WorldWideScience

Sample records for artificial gene fusion

  1. Genetically Controlled Fusion, Exocytosis and Fission of Artificial Vesicles

    DEFF Research Database (Denmark)

    Bönzli, Eva; Hadorn, Maik; De Lucrezia, Davide;

    Artificial vesicles represent ideal candidates as a model for artificial cells. It was shown that artificial genetic programs and the required cellular machinery (cell-free expression systems) can be incorporated into vesicles and allow the synthesis of proteins. Vesicles were shown to fuse...... vesicles in the presence of peptides. This project may present a step towards personalized drug delivery. Specific drugs or prodrugs enclosed into vesicles may be released upon an external signal related to a disease, e.g. a tumor, to activate gene expression and synthesis of fusion peptides to induce...

  2. DNA fusion gene vaccines

    DEFF Research Database (Denmark)

    Holst, Peter Johannes; Bassi, Maria Rosaria; Thomsen, Allan Randrup;

    2010-01-01

    DNA vaccines are versatile and safe, but limited immunogenicity has prevented their use in the clinical setting. Experimentally, immunogenicity may be enhanced by the use of new delivery technologies, by coadministration of cytokines and pathogen-associated molecular patterns, or by fusion...... of antigens into molecular domains that enhance antigen presentation. More specifically, the immunogenicity of DNA vaccines may benefit from increased protein synthesis, increased T-cell help and MHC class I presentation, and the addition of a range of specific cytokines and pathogen-associated molecular...... with viral-vectored vaccines, various synergistic components may need to be incorporated into DNA vaccines. From the perspective of the future clinical use of DNA vaccines, it has been suggested that antigen presentation should be improved and cytokine coadministration attempted. However, even...

  3. Multiple image sensor data fusion through artificial neural networks

    Science.gov (United States)

    With multisensor data fusion technology, the data from multiple sensors are fused in order to make a more accurate estimation of the environment through measurement, processing and analysis. Artificial neural networks are the computational models that mimic biological neural networks. With high per...

  4. Characterization of fusion genes and the significantly expressed fusion isoforms in breast cancer by hybrid sequencing

    OpenAIRE

    Weirather, Jason L.; Afshar, Pegah Tootoonchi; Clark, Tyson A.; Tseng, Elizabeth; Powers, Linda S.; Underwood, Jason G; Zabner, Joseph; Korlach, Jonas; Wong, Wing Hung; Au, Kin Fai

    2015-01-01

    We developed an innovative hybrid sequencing approach, IDP-fusion, to detect fusion genes, determine fusion sites and identify and quantify fusion isoforms. IDP-fusion is the first method to study gene fusion events by integrating Third Generation Sequencing long reads and Second Generation Sequencing short reads. We applied IDP-fusion to PacBio data and Illumina data from the MCF-7 breast cancer cells. Compared with the existing tools, IDP-fusion detects fusion genes at higher precision and ...

  5. Artificial Bee Colony and Its Application for Image Fusion

    Directory of Open Access Journals (Sweden)

    Prabhat Kumar Sharma

    2012-10-01

    Full Text Available Artificial Bee Colony (ABC is one of the latest swarm algorithm based on the intelligent foraging behavior of honey bees introduced in the year 2005 by Karaboga since then it has been used for optimization of various solutions. And it is recently introduced for processing and analysis of images such as segmentation, object recognition and image retrieval. Fusing images from a vast collection of different images has become one of the interesting challenges and has drawn the attention of researchers towards the development of fusion techniques. In this paper, we have proposed the usage of ABC for optimal fusion of multi-temporal images and studied the effect of variation in the source area.

  6. Assessment of fusion gene status in sarcomas using a custom made fusion gene microarray.

    Directory of Open Access Journals (Sweden)

    Marthe Løvf

    Full Text Available Sarcomas are relatively rare malignancies and include a large number of histological subgroups. Based on morphology alone, the differential diagnoses of sarcoma subtypes can be challenging, but the identification of specific fusion genes aids correct diagnostication. The presence of individual fusion products are routinely investigated in Pathology labs. However, the methods used are time-consuming and based on prior knowledge about the expected fusion gene and often the most likely break-point. In this study, 16 sarcoma samples, representing seven different sarcoma subtypes with known fusion gene status from a diagnostic setting, were investigated using a fusion gene microarray. The microarray was designed to detect all possible exon-exon breakpoints between all known fusion genes in a single analysis. An automated scoring of the microarray data from the 38 known sarcoma-related fusion genes identified the correct fusion gene among the top-three hits in 11 of the samples. The analytical sensitivity may be further optimised, but we conclude that a sarcoma-fusion gene microarray is suitable as a time-saving screening tool to identify the majority of the correct fusion genes.

  7. ETS fusion genes in prostate cancer.

    Science.gov (United States)

    Gasi Tandefelt, Delila; Boormans, Joost; Hermans, Karin; Trapman, Jan

    2014-06-01

    Prostate cancer is very common in elderly men in developed countries. Unravelling the molecular and biological processes that contribute to tumor development and progressive growth, including its heterogeneity, is a challenging task. The fusion of the genes ERG and TMPRSS2 is the most frequent genomic alteration in prostate cancer. ERG is an oncogene that encodes a member of the family of ETS transcription factors. At lower frequency, other members of this gene family are also rearranged and overexpressed in prostate cancer. TMPRSS2 is an androgen-regulated gene that is preferentially expressed in the prostate. Most of the less frequent ETS fusion partners are also androgen-regulated and prostate-specific. During the last few years, novel concepts of the process of gene fusion have emerged, and initial experimental results explaining the function of the ETS genes ERG and ETV1 in prostate cancer have been published. In this review, we focus on the most relevant ETS gene fusions and summarize the current knowledge of the role of ETS transcription factors in prostate cancer. Finally, we discuss the clinical relevance of TMRPSS2-ERG and other ETS gene fusions in prostate cancer.

  8. Comparison of SUMO fusion technology with traditional gene fusion systems: Enhanced expression and solubility with SUMO

    OpenAIRE

    Marblestone, Jeffrey G; Edavettal, Suzanne C.; Lim, Yiting; Lim, Peter; Zuo, Xun; Butt, Tauseef R.

    2006-01-01

    Despite the availability of numerous gene fusion systems, recombinant protein expression in Escherichia coli remains difficult. Establishing the best fusion partner for difficult-to-express proteins remains empirical. To determine which fusion tags are best suited for difficult-to-express proteins, a comparative analysis of the newly described SUMO fusion system with a variety of commonly used fusion systems was completed. For this study, three model proteins, enhanced green florescent protei...

  9. The Structural Characterization of Tumor Fusion Genes and Proteins

    OpenAIRE

    Wang, Dandan; Li, Daixi; Qin, Guangrong; Zhang, Wen; Ouyang, Jian; Zhang, Menghuan; Xie, Lu

    2015-01-01

    Chromosomal translocation, which generates fusion proteins in blood tumor or solid tumor, is considered as one of the major causes leading to cancer. Recent studies suggested that the disordered fragments in a fusion protein might contribute to its carcinogenicity. Here, we investigated the sequence feature near the breakpoints in the fusion partner genes, the structure features of breakpoints in fusion proteins, and the posttranslational modification preference in the fusion proteins. Result...

  10. Molecular pathways: targeting ETS gene fusions in cancer.

    Science.gov (United States)

    Feng, Felix Y; Brenner, J Chad; Hussain, Maha; Chinnaiyan, Arul M

    2014-09-01

    Rearrangements, or gene fusions, involving the ETS family of transcription factors are common driving events in both prostate cancer and Ewing sarcoma. These rearrangements result in pathogenic expression of the ETS genes and trigger activation of transcriptional programs enriched for invasion and other oncogenic features. Although ETS gene fusions represent intriguing therapeutic targets, transcription factors, such as those comprising the ETS family, have been notoriously difficult to target. Recently, preclinical studies have demonstrated an association between ETS gene fusions and components of the DNA damage response pathway, such as PARP1, the catalytic subunit of DNA protein kinase (DNAPK), and histone deactylase 1 (HDAC1), and have suggested that ETS fusions may confer sensitivity to inhibitors of these DNA repair proteins. In this review, we discuss the role of ETS fusions in cancer, the preclinical rationale for targeting ETS fusions with inhibitors of PARP1, DNAPK, and HDAC1, as well as ongoing clinical trials targeting ETS gene fusions.

  11. The Structural Characterization of Tumor Fusion Genes and Proteins

    Directory of Open Access Journals (Sweden)

    Dandan Wang

    2015-01-01

    Full Text Available Chromosomal translocation, which generates fusion proteins in blood tumor or solid tumor, is considered as one of the major causes leading to cancer. Recent studies suggested that the disordered fragments in a fusion protein might contribute to its carcinogenicity. Here, we investigated the sequence feature near the breakpoints in the fusion partner genes, the structure features of breakpoints in fusion proteins, and the posttranslational modification preference in the fusion proteins. Results show that the breakpoints in the fusion partner genes have both sequence preference and structural preference. At the sequence level, nucleotide combination AG is preferred before the breakpoint and GG is preferred at the breakpoint. At the structural level, the breakpoints in the fusion proteins prefer to be located in the disordered regions. Further analysis suggests the phosphorylation sites at serine, threonine, and the methylation sites at arginine are enriched in disordered regions of the fusion proteins. Using EML4-ALK as an example, we further explained how the fusion protein leads to the protein disorder and contributes to its carcinogenicity. The sequence and structural features of the fusion proteins may help the scientific community to predict novel breakpoints in fusion genes and better understand the structure and function of fusion proteins.

  12. FusionQ: a novel approach for gene fusion detection and quantification from paired-end RNA-Seq

    OpenAIRE

    Liu, Chenglin; Ma, Jinwen; Chang, ChungChe (Jeff); Zhou, Xiaobo

    2013-01-01

    Background Gene fusions, which result from abnormal chromosome rearrangements, are a pathogenic factor in cancer development. The emerging RNA-Seq technology enables us to detect gene fusions and profile their features. Results In this paper, we proposed a novel fusion detection tool, FusionQ, based on paired-end RNA-Seq data. This tool can detect gene fusions, construct the structures of chimerical transcripts, and estimate their abundances. To confirm the read alignment on both sides of a f...

  13. A Screening Method for the ALK Fusion Gene in NSCLC

    OpenAIRE

    Yoshiko eMurakami; Tetsuya eMitsudomi; Yasushi eYatabe

    2012-01-01

    Lung cancer research has recently made significant progress in understanding the molecular pathogenesis of lung cancer and in developing treatments for it. Such achievements are directly utilized in clinical practice. Indeed, the echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase (ALK) fusion gene was first described in non-small cell lung cancer in 2007, and a molecularly targeted drug against the fusion was approved in 2011. However, lung cancer with the ALK fusion ...

  14. RET fusion gene: translation to personalized lung cancer therapy.

    Science.gov (United States)

    Kohno, Takashi; Tsuta, Koji; Tsuchihara, Katsuya; Nakaoku, Takashi; Yoh, Kiyotaka; Goto, Koichi

    2013-11-01

    Development of lung adenocarcinoma (LADC), the most frequent histological type of lung cancer, depends in many cases on the activation of "driver" oncogenes such as KRAS, epidermal growth factor receptor (EGFR), and anaplastic lymphoma kinase (ALK). Inhibitors that target the EGFR and ALK tyrosine kinases show therapeutic effects against LADCs containing EGFR gene mutations and ALK gene fusions, respectively. Recently, we and others identified the RET fusion gene as a new targetable driver gene in LADC. The RET fusions occur in 1-2% of LADCs. Existing US Food and Drug Administration-approved inhibitors of RET tyrosine kinase show promising therapeutic effects both in vitro and in vivo, as well as in a few patients. Clinical trials are underway to investigate the therapeutic effects of RET tyrosine kinase inhibitors, such as vandetanib (ZD6474) and cabozantinib (XL184), in patients with RET fusion-positive non-small-cell lung cancer. PMID:23991695

  15. Data fusion with artificial neural networks (ANN) for classification of earth surface from microwave satellite measurements

    Science.gov (United States)

    Lure, Y. M. Fleming; Grody, Norman C.; Chiou, Y. S. Peter; Yeh, H. Y. Michael

    1993-01-01

    A data fusion system with artificial neural networks (ANN) is used for fast and accurate classification of five earth surface conditions and surface changes, based on seven SSMI multichannel microwave satellite measurements. The measurements include brightness temperatures at 19, 22, 37, and 85 GHz at both H and V polarizations (only V at 22 GHz). The seven channel measurements are processed through a convolution computation such that all measurements are located at same grid. Five surface classes including non-scattering surface, precipitation over land, over ocean, snow, and desert are identified from ground-truth observations. The system processes sensory data in three consecutive phases: (1) pre-processing to extract feature vectors and enhance separability among detected classes; (2) preliminary classification of Earth surface patterns using two separate and parallely acting classifiers: back-propagation neural network and binary decision tree classifiers; and (3) data fusion of results from preliminary classifiers to obtain the optimal performance in overall classification. Both the binary decision tree classifier and the fusion processing centers are implemented by neural network architectures. The fusion system configuration is a hierarchical neural network architecture, in which each functional neural net will handle different processing phases in a pipelined fashion. There is a total of around 13,500 samples for this analysis, of which 4 percent are used as the training set and 96 percent as the testing set. After training, this classification system is able to bring up the detection accuracy to 94 percent compared with 88 percent for back-propagation artificial neural networks and 80 percent for binary decision tree classifiers. The neural network data fusion classification is currently under progress to be integrated in an image processing system at NOAA and to be implemented in a prototype of a massively parallel and dynamically reconfigurable Modular

  16. [The progress of TMPRSS2-ETS gene fusions and their mechanism in prostate cancer].

    Science.gov (United States)

    Guo, Xiao-Qiang; Gui, Yao-Ting; Cai, Zhi-Ming

    2011-02-01

    The gene fusions between transmembrane protease serine 2 (TMPRSS2) and E26 (ETS) transcription factors are present in over 50% of patients with prostate cancer. TMPRSS2-ERG is the most common gene fusion type. The ERG overexpression induced by TMPRSS2-ERG gene fusion contributes to the development of prostate cancer. Both androgen receptor binding and genotoxic stress induce chromosomal proximity and TMPRSS2-ETS gene fusions. TMPRSS2-ERG gene fusion functions as a biomarker for prostate cancer, which can be easily detected in urine. This review focuses on the characteristics, oncogenic and rearranged mechanism, and clinical application of TMPRSS2-ETS gene fusions.

  17. Multimodality imaging of reporter gene expression using a novel fusion vector in living cells and animals

    Energy Technology Data Exchange (ETDEWEB)

    Gambhir, Sanjiv; Pritha, Ray

    2015-07-14

    Novel double and triple fusion reporter gene constructs harboring distinct imagable reporter genes are provided, as well as applications for the use of such double and triple fusion constructs in living cells and in living animals using distinct imaging technologies.

  18. Multimodality imaging of reporter gene expression using a novel fusion vector in living cells and animals

    Science.gov (United States)

    Gambhir; Sanjiv , Pritha; Ray

    2009-04-28

    Novel double and triple fusion reporter gene constructs harboring distinct imageable reporter genes are provided, as well as applications for the use of such double and triple fusion constructs in living cells and in living animals using distinct imaging technologies.

  19. Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samples

    Directory of Open Access Journals (Sweden)

    Nacu Serban

    2011-01-01

    Full Text Available Abstract Background Readthrough fusions across adjacent genes in the genome, or transcription-induced chimeras (TICs, have been estimated using expressed sequence tag (EST libraries to involve 4-6% of all genes. Deep transcriptional sequencing (RNA-Seq now makes it possible to study the occurrence and expression levels of TICs in individual samples across the genome. Methods We performed single-end RNA-Seq on three human prostate adenocarcinoma samples and their corresponding normal tissues, as well as brain and universal reference samples. We developed two bioinformatics methods to specifically identify TIC events: a targeted alignment method using artificial exon-exon junctions within 200,000 bp from adjacent genes, and genomic alignment allowing splicing within individual reads. We performed further experimental verification and characterization of selected TIC and fusion events using quantitative RT-PCR and comparative genomic hybridization microarrays. Results Targeted alignment against artificial exon-exon junctions yielded 339 distinct TIC events, including 32 gene pairs with multiple isoforms. The false discovery rate was estimated to be 1.5%. Spliced alignment to the genome was less sensitive, finding only 18% of those found by targeted alignment in 33-nt reads and 59% of those in 50-nt reads. However, spliced alignment revealed 30 cases of TICs with intervening exons, in addition to distant inversions, scrambled genes, and translocations. Our findings increase the catalog of observed TIC gene pairs by 66%. We verified 6 of 6 predicted TICs in all prostate samples, and 2 of 5 predicted novel distant gene fusions, both private events among 54 prostate tumor samples tested. Expression of TICs correlates with that of the upstream gene, which can explain the prostate-specific pattern of some TIC events and the restriction of the SLC45A3-ELK4 e4-e2 TIC to ERG-negative prostate samples, as confirmed in 20 matched prostate tumor and normal

  20. Gene Prioritization by Compressive Data Fusion and Chaining.

    Directory of Open Access Journals (Sweden)

    Marinka Žitnik

    2015-10-01

    Full Text Available Data integration procedures combine heterogeneous data sets into predictive models, but they are limited to data explicitly related to the target object type, such as genes. Collage is a new data fusion approach to gene prioritization. It considers data sets of various association levels with the prediction task, utilizes collective matrix factorization to compress the data, and chaining to relate different object types contained in a data compendium. Collage prioritizes genes based on their similarity to several seed genes. We tested Collage by prioritizing bacterial response genes in Dictyostelium as a novel model system for prokaryote-eukaryote interactions. Using 4 seed genes and 14 data sets, only one of which was directly related to the bacterial response, Collage proposed 8 candidate genes that were readily validated as necessary for the response of Dictyostelium to Gram-negative bacteria. These findings establish Collage as a method for inferring biological knowledge from the integration of heterogeneous and coarsely related data sets.

  1. Recurrent gene fusions in prostate cancer: their clinical implications and uses

    NARCIS (Netherlands)

    Hessels, D.; Schalken, J.A.

    2013-01-01

    Gene fusions, resulting from chromosomal rearrangements, have been attributed to leukaemias and soft tissue sarcomas. The recent discovery of a recurrent gene fusion TMPRSS2-ERG in approximately half of the prostate cancers tested indicates that gene fusions also play a role in the onset of common e

  2. Fusion of Biogeography based optimization and Artificial bee colony for identification of Natural Terrain Features

    Directory of Open Access Journals (Sweden)

    Priya Arora

    2012-10-01

    Full Text Available Swarm Intelligence techniques expedite the configuration and collimation of the remarkable ability of group members to reason and learn in an environment of contingency and corrigendum from their peers by sharing information. This paper introduces a novel approach of fusion of two intelligent techniques generally to augment the performance of a single intelligent technique by means of information sharing. Biogeography-based optimization (BBO is a recently developed heuristic algorithm, which proves to be a strong entrant in swarm intelligence with the encouraging and consistent performance. But, as BBO lacks inbuilt property of clustering, its behavior can be replaced with the honey bees of artificial bee colony (ABC, a new swarm intelligent technique. These two methods can be combined to create a new method which is easy to implement and gives more optimized results than the results when BBO is used. We have successfully applied this fusion of techniques for classifying diversified land cover areas in a multispectral remote sensing satellite image. The results illustrate that the proposed approach is very efficient than BBO and highly accurate land cover features can be extracted by using this approach.

  3. Anterior Lumbar Intervertebrai Fusion with Artificial Bone in Place of Autologous Bone

    Institute of Scientific and Technical Information of China (English)

    徐卫国; 陈安民; 冯旭; 印卫锋

    2003-01-01

    The feasibility of anterior lumbar intervertebral fusion with artificial bone in place of au-togenous bone was investigated. Porous hydroxyapatite(HA)/ZrO2 ceramics loading bone morpho-genetic protein (BMP) were implanted after removal of lumbar vertebral disc in rabbits. The adja-cent intervertebral discs were also removed by the same way and autogenous illic bone was implan-ted. SEM observation and biomechanical test were carried out. Compound bone had a bit lower os-teoinductive activity than autogenous bone by SEM(Osteoindutive activity of artificial bone in 12weeks was the same as that of autogenous bone in 9 weeks). Biomechanical test revealed that com-pound bone had lower anti-pull strength than autogenous bone (P<0. 001), but there was no sig-nificant difference in anti-pull strength between compound bone at 12th week and autogenous boneat 9th week (P>0.05). It was concluded that compound bone could be applied for anterior spinalfusion, especially for those patients who can't use autogenous bone.

  4. A Screening Method for the ALK Fusion Gene in NSCLC.

    Science.gov (United States)

    Murakami, Yoshiko; Mitsudomi, Tetsuya; Yatabe, Yasushi

    2012-01-01

    Lung cancer research has recently made significant progress in understanding the molecular pathogenesis of lung cancer and in developing treatments for it. Such achievements are directly utilized in clinical practice. Indeed, the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (ALK) fusion gene was first described in non-small cell lung cancer in 2007, and a molecularly targeted drug against the fusion was approved in 2011. However, lung cancer with the ALK fusion constitutes only a small fraction of lung cancers; therefore, efficient patient selection is crucial for successful treatment using the ALK inhibitor. Currently, RT-PCR, fluorescent in situ hybridization (FISH), and immunohistochemistry are commonly used to detect the ALK fusion. Although FISH is currently the gold standard technique, there are no perfect methods for detecting these genetic alterations. In this article, we discuss the advantages and disadvantages of each method and the possible criteria for selecting patients who are more likely to have the ALK fusion. If we can successfully screen patients, then ALK inhibitor treatment will be the best example of personalized therapy in terms of selecting patients with an uncommon genotype from a larger group with the same tumor phenotype. In other words, the personalized therapy may offer a new challenge for current clinical oncology. PMID:22655265

  5. Nucleoporin Gene Fusions and Hematopoietic Malignancies

    Directory of Open Access Journals (Sweden)

    Birthe Fahrenkrog

    2014-01-01

    Full Text Available Nuclear pore complexes (NPCs are the sole gateways between the nucleus and the cytoplasm of eukaryotic cells and they mediate all macromolecular trafficking between these cellular compartments. Nucleocytoplasmic transport is highly selective and precisely regulated and as such an important aspect of normal cellular function. Defects in this process or in its machinery have been linked to various human diseases, including cancer. Nucleoporins, which are about 30 proteins that built up NPCs, are critical players in nucleocytoplasmic transport and have also been shown to be key players in numerous other cellular processes, such as cell cycle control and gene expression regulation. This review will focus on the three nucleoporins Nup98, Nup214, and Nup358. Common to them is their significance in nucleocytoplasmic transport, their multiple other functions, and being targets for chromosomal translocations that lead to haematopoietic malignancies, in particular acute myeloid leukaemia. The underlying molecular mechanisms of nucleoporin-associated leukaemias are only poorly understood but share some characteristics and are distinguished by their poor prognosis and therapy outcome.

  6. Molecular Principles of Gene Fusion Mediated Rewiring of Protein Interaction Networks in Cancer.

    Science.gov (United States)

    Latysheva, Natasha S; Oates, Matt E; Maddox, Louis; Flock, Tilman; Gough, Julian; Buljan, Marija; Weatheritt, Robert J; Babu, M Madan

    2016-08-18

    Gene fusions are common cancer-causing mutations, but the molecular principles by which fusion protein products affect interaction networks and cause disease are not well understood. Here, we perform an integrative analysis of the structural, interactomic, and regulatory properties of thousands of putative fusion proteins. We demonstrate that genes that form fusions (i.e., parent genes) tend to be highly connected hub genes, whose protein products are enriched in structured and disordered interaction-mediating features. Fusion often results in the loss of these parental features and the depletion of regulatory sites such as post-translational modifications. Fusion products disproportionately connect proteins that did not previously interact in the protein interaction network. In this manner, fusion products can escape cellular regulation and constitutively rewire protein interaction networks. We suggest that the deregulation of central, interaction-prone proteins may represent a widespread mechanism by which fusion proteins alter the topology of cellular signaling pathways and promote cancer. PMID:27540857

  7. Biomechanics of Artificial Disc Replacements Adjacent to a 2-Level Fusion in 4-Level Hybrid Constructs: An In Vitro Investigation

    OpenAIRE

    Liao, Zhenhua; Fogel, Guy R.; Wei, Na; Gu, Hongsheng; Liu, Weiqiang

    2015-01-01

    Background The ideal procedure for multilevel cervical degenerative disc diseases remains controversial. Recent studies on hybrid surgery combining anterior cervical discectomy and fusion (ACDF) and artificial cervical disc replacement (ACDR) for 2-level and 3-level constructs have been reported in the literature. The purpose of this study was to estimate the biomechanics of 3 kinds of 4-level hybrid constructs, which are more likely to be used clinically compared to 4-level arthrodesis. Mate...

  8. Discovering and understanding oncogenic gene fusions through data intensive computational approaches.

    Science.gov (United States)

    Latysheva, Natasha S; Babu, M Madan

    2016-06-01

    Although gene fusions have been recognized as important drivers of cancer for decades, our understanding of the prevalence and function of gene fusions has been revolutionized by the rise of next-generation sequencing, advances in bioinformatics theory and an increasing capacity for large-scale computational biology. The computational work on gene fusions has been vastly diverse, and the present state of the literature is fragmented. It will be fruitful to merge three camps of gene fusion bioinformatics that appear to rarely cross over: (i) data-intensive computational work characterizing the molecular biology of gene fusions; (ii) development research on fusion detection tools, candidate fusion prioritization algorithms and dedicated fusion databases and (iii) clinical research that seeks to either therapeutically target fusion transcripts and proteins or leverages advances in detection tools to perform large-scale surveys of gene fusion landscapes in specific cancer types. In this review, we unify these different-yet highly complementary and symbiotic-approaches with the view that increased synergy will catalyze advancements in gene fusion identification, characterization and significance evaluation. PMID:27105842

  9. Biomechanics of Artificial Disc Replacements Adjacent to a 2-Level Fusion in 4-Level Hybrid Constructs: An In Vitro Investigation.

    Science.gov (United States)

    Liao, Zhenhua; Fogel, Guy R; Wei, Na; Gu, Hongsheng; Liu, Weiqiang

    2015-01-01

    BACKGROUND The ideal procedure for multilevel cervical degenerative disc diseases remains controversial. Recent studies on hybrid surgery combining anterior cervical discectomy and fusion (ACDF) and artificial cervical disc replacement (ACDR) for 2-level and 3-level constructs have been reported in the literature. The purpose of this study was to estimate the biomechanics of 3 kinds of 4-level hybrid constructs, which are more likely to be used clinically compared to 4-level arthrodesis. MATERIAL AND METHODS Eighteen human cadaveric spines (C2-T1) were evaluated in different testing conditions: intact, with 3 kinds of 4-level hybrid constructs (hybrid C3-4 ACDR+C4-6 ACDF+C6-7ACDR; hybrid C3-5ACDF+C5-6ACDR+C6-7ACDR; hybrid C3-4ACDR+C4-5ACDR+C5-7ACDF); and 4-level fusion. RESULTS Four-level fusion resulted in significant decrease in the C3-C7 ROM compared with the intact spine. The 3 different 4-level hybrid treatment groups caused only slight change at the instrumented levels compared to intact except for flexion. At the adjacent levels, 4-level fusion resulted in significant increase of contribution of both upper and lower adjacent levels. However, for the 3 hybrid constructs, significant changes of motion increase far lower than 4P at adjacent levels were only noted in partial loading conditions. No destabilizing effect or hypermobility were observed in any 4-level hybrid construct. CONCLUSIONS Four-level fusion significantly eliminated motion within the construct and increased motion at the adjacent segments. For all 3 different 4-level hybrid constructs, ACDR normalized motion of the index segment and adjacent segments with no significant hypermobility. Compared with the 4-level ACDF condition, the artificial discs in 4-level hybrid constructs had biomechanical advantages compared to fusion in normalizing adjacent level motion. PMID:26694835

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

    International Nuclear Information System (INIS)

    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

  11. Protein functional links in Trypanosoma brucei, identified by gene fusion analysis

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    Trimpalis Philip

    2011-07-01

    Full Text Available Abstract Background Domain or gene fusion analysis is a bioinformatics method for detecting gene fusions in one organism by comparing its genome to that of other organisms. The occurrence of gene fusions suggests that the two original genes that participated in the fusion are functionally linked, i.e. their gene products interact either as part of a multi-subunit protein complex, or in a metabolic pathway. Gene fusion analysis has been used to identify protein functional links in prokaryotes as well as in eukaryotic model organisms, such as yeast and Drosophila. Results In this study we have extended this approach to include a number of recently sequenced protists, four of which are pathogenic, to identify fusion linked proteins in Trypanosoma brucei, the causative agent of African sleeping sickness. We have also examined the evolution of the gene fusion events identified, to determine whether they can be attributed to fusion or fission, by looking at the conservation of the fused genes and of the individual component genes across the major eukaryotic and prokaryotic lineages. We find relatively limited occurrence of gene fusions/fissions within the protist lineages examined. Our results point to two trypanosome-specific gene fissions, which have recently been experimentally confirmed, one fusion involving proteins involved in the same metabolic pathway, as well as two novel putative functional links between fusion-linked protein pairs. Conclusions This is the first study of protein functional links in T. brucei identified by gene fusion analysis. We have used strict thresholds and only discuss results which are highly likely to be genuine and which either have already been or can be experimentally verified. We discuss the possible impact of the identification of these novel putative protein-protein interactions, to the development of new trypanosome therapeutic drugs.

  12. Use of artificial genomes in assessing methods for atypical gene detection.

    Directory of Open Access Journals (Sweden)

    Rajeev K Azad

    2005-11-01

    Full Text Available Parametric methods for identifying laterally transferred genes exploit the directional mutational biases unique to each genome. Yet the development of new, more robust methods--as well as the evaluation and proper implementation of existing methods--relies on an arbitrary assessment of performance using real genomes, where the evolutionary histories of genes are not known. We have used the framework of a generalized hidden Markov model to create artificial genomes modeled after genuine genomes. To model a genome, "core" genes--those displaying patterns of mutational biases shared among large numbers of genes--are identified by a novel gene clustering approach based on the Akaike information criterion. Gene models derived from multiple "core" gene clusters are used to generate an artificial genome that models the properties of a genuine genome. Chimeric artificial genomes--representing those having experienced lateral gene transfer--were created by combining genes from multiple artificial genomes, and the performance of the parametric methods for identifying "atypical" genes was assessed directly. We found that a hidden Markov model that included multiple gene models, each trained on sets of genes representing the range of genotypic variability within a genome, could produce artificial genomes that mimicked the properties of genuine genomes. Moreover, different methods for detecting foreign genes performed differently--i.e., they had different sets of strengths and weaknesses--when identifying atypical genes within chimeric artificial genomes.

  13. Use of Artificial Genomes in Assessing Methods for Atypical Gene Detection.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available Parametric methods for identifying laterally transferred genes exploit the directional mutational biases unique to each genome. Yet the development of new, more robust methods-as well as the evaluation and proper implementation of existing methods-relies on an arbitrary assessment of performance using real genomes, where the evolutionary histories of genes are not known. We have used the framework of a generalized hidden Markov model to create artificial genomes modeled after genuine genomes. To model a genome, "core" genes-those displaying patterns of mutational biases shared among large numbers of genes-are identified by a novel gene clustering approach based on the Akaike information criterion. Gene models derived from multiple "core" gene clusters are used to generate an artificial genome that models the properties of a genuine genome. Chimeric artificial genomes-representing those having experienced lateral gene transfer-were created by combining genes from multiple artificial genomes, and the performance of the parametric methods for identifying "atypical" genes was assessed directly. We found that a hidden Markov model that included multiple gene models, each trained on sets of genes representing the range of genotypic variability within a genome, could produce artificial genomes that mimicked the properties of genuine genomes. Moreover, different methods for detecting foreign genes performed differently-i.e., they had different sets of strengths and weaknesses-when identifying atypical genes within chimeric artificial genomes.

  14. Fusion genes in solid tumors:an emerging target for cancer diagnosis and treatment

    Institute of Scientific and Technical Information of China (English)

    Brittany C. Parker; Wei Zhang

    2013-01-01

    Studies over the past decades have uncovered fusion genes, a class of oncogenes that provide immense diagnostic and therapeutic advantages because of their tumor-specific expression. Originally associated with hemotologic cancers, fusion genes have recently been discovered in a wide array of solid tumors, including sarcomas, carcinomas, and tumors of the central nervous system. Fusion genes are attractive as both therapeutic targets and diagnostic tools due to their inherent expression in tumor tissue alone. Therefore, the discovery and elucidation of fusion genes in various cancer types may provide more effective therapies in the future for cancer patients.

  15. ETS gene fusions in prostate cancer: from discovery to daily clinical practice.

    NARCIS (Netherlands)

    Tomlins, S.A.; Bjartell, A.; Chinnaiyan, A.M.; Jenster, G.; Nam, R.K.; Rubin, M.A.; Schalken, J.A.

    2009-01-01

    CONTEXT: In 2005, fusions between the androgen-regulated transmembrane protease serine 2 gene, TMPRSS2, and E twenty-six (ETS) transcription factors were discovered in prostate cancer. OBJECTIVE: To review advances in our understanding of ETS gene fusions, focusing on challenges affecting translatio

  16. DNA immunization with fusion genes containing HCV core region and HBV core region

    Institute of Scientific and Technical Information of China (English)

    杨莉; 刘晶; 孔玉英; 汪垣; 李光地

    1999-01-01

    The eucaryotic expression plasmids were constructed to express the complete (HCc191) or the truncated (HCc69 and HCc40) HCV core genes, solely or fused with the HBV core gene (HBc144). These constructions were transiently expressed in COS cells under the control of the CMV promoter. The antigenicity of HBc and HCc could be detected in the expression products by ELISA and Western blot. The mice immunized with these expression plasmids efficiently produced the anti-HCc antibodies, and also anti-HBc antibodies when the plasmids contained the fusion genes. In addition, the antibodies induced by the fusion genes were more persistent than those induced by the non-fusion HCV core genes. These indicate that the fusion of HCc genes to HBc gene is in favor of the immunogenicity of HCc, while the immunogenicity of HBc is not affected.

  17. Fusion

    CERN Document Server

    Mahaffey, James A

    2012-01-01

    As energy problems of the world grow, work toward fusion power continues at a greater pace than ever before. The topic of fusion is one that is often met with the most recognition and interest in the nuclear power arena. Written in clear and jargon-free prose, Fusion explores the big bang of creation to the blackout death of worn-out stars. A brief history of fusion research, beginning with the first tentative theories in the early 20th century, is also discussed, as well as the race for fusion power. This brand-new, full-color resource examines the various programs currently being funded or p

  18. A Mutation Affecting the Regulation of a Seca-Lacz Fusion Defines a New Sec Gene

    OpenAIRE

    Riggs, P. D.; Derman, A. I.; Beckwith, J

    1988-01-01

    It was shown previously that the secA gene of Escherichia coli is derepressed in cells that have a defect in protein export. Here it is demonstrated that the β-galactosidase produced by a secA-lacZ gene fusion strain is regulated in the same way. Studies on the fusion strain reveal that the promoter or a site involved in regulation of the secA gene is located considerably upstream from the structural gene. The properties of the fusion strain provide a new selection for mutants that are defect...

  19. Cloning of α-β fusion gene from Clostridium perfringens and its expression

    Institute of Scientific and Technical Information of China (English)

    Jia-Ning Bai; Yan Zhang; Bao-Hua Zhao

    2006-01-01

    AIM: To study the cloning of α-β fusion gene from Clostridium perfringens and the immunogenicity of α-β fusion expression.METHODS: Cloning was accomplished after PCR amplification from strains NCTC64609 and C58-1 of the protective antigen genes of α-toxin and β-toxin. The fragment of the gene was cloned using plasmid pZCPAB. This fragment coded for the gene with the stable expression of α-β fusion gene binding. In order to verify the exact location of the α-β fusion gene, domain plasmids were constructed. The two genes were fused into expression vector pBV221. The expressed α-β fusion protein was identified by ELISA, SDS-PAGE, Western blotting and neutralization assay.RESULTS: The protective α-toxin gene (cpa906) and the β-toxin gene (cpb930) were obtained. The recombinant plasmid pZCPAB carrying α-β fusion gene was constructed and transformed into BL21(DE3). The recombinant strain BL21(DE3)(pZCPAB) was obtained. After the recombinant strain BL21(DE3)(pZCPAB) was induced by 42℃, its expressed product was about 22.14% of total cellular protein at SDS-PAGE and thin-layer gel scanning analysis. Neutralization assay indicated that the antibody induced by immunization with α-β fusion protein could neutralize the toxicity of α-toxin and β-toxin.CONCLUSION: The obtained α-toxin and β-toxin genes are correct. The recombinant strain BL21(DE3)(pZCPAB)could produce α-β fusion protein. This protein can be used for immunization and is immunogenic. The antibody induced by immunization with α-β fusion protein could neutralize the toxicity of α-toxin and β-toxin.

  20. Identification of Gene Mutations and Fusion Genes in Patients with Sézary Syndrome.

    Science.gov (United States)

    Prasad, Aparna; Rabionet, Raquel; Espinet, Blanca; Zapata, Luis; Puiggros, Anna; Melero, Carme; Puig, Anna; Sarria-Trujillo, Yaris; Ossowski, Stephan; Garcia-Muret, Maria P; Estrach, Teresa; Servitje, Octavio; Lopez-Lerma, Ingrid; Gallardo, Fernando; Pujol, Ramon M; Estivill, Xavier

    2016-07-01

    Sézary syndrome is a leukemic form of cutaneous T-cell lymphoma with an aggressive clinical course. The genetic etiology of the disease is poorly understood, with chromosomal abnormalities and mutations in some genes being involved in the disease. The goal of our study was to understand the genetic basis of the disease by looking for driver gene mutations and fusion genes in 15 erythrodermic patients with circulating Sézary cells, 14 of them fulfilling the diagnostic criteria of Sézary syndrome. We have discovered genes that could be involved in the pathogenesis of Sézary syndrome. Some of the genes that are affected by somatic point mutations include ITPR1, ITPR2, DSC1, RIPK2, IL6, and RAG2, with some of them mutated in more than one patient. We observed several somatic copy number variations shared between patients, including deletions and duplications of large segments of chromosome 17. Genes with potential function in the T-cell receptor signaling pathway and tumorigenesis were disrupted in Sézary syndrome patients, for example, CBLB, RASA2, BCL7C, RAMP3, TBRG4, and DAD1. Furthermore, we discovered several fusion events of interest involving RASA2, NFKB2, BCR, FASN, ZEB1, TYK2, and SGMS1. Our work has implications for the development of potential therapeutic approaches for this aggressive disease. PMID:27039262

  1. Gene fusions with lacZ by duplication insertion in the radioresistant bacterium Deinococcus radiodurans

    International Nuclear Information System (INIS)

    Deinococcus radiodurans is the most-studied species of a eubacterial family characterized by extreme resistance to DNA damage. We have focused on developing molecular biological techniques to investigate the genetics of this organism. We report construction of lacZ gene fusions by a method involving both in vitro splicing and the natural transformation of D. radiodurans. Numerous fusion strains were identified by expression of beta-galactosidase. Among these fusion strains, several were inducible by exposure to the DNA-damaging agent mitomycin C, and four of the inducible fusion constructs were cloned in Escherichia coli. Hybridization studies indicate that one of the damage-inducible genes contains a sequence reiterated throughout the D. radiodurans chromosome. Survival measurements show that two of the fusion strains have increased sensitivity to mitomycin C, suggesting that the fusions within these strains inactivate repair functions

  2. Bacteriophage P22 transduction of integrated plasmids: single-step cloning of Salmonella typhimurium gene fusions.

    OpenAIRE

    Mahan, M. J.; Slauch, J M; Mekalanos, J.J. (John J.)

    1993-01-01

    Transcriptional fusions to Salmonella typhimurium chromosomal genes were constructed by integration of a suicide fusion vector into the chromosome by homologous recombination with random cloned chromosomal fragments. We describe here a transductional method using the generalized transducing phage of S. typhimurium, P22, to clone these fusions directly from the bacterial chromosome, in a single step, without the use of restriction enzymes. In this transduction, the phage packages the chromosom...

  3. The Investigation of EWS-FLI-1 Fusion Gene in the Ewing Family of Tumors

    Institute of Scientific and Technical Information of China (English)

    GangFeng; ZhongquanZhao; DonglinWang

    2004-01-01

    There is evidence that 95% of the Ewing family of tumors (EFT) have a EWS-FLI-1 fusion gene. EWS-FL1-1 is a transcription factor with a pivotal function and it is known to bind to a special DNA sequence. Research has demonstrated that the EWS-FLI-1 fusion gene occurrence is related to the EFT, and it has been used to diagnose, treat and serve as a basis for EFT prognosis. We have briefly summarized the progress of the EWS-FLI-1 fusion gene in basic and clinical investigation within the past several years.

  4. Construction and characterization of calreticulin-HBsAg fusion gene recombinant adenovirus expression vector

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To generate recombinant adenoviral vector con-taining calreticulin (CRT)-hepatitis B surface antigen (HBsAg) fusion gene for developing a safe, effective and HBsAg-specific therapeutic vaccine.METHODS: CRT and HBsAg gene were fused using polymerase chain reaction (PCR), endonuclease diges-tion and ligation methods. The fusion gene was cloned into pENTR/D-TOPO transfer vector after the base pairs of DNA (CACC) sequence was added to the 5′ end. Adenoviral expression vector containing CRT-HBsAg fusion gen...

  5. Fusion genes with ALK as recurrent partner in ependymoma-like gliomas

    DEFF Research Database (Denmark)

    Olsen, Thale Kristin; Panagopoulos, Ioannis; Meling, Torstein R;

    2015-01-01

    . Both tumors harbored structural aberrations involving the ALK locus 2p23. Tumor 1 had an unbalanced t(2;14)(p23;q22) translocation which led to the fusion gene KTN1-ALK. Tumor 2 had an interstitial del(2)(p16p23) deletion causing the fusion of CCDC88A and ALK. In both samples, the breakpoint of ALK...

  6. Genetically controlled fusion, exocytosis and fission of artificial vesicles-a roadmap

    DEFF Research Database (Denmark)

    Bönzli, Eva; Hadorn, Maik; de Lucrezia, Davide;

    2011-01-01

    mechanisms are available, e.g. addition of transcription factors (Kelley et al. 2010). Changes in the pH are reported to control the activity of the fusion peptides (Nomura et al. 2004). So far, we successfully enclosed a commercially available cell-free system and expressed eGFP in vesicles as a proof...

  7. LINE FUSION GENES: a database of LINE expression in human genes

    Directory of Open Access Journals (Sweden)

    Park Hong-Seog

    2006-06-01

    Full Text Available Abstract Background Long Interspersed Nuclear Elements (LINEs are the most abundant retrotransposons in humans. About 79% of human genes are estimated to contain at least one segment of LINE per transcription unit. Recent studies have shown that LINE elements can affect protein sequences, splicing patterns and expression of human genes. Description We have developed a database, LINE FUSION GENES, for elucidating LINE expression throughout the human gene database. We searched the 28,171 genes listed in the NCBI database for LINE elements and analyzed their structures and expression patterns. The results show that the mRNA sequences of 1,329 genes were affected by LINE expression. The LINE expression types were classified on the basis of LINEs in the 5' UTR, exon or 3' UTR sequences of the mRNAs. Our database provides further information, such as the tissue distribution and chromosomal location of the genes, and the domain structure that is changed by LINE integration. We have linked all the accession numbers to the NCBI data bank to provide mRNA sequences for subsequent users. Conclusion We believe that our work will interest genome scientists and might help them to gain insight into the implications of LINE expression for human evolution and disease. Availability http://www.primate.or.kr/line

  8. Refined human artificial chromosome vectors for gene therapy and animal transgenesis

    OpenAIRE

    Kazuki, Y.; Hoshiya, H.; Takiguchi, M; Abe, S.; Iida, Y.; Osaki, M.; Katoh, M; Hiratsuka, M; Shirayoshi, Y; HIRAMATSU, K.; Ueno, E; Kajitani, N; Yoshino, T.; Kazuki, K; Ishihara, C.

    2010-01-01

    Human artificial chromosomes (HACs) have several advantages as gene therapy vectors, including stable episomal maintenance, and the ability to carry large gene inserts. We previously developed HAC vectors from the normal human chromosomes using a chromosome engineering technique. However, endogenous genes were remained in these HACs, limiting their therapeutic applications. In this study, we refined a HAC vector without endogenous genes from human chromosome 21 in homologous recombination-pro...

  9. INHIBITION OF APOPTOSIS BY bcr-abl FUSION GENE IN K562 CELLS

    Institute of Scientific and Technical Information of China (English)

    WANG Chun-hong; SUN Bing-zhong; YUAN Yue-chuan

    1999-01-01

    Objective: To investigate the effect of bcr-abl fusion gene on CML cell apoptosis. Methods: Apoptosis of exvivo cultured K562 cells were observed after exposure to synthetic 18 mer antisense oligodeoxynucleotide complementary to the bcr-abl junction (b3a2). Results: Apoptosis of K562 cells was significantly increased associated with inhibition of bcr-abl expression. Conclusion: bcr-abl fusion gene formation due to chromosome translocation may be the major mechanism of CML via inhibition of apoptosis.

  10. Fusion of Biogeography based optimization and Artificial bee colony for identification of Natural Terrain Features

    OpenAIRE

    Priya Arora; Harish Kundra; Dr. V.K Panchal

    2012-01-01

    Swarm Intelligence techniques expedite the configuration and collimation of the remarkable ability of group members to reason and learn in an environment of contingency and corrigendum from their peers by sharing information. This paper introduces a novel approach of fusion of two intelligent techniques generally to augment the performance of a single intelligent technique by means of information sharing. Biogeography-based optimization (BBO) is a recently developed heuristic algorithm, which...

