparable to the classical LDL receptor. Based on previous structural analysis of the human LRP1 gene (Van Leuven et al., 1994, Genomics, 24: 78-89), a strategy was developed to sequence the 89 exons of the LRP1 gene, including partial intron sequences. The gene was amplified from individual genomic DNA by long-range PCR, in 14 amplicons sized between 0.4 and 11 kb that were used as templates for 110 sequencing primers. In total, 48 mutations and intronic polymorphisms were identified. Two previously reported polymorphisms, i.e., in the promoter region and in exon 3, were precisely defined by sequencing. The first expressed mutation, i.e., an alanine to valine transition at position 217 of the LRP precursor protein, was detected on one allele in 2 of 33 individuals. Although the strategy is still subject to refinement, this approach is reported to allow others to analyze genetic differences in the human LRP1 gene, with particular reference to the recently reported association with late-onset Alzheimer disease. Copyright 1998 Academic Press.

  13. APOLOGIZING STRATEGIES REALIZATION OF INDONESIAN: A CASE STUDY OF THE UNIVERSITY OF KUNINGAN STUDENTS

    Directory of Open Access Journals (Sweden)

    Ayang Winda SW

    2014-06-01

    Full Text Available This study examines the apologizing strategies used by 20 Indonesian students of the Kuningan University. A 8-item Discourse Completion Task and interview are used to collect the data to know the apologizing strategies and the dominant strategies they used. This research applied the apologizing speech act of Indonesian in apologizing which is analyzed by using Blum-Kulka (1984. The findings show that there are various strategies used by then when apologizing. That strategies including IFID, addressed, an explanation or account of situation, acknowledgement of responsibility, offer of repair and promise forbearance, phatic and interjection. IFID was used by them as a favorite strategy. Generally, they used different ways when apology depend on power, social distance and ranking of imposition.

  14. Preschool children's social understanding: a pilot study of goals and strategies during conflict situations.

    Science.gov (United States)

    Kazura, Kerry; Flanders, Rachel

    2007-10-01

    This pilot study tested a new enactive measure of social information-processing skills and investigated whether preschool children's goals were related to their strategies during hypothetical conflict situations. Children (13 boys, 12 girls) ages 3 to 6 years (three 3-yr.-olds, three 4-yr.-olds, 11 5-yr.-olds, and eight 6-yr.-olds) engaged in a puppet interview of six hypothetical situations. Significant correlations were found between goals and strategies of the adapted version of Chung and Asher's Children's Conflict Resolution Measure, suggesting that preschool children who endorsed friendship goals tended to select more prosocial strategies (.41). Children who endorsed more retaliation goals tended to select more hostile strategies (.67) but fewer prosocial strategies (-.41), and children who endorsed more avoidance goals tended to select more adult-seeking strategies (.45).

  15. Cooperative Group Performance in Graduate Research Methodology Courses: The Role of Study Coping and Examination-Taking Coping Strategies

    Science.gov (United States)

    Jiao, Qun G.; Collins, Kathleen M. T.; Onwuegbuzie, Anthony J.

    2013-01-01

    This study seeks to examine the extent to which cooperative group members' levels of coping strategies (study and examination-taking coping strategies) and the degree that heterogeneity (variability of study coping strategies and examination-taking coping strategies) predict cooperative groups' levels of achievement in research methodology…

  16. RNA preparation and characterization for gene expression studies

    DEFF Research Database (Denmark)

    Stangegaard, Michael

    2009-01-01

    Much information can be obtained from knowledge of the relative expression level of each gene in the transcriptome. With the current advances in technology as little as a single cell is required as starting material for gene expression experiments. The mRNA from a single cell may be linearly...