  11. The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma

    Science.gov (United States)

    Parker, Brittany C.; Annala, Matti J.; Cogdell, David E.; Granberg, Kirsi J.; Sun, Yan; Ji, Ping; Li, Xia; Gumin, Joy; Zheng, Hong; Hu, Limei; Yli-Harja, Olli; Haapasalo, Hannu; Visakorpi, Tapio; Liu, Xiuping; Liu, Chang-gong; Sawaya, Raymond; Fuller, Gregory N.; Chen, Kexin; Lang, Frederick F.; Nykter, Matti; Zhang, Wei

    2013-01-01

    Fusion genes are chromosomal aberrations that are found in many cancers and can be used as prognostic markers and drug targets in clinical practice. Fusions can lead to production of oncogenic fusion proteins or to enhanced expression of oncogenes. Several recent studies have reported that some fusion genes can escape microRNA regulation via 3′–untranslated region (3′-UTR) deletion. We performed whole transcriptome sequencing to identify fusion genes in glioma and discovered FGFR3-TACC3 fusions in 4 of 48 glioblastoma samples from patients both of mixed European and of Asian descent, but not in any of 43 low-grade glioma samples tested. The fusion, caused by tandem duplication on 4p16.3, led to the loss of the 3′-UTR of FGFR3, blocking gene regulation of miR-99a and enhancing expression of the fusion gene. The fusion gene was mutually exclusive with EGFR, PDGFR, or MET amplification. Using cultured glioblastoma cells and a mouse xenograft model, we found that fusion protein expression promoted cell proliferation and tumor progression, while WT FGFR3 protein was not tumorigenic, even under forced overexpression. These results demonstrated that the FGFR3-TACC3 gene fusion is expressed in human cancer and generates an oncogenic protein that promotes tumorigenesis in glioblastoma. PMID:23298836

  12. Recurrent Fusion Genes in Gastric Cancer: CLDN18-ARHGAP26 Induces Loss of Epithelial Integrity

    Directory of Open Access Journals (Sweden)

    Fei Yao

    2015-07-01

    Full Text Available Genome rearrangements, a hallmark of cancer, can result in gene fusions with oncogenic properties. Using DNA paired-end-tag (DNA-PET whole-genome sequencing, we analyzed 15 gastric cancers (GCs from Southeast Asians. Rearrangements were enriched in open chromatin and shaped by chromatin structure. We identified seven rearrangement hot spots and 136 gene fusions. In three out of 100 GC cases, we found recurrent fusions between CLDN18, a tight junction gene, and ARHGAP26, a gene encoding a RHOA inhibitor. Epithelial cell lines expressing CLDN18-ARHGAP26 displayed a dramatic loss of epithelial phenotype and long protrusions indicative of epithelial-mesenchymal transition (EMT. Fusion-positive cell lines showed impaired barrier properties, reduced cell-cell and cell-extracellular matrix adhesion, retarded wound healing, and inhibition of RHOA. Gain of invasion was seen in cancer cell lines expressing the fusion. Thus, CLDN18-ARHGAP26 mediates epithelial disintegration, possibly leading to stomach H+ leakage, and the fusion might contribute to invasiveness once a cell is transformed.

  13. Low frequency of ESRRA-C11orf20 fusion gene in ovarian carcinomas.

    Science.gov (United States)

    Micci, Francesca; Panagopoulos, Ioannis; Thorsen, Jim; Davidson, Ben; Tropé, Claes Gøran; Heim, Sverre

    2014-02-01

    The identification of recurrent gene fusions in common epithelial cancers--for example, TMPRSS2/ERG in prostate cancer and EML4/ALK in nonsmall cell lung carcinomas--has raised the question of whether fusion genes are pathogenetically important also in ovarian carcinomas. The first recurrent fusion transcript in serous ovarian carcinomas was reported by Salzman et al. in 2011, who used deep paired-end sequencing to detect the fusion gene ESRRA-C11orf20 in 10 out of 67 (15%) serous ovarian carcinomas examined, a finding that holds great promise for our understanding of ovarian tumorigenesis as well as, potentially, for new treatment strategies. We wanted to test how frequent the ESRRA/C11orf20 fusion is in ovarian carcinomas of all subtypes, and therefore examined a series of 230 ovarian carcinomas of which 197 were of the serous subtype and 163 of the 197 were of stages III and IV--that is, the very same carcinoma subset where the fusion transcript had been found. We performed PCR and high-throughput sequencing analyses in search of the fusion transcript. We used the same primers described previously for the detection of the fusion and the same primer combination, but found no ESRRA/C11orf20 fusion in our series. A synthetic DNA plasmid containing the reported ESRRA/C11orf20 fusion was included as a positive control for our PCR experiments. Data from high-throughput sequencing of 23 ovarian carcinomas were screened in search of alternative partner(s) for the ESRRA and/or C11orf20 gene, but none was found. We conclude that the frequency of the ESRRA/C11orf20 gene fusion in serous ovarian carcinomas of stages III and IV must be considerable less than that reported previously (0/163 in our experience compared with 10/67 in the previous study). At the very least, it seems clear that the said fusion cannot be a common pathogenetic event in this tumor type.

  14. Low frequency of ESRRA-C11orf20 fusion gene in ovarian carcinomas.

    Directory of Open Access Journals (Sweden)

    Francesca Micci

    2014-02-01

    Full Text Available The identification of recurrent gene fusions in common epithelial cancers--for example, TMPRSS2/ERG in prostate cancer and EML4/ALK in nonsmall cell lung carcinomas--has raised the question of whether fusion genes are pathogenetically important also in ovarian carcinomas. The first recurrent fusion transcript in serous ovarian carcinomas was reported by Salzman et al. in 2011, who used deep paired-end sequencing to detect the fusion gene ESRRA-C11orf20 in 10 out of 67 (15% serous ovarian carcinomas examined, a finding that holds great promise for our understanding of ovarian tumorigenesis as well as, potentially, for new treatment strategies. We wanted to test how frequent the ESRRA/C11orf20 fusion is in ovarian carcinomas of all subtypes, and therefore examined a series of 230 ovarian carcinomas of which 197 were of the serous subtype and 163 of the 197 were of stages III and IV--that is, the very same carcinoma subset where the fusion transcript had been found. We performed PCR and high-throughput sequencing analyses in search of the fusion transcript. We used the same primers described previously for the detection of the fusion and the same primer combination, but found no ESRRA/C11orf20 fusion in our series. A synthetic DNA plasmid containing the reported ESRRA/C11orf20 fusion was included as a positive control for our PCR experiments. Data from high-throughput sequencing of 23 ovarian carcinomas were screened in search of alternative partner(s for the ESRRA and/or C11orf20 gene, but none was found. We conclude that the frequency of the ESRRA/C11orf20 gene fusion in serous ovarian carcinomas of stages III and IV must be considerable less than that reported previously (0/163 in our experience compared with 10/67 in the previous study. At the very least, it seems clear that the said fusion cannot be a common pathogenetic event in this tumor type.

  15. Stable Expression of Hantavirus H8205 Strain G1/IL-2 Gene and Immune Protection of the Fusion Gene

    Institute of Scientific and Technical Information of China (English)

    XIONG Ying; YUAN Yuan; JIA Min; YU Bing; HUANG Hanju

    2007-01-01

    To explore the feasibility of stable expression of Hantavirus H8205 strain G1 segment and human IL-2 fusion gene in Vero cells, and to examine the immune protection effects on mice vaccinated with this recombinant eukaryotic expression vector containing Hantavirus G1 gene and IL-2 gene. With the help of lipofectamine, the Vero cells were transfected with pcDNA3.1/HisB-IL-2-G1 and the positive cells were selected by G418. IFAT and SDS-PAGE electrophoresis were used to determine the stable transfection and expression of recombinant protein.Each mouse was inoculated with plasmids intramuscularly (i.m.) three times, 2 boosts were given at 2-week intervals, serum anti-hantavirus antibodies were detected by ELISA and neutralizing antibodies (NAb) were detected by Plaque Reduction Neutralization Test. The fusion protein expressed in Vero cells was 78 kD, corresponding to the estimated molecular size. The neutralizing antibody titers of mice with pcDNA3.1/HisB-IL-2-G1 were 1:20-1:80. IL-2/G1 fusion gene could be transferred in Vero cells and stably express the fusion protein. Specific humeral immune responses in mice can be induced with the recombinant eukaryotic expression vector containing the fusion gene, which lays the foundation for further development of therapeutic HTNV vaccine.

  16. Data Fusion Using Different Activation Functions in Artificial Neural Networks for Vehicular Navigation

    Directory of Open Access Journals (Sweden)

    MALLESWARAN M,

    2010-12-01

    Full Text Available Global positioning System (GPS and Inertial Navigation System (INS data can be integrated together to provide a reliable navigation. GPS/INS data integration provides reliable navigation solutions by overcoming each of their shortcomings, including signal blockage for GPS and increase in position errors with time for INS. This paper aims to provide GPS/INS data integration utilizing Artificial Neural Network (ANN architecture. This architecture is based on Feed Forward Neural Networks, which generally includes Radial Basis Function (RBF neural network and Back Propagation neural network (BPN. These are systematic methods for training multi-layer artificial networks. The BPN-ANN and RBF-ANN modules are trained to predict the INS position error and provide accurate positioning of the moving vehicle. This paper also compares performance of theGPS/INS data integration system by using different activation function like Bipolar Sigmoidal Function (BPSF, Binary Sigmoidal Function (BISF, Hyperbolic Tangential Function (HTF and Gaussian Function (GF in BPN-ANN and using Gaussian function in RBF-ANN.

  17. ESRRA-C11orf20 is a recurrent gene fusion in serous ovarian carcinoma.

    Directory of Open Access Journals (Sweden)

    Julia Salzman

    2011-09-01

    Full Text Available Every year, ovarian cancer kills approximately 14,000 women in the United States and more than 140,000 women worldwide. Most of these deaths are caused by tumors of the serous histological type, which is rarely diagnosed before it has disseminated. By deep paired-end sequencing of mRNA from serous ovarian cancers, followed by deep sequencing of the corresponding genomic region, we identified a recurrent fusion transcript. The fusion transcript joins the 5' exons of ESRRA, encoding a ligand-independent member of the nuclear-hormone receptor superfamily, to the 3' exons of C11orf20, a conserved but uncharacterized gene located immediately upstream of ESRRA in the reference genome. To estimate the prevalence of the fusion, we tested 67 cases of serous ovarian cancer by RT-PCR and sequencing and confirmed its presence in 10 of these. Targeted resequencing of the corresponding genomic region from two fusion-positive tumor samples identified a nearly clonal chromosomal rearrangement positioning ESRRA upstream of C11orf20 in one tumor, and evidence of local copy number variation in the ESRRA locus in the second tumor. We hypothesize that the recurrent novel fusion transcript may play a role in pathogenesis of a substantial fraction of serous ovarian cancers and could provide a molecular marker for detection of the cancer. Gene fusions involving adjacent or nearby genes can readily escape detection but may play important roles in the development and progression of cancer.

  18. ESRRA-C11orf20 is a recurrent gene fusion in serous ovarian carcinoma.

    Science.gov (United States)

    Salzman, Julia; Marinelli, Robert J; Wang, Peter L; Green, Ann E; Nielsen, Julie S; Nelson, Brad H; Drescher, Charles W; Brown, Patrick O

    2011-09-01

    Every year, ovarian cancer kills approximately 14,000 women in the United States and more than 140,000 women worldwide. Most of these deaths are caused by tumors of the serous histological type, which is rarely diagnosed before it has disseminated. By deep paired-end sequencing of mRNA from serous ovarian cancers, followed by deep sequencing of the corresponding genomic region, we identified a recurrent fusion transcript. The fusion transcript joins the 5' exons of ESRRA, encoding a ligand-independent member of the nuclear-hormone receptor superfamily, to the 3' exons of C11orf20, a conserved but uncharacterized gene located immediately upstream of ESRRA in the reference genome. To estimate the prevalence of the fusion, we tested 67 cases of serous ovarian cancer by RT-PCR and sequencing and confirmed its presence in 10 of these. Targeted resequencing of the corresponding genomic region from two fusion-positive tumor samples identified a nearly clonal chromosomal rearrangement positioning ESRRA upstream of C11orf20 in one tumor, and evidence of local copy number variation in the ESRRA locus in the second tumor. We hypothesize that the recurrent novel fusion transcript may play a role in pathogenesis of a substantial fraction of serous ovarian cancers and could provide a molecular marker for detection of the cancer. Gene fusions involving adjacent or nearby genes can readily escape detection but may play important roles in the development and progression of cancer.

  19. A simple, flexible and efficient PCR-fusion/Gateway cloning procedure for gene fusion, site-directed mutagenesis, short sequence insertion and domain deletions and swaps

    Directory of Open Access Journals (Sweden)

    Etchells J Peter

    2009-10-01

    Full Text Available Abstract Background The progress and completion of various plant genome sequencing projects has paved the way for diverse functional genomic studies that involve cloning, modification and subsequent expression of target genes. This requires flexible and efficient procedures for generating binary vectors containing: gene fusions, variants from site-directed mutagenesis, addition of protein tags together with domain swaps and deletions. Furthermore, efficient cloning procedures, ideally high throughput, are essential for pyramiding of multiple gene constructs. Results Here, we present a simple, flexible and efficient PCR-fusion/Gateway cloning procedure for construction of binary vectors for a range of gene fusions or variants with single or multiple nucleotide substitutions, short sequence insertions, domain deletions and swaps. Results from selected applications of the procedure which include ORF fusion, introduction of Cys>Ser mutations, insertion of StrepII tag sequence and domain swaps for Arabidopsis secondary cell wall AtCesA genes are demonstrated. Conclusion The PCR-fusion/Gateway cloning procedure described provides an elegant, simple and efficient solution for a wide range of diverse and complicated cloning tasks. Through streamlined cloning of sets of gene fusions and modification variants into binary vectors for systematic functional studies of gene families, our method allows for efficient utilization of the growing sequence and expression data.

  20. Artificial citrate operon and Vitreoscilla hemoglobin gene enhanced mineral phosphate solubilizing ability of Enterobacter hormaechei DHRSS.

    Science.gov (United States)

    Yadav, Kavita; Kumar, Chanchal; Archana, G; Kumar, G Naresh

    2014-10-01

    Mineral phosphate solubilization by bacteria is mediated through secretion of organic acids, among which citrate is one of the most effective. To overproduce citrate in bacterial systems, an artificial citrate operon comprising of genes encoding NADH-insensitive citrate synthase of E. coli and Salmonella typhimurium sodium-dependent citrate transporter was constructed. In order to improve its mineral phosphate solubilizing (MPS) ability, the citrate operon was incorporated into E. hormaechei DHRSS. The artificial citrate operon transformant secreted 7.2 mM citric acid whereas in the native strain, it was undetectable. The transformant released 0.82 mM phosphate in flask studies in buffered medium containing rock phosphate as sole P source. In fermenter studies, similar phenotype was observed under aerobic conditions. However, under microaerobic conditions, no citrate was detected and P release was not observed. Therefore, an artificial citrate gene cluster containing Vitreoscilla hemoglobin (vgb) gene under its native promoter, along with artificial citrate operon under constitutive tac promoter, was constructed and transformed into E. hormaechei DHRSS. This transformant secreted 9 mM citric acid under microaerobic conditions and released 1.0 mM P. Thus, incorporation of citrate operon along with vgb gene improves MPS ability of E. hormaechei DHRSS under buffered, microaerobic conditions mimicking rhizospheric environment.

  1. SYT-SSX fusion genes and prognosis in synovial sarcoma

    Science.gov (United States)

    Mezzelani, A; Mariani, L; Tamborini, E; Agus, V; Riva, C; Lo Vullo, S; Fabbri, A; Stumbo, M; Azzarelli, A; Casali, P G; Gronchi, A; Sozzi, G; Pierotti, M A; Pilotti, S

    2001-01-01

    A case series of 64 synovial sarcomas was characterized for the SYT-SSX fusion transcripts and statistically analysed in order to correlate molecular data with prognosis and morphology. SYT-SSX1 fusion transcript appeared to be an independent, though not reaching statistical significance (P = 0.183), prognostic factor clearly associated with a reduced metastasis-free survival. Regarding the association between transcript type and histologic subtype we found, a borderline P value (P = 0.067) between the SYT-SSX1 transcript and the biphasic subtype which, subsequently expanding the analysis to 70 cases, turned out to be significant. However, we could not confirm the prediction value of the biphasic subtype for the presence of the SYT-SSX1 transcript since in our hands 6 out 33 (18%) biphasic tumours carried the SYT-SSX2 transcript.© 2001 Cancer Research Campaign  http://www.bjcancer.com PMID:11720441

  2. Construction of expression vector for NT4-ADNF-9 fusion gene

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To construct the prokaryotic expression vector bearing fusion gene NT4-ADNF-9 and lay foundation for further study on genetic therapy of neurosensory deafness. Methods By means of asymmetrical primer/ template,double stranded cDNA of activity dependent neurotrophic factor-9 (ADNF-9) was obtained,which included restriction enzymes sites on the two extremities. ADNF-9 cDNA was ligated to the signal and leader peptides of neurotrophin 4 (NT4),and the fusion gene was named NT4-ADNF-9. Then it was subc...

  3. CRTC1-MAML2 gene fusion in mucoepidermoid carcinoma of the lacrimal gland

    DEFF Research Database (Denmark)

    von Holstein, Sarah Linea; Fehr, André; Heegaard, Steffen;

    2012-01-01

    -grade MEC of the lacrimal gland. There were no signs of recurrence or metastases during a five-year follow-up. Using RT-PCR and FISH we demonstrated that the tumor was positive for the CRTC1-MAML2 gene fusion previously shown to be associated with in particular low-grade salivary MECs with favorable...... prognosis. By immunohistochemistry we showed that the majority of tumor cells, including epidermoid, intermediate and mucous producing cells, expressed the CRTC1-MAML2 fusion protein. In contrast, 15 non-MEC lacrimal neoplasm were fusion-negative. Our findings show that lacrimal MEC is not only clinically...... anatomical sites and organs. Moreover, our findings indicate that the CRTC1-MAML2 fusion may be a useful diagnostic and prognostic biomarker for lacrimal MEC....

  4. RELATIVE EXPRESSION AND STABILITY OF A CHROMOSOMALLY INTEGRATED AND PLASMID-BORNE MARKER GENE FUSION IN ENVIRONMENTALLY COMPETENT BACTERIA

    Science.gov (United States)

    A xyIE-iceC transcriptional fusion was created by ligating a DNA fragment harboring the cloned xyIE structural gene from the TOL plasmid of Pseudomonas putida mt-2 into the cloned iceC gene of Pseudomonas syringae Cit7. This fusion construct was integrated into chromosome of Pseu...

  5. Refined human artificial chromosome vectors for gene therapy and animal transgenesis.

    Science.gov (United States)

    Kazuki, Y; Hoshiya, H; Takiguchi, M; Abe, S; Iida, Y; Osaki, M; Katoh, M; Hiratsuka, M; Shirayoshi, Y; Hiramatsu, K; Ueno, E; Kajitani, N; Yoshino, T; Kazuki, K; Ishihara, C; Takehara, S; Tsuji, S; Ejima, F; Toyoda, A; Sakaki, Y; Larionov, V; Kouprina, N; Oshimura, M

    2011-04-01

    Human artificial chromosomes (HACs) have several advantages as gene therapy vectors, including stable episomal maintenance, and the ability to carry large gene inserts. We previously developed HAC vectors from the normal human chromosomes using a chromosome engineering technique. However, endogenous genes were remained in these HACs, limiting their therapeutic applications. In this study, we refined a HAC vector without endogenous genes from human chromosome 21 in homologous recombination-proficient chicken DT40 cells. The HAC was physically characterized using a transformation-associated recombination (TAR) cloning strategy followed by sequencing of TAR-bacterial artificial chromosome clones. No endogenous genes were remained in the HAC. We demonstrated that any desired gene can be cloned into the HAC using the Cre-loxP system in Chinese hamster ovary cells, or a homologous recombination system in DT40 cells. The HAC can be efficiently transferred to other type of cells including mouse ES cells via microcell-mediated chromosome transfer. The transferred HAC was stably maintained in vitro and in vivo. Furthermore, tumor cells containing a HAC carrying the suicide gene, herpes simplex virus thymidine kinase (HSV-TK), were selectively killed by ganciclovir in vitro and in vivo. Thus, this novel HAC vector may be useful not only for gene and cell therapy, but also for animal transgenesis.

  6. Design and characterization of novel recombinant listeriolysin O-protamine fusion proteins for enhanced gene delivery.

    Science.gov (United States)

    Kim, Na Hyung; Provoda, Chester; Lee, Kyung-Dall

    2015-02-01

    To improve the efficiency of gene delivery for effective gene therapy, it is essential that the vector carries functional components that can promote overcoming barriers in various steps leading to the transport of DNA from extracellular to ultimately nuclear compartment. In this study, we designed genetically engineered fusion proteins as a platform to incorporate multiple functionalities in one chimeric protein. Prototypes of such a chimera tested here contain two domains: one that binds to DNA; the other that can facilitate endosomal escape of DNA. The fusion proteins are composed of listeriolysin O (LLO), the endosomolytic pore-forming protein from Listeria monocytogenes, and a 22 amino acid sequence of the DNA-condensing polypeptide protamine (PN), singly or as a pair: LLO-PN and LLO-PNPN. We demonstrate dramatic enhancement of the gene delivery efficiency of protamine-condensed DNA upon incorporation of a small amount of LLO-PN fusion protein and further improvement with LLO-PNPN in vitro using cultured cells. Additionally, the association of anionic liposomes with cationic LLO-PNPN/protamine/DNA complexes, yielding a net negative surface charge, resulted in better in vitro transfection efficiency in the presence of serum. An initial, small set of data in mice indicated that the observed enhancement in gene expression could also be applicable to in vivo gene delivery. This study suggests that incorporation of a recombinant fusion protein with multiple functional components, such as LLO-protamine fusion protein, in a nonviral vector is a promising strategy for various nonviral gene delivery systems. PMID:25521817

  7. Matrix factorization-based data fusion for gene function prediction in baker's yeast and slime mold.

    Science.gov (United States)

    Zitnik, Marinka; Zupan, Blaž

    2014-01-01

    The development of effective methods for the characterization of gene functions that are able to combine diverse data sources in a sound and easily-extendible way is an important goal in computational biology. We have previously developed a general matrix factorization-based data fusion approach for gene function prediction. In this manuscript, we show that this data fusion approach can be applied to gene function prediction and that it can fuse various heterogeneous data sources, such as gene expression profiles, known protein annotations, interaction and literature data. The fusion is achieved by simultaneous matrix tri-factorization that shares matrix factors between sources. We demonstrate the effectiveness of the approach by evaluating its performance on predicting ontological annotations in slime mold D. discoideum and on recognizing proteins of baker's yeast S. cerevisiae that participate in the ribosome or are located in the cell membrane. Our approach achieves predictive performance comparable to that of the state-of-the-art kernel-based data fusion, but requires fewer data preprocessing steps. PMID:24297565

  8. Developing transgenic maize (Zea mays L.) with insect resistance and glyphosate tolerance by fusion gene transformation

    Institute of Scientific and Technical Information of China (English)

    SUN He; LANG Zhi-hong; LU Wei; ZHANG Jie; HE Kang-lai; ZHU Li; LIN Min; HUANG Da-fang

    2015-01-01

    Using linker peptide LP4/2A for multiple gene transformation is considered to be an effective method to stack or pyramid several traits in plants. Bacil us thuringiensis (Bt) cry gene and epsps (5-enolpyruvylshikimate-3-phosphate synthase) gene are two important genes for culturing pest-resistant and glyphosate-tolerant crops. We used linker peptide LP4/2A to connect the Bt cry1Ah gene with the 2mG2-epsps gene and combined the wide-used manA gene as a selective marker to construct one coordinated expression vector cal ed p2EPUHLAGN. The expression vector was transferred into maize by Agrobacterium tumefaciens-mediated transformation, and 60 plants were obtained, 40%of which were positive transformants. Molecular detection demonstrated that the two genes in the fusion vector were expressed simultaneously and spliced correctly in translation processing;meanwhile bioassay detection proved the transgenic maize had preferable pest resistance and glyphosate tolerance. Therefore, linker peptide LP4/2A provided a simple and reliable strategy for producing gene stacking in maize and the result showed that the fusion gene transformation system of LP4/2A was feasible in monocot plants.

  9. IGF1 is a common target gene of Ewing's sarcoma fusion proteins in mesenchymal progenitor cells.

    Directory of Open Access Journals (Sweden)

    Luisa Cironi

    Full Text Available BACKGROUND: The EWS-FLI-1 fusion protein is associated with 85-90% of Ewing's sarcoma family tumors (ESFT, the remaining 10-15% of cases expressing chimeric genes encoding EWS or FUS fused to one of several ets transcription factor family members, including ERG-1, FEV, ETV1 and ETV6. ESFT are dependent on insulin-like growth factor-1 (IGF-1 for growth and survival and recent evidence suggests that mesenchymal progenitor/stem cells constitute a candidate ESFT origin. METHODOLOGY/PRINCIPAL FINDINGS: To address the functional relatedness between ESFT-associated fusion proteins, we compared mouse progenitor cell (MPC permissiveness for EWS-FLI-1, EWS-ERG and FUS-ERG expression and assessed the corresponding expression profile changes. Whereas all MPC isolates tested could stably express EWS-FLI-1, only some sustained stable EWS-ERG expression and none could express FUS-ERG for more than 3-5 days. Only 14% and 4% of the total number of genes that were respectively induced and repressed in MPCs by the three fusion proteins were shared. However, all three fusion proteins, but neither FLI-1 nor ERG-1 alone, activated the IGF1 promoter and induced IGF1 expression. CONCLUSION/SIGNIFICANCE: Whereas expression of different ESFT-associated fusion proteins may require distinct cellular microenvironments and induce transcriptome changes of limited similarity, IGF1 induction may provide one common mechanism for their implication in ESFT pathogenesis.

  10. A gold nanoparticle pentapeptide: gene fusion to induce therapeutic gene expression in mesenchymal stem cells.

    Science.gov (United States)

    Muroski, Megan E; Morgan, Thomas J; Levenson, Cathy W; Strouse, Geoffrey F

    2014-10-22

    Mesenchymal stem cells (MSC) have been identified as having great potential as autologous cell therapeutics to treat traumatic brain injury and spinal injury as well as neuronal and cardiac ischemic events. All future clinical applications of MSC cell therapies must allow the MSC to be harvested, transfected, and induced to express a desired protein or selection of proteins to have medical benefit. For the full potential of MSC cell therapy to be realized, it is desirable to systematically alter the protein expression of therapeutically beneficial biomolecules in harvested MSC cells with high fidelity in a single transfection event. We have developed a delivery platform on the basis of the use of a solid gold nanoparticle that has been surface modified to produce a fusion containing a zwitterionic, pentapeptide designed from Bax inhibiting peptide (Ku70) to enhance cellular uptake and a linearized expression vector to induce enhanced expression of brain-derived neurotrophic factor (BDNF) in rat-derived MSCs. Ku70 is observed to effect >80% transfection following a single treatment of femur bone marrow isolated rat MSCs with efficiencies for the delivery of a 6.6 kbp gene on either a Au nanoparticle (NP) or CdSe/ZnS quantum dot (QD). Gene expression is observed within 4 d by optical measurements, and secretion is observed within 10 d by Western Blot analysis. The combination of being able to selectively engineer the NP, to colocalize biological agents, and to enhance the stability of those agents has provided the strong impetus to utilize this novel class of materials to engineer primary MSCs. PMID:25198921

  11. Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins.

    Science.gov (United States)

    Maeder, Morgan L; Angstman, James F; Richardson, Marcy E; Linder, Samantha J; Cascio, Vincent M; Tsai, Shengdar Q; Ho, Quan H; Sander, Jeffry D; Reyon, Deepak; Bernstein, Bradley E; Costello, Joseph F; Wilkinson, Miles F; Joung, J Keith

    2013-12-01

    Genome-wide studies have defined cell type-specific patterns of DNA methylation that are important for regulating gene expression in both normal development and disease. However, determining the functional significance of specific methylation events remains challenging, owing to the lack of methods for removing such modifications in a targeted manner. Here we describe an approach for efficient targeted demethylation of specific CpGs in human cells using fusions of engineered transcription activator-like effector (TALE) repeat arrays and the TET1 hydroxylase catalytic domain. Using these TALE-TET1 fusions, we demonstrate that modification of critical methylated promoter CpG positions can lead to substantial increases in the expression of endogenous human genes. Our results delineate a strategy for understanding the functional significance of specific CpG methylation marks in the context of endogenous gene loci and validate programmable DNA demethylation reagents with potential utility for research and therapeutic applications.

  12. Identification of leukemia-associated genes by MLL-EEN fusion protein through dysregulation of histone modification and DNA methylation

    OpenAIRE

    Lui, Wing-chi; 呂穎芝

    2012-01-01

    Mixed lineage leukemia (MLL) gene undergoes chromosomal translocation with over 60 different fusion partner genes in human leukemias. The resultant MLL-fusion oncoproteins are profoundly implicated in leukemias with poor prognosis. Epigenetic dysregulations have been frequently reported in MLL-rearranged leukemogenesis. Our study aims to investigate the correlations between epigenetic alterations, including both histone modification and DNA methylation, and gene dysregulation in MLL-rearrange...

  13. MEAF6/PHF1 is a recurrent gene fusion in endometrial stromal sarcoma.

    Science.gov (United States)

    Micci, Francesca; Gorunova, Ludmila; Gatius, Sonia; Matias-Guiu, Xavier; Davidson, Ben; Heim, Sverre; Panagopoulos, Ioannis

    2014-05-28

    The chimeric transcripts described in endometrial stromal sarcomas (ESS) are JAZF1/SUZ12, YWHAE/FAM22, ZC3H7/BCOR, MBTD1/CXorf67, and recombinations of PHF1 with JAZF1, EPC1, and MEAF6. The MEAF6/PHF1 fusion had hitherto been identified in only one tumor. We present two more ESS with MEAF6/PHF1 detected by transcriptome sequencing (case 1) and RT-PCR (case 2), proving that this fusion is recurrent in ESS. The transcript of both cases was an in-frame fusion between exon 5 of MEAF6 and exon 2 of PHF1. Both genes are involved in epigenetic modification, and this may well be their main pathogenetic theme also in ESS tumorigenesis. PMID:24530230

  14. Gene expression, single nucleotide variant and fusion transcript discovery in archival material from breast tumors.

    Directory of Open Access Journals (Sweden)

    Nadine Norton

    Full Text Available Advantages of RNA-Seq over array based platforms are quantitative gene expression and discovery of expressed single nucleotide variants (eSNVs and fusion transcripts from a single platform, but the sensitivity for each of these characteristics is unknown. We measured gene expression in a set of manually degraded RNAs, nine pairs of matched fresh-frozen, and FFPE RNA isolated from breast tumor with the hybridization based, NanoString nCounter (226 gene panel and with whole transcriptome RNA-Seq using RiboZeroGold ScriptSeq V2 library preparation kits. We performed correlation analyses of gene expression between samples and across platforms. We then specifically assessed whole transcriptome expression of lincRNA and discovery of eSNVs and fusion transcripts in the FFPE RNA-Seq data. For gene expression in the manually degraded samples, we observed Pearson correlations of >0.94 and >0.80 with NanoString and ScriptSeq protocols, respectively. Gene expression data for matched fresh-frozen and FFPE samples yielded mean Pearson correlations of 0.874 and 0.783 for NanoString (226 genes and ScriptSeq whole transcriptome protocols respectively, p<2x10(-16. Specifically for lincRNAs, we observed superb Pearson correlation (0.988 between matched fresh-frozen and FFPE pairs. FFPE samples across NanoString and RNA-Seq platforms gave a mean Pearson correlation of 0.838. In FFPE libraries, we detected 53.4% of high confidence SNVs and 24% of high confidence fusion transcripts. Sensitivity of fusion transcript detection was not overcome by an increase in depth of sequencing up to 3-fold (increase from ~56 to ~159 million reads. Both NanoString and ScriptSeq RNA-Seq technologies yield reliable gene expression data for degraded and FFPE material. The high degree of correlation between NanoString and RNA-Seq platforms suggests discovery based whole transcriptome studies from FFPE material will produce reliable expression data. The RiboZeroGold ScriptSeq protocol

  15. Single-Copy Green Fluorescent Protein Gene Fusions Allow Accurate Measurement of Salmonella Gene Expression In Vitro and during Infection of Mammalian Cells

    OpenAIRE

    Hautefort, Isabelle; Proença, Maria José; Hinton, Jay C. D.

    2003-01-01

    We developed a reliable and flexible green fluorescent protein (GFP)-based system for measuring gene expression in individual bacterial cells. Until now, most systems have relied upon plasmid-borne gfp gene fusions, risking problems associated with plasmid instability. We show that a recently developed GFP variant, GFP+, is suitable for assessing bacterial gene expression. Various gfp+ transcriptional fusions were constructed and integrated as single copies into the chromosome of Salmonella e...

  16. Gene fusion analysis in the battle against the African endemic sleeping sickness.

    Directory of Open Access Journals (Sweden)

    Philip Trimpalis

    Full Text Available The protozoan Trypanosoma brucei causes African Trypanosomiasis or sleeping sickness in humans, which can be lethal if untreated. Most available pharmacological treatments for the disease have severe side-effects. The purpose of this analysis was to detect novel protein-protein interactions (PPIs, vital for the parasite, which could lead to the development of drugs against this disease to block the specific interactions. In this work, the Domain Fusion Analysis (Rosetta Stone method was used to identify novel PPIs, by comparing T. brucei to 19 organisms covering all major lineages of the tree of life. Overall, 49 possible protein-protein interactions were detected, and classified based on (a statistical significance (BLAST e-value, domain length etc., (b their involvement in crucial metabolic pathways, and (c their evolutionary history, particularly focusing on whether a protein pair is split in T. brucei and fused in the human host. We also evaluated fusion events including hypothetical proteins, and suggest a possible molecular function or involvement in a certain biological process. This work has produced valuable results which could be further studied through structural biology or other experimental approaches so as to validate the protein-protein interactions proposed here. The evolutionary analysis of the proteins involved showed that, gene fusion or gene fission events can happen in all organisms, while some protein domains are more prone to fusion and fission events and present complex evolutionary patterns.

  17. Identification of target genes of synovial sarcoma-associated fusion oncoprotein using human pluripotent stem cells

    International Nuclear Information System (INIS)

    Highlights: ► We tried to identify targets of synovial sarcoma (SS)-associated SYT–SSX fusion gene. ► We established pluripotent stem cell (PSC) lines with inducible SYT–SSX gene. ► SYT–SSX responsive genes were identified by the induction of SYT–SSX in PSC. ► SS-related genes were selected from database by in silico analyses. ► 51 genes were finally identified among SS-related genes as targets of SYT–SSX in PSC. -- Abstract: Synovial sarcoma (SS) is a malignant soft tissue tumor harboring chromosomal translocation t(X; 18)(p11.2; q11.2), which produces SS-specific fusion gene, SYT–SSX. Although precise function of SYT–SSX remains to be investigated, accumulating evidences suggest its role in gene regulation via epigenetic mechanisms, and the product of SYT–SSX target genes may serve as biomarkers of SS. Lack of knowledge about the cell-of-origin of SS, however, has placed obstacle in the way of target identification. Here we report a novel approach to identify SYT–SSX2 target genes using human pluripotent stem cells (hPSCs) containing a doxycycline-inducible SYT–SSX2 gene. SYT–SSX2 was efficiently induced both at mRNA and protein levels within three hours after doxycycline administration, while no morphological change of hPSCs was observed until 24 h. Serial microarray analyses identified genes of which the expression level changed more than twofold within 24 h. Surprisingly, the majority (297/312, 95.2%) were up-regulated genes and a result inconsistent with the current concept of SYT–SSX as a transcriptional repressor. Comparing these genes with SS-related genes which were selected by a series of in silico analyses, 49 and 2 genes were finally identified as candidates of up- and down-regulated target of SYT–SSX, respectively. Association of these genes with SYT–SSX in SS cells was confirmed by knockdown experiments. Expression profiles of SS-related genes in hPSCs and human mesenchymal stem cells (hMSCs) were strikingly

  18. Identification of target genes of synovial sarcoma-associated fusion oncoprotein using human pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Hayakawa, Kazuo [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Ikeya, Makoto [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Fukuta, Makoto [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Woltjen, Knut [Department of Reprogramming Sciences, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Tamaki, Sakura; Takahara, Naoko; Kato, Tomohisa; Sato, Shingo [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Otsuka, Takanobu [Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Toguchida, Junya, E-mail: togjun@frontier.kyoto-u.ac.jp [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto (Japan)

    2013-03-22

    Highlights: ► We tried to identify targets of synovial sarcoma (SS)-associated SYT–SSX fusion gene. ► We established pluripotent stem cell (PSC) lines with inducible SYT–SSX gene. ► SYT–SSX responsive genes were identified by the induction of SYT–SSX in PSC. ► SS-related genes were selected from database by in silico analyses. ► 51 genes were finally identified among SS-related genes as targets of SYT–SSX in PSC. -- Abstract: Synovial sarcoma (SS) is a malignant soft tissue tumor harboring chromosomal translocation t(X; 18)(p11.2; q11.2), which produces SS-specific fusion gene, SYT–SSX. Although precise function of SYT–SSX remains to be investigated, accumulating evidences suggest its role in gene regulation via epigenetic mechanisms, and the product of SYT–SSX target genes may serve as biomarkers of SS. Lack of knowledge about the cell-of-origin of SS, however, has placed obstacle in the way of target identification. Here we report a novel approach to identify SYT–SSX2 target genes using human pluripotent stem cells (hPSCs) containing a doxycycline-inducible SYT–SSX2 gene. SYT–SSX2 was efficiently induced both at mRNA and protein levels within three hours after doxycycline administration, while no morphological change of hPSCs was observed until 24 h. Serial microarray analyses identified genes of which the expression level changed more than twofold within 24 h. Surprisingly, the majority (297/312, 95.2%) were up-regulated genes and a result inconsistent with the current concept of SYT–SSX as a transcriptional repressor. Comparing these genes with SS-related genes which were selected by a series of in silico analyses, 49 and 2 genes were finally identified as candidates of up- and down-regulated target of SYT–SSX, respectively. Association of these genes with SYT–SSX in SS cells was confirmed by knockdown experiments. Expression profiles of SS-related genes in hPSCs and human mesenchymal stem cells (hMSCs) were strikingly

  19. Construction of expression vector for NT4-ADNF-9 fusion gene

    Institute of Scientific and Technical Information of China (English)

    Guo-xi Zheng; Kang Zhu; Yang Jing; Jun-rong Wei; Hong-liang Zhu

    2009-01-01

    Objective To construct the prokaryotic expression vector bearing fusion gene NT4-ADNF-9 and lay foundation for further study on genetic therapy of neuraseusory deafness. Methods By means of asymmetrical prince/ template, double stranded eDNA of activity dependent neurotrophic factor-9 (ADNF-9) was obtained, which included restriction enzymes sites on the two extremities. ADNF-9 eDNA was ligated to the signal and leader peptides of nenrotrophin 4 (NT4), and the fusion gene was named NT4-ADNF-9. Then it was suheluned into prokaryotic expression vector pBV220, and called pBV220/ NT4-ADNF-9. Results Evidences of DNA sequence analysis and restrtction enzymes digestion showed that we recombined ADNF-9 eDNA to the 3'terminal of the signal and leader peptides of NT4, and the fusion gene was subcluned into pBV220 successfully. Bioactivity of the products was proved that it could support the cell survival and neurite growth in the primary cultures of dorsal root ganglia (DRG) of embryonic day-8 cbicken neurons as compared to the control. Conclusion Prokaryotic expression vector pBV220/NT4-ADNF-9 can be constructed successfully and the bioactivtty is satisfactory.

  20. Artificial selection on brain-expressed genes during the domestication of dog.

    Science.gov (United States)

    Li, Yan; Vonholdt, Bridgett M; Reynolds, Andy; Boyko, Adam R; Wayne, Robert K; Wu, Dong-Dong; Zhang, Ya-Ping

    2013-08-01

    Domesticated dogs have many unique behaviors not found in gray wolves that have augmented their interaction and communication with humans. The genetic basis of such unique behaviors in dogs remains poorly understood. We found that genes within regions highly differentiated between outbred Chinese native dogs (CNs) and wolves show high bias for expression localized to brain tissues, particularly the prefrontal cortex, a specific region responsible for complex cognitive behaviors. In contrast, candidate genes showing high population differentiation between CNs and German Shepherd dogs (GSs) did not demonstrate significant expression bias. These observations indicate that these candidate genes highly expressed in the brain have rapidly evolved. This rapid evolution was probably driven by artificial selection during the primary transition from wolves to ancient dogs and was consistent with the evolution of dog-specific characteristics, such as behavior transformation, for thousands of years.

  1. Detection of EMI4-ALK fusion gene in non-small cell lung cancer and its clinicopathologic correlation

    Institute of Scientific and Technical Information of China (English)

    钟山

    2013-01-01

    Objective To investigate the frequency of EML4-ALK fusion gene in non small-cell lung cancer NSCLC patients,and its correlation with clinicopathologic features.Methods Real-time PCR was used to detect

  2. Biological impact of hepatitis B virus X-hepatitis C virus core fusion gene on

    Institute of Scientific and Technical Information of China (English)

    Ma Zhen; Qin-Hai Shen; Guo-Min Chen; Da-Zhi Zhang

    2008-01-01

    AIM: To investigate the biological impact of hepatitis B virus X- hepatitis C virus core (HBV X-HCV C) fusion gene on hepatoma cells.METHODS: The recombinant adenoviruses AdXC,Ad-X and Ad-C expressing HBV X-HCV C fusion gene,HBVX gene and HCV C gene were constructed,respectively.Hepatoma cells were infected with different recombinant adenoviruses.MTT,colonyforming experiment,FCM,TUNEL assay were performed to observe the biological impact of the HBV X-HCV C fusion gene on liver cells.RESULTS: MTT showed that the Ad-XC group cells grew faster than the other group cells.Colony-forming experiment showed that the colony-forming rate for the Ad-XC group cells was significantly higher than that for the other group cells.FCM analysis showed that Ad-XC/Ad-X/Ad-C infection enhanced the progression of GIS phase in the HepG2 cell cycle.The apoptosis index of the Ad-XC,Ad-X,Ad-C group cells was significantly lower than that of the AdO and control group cells.Semi-quantitative RT-PCR showed that the expression level of c-myc was the highest in AdXC infected cells.Tumor formation was found at the injected site of mice inoculated with Ad-XC-infected LO2 cells,but not in control mice.CONCLUSION: Ad-XC,Ad-X and Ad-C facilitate the proliferation activity of HepG2 cells and inhibit their apoptosis in vitro.The effect of Ad-XC is significantly stronger than that of Ad-X and Ad-C.Up-regulation of c-myc may be one of the mechanisms underlying the synergism of HBVX and HCV C genes on hepatocarcinogenesis in athymic nude mice.

  3. Gene function analysis by artificial microRNAs in Physcomitrella patens.

    KAUST Repository

    Khraiwesh, Basel

    2011-01-01

    MicroRNAs (miRNAs) are ~21 nt long small RNAs transcribed from endogenous MIR genes which form precursor RNAs with a characteristic hairpin structure. miRNAs control the expression of cognate target genes by binding to reverse complementary sequences resulting in cleavage or translational inhibition of the target RNA. Artificial miRNAs (amiRNAs) can be generated by exchanging the miRNA/miRNA sequence of endogenous MIR precursor genes, while maintaining the general pattern of matches and mismatches in the foldback. Thus, for functional gene analysis amiRNAs can be designed to target any gene of interest. During the last decade the moss Physcomitrella patens emerged as a model plant for functional gene analysis based on its unique ability to integrate DNA into the nuclear genome by homologous recombination which allows for the generation of targeted gene knockout mutants. In addition to this, we developed a protocol to express amiRNAs in P. patens that has particular advantages over the generation of knockout mutants and might be used to speed up reverse genetics approaches in this model species.

  4. Expanding the molecular toolbox for Lactococcus lactis: construction of an inducible thioredoxin gene fusion expression system

    LENUS (Irish Health Repository)

    Douillard, Francois P

    2011-08-09

    Abstract Background The development of the Nisin Inducible Controlled Expression (NICE) system in the food-grade bacterium Lactococcus lactis subsp. cremoris represents a cornerstone in the use of Gram-positive bacterial expression systems for biotechnological purposes. However, proteins that are subjected to such over-expression in L. lactis may suffer from improper folding, inclusion body formation and\\/or protein degradation, thereby significantly reducing the yield of soluble target protein. Although such drawbacks are not specific to L. lactis, no molecular tools have been developed to prevent or circumvent these recurrent problems of protein expression in L. lactis. Results Mimicking thioredoxin gene fusion systems available for E. coli, two nisin-inducible expression vectors were constructed to over-produce various proteins in L. lactis as thioredoxin fusion proteins. In this study, we demonstrate that our novel L. lactis fusion partner expression vectors allow high-level expression of soluble heterologous proteins Tuc2009 ORF40, Bbr_0140 and Tuc2009 BppU\\/BppL that were previously insoluble or not expressed using existing L. lactis expression vectors. Over-expressed proteins were subsequently purified by Ni-TED affinity chromatography. Intact heterologous proteins were detected by immunoblotting analyses. We also show that the thioredoxin moiety of the purified fusion protein was specifically and efficiently cleaved off by enterokinase treatment. Conclusions This study is the first description of a thioredoxin gene fusion expression system, purposely developed to circumvent problems associated with protein over-expression in L. lactis. It was shown to prevent protein insolubility and degradation, allowing sufficient production of soluble proteins for further structural and functional characterization.

  5. Origin of the plant Tm-1-like gene via two independent horizontal transfer events and one gene fusion event.

    Science.gov (United States)

    Yang, Zefeng; Liu, Li; Fang, Huimin; Li, Pengcheng; Xu, Shuhui; Cao, Wei; Xu, Chenwu; Huang, Jinling; Zhou, Yong

    2016-01-01

    The Tomato mosaic virus (ToMV) resistance gene Tm-1 encodes a direct inhibitor of ToMV RNA replication to protect tomato from infection. The plant Tm-1-like (Tm-1L) protein is predicted to contain an uncharacterized N-terminal UPF0261 domain and a C-terminal TIM-barrel signal transduction (TBST) domain. Homologous searches revealed that proteins containing both of these two domains are mainly present in charophyte green algae and land plants but absent from glaucophytes, red algae and chlorophyte green algae. Although Tm-1 homologs are widely present in bacteria, archaea and fungi, UPF0261- and TBST-domain-containing proteins are generally encoded by different genes in these linages. A co-evolution analysis also suggested a putative interaction between UPF0261- and TBST-domain-containing proteins. Phylogenetic analyses based on homologs of these two domains revealed that plants have acquired UPF0261- and TBST-domain-encoding genes through two independent horizontal gene transfer (HGT) events before the origin of land plants from charophytes. Subsequently, gene fusion occurred between these two horizontally acquired genes and resulted in the origin of the Tm-1L gene in streptophytes. Our results demonstrate a novel evolutionary mechanism through which the recipient organism may acquire genes with functional interaction through two different HGT events and further fuse them into one functional gene. PMID:27647002

  6. Origin of the plant Tm-1-like gene via two independent horizontal transfer events and one gene fusion event.

    Science.gov (United States)

    Yang, Zefeng; Liu, Li; Fang, Huimin; Li, Pengcheng; Xu, Shuhui; Cao, Wei; Xu, Chenwu; Huang, Jinling; Zhou, Yong

    2016-01-01

    The Tomato mosaic virus (ToMV) resistance gene Tm-1 encodes a direct inhibitor of ToMV RNA replication to protect tomato from infection. The plant Tm-1-like (Tm-1L) protein is predicted to contain an uncharacterized N-terminal UPF0261 domain and a C-terminal TIM-barrel signal transduction (TBST) domain. Homologous searches revealed that proteins containing both of these two domains are mainly present in charophyte green algae and land plants but absent from glaucophytes, red algae and chlorophyte green algae. Although Tm-1 homologs are widely present in bacteria, archaea and fungi, UPF0261- and TBST-domain-containing proteins are generally encoded by different genes in these linages. A co-evolution analysis also suggested a putative interaction between UPF0261- and TBST-domain-containing proteins. Phylogenetic analyses based on homologs of these two domains revealed that plants have acquired UPF0261- and TBST-domain-encoding genes through two independent horizontal gene transfer (HGT) events before the origin of land plants from charophytes. Subsequently, gene fusion occurred between these two horizontally acquired genes and resulted in the origin of the Tm-1L gene in streptophytes. Our results demonstrate a novel evolutionary mechanism through which the recipient organism may acquire genes with functional interaction through two different HGT events and further fuse them into one functional gene.

  7. Multiscale Modeling of Gene-Behavior Associations in an Artificial Neural Network Model of Cognitive Development.

    Science.gov (United States)

    Thomas, Michael S C; Forrester, Neil A; Ronald, Angelica

    2016-01-01

    In the multidisciplinary field of developmental cognitive neuroscience, statistical associations between levels of description play an increasingly important role. One example of such associations is the observation of correlations between relatively common gene variants and individual differences in behavior. It is perhaps surprising that such associations can be detected despite the remoteness of these levels of description, and the fact that behavior is the outcome of an extended developmental process involving interaction of the whole organism with a variable environment. Given that they have been detected, how do such associations inform cognitive-level theories? To investigate this question, we employed a multiscale computational model of development, using a sample domain drawn from the field of language acquisition. The model comprised an artificial neural network model of past-tense acquisition trained using the backpropagation learning algorithm, extended to incorporate population modeling and genetic algorithms. It included five levels of description-four internal: genetic, network, neurocomputation, behavior; and one external: environment. Since the mechanistic assumptions of the model were known and its operation was relatively transparent, we could evaluate whether cross-level associations gave an accurate picture of causal processes. We established that associations could be detected between artificial genes and behavioral variation, even under polygenic assumptions of a many-to-one relationship between genes and neurocomputational parameters, and when an experience-dependent developmental process interceded between the action of genes and the emergence of behavior. We evaluated these associations with respect to their specificity (to different behaviors, to function vs. structure), to their developmental stability, and to their replicability, as well as considering issues of missing heritability and gene-environment interactions. We argue that gene

  8. PCR-based diversity estimates of artificial and environmental 18S rRNA gene libraries.

    Science.gov (United States)

    Potvin, Marianne; Lovejoy, Connie

    2009-01-01

    Environmental clone libraries constructed using small subunit ribosomal RNA (rRNA) or other gene-specific primers have become the standard molecular approach for identifying microorganisms directly from their environment. This technique includes an initial polymerase chain reaction (PCR) amplification step of a phylogenetically useful marker gene using universal primers. Although it is acknowledged that such primers introduce biases, there have been few studies if any to date systematically examining such bias in eukaryotic microbes. We investigated some implications of such bias by constructing clone libraries using several universal primer pairs targeting rRNA genes. Firstly, we constructed artificial libraries using a known mix of small cultured pelagic arctic algae with representatives from five major lineages and secondly we investigated environmental samples using several primer pairs. No primer pair retrieved all of the original algae in the artificial clone libraries and all showed a favorable bias toward the dinoflagellate Polarella glacialis and a bias against the prasinophyte Micromonas and a pennate diatom. Several other species were retrieved by only one primer pair tested. Despite this, sequences from nine environmental libraries were diverse and contained representatives from all major eukaryotic clades expected in marine samples. Further, libraries from the same sample grouped together using Bray-Curtis clustering, irrespective of primer pairs. We conclude that environmental PCR-based techniques are sufficient to compare samples, but the total diversity will probably always be underestimated and relative abundance estimates should be treated with caution.

  9. Membrane fusion inducers, chloroquine and spermidine increase lipoplex-mediated gene transfection

    Energy Technology Data Exchange (ETDEWEB)

    Wong-Baeza, Carlos; Bustos, Israel; Serna, Manuel; Tescucano, Alonso; Alcantara-Farfan, Veronica; Ibanez, Miguel [Biochemistry Department, National Polytechnic Institute (IPN), Mexico City 11340 (Mexico); Montanez, Cecilia [Department of Genetics and Molecular Biology, Centre for Research and Advanced Studies (CINVESTAV), IPN, Mexico City 07360 (Mexico); Wong, Carlos [Biochemistry Department, National Polytechnic Institute (IPN), Mexico City 11340 (Mexico); Baeza, Isabel, E-mail: ibaeza@encb.ipn.mx [Biochemistry Department, National Polytechnic Institute (IPN), Mexico City 11340 (Mexico)

    2010-05-28

    Gene transfection into mammalian cells can be achieved with viral and non-viral vectors. Non-viral vectors, such as cationic lipids that form lipoplexes with DNA, are safer and more stable than viral vectors, but their transfection efficiencies are lower. Here we describe that the simultaneous treatment with a membrane fusion inducer (chlorpromazine or procainamide) plus the lysosomotropic agent chloroquine increases lipoplex-mediated gene transfection in human (HEK293 and C-33 A) and rat (PC12) cell lines (up to 9.2-fold), as well as in situ in BALB/c mice spleens and livers (up to 6-fold); and that the polyamine spermidine increases lipoplex-mediated gene transfection and expression in cell cultures. The use of these four drugs provides a novel, safe and relatively inexpensive way to considerably increase lipoplex-mediated gene transfection efficiency.

  10. Wnt signaling induces transcription, spatial proximity, and translocation of fusion gene partners in human hematopoietic cells.

    Science.gov (United States)

    Ugarte, Giorgia D; Vargas, Macarena F; Medina, Matías A; León, Pablo; Necuñir, David; Elorza, Alvaro A; Gutiérrez, Soraya E; Moon, Randall T; Loyola, Alejandra; De Ferrari, Giancarlo V

    2015-10-01

    Chromosomal translocations are frequently associated with a wide variety of cancers, particularly hematologic malignancies. A recurrent chromosomal abnormality in acute myeloid leukemia is the reciprocal translocation t(8;21) that fuses RUNX1 and ETO genes. We report here that Wnt/β-catenin signaling increases the expression of ETO and RUNX1 genes in human hematopoietic progenitors. We found that β-catenin is rapidly recruited into RNA polymerase II transcription factories (RNAPII-Ser5) and that ETO and RUNX1 genes are brought into close spatial proximity upon Wnt3a induction. Notably, long-term treatment of cells with Wnt3a induces the generation a frequent RUNX1-ETO translocation event. Thus, Wnt/β-catenin signaling induces transcription and translocation of RUNX1 and ETO fusion gene partners, opening a novel window to understand the onset/development of leukemia. PMID:26333776

  11. Phage p1-derived artificial chromosomes facilitate heterologous expression of the FK506 gene cluster.

    Directory of Open Access Journals (Sweden)

    Adam C Jones

    Full Text Available We describe a procedure for the conjugative transfer of phage P1-derived Artificial Chromosome (PAC library clones containing large natural product gene clusters (≥70 kilobases to Streptomyces coelicolor strains that have been engineered for improved heterologous production of natural products. This approach is demonstrated using the gene cluster for FK506 (tacrolimus, a clinically important immunosuppressant of high commercial value. The entire 83.5 kb FK506 gene cluster from Streptomyces tsukubaensis NRRL 18488 present in one 130 kb PAC clone was introduced into four different S. coelicolor derivatives and all produced FK506 and smaller amounts of the related compound FK520. FK506 yields were increased by approximately five-fold (from 1.2 mg L(-1 to 5.5 mg L(-1 in S. coelicolor M1146 containing the FK506 PAC upon over-expression of the FK506 LuxR regulatory gene fkbN. The PAC-based gene cluster conjugation methodology described here provides a tractable means to evaluate and manipulate FK506 biosynthesis and is readily applicable to other large gene clusters encoding natural products of interest to medicine, agriculture and biotechnology.

  12. Analysis of EML4-ALK Gene Fusion Mutation in Patients 
with Non-small Cell Lung Cancer

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    Xuzhou WANG

    2015-02-01

    Full Text Available Background and objective Non-small cell lung cancer (NSCLC is the main type of lung cancer, and the related locus mutation detection research has become a hot direction of molecular targeted therapy, studying on gene mutation status of echinodem microtubule associated protein like 4-Anaplastic lymphoma kinase (EML4-ALK and epidermal growth factor receptor (EGFR, detecting the sensitivity of EML4-ALK gene fusion and gene mutation of EGFR. Methods EML4-ALK gene fusion in 85 cases of paraffin embedded tumor tissue and adjacent lung tissue was detected with the application of immunohistochemistry (IHC, Scorpions amplification refractory mutation system (Scorpions ARMS fluorescence quantitative PCR and fluorescence in situ hybridization (FISH technology, and EGFR gene in 18, 19, 20 and 21 exon mutation status was detected with the application of ARMS method. Results In 115 cases of NSCLC, IHC showed 32 cases with ALK (D5F3 expression, the expression rate was 27.8%; ARMS showed 27 cases with EML4-ALK fusion gene mutation, the mutation detection rate was 23.5%; 53 cases were detected with EGFR mutation, the mutation rate was 46%. While FISH showed 23 cases with EML4-ALK fusion gene mutation, the detection rate was 20%, slightly lower than the ARMS detection results, suggesting that ARMS more sensitive. Conclusion The application of IHC, ARMS fluorescence quantitative PCR and FISH technology can make a rapid and accurate evaluation of EML4-ALK gene fusion.

  13. Biomechanics of Hybrid Anterior Cervical Fusion and Artificial Disc Replacement in 3-Level Constructs: An In Vitro Investigation

    OpenAIRE

    Liao, Zhenhua; Fogel, Guy R.; Pu, Ting; Gu, Hongsheng; Liu, Weiqiang

    2015-01-01

    Background The ideal surgical approach for cervical disk disease remains controversial, especially for multilevel cervical disease. The purpose of this study was to investigate the biomechanics of the cervical spine after 3-level hybrid surgery compared with 3-level anterior cervical discectomy and fusion (ACDF). Material/Methods Eighteen human cadaveric spines (C2-T1) were evaluated under displacement-input protocol. After intact testing, a simulated hybrid construct or fusion construct was ...

  14. Transforming activity of a novel mutant of HPV16 E6E7 fusion gene.

    Science.gov (United States)

    Xie, Qiang; Zhou, Zhi-Xiang; Li, Ze-Lin; Zeng, Yi

    2011-06-01

    An optimized recombinant HPV16 E6E7 fusion gene (HPV16 ofE6E7) was constructed according to codon usage for mammalian cell expression, and a mutant of HPV16 ofE6E7 fusion gene (HPV16 omfE6E7) was generated by site-directed mutagenesis at L57G, C113R for the E6 protein and C24G, E26G for the E7 protein for HPV16 ofE6E7 [patent pending (CN 101100672)]. The HPV16 omfE6E7 gene constructed in this work not only lost the transformation capability to NIH 3T3 cells and tumorigenicity in SCID mice, but also maintained very good stability and antigenicity. These results suggests that the HPV16 omfE6E7 gene should undergo further study for application as a safe antigen-specific therapeutic vaccine for HPV16-associated tumors. PMID:21667341

  15. Molecular evolution of the fusion protein gene in human respiratory syncytial virus subgroup A.

    Science.gov (United States)

    Kimura, Hirokazu; Nagasawa, Koo; Tsukagoshi, Hiroyuki; Matsushima, Yuki; Fujita, Kiyotaka; Yoshida, Lay Myint; Tanaka, Ryota; Ishii, Haruyuki; Shimojo, Naoki; Kuroda, Makoto; Ryo, Akihide

    2016-09-01

    We studied the molecular evolution of the fusion protein (F) gene in the human respiratory syncytial virus subgroup A (HRSV-A). We performed time-scaled phylogenetic analyses using the Bayesian Markov chain Monte Carlo (MCMC) method. We also conducted genetic distance (p-distance), positive/negative selection, and Bayesian skyline plot analyses. Furthermore, we mapped the amino acid substitutions of the protein. The MCMC-constructed tree indicated that the HRSV F gene diverged from the bovine RSV (BRSV) gene approximately 550years ago and had a relatively low substitution rate (7.59×10(-4) substitutions/site/year). Moreover, a common ancestor of HRSV-A and -B diverged approximately 280years ago, which has since formed four distinct clusters. The present HRSV-A strains were assigned six genotypes based on F gene sequences and attachment glycoprotein gene sequences. The present strains exhibited high F gene sequence similarity values and low genetic divergence. No positive selection sites were identified; however, 50 negative selection sites were identified. F protein amino acid substitutions at 17 sites were distributed in the F protein. The effective population size of the gene has remained relatively constant, but the population size of the prevalent genotype (GA2) has increased in the last 10years. These results suggest that the HRSV-AF gene has evolved independently and formed some genotypes. PMID:27291709

  16. Knockdown of Polyphenol Oxidase Gene Expression in Potato (Solanum tuberosum L.) with Artificial MicroRNAs.

    Science.gov (United States)

    Chi, Ming; Bhagwat, Basdeo; Tang, Guiliang; Xiang, Yu

    2016-01-01

    It is of great importance and interest to develop crop varieties with low polyphenol oxidase (PPO) activity for the food industry because PPO-mediated oxidative browning is a main cause of post-harvest deterioration and quality loss of fresh produce and processed foods. We recently demonstrated that potato tubers with reduced browning phenotypes can be produced by inhibition of the expression of several PPO gene isoforms using artificial microRNA (amiRNA) technology. The approach introduces a single type of 21-nucleotide RNA population to guide silencing of the PPO gene transcripts in potato tissues. Some advantages of the technology are: small RNA molecules are genetically transformed, off-target gene silencing can be avoided or minimized at the stage of amiRNA designs, and accuracy and efficiency of the processes can be detected at every step using molecular biological techniques. Here we describe the methods for transformation and regeneration of potatoes with amiRNA vectors, detection of the expression of amiRNAs, identification of the cleaved product of the target gene transcripts, and assay of the expression level of PPO gene isoforms in potatoes. PMID:26843174

  17. Footprints of natural and artificial selection for photoperiod pathway genes in Oryza.

    Science.gov (United States)

    Huang, Chao-Li; Hung, Cheng-Yu; Chiang, Yu-Chung; Hwang, Chi-Chuan; Hsu, Tsai-Wen; Huang, Chi-Chun; Hung, Kuo-Hsiang; Tsai, Kun-Chan; Wang, Kuo-Hsiung; Osada, Naoki; Schaal, Barbara Anna; Chiang, Tzen-Yuh

    2012-06-01

    Asian rice, Oryza sativa, consists of two major subspecies, indica and japonica, which are physiologically differentiated and adapted to different latitudes. Genes for photoperiod sensitivity are likely targets of selection along latitude. We examined the footprints of natural and artificial selections for four major genes of the photoperiod pathway, namely PHYTOCHROME B (PhyB), HEADING DATE 1 (Hd1), HEADING DATE 3a (Hd3a), and EARLY HEADING DATE 1 (Ehd1), by investigation of the patterns of nucleotide polymorphisms in cultivated and wild rice. Geographical subdivision between tropical and subtropical O. rufipogon was found for all of the photoperiod genes in plants divided by the Tropic of Cancer (TOC). All of these genes, except for PhyB, were characterized by the existence of clades that split a long time ago and that corresponded to latitudinal subdivisions, and revealed a likely diversifying selection. Ssp. indica showed close affinity to tropical O. rufipogon for all genes, while ssp. japonica, which has a much wider range of distribution, displayed complex patterns of differentiation from O. rufipogon, which reflected various agricultural needs in relation to crop yield. In japonica, all genes, except Hd3a, were genetically differentiated at the TOC, while geographical subdivision occurred at 31°N in Hd3a, probably the result of varying photoperiods. Many other features of the photoperiod genes revealed domestication signatures, which included high linkage disequilibrium (LD) within genes, the occurrence of frequent and recurrent non-functional Hd1 mutants in cultivated rice, crossovers between subtropical and tropical alleles of Hd1, and significant LD between Hd1 and Hd3a in japonica and indica.

  18. Structural analysis of the genome of breast cancer cell line ZR-75-30 identifies twelve expressed fusion genes

    Directory of Open Access Journals (Sweden)

    Schulte Ina

    2012-12-01

    Full Text Available Abstract Background It has recently emerged that common epithelial cancers such as breast cancers have fusion genes like those in leukaemias. In a representative breast cancer cell line, ZR-75-30, we searched for fusion genes, by analysing genome rearrangements. Results We first analysed rearrangements of the ZR-75-30 genome, to around 10kb resolution, by molecular cytogenetic approaches, combining array painting and array CGH. We then compared this map with genomic junctions determined by paired-end sequencing. Most of the breakpoints found by array painting and array CGH were identified in the paired end sequencing—55% of the unamplified breakpoints and 97% of the amplified breakpoints (as these are represented by more sequence reads. From this analysis we identified 9 expressed fusion genes: APPBP2-PHF20L1, BCAS3-HOXB9, COL14A1-SKAP1, TAOK1-PCGF2, TIAM1-NRIP1, TIMM23-ARHGAP32, TRPS1-LASP1, USP32-CCDC49 and ZMYM4-OPRD1. We also determined the genomic junctions of a further three expressed fusion genes that had been described by others, BCAS3-ERBB2, DDX5-DEPDC6/DEPTOR and PLEC1-ENPP2. Of this total of 12 expressed fusion genes, 9 were in the coamplification. Due to the sensitivity of the technologies used, we estimate these 12 fusion genes to be around two-thirds of the true total. Many of the fusions seem likely to be driver mutations. For example, PHF20L1, BCAS3, TAOK1, PCGF2, and TRPS1 are fused in other breast cancers. HOXB9 and PHF20L1 are members of gene families that are fused in other neoplasms. Several of the other genes are relevant to cancer—in addition to ERBB2, SKAP1 is an adaptor for Src, DEPTOR regulates the mTOR pathway and NRIP1 is an estrogen-receptor coregulator. Conclusions This is the first structural analysis of a breast cancer genome that combines classical molecular cytogenetic approaches with sequencing. Paired-end sequencing was able to detect almost all breakpoints, where there was adequate read depth. It supports

  19. Studying Gene Expression: Database Searches and Promoter Fusions to Investigate Transcriptional Regulation in Bacteria

    Directory of Open Access Journals (Sweden)

    Betsy M. Martinez- Vaz

    2010-04-01

    Full Text Available A laboratory project was designed to illustrate how to search biological databases and utilize the information provided by these resources to investigate transcriptional regulation in Escherichia coli. The students searched several databases (NCBI Genomes, RegulonDB and EcoCyc to learn about gene function, regulation, and the organization of transcriptional units. A fluorometer and GFP promoter fusions were used to obtain fluorescence data and measure changes in transcriptional activity. The class designed and performed experiments to investigate the regulation of genes necessary for biosynthesis of amino acids and how expression is affected by environmental signals and transcriptional regulators. Assessment data showed that this activity enhanced students’ knowledge of databases, reporter genes and transcriptional regulation.

  20. Comprehensive protein-based artificial microRNA screens for effective gene silencing in plants.

    Science.gov (United States)

    Li, Jian-Feng; Chung, Hoo Sun; Niu, Yajie; Bush, Jenifer; McCormack, Matthew; Sheen, Jen

    2013-05-01

    Artificial microRNA (amiRNA) approaches offer a powerful strategy for targeted gene manipulation in any plant species. However, the current unpredictability of amiRNA efficacy has limited broad application of this promising technology. To address this, we developed epitope-tagged protein-based amiRNA (ETPamir) screens, in which target mRNAs encoding epitope-tagged proteins were constitutively or inducibly coexpressed in protoplasts with amiRNA candidates targeting single or multiple genes. This design allowed parallel quantification of target proteins and mRNAs to define amiRNA efficacy and mechanism of action, circumventing unpredictable amiRNA expression/processing and antibody unavailability. Systematic evaluation of 63 amiRNAs in 79 ETPamir screens for 16 target genes revealed a simple, effective solution for selecting optimal amiRNAs from hundreds of computational predictions, reaching ∼100% gene silencing in plant cells and null phenotypes in transgenic plants. Optimal amiRNAs predominantly mediated highly specific translational repression at 5' coding regions with limited mRNA decay or cleavage. Our screens were easily applied to diverse plant species, including Arabidopsis thaliana, tobacco (Nicotiana benthamiana), tomato (Solanum lycopersicum), sunflower (Helianthus annuus), Catharanthus roseus, maize (Zea mays) and rice (Oryza sativa), and effectively validated predicted natural miRNA targets. These screens could improve plant research and crop engineering by making amiRNA a more predictable and manageable genetic and functional genomic technology.

  1. The prognostic value of PCA3, the fusion gene TMPRSS2:ERG and other markers in prostate cancer

    OpenAIRE

    HOLÁ, Hana

    2014-01-01

    The aim of this thesis was to assess the presence of fusion gene TMPRSS2:ERG and expressions of PCA3, miR23b, miR26 and miR221 in PCa. PSA was measured in peripheral blood and tumor tissue (FFPE samples). The presence of fusion gene TMPRSS2:ERG and expression of PCA3 gene and miRNA in FFPE tumor tissue was analysed by RT real-time PCR. This determination would help to identify patients with high-risk tumors.

  2. A case of lung adenocarcinoma harboring EGFR mutation and EML4-ALK fusion gene

    Directory of Open Access Journals (Sweden)

    Tanaka Hisashi

    2012-11-01

    Full Text Available Abstract Background Lung cancer is the leading cause of cancer-related death worldwide. Epidermal growth factor receptor (EGFR - tyrosine kinase inhibitor (TKI is used for the patients with EGFR-mutant lung cancer. Recently, phase III studies in the patients with EGFR-mutant demonstrated that EGFR-TKI monotherapy improved progression-free survival compared with platinum-doublet chemotherapy. The echinoderm microtubule-associated protein-like 4 (EML4 - anaplastic lymphoma kinase (ALK fusion oncogene represents one of the newest molecular targets in non-small cell lung cancer (NSCLC. Patients who harbor EML4-ALK fusions have been associated with a lack of EGFR or KRAS mutations. Case presentation We report a 39-year-old patient diagnosed as adenocarcinoma harboring EGFR mutation and EML4-ALK fusion gene. We treated this patient with erlotinib as the third line therapy, but no clinical benefit was obtained. Conclusion We experienced a rare case with EGFR mutation and EML4-ALK. Any clinical benefit using EGFR-TKI was not obtained in our case. The therapeutic choice for the patients with more than one driver mutations is unclear. We needs further understanding of the lung cancer molecular biology and the biomarker infomation.

  3. Prokaryotic ancestry and gene fusion of a dual localized peroxiredoxin in malaria parasites

    Directory of Open Access Journals (Sweden)

    Carine F. Djuika

    2015-01-01

    Full Text Available Horizontal gene transfer has emerged as a crucial driving force for the evolution of eukaryotes. This also includes Plasmodium falciparum and related economically and clinically relevant apicomplexan parasites, whose rather small genomes have been shaped not only by natural selection in different host populations but also by horizontal gene transfer following endosymbiosis. However, there is rather little reliable data on horizontal gene transfer between animal hosts or bacteria and apicomplexan parasites. Here we show that apicomplexan homologues of peroxiredoxin 5 (Prx5 have a prokaryotic ancestry and therefore represent a special subclass of Prx5 isoforms in eukaryotes. Using two different immunobiochemical approaches, we found that the P. falciparum Prx5 homologue is dually localized to the parasite plastid and cytosol. This dual localization is reflected by a modular Plasmodium-specific gene architecture consisting of two exons. Despite the plastid localization, our phylogenetic analyses contradict an acquisition by secondary endosymbiosis and support a gene fusion event following a horizontal prokaryote-to-eukaryote gene transfer in early apicomplexans. The results provide unexpected insights into the evolution of apicomplexan parasites as well as the molecular evolution of peroxiredoxins, an important family of ubiquitous, usually highly concentrated thiol-dependent hydroperoxidases that exert functions as detoxifying enzymes, redox sensors and chaperones.

  4. Decoding of exon splicing patterns in the human RUNX1-RUNX1T1 fusion gene.

    Science.gov (United States)

    Grinev, Vasily V; Migas, Alexandr A; Kirsanava, Aksana D; Mishkova, Olga A; Siomava, Natalia; Ramanouskaya, Tatiana V; Vaitsiankova, Alina V; Ilyushonak, Ilia M; Nazarov, Petr V; Vallar, Laurent; Aleinikova, Olga V

    2015-11-01

    The t(8;21) translocation is the most widespread genetic defect found in human acute myeloid leukemia. This translocation results in the RUNX1-RUNX1T1 fusion gene that produces a wide variety of alternative transcripts and influences the course of the disease. The rules of combinatorics and splicing of exons in the RUNX1-RUNX1T1 transcripts are not known. To address this issue, we developed an exon graph model of the fusion gene organization and evaluated its local exon combinatorics by the exon combinatorial index (ECI). Here we show that the local exon combinatorics of the RUNX1-RUNX1T1 gene follows a power-law behavior and (i) the vast majority of exons has a low ECI, (ii) only a small part is represented by "exons-hubs" of splicing with very high ECI values, and (iii) it is scale-free and very sensitive to targeted skipping of "exons-hubs". Stochasticity of the splicing machinery and preferred usage of exons in alternative splicing can explain such behavior of the system. Stochasticity may explain up to 12% of the ECI variance and results in a number of non-coding and unproductive transcripts that can be considered as a noise. Half-life of these transcripts is increased due to the deregulation of some key genes of the nonsense-mediated decay system in leukemia cells. On the other hand, preferred usage of exons may explain up to 75% of the ECI variability. Our analysis revealed a set of splicing-related cis-regulatory motifs that can explain "attractiveness" of exons in alternative splicing but only when they are considered together. Cis-regulatory motifs are guides for splicing trans-factors and we observed a leukemia-specific profile of expression of the splicing genes in t(8;21)-positive blasts. Altogether, our results show that alternative splicing of the RUNX1-RUNX1T1 transcripts follows strict rules and that the power-law component of the fusion gene organization confers a high flexibility to this process.

  5. A clinical and laboratory study of chronic myeloid leukemia with atypical BCR-ABL fusion gene subtypes

    Institute of Scientific and Technical Information of China (English)

    桂晓敏

    2014-01-01

    Objective To explore the clinical and laboratory features of chronic myeloid leukemia(CML)with atypical e14a3 and e19a2 BCR-ABL fusion gene subtypes.Methods We retrospectively analyzed a cohort of CML patients with Ph chromosome positive confirmed by cytogenetic and FISH but classical e13a3(b2a2),e14a2(b3a2)and e1a2 fusion transcripts negative identified by

  6. Spatial and temporal analysis of gene expression during growth and fusion of the mouse facial prominences.

    Directory of Open Access Journals (Sweden)

    Weiguo Feng

    Full Text Available Orofacial malformations resulting from genetic and/or environmental causes are frequent human birth defects yet their etiology is often unclear because of insufficient information concerning the molecular, cellular and morphogenetic processes responsible for normal facial development. We have, therefore, derived a comprehensive expression dataset for mouse orofacial development, interrogating three distinct regions - the mandibular, maxillary and frontonasal prominences. To capture the dynamic changes in the transcriptome during face formation, we sampled five time points between E10.5-E12.5, spanning the developmental period from establishment of the prominences to their fusion to form the mature facial platform. Seven independent biological replicates were used for each sample ensuring robustness and quality of the dataset. Here, we provide a general overview of the dataset, characterizing aspects of gene expression changes at both the spatial and temporal level. Considerable coordinate regulation occurs across the three prominences during this period of facial growth and morphogenesis, with a switch from expression of genes involved in cell proliferation to those associated with differentiation. An accompanying shift in the expression of polycomb and trithorax genes presumably maintains appropriate patterns of gene expression in precursor or differentiated cells, respectively. Superimposed on the many coordinated changes are prominence-specific differences in the expression of genes encoding transcription factors, extracellular matrix components, and signaling molecules. Thus, the elaboration of each prominence will be driven by particular combinations of transcription factors coupled with specific cell:cell and cell:matrix interactions. The dataset also reveals several prominence-specific genes not previously associated with orofacial development, a subset of which we externally validate. Several of these latter genes are components of

  7. Spatial and temporal analysis of gene expression during growth and fusion of the mouse facial prominences.

    Science.gov (United States)

    Feng, Weiguo; Leach, Sonia M; Tipney, Hannah; Phang, Tzulip; Geraci, Mark; Spritz, Richard A; Hunter, Lawrence E; Williams, Trevor

    2009-12-16

    Orofacial malformations resulting from genetic and/or environmental causes are frequent human birth defects yet their etiology is often unclear because of insufficient information concerning the molecular, cellular and morphogenetic processes responsible for normal facial development. We have, therefore, derived a comprehensive expression dataset for mouse orofacial development, interrogating three distinct regions - the mandibular, maxillary and frontonasal prominences. To capture the dynamic changes in the transcriptome during face formation, we sampled five time points between E10.5-E12.5, spanning the developmental period from establishment of the prominences to their fusion to form the mature facial platform. Seven independent biological replicates were used for each sample ensuring robustness and quality of the dataset. Here, we provide a general overview of the dataset, characterizing aspects of gene expression changes at both the spatial and temporal level. Considerable coordinate regulation occurs across the three prominences during this period of facial growth and morphogenesis, with a switch from expression of genes involved in cell proliferation to those associated with differentiation. An accompanying shift in the expression of polycomb and trithorax genes presumably maintains appropriate patterns of gene expression in precursor or differentiated cells, respectively. Superimposed on the many coordinated changes are prominence-specific differences in the expression of genes encoding transcription factors, extracellular matrix components, and signaling molecules. Thus, the elaboration of each prominence will be driven by particular combinations of transcription factors coupled with specific cell:cell and cell:matrix interactions. The dataset also reveals several prominence-specific genes not previously associated with orofacial development, a subset of which we externally validate. Several of these latter genes are components of bidirectional

  8. Evolution by Pervasive Gene Fusion in Antibiotic Resistance and Antibiotic Synthesizing Genes

    Directory of Open Access Journals (Sweden)

    Orla Coleman

    2015-03-01

    Full Text Available Phylogenetic (tree-based approaches to understanding evolutionary history are unable to incorporate convergent evolutionary events where two genes merge into one. In this study, as exemplars of what can be achieved when a tree is not assumed a priori, we have analysed the evolutionary histories of polyketide synthase genes and antibiotic resistance genes and have shown that their history is replete with convergent events as well as divergent events. We demonstrate that the overall histories of these genes more closely resembles the remodelling that might be seen with the children’s toy Lego, than the standard model of the phylogenetic tree. This work demonstrates further that genes can act as public goods, available for re-use and incorporation into other genetic goods.

  9. Horizontal gene transfers and cell fusions in microbiology, immunology and oncology (Review).

    Science.gov (United States)

    Sinkovics, Joseph G

    2009-09-01

    Evolving young genomes of archaea, prokaryota and unicellular eukaryota were wide open for the acceptance of alien genomic sequences, which they often preserved and vertically transferred to their descendants throughout three billion years of evolution. Established complex large genomes, although seeded with ancestral retroelements, have come to regulate strictly their integrity. However, intruding retroelements, especially the descendents of Ty3/Gypsy, the chromoviruses, continue to find their ways into even the most established genomes. The simian and hominoid-Homo genomes preserved and accommodated a large number of endogenous retroviral genomic segments. These retroelements may mature into exogenous retroviruses, or into functional new genes. Phages and viruses have been instrumental in incorporating and transferring host cell genes. These events profoundly influenced and altered the course of evolution. Horizontal (lateral) gene transfers (HGT) overwhelmed the genomes of the ancient protocells and the evolving unicellular microorganisms, actually leading to their Cambrian explosion. While the rigidly organized genomes of multicellular organisms increasingly resist H/LGT, de-differentiated cells assuming the metabolism of their onto- or phylogenetic ancestors, open up widely to the practice of H/LGT by direct transfer, or to transfers mediated by viruses, or by cell fusions. This activity is intensified in malignantly transformed cells, thus rendering these subjects receptive to therapy with oncolytic viruses and with viral vectors of tumor-suppressive or immunogenic genetic materials. Naturally formed hybrids of dendritic and tumor cells are often tolerogenic, whereas laboratory products of these unisons may be immunogenic in the hosts of origin. As human breast cancer stem cells are induced by a treacherous class of CD8+ T cells to undergo epithelial to mesenchymal (ETM) transition and to yield to malignant transformation by the omnipresent proto

  10. Ethanol utilization regulatory protein: profile alignments give no evidence of origin through aldehyde and alcohol dehydrogenase gene fusion.

    OpenAIRE

    Nicholas, H B; Persson, B; Jörnvall, H; Hempel, J.

    1995-01-01

    The suggestion that the ethanol regulatory protein from Aspergillus has its evolutionary origin in a gene fusion between aldehyde and alcohol dehydrogenase genes (Hawkins AR, Lamb HK, Radford A, Moore JD, 1994, Gene 146:145-158) has been tested by profile analysis with aldehyde and alcohol dehydrogenase family profiles. We show that the degree and kind of similarity observed between these profiles and the ethanol regulatory protein sequence is that expected from random sequences of the same c...

  11. Acquiring transgenic tobacco plants with insect resistance and glyphosate tolerance by fusion gene transformation.

    Science.gov (United States)

    Sun, He; Lang, Zhihong; Zhu, Li; Huang, Dafang

    2012-10-01

    The advantages of gene 'stacking' or 'pyramiding' are obvious in genetically modified (GM) crops, and several different multi-transgene-stacking methods are available. Using linker peptides for multiple gene transformation is considered to be a good method to meet a variety of needs. In our experiment, the Bt cry1Ah gene, which encodes the insect-resistance protein, and the mG ( 2 ) -epsps gene, which encodes the glyphosate-tolerance protein, were connected by a 2A or LP4/2A linker. Linker 2A is a peptide from the foot-and-mouth disease virus (FMDV) that has self-cleavage activity. LP4 is a peptide from Raphanus sativus seeds that has a recognition site and is cleaved by a protease. LP4/2A is a hybrid peptide that contains the first 9 amino acids of LP4 and 20 amino acids from 2A. We used the linker peptide to construct four coordinated expression vectors: pHAG, pHLAG, pGAH and pGLAH. Two single gene expression vectors, pSAh and pSmG(2), were used as controls. The six expression vectors and the pCAMBIA2301 vector were transferred into tobacco by Agrobacterium tumefaciens-mediated transformation, and 529 transformants were obtained. Molecular detection and bioassay detection data demonstrated that the transgenic tobaccos possessed good pest resistance and glyphosate tolerance. The two genes in the fusion vector were expressed simultaneously. The plants with the genes linked by the LP4/2A peptide showed better pest resistance and glyphosate tolerance than the plants with the genes linked by 2A. The expression level of the two genes linked by LP4/2A was not significantly different from the single gene vector. Key message The expression level of the two genes linked by LP4/2A was higher than those linked by 2A and was not significantly different from the single gene vector.

  12. Anti-colorectal cancer effect of interleukin-2 and interferon-β fusion gene driven by carcinoembryonic antigen promoter

    Directory of Open Access Journals (Sweden)

    Wang Y

    2016-05-01

    Full Text Available Yan Wang, Mengchun Wang, Yan LiDepartment of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaAbstract: This study was designed to investigate the antitumor effects of combined interleukin-2/interferon-β-based gene therapy in colorectal cancer. Transfection of the fusion gene expression plasmid induced significant apoptosis of Lovo cells. Additionally, the fusion gene exhibited strong inhibitory activity against tumor growth and apoptosis when being injected into the nude mice implanted with human colon cancer cells. Furthermore, the tail-vein injection showed a more notable effect than direct injection into tumor. These results suggest that the combined interleukin-2/interferon-β-based gene therapy with the carcinoembryonic antigen promoter might be an effective antitumor strategy.Keywords: apoptosis, interferon-β, interleukin-2, antitumor, combined gene therapy

  13. Artificial selection for a green revolution gene during japonica rice domestication.

    Science.gov (United States)

    Asano, Kenji; Yamasaki, Masanori; Takuno, Shohei; Miura, Kotaro; Katagiri, Satoshi; Ito, Tomoko; Doi, Kazuyuki; Wu, Jianzhong; Ebana, Kaworu; Matsumoto, Takashi; Innan, Hideki; Kitano, Hidemi; Ashikari, Motoyuki; Matsuoka, Makoto

    2011-07-01

    The semidwarf phenotype has been extensively selected during modern crop breeding as an agronomically important trait. Introduction of the semidwarf gene, semi-dwarf1 (sd1), which encodes a gibberellin biosynthesis enzyme, made significant contributions to the "green revolution" in rice (Oryza sativa L.). Here we report that SD1 was involved not only in modern breeding including the green revolution, but also in early steps of rice domestication. We identified two SNPs in O. sativa subspecies (ssp.) japonica SD1 as functional nucleotide polymorphisms (FNPs) responsible for shorter culm length and low gibberellin biosynthetic activity. Genetic diversity analysis among O. sativa ssp. japonica and indica, along with their wild ancestor O. rufipogon Griff, revealed that these FNPs clearly differentiate the japonica landrace and O. rufipogon. We also found a dramatic reduction in nucleotide diversity around SD1 only in the japonica landrace, not in the indica landrace or O. rufipogon. These findings indicate that SD1 has been subjected to artificial selection in rice evolution and that the FNPs participated in japonica domestication, suggesting that ancient humans already used the green revolution gene.

  14. Artificial Neural Networks and Gene Expression Programing based age estimation using facial features

    Directory of Open Access Journals (Sweden)

    Baddrud Z. Laskar

    2015-10-01

    Full Text Available This work is about estimating human age automatically through analysis of facial images. It has got a lot of real-world applications. Due to prompt advances in the fields of machine vision, facial image processing, and computer graphics, automatic age estimation via faces in computer is one of the dominant topics these days. This is due to widespread real-world applications, in areas of biometrics, security, surveillance, control, forensic art, entertainment, online customer management and support, along with cosmetology. As it is difficult to estimate the exact age, this system is to estimate a certain range of ages. Four sets of classifications have been used to differentiate a person’s data into one of the different age groups. The uniqueness about this study is the usage of two technologies i.e., Artificial Neural Networks (ANN and Gene Expression Programing (GEP to estimate the age and then compare the results. New methodologies like Gene Expression Programing (GEP have been explored here and significant results were found. The dataset has been developed to provide more efficient results by superior preprocessing methods. This proposed approach has been developed, tested and trained using both the methods. A public data set was used to test the system, FG-NET. The quality of the proposed system for age estimation using facial features is shown by broad experiments on the available database of FG-NET.

  15. Rapid and efficient introduction of a foreign gene into bacterial artificial chromosome-cloned varicella vaccine by Tn7-mediated site-specific transposition

    International Nuclear Information System (INIS)

    Using a rapid and reliable system based on Tn7-mediated site-specific transposition, we have successfully constructed a recombinant Oka varicella vaccine (vOka) expressing the mumps virus (MuV) fusion protein (F). The backbone of the vector was our previously reported vOka-BAC (bacterial artificial chromosome) genome. We inserted the transposon Tn7 attachment sequence, LacZα-mini-attTn7, into the region between ORF12 and ORF13 to generate a vOka-BAC-Tn genome. The MuV-F expressing cassette was transposed into the vOka-BAC genome at the mini-attTn7 transposition site. MuV-F protein was expressed in recombinant virus, rvOka-F infected cells. In addition, the MuV-F protein was cleaved in the rvOka-F infected cells as in MuV-infected cells. The growth of rvOka-F was similar to that of the original recombinant vOka without the F gene. Thus, we show that Tn7-mediated transposition is an efficient method for introducing a foreign gene expression cassette into the vOka-BAC genome as a live virus vector.

  16. Construction of hpaA gene from a clinical isolate of Helicobacter pyloriand identification of fusion protein

    Institute of Scientific and Technical Information of China (English)

    Ya-Fei Mao; Jie Yan; Li-Wei Li; Shu-Ping Li

    2003-01-01

    AIM: To clone hpaA gene from a clinical strain of Helicobacter pylori and to construct the expression vector of the gene and to identify immunity of the fusion protein.METHODS: The hpaA gene from a clinical isolate Y06 of H.pylori was amplified by high fidelity PCR. The nucleotide sequence of the target DNA amplification fragment was sequenced after T-A cloning. The recombinant expression vector inserted with hpaA gene was constructed. The expression of HpaA fusion protein in E. coli BL21DE3 induced by IPTG at different dosages was examined by SDS-PAGE.Western blot with commercial antibody against whole cell of H. pylorias well as immunodiffusion assay with selfprepared rabbit antiserum against HpaA fusion protein were applied to determine immunity of the fusion protein. ELISA was used to detect the antibody against HpaA in sera of 125 patients infected with H. pylori and to examine HpaA expression of 109 clinical isolates of H. pylori.RESULTS: In comparison with the reported corresponding sequences, the homologies of nucleotide and putative amino acid sequences of the cloned hpaA gene were from 94.25-97.32 % and 95.38-98.46 %, respectively. The output of HpaA fusion protein in its expression system of pET32ahpaA-BL21DE3 was approximately 40 % of the total bacterial proteins. HpaA fusion protein was able to combine with the commercial antibody against whole cell of H. pyloriand to induce rabbit producing specific antiserum with 1:4immunodiffusion titer after the animal was immunized with the fusion protein. 81.6 % of the serum samples from 125patients infected with H.pylori(102/125) were positive for HpaA antibody and all of the tested isolates of H.pylori(109/109) were detectable for HpaA.CONCLUSION: A prokaryotic expression system with high efficiency of H.pylorihpaA gene was successfully established.The HpaA expressing fusion protein showed satisfactory immunoreactivity and antigenicity. High frequencies of HpaA expression in different H. pyloriclinicalstrains

  17. Loss of the NKX3.1 tumorsuppressor promotes the TMPRSS2-ERG fusion gene expression in prostate cancer

    International Nuclear Information System (INIS)

    In normal prostate epithelium the TMPRSS2 gene encoding a type II serine protease is directly regulated by male hormones through the androgen receptor. In prostate cancer ERG protooncogene frequently gains hormonal control by seizing gene regulatory elements of TMPRSS2 through genomic fusion events. Although, the androgenic activation of TMPRSS2 gene has been established, little is known about other elements that may interact with TMPRSS2 promoter sequences to modulate ERG expression in TMPRSS2-ERG gene fusion context. Comparative genomic analyses of the TMPRSS2 promoter upstream sequences and pathway analyses were performed by the Genomatix Software. NKX3.1 and ERG genes expressions were evaluated by immunoblot or by quantitative Real-Time PCR (qRT-PCR) assays in response to siRNA knockdown or heterologous expression. QRT-PCR assay was used for monitoring the gene expression levels of NKX3.1-regulated genes. Transcriptional regulatory function of NKX3.1 was assessed by luciferase assay. Recruitment of NKX3.1 to its cognate elements was monitored by Chromatin Immunoprecipitation assay. Comparative analysis of the TMPRSS2 promoter upstream sequences among different species revealed the conservation of binding sites for the androgen inducible NKX3.1 tumor suppressor. Defects of NKX3.1, such as, allelic loss, haploinsufficiency, attenuated expression or decreased protein stability represent established pathways in prostate tumorigenesis. We found that NKX3.1 directly binds to TMPRSS2 upstream sequences and negatively regulates the expression of the ERG protooncogene through the TMPRSS2-ERG gene fusion. These observations imply that the frequently noted loss-of-function of NKX3.1 cooperates with the activation of TMPRSS2-ERG fusions in prostate tumorigenesis

  18. Drosophila Erect wing (Ewg) controls mitochondrial fusion during muscle growth and maintenance by regulation of the Opa1-like gene.

    Science.gov (United States)

    Rai, Mamta; Katti, Prasanna; Nongthomba, Upendra

    2014-01-01

    Mitochondrial biogenesis and morphological changes are associated with tissue-specific functional demand, but the factors and pathways that regulate these processes have not been completely identified. A lack of mitochondrial fusion has been implicated in various developmental and pathological defects. The spatiotemporal regulation of mitochondrial fusion in a tissue such as muscle is not well understood. Here, we show in Drosophila indirect flight muscles (IFMs) that the nuclear-encoded mitochondrial inner membrane fusion gene, Opa1-like, is regulated in a spatiotemporal fashion by the transcription factor/co-activator Erect wing (Ewg). In IFMs null for Ewg, mitochondria undergo mitophagy and/or autophagy accompanied by reduced mitochondrial functioning and muscle degeneration. By following the dynamics of mitochondrial growth and shape in IFMs, we found that mitochondria grow extensively and fuse during late pupal development to form the large tubular mitochondria. Our evidence shows that Ewg expression during early IFM development is sufficient to upregulate Opa1-like, which itself is a requisite for both late pupal mitochondrial fusion and muscle maintenance. Concomitantly, by knocking down Opa1-like during early muscle development, we show that it is important for mitochondrial fusion, muscle differentiation and muscle organization. However, knocking down Opa1-like, after the expression window of Ewg did not cause mitochondrial or muscle defects. This study identifies a mechanism by which mitochondrial fusion is regulated spatiotemporally by Ewg through Opa1-like during IFM differentiation and growth.

  19. Propagating gene expression fronts in a one-dimensional coupled system of artificial cells

    Science.gov (United States)

    Tayar, Alexandra M.; Karzbrun, Eyal; Noireaux, Vincent; Bar-Ziv, Roy H.

    2015-12-01

    Living systems employ front propagation and spatiotemporal patterns encoded in biochemical reactions for communication, self-organization and computation. Emulating such dynamics in minimal systems is important for understanding physical principles in living cells and in vitro. Here, we report a one-dimensional array of DNA compartments in a silicon chip as a coupled system of artificial cells, offering the means to implement reaction-diffusion dynamics by integrated genetic circuits and chip geometry. Using a bistable circuit we programmed a front of protein synthesis propagating in the array as a cascade of signal amplification and short-range diffusion. The front velocity is maximal at a saddle-node bifurcation from a bistable regime with travelling fronts to a monostable regime that is spatially homogeneous. Near the bifurcation the system exhibits large variability between compartments, providing a possible mechanism for population diversity. This demonstrates that on-chip integrated gene circuits are dynamical systems driving spatiotemporal patterns, cellular variability and symmetry breaking.

  20. Efficient transformation and artificial miRNA gene silencing in Lemna minor.

    Science.gov (United States)

    Cantó-Pastor, A; Mollá-Morales, A; Ernst, E; Dahl, W; Zhai, J; Yan, Y; Meyers, B C; Shanklin, J; Martienssen, R

    2015-01-01

    Despite rapid doubling time, simple architecture and ease of metabolic labelling, a lack of genetic tools in the Lemnaceae (duckweed) has impeded the full implementation of this organism as a model for biological research. Here, we present technologies to facilitate high-throughput genetic studies in duckweed. We developed a fast and efficient method for producing Lemna minor stable transgenic fronds via Agrobacterium-mediated transformation and regeneration from tissue culture. Additionally, we engineered an artificial microRNA (amiRNA) gene silencing system. We identified a Lemna gibba endogenous miR166 precursor and used it as a backbone to produce amiRNAs. As a proof of concept we induced the silencing of CH42, a magnesium chelatase subunit, using our amiRNA platform. Expression of CH42 in transgenic L. minor fronds was significantly reduced, which resulted in reduction of chlorophyll pigmentation. The techniques presented here will enable tackling future challenges in the biology and biotechnology of Lemnaceae. PMID:24989135

  1. Gene fusion detection in formalin-fixed paraffin-embedded benign fibrous histiocytomas using fluorescence in situ hybridization and RNA sequencing.