  17. Influence of the experimental design of gene expression studies on the inference of gene regulatory networks: environmental factors

    Directory of Open Access Journals (Sweden)

    Frank Emmert-Streib

    2013-02-01

    Full Text Available The inference of gene regulatory networks gained within recent years a considerable interest in the biology and biomedical community. The purpose of this paper is to investigate the influence that environmental conditions can exhibit on the inference performance of network inference algorithms. Specifically, we study five network inference methods, Aracne, BC3NET, CLR, C3NET and MRNET, and compare the results for three different conditions: (I observational gene expression data: normal environmental condition, (II interventional gene expression data: growth in rich media, (III interventional gene expression data: normal environmental condition interrupted by a positive spike-in stimulation. Overall, we find that different statistical inference methods lead to comparable, but condition-specific results. Further, our results suggest that non-steady-state data enhance the inferability of regulatory networks.

  18. Association study between methylenetetrahydrofolate reductase gene polymorphisms and Graves' disease.

    Science.gov (United States)

    Mao, Renfang; Fan, Yihui; Zuo, Lulu; Geng, Dongfeng; Meng, Fantao; Zhu, Jing; Li, Qiang; Qiao, Hong; Jin, Yan; Bai, Jing; Fu, Songbin

    2010-10-01

    5,10-Methylenetetrahydrofolate reductase (MTHFR) catalyzes the metabolism of folate and nucleotides, which are essential for DNA synthesis and methylation. It is highly polymorphic, and its variant genotypes result in lower enzymatic activity and higher plasma homocysteine. Previous studies have provided evidence that a high prevalence of MTHFR gene polymorphisms is frequently detected in patients with autoimmune disease, suggesting a novel genetic association with autoimmune disorders. However, the genetic association between MTHFR and Graves' disease (GD), one of the most common autoimmune diseases, has not been studied. Here, we designed a clinic-based case-control study including 199 GD cases and 235 healthy controls to examine the associations between three common MTHFR polymorphisms (i.e., C677T, A1298C, and G1793A) and GD. Surprisingly, logistic regression analysis shows MTHFR 677CT + TT genotypes are associated with an approximately 42% reduction in the risk of GD in women (adjusted OR = 0.58, 95% CI = 0.3-0.9), compared to the CC genotype, indicating a significant protective effect of 677CT + TT genotypes. Our result provides epidemiological evidence that MTHFR mutation (C677T) protects women from GD. The protective effect, possibly obtained by influencing DNA methylation, should be confirmed in a large number of cohorts. Copyright © 2010 John Wiley & Sons, Ltd.

  19. Factors Determining Bank Competitive Strategy: An Empirical Study on Local Development Banks (LDBS in Indonesia

    Directory of Open Access Journals (Sweden)

    Ahmad IRFAN

    2017-12-01

    Full Text Available Many studies have been investigating determinants of the company's competitive strategy. Nevertheless, there have insufficient studies conducted to investigate the determinants of competitive strategy on banking industry, particularly on Local development banks (LDBS. This study is aimed at filling in the literature. This study surveyed top executives of twenty-six local development banks in Indonesia and employed PLS approach to answer the research questions. The result shows that three groups of variables, i.e., innovation management, company resource management, and adoption of technology influence the development of competitive strategy in local development banks.

  20. The application of radiobiological study by gene chip technique

    International Nuclear Information System (INIS)

    Li Yu; Li Yao

    2002-01-01

    The responses to ionizing radiation are complex and are regulated by a number of overlapping molecular pathways. One such stress-signaling pathway involves p53, which regulates the expression of over 100 genes already identified. It is also becoming increasingly apparent that the pattern of stress gene expression has some cell type specificity. It may be possible to exploit these differences in stress gene responsiveness as molecular markers through the use of a combined informatics and functional genomic approach. The techniques of micro-array analysis potentially offer the opportunity to monitor changes in gene expression across the entire set of expressed genes in a cell or organism. It again highlights the importance of a cellular context to genotoxic stress responses; it also raises the prospect of expression profiling of cell lines, tissues, and tumors. Such profiles may have a predictive value in cancer therapy regimens, or identification of exposures to environmental toxins