    Science.gov (United States)

    Walther, Charles; Hofvander, Jakob; Nilsson, Jenny; Magnusson, Linda; Domanski, Henryk A; Gisselsson, David; Tayebwa, Johnbosco; Doyle, Leona A; Fletcher, Christopher D M; Mertens, Fredrik

    2015-09-01

    Benign fibrous histiocytomas (FH) can be subdivided into several morphological and clinical subgroups. Recently, gene fusions involving either one of two protein kinase C genes (PRKCB and PRKCD) or the ALK gene were described in FH. We here wanted to evaluate the frequency of PRKCB and PRKCD gene fusions in FH. Using interphase fluorescence in situ hybridization on sections from formalin-fixed paraffin-embedded (FFPE) tumors, 36 cases could be analyzed. PRKCB or PRKCD rearrangements were seen in five tumors: 1/7 regular, 0/3 aneurysmal, 0/6 cellular, 2/7 epithelioid, 0/1 atypical, 2/10 deep, and 0/2 metastatic lesions. We also evaluated the status of the ALK gene in selected cases, finding rearrangements in 3/7 epithelioid and 0/1 atypical lesions. To assess the gene fusion status of FH further, deep sequencing of RNA (RNA-Seq) was performed on FFPE tissue from eight cases with unknown gene fusion status, as well as on two FH and six soft tissue sarcomas with known gene fusions; of the latter eight positive controls, the expected fusion transcript was found in all but one, while 2/8 FH with unknown genetic status showed fusion transcripts, including a novel KIRREL/PRKCA chimera. Thus, also a third member of the PRKC family is involved in FH tumorigenesis. We conclude that gene fusions involving PRKC genes occur in several morphological (regular, cellular, aneurysmal, epithelioid) and clinical (cutaneous, deep) subsets of FH, but they seem to account for only a minority of the cases. In epithelioid lesions, however, rearrangements of PRKC or ALK were seen, as mutually exclusive events, in the majority (5/7) of cases. Finally, the study also shows that RNA-Seq is a promising tool for identifying gene fusions in FFPE tissues.

  2. Genome-wide identification of genes with amplification and/or fusion in small cell lung cancer.

    Science.gov (United States)

    Iwakawa, Reika; Takenaka, Masataka; Kohno, Takashi; Shimada, Yoko; Totoki, Yasushi; Shibata, Tatsuhiro; Tsuta, Koji; Nishikawa, Ryo; Noguchi, Masayuki; Sato-Otsubo, Aiko; Ogawa, Seishi; Yokota, Jun

    2013-09-01

    To obtain a landscape of gross genetic alterations in small cell lung cancer (SCLC), genome-wide copy number analysis and whole-transcriptome sequencing were performed in 58 and 42 SCLCs, respectively. Focal amplification of known oncogene loci, MYCL1 (1p34.2), MYCN (2p24.3), and MYC (8q24.21), was frequently and mutually exclusively detected. MYCL1 and MYC were co-amplified with other regions on either the same or the different chromosome in several cases. In addition, the 9p24.1 region was identified as being amplified in SCLCs without amplification of MYC family oncogenes. Notably, expression of the KIAA1432 gene in this region was significantly higher in KIAA1432 amplified cells than in non-amplified cells, and its mRNA expression showed strong correlations with the copy numbers. Thus, KIAA1432 is a novel gene activated by amplification in SCLCs. By whole-transcriptome sequencing, a total of 60 fusion transcripts, transcribed from 95 different genes, were identified as being expressed in SCLC cells. However, no in-frame fusion transcripts were recurrently detected in ≥2 SCLCs, and genes in the amplified regions, such as PVT1 neighboring MYC and RLF in MYCL1 amplicons, were recurrently fused with genes in the same amplicons or with those in different amplicons on either the same or different chromosome. Thus, it was indicated that amplification and fusion of several genes on chromosomes 1 and 8 occur simultaneously but not sequentially through chromothripsis in the development of SCLC, and amplification rather than fusion of genes plays an important role in its development. PMID:23716474

  3. Fusion of ZMYND8 and RELA genes in acute erythroid leukemia

    DEFF Research Database (Denmark)

    Panagopoulos, Ioannis; Micci, Francesca; Thorsen, Jim;

    2013-01-01

    Acute erythroid leukemia was diagnosed in a 4-month-old boy. Cytogenetic analysis of bone marrow (BM) cells showed a t(11;20)(p11;q11) translocation. RNA extracted from the BM was sequenced and analyzed for fusion transcripts using the software FusionMap. A ZMYND8-RELA fusion was ranked first. RT...

  4. Expression of human beta-globin genes in transgenic mice: effects of a flanking metallothionein-human growth hormone fusion gene.

    OpenAIRE

    Townes, T M; Chen, H. Y.; Lingrel, J B; Palmiter, R. D.; Brinster, R. L.

    1985-01-01

    In an attempt to place a human beta-globin gene in an open chromatin domain regardless of its site of integration in the mouse genome, we microinjected into fertilized mouse eggs a construct in which the human beta-globin gene and a mouse metallothionein-human growth hormone fusion gene were juxtaposed and oriented in opposite directions. Mice that developed from injected eggs and that grew larger than normal were analyzed for human beta-globin mRNA. The globin genes were not expressed in ery...

  5. The Study on BCR/ABL Fusion Gene in Adult Acute Lymphoblastic Leukemia

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In order to assess the significance of BCR/ABC fusion gene in adult acute lymphoblastic Leukemia (ALL), 28 patients who were diagnosed as ALL were enrolled to detect BCR/ABC gene using nested-RT PCR. The results showed that 9 cases (31.25%) were BCR/ABL positive ,and expressed P210 subtype. A mong them 7 cases were B-ALL, and one was T-ALL. The diagnosis was proved by monoclonal antibodies recognition by indirect immunofluorescence. Adult patients with BCR/ABL positive ALL were significantly older (p<0. 01) and had higher WBC count (p<0. 01) as compared with BCR/ABL-negative patients. There was no significant difference in sex, hemoglobin and splenomegaly between two group (p>0. 05). The induc tion failure rate was high in BCR/ABL positive patients and those who achieved complete remission usually relapsed earlier. In conclusion, adult ALL patients with BCR/ABL-positive have poorer prognosis.

  6. Establishment of cells to monitor Microprocessor through fusion genes of microRNA and GFP.

    Science.gov (United States)

    Tsutsui, Motomu; Hasegawa, Hitoki; Adachi, Koichi; Miyata, Maiko; Huang, Peng; Ishiguro, Naoki; Hamaguchi, Michinari; Iwamoto, Takashi

    2008-08-01

    Microprocessor, the complex of Drosha and DGCR8, promotes the processing of primary microRNA to precursor microRNA, which is a crucial step for microRNA maturation. So far, no convenient assay systems have been developed for observing this step in vivo. Here we report the establishment of highly sensitive cellular systems where we can visually monitor the function of Microprocessor. During a series of screening of transfectants with fusion genes of the EGFP cDNA and primary microRNA genes, we have obtained certain cell lines where introduction of siRNA against DGCR8 or Drosha strikingly augments GFP signals. In contrast, these cells have not responded to Dicer siRNA; thus they have a unique character that GFP signals should be negatively and specifically correlated to the action of Microprocessor among biogenesis of microRNA. These cell lines can be useful tools for real-time analysis of Microprocessor action in vivo and identifying its novel modulators.

  7. Gene fusions and gene duplications: relevance to genomic annotation and functional analysis

    Directory of Open Access Journals (Sweden)

    Riley Monica

    2005-03-01

    Full Text Available Abstract Background Escherichia coli a model organism provides information for annotation of other genomes. Our analysis of its genome has shown that proteins encoded by fused genes need special attention. Such composite (multimodular proteins consist of two or more components (modules encoding distinct functions. Multimodular proteins have been found to complicate both annotation and generation of sequence similar groups. Previous work overstated the number of multimodular proteins in E. coli. This work corrects the identification of modules by including sequence information from proteins in 50 sequenced microbial genomes. Results Multimodular E. coli K-12 proteins were identified from sequence similarities between their component modules and non-fused proteins in 50 genomes and from the literature. We found 109 multimodular proteins in E. coli containing either two or three modules. Most modules had standalone sequence relatives in other genomes. The separated modules together with all the single (un-fused proteins constitute the sum of all unimodular proteins of E. coli. Pairwise sequence relationships among all E. coli unimodular proteins generated 490 sequence similar, paralogous groups. Groups ranged in size from 92 to 2 members and had varying degrees of relatedness among their members. Some E. coli enzyme groups were compared to homologs in other bacterial genomes. Conclusion The deleterious effects of multimodular proteins on annotation and on the formation of groups of paralogs are emphasized. To improve annotation results, all multimodular proteins in an organism should be detected and when known each function should be connected with its location in the sequence of the protein. When transferring functions by sequence similarity, alignment locations must be noted, particularly when alignments cover only part of the sequences, in order to enable transfer of the correct function. Separating multimodular proteins into module units makes

  8. Design and optimization of Artificial Neural Networks for the modelling of superconducting magnets operation in tokamak fusion reactors

    Science.gov (United States)

    Froio, A.; Bonifetto, R.; Carli, S.; Quartararo, A.; Savoldi, L.; Zanino, R.

    2016-09-01

    In superconducting tokamaks, the cryoplant provides the helium needed to cool different clients, among which by far the most important one is the superconducting magnet system. The evaluation of the transient heat load from the magnets to the cryoplant is fundamental for the design of the latter and the assessment of suitable strategies to smooth the heat load pulses, induced by the intrinsically pulsed plasma scenarios characteristic of today's tokamaks, is crucial for both suitable sizing and stable operation of the cryoplant. For that evaluation, accurate but expensive system-level models, as implemented in e.g. the validated state-of-the-art 4C code, were developed in the past, including both the magnets and the respective external cryogenic cooling circuits. Here we show how these models can be successfully substituted with cheaper ones, where the magnets are described by suitably trained Artificial Neural Networks (ANNs) for the evaluation of the heat load to the cryoplant. First, two simplified thermal-hydraulic models for an ITER Toroidal Field (TF) magnet and for the ITER Central Solenoid (CS) are developed, based on ANNs, and a detailed analysis of the chosen networks' topology and parameters is presented and discussed. The ANNs are then inserted into the 4C model of the ITER TF and CS cooling circuits, which also includes active controls to achieve a smoothing of the variation of the heat load to the cryoplant. The training of the ANNs is achieved using the results of full 4C simulations (including detailed models of the magnets) for conventional sigmoid-like waveforms of the drivers and the predictive capabilities of the ANN-based models in the case of actual ITER operating scenarios are demonstrated by comparison with the results of full 4C runs, both with and without active smoothing, in terms of both accuracy and computational time. Exploiting the low computational effort requested by the ANN-based models, a demonstrative optimization study has been

  9. The NAB2-STAT6 gene fusion in solitary fibrous tumor can be reliably detected by anchored multiplexed PCR for targeted next-generation sequencing.

    Science.gov (United States)

    Guseva, Natalya V; Tanas, Munir R; Stence, Aaron A; Sompallae, Ramakrishna; Schade, Jenna C; Bossler, Aaron D; Bellizzi, Andrew M; Ma, Deqin

    2016-01-01

    Solitary fibrous tumor (SFT) is a mesenchymal tumor of fibroblastic origin, which can affect any region of the body. 10-15% of SFTs metastasize and metastatic tumors are uniformly lethal with no effective therapies. The behavior of SFT is difficult to predict based on morphology. Recently, an intrachromosomal gene fusion between NAB2 and STAT6 was identified as the defining driving genetic event of SFT and different fusion types correlated with tumor histology and behavior. Due to the proximity of NAB2 and STAT6 on chromosome 12, this fusion may be missed by fluorescence in-situ hybridization. We evaluated 12 SFTs from 10 patients. All tumors showed strong nuclear staining for STAT6 by immunohistochemistry (IHC). The same formalin-fixed, paraffin-embedded blocks for IHC were used for gene fusion detection by a next-generation sequencing (NGS)-based assay. Targeted RNA fusion sequencing for gene fusions was performed using the Universal RNA Fusion Detection Kit, the Archer(™) FusionPlex(™) Sarcoma Panel and the Ion Torrent PGM, and data were analyzed using the Archer Analysis Pipeline 3.3. All tumors were positive for NAB2-STAT6 fusion. Six types of fusions were detected: NAB2ex4-STAT6ex2, NAB2ex2-STAT6ex5, NAB2ex6-STAT6ex16, NAB2ex6-STAT6ex17, NAB2ex3-STAT6ex18 and NAB2intron6-STAT6Ex17. The NGS findings were confirmed by RT-PCR followed by Sanger sequencing. No STAT6 fusion was detected in selected morphologic mimics of SFT. The assay also allows for detection of novel fusions and can detect NAB2-STAT6 fusions at a single-base resolution. PMID:27292373

  10. Construction and Expression of Methionine-rich and Lysine-rich Fusion Gene inBacillus natto

    Institute of Scientific and Technical Information of China (English)

    Zhang Shuang; Luo Chao-chao; Wu Cai-xia; Gao Xue-jun

    2015-01-01

    Methionine and lysine are restrictive essential amino acids of livestock, they are also the most attentive indexes in the feed production to carry out the quality control and quality evaluation. Their contents in feed directly affect livestock protein synthesis. Bacillus natto has excellent probiotic properties. In this experiment, we used the genetic engineering method, fusion PCR technique, to connect methionine-rich gene (zein) from maize endosperm protein with lysine-rich gene (Cflr) from the pepper anther, then the fusion gene was inserted into the expression vector pHT43, and the recombinant plasmid pHT43/zein-Cflr was constructed. The recombinant plasmid was transferred intoBacillus natto, and induced by IPTG for the expression of the fusion gene. We found an apparent band at 40 ku site for the recombinant strain by SDS-PAGE. The contents of methionine and lysine were individually detected with HPLC, the quantities of methionine and lysine in the recombinant strain increased by 18.37% and 24.68% than the wild one, respectively. We also verified the stability of the recombinant bacterium during passaging, and found the stability was 100%. This study provided research-basis for the application of the recombinedBacillus nattoas feed additive.

  11. Prevention of adverse events of interferon γ gene therapy by gene delivery of interferon γ-heparin-binding domain fusion protein in mice.

    Science.gov (United States)

    Ando, Mitsuru; Takahashi, Yuki; Yamashita, Takuma; Fujimoto, Mai; Nishikawa, Makiya; Watanabe, Yoshihiko; Takakura, Yoshinobu

    2014-01-01

    Sustained gene delivery of interferon (IFN) γ can be an effective treatment, but our previous study showed high levels of IFNγ-induced adverse events, including the loss of body weight. These unwanted events could be reduced by target-specific delivery of IFNγ after in vivo gene transfer. To achieve this, we selected the heparin-binding domain (HBD) of extracellular superoxide dismutase as a molecule to anchor IFNγ to the cell surface. We designed three IFNγ derivatives, IFNγ-HBD1, IFNγ-HBD2, and IFNγ-HBD3, each of which had 1, 2, or 3 HBDs, respectively. Each plasmid-encoding fusion proteins was delivered to the liver, a model target in this study, by hydrodynamic tail vein injection. The serum concentration of IFNγ-HBD2 and IFNγ-HBD3 after gene delivery was lower than that of IFNγ or IFNγ-HBD1. Gene delivery of IFNγ-HBD2, but not of IFNγ-HBD3, effectively increased the mRNA expression of IFNγ-inducible genes in the liver, suggesting liver-specific distribution of IFNγ-HBD2. Gene delivery of IFNγ-HBD2-suppressed tumor growth in the liver as efficiently as that of IFNγ with much less symptoms of adverse effects. These results indicate that the adverse events of IFNγ gene transfer can be prevented by gene delivery of IFNγ-HBD2, a fusion protein with high cell surface affinity. PMID:26015966

  12. The “Grep” Command But Not FusionMap, FusionFinder or ChimeraScan Captures the CIC-DUX4 Fusion Gene from Whole Transcriptome Sequencing Data on a Small Round Cell Tumor with t(4;19)(q35;q13)

    OpenAIRE

    Ioannis Panagopoulos; Ludmila Gorunova; Bodil Bjerkehagen; Sverre Heim

    2014-01-01

    Whole transcriptome sequencing was used to study a small round cell tumor in which a t(4;19)(q35;q13) was part of the complex karyotype but where the initial reverse transcriptase PCR (RT-PCR) examination did not detect a CIC-DUX4 fusion transcript previously described as the crucial gene-level outcome of this specific translocation. The RNA sequencing data were analysed using the FusionMap, FusionFinder, and ChimeraScan programs which are specifically designed to identify fusion genes. Fusio...

  13. Cloned s-Lap Gene Coding Area, Expression and Localizationof s-Lap/GFP Fusion Protein in Mammal Cells

    Institute of Scientific and Technical Information of China (English)

    SONG Yi-shu; SONG Zhi-yu; LI Hong-jun; Wu Yin; BAO Yong-li; TAN Da-peng; LI Yu-xin

    2005-01-01

    s-Lap is a new gene sequence from pig retinal pigment epithelial(RPE) cells, which was found and cloned in the early period of apoptosis of RPE cells damaged with visible light. We cloned the coding area sequence of the novel gene of s-Lap and constructed its recombinant eukaryotic plasmid pcDNA3.1-GFP/s-lap with the recombinant DNA technique. The expression and localization of s-lap/GFP fusion protein in CHO and B16 cell lines were studied with the instantaneously transfected pcDNA3.1-GFP/s-lap recombinant plasmid. s-Lap/GFP fusion protein can be expressed in CHO and B16 cells with a high rate expression in the nuclei.

  14. A human ESC model for MLL-AF4 leukemic fusion gene reveals an impaired early hematopoietic-endothelial specification

    Institute of Scientific and Technical Information of China (English)

    Clara Bueno; Agustin F Femández; Mario F Fraga; Inmaculada Moreno-Gimeno; Deborah Burks; Maria del Carmen Plaza-Calonge; Juan C Rodríguez-Manzaneque; Pablo Menendez; Rosa Montes; Gustavo J Melen; Verónica Ramos-Mejia; Pedro J Real; Verónica Ayllón; Laura Sanchez; Gertrudis Ligero; Iván Gutierrez-Aranda

    2012-01-01

    The MLL-AF4 fusion gene is a hallmark genomic aberration in high-risk acute lymphoblastic leukemia in inants.Although it is well established that MLL-AF4 arises prenatally during human development,its effects on hematopoieric development in utero remain unexplored.We have created a human-specific cellular system to study early hemato-endothelial development in MLL-AF4-expressing human embryonic stem cells (hESCs).Functional studies,clonal analysis and gene expression profiling reveal that expression of MLL-AF4 in hESCs has a phenotypic,functional and gene expression impact.MLL-AF4 acts as a global transcriptional activator and a positive regulator of homeobox gene expression in hESCs.Functionally,MLL-AF4 enhances the specification of hemogenic precursors from hESCs but strongly impairs further hematopoietic commitment in favor of an endothelial cell fate.MLL-AF4 hESCs are transcriptionally primed to differentiate towards hemogenic precursors prone to endothelial maturation,as reflected by the marked upregulation of master genes associated to vascular-endothelial functions and early hematopoiesis.Furthermore,we report that MLL-AF4 expression is not sufficient to transform hESC-derived hematopoietic cells.This work illustrates how hESCs may provide unique insights into human development and further our understanding of how leukemic fusion genes,known to arise prenatally,regulate human embryonic hematopoietic specification.

  15. Genomic binding and regulation of gene expression by the thyroid carcinoma-associated PAX8-PPARG fusion protein

    OpenAIRE

    Zhang, Yanxiao; Yu, Jingcheng; Lee, Chee; Xu, Bin; Sartor, Maureen A.; Koenig, Ronald J.

    2015-01-01

    A chromosomal translocation results in production of an oncogenic PAX8-PPARG fusion protein (PPFP) in thyroid carcinomas. PAX8 is a thyroid transcription factor, and PPARG is a transcription factor that plays important roles in adipocytes and macrophages. PPFP retains the DNA binding domains of both proteins; however, the genomic binding sites of PPFP have not been identified, and only limited data exist to characterize gene expression in PPFP thyroid carcinomas. Therefore, the oncogenic func...

  16. [Expression of SET-NUP214 fusion gene in patients with T-cell acute lymphoblastic leukemia and its clinical significance].

    Science.gov (United States)

    Dai, Hai-Ping; Wang, Qian; Wu, Li-Li; Ping, Na-Na; Wu, Chun-Xiao; Xie, Jun-Dan; Pan, Jin-Lan; Xue, Yong-Quan; Wu, De-Pei; Chen, Su-Ning

    2012-10-01

    This study was aimed to investigate the occurrence and clinical significance of the SET-NUP214 fusion gene in patients with T-cell acute lymphoblastic leukemia (T-ALL), analyse clinical and biological characteristics in this disease. RT-PCR was used to detect the expression of SET-NUP214 fusion gene in 58 T-ALL cases. Interphase FISH and Array-CGH were used to detect the deletion of 9q34. Direct sequencing was applied to detect mutations of PHF6 and NOTCH1. The results showed that 6 out of 58 T-ALL cases (10.3%) were detected to have the SET-NUP214 fusion gene by RT-PCR. Besides T-lineage antigens, expression of CD13 and(or) CD33 were detected in all the 6 cases. Deletions of 9q34 were detected in 4 out of the 6 patients by FISH. Array-CGH results of 3 SET-NUP214 positive T-ALL patients confirmed that this fusion gene was resulted from a cryptic deletion of 9q34.11q34.13. PHF6 and NOTCH1 gene mutations were found in 4 and 5 out of 6 SET-NUP214 positive T-ALL patients, respectively. It is concluded that SET-NUP214 fusion gene is often resulted from del(9)(q34). PHF6 and NOTCH1 mutations may be potential leukemogenic event in SET-NUP214 fusion gene.

  17. Characterization of foot-and-mouth disease virus gene products with antisera against bacterially synthesized fusion proteins.

    OpenAIRE

    Strebel, K; De Beck, E.; K Strohmaier; Schaller, H

    1986-01-01

    Defined segments of the cloned foot-and-mouth disease virus genome corresponding to all parts of the coding region were expressed in Escherichia coli as fusions to the N-terminal part of the MS2-polymerase gene under the control of the inducible lambda PL promoter. All constructs yielded large amounts of proteins, which were purified and used to raise sequence-specific antisera in rabbits. These antisera were used to identify the corresponding viral gene products in 35S-labeled extracts from ...

  18. Identification of a novel SEPT9-ABL1 fusion gene in a patient with T-cell prolymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Rikio Suzuki

    2014-01-01

    Full Text Available T-cell prolymphocytic leukemia (T-PLL, a rare type of peripheral T-cell leukemia, is characterized by marked splenomegaly with rapidly progressive lymphocytosis and a poor prognosis. Nine kinds of ABL1 chimeric genes have been identified in various kinds of hematological malignancies, such as chronic myeloid leukemia and B- or T-lymphoblastic leukemia. However, there have been no reports describing T-PLL cases with ABL1 rearrangements. We herein report a case of T-PLL with a novel SEPT9-ABL1 fusion gene which induced strong resistance to tyrosine kinase inhibitors such as imatinib and dasatinib.

  19. Antitumor effects and radiosensitization of cytosine deaminase and thymidine kinase fusion suicide gene on colorectal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    De-Hua Wu; Li Liu; Long-Hua Chen

    2005-01-01

    AIM: To investigate the killing effect and radiosensitization of double suicide gene mediated by adenovirus on colorectal carcinoma cells.METHODS: Colorectal carcinoma cell line SW480 was transfected with adenovirus expression vector containing cytosine deaminase (CD) and thymidine kinase (Tk) fusion gene. The expression of CD-TK fusion gene was detected by reverse transcriptase-polymerase chain reaction. The toxic effect of ganciclovir (GCV) and 5-fiuorocytosine (5FC) on infected cells was determined by MTT assay. The radiosensitization of double suicide gene was evaluated by clonogenic assay.RESULTS: After prodrugs were used, the survival rate of colorectal carcinoma cells was markedly decreased. When GCV and 5-FC were used in combination, the cytotoxicity and bystandereffect were markedly superior to a single prodrug (x2 = 30.371, P<0.01). Both GCV and 5-FC could sensitize colorectal carcinoma cells to the toxic effect of radiation, and greater radiosensitization was achieved when both prodrug were used in combination. CONCLUSION: CD-TK double suicide gene can kill and radiosensitize colorectal carcinoma cells.

  20. Characterization of foot-and-mouth disease virus gene products with antisera against bacterially synthesized fusion proteins

    International Nuclear Information System (INIS)

    Defined segments of the cloned foot-and-mouth disease virus genome corresponding to all parts of the coding region were expressed in Escherichia coli as fusions to the N-terminal part of the MS2-polymerase gene under the control of the inducible λPL promoter. All constructs yielded large amounts of proteins, which were purified and used to raise sequence-specific antisera in rabbits. These antisera were used to identify the corresponding viral gene products in 35S-labeled extracts from foot-and-mouth disease virus-infected BHK cells. This allowed us to locate unequivocally all mature foot-and-mouth disease virus gene products in the nucleotide sequence, to identify precursor-product relationships, and to detect several foot-and mouth disease virus gene products not previously identified in vivo or in vitro

  1. TMPRSS2-ERG Gene Fusion Causing ERG Overexpression Precedes Chromosome Copy Number Changes in Prostate Carcinomas, Paired HGPIN Lesions

    Directory of Open Access Journals (Sweden)

    Nuno Cerveira

    2006-10-01

    Full Text Available TMPRSS2-ETS gene fusions have been found recurrently in prostate carcinomas, but not in the presumed precursor lesion, high-grade prostatic intraepithelial neoplasia (HGPIN. However, HGPIN lesions may share chromosomal changes with prostate cancer. To determine the relative order of genetic events in prostate carcinogenesis, we have analyzed 34 prostate carcinomas, 19 paired HGPIN lesions, 14 benign prostate hyperplasias, 11 morphologically normal prostatic tissues for TMPRSS2-ERG, TMPRSS2-ETV1 rearrangements, genomic imbalances. TMPRSS2 exon 1 was fused in-frame with ERG exon 4 in 17 of 34 (50% prostate carcinomas, in 4 of 19 (21% HGPIN lesions, but in none of controls. The findings were further validated by sequencing analysis, by the real-time polymerase chain reaction quantification of TMPRSS2-ERG fusion transcript, the ERG exons 5/6:exons 1/2 expression ratio. Chromosome copy number changes were detected by comparative genomic hybridization in 42% of clinically confined carcinomas, in none of the 16 HGPIN lesions analyzed. We demonstrate for the first time that the TMPRSS2-ERG fusion gene can be detected in a proportion of HGPIN lesions, that this molecular rearrangement is an early event that may precede chromosome-level alterations in prostate carcinogenesis.

  2. A sensitive HIV-1 envelope induced fusion assay identifies fusion enhancement of thrombin

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, De-Chun; Zhong, Guo-Cai; Su, Ju-Xiang [Department of Microbiology, Harbin Medical University, 194 Xuefu Road, Harbin, Heilongjiang 150081 (China); Liu, Yan-Hong [Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, Heilongjiang 150081 (China); Li, Yan; Wang, Jia-Ye [Department of Microbiology, Harbin Medical University, 194 Xuefu Road, Harbin, Heilongjiang 150081 (China); Hattori, Toshio [Department of Emerging Infectious Diseases, Division of Internal Medicine, Graduate School of Medicine, Tohoku University, Sendai 9808574 (Japan); Ling, Hong, E-mail: lingh@ems.hrbmu.edu.cn [Department of Microbiology, Harbin Medical University, 194 Xuefu Road, Harbin, Heilongjiang 150081 (China); Department of Parasitology, Harbin Medical University, 194 Xuefu Road, Harbin, Heilongjiang 150081 (China); Key Lab of Heilongjiang Province for Infection and Immunity, Key Lab of Heilongjiang Province Education Bureau for Etiology, Harbin, Heilongjiang 150081 (China); Zhang, Feng-Min, E-mail: fengminzhang@yahoo.com.cn [Department of Microbiology, Harbin Medical University, 194 Xuefu Road, Harbin, Heilongjiang 150081 (China); Key Lab of Heilongjiang Province for Infection and Immunity, Key Lab of Heilongjiang Province Education Bureau for Etiology, Harbin, Heilongjiang 150081 (China)

    2010-01-22

    To evaluate the interaction between HIV-1 envelope glycoprotein (Env) and target cell receptors, various cell-cell-fusion assays have been developed. In the present study, we established a novel fusion system. In this system, the expression of the sensitive reporter gene, firefly luciferase (FL) gene, in the target cells was used to evaluate cell fusion event. Simultaneously, constitutively expressed Renilla luciferase (RL) gene was used to monitor effector cell number and viability. FL gave a wider dynamic range than other known reporters and the introduction of RL made the assay accurate and reproducible. This system is especially beneficial for investigation of potential entry-influencing agents, for its power of ruling out the false inhibition or enhancement caused by the artificial cell-number variation. As a case study, we applied this fusion system to observe the effect of a serine protease, thrombin, on HIV Env-mediated cell-cell fusion and have found the fusion enhancement activity of thrombin over two R5-tropic HIV strains.

  3. Rapid assessment of gene function in the circadian clock using artificial microRNA in Arabidopsis mesophyll protoplasts.

    Science.gov (United States)

    Kim, Jeongsik; Somers, David E

    2010-10-01

    Rapid assessment of the effect of reduced levels of gene products is often a bottleneck in determining how to proceed with an interesting gene candidate. Additionally, gene families with closely related members can confound determination of the role of even a single one of the group. We describe here an in vivo method to rapidly determine gene function using transient expression of artificial microRNAs (amiRNAs) in Arabidopsis (Arabidopsis thaliana) mesophyll protoplasts. We use a luciferase-based reporter of circadian clock activity to optimize and validate this system. Protoplasts transiently cotransfected with promoter-luciferase and gene-specific amiRNA plasmids sustain free-running rhythms of bioluminescence for more than 6 d. Using both amiRNA plasmids available through the Arabidopsis Biological Resource Center, as well as custom design of constructs using the Weigel amiRNA design algorithm, we show that transient knockdown of known clock genes recapitulates the same circadian phenotypes reported in the literature for loss-of-function mutant plants. We additionally show that amiRNA designed to knock down expression of the casein kinase II β-subunit gene family lengthens period, consistent with previous reports of a short period in casein kinase II β-subunit overexpressors. Our results demonstrate that this system can facilitate a much more rapid analysis of gene function by obviating the need to initially establish stably transformed transgenics to assess the phenotype of gene knockdowns. This approach will be useful in a wide range of plant disciplines when an endogenous cell-based phenotype is observable or can be devised, as done here using a luciferase reporter.

  4. Bifunctional chimeric SuperCD suicide gene -YCD: YUPRT fusion is highly effective in a rat hepatoma model

    Institute of Scientific and Technical Information of China (English)

    Florian Graepler; Ulrike A Lauer; Reinhard Vonthein; Michael Gregor; Sorin Armeanu; Michael Bitzer; Ulrich M. Lauer; Marie-Luise Lemken; Wolfgang A Wybranietz; Ulrike Schmidt; Irina Smirnow; Christine D Groβ; Martin Spiegel; Andrea Schenk; Hansj(o)rg Graf

    2005-01-01

    AIM: To investigate the effects of catalytically superior gene-directed enzyme prodrug therapy systems on a rat hepatoma model.METHODS: To increase hepatoma cell chemosensitivity for the prodrug 5-fluorocytosine (5-FC), we generated a chimeric bifunctional SuperCD suicide gene, a fusion of the yeast cytosine deaminase (YCD) and the yeast uracil phosphoribosyltransferase (YUPRT) gene.RESULTS: In vitro stably transduced Morris rat hepatoma cells (MH) expressing the bifunctional SuperCD suicide gene (MH SuperCD) showed a clearly marked enhancement in cell killing when incubated with 5-FC as compared with MH ceils stably expressing YCD solely (MH YCD) or the cytosine deaminase gene of bacterial origin(MH BCD), respectively. In vivo, MH SuperCD tumors implanted both subcutaneously as well as orthotopically into the livers of syngeneic ACI rats demonstrated significant tumor regressions (P<0.01) under both high dose as well as low dose systemic 5-FC application,whereas MH tumors without transgene expression (MH naive) showed rapid progression. For the first time, an order of in vivo suicide gene effectiveness (SuperCD>>YCD > > BCD > > > negative control) was defi ned as a result of a directin vivo comparison of all three suicide genes.CONCLUSION: Bifunctional SuperCD suicide gene expression is highly effective in a rat hepatoma model,thereby significantly improving both the therapeutic index and the efficacy of hepatocellular carcinoma killing by fluorocytosine.

  5. Analysis of NAB2-STAT6 Gene Fusion in 17 Cases of Meningeal Solitary Fibrous Tumor/Hemangiopericytoma: Review of the Literature.

    Science.gov (United States)

    Yuzawa, Sayaka; Nishihara, Hiroshi; Wang, Lei; Tsuda, Masumi; Kimura, Taichi; Tanino, Mishie; Tanaka, Shinya

    2016-08-01

    Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a mesenchymal tumor that can affect virtually any region of the body. SFT/HPC of the thoracic cavity and soft tissue has been histologically considered a single biological entity termed SFT; in fact, NAB2-STAT6 gene fusion was recently identified in both diseases. In contrast, meningeal SFT and HPC still need to be investigated in detail with regard to gene fusion variants. The aim of this study was to verify the frequency of NAB2-STAT6 fusion and the relationship between fusion variants and clinicopathologic findings of SFT/HPC, especially meningeal SFT/HPC. We examined the NAB2-STAT6 fusion by reverse transcription polymerase chain reaction with 4 cases of meningeal SFT and 13 cases of meningeal HPC. NAB2-STAT6 fusion transcripts were identified in 12 of 17 cases, including NAB2ex6-STAT6ex17 (4/17, 24%), NAB2ex6-STAT6ex16 and NAB2ex4-STAT6ex2 (3/17, 18%, respectively), and NAB2ex5-STAT6ex16 (2/17, 12%). Three cases showed a pseudopapillary pattern, and 2 of them carried NAB2ex6-STAT6ex17. In addition, our meta-analysis revealed that the major fusion variant in meningeal SFT/HPC was NAB2ex6-STAT6ex16/17 (29/54, 54%), which was also common in soft tissue and intraperitoneum/retroperitoneum but rare in thoracic SFT. Fusion variant significantly correlated with age and histologic diagnosis in meningeal SFT/HPC but not with prognosis. Our results represented that meningeal SFT and HPC were in a single biological spectrum with NAB2-STAT6 gene fusion as was nonmeningeal SFT and further confirmed the organ-specific tumorigenic process and morphologic differences on the basis of fusion variants in meningeal SFT/HPC. PMID:26927892

  6. Construction of an Americn mink Bacterial Artificial Chromosome (BAC) library and sequencing candidate genes important for the fur industry

    DEFF Research Database (Denmark)

    Anistoroaei, Razvan Marian; Hallers, Boudewijn ten; Nefedov, Michael;

    2011-01-01

    contigs (184 kb in average) were assembled. Knowing the complete sequences of these candidate genes will enable confirmation of the association with a phenotype and the finding of causative mutations for the targeted phenotypes.Additionally, 1577 BAC clones were end sequenced; 2505 BAC end sequences (80......BACKGROUND: Bacterial artificial chromosome (BAC) libraries continue to be invaluable tools for the genomic analysis of complex organisms. Complemented by the newly and fast growing deep sequencing technologies, they provide an excellent source of information in genomics projects. RESULTS: Here, we...... consisting of 18,432 clones spotted in duplicate, have been produced for hybridization screening and are publicly available. Overgo probes derived from expressed sequence tags (ESTs), representing 21 candidate genes for traits important for the mink industry, were used to screen the BAC library...

  7. The artificial gene Jazz, a transcriptional regulator of utrophin, corrects the dystrophic pathology in mdx mice.

    Science.gov (United States)

    Di Certo, Maria Grazia; Corbi, Nicoletta; Strimpakos, Georgios; Onori, Annalisa; Luvisetto, Siro; Severini, Cinzia; Guglielmotti, Angelo; Batassa, Enrico Maria; Pisani, Cinzia; Floridi, Aristide; Benassi, Barbara; Fanciulli, Maurizio; Magrelli, Armando; Mattei, Elisabetta; Passananti, Claudio

    2010-03-01

    The absence of the cytoskeletal protein dystrophin results in Duchenne muscular dystrophy (DMD). The utrophin protein is the best candidate for dystrophin replacement in DMD patients. To obtain therapeutic levels of utrophin expression in dystrophic muscle, we developed an alternative strategy based on the use of artificial zinc finger transcription factors (ZF ATFs). The ZF ATF 'Jazz' was recently engineered and tested in vivo by generating a transgenic mouse specifically expressing Jazz at the muscular level. To validate the ZF ATF technology for DMD treatment we generated a second mouse model by crossing Jazz-transgenic mice with dystrophin-deficient mdx mice. Here, we show that the artificial Jazz protein restores sarcolemmal integrity and prevents the development of the dystrophic disease in mdx mice. This exclusive animal model establishes the notion that utrophin-based therapy for DMD can be efficiently developed using ZF ATF technology and candidates Jazz as a novel therapeutic molecule for DMD therapy.

  8. Retrovirus-mediated transfer of the fusion gene encoding EGFP-BMP2 in mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Zhang Yingang; Guo Xiong; Liu Zheng; Wang Shijie

    2007-01-01

    Objective To develop retrovirus-mediated transfer of the fusion gene encoding EGFP-BMP2 in mesenchymal stem cells. Methods Mesenchymal stem cells from New Zealand white rabbits were transduced with retroviral pLEGFP-BMP2 vector by the optimized retroviral transduction protocol. Fluorescent microscopy's examination was to evaluate the results of the transduction, flow cytometer's analysis was to evaluate the transduction efficiency and the Fluorescence-activated cell sorting method was to sort the transduced cells. Bioactivity test from C2C12K4 cells was to show the expression and bio-activity of the fusion gene. Results Fluorescent microscopy showed the success of the transduction. By flow cytometer's analysis, the mean efficiency of the transduction with EGFP was (42.8±6.1)% SD. Transduced cells were sorted efficiently by the fluorescence-activated cell sorting method and after sorting, almost of those showed the expression of BMP2. Fluorescently and strongly bioactivity test for C2C12K4 cells demonstrated that fluorescent materials were located the surface of cells and the activity of luciferase increased compared with the control. Analysis of long-term expression showed there was no difference between 2 week-time point and 3 month-time point of culture post-sorting. Conclusion Mesenchymal stem cells can be transduced efficiently by retrovirus-mediated transfer of the fusion gene encoding EGFP-BMP2, the highly pure transduced cells are obtained by the fluorescence-activated cell sorting technique, the expressed chimeric protein embraced the double bioactivity of EGFP and BMP2, and moreover, the expression had not attenuated over time.

  9. Artificially inserting a reticuloendotheliosis virus long terminal repeat into a bacterial artificial chromosome clone of Marek's disease virus (MDV) alters expression of nearby MDV genes.

    Science.gov (United States)

    Kim, Taejoong; Mays, Jody; Fadly, Aly; Silva, Robert F

    2011-06-01

    Researchers reported that co-cultivating the JM/102W strain of Marek's disease virus (MDV) with reticuloendotheliosis virus (REV) resulted in an REV long terminal repeat (LTR) being inserted into the internal repeat short (IRS) region of JM/102W. When the resulting recombinant virus was serially passed in cell culture, the initial LTR was duplicated and a second LTR spontaneously appeared in the terminal repeat short (TRS) region of the MDV genome. The virus, designated RM1, was significantly attenuated but still induced severe bursal and thymic atrophy (Isfort et al. PNAS 89:991-995). To determine whether the altered phenotype was due solely to the LTR, we cloned the LTR from the RM1 IRS region and inserted it into the IRS region of a very virulent bacterial artificial clone (BAC) of the Md5 strain of MDV, which we designated rMd5-RM1-LTR. During blind passage in duck embryo fibroblast cultures, the initial LTR in the rMd5-RM1-LTR was also duplicated, with LTRs appearing in both IRS and TRS regions of the MDV genome. The inserted LTR sequences and transcripts associated with the MDV open reading frames MDV085, MDV086, SORF2, US1, and US10 were molecularly characterized. The parental Md5 BAC contains a family of transcripts of 3, 2, and 1 kb that all terminate at the end of the US10 gene. The rMd5-RM1-LTR and RM1 viruses both express an additional 4 kb transcript that originates in the LTR and also terminates after US10. Collectively, the data suggest that our engineered rMd5-RM1-LTR virus very closely resembles the RM1 virus in its structure and transcription patterns.

  10. Expression of Chlamydomonas actin-gfp fusion gene in to-bacco suspension cell and polymerization of the actin-gfp protein in vitro

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The fusion gene of actin (cDNA of Chlamydo- monas reinhardtii) and green fluorescence protein (gfp) had been constructed into two expression vectors which could be expressed in E. coli and tobacco suspension cells BY2. The correct expression was observed in E. coli and BY2 with a fluorescence microscopy. The fusion protein, which took part in the membrane skeleton, was mainly located peripherally along the membrane, specially the fusion protein was dis-tributed around nucleus and cell plate, while the fusion pro-tein also forms F-actin in the cell. The fusion protein was purified from Bl21plus by ammonium sulfate fractionation, ion exchange chromatography and hydrophobic interaction chromatography. The purified production could polymerize into F-actin when the actin polymerizing buffer was added. It was demonstrated that the characteristics and function of actin in Chlamydomonas was similar with those of animals and higher plants.

  11. FGFR3–TACC3: A novel gene fusion in cervical cancer

    Directory of Open Access Journals (Sweden)

    Benedito A. Carneiro

    2015-08-01

    Full Text Available Cervical cancer epitomizes the success of cancer prevention through the human papillomavirus (HPV vaccine, but significant challenges remain in the treatment of advanced disease. We report the first three cases of cervical carcinoma harboring an FGFR3–TACC3 fusion, which serves as a novel therapeutic target. The fusion, identified by comprehensive genomic profiling, activates the FGFR pathway that has been implicated in HPV-driven carcinogenesis. One of the patients whose tumor contained the FGFR3–TACC3 fusion was treated with an investigational FGFR tyrosine kinase inhibitor. Concomitant molecular alterations involving the PI3K/AKT/mTOR and RAF/MEK pathways were also identified and suggest other treatment strategies that deserve investigation. This case series highlights the role of comprehensive genomic profiling in the identification of new therapeutic targets and in targeted therapy selection for patients with cervical cancer.

  12. ESRRA-C11orf20 Is a Recurrent Gene Fusion in Serous Ovarian Carcinoma

    OpenAIRE

    Salzman, Julia; Marinelli, Robert J.; Wang, Peter L.; Green, Ann E.; Julie S Nielsen; Nelson, Brad H; Drescher, Charles W.; Brown, Patrick O.

    2011-01-01

    Every year, ovarian cancer kills approximately 14,000 women in the United States and more than 140,000 women worldwide. Most of these deaths are caused by tumors of the serous histological type, which is rarely diagnosed before it has disseminated. By deep paired-end sequencing of mRNA from serous ovarian cancers, followed by deep sequencing of the corresponding genomic region, we identified a recurrent fusion transcript. The fusion transcript joins the 5′ exons of ESRRA, encoding a ligand-in...

  13. Epitope-tagged protein-based artificial miRNA screens for optimized gene silencing in plants.

    Science.gov (United States)

    Li, Jian-Feng; Zhang, Dandan; Sheen, Jen

    2014-04-01

    Artificial miRNA (amiRNA) technology offers highly specific gene silencing in diverse plant species. The principal challenge in amiRNA application is to select potent amiRNAs from hundreds of bioinformatically designed candidates to enable maximal target gene silencing at the protein level. To address this issue, we developed the epitope-tagged protein-based amiRNA (ETPamir) screens, in which single or multiple potential target genes encoding epitope-tagged proteins are constitutively or inducibly coexpressed with individual amiRNA candidates in plant protoplasts. Accumulation of tagged proteins, detected by immunoblotting with commercial tag antibodies, inversely and quantitatively reflects amiRNA efficacy in vivo. The core procedure, from protoplast isolation to identification of optimal amiRNA, can be completed in 2-3 d. The ETPamir screens circumvent the limited availability of plant antibodies and the complexity of plant amiRNA silencing at target mRNA and/or protein levels. The method can be extended to verify predicted target genes for endogenous plant miRNAs.

  14. Characterization of Gene Expression Patterns among Artificially Developed Cancer Stem Cells Using Spherical Self-Organizing Map

    Science.gov (United States)

    Seno, Akimasa; Kasai, Tomonari; Ikeda, Masashi; Vaidyanath, Arun; Masuda, Junko; Mizutani, Akifumi; Murakami, Hiroshi; Ishikawa, Tetsuya; Seno, Masaharu

    2016-01-01

    We performed gene expression microarray analysis coupled with spherical self-organizing map (sSOM) for artificially developed cancer stem cells (CSCs). The CSCs were developed from human induced pluripotent stem cells (hiPSCs) with the conditioned media of cancer cell lines, whereas the CSCs were induced from primary cell culture of human cancer tissues with defined factors (OCT3/4, SOX2, and KLF4). These cells commonly expressed human embryonic stem cell (hESC)/hiPSC-specific genes (POU5F1, SOX2, NANOG, LIN28, and SALL4) at a level equivalent to those of control hiPSC 201B7. The sSOM with unsupervised method demonstrated that the CSCs could be divided into three groups based on their culture conditions and original cancer tissues. Furthermore, with supervised method, sSOM nominated TMED9, RNASE1, NGFR, ST3GAL1, TNS4, BTG2, SLC16A3, CD177, CES1, GDF15, STMN2, FAM20A, NPPB, CD99, MYL7, PRSS23, AHNAK, and LOC152573 genes commonly upregulating among the CSCs compared to hiPSC, suggesting the gene signature of the CSCs.

  15. Characterization of Gene Expression Patterns among Artificially Developed Cancer Stem Cells Using Spherical Self-Organizing Map.

    Science.gov (United States)

    Seno, Akimasa; Kasai, Tomonari; Ikeda, Masashi; Vaidyanath, Arun; Masuda, Junko; Mizutani, Akifumi; Murakami, Hiroshi; Ishikawa, Tetsuya; Seno, Masaharu

    2016-01-01

    We performed gene expression microarray analysis coupled with spherical self-organizing map (sSOM) for artificially developed cancer stem cells (CSCs). The CSCs were developed from human induced pluripotent stem cells (hiPSCs) with the conditioned media of cancer cell lines, whereas the CSCs were induced from primary cell culture of human cancer tissues with defined factors (OCT3/4, SOX2, and KLF4). These cells commonly expressed human embryonic stem cell (hESC)/hiPSC-specific genes (POU5F1, SOX2, NANOG, LIN28, and SALL4) at a level equivalent to those of control hiPSC 201B7. The sSOM with unsupervised method demonstrated that the CSCs could be divided into three groups based on their culture conditions and original cancer tissues. Furthermore, with supervised method, sSOM nominated TMED9, RNASE1, NGFR, ST3GAL1, TNS4, BTG2, SLC16A3, CD177, CES1, GDF15, STMN2, FAM20A, NPPB, CD99, MYL7, PRSS23, AHNAK, and LOC152573 genes commonly upregulating among the CSCs compared to hiPSC, suggesting the gene signature of the CSCs. PMID:27559294

  16. Impact of different colours of artificial light at night on melatonin rhythm and gene expression of gonadotropins in European perch.