  1. Empirical Studies on English Vocabulary Learning Strategies in Mainland China over the Past Two Decades

    Directory of Open Access Journals (Sweden)

    Zhongxin Dai

    2015-02-01

    Full Text Available Wen and Wang (2004 reviewed the empirical studies over the past two decades (from 1984 to 2003 on learning strategies that Chinese EFL learners used. This article, following their methodological framework, reviews about 45 empirical studies on Chinese EFL learners’ English vocabulary learning strategies, conducted by Mainland Chinese scholars over the past two decades. The review shows that more than half of the Chinese scholars are interested in questionnaire investigation of EFL learners’ preferences for vocabulary learning. The reports of the questionnaire investigations indicate that most Chinese EFL learners prefer rote learning of vocabulary to learning vocabulary in context or through language use. The experimental studies suggest that strategies-based instruction results in the learners’ vocabulary achievement. Cognitive and metacognitive strategies are the two groups of strategies that Chinese researchers show particular interest in.

  2. Strategies and Challenges for Creating an Inclusive Study Abroad Program

    Science.gov (United States)

    Link, Tanja C.

    2016-01-01

    In 2013, 14,304,467 U.S. students participated in a study abroad program related to their academic course work, marking an average increase of 5.2% to the previous year among the reporting institutions. Students with disabilities continue to be significantly underrepresented in such programs. Given the consistent popularity of studying abroad, its…

  3. Recruitment and retention strategies and methods in the HEALTHY study

    Science.gov (United States)

    HEALTHY was a 3-year middle school-based primary prevention trial to reduce modifiable risk factors for type 2 diabetes in youth. The study was conducted at seven centers across the country. This paper describes the recruitment and retention activities employed in the study. Schools and students wer...

  4. Competent Adolescent Readers' Use of Internet Reading Strategies: A Think-Aloud Study

    Science.gov (United States)

    Cho, Byeong-Young

    2014-01-01

    The purpose of this study was to investigate the type, pattern, and complexity of Internet reading strategies used by seven accomplished high school readers. Individual participants performed an academic Internet reading task with the goal of developing critical questions about their chosen controversial topic. Strategies for Internet reading were…

  5. Developing Reading Comprehension through Metacognitive Strategies: A Review of Previous Studies

    Science.gov (United States)

    Channa, Mansoor Ahmed; Nordin, Zaimuariffudin Shukri; Siming, Insaf Ali; Chandio, Ali Asgher; Koondher, Mansoor Ali

    2015-01-01

    This paper has reviewed the previous studies on metacognitive strategies based on planning, monitoring, and evaluating in order to develop reading comprehension. The main purpose of this review in metacognition, and reading domain is to help readers to enhance their capabilities and power reading through these strategies. The researchers reviewed…

  6. A Comparative Study of Reading Strategies Used by Chinese English Majors

    Science.gov (United States)

    Zhou, Xiaoqiong; Zhao, Yonggang

    2014-01-01

    In this thesis, by means of questionnaire, we made an investigation into the reading strategies used by Chinese first-year and third-year English majors. The purpose of this study attempts to identify the typical types of reading strategies among English majors in a normal university of China, and also, to examine what differences exist in…

  7. Supporting English Language Learners in Social Studies: Language-Focused Strategies

    Science.gov (United States)

    Zhang, Ying

    2017-01-01

    With the significant enrollment increase of English Language Learners (ELLs) nationwide, social studies teachers face challenges to educate these students. As a response to the literature of preparing all content teachers to work with ELLs, this article introduces three teacher-friendly language-focused strategies. These strategies help social…

  8. Enhancing Foreign Language Learning through Listening Strategies Delivered in L1: An Experimental Study

    Science.gov (United States)