    Science.gov (United States)

    Brüning, Anika; Hölker, Franz; Franke, Steffen; Kleiner, Wibke; Kloas, Werner

    2016-02-01

    The distribution and intensity of artificial light at night, commonly referred to as light pollution, is consequently rising and progressively also ecological implications come to light. Low intensity light is known to suppress nocturnal melatonin production in several fish species. This study aims to examine the least suppressive light colour for melatonin excreted into the holding water and the influence of different light qualities and quantities in the night on gene expression of gonadotropins in fish. European perch (Perca fluviatilis) were exposed to light of different wavelengths during the night (blue, green, and red). Melatonin concentrations were measured from water samples every 3h during a 24h period. Gene expression of gonadotropins was measured in perch exposed to different light colours and was additionally examined for perch subjected to different intensities of white light (0 lx, 1 lx, 10 lx, 100 lx) during the night. All different light colours caused a significant drop of melatonin concentration; however, blue light was least suppressive. Gene expression of gonadotropins was not influenced by nocturnal light of different light colours, but in female perch gonadotropin expression was significantly reduced by white light already at the lowest level (1 lx). We conclude that artificial light with shorter wavelengths at night is less effective in disturbing biological rhythms of perch than longer wavelengths, coinciding with the light situation in freshwater habitats inhabited by perch. Different light colours in the night showed no significant effect on gonadotropin expression, but white light in the night can disturb reproductive traits already at very low light intensities. These findings indicate that light pollution has not only the potential to disturb the melatonin cycle but also the reproductive rhythm and may therefore have implications on whole species communities. PMID:26584071

  17. Staphylococcus aureus Cell Wall Stress Stimulon Gene-lacZ Fusion Strains: Potential for Use in Screening for Cell Wall-Active Antimicrobials▿

    OpenAIRE

    Steidl, Rebecca; Pearson, Stacy; Stephenson, Robert E.; Ledala, Nagender; Sitthisak, Sutthirat; Wilkinson, Brian J; Jayaswal, Radheshyam K.

    2008-01-01

    lacZ fusion strains were constructed using the promoters of five cell wall stress stimulon genes: pbp2, tcaA, vraSR, sgtB, and lytR. All fusion strains were induced only in the presence of cell wall-active antibiotics, suggesting the potential of these strains for use in high-throughput screening for new cell wall-active agents.

  18. Analysis of a MULE-cyanide hydratase gene fusion in Verticillium dahliae

    Science.gov (United States)

    The genome of the phytopathogenic fungus Verticillium dahliae encodes numerous Class II “cut-and-paste” transposable elements, including those of a small group of MULE transposons. We have previously identified a fusion event between a MULE transposon sequence and sequence encoding a cyanide hydrata...

  19. Analysis of expression of the alpha-toxin gene (hla) of Staphylococcus aureus by using a chromosomally encoded hla::lacZ gene fusion.

    OpenAIRE

    Ohlsen, K; Koller, K P; Hacker, J

    1997-01-01

    The staphylococcal alpha-toxin (Hla) is a major virulence factor contributing to Staphylococcus aureus pathogenesis. To elucidate the conditions influencing hla expression, the determinant was fused to lacZ, the reporter gene coding for beta-galactosidase. The hla::lacZ fusion was integrated into the chromosome of the wild-type S. aureus strain Wood 46, leading to the variant Wood 46-3. Alpha-toxin expression was found to be dependent on temperature, showing a maximum at 42 degrees C. Further...

  20. Construction of prokaryotic expression system of TGF-β1 epitope gene and identification of recombinant fusion protein immunity

    Institute of Scientific and Technical Information of China (English)

    Yong-Hong Guo; Zhi-Ming Hao; Jin-Yan Luo; Jun-Hong Wang

    2005-01-01

    AIM: To insert the constructed TGF-β1the el loop of C-terminus of truncated hepatitis B core antigen to increase TGF-β1expression system and to identify immunity of the expressed recombinant protein in order to exploit the possibility for obtaining anti- TGF-β1METHODS: The TGF-β1mature TGF-β1TGF-32) was amplified by polymerase chain reaction from the recombinant pGEM-7z/TGF-β1HBcAg gene fragments (encoding HBcAg from 1-71 and 89-144 amino acid residues) were amplified from PYTA1-HBcAg vector. The recombinant vector pGEMEX-1 was used to insert HBcAg1-71, TGF-β1into restrictive endonuclease enzyme and ligated with T4ligase. The fusion gene fragments HBcAg1-71-TGF-β1HBcAg89-144 were recloned to pET28a(+) and the DNA sequence was confirmed by the dideoxy chain termination method. The recombinant vector pET28a (+)/CTC was transformed and expressed in E.. Coli BL21 (DE3)under induction of IPTG. After purification with Ni+2-NTA agarose resins, the antigenicity of purified protein was detected by ELISA and Western blot and visualized under electron microscope.RESULTS: Enzyme digestion analysis and sequencing showed that TGF-β1loop of C-terminus of truncated hepatitis B core antigen.SDS-PAGE analysis showed that relative molecular mass(Mr) of the expressed product by pET28a (+)/CTC was Mr 24 600.The output of the target recombinant protein was approximately 34.8% of the total bacterial protein,mainly presented in the form of inclusion body. Western blotting and ELISA demonstrated that the fusion protein could combine with anti-TGF-β1not with anti-HBcAg. The purity of protein was about 90% and the protein was in the form of self-assembling particles visualized under electron microscope. This fusion protein had good anti-TGF-β1could be used as anti-TGF-β1CONCLUSION: A recombinant prokaryotic expression system with high expression efficiency of the target TGF- epitope gene was successfully established.The fusion protein is in the form of self-assembling particles

  1. Synergistic antitumor effect of a human papillomavirus DNA vaccine harboring E6E7 fusion gene and vascular endothelial growth factor receptor 2 gene.

    Science.gov (United States)

    Gao, Jie; Fan, Lei; Ma, Wei; Xiao, Huan

    2016-09-01

    Human papillomavirus (HPV) has been identified as the primary etiological factor in cervical cancer as well as in subsets of anogenital and oropharyngeal cancers. The two HPV viral oncoproteins, E6 and E7, are uniquely and consistently expressed in all HPV-infected cells and are therefore promising targets for therapeutic vaccination. In order to achieve a synergistic antitumor and anti-angiogenesis effect, we designed and constructed a novel DNA vaccine that can express the HPV 16 E6E7 fusion protein and VEGFR2 in the same reading frame. A series of DNA plasmids encoding E6E7, VEGFR2 and their conjugates were constructed and injected into mice. The resultant humoral and cellular immune responses were detected by ELISA and enzyme-linked immunospot (ELISPOT), respectively. To evaluate the antitumor efficacy of these plasmids, tumor-bearing mice expressing the E6E7 fusion protein were constructed. After injection into the tumor-bearing mouse model, the plasmid harboring the E6E7 fusion gene and VEGFR2 showed stronger inhibition of tumor growth than the plasmid expressing E6E7 or VEGFR2 alone, which indicated that the combination of E6E7 and VEGFR2 could exert a synergistic antitumor effect. These observations emphasize the potential of a synergistic antitumor and anti-angiogenesis strategy using a DNA vaccine, which could be a promising approach for tumor immunotherapy. PMID:27515281

  2. Biosensing of BCR/ABL fusion gene using an intensity-interrogation surface plasmon resonance imaging system

    Science.gov (United States)

    Wu, Jiangling; Huang, Yu; Bian, Xintong; Li, DanDan; Cheng, Quan; Ding, Shijia

    2016-10-01

    In this work, a custom-made intensity-interrogation surface plasmon resonance imaging (SPRi) system has been developed to directly detect a specific sequence of BCR/ABL fusion gene in chronic myelogenous leukemia (CML). The variation in the reflected light intensity detected from the sensor chip composed of gold islands array is proportional to the change of refractive index due to the selective hybridization of surface-bound DNA probes with target ssDNA. SPRi measurements were performed with different concentrations of synthetic target DNA sequence. The calibration curve of synthetic target sequence shows a good relationship between the concentration of synthetic target and the change of reflected light intensity. The detection limit of this SPRi measurement could approach 10.29 nM. By comparing SPRi images, the target ssDNA and non-complementary DNA sequence are able to be distinguished. This SPRi system has been applied for assay of BCR/ABL fusion gene extracted from real samples. This nucleic acid-based SPRi biosensor therefore offers an alternative high-effective, high-throughput label-free tool for DNA detection in biomedical research and molecular diagnosis.

  3. Inactivation of encapsulated cells and their therapeutic effects by means of TGL triple-fusion reporter/biosafety gene.

    Science.gov (United States)

    Santos, Edorta; Larzabal, Leyre; Calvo, Alfonso; Orive, Gorka; Pedraz, José Luis; Hernández, Rosa Ma

    2013-01-01

    The immobilization of cells within alginate-poly-l-lysine-alginate (APA) microcapsules has been demonstrated to be an effective technology design for long term delivery of therapeutic products. Despite promising advances, biosafety aspects still remain to be improved. Here, we describe a complete characterization of the strategy based on TGL triple-fusion reporter gene--which codifies for Herpes Simplex virus type 1 thymidine-kinase (HSV1-TK), green fluorescent protein (GFP) and Firefly Luciferase--(SFG(NES)TGL) to inactivate encapsulated cells and their therapeutic effects. Myoblasts genetically engineered to secrete erythropoietin (EPO) were retroviraly transduced with the SFG(NES)TGL plasmid to further characterize their ganciclovir (GCV)-mediated inactivation process. GCV sensitivity of encapsulated cells was 100-fold lower when compared to cells plated onto 2D surfaces. However, the number of cells per capsule and EPO secretion decayed to less than 15% at the same time that proliferation was arrested after 14 days of GCV treatment in vitro. In vivo, ten days of GCV treatment was enough to restore the increased hematocrit levels of mice implanted with encapsulated TGL-expressing and EPO-secreting cells. Altogether, these results show that TGL triple-fusion reporter gene may be a good starting point in the search of a suitable biosafety strategy to inactivate encapsulated cells and control their therapeutic effects. PMID:23174140

  4. Dysregulation of gene expression in the artificial human trisomy cells of chromosome 8 associated with transformed cell phenotypes.

    Directory of Open Access Journals (Sweden)

    Hisakatsu Nawata

    Full Text Available A change in chromosome number, known as aneuploidy, is a common characteristic of cancer. Aneuploidy disrupts gene expression in human cancer cells and immortalized human epithelial cells, but not in normal human cells. However, the relationship between aneuploidy and cancer remains unclear. To study the effects of aneuploidy in normal human cells, we generated artificial cells of human primary fibroblast having three chromosome 8 (trisomy 8 cells by using microcell-mediated chromosome transfer technique. In addition to decreased proliferation, the trisomy 8 cells lost contact inhibition and reproliferated after exhibiting senescence-like characteristics that are typical of transformed cells. Furthermore, the trisomy 8 cells exhibited chromosome instability, and the overall gene expression profile based on microarray analyses was significantly different from that of diploid human primary fibroblasts. Our data suggest that aneuploidy, even a single chromosome gain, can be introduced into normal human cells and causes, in some cases, a partial cancer phenotype due to a disruption in overall gene expression.

  5. Cellular automata-based artificial life system of horizontal gene transfer

    Directory of Open Access Journals (Sweden)

    Ji-xin Liu

    2016-02-01

    Full Text Available Mutation and natural selection is the core of Darwin's idea about evolution. Many algorithms and models are based on this idea. However, in the evolution of prokaryotes, more and more researches have indicated that horizontal gene transfer (HGT would be much more important and universal than the authors had imagined. Owing to this mechanism, the prokaryotes not only become adaptable in nearly any environment on Earth, but also form a global genetic bank and a super communication network with all the genes of the prokaryotic world. Under this background, they present a novel cellular automata model general gene transfer to simulate and study the vertical gene transfer and HGT in the prokaryotes. At the same time, they use Schrodinger's life theory to formulate some evaluation indices and to discuss the intelligence and cognition of prokaryotes which is derived from HGT.

  6. Introduction of a chimeric gene encoding an oryzacystatin-β-glucuronidase fusion protein into rice protoplasts and regeneration of transformed plants.

    Science.gov (United States)

    Hosoyama, H; Irie, K; Abe, K; Arai, S

    1995-12-01

    In order to construct transgenic rice plant with an introduced oryzacystatin (OC)-β-glucuronidase (GUS) fusion gene, we first introduced it into rice protoplasts by electroporation, together with a marker gene conferring hygromycinresistance (pUC-HPH). In a transient assay using the transfected protoplasts, both OC and GUS activities were detected. The GUS activity was higher when the OC-GUS fusion protein was expressed than when only a single GUS protein was expressed. Next, to isolate stable transformants, hygromycin-resistant calli were selected. Forty one out of 116 hygromycin-resistant calli expressed a 2.2 kb mRNA transcribed from the chimeric gene and their extracts exhibited the activities of both OC and GUS. Finally, the transgenic calli were regenerated into rice plants whose tissues (leaves, roots and seeds) exhibited GUS activity probably derived from the fusion protein. PMID:24185770

  7. Precise cloning and tandem integration of large polyketide biosynthetic gene cluster using Streptomyces artificial chromosome system

    OpenAIRE

    Nah, Hee-Ju; Woo, Min-Woo; Choi, Si-Sun; Kim, Eung-Soo

    2015-01-01

    Background Direct cloning combined with heterologous expression of a secondary metabolite biosynthetic gene cluster has become a useful strategy for production improvement and pathway modification of potentially valuable natural products present at minute quantities in original isolates of actinomycetes. However, precise cloning and efficient overexpression of an entire biosynthetic gene cluster remains challenging due to the ineffectiveness of current genetic systems in manipulating large-si...

  8. Functional expression of the FeMo-cofactor-specific biosynthetic genes nifEN as a NifE-N fusion protein synthesizing unit in Azotobacter vinelandii.

    Science.gov (United States)

    Suh, Man Hee; Pulakat, Lakshmi; Gavini, Nara

    2002-11-29

    The nifEN encodes an E2N2 tetrameric metalloprotein complex that serves as scaffold for assembly of the FeMo cofactor of nitrogenase. In most diazotrophs, the NifE and NifN are translated as separate polypeptides and then assembled into tetrameric E2N2 complex. However, in Anabaena variabilis which has two nif clusters that encode two different NifEN complexes, the NifEN2 is encoded by a single nifE-N like gene, which has high homology to the NifE at amino-terminus and to the NifN at the carboxy-terminus. These observations implied that a metalloprotein like NifEN can accommodate large variations in their amino acid composition and also in the way they are synthesized (as two separate proteins or as a single protein) and yet remain functional. In Azotobacter vinelandii NifE and NifN are synthesized separately. To test whether NifEN could retain its functionality when encoded by a single gene, we generated a translational fusion of the nifE and nifN genes of A. vinelandii that could encode a large NifE-N fusion protein. When expressed in the nifEN-minus strain of A. vinelandii, the nifE-N gene fusion could complement the NifEN function. Western blot analysis by using polyclonal NifEN antibodies revealed that the complementing nifEN product is a large NifE-N fusion protein unit. The fact that the gene fusion of nifE-N specifies a functional NifE-N fusion protein reflects that these metalloproteins can accommodate a wide range of flexibility in their gene organization, structure, and assembly. PMID:12437975

  9. Development of GFP fusions for examination of the effects of the space environment on gene expression in Escherichia coli

    Science.gov (United States)

    Mancinelli, R.; Fahlen, T.

    The goal of the In situ Space Gene Expression on Nano-satillites (ISGEN) program is to be ready to fly technology that can support a fully automated experiment to quantify changes in model organisms in situ in low earth orbit in a free flyer platform in less than two years. A straightforward gene expression assay that meets the ISGEN flight objective for testing flight hardware as well as return data regarding the effects of microgravity on gene expression has been developed. Escherichia coli K-12, a bacterium that exhibits changes in its growth pattern when flown in micro-gravity on the Space Shuttle, was used. The scientific objective of this work is to determine if there is a discernable change in metabolic and stress pathway gene expression due to growth in the space environment. To that end, we have linked the green fluorescent protein (GFP) reporter gfp to phoP, a gene that responds to extracellular Mg2+ levels, and pykF, a gene involved in the glycolytic pathway that responds to changes in intracellular pyruvate. These genes respond to the metabolic needs of the cell and may be altered in the micro-gravity environment. E. coli cells containing a plasmid encoding the phoP-gfp-mut3 reporter construct were grown with or without MgSO_4. The effect of the added MgSO_4 is the repression of the expression of GFP. This is the expected result if GFP expression were under the control of a magnesium-regulated promoter such as phoP. Consistent with the negative feedback loop, we observe repression of GFP production in cells containing our pykF-gfp plasmid construct, when grown in the presence of excess glucose. Thus, the pykF-gfp fusion functions as a glucose sensor.

  10. The artificial zinc finger coding gene 'Jazz' binds the utrophin promoter and activates transcription.

    Science.gov (United States)

    Corbi, N; Libri, V; Fanciulli, M; Tinsley, J M; Davies, K E; Passananti, C

    2000-06-01

    Up-regulation of utrophin gene expression is recognized as a plausible therapeutic approach in the treatment of Duchenne muscular dystrophy (DMD). We have designed and engineered new zinc finger-based transcription factors capable of binding and activating transcription from the promoter of the dystrophin-related gene, utrophin. Using the recognition 'code' that proposes specific rules between zinc finger primary structure and potential DNA binding sites, we engineered a new gene named 'Jazz' that encodes for a three-zinc finger peptide. Jazz belongs to the Cys2-His2 zinc finger type and was engineered to target the nine base pair DNA sequence: 5'-GCT-GCT-GCG-3', present in the promoter region of both the human and mouse utrophin gene. The entire zinc finger alpha-helix region, containing the amino acid positions that are crucial for DNA binding, was specifically chosen on the basis of the contacts more frequently represented in the available list of the 'code'. Here we demonstrate that Jazz protein binds specifically to the double-stranded DNA target, with a dissociation constant of about 32 nM. Band shift and super-shift experiments confirmed the high affinity and specificity of Jazz protein for its DNA target. Moreover, we show that chimeric proteins, named Gal4-Jazz and Sp1-Jazz, are able to drive the transcription of a test gene from the human utrophin promoter.

  11. Development of series of gateway binary vectors, pGWBs, for realizing efficient construction of fusion genes for plant transformation.

    Science.gov (United States)

    Nakagawa, Tsuyoshi; Kurose, Takayuki; Hino, Takeshi; Tanaka, Katsunori; Kawamukai, Makoto; Niwa, Yasuo; Toyooka, Kiminori; Matsuoka, Ken; Jinbo, Tetsuro; Kimura, Tetsuya

    2007-07-01

    We developed a new series of binary vectors useful for Gateway cloning to facilitate transgenic experiments in plant biotechnology. The new system, Gateway Binary Vectors (pGWBs) realized efficient cloning, constitutive expression using the cauliflower mosaic virus (CaMV) 35S promoter and the construction of fusion genes by simple clonase reaction with an entry clone. The reporters employable in this system are beta-glucuronidase (GUS), synthetic green fluorescent protein with S65T mutation (sGFP), luciferase (LUC), enhanced yellow fluorescent protein (EYFP), and enhanced cyan fluorescent protein (ECFP). The tags available are 6xHis, FLAG, 3xHA, 4xMyc, 10xMyc, GST, T7-epitope, and tandem affinity purification (TAP). In total, 13 kinds of reporter or tag were arranged and were almost applicable to both N- and C-fusions. The pGWBs could be used for many purposes, such as promoter::reporter analysis, observation of subcellular localization by the expression of proteins fused to a reporter or tag, and analysis of protein-protein interaction by copurification and immunodetection experiments. The pGWBs were constructed with modified pBI101 containing a CaMV35S promoter-driven hygromycin phosphotransferase (HPT) gene as the second selection marker. We also constructed pGWBs with the marker HPT driven by the nopaline synthase promoter. By using the pGWB system, the expression of tagged proteins, and the localization of GFP-fused proteins were easily analyzed. Moreover, tissue-specific and inducible gene expression using a promoter was also monitored with pGWBs. It is expected that, the pGWB system will serve as a powerful tool for plasmid construction in plant research. PMID:17697981

  12. Multiscale Modeling of Gene-Behavior Associations in an Artificial Neural Network Model of Cognitive Development

    Science.gov (United States)

    Thomas, Michael S. C.; Forrester, Neil A.; Ronald, Angelica

    2016-01-01

    In the multidisciplinary field of developmental cognitive neuroscience, statistical associations between levels of description play an increasingly important role. One example of such associations is the observation of correlations between relatively common gene variants and individual differences in behavior. It is perhaps surprising that such…

  13. Horizontal Transmission and Retention of Malignancy, as well as Functional Human Genes, After Spontaneous Fusion of Human Glioblastoma and Hamster Host Cells In Vivo

    Science.gov (United States)

    Goldenberg, David M.; Zagzag, David; Heselmeyer-Haddad, Kerstin M.; Berroa Garcia, Lissa Y; Ried, Thomas; Loo, Meiyu; Chang, Chien-Hsing; Gold, David V.

    2011-01-01

    Cell fusion in vitro has been used to study cancer, gene mapping and regulation, and the production of antibodies via hybridomas. However, in-vivo heterosynkaryon formation by cell-cell fusion has received less attention. This investigation describes the spontaneous fusion of a human glioblastoma with normal hamster cells after xenogeneic transplantation, resulting in malignant cells that express both human and hamster genes and gene products, and retention of glioblastoma traits with an enhanced ability to metastasize. Three of 7 human genes found showed translation of their proteins during serial propagation in vivo or in vitro for years; namely, CD74, CXCR4, and PLAGL2, each implicated with malignancy or glioblastoma. This supports the thesis that genetic hybridization of cancer and normal cells can transmit malignancy and also, as first described herein, regulatory genes involved in the tumor’s organotypic morphology. Evidence also is increasing that even cell-free human cancer DNA can induce malignancy and transfer genetic information to normal cells. Hence, we posit that the transfer of genetic information between tumor and stromal cells, whether by cell-cell fusion or other mechanisms, is implicated in the progression of malignancy, and may further define the crosstalk between cancer cells and their stromal neighbors. PMID:21796629

  14. Artificial vision.

    Science.gov (United States)

    Zarbin, M; Montemagno, C; Leary, J; Ritch, R

    2011-09-01

    A number treatment options are emerging for patients with retinal degenerative disease, including gene therapy, trophic factor therapy, visual cycle inhibitors (e.g., for patients with Stargardt disease and allied conditions), and cell transplantation. A radically different approach, which will augment but not replace these options, is termed neural prosthetics ("artificial vision"). Although rewiring of inner retinal circuits and inner retinal neuronal degeneration occur in association with photoreceptor degeneration in retinitis pigmentosa (RP), it is possible to create visually useful percepts by stimulating retinal ganglion cells electrically. This fact has lead to the development of techniques to induce photosensitivity in cells that are not light sensitive normally as well as to the development of the bionic retina. Advances in artificial vision continue at a robust pace. These advances are based on the use of molecular engineering and nanotechnology to render cells light-sensitive, to target ion channels to the appropriate cell type (e.g., bipolar cell) and/or cell region (e.g., dendritic tree vs. soma), and on sophisticated image processing algorithms that take advantage of our knowledge of signal processing in the retina. Combined with advances in gene therapy, pathway-based therapy, and cell-based therapy, "artificial vision" technologies create a powerful armamentarium with which ophthalmologists will be able to treat blindness in patients who have a variety of degenerative retinal diseases.

  15. Development of a Safeguard System Using an Episomal Mammalian Artificial Chromosome for Gene and Cell Therapy

    Science.gov (United States)

    Uno, Narumi; Uno, Katsuhiro; Komoto, Shinya; Suzuki, Teruhiko; Hiratsuka, Masaharu; Osaki, Mitsuhiko; Kazuki, Yasuhiro; Oshimura, Mitsuo

    2015-01-01

    The development of a safeguard system to remove tumorigenic cells would allow safer clinical applications of stem cells for the treatment of patients with an intractable disease including genetic disorders. Such safeguard systems should not disrupt the host genome and should have long-term stability. Here, we attempted to develop a tumor-suppressing mammalian artificial chromosome containing a safeguard system that uses the immune rejection system against allogeneic tissue from the host. For proof-of-concept of the safeguard system, B16F10 mouse melanoma cells expressing the introduced H2-K(d) major histocompatibility complex (MHC class I)-allogenic haplotype were transplanted into recipient C57BL/6J mice expressing MHC H2-K(b). Subcutaneous implantation of B16F10 cells into C57BL/6J mice resulted in high tumorigenicity. The volume of tumors derived from B16F10 cells expressing allogenic MHC H2-K(d) was decreased significantly (P < 0.01). Suppression of MHC H2-K(d)-expressing tumors in C57BL/6J mice was enhanced by immunization with MHC H2-K(d)-expressing splenocytes (P < 0.01). These results suggest that the safeguard system is capable of suppressing tumor formation by the transplanted cells. PMID:26670279

  16. Expression pattern of the septin gene family in acute myeloid leukemias with and without MLL-SEPT fusion genes

    NARCIS (Netherlands)

    Santos, Joana; Cerveira, Nuno; Bizarro, Susana; Ribeiro, Franclim R.; Correia, Cecilia; Torres, Lurdes; Lisboa, Susana; Vieira, Joana; Mariz, Jose M.; Norton, Lucilia; Snijder, Simone; Mellink, Clemens H.; Buijs, Arjan; Shih, Lee-Yung; Strehl, Sabine; Micci, Francesca; Heim, Sverre; Teixeira, Manuel R.

    2010-01-01

    Septins are proteins associated with crucial steps in cell division and cellular integrity. In humans, 14 septin genes have been identified, of which five (SEPT2, SEPT5, SEPT6, SEPT9, and SEPT11) are known to participate in reciprocal translocations with the MLL gene in myeloid neoplasias. We have r

  17. Reversible male sterility in eggplant (Solanum melongena L.) by artificial microRNA-mediated silencing of general transcription factor genes.

    Science.gov (United States)

    Toppino, Laura; Kooiker, Maarten; Lindner, Matias; Dreni, Ludovico; Rotino, Giuseppe L; Kater, Martin M

    2011-08-01

    Since decades, plant male sterility is considered a powerful tool for biological containment to minimize unwanted self-pollination for hybrid seed production. Furthermore, prevention of pollen dispersal also answers to concerns regarding transgene flow via pollen from Genetically Modified (GM) crops to traditional crop fields or wild relatives. We induced male sterility by suppressing endogenous general transcription factor genes, TAFs, using anther-specific promoters combined with artificial microRNA (amiRNA) technology (Schwab et al., 2006). The system was made reversible by the ethanol inducible expression of an amiRNA-insensitive form of the target gene. We provide proof of concept in eggplant, a cultivated crop belonging to the Solanaceae family that includes many important food crops. The transgenic eggplants that we generated are completely male sterile and fertility can be fully restored by short treatments with ethanol, confirming the efficiency but also the reliability of the system in view of open field cultivation. By combining this system with induced parthenocarpy (Rotino et al., 1997), we provide a novel example of complete transgene containment in eggplant, which enables biological mitigation measures for the benefit of coexistence or biosafety purposes for GM crop cultivation. PMID:20955179

  18. A novel recurrent NPM1-TYK2 gene fusion in cutaneous CD30-positive lymphoproliferative disorders.

    Science.gov (United States)

    Velusamy, Thirunavukkarasu; Kiel, Mark J; Sahasrabuddhe, Anagh A; Rolland, Delphine; Dixon, Catherine A; Bailey, Nathanael G; Betz, Bryan L; Brown, Noah A; Hristov, Alexandra C; Wilcox, Ryan A; Miranda, Roberto N; Medeiros, L Jeffrey; Jeon, Yoon K; Inamdar, Kedar V; Lim, Megan S; Elenitoba-Johnson, Kojo S J

    2014-12-11

    The spectrum of cutaneous CD30-positive lymphoproliferative disorders (LPDs) includes lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma. Chromosomal translocations targeting tyrosine kinases in CD30-positive LPDs have not been described. Using whole-transcriptome sequencing, we identified a chimeric fusion involving NPM1 (5q35) and TYK2 (19p13) that encodes an NPM1-TYK2 protein containing the oligomerization domain of NPM1 and an intact catalytic domain in TYK2. Fluorescence in situ hybridization revealed NPM1-TYK2 fusions in 2 of 47 (4%) primary cases of CD30-positive LPDs and was absent in other mature T-cell neoplasms (n = 151). Functionally, NPM1-TYK2 induced constitutive TYK2, signal transducer and activator of transcription 1 (STAT1), STAT3, and STAT5 activation. Conversely, a kinase-defective NPM1-TYK2 mutant abrogated STAT1/3/5 signaling. Finally, short hairpin RNA-mediated silencing of TYK2 abrogated lymphoma cell growth. This is the first report of recurrent translocations involving TYK2, and it highlights the novel therapeutic opportunities in the treatment of CD30-positive LPDs with TYK2 translocations. PMID:25349176

  19. TALE-PvuII fusion proteins--novel tools for gene targeting.

    Science.gov (United States)

    Yanik, Mert; Alzubi, Jamal; Lahaye, Thomas; Cathomen, Toni; Pingoud, Alfred; Wende, Wolfgang

    2013-01-01

    Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA-cleavage module. This architecture is also used by TALE nucleases (TALENs), in which the DNA-binding modules of the ZFNs have been replaced by DNA-binding domains based on transcription activator like effector (TALE) proteins. Both TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI to induce double-strand DNA cleavage at the target site after recognition of the target DNA by the respective DNA-binding module. TALENs seem to have an advantage over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we present evidence that variant TALENs can be produced by replacing the catalytic domain of FokI with the restriction endonuclease PvuII. These fusion proteins recognize only the composite recognition site consisting of the target site of the TALE protein and the PvuII recognition sequence (addressed site), but not isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess of protein over DNA and long incubation times. In vitro, their preference for an addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion proteins are active in cellula with minimal cytotoxicity.

  20. End-to-end gene fusions and their impact on the production of multifunctional biomass degrading enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Rizk, Mazen, E-mail: mazen.rizk@tuhh.de [Institute of Technical Microbiology, Hamburg University of Technology (TUHH), Kasernenstr. 12, D-21073 Hamburg (Germany); Antranikian, Garabed, E-mail: antranikian@tuhh.de [Institute of Technical Microbiology, Hamburg University of Technology (TUHH), Kasernenstr. 12, D-21073 Hamburg (Germany); Elleuche, Skander, E-mail: skander.elleuche@tuhh.de [Institute of Technical Microbiology, Hamburg University of Technology (TUHH), Kasernenstr. 12, D-21073 Hamburg (Germany)

    2012-11-09

    Highlights: Black-Right-Pointing-Pointer Multifunctional enzymes offer an interesting approach for biomass degradation. Black-Right-Pointing-Pointer Size and conformation of separate constructs play a role in the effectiveness of chimeras. Black-Right-Pointing-Pointer A connecting linker allows for maximal flexibility and increased thermostability. Black-Right-Pointing-Pointer Genes with functional similarities are the best choice for fusion candidates. -- Abstract: The reduction of fossil fuels, coupled with its increase in price, has made the search for alternative energy resources more plausible. One of the topics gaining fast interest is the utilization of lignocellulose, the main component of plants. Its primary constituents, cellulose and hemicellulose, can be degraded by a series of enzymes present in microorganisms, into simple sugars, later used for bioethanol production. Thermophilic bacteria have proven to be an interesting source of enzymes required for hydrolysis since they can withstand high and denaturing temperatures, which are usually required for processes involving biomass degradation. However, the cost associated with the whole enzymatic process is staggering. A solution for cost effective and highly active production is through the construction of multifunctional enzyme complexes harboring the function of more than one enzyme needed for the hydrolysis process. There are various strategies for the degradation of complex biomass ranging from the regulation of the enzymes involved, to cellulosomes, and proteins harboring more than one enzymatic activity. In this review, the construction of multifunctional biomass degrading enzymes through end-to-end gene fusions, and its impact on production and activity by choosing the enzymes and linkers is assessed.

  1. From amplification to gene in thyroid cancer: A high-resolution mapped bacterial-artificial-chromosome resource for cancer chromosome aberrations guides gene discovery after comparative genome hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Chen, X.N.; Gonsky, R.; Korenberg, J.R. [UCLA School of Medicine, Los Angeles, CA (United States). Cedars-Sinai Research Inst.; Knauf, J.A.; Fagin, J.A. [Univ. of Cincinnati, OH (United States). Div. of Endocrinology/Metabolism; Wang, M.; Lai, E.H. [Univ. of North Carolina, Chapel Hill, NC (United States). Dept. of Pharmacology; Chissoe, S. [Washington Univ. School of Medicine, St. Louis, MO (United States). Genome Sequencing

    1998-08-01

    Chromosome rearrangements associated with neoplasms provide a rich resource for definition of the pathways of tumorigenesis. The power of comparative genome hybridization (CGH) to identify novel genes depends on the existence of suitable markers, which are lacking throughout most of the genome. The authors now report a general approach that translates CGH data into higher-resolution genomic-clone data that are then used to define the genes located in aneuploid regions. They used CGH to study 33 thyroid-tumor DNAs and two tumor-cell-line DNAs. The results revealed amplifications of chromosome band 2p21, with less-intense amplification on 2p13, 19q13.1, and 1p36 and with least-intense amplification on 1p34, 1q42, 5q31, 5q33-34, 9q32-34, and 14q32. To define the 2p21 region amplified, a dense array of 373 FISH-mapped chromosome 2 bacterial artificial chromosomes (BACs) was constructed, and 87 of these were hybridized to a tumor-cell line. Four BACs carried genomic DNA that was amplified in these cells. The maximum amplified region was narrowed to 3--6 Mb by multicolor FISH with the flanking BACs, and the minimum amplicon size was defined by a contig of 420 kb. Sequence analysis of the amplified BAC 1D9 revealed a fragment of the gene, encoding protein kinase C epsilon (PKC{epsilon}), that was then shown to be amplified and rearranged in tumor cells. In summary, CGH combined with a dense mapped resource of BACs and large-scale sequencing has led directly to the definition of PKC{epsilon} as a previously unmapped candidate gene involved in thyroid tumorigenesis.

  2. Glucose-responsive artificial promoter-mediated insulin gene transfer improves glucose control in diabetic mice

    Institute of Scientific and Technical Information of China (English)

    Jaeseok Han; Eung-Hwi Kim; Woohyuk Choi; Hee-Sook Jun

    2012-01-01

    AIM:To investigate the effect of insulin gene therapy using a glucose-responsive synthetic promoter in type 2 diabetic obese mice.METHODS:We employed a recently developed novel insulin gene therapy strategy using a synthetic promoter that regulates insulin gene expression in the liver in response to blood glucose level changes.We intravenously administered a recombinant adenovirus expressing furin-cleavable rat insulin under the control of the synthetic promoter (rAd-SP-rINSfur) into diabetic Leprdb/db mice.A recombinant adenovirus expressing β-galactosidase under the cytomegalovirus promoter was used as a control (rAd-CMV-βgal).Blood glucose levels and body weights were monitored for 50 d.Glucose and insulin tolerance tests were performed.Immunohistochemical staining was performed to investigate islet morphology and insulin content.RESULTS:Administration of rAd-SP-rINSfur lowered blood glucose levels and normoglycemia was maintained for 50 d,whereas the rAd-CMV-βgal control virus-injected mice remained hyperglycemic.Glucose tolerance tests showed that rAd-SP-rINSfur-treated mice cleared exogenous glucose from the blood more efficiently than control virus-injected mice at 4 wk [area under the curve (AUC):21 508.80 ± 2248.18 vs 62 640.00 ± 5014.28,P < 0.01] and at 6 wk (AUC:29 956.60 ± 1757.33 vs 60 016.60 ± 3794.47,P < 0.01).In addition,insulin sensitivity was also significantly improved in mice treated with rAd-SP-rINSfur compared with rAd-CMV-βgal-treated mice (AUC:9150.17±1007.78 vs 11 994.20 ± 474.40,P < 0.05).The islets from rAd-SP-rINSfur-injected mice appeared to be smaller and to contain a higher concentration of insulin than those from rAd-CMV-βgal-injected mice.CONCLUSION:Based on these results,we suggest that insulin gene therapy might be one therapeutic option for remission of type 2 diabetes.

  3. pBaSysBioll : an integrative plasmid generating gfp transcriptional fusions for high-throughput analysis of gene expression in Bacillus subtilis

    NARCIS (Netherlands)

    Botella, Eric; Fogg, Mark; Jules, Matthieu; Piersma, Sjouke; Doherty, Geoff; Hansen, Annette; Denham, Emma. L.; Le Chat, Ludovic; Veiga, Patrick; Bailey, Kirra; Lewis, Peter J.; van Dijl, Jan Maarten; Aymerich, Stephane; Wilkinson, Anthony J.; Devine, Kevin M.

    2010-01-01

    Plasmid pBaSysBioll was constructed for high-throughput analysis of gene expression in Bacillus subtilis. It is an integrative plasmid with a ligation-independent cloning (LIC) site, allowing the generation of transcriptional gfpmut3 fusions with desired promoters. Integration is by a Campbell-type

  4. Fusion protein gene nucleotide sequence similarities, shared antigenic sites and phylogenetic analysis suggest that phocid distemper virus 2 and canine distemper virus belong to the same virus entity.

    NARCIS (Netherlands)

    I.K.G. Visser (Ilona); R.W.J. van der Heijden (Roger); M.W.G. van de Bildt (Marco); M.J.H. Kenter (Marcel); C. Örvell; A.D.M.E. Osterhaus (Albert)

    1993-01-01

    textabstractNucleotide sequencing of the fusion protein (F) gene of phocid distemper virus-2 (PDV-2), recently isolated from Baikal seals (Phoca sibirica), revealed an open reading frame (nucleotides 84 to 2075) with two potential in-frame ATG translation initiation codons. We suggest that the secon

  5. Tethering of the conserved piggyBac transposase fusion protein CSB-PGBD3 to chromosomal AP-1 proteins regulates expression of nearby genes in humans.

    Directory of Open Access Journals (Sweden)

    Lucas T Gray

    2012-09-01

    Full Text Available The CSB-PGBD3 fusion protein arose more than 43 million years ago when a 2.5-kb piggyBac 3 (PGBD3 transposon inserted into intron 5 of the Cockayne syndrome Group B (CSB gene in the common ancestor of all higher primates. As a result, full-length CSB is now coexpressed with an abundant CSB-PGBD3 fusion protein by alternative splicing of CSB exons 1-5 to the PGBD3 transposase. An internal deletion of the piggyBac transposase ORF also gave rise to 889 dispersed, 140-bp MER85 elements that were mobilized in trans by PGBD3 transposase. The CSB-PGBD3 fusion protein binds MER85s in vitro and induces a strong interferon-like innate antiviral immune response when expressed in CSB-null UVSS1KO cells. To explore the connection between DNA binding and gene expression changes induced by CSB-PGBD3, we investigated the genome-wide DNA binding profile of the fusion protein. CSB-PGBD3 binds to 363 MER85 elements in vivo, but these sites do not correlate with gene expression changes induced by the fusion protein. Instead, CSB-PGBD3 is enriched at AP-1, TEAD1, and CTCF motifs, presumably through protein-protein interactions with the cognate transcription factors; moreover, recruitment of CSB-PGBD3 to AP-1 and TEAD1 motifs correlates with nearby genes regulated by CSB-PGBD3 expression in UVSS1KO cells and downregulated by CSB rescue of mutant CS1AN cells. Consistent with these data, the N-terminal CSB domain of the CSB-PGBD3 fusion protein interacts with the AP-1 transcription factor c-Jun and with RNA polymerase II, and a chimeric CSB-LacI construct containing only the N-terminus of CSB upregulates many of the genes induced by CSB-PGBD3. We conclude that the CSB-PGBD3 fusion protein substantially reshapes the transcriptome in CS patient CS1AN and that continued expression of the CSB-PGBD3 fusion protein in the absence of functional CSB may affect the clinical presentation of CS patients by directly altering the transcriptional program.

  6. In-vitro activation of cytotoxic T lymphocytes by fusion of mouse hepatocellular carcinoma cells and lymphotactin gene-modified dendritic cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the in-vitro activation of cytotoxic T lymphocytes (CTLs) by fusion of mouse hepatocellular carcinoma (HCC) cells and lymphotactin gene-modified dendritic cells (DCs).METHODS: Lymphotactin gene modified DCs (DCLptn) were prepared by lymphotactin recombinant adenovirus transduction of mature DCs which differentiated from mouse bone marrow cells by stimulation with granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-α). DCLptn and H22 fusion was prepared using 50% PEG. Lymphotactin gene and protein expression levels were measured by RT-PCR and ELISA, respectively. Lymphotactin chemotactic responses were examined by in-vitro chemotaxis assay. In-vitro activation of CTLs by DCLptn/H22 fusion was measured by detecting CD25 expression and cytokine production after autologous T cell stimulation. Cytotoxic function of activated T lymphocytes stimulated with DCLptn/H22 cells was determined by LDH cytotoxicity assay.RESULTS: Lymphotactin gene could be efficiently transduced to DCs by adenovirus vector and showed an effective biological activity. After fusion, the hybrid DCLptn/H22 cells acquired the phenotypes of both DCLptn and H22 cells. In T cell proliferation assay, flow cytometry showed a very high CD25 expression, and cytokine release assay showed a significantly higher concentration of IFN-γ and IL-2 in DCLptn/H22 group than in DCLptn, DCLptn+H22, DC/H22 or H22 groups. Cytotoxicity assay revealed that T cells derived from DCLptn/H22 group had much higher anti-tumor activity than those derived from DCLptn, H22, DCLptn + H22, DC/H22 groups.CONCLUSION: Lymphotactin gene-modified dendritoma induces T-cell proliferation and strong CTL reaction against allogenic HCC cells. Immunization-engineered fusion hybrid vaccine is an attractive strategy in prevention and treatment of HCC metastases.

  7. Cloning of rabies virus fusion gene pVax-G/N%狂犬病毒融合基因pVax-G/N的克隆

    Institute of Scientific and Technical Information of China (English)

    王政; 王小英; 蔡苗

    2012-01-01

    Object To construct rabies virus gene expression fusion vector of N and G genes for laying the foundation of the study on fusion gene vaccine. Methods Molecular biology technology was being employed to clone hydrophobic poison G and N gene from the plasmid pVax-G. After the success of the connection and appraisal,the cloned G and N gene were connected with wine yeast expression vector pYes2. And then the recombinant plasmid of G and N gene were appraised by restriction enzyme digestion and sequencing. Results The sequencing result of fusion gene pVax-G/N was consistent with excepted results. Conclusion Fusion expression vector of pYes2-pVax-C/N were successfully constructed, which would lay the foundation to study further on the stability and safety of rabies vaccine.%目的 构建狂犬病病毒C基因和N基因的融合表达载体,为研究融合基因疫苗打下基础.方法 利用分子生物学技术从质粒pVax-G中克隆出狂犬病毒G和N基因,经连接及鉴定成功后与酿酒酵母表达载体pYes2连接,并进行酶切及测序鉴定.结果 融合基因pVax-G/N测序结果与预期完全符合.结论 成功构建了融合表达载体pYes2-pVax-G/N,为进一步研究稳定、安全的狂犬病疫苗奠定基础.

  8. DETECTION OF MENDELIAN AND GENOTYPE FREQUENCY OF GROWTH HORMONE GENE IN ONGOLE CROSSBRED CATTLE MATED BY THE ARTIFICIAL INSEMINATION TECHNIQUE

    Directory of Open Access Journals (Sweden)

    U. Paputungan

    2012-06-01

    Full Text Available The objectives of this study were to detect the Mendelian mode inheritance of growth hormone (GH and to establish genotype frequency of GH gene in Ongole-crossbred cattle mated by the artificial insemination (AI technique. Total of 76 blood samples were collected from Ongole-crossbred cows and bulls (G0, and their progenies (G1 at the Tumaratas AI service center in North Sulawesi province, Indonesia. All blood samples were screened for the presence of GH locus using a PCR-RFLP method involving restricted enzyme Msp1 on 1.2 % of agarose gel. Data were analyzed using statistical program function in Excel XP. The results showed that GH locus using alleles of Msp1+ and Msp1- enzyme restriction in Ongole-crossbred cows and bulls was inherited to their Ongole-crossbred progenies following the Mendelian mode inheritance. This Mendelian inheritance generated by AI technique was not under genetic equilibrium for the Msp1 genotype frequencies in groups of G0 and G1. The breeding program using genotypes of bulls and cows (G0 for generating the genotype of GH Msp1 enzyme restriction by AI technique should be maintained to increase these various allele dispersion rates for breeding under genetic equilibrium of the Ongole-crossbred cattle population.

  9. Identification of varieties and gene flow in Douglas fir exemplified in artificially established stands in Germany

    Directory of Open Access Journals (Sweden)

    Barbara Fussi

    2013-12-01

    Full Text Available Douglas-fir [Pseudotsuga menziesii (Mirb. Franco] is an economically valuable non-native tree species in Germany and is considered very promising in view of global climate change. Therefore, the genetic characterization of Douglas-fir populations and seed stands in Germany is essential. We studied coastal and interior Douglas-fir varieties, both present in Germany, by using eleven isoenzyme and four microsatellite loci. By analyzing eight reference populations of known origin we were able to identify the two varieties on the population level using Bayesian and distance based methods. Seven populations present in Bavaria were then successfully assigned to one of the two varieties. Within varieties we found stronger grouping within the interior variety than within the coastal one. Despite lower differences within coastal Douglas-fir we have first indications for the origin of two populations. For two Bavarian populations, natural regeneration was included and genetic data revealed no significant genetic difference between adults and offspring. The parentage analysis for one of the studied stands revealed that a large proportion of adults took part in the reproduction, but some trees were more successful than others in transferring their genes to the next generation. Our study was able to improve variety identification of Douglas-fir using isoenzyme markers and nuclear microsatellites and study reproductive patterns, both are important issues for the management of Douglas-fir stands in Bavaria.

  10. Secretory breast carcinomas with ETV6-NTRK3 fusion gene belong to the basal-like carcinoma spectrum.

    Science.gov (United States)

    Laé, Marick; Fréneaux, Paul; Sastre-Garau, Xavier; Chouchane, Olfa; Sigal-Zafrani, Brigitte; Vincent-Salomon, Anne

    2009-02-01

    Secretory breast carcinomas (carcinoma. A series of six secretory breast carcinomas were identified in our files. The ETV6 rearrangement was confirmed in all cases by fluorescence in situ hybridization. Immunophenotype was assessed with anti-ER, PR, ERBB2, KIT, EGFR, E-cadherin, vimentin, PS100, smooth muscle actin, basal (CK5/6 and 14), luminal cytokeratins (CK8/18) and p63 antibodies. In situ and invasive components shared the same immunoprofile and were ER, PR, ERBB2 negative with expression of basal cytokeratins. ETV6 gene alterations were present in both in situ and invasive components, highlighting their genetic similarities. The immunoprofile data (triple-negative with expression of basal markers) showed that secretory breast carcinomas with ETV6-NTRK3 fusion gene belong to the phenotypic basal-like spectrum of breast carcinomas. These results support the hypothesis that secretory breast carcinomas have immunohistochemical and genetic features that distinguish them from other basal-like tumors of the breast.

  11. Ewing Sarcoma With ERG Gene Rearrangements: A Molecular Study Focusing on the Prevalence of FUS-ERG and Common Pitfalls in Detecting EWSR1-ERG Fusions by FISH

    Science.gov (United States)

    Chen, Sonja; Deniz, Kemal; Sung, Yun-Shao; Zhang, Lei; Dry, Sarah; Antonescu, Cristina R.

    2016-01-01

    The genetics of Ewing sarcoma (ES) are characterized by a canonical fusion involving EWSR1 gene and a member of the ETS family of transcription factors, such as FLI1 and ERG. In fact, ERG gene rearrangements represent the second most common molecular alteration, with EWSR1-ERG being identified in 5–10% of cases, while only a handful of reports document a FUS-ERG fusion. In this study, we focus on ES with ERG gene abnormalities, specifically to investigate the prevalence and clinicopathologic features of FUS-ERG fusions in a large cohort of small blue round cell tumors (SBRCTs) and compare to the eight reported FUS-positive ES. Among the 85 SBRCTs tested, seven (8.2%) cases harbored FUS gene rearrangements; six fused to ERG and one with FEV. During this investigation we came across a number of ERG-rearranged ES lacking both EWSR1 and FUS abnormalities by FISH. In one case, RNA sequencing identified an EWSR1-ERG transcript despite the negative EWSR1 rearrangements by FISH. Additional 3-color FISH fusion assay demonstrated the fusion of EWSR1 and ERG signals in all four cases negative for break-apart EWSR1 FISH. These results emphasize a potential pitfall of relying on EWSR1 FISH assay alone for diagnosis of ES. In cases with classic morphology and/or strong CD99 and ERG immunoreactivity, additional molecular testing should be applied, such as ERG FISH or RT-PCR/next generation sequencing, for a more definitive diagnosis. Although our study group is small, there were no differences noted between the clinical, morphologic features and immunoprofile of the different subsets of ERG-rearranged SBRCTs. PMID:26690869

  12. Bioinformatic analysis of patient-derived ASPS gene expressions and ASPL-TFE3 fusion transcript levels identify potential therapeutic targets.

    Directory of Open Access Journals (Sweden)

    David G Covell

    Full Text Available Gene expression data, collected from ASPS tumors of seven different patients and from one immortalized ASPS cell line (ASPS-1, was analyzed jointly with patient ASPL-TFE3 (t(X;17(p11;q25 fusion transcript data to identify disease-specific pathways and their component genes. Data analysis of the pooled patient and ASPS-1 gene expression data, using conventional clustering methods, revealed a relatively small set of pathways and genes characterizing the biology of ASPS. These results could be largely recapitulated using only the gene expression data collected from patient tumor samples. The concordance between expression measures derived from ASPS-1 and both pooled and individual patient tumor data provided a rationale for extending the analysis to include patient ASPL-TFE3 fusion transcript data. A novel linear model was exploited to link gene expressions to fusion transcript data and used to identify a small set of ASPS-specific pathways and their gene expression. Cellular pathways that appear aberrantly regulated in response to the t(X;17(p11;q25 translocation include the cell cycle and cell adhesion. The identification of pathways and gene subsets characteristic of ASPS support current therapeutic strategies that target the FLT1 and MET, while also proposing additional targeting of genes found in pathways involved in the cell cycle (CHK1, cell adhesion (ARHGD1A, cell division (CDC6, control of meiosis (RAD51L3 and mitosis (BIRC5, and chemokine-related protein tyrosine kinase activity (CCL4.

  13. Detection of the SYT-SSX Fusion Gene in Synovial Sarcoma%滑膜肉瘤融合基因SYT-SSX检测

    Institute of Scientific and Technical Information of China (English)

    杨翎; 范钦和; 张炜明

    2004-01-01

    目的:研究采用逆转录-聚合酶链反应的方法在滑膜肉瘤石蜡包埋组织中检测SYT-SSX融合基因的可行性和临床意义.方法:收集20例滑膜肉瘤标本,均为甲醛固定,石蜡包埋组织.SYT-SSX融合基因采用逆转录-聚合酶链反应(RT-PCR)检测.看家基因PBGD作为内参照.结果:所有标本均可检测到PBGDmRNA的表达.18例检测到融合基因SYT-SSX的表达,其中,SYT-SSX1型占12例,SYT-SSX2型占6例(4例为单相型滑膜肉瘤).结论:在滑膜肉瘤甲醛固定,石蜡包埋组织中用RT-PCR方法检测SYT-SSX融合基因是可行的,有较高的敏感性.融合基因亚型与滑膜肉瘤组织学分型有一定关系,可为预后提供重要信息.%Objective: To investigate the feasibility and significance of detecting SYT-SSX fusion gene in paraffin-embedded tissues of synovial sarcoma (SS) by reverse-transcriptase polymerase chain reaction(RT-PCR) methods. Methods: Twenty cases of SS tumors from archival materials were collected and all samples were formalin-fixed and paraffin-embedded (FFPE). SYT-SSX fusion transcript was detected by RT-PCR. Home-keeping gene Porphobilinogen Deaminase (PBGD) was regarded as intemal control. Results: PBGD mRNA was detected in all 20 tumor cases (100%). SYT-SSX fusion transcript was detected in 18 tumor cases (90%). In 18 SYT-SSX positive SS cases, there are 12 present SYT-SSX1 fusion transcript and 6 present SYT-SSX2 fusion transcript. SYT-SSX1 fusion transcript can be seen in 9 monophasic SS and 3 biphasic SS. In 6 SYT- SSX2 positive SS cases, 4 were monophasic SS and 2 were biphasic. Conclusion: Detection of SYT-SSX fusion transcripts in FFPE tissues for diagnosis of SS is feasible and sensitive. Subtypes of SYT-SSX fusion gene may provide prognosis information.

  14. Fusion of the TBL1XR1 and HMGA1 genes in splenic hemangioma with t(3;6)(q26;p21).

    Science.gov (United States)

    Panagopoulos, Ioannis; Gorunova, Ludmila; Bjerkehagen, Bodil; Lobmaier, Ingvild; Heim, Sverre

    2016-03-01

    RNA-sequencing of a splenic hemangioma with the karyotype 45~47,XX,t(3;6)(q26;p21) showed that this translocation generated a chimeric TBL1XR1-HMGA1 gene. This is the first time that this tumor has been subjected to genetic analysis, but the finding of an acquired clonal chromosome abnormality in cells cultured from the lesion and the presence of the TBL1XR1-HMGA1 fusion in them strongly favor the conclusion that splenic hemangiomas are of a neoplastic nature. Genomic PCR confirmed the presence of the TBL1XR1-HMGA1 fusion gene, and RT-PCR together with Sanger sequencing verified the presence of the fusion transcripts. The molecular consequences of the t(3;6) would be substantial. The cells carrying the translocation would retain only one functional copy of the wild-type TBL1XR1 gene while the other, rearranged allele could produce a putative truncated form of TBL1XR1 protein containing the LiSH and F-box-like domains. In the TBL1XR1-HMGA1 fusion transcript, furthermore, untranslated exons of HMGA1 are replaced by the first 5 exons of the TBL1XR1 gene. The result is that the entire coding region of HMGA1 comes under the control of the TBL1XR1 promoter, bringing about dysregulation of HMGA1. This is reminiscent of similar pathogenetic mechanisms involving high mobility genes in benign connective tissue tumors such as lipomas and leiomyomas.

  15. Fusion of the TBL1XR1 and HMGA1 genes in splenic hemangioma with t(3;6)(q26;p21)

    Science.gov (United States)

    PANAGOPOULOS, IOANNIS; GORUNOVA, LUDMILA; BJERKEHAGEN, BODIL; LOBMAIER, INGVILD; HEIM, SVERRE

    2016-01-01

    RNA-sequencing of a splenic hemangioma with the karyotype 45~47,XX,t(3;6)(q26;p21) showed that this translocation generated a chimeric TBL1XR1-HMGA1 gene. This is the first time that this tumor has been subjected to genetic analysis, but the finding of an acquired clonal chromosome abnormality in cells cultured from the lesion and the presence of the TBL1XR1-HMGA1 fusion in them strongly favor the conclusion that splenic hemangiomas are of a neoplastic nature. Genomic PCR confirmed the presence of the TBL1XR1-HMGA1 fusion gene, and RT-PCR together with Sanger sequencing verified the presence of the fusion transcripts. The molecular consequences of the t(3;6) would be substantial. The cells carrying the translocation would retain only one functional copy of the wild-type TBL1XR1 gene while the other, rearranged allele could produce a putative truncated form of TBL1XR1 protein containing the LiSH and F-box-like domains. In the TBL1XR1-HMGA1 fusion transcript, furthermore, untranslated exons of HMGA1 are replaced by the first 5 exons of the TBL1XR1 gene. The result is that the entire coding region of HMGA1 comes under the control of the TBL1XR1 promoter, bringing about dysregulation of HMGA1. This is reminiscent of similar pathogenetic mechanisms involving high mobility genes in benign connective tissue tumors such as lipomas and leiomyomas. PMID:26708416

  16. Identification of a lung adenocarcinoma cell line with CCDC6-RET fusion gene and the effect of RET inhibitors in vitro and in vivo.

    Science.gov (United States)

    Suzuki, Makito; Makinoshima, Hideki; Matsumoto, Shingo; Suzuki, Ayako; Mimaki, Sachiyo; Matsushima, Koutatsu; Yoh, Kiyotaka; Goto, Koichi; Suzuki, Yutaka; Ishii, Genichiro; Ochiai, Atsushi; Tsuta, Koji; Shibata, Tatsuhiro; Kohno, Takashi; Esumi, Hiroyasu; Tsuchihara, Katsuya

    2013-07-01

    Rearrangements of the proto-oncogene RET are newly identified potential driver mutations in lung adenocarcinoma (LAD). However, the absence of cell lines harboring RET fusion genes has hampered the investigation of the biological relevance of RET and the development of RET-targeted therapy. Thus, we aimed to identify a RET fusion positive LAD cell line. Eleven LAD cell lines were screened for RET fusion transcripts by reverse transcription-polymerase chain reaction. The biological relevance of the CCDC6-RET gene products was assessed by cell growth, survival and phosphorylation of ERK1/2 and AKT with or without the suppression of RET expression using RNA interference. The efficacy of RET inhibitors was evaluated in vitro using a culture system and in an in vivo xenograft model. Expression of the CCDC6-RET fusion gene in LC-2/ad cells was demonstrated by the mRNA and protein levels, and the genomic break-point was confirmed by genomic DNA sequencing. Mutations in KRAS and EGFR were not observed in the LC-2/ad cells. CCDC6-RET was constitutively active, and the introduction of a siRNA targeting the RET 3' region decreased cell proliferation by downregulating RET and ERK1/2 phosphorylation. Moreover, treatment with RET-inhibitors, including vandetanib, reduced cell viability, which was accompanied by the downregulation of the AKT and ERK1/2 signaling pathways. Vandetanib exhibited anti-tumor effects in the xenograft model. Endogenously expressing CCDC6-RET contributed to cell growth. The inhibition of kinase activity could be an effective treatment strategy for LAD. LC-2/ad is a useful model for developing fusion RET-targeted therapy. PMID:23578175

  17. Mutations in the Drosophila pushover gene confer increased neuronal excitability and spontaneous synaptic vesicle fusion

    Energy Technology Data Exchange (ETDEWEB)

    Richards, S.; Hillman, T.; Stern, M. [Rice Univ., Houston, TX (United States)

    1996-04-01

    We describe the identification of a gene called pushover (push), which affects both behavior and synaptic transmission at the neuromuscular junction. Adults carrying either of two mutations in push exhibit sluggishness, uncoordination, a defective escape response, and male sterility. Larvae defective in push exhibit increased release of transmitter at the neuromuscular junction. In particular, the frequency of spontaneous transmitter release and the amount of transmitter release evoked by nerve stimulation are each increased two- to threefold in push mutants at the lowest external [(Ca{sup 2+})] tested (0.15 mM). Furthermore, these mutants are more sensitive than wild type to application of the potassium channel-blocking drug quinidine: following quinidine application, push mutants, but not wild-type, display repetitive firing of the motor axon, leading to repetitive muscle postsynaptic potentials. The push gene thus might affect both neuronal excitability and the transmitter release process. Complementation tests and recombinational mapping suggest that the push mutations are allelic to a previously identified P-element-induced mutation, which also causes behavorial abnormalities and male sterility. 43 refs., 5 figs., 1 tab.

  18. Genes encoding Cher-TPR fusion proteins are predominantly found in gene clusters encoding chemosensory pathways with alternative cellular functions.

    Science.gov (United States)

    Muñoz-Martínez, Francisco; García-Fontana, Cristina; Rico-Jiménez, Miriam; Alfonso, Carlos; Krell, Tino

    2012-01-01

    Chemosensory pathways correspond to major signal transduction mechanisms and can be classified into the functional families flagellum-mediated taxis, type four pili-mediated taxis or pathways with alternative cellular functions (ACF). CheR methyltransferases are core enzymes in all of these families. CheR proteins fused to tetratricopeptide repeat (TPR) domains have been reported and we present an analysis of this uncharacterized family. We show that CheR-TPRs are widely distributed in GRAM-negative but almost absent from GRAM-positive bacteria. Most strains contain a single CheR-TPR and its abundance does not correlate with the number of chemoreceptors. The TPR domain fused to CheR is comparatively short and frequently composed of 2 repeats. The majority of CheR-TPR genes were found in gene clusters that harbor multidomain response regulators in which the REC domain is fused to different output domains like HK, GGDEF, EAL, HPT, AAA, PAS, GAF, additional REC, HTH, phosphatase or combinations thereof. The response regulator architectures coincide with those reported for the ACF family of pathways. Since the presence of multidomain response regulators is a distinctive feature of this pathway family, we conclude that CheR-TPR proteins form part of ACF type pathways. The diversity of response regulator output domains suggests that the ACF pathways form a superfamily which regroups many different regulatory mechanisms, in which all CheR-TPR proteins appear to participate. In the second part we characterize WspC of Pseudomonas putida, a representative example of CheR-TPR. The affinities of WspC-Pp for S-adenosylmethionine and S-adenosylhomocysteine were comparable to those of prototypal CheR, indicating that WspC-Pp activity is in analogy to prototypal CheRs controlled by product feed-back inhibition. The removal of the TPR domain did not impact significantly on the binding constants and consequently not on the product feed-back inhibition. WspC-Pp was found to be

  19. Genes encoding Cher-TPR fusion proteins are predominantly found in gene clusters encoding chemosensory pathways with alternative cellular functions.

    Directory of Open Access Journals (Sweden)

    Francisco Muñoz-Martínez

    Full Text Available Chemosensory pathways correspond to major signal transduction mechanisms and can be classified into the functional families flagellum-mediated taxis, type four pili-mediated taxis or pathways with alternative cellular functions (ACF. CheR methyltransferases are core enzymes in all of these families. CheR proteins fused to tetratricopeptide repeat (TPR domains have been reported and we present an analysis of this uncharacterized family. We show that CheR-TPRs are widely distributed in GRAM-negative but almost absent from GRAM-positive bacteria. Most strains contain a single CheR-TPR and its abundance does not correlate with the number of chemoreceptors. The TPR domain fused to CheR is comparatively short and frequently composed of 2 repeats. The majority of CheR-TPR genes were found in gene clusters that harbor multidomain response regulators in which the REC domain is fused to different output domains like HK, GGDEF, EAL, HPT, AAA, PAS, GAF, additional REC, HTH, phosphatase or combinations thereof. The response regulator architectures coincide with those reported for the ACF family of pathways. Since the presence of multidomain response regulators is a distinctive feature of this pathway family, we conclude that CheR-TPR proteins form part of ACF type pathways. The diversity of response regulator output domains suggests that the ACF pathways form a superfamily which regroups many different regulatory mechanisms, in which all CheR-TPR proteins appear to participate. In the second part we characterize WspC of Pseudomonas putida, a representative example of CheR-TPR. The affinities of WspC-Pp for S-adenosylmethionine and S-adenosylhomocysteine were comparable to those of prototypal CheR, indicating that WspC-Pp activity is in analogy to prototypal CheRs controlled by product feed-back inhibition. The removal of the TPR domain did not impact significantly on the binding constants and consequently not on the product feed-back inhibition. WspC-Pp was

  20. Using a GFP-gene fusion technique to study the cell cycle-dependent distribution of calmodulin in living cells

    Institute of Scientific and Technical Information of China (English)

    李朝军; 吕品; 张东才

    1999-01-01

    In this study, a green fluorescent protein (GFP)-calmodulin (CaM) fusion gene method was used to examine the distribution of calmodulin during various stages of cell cycle. First, it was found that the distribution of CaM in living cells changes with the cell cycle. CaM was found mainly in the cytoplasm during G1 phase. It began to move into the nucleus when the cell entered S phase. At G2 phase, CaM became more concentrated in the nucleus than in cytoplasm. Second, the accumulation of CaM in the nucleus during G2 phase appeared to be related to the onset of mitosis, since inhibiting the activation of CaM at this stage resulted in blocking the nuclear membrane breakdown and chromatin condensation. Finally, after the cell entered mitosis, a high concentration of CaM was found at the polar regions of the mitotic spindle. At this time, inhibiting the activity of CaM would cause a disruption of the spindle structure. The relationship between the stage-specific distribution of CaM and its function in regulat

  1. A simple, rapid, low-cost technique for naked-eye detection of urine-isolated TMPRSS2:ERG gene fusion RNA

    Science.gov (United States)

    Koo, Kevin M.; Wee, Eugene J. H.; Mainwaring, Paul N.; Trau, Matt

    2016-01-01

    The TMPRSS2:ERG gene fusion is one of a series of highly promising prostate cancer (PCa) biomarker alternatives to the controversial serum PSA. Current methods for detecting TMPRSS2:ERG are limited in terms of long processing time, high cost and the need for specialized equipment. Thus, there is an unmet need for less complex, faster, and cheaper methods to enable gene fusion detection in the clinic. We describe herein a simple, rapid and inexpensive assay which combines robust isothermal amplification technique with a novel visualization method for evaluating urinary TMPRSS2:ERG status at less than USD 5 and with minimal equipment. The assay is sensitive, and rapidly detects as low as 105 copies of TMPRSS2:ERG transcripts while maintaining high levels of specificity. PMID:27470540

  2. A simple, rapid, low-cost technique for naked-eye detection of urine-isolated TMPRSS2:ERG gene fusion RNA.

    Science.gov (United States)

    Koo, Kevin M; Wee, Eugene J H; Mainwaring, Paul N; Trau, Matt

    2016-01-01

    The TMPRSS2:ERG gene fusion is one of a series of highly promising prostate cancer (PCa) biomarker alternatives to the controversial serum PSA. Current methods for detecting TMPRSS2:ERG are limited in terms of long processing time, high cost and the need for specialized equipment. Thus, there is an unmet need for less complex, faster, and cheaper methods to enable gene fusion detection in the clinic. We describe herein a simple, rapid and inexpensive assay which combines robust isothermal amplification technique with a novel visualization method for evaluating urinary TMPRSS2:ERG status at less than USD 5 and with minimal equipment. The assay is sensitive, and rapidly detects as low as 10(5) copies of TMPRSS2:ERG transcripts while maintaining high levels of specificity. PMID:27470540

  3. Artificial intelligence

    CERN Document Server

    Hunt, Earl B

    1975-01-01

    Artificial Intelligence provides information pertinent to the fundamental aspects of artificial intelligence. This book presents the basic mathematical and computational approaches to problems in the artificial intelligence field.Organized into four parts encompassing 16 chapters, this book begins with an overview of the various fields of artificial intelligence. This text then attempts to connect artificial intelligence problems to some of the notions of computability and abstract computing devices. Other chapters consider the general notion of computability, with focus on the interaction bet

  4. Spatial Localization of Genes Determined by Intranuclear DNA Fragmentation with the Fusion Proteins Lamin KRED and Histone KRED und Visible Light

    OpenAIRE

    Waldeck, Waldemar; Mueller, Gabriele; Glatting, Karl-Heinz; Hotz-Wagenblatt, Agnes; Diessl, Nicolle; Chotewutmonti, Sasithorn; Langowski, Jörg; Semmler, Wolfhard; Wiessler, Manfred; Braun, Klaus

    2013-01-01

    The highly organized DNA architecture inside of the nuclei of cells is accepted in the scientific world. In the human genome about 3 billion nucleotides are organized as chromatin in the cell nucleus. In general, they are involved in gene regulation and transcription by histone modification. Small chromosomes are localized in a central nuclear position whereas the large chromosomes are peripherally positioned. In our experiments we inserted fusion proteins consisting of a component of the nuc...

  5. Frequency of the ETV6-RUNX1, BCR-ABL1, TCF3-PBX1, and MLL-AFF1 fusion genes in Guatemalan pediatric acute lymphoblastic leukemia patients and their ethnic associations.

    Science.gov (United States)

    Carranza, Claudia; Granados, Lilian; Morales, Oneida; Jo, Wendy; Villagran, Swuanny; Tinti, Damaris; Villegas, Mauricio; Antillón, Federico; Torselli, Silvana; Silva, Gabriel

    2013-06-01

    Fusion genes involved in acute lymphoblastic leukemia (ALL) occur mostly due to genetic and environmental factors, and only a limited number of studies have reported any ethnic influence. This study assesses whether an ethnic influence has an effect on the frequency of any of the four fusion genes: BCR-ABL1, ETV6-RUNX1, TCF3-PBX1, and MLL-AFF1 found in ALL. To study this ethnic influence, mononuclear cells were obtained from bone marrow samples from 143 patients with ALL. We performed RNA extraction and reverse transcription, then assessed the quality of the cDNA by amplifying the ABL1 control gene, and finally evaluated the presence of the four transcripts by multiplex polymerase chain reaction. We found 10 patients who had the BCR-ABL1 fusion gene (7%); 3 patients (2%) were TCF3-PBX1 positive; and 6 patients (4.5%) were ETV6-RUNX1 positive. The incidence of this last fusion gene is quite low when compared to the values reported in most countries. The low incidence of the ETV6-RUNX1 fusion gene found in Guatemala matches the incidence rates that have been reported in Spain and Indian Romani. Since it is known that an ethnic resemblance exists among these three populations, as shown by ancestral marker studies, the ALL data suggests an ethnic influence on the occurrence and frequency of this particular fusion gene.

  6. Intraparenchymal mesenchymal chondrosarcoma of the frontal lobe--a case report and molecular detection of specific gene fusions from archival FFPE sample.

    Science.gov (United States)

    Sajjad, Emir Ahmed; Sikora, Katarzyna; Paciejewski, Tomasz; Garbicz, Filip; Paskal, Wiktor; Szacht, Milena; Grajkowska, Wieslawa; Włodarski, Pawel Krzysztof

    2015-01-01

    Mesenchymal chondrosarcoma is a rare tumor of cartilaginous origin characterized by its bimorphic pattern composed of highly undifferentiated small round cells separated by islands of well-differentiated hyaline cartilage. It exhibits higher malignancy and earlier occurrence in comparison to classic chondrosarcomas. Recently identified HEY1-NCOA2 and IRF2BP2-CDX1 gene fusions confirm their distinct molecular origin and pose a promising diagnostic marker. The majority of cases arise from craniofacial bones. In this study, we present a rare case of mesenchymal chondrosarcoma encompassed within the brain parenchyma of the frontal lobe without any dural or bone attachment. We demonstrate histopathological findings and confirm the HEY1-NCOA2 gene fusion in a formalin-fixed paraffin-embedded archival sample using simple reverse transcription polymerase chain reaction (RT-PCR) method. IRF2BP2-CDX1 gene fusion was absent in the analyzed sample. The clinical follow-up is also presented with a review of treatment modalities for this entity.

  7. Atrophic dermatofibrosarcoma protuberans with the fusion gene COL1A1-PDGFB detected by RT-PCR using only a single primer pair.

    Science.gov (United States)

    Xu, Wen-Jun; Wang, Ju-Sheng

    2015-01-01

    Dermatofibrosarcoma protuberans (DFSPs) is an uncommon dermal tumor of intermediate to low-grade malignancy. A few patients have clinically persistent plaques that might be atrophic, and they are difficult to be diagnosed clinically. With the development of cytogenetic and molecular biology techniques, the detection of fusion transcripts of the collagen type 1a1 (COL1A1) and platelet-derived growth factor-BB (PDGFB) genes has been recognized as a reliable and valuable molecular tool for the diagnosis of DFSPs. We reported a 24-year-old woman who had a 2 years history of atrophic DFSPs, and detected the gene fusion between COL1A1 to PDGFB by one-step method of RT-PCR using only a single primer pair. The gene fusion detected by this rapid and efficient one-step method in our patient appears to be the first report of atrophic DFSPs, and we detected a novel COL1A1 breakpoint between exon 2 and exon 3.

  8. Investigating effect of fusion gene therapy by MR diffusion-weighted imaging in a rat C6 glioma model

    International Nuclear Information System (INIS)

    Objective: To evaluate the use of diffusion-weighted imaging (DWI) for early detection of tumor response to Angiostatin-Endostatin (Statin-AE) fusion gene therapy in a rat C6 glioma model. Methods: Fifty male wistar rats with C6 tumor cells implanted into the striatum were examined by a 3.0T MR scanner, then the rats bearing tumors were divided into two groups, treatment group and control group. Rats in the treatment group received 107 plaque forming unit (pfu) recombinant herps simplex viral (R-HSV) mediated Statin-AE fusion gene therapy on day 7, and then the tumors were conformed on MRI. Conventional MR and DWI examination were acquired on 1, 2, 3 weeks after implantation with a 5-inch surface coil. Two (1 w), eight (2 w) and all the residual rats (3 w) of each group were sacrificed to perform the histopathological examination after each MRI examination. Pretreatment and post treatment tumor volumes and apparent diffusion coefficient (ADC) values were calculated. Bank sum test and t test were employed for statistical analysis. Results: On MRI, 43 rats demonstrated tumors on day 7 with a successful rate of 86%. On week 2, the tumor volumes of the controls and treatment group were 90. 6 and 91.64 mm3 , with no significant difference (Z=-0.14, P>0.05). On week 3, the tumor volumes of the controls and treatment group were 156.64 and 29.64 mm3, and a significant difference was observed (Z=-3.45, P-3 and (0.99 ± 0.08) x 10-3mm2/s, and the values of the tumor peripheral parts of the two groups were (1.00 ± 0.25) x 10-3 and (0.83 ± 0.12) x 10-3 mm2/s, the ADC values of both tumor centers and peripheral parts of the treatment group were significantly higher than those of the control group (t=-0.82 and -0.46, P-3 and (0.99 ± 0.09) x 10-3mm2/s, and the values of the tumor peripheral parts of the two groups were (0.81±0.19) x 10-3 and (0.78±0.11) x 10-3 mm2/s, there were no statistical difference between the two groups (t=0.82, and -0.46, P<0.05). HE stained slices

  9. Data fusion mathematics theory and practice

    CERN Document Server

    Raol, Jitendra R

    2015-01-01

    Fills the Existing Gap of Mathematics for Data FusionData fusion (DF) combines large amounts of information from a variety of sources and fuses this data algorithmically, logically and, if required intelligently, using artificial intelligence (AI). Also, known as sensor data fusion (SDF), the DF fusion system is an important component for use in various applications that include the monitoring of vehicles, aerospace systems, large-scale structures, and large industrial automation plants. Data Fusion Mathematics: Theory and Practice offers a comprehensive overview of data fusion, and provides a

  10. Paired Box Gene 8-Peroxisome Proliferator-Activated Receptor-γ Fusion Protein and Loss of Phosphatase and Tensin Homolog Synergistically Cause Thyroid Hyperplasia in Transgenic Mice

    OpenAIRE

    Diallo-Krou, Ericka; Yu, Jingcheng; Colby, Lesley A.; Inoki, Ken; Wilkinson, John E.; Thomas, Dafydd G.; Giordano, Thomas J.; Koenig, Ronald J.

    2009-01-01

    Approximately 35% of follicular thyroid carcinomas and a small fraction of follicular adenomas are associated with a t(2;3)(q13;p25) chromosomal translocation that fuses paired box gene 8 (PAX8) with the peroxisome proliferator-activated receptor-γ gene (PPARG), resulting in expression of a PAX8-PPARγ fusion protein, PPFP. The mechanism by which PPFP contributes to follicular thyroid neoplasia is poorly understood. Therefore, we have created mice with thyroid-specific expression of PPFP. At 1...

  11. Artificial vision workbench.

    Science.gov (United States)

    Frenger, P

    1997-01-01

    Machine vision is an important component of medical systems engineering. Inexpensive miniature solid state cameras are now available. This paper describes how these devices can be used as artificial retinas, to take snapshots and moving pictures in monochrome or color. Used in pairs, they produce a stereoscopic field of vision and enable depth perception. Macular and peripheral vision can be simulated electronically. This paper also presents the author's design of an artificial orbit for this synthetic eye. The orbit supports the eye, protects it, and provides attachment points for the ocular motion control system. Convergence and image fusion can be produced, and saccades simulated, along with the other ocular motions. The use of lenses, filters, irises and focusing mechanisms are also discussed. Typical camera-computer interfaces are described, including the use of "frame grabbers" and analog-to-digital image conversion. Software programs for eye positioning, image manipulation, feature extraction and object recognition are discussed, including the application of artificial neural networks.

  12. The role of the Aspergillus niger furin-type protease gene in processing of fungal proproteins and fusion proteins: Evidence for alternative processing of recombinant (fusion-) proteins

    NARCIS (Netherlands)

    Punt, P.J.; Drint-Kuijvenhoven, A.; Lokman, B.C.; Spencer, J.A.; Jeenes, D.; Archer, D.A.; Hondel, C.A.M.J.J. van den

    2003-01-01

    We have characterized growth and protein processing characteristics of Aspergillus niger strains carrying a disrupted allele of the previously cloned and characterized kexB gene [Appl. Environ. Microbiol. 66 (2000) 363] encoding a furin-type endoprotease. Deletion of the single-copy gene confirms it

  13. Genetic interaction between Tmprss2-ERG gene fusion and Nkx3.1-loss does not enhance prostate tumorigenesis in mouse models.

    Directory of Open Access Journals (Sweden)

    Douglas E Linn

    Full Text Available Gene fusions involving ETS family transcription factors (mainly TMPRSS2-ERG and TMPRSS2-ETV1 fusions have been found in ~50% of human prostate cancer cases. Although expression of TMPRSS2-ERG or TMPRSS2-ETV1 fusion alone is insufficient to initiate prostate tumorigenesis, they appear to sensitize prostate epithelial cells for cooperation with additional oncogenic mutations to drive frank prostate adenocarcinoma. To search for such ETS-cooperating oncogenic events, we focused on a well-studied prostate tumor suppressor NKX3.1, as loss of NKX3.1 is another common genetic alteration in human prostate cancer. Previous studies have shown that deletions at 8p21 (harboring NKX3.1 and 21q22 (resulting in TMPRSS2-ERG fusion were both present in a subtype of prostate cancer cases, and that ERG can lead to epigenetic silencing of NKX3.1 in prostate cancer cells, whereas NKX3.1 can in turn negatively regulate TMPRSS2-ERG fusion expression via suppression of the TMPRSS2 promoter activity. We recently generated knockin mouse models for TMPRSS2-ERG and TMPRSS2-ETV1 fusions, utilizing the endogenous Tmprss2 promoter. We crossed these knockin models to an Nkx3.1 knockout mouse model. In Tmprss2-ERG;Nkx3.1+/- (or -/- male mice, although we observed a slight but significant upregulation of Tmprss2-ERG fusion expression upon Nkx3.1 loss, we did not detect any significant cooperation between these two genetic events to enhance prostate tumorigenesis in vivo. Furthermore, retrospective analysis of a previously published human prostate cancer dataset revealed that within ERG-overexpressing prostate cancer cases, NKX3.1 loss or deletion did not predict biochemical relapse after radical prostatectomy. Collectively, these data suggest that although TMPRSS2-ERG fusion and loss of NKX3.1 are among the most common mutational events found in prostate cancer, and although each of them can sensitize prostate epithelial cells for cooperating with other oncogenic events, these

  14. A YAC contig encompassing the XRCC5 (Ku80) DNA repair gene and complementation of defective cells by YAC protoplast fusion

    Energy Technology Data Exchange (ETDEWEB)

    Blunt, T.; Priestley, A.; Hafezparast, M.; McMillan, T. [Univ. of Sussex, Brighton (United Kingdom)] [and others

    1995-11-20

    The Chinese hamster ovary xrs mutants are sensitive to ionizing radiation, defective in DNA double-strand break rejoining, and unable to carry out V(D)J recombination effectively. Recently, the gene defective in these mutants, XRCC5, has been shown to encode Ku80, a component of the Ku protein and DNA-dependent protein kinase. We present here a YAC contig involving 25 YACs mapping to the region 2q33-q34, which encompasses the XRCC5 gene. Eight new markers for this region of chromosome 2 are identified. YACs encoding the Ku80 gene were transferred to xrs cells by protoplast fusion, and complementation of all the defective phenotypes has been obtained with two YACs. We discuss the advantages and disadvantages of this approach as a strategy for cloning human genes complementing defective rodent cell lines. 44 refs., 2 figs., 4 tabs.

  15. Pandemic H1N1 influenza A directly induces a robust and acute inflammatory gene signature in primary human bronchial epithelial cells downstream of membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Paquette, Stéphane G. [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario (Canada); Banner, David [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Chi, Le Thi Bao [Department of Microbiology, Hue University of Medicine and Pharmacy, Thua Thien Hue (Viet Nam); Carlo Urbani Centre, Hue University of Medicine and Pharmacy, Thua Thien Hue (Viet Nam); Leon, Alberto J. [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); International Institute of Infection and Immunity, Shantou University Medical College, Shantou, Guangdong (China); Xu, Luoling; Ran, Longsi [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Huang, Stephen S.H. [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario (Canada); Farooqui, Amber [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); International Institute of Infection and Immunity, Shantou University Medical College, Shantou, Guangdong (China); and others

    2014-01-05

    Pandemic H1N1 influenza A (H1N1pdm) elicits stronger pulmonary inflammation than previously circulating seasonal H1N1 influenza A (sH1N1), yet mechanisms of inflammatory activation in respiratory epithelial cells during H1N1pdm infection are unclear. We investigated host responses to H1N1pdm/sH1N1 infection and virus entry mechanisms in primary human bronchial epithelial cells in vitro. H1N1pdm infection rapidly initiated a robust inflammatory gene signature (3 h post-infection) not elicited by sH1N1 infection. Protein secretion inhibition had no effect on gene induction. Infection with membrane fusion deficient H1N1pdm failed to induce robust inflammatory gene expression which was rescued with restoration of fusion ability, suggesting H1N1pdm directly triggered the inflammatory signature downstream of membrane fusion. Investigation of intra-virion components revealed H1N1pdm viral RNA (vRNA) triggered a stronger inflammatory phenotype than sH1N1 vRNA. Thus, our study is first to report H1N1pdm induces greater inflammatory gene expression than sH1N1 in vitro due to direct virus–epithelial cell interaction. - Highlights: • We investigated H1N1pdm/sH1N1 infection in primary epithelial cells. • H1N1pdm directly initiated a robust inflammatory gene signature, sH1N1 did not. • H1N1pdm viral RNA triggered a stronger response than sH1N1. • H1N1pdm induces greater response due to direct virus–cell interaction. • These results have potential to impact vaccine and therapeutic development.

  16. Data Fusion Method for Manufacturing Measurement

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A data fusion method of online multisensors is prop os ed in this paper based on artificial neuron. First, the dynamic data fusion mode l on artificial neuron is built. Then the calibration of data fusion is discusse d with self-adaptive weighing technique. Finally performance of the method is d emonstrated by an online vibration measurement case. The results show that the f used data are more stable, sensitive, accurate, reliable than that of single sen sor data.Data Fusion Method for Manufacturing Measure...

  17. Artificial Limbs

    Science.gov (United States)

    ... you are missing an arm or leg, an artificial limb can sometimes replace it. The device, which ... activities such as walking, eating, or dressing. Some artificial limbs let you function nearly as well as ...

  18. Limited inter- and intra-patient sequence diversity of the genetic lineage a human metapneumovirus fusion gene

    DEFF Research Database (Denmark)

    Winther, T.N.; Madsen, C.D.; Pedersen, Anders Gorm;

    2005-01-01

    Human metapneumovirus (hMPV) is associated with respiratory tract illness especially in young children. Two hMPV genetic lineages, A and B, and four sublineages A1, A2 and B1, B2 have been defined. Infection with hMPV occurs through membrane fusion mediated by the hMPV fusion (F) protein. In this......Human metapneumovirus (hMPV) is associated with respiratory tract illness especially in young children. Two hMPV genetic lineages, A and B, and four sublineages A1, A2 and B1, B2 have been defined. Infection with hMPV occurs through membrane fusion mediated by the hMPV fusion (F) protein...

  19. Limited inter- and intra-patient sequence diversity of the genetic lineage A human metapneumovirus fusion gene

    DEFF Research Database (Denmark)

    Winther, Thilde Nordmann; Madsen, Chris D; Pedersen, Anders;

    2005-01-01

    Human metapneumovirus (hMPV) is associated with respiratory tract illness especially in young children. Two hMPV genetic lineages, A and B, and four sublineages A1, A2 and B1, B2 have been defined. Infection with hMPV occurs through membrane fusion mediated by the hMPV fusion (F) protein. In this......Human metapneumovirus (hMPV) is associated with respiratory tract illness especially in young children. Two hMPV genetic lineages, A and B, and four sublineages A1, A2 and B1, B2 have been defined. Infection with hMPV occurs through membrane fusion mediated by the hMPV fusion (F) protein...

  20. Horizontal transmission of malignancy: in-vivo fusion of human lymphomas with hamster stroma produces tumors retaining human genes and lymphoid pathology.

    Directory of Open Access Journals (Sweden)

    David M Goldenberg

    Full Text Available We report the in-vivo fusion of two Hodgkin lymphomas with golden hamster cheek pouch cells, resulting in serially-transplanted (over 5-6 years GW-532 and GW-584 heterosynkaryon tumor cells displaying both human and hamster DNA (by FISH, lymphoma-like morphology, aggressive metastasis, and retention of 7 human genes (CD74, CXCR4, CD19, CD20, CD71, CD79b, and VIM out of 24 tested by PCR. The prevalence of B-cell restricted genes (CD19, CD20, and CD79b suggests that this uniform population may be the clonal initiating (malignant cells of Hodgkin lymphoma, despite their not showing translation to their respective proteins by immunohistochemical analysis. This is believed to be the first report of in-vivo cell-cell fusion of human lymphoma and rodent host cells, and may be a method to disclose genes regulating both organoid and metastasis signatures, suggesting that the horizontal transfer of tumor DNA to adjacent stromal cells may be implicated in tumor heterogeneity and progression. The B-cell gene signature of the hybrid xenografts suggests that Hodgkin lymphoma, or its initiating cells, is a B-cell malignancy.

  1. Involvement of primary mesenchymal precursors and hematopoietic bone marrow cells from chronic myeloid leukemia patients by BCR-ABL1 fusion gene.

    Science.gov (United States)

    Chandia, Mauricio; Sayagués, José-María; Gutiérrez, María-Laura; Chillón, María-Laura; Aristizábal, José-Alejandro; Corrales, Alejandro; Castellanos, Marta; Melón, Alberto; Sánchez, María-Luz; Bárcena, Paloma; Matarraz, Sergio; González-González, María; Barrena, Susana; López, Antonio; Cañizo, María-Consuelo; Sánchez-Guijo, Fermín; Orfao, Alberto

    2014-03-01

    For decades now, it is well established that chronic myeloid leukemia (CML) is a hematopoietic stem cell(HPC) disorder. However, it remains to be determined whether BCR-ABL1 gene rearrangement occurs in a HPC or at an earlier stem cell and whether the degree of involvement of hematopoiesis by the BCR-ABL1 fusion gene relates to the response to therapy. Here, we have investigated by interphase fluorescence in situ hybridization (iFISH) the distribution of BCR-ABL1 fusion gene in FACS-sorted bone marrow (BM) populations of mesenchymal precursor cells (MPC) and other hematopoietic cell populations from 18 newly diagnosed CML patients. Overall, our results showed systematic involvement at relatively high percentages of BM maturing neutrophils (97%615%), basophils (95%612%), eosinophils (90%68%), CD341 precursors cells (90%67%),monocytes (84%630%), nucleated red blood cells (87%624%), and mast cells (77%633%). By contrast, MPC(30%634%), B-cells (15%627%), T-lymphocytes (50%626%), and NK-cells (35%634%) were involved at lower percentages. In 8/18 CML patients, 2 tumor BCR-ABL11 subclones were detected by iFISH. Of note, all tumor cell subclones were systematically detected in CD341 cells, whereas MPC were only involved by the ancestral tumor cell subclone. In summary, here we confirm the presence at diagnosis of the BCR-ABL1 fusion gene inMPC, CD341 precursors, and other different BM hematopoietic myeloid cell lineages from CML patients,including also in a significant fraction of cases, a smaller percentage of T, B, and NK lymphocytes.Interestingly, involvement of MPC was restricted to the ancestral BCR-ABL11 subclone. PMID:24779036

  2. EMP Fusion

    OpenAIRE

    KUNTAY, Isık

    2010-01-01

    This paper introduces a novel fusion scheme, called EMP Fusion, which has the promise of achieving breakeven and realizing commercial fusion power. The method is based on harnessing the power of an electromagnetic pulse generated by the now well-developed flux compression technology. The electromagnetic pulse acts as a means of both heating up the plasma and confining the plasma, eliminating intermediate steps. The EMP Fusion device is simpler compared to other fusion devices and this reduces...

  3. A novel system for simultaneous or sequential integration of multiple gene-loading vectors into a defined site of a human artificial chromosome.

    Directory of Open Access Journals (Sweden)

    Teruhiko Suzuki

    Full Text Available Human artificial chromosomes (HACs are gene-delivery vectors suitable for introducing large DNA fragments into mammalian cells. Although a HAC theoretically incorporates multiple gene expression cassettes of unlimited DNA size, its application has been limited because the conventional gene-loading system accepts only one gene-loading vector (GLV into a HAC. We report a novel method for the simultaneous or sequential integration of multiple GLVs into a HAC vector (designated as the SIM system via combined usage of Cre, FLP, Bxb1, and φC31 recombinase/integrase. As a proof of principle, we first attempted simultaneous integration of three GLVs encoding EGFP, Venus, and TdTomato into a gene-loading site of a HAC in CHO cells. These cells successfully expressed all three fluorescent proteins. Furthermore, microcell-mediated transfer of HACs enabled the expression of those fluorescent proteins in recipient cells. We next demonstrated that GLVs could be introduced into a HAC one-by-one via reciprocal usage of recombinase/integrase. Lastly, we introduced a fourth GLV into a HAC after simultaneous integration of three GLVs by FLP-mediated DNA recombination. The SIM system expands the applicability of HAC vectors and is useful for various biomedical studies, including cell reprogramming.

  4. Construction of prokaryotic expression system of ItB-ureB fusion gene and identification of the recombinant protein immunity and adjuvanticity

    Institute of Scientific and Technical Information of China (English)

    Jie Yan; Yuan Wang; Shi-He Shao; Ya-Fei Mao; Hua-Wen Li; Yi-Hui Luo

    2004-01-01

    AIM: To construct ItB-ureB fusion gene and its prokaryotic expression system and identify immunity and adjuvanticity of the expressed recombinant protein.METHODS: The ureB gene from a clinical Helicobacterpylori(Hpylori) strain Y06 and the ItB gene from Escherichiacoli(E coli) strain 44851 were linked into ItB-ureB fusiongene by PCR. The fusion gene sequence was analyzedafter T-A cloning. A prokaryotic recombinant expressionvector pET32a inserted with ItB-ureB fusion gene (pET32aItB-ureB) was constructed. Expression of the recombinantLTB-UreB protein (rLTB-UreB)in E. coliBL21DE3 inducedby isopropylthio-β-D-galactoside (IPTG) at differentconcentrations was detected by SDS-PAGE. Western blot assays were used to examine the immunoreaction of rLTBUreB by a commercial antibody against whole cell of H pylori and a self-prepared rabbit anti-rUreB serum, respectively, and determine the antigenicity of the recombinant proteinon inducing specific antibody in rabbits. GM1-ELISA wasused to demonstrate the adjuvanticity of rLTB-UreB. Immunoreaction of rLTB-UreB to the UreB antibody positivesera from 125 gastric patients was determined by using ELISA. RESULTS: In comparison with the corresponding sequences of original genes, the nucleotide sequence homologies of the cloned ItB-ureB fusion gene were 100%. IPTG withdifferent dosages of 0.1-1.0 mmol/L could efficiently inducepET32a-ItB-ureB-E.coli BL21DE3 to express the rLTB-UreB. The output of the target recombinant protein expressed by pET32a-ureB-E. coli BL21DE3 was approximately 35%of the total bacterial proteins. rLTB-UreB mainly presented in the form of inclusion body. Western blotting results demonstrated that rLTB-UreB could combine with the commercial antibody against whole cell of H pylori andanti-rUreB serum as well as induce rabbit to produce specific antibody. The strong ability of rLTB-UreB bindingbovine GM1 indicated the existence of adjuvanticity of the recombinant protein. All the UreB antibody positive sera from

  5. Temsirolimus in the treatment of renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion proteins: a case report and review of literature

    Directory of Open Access Journals (Sweden)

    James Brown

    2009-12-01

    Full Text Available Xp11.2 translocation renal cell carcinomas (TRCCs are a rare family of tumors newly recognized by the World Health Organization (WHO in 2004. These tumors result in the fusion of partner genes to the TFE3 gene located on Xp11.2. They are most common in the pediatric population, but have been recently implicated in adult renal cell carcinoma (RCC presenting at an early age. TFE3-mediated direct transcriptional upregulation of the Met tyrosine kinase receptor triggers dramatic activation of downstream signaling pathways including the protein kinase B (Akt/phosphatidylinositol-3 kinase (PI3K and mammalian target of rapamycin (mTOR pathways. Temsirolimus is an inhibitor of mammalian target of rapamycin (mTOR kinase, a component of intracellular signaling pathways involved in the growth and proliferation of malignant cells. Here we present a case of a 22-year old female who has been treated with temsirolimus for her Xp11.2/TFE3 gene fusion RCC.

  6. Mars manned fusion spaceship

    Science.gov (United States)

    Hedrick, James; Buchholtz, Brent; Ward, Paul; Freuh, Jim; Jensen, Eric

    1991-01-01

    Fusion Propulsion has an enormous potential for space exploration in the near future. In the twenty-first century, a usable and efficient fusion rocket will be developed and in use. Because of the great distance between other planets and Earth, efficient use of time, fuel, and payload is essential. A nuclear spaceship would provide greater fuel efficiency, less travel time, and a larger payload. Extended missions would give more time for research, experiments, and data acquisition. With the extended mission time, a need for an artificial environment exists. The topics of magnetic fusion propulsion, living modules, artificial gravity, mass distribution, space connection, and orbital transfer to Mars are discussed. The propulsion system is a magnetic fusion reactor based on a tandem mirror design. This allows a faster, shorter trip time and a large thrust to weight ratio. The fuel proposed is a mixture of deuterium and helium-3. Helium-3 can be obtained from lunar mining. There will be minimal external radiation from the reactor resulting in a safe, efficient propulsion system.