    Bozorgian, Hossein; Pillay, Hitendra

    2013-01-01

    Listening used in language teaching refers to a complex process that allows us to understand spoken language. The current study, conducted in Iran with an experimental design, investigated the effectiveness of teaching listening strategies delivered in L1 (Persian) and its effect on listening comprehension in L2. Five listening strategies:…

  9. Quality Assurance Strategies of Higher Education in Iraq and Kurdistan: A Case Study

    Science.gov (United States)

    Kaghed, Nabeel; Dezaye, Ahmed

    2009-01-01

    This paper reports on two different strategies that have been implemented in Iraq to improve quality assurance in the higher education sector in Iraq. One strategy has been developed by the Ministry of Higher Education and Scientific Research in Baghdad. It involved conducting a pilot study at the University of Babylon. This pilot included…

  10. Achievement Strategies during University Studies Predict Early Career Burnout and Engagement

    Science.gov (United States)

    Salmela-Aro, Katariina; Tolvanen, Asko; Nurmi, Jari-Erik

    2009-01-01

    To examine whether individuals' achievement strategies measured during university studies would have an impact on work burnout and work engagement measured 10, 14 and 17 years later, 292 university students completed the SAQ strategy questionnaire three times while at university, and the work burnout inventory three times and work engagement…

  11. EFL Learners' Self-Perceived Strategy Use across Various Intelligence Types: A Case Study

    Science.gov (United States)

    Tahriri, Abdorreza; Divsar, Hoda

    2011-01-01

    Increasing attention paid to learner-centered pedagogy in recent years has highlighted the examination of intelligence and language learning strategies (LLSs) among others. This study explores EFL learners' perceived use of language learning strategies across various intelligence types as reflected in Gardner's 1983 Multiple Intelligences Theory.…

  12. A Qualitative Study into L2 Writing Strategies of University Students

    Science.gov (United States)

    Raoofi, Saeid; Chan, Swee Heng; Mukundan, Jayakaran; Rashid, Sabariah Md

    2014-01-01

    This study reports on an investigation into writing strategies of Malaysian university students learning English as a second language. Qualitative data were collected from 21 undergraduate university students aged 19 to 21. The students interviewed reported using a variety of writing strategies. It was also found that all of the participants…

  13. A Cross-Cultural Validation Study of the "Language Learning Strategy Scale" and Its Applications.

    Science.gov (United States)

    Benjamin, Jane; Chen, Yih-Lan E.; Walker, Brenda

    The underlying factor structure of the Language Learning Strategy Scale (LLSS) (Y. Chen, 2001) was examined to determine its consistency across 2 distinct cultures. Variables that affected students' language learning were also identified. The validation study for the LLSS suggested a three-factor model of functional strategies, deep-processing…

  14. Learning and examination strategies: a case study of students of a ...

    African Journals Online (AJOL)

    Journal of Business Research ... Abstract. This study examines the learning strategies adopted by some students of a public university in Ghana, why they use those strategies and how they approach examinations. ... Each focus group consisted of eight students who were selected based on their academic performances.

  15. How Does Studying Abroad Change Chinese Students' Choices of Reading Strategies

    Science.gov (United States)

    Liu, Jie

    2016-01-01

    This study explores how a change of learning environment from China to the United Kingdom affects Chinese international master's students' use of strategies in academic reading. Think aloud was used at two time points in one academic year among 15 participants. To capture the complexity of the academic reading, reading strategies were categorized…

  16. Learning and Studying Strategies Used by General Chemistry Students with Different Affective Characteristics

    Science.gov (United States)

    Chan, Julia Y. K.; Bauer, Christopher F.