  7. Fusion protein gene nucleotide sequence similarities, shared antigenic sites and phylogenetic analysis suggest that phocid distemper virus 2 and canine distemper virus belong to the same virus entity.

    OpenAIRE

    Visser, Ilona; Heijden, Roger; van de Bildt, Marco; Kenter, Marcel; Örvell, C.; Osterhaus, Albert

    1993-01-01

    textabstractNucleotide sequencing of the fusion protein (F) gene of phocid distemper virus-2 (PDV-2), recently isolated from Baikal seals (Phoca sibirica), revealed an open reading frame (nucleotides 84 to 2075) with two potential in-frame ATG translation initiation codons. We suggest that the second in-frame ATG triplet at positions 264 to 266 initiates the translation, resulting in a protein of 537 amino acid residues with a calculated M(r) of 63,035. The putative F1/F2 cleavage site, locat...

  8. Molecular Characterization of TMPRSS2-ERG Gene Fusion in the NCI-H660 Prostate Cancer Cell Line: A New Perspective for an Old Model

    Directory of Open Access Journals (Sweden)

    Kirsten D. Mertz

    2007-03-01

    Full Text Available Recent studies have established that a significant fraction of prostate cancers harbor a signature gene fusion between the 5' region of androgen-regulated TMPRSS2 and an ETS family transcription factor, most commonly ERG. Studies on the molecular mechanisms and functional consequences of this important chromosomal rearrangement are currently limited to the VCaP cell line derived from a vertebral bone metastasis of a hormone-refractory prostate tumor. Here we report on the NCI-H660 cell line, derived from a metastasic site of an extrapulmonary small cell carcinoma arising from the prostate. NCI-H660 harbors TMPRSS2-ERG fusion with a homozygous intronic deletion between TMPRSS2 and ERG. We demonstrate this by real-time quantitative polymerase chain reaction, a two-stage dual-color interphase fluorescence in situ hybridization (FISH assay testing for TMPRSS2 and ERG break-aparts, and single-nucleotide polymorphism oligonucleotide arrays. The deletion is consistent with the common intronic deletion found on chromosome 21q22.2-3 in human prostate cancer samples. We demonstrate the physical juxtaposition of TMPRSS2 and ERG on the DNA level by fiber FISH. The androgen receptor-negative NCI-H660 cell line expresses ERG in an androgen-independent fashion. This in vitro model system has the potential to provide important pathobiologic insights into TMPRSS2-ERG fusion prostate cancer.

  9. Transformation of Arabidopsis by Rice OsWRKY78:: GFP Fusion Gene and Subcellular Localization of OsWRKY78 Protein

    Institute of Scientific and Technical Information of China (English)

    Shunzhi LIU; Mei ZHANG; Xin TANG; Xiaolan WANG

    2012-01-01

    [Objective] The study was to understand the subcellular localization of OsWRKY78 protein in plants. [Method] Primers specific for OsWRKY78 gene were designed according to the OsWRKY78 full length sequence in Genbank. The gene was cloned by RT-PCR method. The gene was then recombined into a plasmid ex- pression vector carrying green fluorescent protein (GFP) gene, pBinGFP. The re- combinant was confirmed by PCR and enzyme digestion. The recombinant plasmid pBinGFP-OsWRKY was transformed into Arabidopsis through Agrobacterium tume- faciens strain GV3101 and transgenic plants were obtained. [Result] Measured by fluorescence microscopy, the expression of OsWRKY78 and GFP fusion protein in root tip cells was localized in the nucleus. [Conclusion] This study laid the foundation for further investigating the function of OsWRKY78 gene and its role in related sig- nal transduction and provided theoretical basis for exploring the relation between OsWRKY78 gene and brown planthoppers.

  10. [Construction of fusion gene vaccine of WT1 multi-epitope fused with stimulating epitope of mycobacterium tuberculosis heat shock protein 70 and its expression and immunogenicity].

    Science.gov (United States)

    Tian, Wei-Wei; Qiao, Zhen-Hua; Yang, Lin-Hua; Wang, Hong-Wei; Tang, Yan-Hong; Bian, Si-Cheng

    2011-04-01

    This study was purposed to construct a fusion DNA vaccine containing WT1 multi-epitope and stimulating epitope of mycobacterium tuberculosis heat shock protein 70 and to detect its expression and immunogenicity. On the basis of published data, a multi-epitope gene (Multi-WT1) containing three HLA *0201-restricted CTL epitopes: one HLA*2402-restricted CTL epitope, two Th epitopes and one universal Th Pan-DR epitope (PADRE) was constructed. DNA-coding sequence was modified by Computer-Aided Design (CAD) to optimize proteasome-mediated epitope processing through the introduction of different amino acid spacer sequences. The synthetic nucleotide sequence was then inserted into an eukaryotic vector to construct the plasmid pcDNA3.1-WT1.For enhancing CTL activity, HSP70 fragment including stimulatory domain P407-426 was amplified by PCR from mycobacterial HSP70 gene and cloned into pcDNA3.1(+). Then Multi-WT1 was fused to the N-terminal of pcDNA3.1-mHSP70(407-426) to make the multi-epitope fusion gene vaccine pcDNA3.1-WT1-mHSP70(407-426). HEK-293T cells were transfected with this vaccine and the expressed product was identified by RT-PCR. Enzyme-linked immunospot assay (ELISPOT) was used to evaluate the immunological responses elicited by vaccine. The results showed that the most of WT1 epitopes could be correctly cleaved which was confirmed by software Net Chop 3.1 and PAPROCIanalysis. RT-PCR showed correct expression of target gene in HEK293T cells and ELISPOT showed specific T-cell responses. It is concluded that the eukaryotic expression vector PcDNA3.1-WT1-mHSP70(407-426) fusion gene has been successfully constructed and the immunity response is also elicited, which is a good candidate for further research of DNA vaccine.

  11. Genetic transformation of peanut (Arachis hypogaea L.) using cotyledonary node as explant and a promoterless gus::nptII fusion gene based vector

    Indian Academy of Sciences (India)

    T Swathi Anuradha; S K Jami; R S Datla; P B Kirti

    2006-06-01

    We have generated putative promoter tagged transgenic lines in Arachis hypogaea cv JL-24 using cotyledonary node (CN) as an explant and a promoterless gus::nptII bifunctional fusion gene mediated by Agrobacterium transformation. MS medium fortified with 6-benzylaminopurine (BAP) at 4 mg/l in combination with 0.1 mg/l -napthaleneacetic acid (NAA) was the most effective out of the various BAP and NAA combinations tested in multiple shoot bud formation. Parameters enhancing genetic transformation viz. seedling age, Agrobacterium genetic background and co-cultivation periods were studied by using the binary vector p35SGUSINT. Genetic transformation with CN explants from 6-dayold seedlings co-cultivated with Agrobacterium GV2260 strain for 3 days resulted in high kanamycin resistant shoot induction percentage (45%); approximately 31% transformation frequency was achieved with p35S GUSINT in -glucuronidase (GUS) assays. Among the in vivo GUS fusions studied with promoterless gus::nptII construct, GUS-positive sectors occupied 38% of the total transient GUS percentage. We have generated over 141 putative T0 plants by using the promoterless construct and transferred them to the field. Among these, 82 plants survived well in the green house and 5 plants corresponding to 3.54% showed stable integration of the fusion gene as evidenced by GUS, polymerase chain reaction (PCR) and Southern blot analyses. Twenty-four plants were positive for GUS showing either tissue-specific expression or blue spots in at least one plant part. The progeny of 15 T0 plants indicated Mendelian inheritance pattern of segregation for single-copy integration. The tissue-specific GUS expression patterns were more or less similar in both T0 and corresponding T1 progeny plants. We present the differential patterns of GUS expression identified in the putative promoter-tagged transgenic lines in the present communication.

  12. Fusion rings and fusion ideals

    DEFF Research Database (Denmark)

    Andersen, Troels Bak

    This dissertation investigates fusion rings, which are Grothendieck groups of rigid, monoidal, semisimple, abelian categories. Special interest is in rational fusion rings, i.e., fusion rings which admit a finite basis, for as commutative rings they may be presented as quotients of polynomial rings...... by the so-called fusion ideals. The fusion rings of Wess-Zumino-Witten models have been widely studied and are well understood in terms of precise combinatorial descriptions and explicit generating sets of the fusion ideals. They also appear in another, more general, setting via tilting modules for quantum...

  13. Phylogenetic analysis of Amphioxus genes of the proprotein convertase family, including aPC6C, a marker of epithelial fusions during embryology

    Directory of Open Access Journals (Sweden)

    Stéphanie Bertrand, Alain Camasses, Mathilde Paris, Nicholas D. Holland, Hector Escriva

    2006-01-01

    Full Text Available The proprotein convertases (PCs comprise a family of subtilisin-like endoproteases that activate precursor proteins (including, prohormones, growth factors, and adhesion molecules during their transit through secretory pathways or at the cell surface. To explore the evolution of the PC gene family in chordates, we made a phylogenetic analysis of PC genes found in databases, with special attention to three PC genes of the cephalochordate amphioxus, the closest living invertebrate relative to the vertebrates. Since some vertebrate PC genes are essential for early development, we investigated the expression pattern of the C isoform of the amphioxus PC6 gene (aPC6C. In amphioxus embryos and larvae, aPC6C is expressed at places where epithelia fuse. Several kinds of fusions occur: ectoderm-to-ectoderm during neurulation; mesoderm-to-ectoderm during formation of the preoral ciliated pit; and endoderm-to-ectoderm during formation of the mouth, pharyngeal slits, anus, and external opening of the club-shaped gland. Presumably, at all these sites, aPC6C is activating proteins favoring association between previously disjunct cell populations.

  14. Membrane fusion

    DEFF Research Database (Denmark)

    Bendix, Pól Martin

    2015-01-01

    At Stanford University, Boxer lab, I worked on membrane fusion of small unilamellar lipid vesicles to flat membranes tethered to glass surfaces. This geometry closely resembles biological systems in which liposomes fuse to plasma membranes. The fusion mechanism was studied using DNA zippering...... between complementary strands linked to the two apposing membranes closely mimicking the zippering mechanism of SNARE fusion complexes....

  15. Artificial blood

    Directory of Open Access Journals (Sweden)

    Sarkar Suman

    2008-01-01

    Full Text Available Artificial blood is a product made to act as a substitute for red blood cells. While true blood serves many different functions, artificial blood is designed for the sole purpose of transporting oxygen and carbon dioxide throughout the body. Depending on the type of artificial blood, it can be produced in different ways using synthetic production, chemical isolation, or recombinant biochemical technology. Development of the first blood substitutes dates back to the early 1600s, and the search for the ideal blood substitute continues. Various manufacturers have products in clinical trials; however, no truly safe and effective artificial blood product is currently marketed. It is anticipated that when an artificial blood product is available, it will have annual sales of over $7.6 billion in the United States alone.

  16. TMPRSS2-ERG基因融合在前列腺癌中研究新进展%Recent Research Progress of TMPRSS2-ERG Gene Fusions in Prostate Cancer

    Institute of Scientific and Technical Information of China (English)

    郭琦

    2012-01-01

    TMPRSS2-ERG fusion is the most common subtype of gene fusions in prostate cancer. Interacting with AK,PARP1 and DNA-PKcs,NE-kB and CR1SP3 ,TMPRSS2-ERG fusion gene leads to the genesis of prostate cancer. By fluorescence in situ hybridization and immunohistochemistry, TMPRSS2-ERG fusion gene and the related protein have a higher positive rate in specimen of prostate cancer. Lrinary detection of TMPRSS2-ERG fusion gene also has a higher specificity and positive predictive value.%TMPRSS2-ERG基因融合是前列腺癌中最常出现的基因融合类型.TMPRSS2-ERG融合基因通过与雄激素受体、多聚ADP-核糖聚合酶1和DNA-PKcs、核因子κB和富含半胱氨酸分泌蛋白3的相互作用介导前列腺癌的发生.利用荧光原位杂交技术和免疫组织化学技术检测前列腺癌标本中融合基因发生及其蛋白表达,具有较高的阳性率;尿液 TMPRSS2-ERG 融合基因检测有较高的特异度和阳性预测值.

  17. Characterization of a novel fusion gene EML4-NTRK3 in a case of recurrent congenital fibrosarcoma.

    Science.gov (United States)

    Tannenbaum-Dvir, Sarah; Glade Bender, Julia L; Church, Alanna J; Janeway, Katherine A; Harris, Marian H; Mansukhani, Mahesh M; Nagy, Peter L; Andrews, Stuart J; Murty, Vundavalli V; Kadenhe-Chiweshe, Angela; Connolly, Eileen P; Kung, Andrew L; Dela Cruz, Filemon S

    2015-10-01

    We describe the clinical course of a recurrent case of congenital fibrosarcoma diagnosed in a 9-mo-old boy with a history of hemimelia. Following complete surgical resection of the primary tumor, the patient subsequently presented with bulky bilateral pulmonary metastases 6 mo following surgery. Molecular characterization of the tumor revealed the absence of the prototypical ETV6-NTRK3 translocation. However, tumor characterization incorporating cytogenetic, array comparative genomic hybridization, and RNA sequencing analyses, revealed a somatic t(2;15)(2p21;15q25) translocation resulting in the novel fusion of EML4 with NTRK3. Cloning and expression of EML4-NTRK3 in murine fibroblast NIH 3T3 cells revealed a potent tumorigenic phenotype as assessed in vitro and in vivo. These results demonstrate that multiple fusion partners targeting NTRK3 can contribute to the development of congenital fibrosarcoma. PMID:27148571

  18. What are artificial neural networks?

    DEFF Research Database (Denmark)

    Krogh, Anders

    2008-01-01

    Artificial neural networks have been applied to problems ranging from speech recognition to prediction of protein secondary structure, classification of cancers and gene prediction. How do they work and what might they be good for? Udgivelsesdato: 2008-Feb......Artificial neural networks have been applied to problems ranging from speech recognition to prediction of protein secondary structure, classification of cancers and gene prediction. How do they work and what might they be good for? Udgivelsesdato: 2008-Feb...

  19. Retrovirus-mediated transfer of the fusion gene encoding EGFP-BMP_2 in mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Bone marrow mesenchymal stemcells(MSCs)are pluripotential stemcells that have the capacitytodifferentiate into chondrocytes and osteoblasts[1].Ithas been well documented that bone morphogeneticproteins(BMPs),a group of proteins belonging tothe TGF-βsuperfamily,can induce bone for mationbothin vivoandin vitroas well as promote osteo-blastic differentiation of MSC[2].HeterologousBMP2is successfully transferred to MSCs and genetherapy is employed based on repairing bony andcartilage defects,spinal fusion[3-5]....

  20. Identification of a recurrent transforming UBR5–ZNF423 fusion gene in EBV-associated nasopharyngeal carcinoma

    OpenAIRE

    Chung, Grace TY; Lung, Raymond WM; Hui, Angela BY; Yip, Kevin YL; Woo, John KS; Chow, Chit; Tong, Carol YK; Lee, Sau-Dan; Yuen, Jessie WF; Lun, Samantha WM; Tso, Ken KY; Wong, Nathalie; Tsao, Sai-Wah; Yip, Timothy TC; Busson, Pierre

    2013-01-01

    Nasopharyngeal carcinoma (NPC) is a distinct type of head and neck cancer which is prevalent in southern China, south-east Asia and northern Africa. The development and stepwise progression of NPC involves accumulation of multiple gross genetic changes during the clonal expansion of Epstein–Barr virus (EBV)-infected nasopharyngeal epithelial cell population. Here, using paired-end whole-transcriptome sequencing, we discovered a number of chimeric fusion transcripts in a panel of EBV-positive ...

  1. Preliminary Results of Noninvasive Detection of TMPRSS2:ERG Gene Fusion in a Cohort of Patients With Localized Prostate Cancer

    OpenAIRE

    Tavukcu, Hasan Huseyin; Mangir, Naside; Ozyurek, Mustafa; Turkeri, Levent

    2013-01-01

    Purpose The aim of this study was to evaluate TMPRSS2:ERG fusion rates in tissue, urine, blood, and pubic hair samples in a cohort of patients with localized prostate cancer and to correlate these findings with various clinicopathological parameters. Materials and Methods A cohort of 40 patients undergoing radical prostatectomy for localized prostate cancer (RRP group) and 10 control patients undergoing prostate biopsy were enrolled between 2006 and 2008. Urine, pubic hair, and peripheral blo...

  2. Improvement of acetic acid tolerance of Saccharomyces cerevisiae using a zinc-finger-based artificial transcription factor and identification of novel genes involved in acetic acid tolerance.

    Science.gov (United States)

    Ma, Cui; Wei, Xiaowen; Sun, Cuihuan; Zhang, Fei; Xu, Jianren; Zhao, Xinqing; Bai, Fengwu

    2015-03-01

    Acetic acid is present in cellulosic hydrolysate as a potent inhibitor, and the superior acetic acid tolerance of Saccharomyces cerevisiae ensures good cell viability and efficient ethanol production when cellulosic raw materials are used as substrates. In this study, a mutant strain of S. cerevisiae ATCC4126 (Sc4126-M01) with improved acetic acid tolerance was obtained through screening strains transformed with an artificial zinc finger protein transcription factor (ZFP-TF) library. Further analysis indicated that improved acetic acid tolerance was associated with improved catalase (CAT) activity. The ZFP coding sequence associated with the improved phenotype was identified, and real-time RT-PCR analysis revealed that three of the possible genes involved in the enhanced acetic acid tolerance regulated by this ZFP-TF, namely YFL040W, QDR3, and IKS1, showed decreased transcription levels in Sc4126-M01 in the presence of acetic acid, compared to those in the control strain. Sc4126-M01 mutants having QDR3 and IKS1 deletion (ΔQDR3 and ΔIKS1) exhibited higher acetic acid tolerance than the wild-type strain under acetic acid treatment. Glucose consumption rate and ethanol productivity in the presence of 5 g/L acetic acid were improved in the ΔQDR3 mutant compared to the wild-type strain. Our studies demonstrated that the synthetic ZFP-TF library can be used to improve acetic acid tolerance of S. cerevisiae and that the employment of an artificial transcription factor can facilitate the exploration of novel functional genes involved in stress tolerance of S. cerevisiae. PMID:25698512

  3. Delivery of human NKG2D-IL-15 fusion gene by chitosan nanoparticles to enhance antitumor immunity

    International Nuclear Information System (INIS)

    Nanoparticles are becoming promising carriers for gene delivery because of their high capacity in gene loading and low cell cytotoxicity. In this study, a chitosan-based nanoparticle encapsulated within a recombinant pcDNA3.1-dsNKG2D-IL-15 plasmid was generated. The fused dsNKG2D-IL-15 gene fragment consisted of double extracellular domains of NKG2D with IL-15 gene at downstream. The average diameter of the gene nanoparticles ranged from 200 nm to 400 nm, with mean zeta potential value of 53.8 ± 6.56 mV. The nanoparticles which were loaded with the dsNKG2D-IL-15 gene were uptaken by tumor cells with low cytotoxicity. Tumor cells pre-transfected by gene nanopartilces stimulated NK and T cells in vitro. Intramuscular injection of gene nanoparticles suppressed tumor growth and prolonged survival of tumor-bearing mice through activation of NK and CD8+ T cells. Thus, chitosan-based nanoparticle delivery of dsNKG2D-IL-15 gene vaccine can be potentially used for tumor therapy. - Highlights: • Generation of a nanoparticle for delivery of dsNKG2D-IL-15 gene. • Characterization of the gene nanoparticle. • Antitumor activity mediated by the gene nanoparticle

  4. Delivery of human NKG2D-IL-15 fusion gene by chitosan nanoparticles to enhance antitumor immunity

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Chen; Jie, Leng; Yongqi, Wang [Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, 225009 (China); Weiming, Xiao [Department of Gastroenterology, The Second Clinical Medical College, Yangzhou University, Yangzhou, 225009 (China); Juqun, Xi [Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, 225009 (China); Yanbing, Ding [Department of Gastroenterology, The Second Clinical Medical College, Yangzhou University, Yangzhou, 225009 (China); Li, Qian [Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, 225009 (China); Xingyuan, Pan [Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, 225009 (China); Mingchun, Ji [Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, 225009 (China); Weijuan, Gong, E-mail: wjgong@yzu.edu.cn [Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, 225009 (China); Department of Gastroenterology, The Second Clinical Medical College, Yangzhou University, Yangzhou, 225009 (China); Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, 225009 (China); Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, 225009 (China); Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009 (China)

    2015-07-31

    Nanoparticles are becoming promising carriers for gene delivery because of their high capacity in gene loading and low cell cytotoxicity. In this study, a chitosan-based nanoparticle encapsulated within a recombinant pcDNA3.1-dsNKG2D-IL-15 plasmid was generated. The fused dsNKG2D-IL-15 gene fragment consisted of double extracellular domains of NKG2D with IL-15 gene at downstream. The average diameter of the gene nanoparticles ranged from 200 nm to 400 nm, with mean zeta potential value of 53.8 ± 6.56 mV. The nanoparticles which were loaded with the dsNKG2D-IL-15 gene were uptaken by tumor cells with low cytotoxicity. Tumor cells pre-transfected by gene nanopartilces stimulated NK and T cells in vitro. Intramuscular injection of gene nanoparticles suppressed tumor growth and prolonged survival of tumor-bearing mice through activation of NK and CD8{sup +} T cells. Thus, chitosan-based nanoparticle delivery of dsNKG2D-IL-15 gene vaccine can be potentially used for tumor therapy. - Highlights: • Generation of a nanoparticle for delivery of dsNKG2D-IL-15 gene. • Characterization of the gene nanoparticle. • Antitumor activity mediated by the gene nanoparticle.

  5. Cloning and Prokaryotic Expression of VEGF-SLC Fusion Gene%VEGF-SLC融合基因的克隆与原核表达

    Institute of Scientific and Technical Information of China (English)

    蒋攀; 陈全; 郑毅; 刘革力; 张璐瑜

    2011-01-01

    目的 构建血管内皮生长因子(Vascular endothelial growthfactor,VEGF)-次级淋巴组织趋化因子(Secondary lymphoid-fissue chemokine,SLC)融合基因(VEGF-SLC)的原核表达质粒,表达并纯化重组VEGF-SLC融合蛋白.方法 利用Gene SOEing法扩增VEGF-SLC基因,将融合基因插入载体pQE30,构建重组表达质粒pQE30-VEGF-SLC,转化大肠杆菌M15,IPTG诱导表达.表达产物经SDS-PAGE和Western blot鉴定后,用Ni-Agarose His标签蛋白纯化试剂盒纯化.结果 重组表达质粒经双酶切和测序证明构建正确;表达的重组融合蛋白相对分子质量约28 000,诱导5 h表达量最高,约占菌体总蛋白的19%,主要以包涵体形式存在,可与鼠抗人VEGF单抗特异性结合;纯化的重组融合蛋白纯度可达90%以上.结论 已成功在大肠杆菌中表达并纯化了重组VEGF-SLC融合蛋白,为进一步研究其生物学活性及其靶向抗肿瘤效应以及开发肺癌等肿瘤的靶向生物制剂奠定了基础.%Objective To construct a prokaryotic expression vector for vascular endothelial growth factor (VEGF)-secondary lymphoid-tissue chemokine (SLC) fusion gene and purify the expressed fusion protein. Methods VEGF-SLC gene was amplified by Gene SOEing and inserted into vector pQE30. The constructed recombinant plasmid pQE30-VEGF-SLC was transformed to E. coli M15 for expression under induction of IPTG. The expressed product was identified by SDS-PAGE and Western blot, then purified by Ni-Agarose His-tagged protein purification kit. Results Both restriction analysis and sequencing proved that recombinant plasmid pQE30-VEGF-SLC was constructed correctly. The relative molecular mass of expressed recombinant fusion protein was about 28 000.The expression level reached a peak value 5 h after induction, which accounted for about 19% of total somatic protein. The expressed product mainly existed in a form of inclusion body, showed specific binding to mouse anti-human VEGF monoclonal antibody, and

  6. TMPRSS2:ERG融合基因与前列腺原位癌和外周转移癌的相关性研究%Relationship between TMPRSS2:ERG fusion gene and primary and metastatic prostate cancer

    Institute of Scientific and Technical Information of China (English)

    毛易捷; 史伟峰; 李青

    2013-01-01

    Objective To evaluate the relationship between primary and metastatic prostate cancers (PCa) with fusion gene of transmembrane protease, serine 2(TMPRSS2) gene and ETS related gene(ERG).Methods Fluorescence in situ hybridization was used to evaluated the rearrangement of ERG gene(TMPRSS2:ERG fusion gene) in 24 patients with PCa.Results In 6 patients with primary PCa, 4 cases were with TMPRSS2:ERG fusion gene.In 18 patients with metastatic PCa, 14 cases were with this fusion gene.In multifocal prostate cancer, the status of this fusion gene was concordant between primary tumor focus and metastasis in all cases.Conclusion There might be a close relationship between TMPRSS2: ERG fusion gene and primary and metastatic PCa.Positivity of this fusion gene could suggest the susceptibility of metastasis, which lead to death.%目的 分析跨膜丝氨酸蛋白酶2 (TMPRSS2)基因和ETS转录因子家族成员相关基因(ERG)融合基因与前列腺原位癌和外周转移癌的相关性.方法 采用荧光原位杂交技术对24例前列腺癌(PCa)患者组织标本进行TMPRSS2:ERG融合基因检测,评价TMPRSS2:ERG与前列腺原位癌和外周转移癌的相关性.结果 6例PCa原发癌患者中,4例检出TMPRSS2:ERG融合基因;18例转移性PCa患者中,14例检出该融合基因.外周淋巴结组织标本TMPRSS2:ERG融合基因阳性率为100%(8/8).14例融合基因阳性转移性PCa患者原发病灶和转移病灶具有一致的融合基因情况.结论 TMPRSS2:ERG融合基因具有较高的PCa诊断特异性和敏感性;应对该融合基因阳性患者尽早采取综合、有效的治疗措施,从而延长患者生存期.

  7. Fusion protein Isl1-Lhx3 specifies motor neuron fate by inducing motor neuron genes and concomitantly suppressing the interneuron programs.

    Science.gov (United States)

    Lee, Seunghee; Cuvillier, James M; Lee, Bora; Shen, Rongkun; Lee, Jae W; Lee, Soo-Kyung

    2012-02-28

    Combinatorial transcription codes generate the myriad of cell types during development and thus likely provide crucial insights into directed differentiation of stem cells to a specific cell type. The LIM complex composed of Isl1 and Lhx3 directs the specification of spinal motor neurons (MNs) in embryos. Here, we report that Isl1-Lhx3, a LIM-complex mimicking fusion, induces a signature of MN transcriptome and concomitantly suppresses interneuron differentiation programs, thereby serving as a potent and specific inducer of MNs in stem cells. We show that an equimolar ratio of Isl1 and Lhx3 and the LIM domain of Lhx3 are crucial for generating MNs without up-regulating interneuron genes. These led us to design Isl1-Lhx3, which maintains the desirable 1:1 ratio of Isl1 and Lhx3 and the LIM domain of Lhx3. Isl1-Lhx3 drives MN differentiation with high specificity and efficiency in the spinal cord and embryonic stem cells, bypassing the need for sonic hedgehog (Shh). RNA-seq analysis revealed that Isl1-Lhx3 induces the expression of a battery of MN genes that control various functional aspects of MNs, while suppressing key interneuron genes. Our studies uncover a highly efficient method for directed MN generation and MN gene networks. Our results also demonstrate a general strategy of using embryonic transcription complexes for producing specific cell types from stem cells. PMID:22343290

  8. Artificial urushi.

    Science.gov (United States)

    Kobayashi, S; Uyama, H; Ikeda, R

    2001-11-19

    A new concept for the design and laccase-catalyzed preparation of "artificial urushi" from new urushiol analogues is described. The curing proceeded under mild reaction conditions to produce the very hard cross-linked film (artificial urushi) with a high gloss surface. A new cross-linkable polyphenol was synthesized by oxidative polymerization of cardanol, a phenol derivative from cashew-nut-shell liquid, by enzyme-related catalysts. The polyphenol was readily cured to produce the film (also artificial urushi) showing excellent dynamic viscoelasticity. PMID:11763444

  9. Artificial intelligence

    CERN Document Server

    Ennals, J R

    1987-01-01

    Artificial Intelligence: State of the Art Report is a two-part report consisting of the invited papers and the analysis. The editor first gives an introduction to the invited papers before presenting each paper and the analysis, and then concludes with the list of references related to the study. The invited papers explore the various aspects of artificial intelligence. The analysis part assesses the major advances in artificial intelligence and provides a balanced analysis of the state of the art in this field. The Bibliography compiles the most important published material on the subject of

  10. Artificial Reefs

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — An artificial reef is a human-made underwater structure, typically built to promote marine life in areas with a generally featureless bottom, control erosion, block...

  11. Fusion breeder

    International Nuclear Information System (INIS)

    The fusion breeder is a fusion reactor designed with special blankets to maximize the transmutation by 14 MeV neutrons of uranium-238 to plutonium or thorium to uranium-233 for use as a fuel for fission reactors. Breeding fissile fuels has not been a goal of the US fusion energy program. This paper suggests it is time for a policy change to make the fusion breeder a goal of the US fusion program and the US nuclear energy program. The purpose of this paper is to suggest this policy change be made and tell why it should be made, and to outline specific research and development goals so that the fusion breeder will be developed in time to meet fissile fuel needs

  12. Genetic variability available through cell fusion

    Energy Technology Data Exchange (ETDEWEB)

    Smith, H.H.; Mastrangelo-Hough, I.A.

    1977-01-01

    Results are reported for the following studies: plant hybridization through protoplast fusion using species of Nicotiana and Petunia; chromosome instability studies on culture-induced chromosome changes and chromosome elimination; chloroplast distribution in parasexual hybrids; chromosomal introgression following fusion; plant-animal fusion; and microcell-mediated chromosome transfer and chromosome-mediated gene transfer. (HLW)

  13. Spatial localization of genes determined by intranuclear DNA fragmentation with the fusion proteins lamin KRED and histone KRED und visible light.

    Science.gov (United States)

    Waldeck, Waldemar; Mueller, Gabriele; Glatting, Karl-Heinz; Hotz-Wagenblatt, Agnes; Diessl, Nicolle; Chotewutmonti, Sasithorn; Langowski, Jörg; Semmler, Wolfhard; Wiessler, Manfred; Braun, Klaus

    2013-01-01

    The highly organized DNA architecture inside of the nuclei of cells is accepted in the scientific world. In the human genome about 3 billion nucleotides are organized as chromatin in the cell nucleus. In general, they are involved in gene regulation and transcription by histone modification. Small chromosomes are localized in a central nuclear position whereas the large chromosomes are peripherally positioned. In our experiments we inserted fusion proteins consisting of a component of the nuclear lamina (lamin B1) and also histone H2A, both combined with the light inducible fluorescence protein KillerRed (KRED). After activation, KRED generates reactive oxygen species (ROS) producing toxic effects and may cause cell death. We analyzed the spatial damage distribution in the chromatin after illumination of the cells with visible light. The extent of DNA damage was strongly dependent on its localization inside of nuclei. The ROS activity allowed to gain information about the location of genes and their functions via sequencing and data base analysis of the double strand breaks of the isolated DNA. A connection between the damaged gene sequences and some diseases was found.

  14. Spatial Localization of Genes Determined by Intranuclear DNA Fragmentation with the Fusion Proteins Lamin KRED and Histone KRED und Visible Light

    Science.gov (United States)

    Waldeck, Waldemar; Mueller, Gabriele; Glatting, Karl-Heinz; Hotz-Wagenblatt, Agnes; Diessl, Nicolle; Chotewutmonti, Sasithorn; Langowski, Jörg; Semmler, Wolfhard; Wiessler, Manfred; Braun, Klaus

    2013-01-01

    The highly organized DNA architecture inside of the nuclei of cells is accepted in the scientific world. In the human genome about 3 billion nucleotides are organized as chromatin in the cell nucleus. In general, they are involved in gene regulation and transcription by histone modification. Small chromosomes are localized in a central nuclear position whereas the large chromosomes are peripherally positioned. In our experiments we inserted fusion proteins consisting of a component of the nuclear lamina (lamin B1) and also histone H2A, both combined with the light inducible fluorescence protein KillerRed (KRED). After activation, KRED generates reactive oxygen species (ROS) producing toxic effects and may cause cell death. We analyzed the spatial damage distribution in the chromatin after illumination of the cells with visible light. The extent of DNA damage was strongly dependent on its localization inside of nuclei. The ROS activity allowed to gain information about the location of genes and their functions via sequencing and data base analysis of the double strand breaks of the isolated DNA. A connection between the damaged gene sequences and some diseases was found. PMID:23869190

  15. An MSC2 Promoter-lacZ Fusion Gene Reveals Zinc-Responsive Changes in Sites of Transcription Initiation That Occur across the Yeast Genome

    Science.gov (United States)

    Wu, Yi-Hsuan; Taggart, Janet; Song, Pamela Xiyao; MacDiarmid, Colin; Eide, David J.

    2016-01-01

    The Msc2 and Zrg17 proteins of Saccharomyces cerevisiae form a complex to transport zinc into the endoplasmic reticulum. ZRG17 is transcriptionally induced in zinc-limited cells by the Zap1 transcription factor. In this report, we show that MSC2 mRNA also increases (~1.5 fold) in zinc-limited cells. The MSC2 gene has two in-frame ATG codons at its 5’ end, ATG1 and ATG2; ATG2 is the predicted initiation codon. When the MSC2 promoter was fused at ATG2 to the lacZ gene, we found that unlike the chromosomal gene this reporter showed a 4-fold decrease in lacZ mRNA in zinc-limited cells. Surprisingly, β-galactosidase activity generated by this fusion gene increased ~7 fold during zinc deficiency suggesting the influence of post-transcriptional factors. Transcription of MSC2ATG2-lacZ was found to start upstream of ATG1 in zinc-replete cells. In zinc-limited cells, transcription initiation shifted to sites just upstream of ATG2. From the results of mutational and polysome profile analyses, we propose the following explanation for these effects. In zinc-replete cells, MSC2ATG2-lacZ mRNA with long 5’ UTRs fold into secondary structures that inhibit translation. In zinc-limited cells, transcripts with shorter unstructured 5’ UTRs are generated that are more efficiently translated. Surprisingly, chromosomal MSC2 did not show start site shifts in response to zinc status and only shorter 5’ UTRs were observed. However, the shifts that occur in the MSC2ATG2-lacZ construct led us to identify significant transcription start site changes affecting the expression of ~3% of all genes. Therefore, zinc status can profoundly alter transcription initiation across the yeast genome. PMID:27657924

  16. Fusion of the Tumor-Suppressor Gene CHEK2 and the Gene for the Regulatory Subunit B of Protein Phosphatase 2 PPP2R2A in Childhood Teratoma

    Directory of Open Access Journals (Sweden)

    Yuesheng Jin

    2006-05-01

    Full Text Available We characterized the molecular genetic consequences of a balanced chromosome translocation t(8;22(p21; q12, which occurred as the sole cytogenetic aberration in short-term cultured cells from an intrathoracic mature teratoma in a 15-year-old girl. Fluorescence in situ hybridization and reverse transcription- polymerase chain reaction disclosed that t(8;22 resulted in the fusion of the genes PPP2R2A and CHEK2, with an inserted fragment belonging to class I endogenous retrovirus-related sequences at the junction. Sequencing of the two genes did not reveal any additional mutation. None of the three detected PPP2R2A/CHEK2 fusion transcripts resulted in an in-frame PPP2R2A/CHEK2 chimerical open reading frame; however, in all of them, the known open reading frame of CHEK2 was preserved. Thus, promoter swapping leading to deregulated CHEK2 expression would be the most likely oncogenic mechanism. Whereas inactivating mutations of CHEK2 previously have been described in a variety of sporadic tumors and in inherited cancer-predisposing syndromes, PPP2R2A, encoding a regulatory subunit of the multimeric enzyme phosphatase 2, has not been directly implicated in tumorigenesis. Our findings suggest that deregulation of CHEK2 and/or PPP2R2A is of pathogenetic importance in at least a subset of germ cell tumors.

  17. Polymorphisms of estrogen metabolism-related genes ESR1 , UGT2B17 , and UGT1A1 are not associated with osteoporosis in artificial menopausal Japanese women

    Directory of Open Access Journals (Sweden)

    Megumi Yokota

    2015-09-01

    Full Text Available Introduction : Bilateral salpingo-oophorectomy (BSO is a risk factor for osteoporosis. Previous studies have reported an association between genetic polymorphisms and the risk of developing osteoporosis. However, the relationship between osteoporosis and genetic polymorphisms in Japanese women treated with BSO is not well understood. To improve the quality of life for post-BSO patients, it is important to determine the genetic factors that influence their risk for osteoporosis. The aim of this study was to investigate the association between gene variations of estrogen metabolism-related genes and osteoporosis in surgically menopausal patients, which may improve the quality of life for surgically menopausal patients. Material and methods : This study included 203 menopausal women treated with BSO because of gynecologic disorders. One hundred and twenty-six women with artificial (surgical menopause, who had undergone BSO in the premenopausal period, were compared with 77 women with natural menopause, who had undergone BSO in the postmenopausal period. The women were tested for bone mineral density to diagnose osteoporosis. Polymorphisms of estrogen receptor 1 ( ESR1 and UDP-glucuronosyl transferase (UGT genes UGT2B17 and UGT1A1 were analyzed, and their association with bone mass and osteoporosis was statistically evaluated. Results : No significant association was found between osteoporosis and polymorphisms in ESR1 , UGT2B17 , or UGT1A1 in both groups, suggesting that BSO might be a more significant physiological factor in influencing bone mass density compared to genetic variations. Conclusions : These results suggest that the ESR1 , UGT2B17 , and UGT1A1 polymorphisms are not genetic factors affecting osteoporosis in postmenopausal Japanese women.

  18. Bringing functions together with fusion enzymes--from nature's inventions to biotechnological applications.

    Science.gov (United States)

    Elleuche, Skander

    2015-02-01

    It is a mammoth task to develop a modular protein toolbox enabling the production of posttranslational organized multifunctional enzymes that catalyze reactions in complex pathways. However, nature has always guided scientists to mimic evolutionary inventions in the laboratory and, nowadays, versatile methods have been established to experimentally connect enzymatic activities with multiple advantages. Among the oldest known natural examples is the linkage of two or more juxtaposed proteins catalyzing consecutive, non-consecutive, or opposing reactions by a native peptide bond. There are multiple reasons for the artificial construction of such fusion enzymes including improved catalytic activities, enabled substrate channelling by proximity of biocatalysts, higher stabilities, and cheaper production processes. To produce fused proteins, it is either possible to genetically fuse coding open reading frames or to connect proteins in a posttranslational process. Molecular biology techniques that have been established for the production of end-to-end or insertional fusions include overlap extension polymerase chain reaction, cloning, and recombination approaches. Depending on their flexibility and applicability, these methods offer various advantages to produce fusion genes in high throughput, different orientations, and including linker sequences to maximize the flexibility and performance of fusion partners. In this review, practical techniques to fuse genes are highlighted, enzymatic parameters to choose adequate enzymes for fusion approaches are summarized, and examples with biotechnological relevance are presented including a focus on plant biomass-degrading glycosyl hydrolases.

  19. Construction, expression and immunoassay detection of recombinant plasmid encoding fusion protein of Roman chicken complement C3d and Newcastle disease virus F gene.

    Science.gov (United States)

    Liu, D; Niu, Z-X

    2008-12-01

    The terminal degradation product (C3d) of mammalian complement component C3 plays an important role in modulation of the adaptive immune response through the interaction with complement receptor type 2 (CR2) on B cells. In this study, the gene fragment coding for the complement protein C3d (chC3d) from Roman chicken was cloned and expressed as a fusion protein for its application in the vaccine study of chicken, and for in vitro experiments. The chC3d fragment strengthened B-cell responses when complexed with antigen. Three potential vaccine construct units were engineered to contain two, four and six copies of chC3d coding gene linked to the F gene of Newcastle disease virus (NDV), an economically important pathogen of chicken that is classified as a list A contagious disease of poultry by the Office International des Epizooties. The cloned chC3d protein and different repeats of C3d proteins in addition to the F gene of NDV were generated separately in Escherichia coli and chicken embryo fibroblast cells with the help of expression vectors. All recombinant proteins were analysed by SDS-PAGE and Western blotting. Analysis of the immunogenicity of different repeats of C3d revealed that chC3d had an enhancing effect on the immunogenicity of antigens, and that six or more repeats of C3d may be necessary for efficient enhancement of antigen-specific immune responses. To date, published research into the adjuvant activities of C3d has been limited to experiments in mice, rabbits and cattle. The adjuvant properties of C3d have not been assessed in poultry using homologous C3d in association with antigens relevant to the target species. The Roman chicken C3d fusion proteins described in this study is the first report and will provide a basis for immunization trials in chicken, studies of receptor binding and cell activation of chicken lymphocytes, and investigations of new types of vaccines, including recombinant vaccines and DNA vaccines for future use against other

  20. Application of bone morphogenetic protein 2 loaded nano-hydroxyapatite artificial bone in the correction and fusion of adult idiopathic scoliosis%骨形态发生蛋白2纳米人工骨在成人特发性脊柱畸形矫正融合中的应用

    Institute of Scientific and Technical Information of China (English)

    胡文; 黄旗凯; 苏佳灿; 李明

    2012-01-01

    背景:复合骨形态发生蛋白2 纳米人工骨具有独特的生物特性,模仿天然骨的成分及结构特征,可为细胞提供与天然骨相类似的微环境.目的:观察复合骨形态发生蛋白2 纳米人工骨与同种异体骨植骨在成人特发性脊柱畸形矫正融合的临床效果.方法:回顾分析69 例成人特发性脊柱侧弯患者资料,分别采用复合骨形态发生蛋白2 纳米人工骨移植36 例,同种异体骨移植33 例,植骨后第3,6 个月拍摄脊柱全长正侧位片,观察植骨融合情况.结果与结论:69 例患者畸形明显矫正,3,6 个月的影像学观测两组均可见骨小梁生长.植骨后6 个月,复合骨形态发生蛋白2 纳米人工骨组明显融合33 例,同种异体骨组26 例.复合骨形态发生蛋白2 纳米人工骨组早期融合率高于同种异体骨组(P < 0.05).提示成人特发性脊柱侧凸后路矫形手术中,复合骨形态发生蛋白2 纳米人工骨是比较理想的骨移植材料,在融合效果方面优于同种异体骨.%BACKGROUND: Bone morphogenetic protein 2 (BMP-2) loaded nano-hydroxyapatite artificial bone has unique biological properties that can imitate the component and structure of natural bone. It can provide cells a microenvironment which is similar to that of natural bone. OBJECTIVE: To investigate the clinical effects of BMP-2 loaded nano-hydroxyapatite artificial bone and allogeneic bone grafting on the correction and fusion of adult idiopathic scoliosis. METHODS: A retrospective review of 69 patients with adult idiopathic scoliosis was performed. These patients were randomly divided into two groups: group A and group B. In group A, 36 patients were received BMP-2 loaded nano-hydroxyapatite artificial bone; in group B, 33 patients were received allogeneic bone grafting. The anterioposterior and lateral full spinal films were taken at 3 and 6 months after operation, and the spinal fusion status in the two groups were observed and compared. RESULTS

  1. Image fusion

    Science.gov (United States)

    Pavel, M.

    1993-01-01

    The topics covered include the following: a system overview of the basic components of a system designed to improve the ability of a pilot to fly through low-visibility conditions such as fog; the role of visual sciences; fusion issues; sensor characterization; sources of information; image processing; and image fusion.

  2. Switch-like reprogramming of gene expression after fusion of multinucleate plasmodial cells of two Physarum polycephalum sporulation mutants

    Energy Technology Data Exchange (ETDEWEB)

    Walter, Pauline; Hoffmann, Xenia-Katharina; Ebeling, Britta; Haas, Markus; Marwan, Wolfgang, E-mail: wolfgang.marwan@ovgu.de

    2013-05-24

    Highlights: •We investigate reprogramming of gene expression in multinucleate single cells. •Cells of two differentiation control mutants are fused. •Fused cells proceed to alternative gene expression patterns. •The population of nuclei damps stochastic fluctuations in gene expression. •Dynamic processes of cellular reprogramming can be observed by repeated sampling of a cell. -- Abstract: Nonlinear dynamic processes involving the differential regulation of transcription factors are considered to impact the reprogramming of stem cells, germ cells, and somatic cells. Here, we fused two multinucleate plasmodial cells of Physarum polycephalum mutants defective in different sporulation control genes while being in different physiological states. The resulting heterokaryons established one of two significantly different expression patterns of marker genes while the plasmodial halves that were fused to each other synchronized spontaneously. Spontaneous synchronization suggests that switch-like control mechanisms spread over and finally control the entire plasmodium as a result of cytoplasmic mixing. Regulatory molecules due to the large volume of the vigorously streaming cytoplasm will define concentrations in acting on the population of nuclei and in the global setting of switches. Mixing of a large cytoplasmic volume is expected to damp stochasticity when individual nuclei deliver certain RNAs at low copy number into the cytoplasm. We conclude that spontaneous synchronization, the damping of molecular noise in gene expression by the large cytoplasmic volume, and the option to take multiple macroscopic samples from the same plasmodium provide unique options for studying the dynamics of cellular reprogramming at the single cell level.

  3. Artificial intelligence

    International Nuclear Information System (INIS)

    A vivid example of the growing need for frontier physics experiments to make use of frontier technology is in the field of artificial intelligence and related themes. This was reflected in the second international workshop on 'Software Engineering, Artificial Intelligence and Expert Systems in High Energy and Nuclear Physics' which took place from 13-18 January at France Telecom's Agelonde site at La Londe des Maures, Provence. It was the second in a series, the first having been held at Lyon in 1990

  4. Artificial Intelligence

    CERN Document Server

    Warwick, Kevin

    2011-01-01

    if AI is outside your field, or you know something of the subject and would like to know more then Artificial Intelligence: The Basics is a brilliant primer.' - Nick Smith, Engineering and Technology Magazine November 2011 Artificial Intelligence: The Basics is a concise and cutting-edge introduction to the fast moving world of AI. The author Kevin Warwick, a pioneer in the field, examines issues of what it means to be man or machine and looks at advances in robotics which have blurred the boundaries. Topics covered include: how intelligence can be defined whether machines can 'think' sensory

  5. Structural and functional studies of FKHR-PAX3, a reciprocal fusion gene of the t(2;13 chromosomal translocation in alveolar rhabdomyosarcoma.