    2016-01-01

    Students in general chemistry were partitioned into three groups by cluster analysis of six affective characteristics (emotional satisfaction, intellectual accessibility, chemistry self-concept, math self-concept, self-efficacy, and test anxiety). The at-home study strategies for exam preparation and in-class learning strategies differed among the…

  17. Cross-Cultural Pedagogy: Practical Strategies for a Successful Interprofessional Study Abroad Course

    Science.gov (United States)

    Bai, Jieru; Larimer, Susan; Riner, Mary Beth

    2016-01-01

    This article discusses some practical strategies for designing and implementing a cross-cultural interprofessional study abroad course, including pre-departure preparation, facilitating small groups with local students, establishing a weekly theme, utilizing role-play and reflective assignments, and implementing meaningful evaluation strategies.…

  18. Comparing Two Story-Writing Mnemonic Strategies: A Randomized Control Trial Study

    Science.gov (United States)

    Dunn, Michael

    2013-01-01

    Educators often use mnemonic strategies as a prime method to help children who struggle with writing. This study analyzed 12 fourth-grade students' stories during their participation in one of three groups. The first group learned the Ask, Reflect, Text (ART) mnemonic strategy with art media in the pre-writing/planning phase. The second group used…

  19. Flooding impairs Fe uptake and distribution in Citrus due to the strong down-regulation of genes involved in Strategy I responses to Fe deficiency in roots.

    Directory of Open Access Journals (Sweden)

    Mary-Rus Martínez-Cuenca

    Full Text Available This work determines the ffects of long-term anoxia conditions--21 days--on Strategy I responses to iron (Fe deficiency in Citrus and its impact on Fe uptake and distribution. The study was carried out in Citrus aurantium L. seedlings grown under flooding conditions (S and in both the presence (+Fe and absence of Fe (-Fe in nutritive solution. The results revealed a strong down-regulation (more than 65% of genes HA1 and FRO2 coding for enzymes proton-ATPase and Ferric-Chelate Reductase (FC-R, respectively, in -FeS plants when compared with -Fe ones. H+-extrusion and FC-R activity analyses confirmed the genetic results, indicating that flooding stress markedly repressed acidification and reduction responses to Fe deficiency (3.1- and 2.0-fold, respectively. Waterlogging reduced by half Fe concentration in +FeS roots, which led to 30% up-regulation of Fe transporter IRT1, although this effect was unable to improve Fe absorption. Consequently, flooding inhibited 57Fe uptake in +Fe and -Fe seedlings (29.8 and 66.2%, respectively and 57Fe distribution to aerial part (30.6 and 72.3%, respectively. This evidences that the synergistic action of both enzymes H+-ATPase and FC-R is the preferential regulator of the Fe acquisition system under flooding conditions and, hence, their inactivation implies a limiting factor of citrus in their Fe-deficiency tolerance in waterlogged soils.

  20. Real-time monitoring of circadian clock oscillations in primary cultures of mammalian cells using Tol2 transposon-mediated gene transfer strategy

    Directory of Open Access Journals (Sweden)

    Yamanaka Iori

    2010-01-01

    Full Text Available Abstract Background The circadian rhythm in mammals is orchestrated by a central pacemaker in the brain, but most peripheral tissues contain their own intrinsic circadian oscillators. The circadian rhythm is a fundamental biological system in mammals involved in the regulation of various physiological functions such as behavior, cardiovascular functions and energy metabolism. Thus, it is important to understand the correlation between circadian oscillator and physiological functions in peripheral tissues. However, it is still difficult to investigate the molecular oscillator in primary culture cells. Results In this study, we used a novel Tol2 transposon based Dbp promoter or Bmal1 promoter driven luciferase reporter vector system to detect and analyze the intrinsic molecular oscillator in primary culture cells (mouse embryonic fibroblasts, fetal bovine heart endothelial cells and rat astrocytes. The results showed circadian molecular oscillations in all examined primary culture cells. Moreover, the phase relationship between Dbp promoter driven and Bmal1 promoter driven molecular rhythms were almost anti-phase, which suggested that these reporters appropriately read-out the intrinsic cellular circadian clock. Conclusions Our results indicate that gene transfer strategy using the Tol2 transposon system of a useful and safe non-viral vector is a powerful tool for investigating circadian rhythms in peripheral tissues.