    Directory of Open Access Journals (Sweden)

    Qiande Hu

    Full Text Available Alveolar rhabdomyosarcoma (ARMS is an aggressive pediatric cancer of skeletal muscle. More than 70% of ARMS tumors carry balanced t(2;13 chromosomal translocation that leads to the production of two novel fusion genes, PAX3-FKHR and FKHR-PAX3. While the PAX3-FKHR gene has been intensely studied, the reciprocal FKHR-PAX3 gene has rarely been described. We report here the cloning and functional characterization of the FKHR-PAX3 gene as the first step towards a better understanding of its potential impact on ARMS biology. From RH30 ARMS cells, we detected and isolated three versions of FKHR-PAX3 cDNAs whose C-terminal sequences corresponded to PAX3c, PAX3d, and PAX3e isoforms. Unlike the nuclear-specific localization of PAX3-FKHR, the reciprocal FKHR-PAX3 proteins stayed predominantly in the cytoplasm. FKHR-PAX3 potently inhibited myogenesis in both non-transformed myoblast cells and ARMS cells. We showed that FKHR-PAX3 was not a classic oncogene but could act as a facilitator in oncogenic pathways by stabilizing PAX3-FKHR expression, enhancing cell proliferation, clonogenicity, anchorage-independent growth, and matrix adhesion in vitro, and accelerating the onset of tumor formation in xenograft mouse model in vivo. In addition to these pro-oncogenic behaviors, FKHR-PAX3 also negatively affected cell migration and invasion in vitro and lung metastasis in vivo. Taken together, these functional characteristics suggested that FKHR-PAX3 might have a critical role in the early stage of ARMS development.

  6. An ancient history of gene duplications, fusions and losses in the evolution of APOBEC3 mutators in mammals

    Directory of Open Access Journals (Sweden)

    Münk Carsten

    2012-05-01

    Full Text Available Abstract Background The APOBEC3 (A3 genes play a key role in innate antiviral defense in mammals by introducing directed mutations in the DNA. The human genome encodes for seven A3 genes, with multiple splice alternatives. Different A3 proteins display different substrate specificity, but the very basic question on how discerning self from non-self still remains unresolved. Further, the expression of A3 activity/ies shapes the way both viral and host genomes evolve. Results We present here a detailed temporal analysis of the origin and expansion of the A3 repertoire in mammals. Our data support an evolutionary scenario where the genome of the mammalian ancestor encoded for at least one ancestral A3 gene, and where the genome of the ancestor of placental mammals (and possibly of the ancestor of all mammals already encoded for an A3Z1-A3Z2-A3Z3 arrangement. Duplication events of the A3 genes have occurred independently in different lineages: humans, cats and horses. In all of them, gene duplication has resulted in changes in enzyme activity and/or substrate specificity, in a paradigmatic example of convergent adaptive evolution at the genomic level. Finally, our results show that evolutionary rates for the three A3Z1, A3Z2 and A3Z3 motifs have significantly decreased in the last 100 Mya. The analysis constitutes a textbook example of the evolution of a gene locus by duplication and sub/neofunctionalization in the context of virus-host arms race. Conclusions Our results provide a time framework for identifying ancestral and derived genomic arrangements in the APOBEC loci, and to date the expansion of this gene family for different lineages through time, as a response to changes in viral/retroviral/retrotransposon pressure.

  7. Artificial sweeteners

    DEFF Research Database (Denmark)

    Raben, Anne Birgitte; Richelsen, Bjørn

    2012-01-01

    Artificial sweeteners can be a helpful tool to reduce energy intake and body weight and thereby risk for diabetes and cardiovascular diseases (CVD). Considering the prevailing diabesity (obesity and diabetes) epidemic, this can, therefore, be an important alternative to natural, calorie-containin...

  8. Proteome-wide identification of novel binding partners to the oncogenic fusion gene protein, NPM-ALK, using tandem affinity purification and mass spectrometry.

    Science.gov (United States)

    Wu, Fang; Wang, Peng; Young, Leah C; Lai, Raymond; Li, Liang

    2009-02-01

    Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), an oncogenic fusion gene protein that is characteristically found in a subset of anaplastic large cell lymphomas, promotes tumorigenesis through its functional and physical interactions with various biologically important proteins. The identification of these interacting proteins has proven to be useful to further our understanding of NPM-ALK-mediated tumorigenesis. For the first time, we performed a proteome-wide identification of NPM-ALK-binding proteins using tandem affinity purification and a highly sensitive mass spectrometric technique. Tandem affinity purification is a recently developed method that carries a lower background and higher sensitivity compared with the conventional immunoprecipitation-based protein purification protocols. The NPM-ALK gene was cloned into an HB-tagged vector and expressed in GP293 cells. Three independent experiments were performed and the reproducibility of the data was 68%. The vast majority of the previously reported NPM-ALK-binding proteins were detected. We also identified proteins that are involved in various cellular processes that were not previously described in association with NPM-ALK, such as MCM6 and MSH2 (DNA repair), Nup98 and importin 8 (subcellular protein transport), Stim1 (calcium signaling), 82Fip (RNA regulation), and BAG2 (proteosome degradation). We believe that these data highlight the functional diversity of NPM-ALK and provide new research directions for the study of the biology of this oncoprotein.

  9. Heterogeneous breakpoints on the immunoglobulin genes are involved in fusion with the 5' region of BCL2 in B-cell tumors.

    Science.gov (United States)

    Yonetani, N; Ueda, C; Akasaka, T; Nishikori, M; Uchiyama, T; Ohno, H

    2001-09-01

    The 5' flanking region of the BCL2 gene (5'-BCL2) is a breakpoint cluster of rearrangements with immunoglobulin genes (IGs). In contrast to t(14;18)(q32;q21) affecting the 3' region of BCL2, 5'-BCL2 can fuse to not only the heavy chain gene (IGH), but also two light chain gene (IGL) loci. We report here cloning and sequencing of a total of eleven 5'-BCL2 / IGs junctional areas of B-cell tumors, which were amplified by long-distance polymerase chain reaction-based assays. The breakpoints on 5'-BCL2 were distributed from 378 to 2312 bp upstream of the translational initiation site and, reflecting the alteration of regulatory sequences of BCL2, 5'-BCL2 / IGs-positive cells showed markedly higher levels of BCL2 expression than those of t(14;18)-positive cells. In contrast, the breakpoints on the IGs were variable. Two 5'-BCL2 / IGH and two 5'-BCL2 / IGLkappa junctions occurred 5' of the joining (J) segments, suggesting operation of an erroneous variable (V) / diversity (D) / J and V / J rearrangement mechanism. However, two other 5'-BCL2 / IGH junctions affected switch regions, and the kappa-deleting element, which is located 24 kb downstream of the constant region of IGLkappa, followed the 5'-BCL2 in another case. One 5'-BCL2 / IGLkappa and two 5'-BCL2 / IGLlambda junctions involved intronic regions where the normal recombination process does not occur. In the remaining one case, the 5'-BCL2 fused 3' of a Vlambda gene that was upstream of another Vlambda / Jlambda complex carrying a non-producing configuration, indicating that the receptor editing mechanism was likely involved in this rearrangement. Our study revealed heterogeneous anatomy of the 5'-BCL2 / IGs fusion gene leading to transcriptional activation of BCL2, and suggested that the mechanisms underlying the formation of this particular oncogene / IGs recombination are not identical to those of t(14;18).

  10. Gene Amplification by PCR and Subcloning into a GFP-Fusion Plasmid Expression Vector as a Molecular Biology Laboratory Course

    Science.gov (United States)

    Bornhorst, Joshua A.; Deibel, Michael A.; Mulnix, Amy B.

    2004-01-01

    A novel experimental sequence for the advanced undergraduate laboratory course has been developed at Earlham College. Utilizing recent improvements in molecular techniques for a time-sensitive environment, undergraduates were able to create a chimera of a selected gene and green fluorescent protein (GFP) in a bacterial expression plasmid over the…

  11. On the development of an artificial intervertebral disc

    NARCIS (Netherlands)

    Eijkelkamp, Marcus Franciscus

    2002-01-01

    Degenerative disc disease is one of the causes of low back pain. There are two major surgical interventions: spinal fusion and implantation of an artificial intervertebral disc. Spinal fusion alters the biomechanics of the spine, which may lead to further degeneration of the surrounding tissues and

  12. Robust, synergistic regulation of human gene expression using TALE activators.

    Science.gov (United States)

    Maeder, Morgan L; Linder, Samantha J; Reyon, Deepak; Angstman, James F; Fu, Yanfang; Sander, Jeffry D; Joung, J Keith

    2013-03-01

    Artificial activators designed using transcription activator-like effector (TALE) technology have broad utility, but previous studies suggest that these monomeric proteins often exhibit low activities. Here we demonstrate that TALE activators can robustly function individually or in synergistic combinations to increase expression of endogenous human genes over wide dynamic ranges. These findings will encourage applications of TALE activators for research and therapy, and guide design of monomeric TALE-based fusion proteins.

  13. Construction of a yeast artificial chromosome contig encompassing the human acidic fibroblast growth factor (FGF1) gene: Toward the cloning of the ANLL/MDS tumor-suppressor gene

    Energy Technology Data Exchange (ETDEWEB)

    Chiu, Ing-Ming; Gilmore, E.C.; Liu, Yang; Payson, R.A. (Ohio State Univ., Columbus, OH (United States))

    1994-02-01

    The region surrounding the human acidic fibroblast growth factor (FGF1) locus on chromosome 5q31 is of particular interest since it represents a critical region consistently lost in acute nonlymphocytic leukemia (ANLL) or myelodysplastic syndrome (MDS) patients who have a demonstrable deletion of the distal portion of the long arm of chromosome 5. It is proposed that an ANLL/MDS leukemia suppressor gene resides on 5q31. The authors have previously shown that the gene is most likely localized between FGF1 and PDGFRB/CSF1R loci. The region has also been linked to at least four other genetic diseases, Treacher Collins syndrome, diastrophic dysplasia, limb-girdle muscular dystrophy, and an autosomal dominant deafness, by linkage analysis. Here, they describe yeast artificial chromosomes (YAC) spanning 450 kb around the FGF1 gene. Six YAC clones were isolated from a human YAC library and their restriction enzyme maps were determined. The overlap of the clones with each other and with FGF1 cosmid and phage clones was characterized. Three of the YAC clones were found to contain the entire FGF1 gene, which spans more than 100 kb. Proximal and distal ends of several of these YAC clones were isolated for further overlap cloning. The proximal ends of both Y2 and Y4 were localized to previously isolated FGF1 DNA by sequence analysis. The distal ends of these two clones also hybridized to a human-hamster hybrid containing chromosome 5 as the only human genetic material. These results suggest that these YAC clones represent colinear DNA around the FGF1 locus. None of the YAC clones were found to contain the CD 14 and GRL genes, the closest known proximal and distal markers (relative to the centromere) to the FGF1 gene, respectively. This contig is useful for the overlap cloning of the 5q31 region and for reverse genetic strategies for the isolation of disease genes in the region. 46 refs., 7 figs., 5 tabs.

  14. Artificial fertilization in corn and prospects of its use

    Directory of Open Access Journals (Sweden)

    T. M. Satarova

    2006-02-01

    Full Text Available Summarizing article is devoted to the results and perspectives of artificial fertilization in vitro in maize. The methods of purification of male and female gametes, their fusion, production of endosperm and zygotes, which are able to produce the embryo, are described. The possibilities of the combination of the transgenic technique and the technique of the artificial fertilization are estimated.

  15. Cold fusion

    International Nuclear Information System (INIS)

    So called 'cold fusion phenomena' are not confirmed yet. Excess heat generation is very delicate one. Neutron generation is most reliable results, however, the records are erratic and the same results could not be repeated. So there is no reason to exclude the malfunction of testing instruments. The same arguments arise in recording 4He, 3He, 3H, which are not rich in quantity basically. An experiment where plenty of 4He were recorded is attached in appendix. The problem is that we are trying to search cold fusion which is permitted by nature or not. The famous tunneling effect in quantum mechanics will answer it, however, the most fusion rate is known to be negligible. The focus of this project is on the theme that how to increase that negligible fusion rate. 6 figs, 4 tabs, 1512 refs. (Author)

  16. Cold fusion

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Suk Yong; Sung, Ki Woong; Kang, Joo Sang; Lee, Jong Jik [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1995-02-01

    So called `cold fusion phenomena` are not confirmed yet. Excess heat generation is very delicate one. Neutron generation is most reliable results, however, the records are erratic and the same results could not be repeated. So there is no reason to exclude the malfunction of testing instruments. The same arguments arise in recording {sup 4}He, {sup 3}He, {sup 3}H, which are not rich in quantity basically. An experiment where plenty of {sup 4}He were recorded is attached in appendix. The problem is that we are trying to search cold fusion which is permitted by nature or not. The famous tunneling effect in quantum mechanics will answer it, however, the most fusion rate is known to be negligible. The focus of this project is on the theme that how to increase that negligible fusion rate. 6 figs, 4 tabs, 1512 refs. (Author).

  17. Prognostic and therapeutic role of targetable lesions in B-lineage acute lymphoblastic leukemia without recurrent fusion genes.

    Science.gov (United States)

    Messina, Monica; Chiaretti, Sabina; Wang, Jiguang; Fedullo, Anna Lucia; Peragine, Nadia; Gianfelici, Valentina; Piciocchi, Alfonso; Brugnoletti, Fulvia; Di Giacomo, Filomena; Pauselli, Simona; Holmes, Antony B; Puzzolo, Maria Cristina; Ceglie, Giulia; Apicella, Valerio; Mancini, Marco; Te Kronnie, Geertruy; Testi, Anna Maria; Vitale, Antonella; Vignetti, Marco; Guarini, Anna; Rabadan, Raul; Foà, Robin

    2016-03-22

    To shed light into the molecular bases of B-lineage acute lymphoblastic leukemia lacking known fusion transcripts, i.e. BCR-ABL1, ETV6-RUNX1, E2A-PBX1, and MLL rearrangements (B-NEG ALL) and the differences between children, adolescents/young adults (AYA) and adults, we analyzed 168 B-NEG ALLs by genome-wide technologies. This approach showed that B-NEG cases carry 10.5 mutations and 9.1 copy-number aberrations/sample. The most frequently mutated druggable pathways were those pertaining to RAS/RTK (26.8%) and JAK/STAT (12.5%) signaling. In particular, FLT3 and JAK/STAT mutations were detected mainly in AYA and adults, while KRAS and NRAS mutations were more frequent in children. RAS/RTK mutations negatively affected the outcome of AYA and adults, but not that of children. Furthermore, adult B-NEG ALL carrying JAK/STAT mutations had a shorter survival. In vitro experiments showed that FLT3 inhibitors reduced significantly the proliferation of FLT3-mutated primary B-NEG ALL cells. Likewise, PI3K/mTOR inhibitors reduced the proliferation of primary cells harboring RAS and IL7R mutations. These results refine the genetic landscape of B-NEG ALL and suggest that the different distribution of lesions and their prognostic impact might sustain the diverse outcome between children, adults and partly AYA - whose genomic scenario is similar to adults - and open the way to targeted therapeutic strategies. PMID:26883104

  18. Fusion energy

    International Nuclear Information System (INIS)

    The efforts of the Chemical Technology Division in fusion energy include the areas of fuel handling, processing, and containment. Current studies are concerned largely with the development of vacuum pumps for fusion reactors and experiments and with development and evaluation of techniques for recovering tritium from solid or liquid breeding blankets. In addition, a small effort is devoted to support of the ORNL design of a major Tokamak experiment, The Next Step (TNS)

  19. Artificial Intelligence.

    Science.gov (United States)

    Lawrence, David R; Palacios-González, César; Harris, John

    2016-04-01

    It seems natural to think that the same prudential and ethical reasons for mutual respect and tolerance that one has vis-à-vis other human persons would hold toward newly encountered paradigmatic but nonhuman biological persons. One also tends to think that they would have similar reasons for treating we humans as creatures that count morally in our own right. This line of thought transcends biological boundaries-namely, with regard to artificially (super)intelligent persons-but is this a safe assumption? The issue concerns ultimate moral significance: the significance possessed by human persons, persons from other planets, and hypothetical nonorganic persons in the form of artificial intelligence (AI). This article investigates why our possible relations to AI persons could be more complicated than they first might appear, given that they might possess a radically different nature to us, to the point that civilized or peaceful coexistence in a determinate geographical space could be impossible to achieve.

  20. Requirements for an artificial intervertebral disc

    NARCIS (Netherlands)

    Eijkelkamp, MF; van Donkelaar, CC; Veldhuizen, AG; van Horn, [No Value; Huyghe, JM; Verkerke, GJ

    2001-01-01

    Intervertebral disc degeneration is an important social and economic problem. Presently available artificial intervertebral discs (AIDs) are insufficient and the main surgical intervention is still spinal fusion. The objective of the present study is to present a list of requirements for the develop

  1. Development of novel prime-boost strategies based on a tri-gene fusion recombinant L. tarentolae vaccine against experimental murine visceral leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Noushin Saljoughian

    Full Text Available Visceral leishmaniasis (VL is a vector-borne disease affecting humans and domestic animals that constitutes a serious public health problem in many countries. Although many antigens have been examined so far as protein- or DNA-based vaccines, none of them conferred complete long-term protection. The use of the lizard non-pathogenic to humans Leishmania (L. tarentolae species as a live vaccine vector to deliver specific Leishmania antigens is a recent approach that needs to be explored further. In this study, we evaluated the effectiveness of live vaccination in protecting BALB/c mice against L. infantum infection using prime-boost regimens, namely Live/Live and DNA/Live. As a live vaccine, we used recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinases (CPA and CPB without its unusual C-terminal extension (CPB(-CTE as a tri-fusion gene. For DNA priming, the tri-fusion gene was encoded in pcDNA formulated with cationic solid lipid nanoparticles (cSLN acting as an adjuvant. At different time points post-challenge, parasite burden and histopathological changes as well as humoral and cellular immune responses were assessed. Our results showed that immunization with both prime-boost A2-CPA-CPB(-CTE-recombinant L. tarentolae protects BALB/c mice against L. infantum challenge. This protective immunity is associated with a Th1-type immune response due to high levels of IFN-γ production prior and after challenge and with lower levels of IL-10 production after challenge, leading to a significantly higher IFN-γ/IL-10 ratio compared to the control groups. Moreover, this immunization elicited high IgG1 and IgG2a humoral immune responses. Protection in mice was also correlated with a high nitric oxide production and low parasite burden. Altogether, these results indicate the promise of the A2-CPA-CPB(-CTE-recombinant L. tarentolae as a safe live vaccine candidate against VL.

  2. Artificial intelligence

    OpenAIRE

    Duda, Antonín

    2009-01-01

    Abstract : Issue of this work is to acquaint the reader with the history of artificial inteligence, esspecialy branch of chess computing. Main attention is given to progress from fifties to the present. The work also deals with fighting chess programs against each other, and against human opponents. The greatest attention is focused on 1997 and duel Garry Kasparov against chess program Deep Blue. The work is divided into chapters according to chronological order.

  3. Artificial senses for characterization of food quality

    Institute of Scientific and Technical Information of China (English)

    HUANG Yan-bo; LAN Yu-bin; R.E. Lacey

    2004-01-01

    Food quality is of primary concern in the food industry and to the consumer. Systems that mimic human senses have been developed and applied to the characterization of food quality. The five primary senses are: vision, hearing, smell, taste and touch.In the characterization of food quality, people assess the samples sensorially and differentiate "good" from "bad" on a continuum.However, the human sensory system is subjective, with mental and physical inconsistencies, and needs time to work. Artificial senses such as machine vision, the electronic ear, electronic nose, electronic tongue, artificial mouth and even artificial the head have been developed that mimic the human senses. These artificial senses are coordinated individually or collectively by a pattern recognition technique, typically artificial neural networks, which have been developed based on studies of the mechanism of the human brain. Such a structure has been used to formulate methods for rapid characterization of food quality. This research presents and discusses individual artificial sensing systems. With the concept of multi-sensor data fusion these sensor systems can work collectively in some way. Two such fused systems, artificial mouth and artificial head, are described and discussed. It indicates that each of the individual systems has their own artificially sensing ability to differentiate food samples. It further indicates that with a more complete mimic of human intelligence the fused systems are more powerful than the individual systems in differentiation of food samples.

  4. 纤维蛋白胶复合自体骨髓与人工骨促进脊柱融合的现状与展望%Fibrin sealant combined with autologous bone marrow and artificial bone to promote spine fusion

    Institute of Scientific and Technical Information of China (English)

    蔡志刚; 芮钢

    2011-01-01

    背景:如何利用纤维蛋白胶的黏合性在术中复合自体骨髓与人工骨来提高脊柱融合的成功率,得进一步研究.目的:综述纤维蛋白胶的研究背景、成分、作用原理及理化特性,维蛋白胶及自体骨髓复合人工骨在脊柱融合中应用的现状.方法:由第一作者检索1994/2010 CNKI系列数据库及PubMed数据库有关纤维蛋白胶的研究背景、成分、作用原理及理化特性,维蛋白胶在构建组织工程骨及修复骨缺损中的应用,体骨髓复合人工骨移植在修复骨缺损中的应用,柱融合中植骨方法应用等方面的文献.结果与结论:自体骨髓复合人工骨移植修复骨缺损在临床取得了较好的疗效,此在脊柱融合中利用自体骨髓复合人工骨来提高脊柱融合率应该是可行的方案,以往自体骨髓混合人工骨的过程相对简单,由于自体骨髓流动性大,射后容易流失,显降低了自体骨髓的成骨作用.因此设想在临床手术中,用纤维蛋白胶的黏合特性将自体骨髓与人工骨黏合在一起,入脊柱关节突、横突部位,分发挥骨髓的最大成骨作用,将是临床一个提高脊柱融合率的简易、快速、有效的方法,待进一步的深入研究.%BACKGROUND: How to use the adhesion of fibrin glue to combine with autologous bone marrow and artificial bone to increase the success rate of spinal fusion in surgery, it is worthy of further study.OBJECTIVE: To review the research background, composition, function theory, physical and chemical properties of fibrin glue,the present of fibrin glue, autologous bone marrow combined with artificial bone in spinal fusion.METHODS: China Knowledge Resources Library-CNKI Series Database (1994 to 2010) and PubMed database were retrieved by the first author for literatures concerning the research background, composition, function theory and physical and chemical properties of fibrin glue, the application of fibrin glue in bone tissue engineering

  5. Artificial cervical disc replacement and anterior cervical decompression and fusion for the treatment of single segmental cervical disc herniation:a 3-year follow-up%颈椎人工间盘置换与前路减压融合修复单节段颈椎间盘突出症:3年随访

    Institute of Scientific and Technical Information of China (English)

    程俊杰; 眭江涛; 马原; 田慧中

    2015-01-01

    stages. Artificial disc replacement can not only play a role in mitigation of cervical disease neurological symptoms and signs, but also maintain stability and semental activity of cervical spine, and reduce secondary adjacent segmental degeneration. These two methods which applied in cervical degenerative intervertebral disc herniation stil remain controversial. OBJECTIVE:To investigate the short-term effect of artificial cervical disc replacement and anterior cervical decompression and fusion for the treatment of single segmental cervical disc herniation. METHODS:Total y 48 patients with single segment radiculopathy or myelopathy cervical diseases induced by cervical disc herniation that required surgery and received a three-month fol ow-up were included and retrospectively analyzed. These patients were divided into replacement group (n=21) and fusion group (n=27) according to the different repair programs. Patients in the replacement group were subjected to Prestige LP cervical artificial disc replacement, and patients in the fusion group were subjected to disc fusion using interbody fusion cage of Johnson or al ogeneic fibularing. They were fol owed up at 1 week, 3, 6, 12, 24, 36 months after treatment. Complications were recorded during the fol ow-up. The pain of patients was evaluated using neck and upper limb pain visual analogue scale scores. The therapeutic effect was evaluated using Japanese Orthopaedic Association (JOA) score. The clinical symptoms improvement and daily functional status of patients after treatment were evaluated using cervical disability index. RESULTS AND CONCLUSION:During the final fol ow-up, the fusion rate in fusion group was 93%(25/27). Comparisons between groups:at the 1 week and final fol ow-up after treatment, the visual analog scale scores of neck and upper limbs and cervical dysfunction indexes were al lower than those before treatment;the Japanese Orthopaedic Association scores were higher than those before treatment (P0.05). The

  6. Characterization of recombinant CEL-I, a GalNAc-specific C-type lectin, expressed in Escherichia coli using an artificial synthetic gene.

    Science.gov (United States)

    Hatakeyama, Tomomitsu; Shiba, Kouhei; Matsuo, Noriaki; Fujimoto, Tokiko; Oda, Tatsuya; Sugawara, Hajime; Aoyagi, Haruhiko

    2004-01-01

    CEL-I is a C-type lectin isolated from the Holothuroidea Cucumaria echinata. This lectin shows very high N-acetylgalactosamine-binding specificity. We constructed an artificial gene encoding recombinant CEL-I (rCEL-I) using a combination of synthetic oligonucleotides, and expressed it in Escherichia coli cells. Since the recombinant protein was obtained as inclusion bodies, the latter were solubilized using urea and 2-mercaptoethanol, and the protein was refolded during the purification and dialysis steps. The purified rCEL-I showed comparable hemagglutinating activity to that of native CEL-I at relatively high Ca(2+)-concentrations, whereas it was weaker at lower Ca(2+)-concentrations due to decreased Ca(2+)-binding affinity. rCEL-I exhibited similar carbohydrate-binding specificity to native CEL-I, including strong GalNAc-binding specificity, as examined by hemagglutination inhibition assay. Comparison of the far UV-CD spectra of recombinant and native CEL-I revealed that the two proteins undergo a similar conformational change upon binding of Ca(2+). Single crystals of rCEL-I were also obtained under the same conditions as those used for the native protein, suggesting that they have similar tertiary structures. Although native CEL-I exhibited strong cytotoxicity toward cultured cells, rCEL-I showed low cytotoxicity. These results indicate that rCEL-I has a tertiary structure and carbohydrate-binding specificity similar to those of native CEL-I. Howeger, there is a subtle difference in the properties between the two proteins probably due to the additional methionine residue at the N-terminus of rCEL-I. PMID:14999015

  7. The construction of a yeast artificial chromosome (YAC) contig in the vicinity of the Usher syndrome type IIa (USH2A) gene in 1q41

    Energy Technology Data Exchange (ETDEWEB)

    Sumegi, Janos; Wang, Ji-Yi; Zhen, Dong-Kai [Univ. of Nebraska Medical Center, Omaha, NE (United States)] [and others

    1996-07-01

    The gene for Usher syndrome type II (USH2A), and autosomal recessive syndromic deafness, has been mapped to a region of 1q41 flanked proximally by D1S217 and distally by D1S439. Using sequence-tagged sites (STSs) within the region, a total of 21 yeast artificial chromosome (YAC) clones were isolated and ordered into a single contig that spans approximately 11.0 Mb. The order of microsatellite and STS markers in this region was established as D1S505-D1S425-DXS217-D1S556-D1S237-D1S474-EB1-KB6-AFM144XF2-KB1-KB4-D1S229-D1S490-D1S227-TGF{beta}2-D1S439. Analysis of newly positioned polymorphic markers in recombinant individuals in two Usher syndrome type IIa families has enabled us to identify DXS474 and AFM144XF2 as two flanking markers for the Usher type IIa locus. The physical distance between the two markers is 1.0 Mb. This region is covered by eight YACs from the CEPH library: 945f7, 867g9, 762a6, 919h3, 794b8, 785h4, 848b9, and 841g2. A long range physical map of the Usher type IIa critical region, using MluI, BssHII, NotI, EagI, and SacII, has been developed. 41 refs., 5 figs.

  8. Increased production of wax esters in transgenic tobacco plants by expression of a fatty acid reductase:wax synthase gene fusion.

    Science.gov (United States)

    Aslan, Selcuk; Hofvander, Per; Dutta, Paresh; Sun, Chuanxin; Sitbon, Folke

    2015-12-01

    Wax esters are hydrophobic lipids consisting of a fatty acid moiety linked to a fatty alcohol with an ester bond. Plant-derived wax esters are today of particular concern for their potential as cost-effective and sustainable sources of lubricants. However, this aspect is hampered by the fact that the level of wax esters in plants generally is too low to allow commercial exploitation. To investigate whether wax ester biosynthesis can be increased in plants using transgenic approaches, we have here exploited a fusion between two bacterial genes together encoding a single wax ester-forming enzyme, and targeted the resulting protein to chloroplasts in stably transformed tobacco (Nicotiana benthamiana) plants. Compared to wild-type controls, transgenic plants showed both in leaves and stems a significant increase in the total level of wax esters, being eight-fold at the whole plant level. The profiles of fatty acid methyl ester and fatty alcohol in wax esters were related, and C16 and C18 molecules constituted predominant forms. Strong transformants displayed certain developmental aberrations, such as stunted growth and chlorotic leaves and stems. These negative effects were associated with an accumulation of fatty alcohols, suggesting that an adequate balance between formation and esterification of fatty alcohols is crucial for a high wax ester production. The results show that wax ester engineering in transgenic plants is feasible, and suggest that higher yields may become achieved in the near future.

  9. Cybridization in Nicotiana tabacum L. using double inactivation of parental protoplasts and post-fusion selection based on nuclear-encoded and chloroplast-encoded marker genes.

    Science.gov (United States)

    Matibiri, E A; Mantell, S H

    1994-09-01

    An effective selection system preceded by double inactivation of parental protoplasts was used to transfer Nicotiana suaveolens Leh. cytoplasmic male sterility into a commercial tobacco (N. tabacum L.) breeding line. Mesophyll protoplasts from transformed plants of N. tabacum cultivar WZ2-3-1-1 possessing a neomycin phosphotransferase II gene were used as the nuclear donors, while those isolated from N. suaveolens plants carrying a chloroplast mutation for resistance to spectinomycin, induced using nitrosomethyl urea, were the cytoplasm donors in somatic cybridizations. Prior to fusion, nuclear donor protoplasts were inactivated with iodoacetamide or rhodamine 6G, while those of the cytoplasm donor were inactivated by X-irradiation. The resultant microcalli were cultured on a shoot regeneration medium containing both kanamycin and spectinomycin to select cybrids. Only regenerants that had typical characteristics of the N. tabacum cultivar were selected for transfer to the glasshouse. Four putative cytoplasmic male-sterile (CMS) plants, out of a total of 44 regenerated plants transferred to the glasshouse, were obtained. Intraspecific somatic transfers of the CMS trait between N. tabacum cultivars with distinctlydifferent morphologies using single inactivation and nonselective shoot regeneration medium were demonstrated. The implications of the results for practical tobacco breeding as a means of circumventing lengthy backcrossing procedures are discussed. PMID:24186256

  10. Over-expression of BvMTSH, a fusion gene for maltooligosyltrehalose synthase and maltooligosyltrehalose trehalohydrolase, enhances drought tolerance in transgenic rice.

    Science.gov (United States)

    Joo, Joungsu; Choi, Hae Jong; Lee, Youn Hab; Lee, Sarah; Lee, Choong Hwan; Kim, Chung Ho; Cheong, Jong-Joo; Choi, Yang Do; Song, Sang Ik

    2014-01-01

    Plant abiotic stress tolerance has been modulated by engineering the trehalose synthesis pathway. However, many stress-tolerant plants that have been genetically engineered for the trehalose synthesis pathway also show abnormal development. The metabolic intermediate trehalose 6-phosphate has the potential to cause aberrations in growth. To avoid growth inhibition by trehalose 6-phosphate, we used a gene that encodes a bifunctional in-frame fusion (BvMTSH) of maltooligosyltrehalose synthase (BvMTS) and maltooligosyltrehalose trehalohydrolase (BvMTH) from the nonpathogenic bacterium Brevibacterium helvolum. BvMTS converts maltooligosaccharides into maltooligosyltrehalose and BvMTH releases trehalose. Transgenic rice plants that over-express BvMTSH under the control of the constitutive rice cytochrome c promoter (101MTSH) or the ABA-inducible Ai promoter (105MTSH) show enhanced drought tolerance without growth inhibition. Moreover, 101MTSH and 105MTSH showed an ABA-hyposensitive phenotype in the roots. Our results suggest that over-expression of BvMTSH enhances drought-stress tolerance without any abnormal growth and showes ABA hyposensitive phenotype in the roots. PMID:24209631

  11. Coupling a universal DNA circuit with graphene sheets/polyaniline/AuNPs nanocomposites for the detection of BCR/ABL fusion gene

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xueping [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Wang, Li [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Department of Medical Laboratory, Chongqing Emergency Medical Center (Chongqing The Fourth Hospital), Chongqing, 400016 (China); Sheng, Shangchun [The No.2 Peoples' Hospital of Yibin, Sichuan, 644000 (China); Wang, Teng; Yang, Juan [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Xie, Guoming, E-mail: guomingxie@cqmu.edu.cn [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Feng, Wenli, E-mail: fengwlcqmu@sina.com [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China)

    2015-08-19

    This article described a novel method by coupling a universal DNA circuit with graphene sheets/polyaniline/AuNPs nanocomposites (GS/PANI/AuNPs) for highly sensitive and specific detection of BCR/ABL fusion gene (bcr/abl) in chronic myeloid leukemia (CML). DNA circuit known as catalyzed hairpin assembly (CHA) is enzyme-free and can be simply operated to achieve exponential amplification, which has been widely employed in biosensing. However, application of CHA has been hindered by the need of specially redesigned sequences for each single-stranded DNA input. Herein, a transducer hairpin (HP) was designed to obtain a universal DNA circuit with favorable signal-to-background ratio. To further improve signal amplification, GS/PANI/AuNPs with excellent conductivity and enlarged effective area were introduced into this DNA circuit. Consequently, by combining the advantages of CHA and GS/PANI/AuNPs, bcr/abl could be detected in a linear range from 10 pM to 20 nM with a detection limit of 1.05 pM. Moreover, this protocol showed excellent specificity, good stability and was successfully applied for the detection of real sample, which demonstrated its great potential in clinical application. - Highlights: • A transducer hairpin was designed to improve the versatility of DNA circuit. • GS/PANI/AuNPs were introduced to the DNA circuit for further signal amplification. • The established biosensor displayed high sensitivity and good specificity.

  12. Coupling a universal DNA circuit with graphene sheets/polyaniline/AuNPs nanocomposites for the detection of BCR/ABL fusion gene

    International Nuclear Information System (INIS)

    This article described a novel method by coupling a universal DNA circuit with graphene sheets/polyaniline/AuNPs nanocomposites (GS/PANI/AuNPs) for highly sensitive and specific detection of BCR/ABL fusion gene (bcr/abl) in chronic myeloid leukemia (CML). DNA circuit known as catalyzed hairpin assembly (CHA) is enzyme-free and can be simply operated to achieve exponential amplification, which has been widely employed in biosensing. However, application of CHA has been hindered by the need of specially redesigned sequences for each single-stranded DNA input. Herein, a transducer hairpin (HP) was designed to obtain a universal DNA circuit with favorable signal-to-background ratio. To further improve signal amplification, GS/PANI/AuNPs with excellent conductivity and enlarged effective area were introduced into this DNA circuit. Consequently, by combining the advantages of CHA and GS/PANI/AuNPs, bcr/abl could be detected in a linear range from 10 pM to 20 nM with a detection limit of 1.05 pM. Moreover, this protocol showed excellent specificity, good stability and was successfully applied for the detection of real sample, which demonstrated its great potential in clinical application. - Highlights: • A transducer hairpin was designed to improve the versatility of DNA circuit. • GS/PANI/AuNPs were introduced to the DNA circuit for further signal amplification. • The established biosensor displayed high sensitivity and good specificity

  13. Genetic diversity, seasonality and transmission network of human metapneumovirus: identification of a unique sub-lineage of the fusion and attachment genes.

    Science.gov (United States)

    Chow, Wei Zhen; Chan, Yoke Fun; Oong, Xiang Yong; Ng, Liang Jie; Nor'E, Siti Sarah; Ng, Kim Tien; Chan, Kok Gan; Hanafi, Nik Sherina; Pang, Yong Kek; Kamarulzaman, Adeeba; Tee, Kok Keng

    2016-01-01

    Human metapneumovirus (HMPV) is an important viral respiratory pathogen worldwide. Current knowledge regarding the genetic diversity, seasonality and transmission dynamics of HMPV among adults and children living in tropical climate remains limited. HMPV prevailed at 2.2% (n = 86/3,935) among individuals presented with acute respiratory tract infections in Kuala Lumpur, Malaysia between 2012 and 2014. Seasonal peaks were observed during the northeast monsoon season (November-April) and correlated with higher relative humidity and number of rainy days (P < 0.05). Phylogenetic analysis of the fusion and attachment genes identified the co-circulation of three known HMPV sub-lineages, A2b and B1 (30.2% each, 26/86) and B2 (20.9%, 18/86), with genotype shift from sub-lineage B1 to A2b observed in 2013. Interestingly, a previously unrecognized sub-lineage of A2 was identified in 18.6% (16/86) of the population. Using a custom script for network construction based on the TN93 pairwise genetic distance, we identified up to nine HMPV transmission clusters circulating as multiple sub-epidemics. Although no apparent major outbreak was observed, the increased frequency of transmission clusters (dyads) during seasonal peaks suggests the potential roles of transmission clusters in driving the spread of HMPV. Our findings provide essential information for therapeutic research, prevention strategies, and disease outbreak monitoring of HMPV. PMID:27279080

  14. RT-PCR ANALYSIS OF E2A-PBX1, TEL-AML1, BCR-ABL AND MLL-AF4 FUSION GENE TRANSCRIPTS IN B-LINEAGE ACUTE LYMPHOBLASTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Iuliu-Cristian Ivanov

    2013-11-01

    Full Text Available Acute lymphoblastic leukemia represents a heterogeneous group of hematological malignancies, defined by clonal proliferation of lymphoid cells. Immunophenotyping by flow cytometry and molecular analysis for the detection of genetic anomalies are clinical standard procedures for diagnosis, sub-classification and post-therapeutic evaluation. Samples from 105 patients diagnosed with acute lymphoblastic leukemia were immunophenotyped at diagnosis and were investigated by molecular analysis in order to identify the occurrence of four fusion genes: MLL-AF4, TEL-AML-1, BCR-ABL-p190, E2A-PBX-1. There were no associations found between the immunophenotype and the presence of any fusion genes evaluated. Both methods in combination remain a prerequisite for an improved subclassification of hematological malignancies, therapeutic decision, and evaluation of treatment response.

  15. Unintended Changes in Genetically Modified Rice Expressing the Lysine-Rich Fusion Protein Gene Revealed by a Proteomics Approach

    Institute of Scientific and Technical Information of China (English)

    ZHAO Xiang-xiang; TANG Tang; LIU Fu-xia; LU Chang-li; HU Xiao-lan; JI Li-lian; LIU Qiao-quan

    2013-01-01

    Development of new technologies for evaluating genetically modiifed (GM) crops has revealed that there are unintended insertions and expression changes in GM crops. Proifling techniques are non-targeted approaches and are capable of detecting more unintended changes in GM crops. Here, we report the application of a comparative proteomic approach to investigate the protein proifle differences between a GM rice line, which has a lysine-rich protein gene, and its non-transgenic parental line. Proteome analysis by two-dimensional gel electrophoresis (2-DE) and mass spectrum analysis of the seeds identiifed 22 differentially expressed protein spots. Apart from a number of glutelins that were detected as targeted proteins in the GM line, the majority of the other changed proteins were involved in carbohydrate metabolism, protein synthesis and stress responses. These results indicated that the altered proteins were not associated with plant allergens or toxicity.

  16. Expression of the RET/PTC fusion gene as a marker for papillary carcinoma in Hashimoto's thyroiditis

    DEFF Research Database (Denmark)

    Wirtschafter, A; Schmidt, R; Rosen, D;

    1997-01-01

    Hashimoto's thyroiditis is an inflammatory disease of the thyroid gland with autoimmune etiology. Patients afflicted with Hashimoto's have a higher risk of thyroid malignancies such as papillary thyroid carcinoma. In the present study, we investigated the frequency of papillary thyroid carcinoma...... specific genes in patients diagnosed with Hashimoto's disease. The newly identified oncogenes RET/PTC1 and RET/PTC3 provide useful and specific markers of the early stages of papillary carcinoma as they are highly specific for malignant cells. Using a sensitive and specific reverse transcriptase......-polymerase chain reaction (RT-PCR) assay, we found messenger RNA (mRNA) expression for the RET/PTC1 and RET/PTC3 oncogenes in 95% of the Hashimoto's patients studied. All Hashimoto's patients presenting without histopathologic evidence of papillary thyroid cancer showed molecular genetic evidence of cancer...

  17. AI/Simulation Fusion Project at Lawrence Livermore National Laboratory

    International Nuclear Information System (INIS)

    This presentation first discusses the motivation for the AI Simulation Fusion project. After discussing very briefly what expert systems are in general, what object oriented languages are in general, and some observed features of typical combat simulations, it discusses why putting together artificial intelligence and combat simulation makes sense. We then talk about the first demonstration goal for this fusion project

  18. ARTIFICIAL LIVING SYSTEM AND ITS COMPLEXITY

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yongguang

    2001-01-01

    In this paper the author shows some artificial living systems, whose basic life characteristics are explored, especially the differentiation in evolution from single cellular to multi-cellular organism. In addition, the author discusses diversity and evolvability also.The author gives a modified entropy function to measure the diversity. Finally, the author drops an open problem about the structure of "gene" of artificial living systems, so that we can measure the evolutionary order between the artificial living systems.

  19. Quantitative PCR detection of NPM/ALK fusion gene and CD30 gene expression in patients with anaplastic large cell lymphoma--residual disease monitoring and a correlation with the disease status.

    Science.gov (United States)

    Kalinova, Marketa; Krskova, Lenka; Brizova, Helena; Kabickova, Edita; Kepak, Tomas; Kodet, Roman

    2008-01-01

    Anaplastic large cell lymphoma (ALCL) represents a heterogeneous group of malignant lymphoproliferative diseases with a consistent expression of the cytokine receptor CD30. ALCL is frequently associated with a NPM/ALK fusion gene which is found in up to 75% of pediatric ALCLs. Real-time quantitative RT-PCR (RQ-RT-PCR) of NPM/ALK and CD30 gene expression was employed to analyze minimal residual disease (MRD) in 10 patients with NPM/ALK positive ALCL in 79 follow-up bone marrow (BM) and/or peripheral blood (PB) samples. In all BM samples from relapses and/or closely before a relapse, BM samples revealed NPM/ALK and CD30 positivity in at least one of the iliac BM trephines. Five out of nine relapses were preceded or were accompanied by minimally half log increased NPM/ALK levels in the BM. We found that RQ-RT-PCR of the CD30 expression is not suitable for MRD detection--only two relapses were accompanied by an increase of the CD30 level above a level which was detected in BM/PB samples from healthy individuals. RQ-RT-PCR of NPM/ALK expression is a promising and rapid approach for monitoring MRD.

  20. FISH技术在儿童ALL常见融合基因检测中的应用价值%Value of fluorescence in situ hybridization in Identification of fusion gene in pediatric cases with acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    徐雪琴; 林小玲; 谢番妮; 郑昭科; 唐少华

    2013-01-01

    Objective:To discuss the role of interphase fluorescence in situ hybridization (I-FISH) in TELAML1 and BCR/ABL fusion gene detection in pediatric cases with acute lymphoblastic leukemia.Methods:Dual color I-FISH and conventional cytogenetic analysis (CCA) were combined to detect t(12;21) TEL/AML1 and t(9;22) BCR/ABL fusion gene in bone marrow mononuclear cells from 35 newly and 4 oddly pediatric ALL patients.Results:Twelve cases were found the TEL/AML1 fusion gene by FISH (30.8%).But no dubious t (12; 21) gene was detected by CCA.Four cases were found the BCR/ABL fusion gene by FISH (10.3%).Only 1 case was found dubious t (9;22) gene by CCA,the incidence was 2.5%.TEL/AML1 fusion gene was more than BCR/ABL fusion gene in pediatric ALL patients and showed lower peripheral tumor load in diagnosis.Conclusion:Dual color IFISH is more sensitive and specific than conventional,cytogenetic analysis (CCA)in the identification of TELAML1 and BCP/ABL fusion gene.So it is playing a significant role in diagnosis and therapy of pediatric cases with acute lymphoblastic leukemia.%目的:探讨双色间期荧光原位杂交(I-FISH)技术在儿童急性淋巴细胞白血病TEL/AML1和BCR/ABL融合基因检测中的应用价值.方法:联合双色间期荧光原位杂交(I-FISH)技术和常规染色体核型分析技术(CCA)对35例儿童初治ALL和4例儿童复发ALL的骨髓有核细胞进行t(12;21) TEL/AML1和t(9;22)BCR/ABL融合基因进行检测.结果:12例患几经FISH检测发现TEL/AML1融合基因,占总病例的30.8%;而CCA检测均未发现有可疑t(12;21).4例患儿经FISH检测发现BCR/ABL融合基因,占总病例的10.3%;而CCA检测发现1例可疑t(9;22),占总病例的2.5%.TEL/AML1在儿童ALL中阳性率较BCR/ABL高,该融合基因阳性的患儿病情较轻.结论:FISH技术较常规染色体核型分析技术特异性强、敏感度高,可以有效检测出TEL/AML1和BCR/ABL融合基因,从而为儿童ALL的诊断和个体化治疗方案提供重要的依据.

  1. Fusion Machinery

    DEFF Research Database (Denmark)

    Sørensen, Jakob Balslev; Milosevic, Ira

    2015-01-01

    the vesicular SNARE VAMP2/synaptobrevin-2 and the target (plasma membrane) SNAREs SNAP25 and syntaxin-1 results in fusion and release of neurotransmitter, synchronized to the electrical activity of the cell by calcium influx and binding to synaptotagmin. Formation of the SNARE complex is tightly regulated...... and appears to start with syntaxin-1 bound to an SM (Sec1/Munc18-like) protein. Proteins of the Munc13-family are responsible for opening up syntaxin and allowing sequential binding of SNAP-25 and VAMP2/synaptobrevin-2. N- to C-terminal “zippering” of the SNARE domains leads to membrane fusion...

  2. Saccharomyces cerevisiae nuclear fusion requires prior activation by alpha factor.

    OpenAIRE

    Rose, M D; Price, B R; Fink, G. R.

    1986-01-01

    We have developed a protocol for efficient fusion of spheroplasts of the same mating type. Nuclear fusion in this whole-cell system is also efficient and closely parallels nuclear fusion in heterosexual mating of intact cells. In the spheroplast fusion system, nuclear fusion is dependent on both the KAR1 gene and prior exposure to alpha factor. The major products of nuclear fusion in the spheroplast fusion assay were true diploids that were homozygous at the mating-type locus. An additional 1...

  3. Short fusion

    CERN Multimedia

    2002-01-01

    French and UK researchers are perfecting a particle accelerator technique that could aid the quest for fusion energy or make X-rays that are safer and produce higher-resolution images. Led by Dr Victor Malka from the Ecole Nationale Superieure des Techniques Avancees in Paris, the team has developed a better way of accelerating electrons over short distances (1 page).

  4. Magnetic fusion

    International Nuclear Information System (INIS)

    This document is a detailed lecture on thermonuclear fusion. The basic physics principles are recalled and the technological choices that have led to tokamaks or stellarators are exposed. Different aspects concerning thermonuclear reactors such as safety, economy and feasibility are discussed. Tore-supra is described in details as well as the ITER project

  5. Clinical application of anterior cervical subtotal corpectomy and fusion with n-HA/PA66 composite artificial vertebral body for cervical spondylosis%纳米羟基磷灰石/聚酰胺66复合人工椎体在颈椎病前路椎体次全切除术中的临床应用

    Institute of Scientific and Technical Information of China (English)

    张文志; 王潇; 段丽群; 尚希福; 许翔; 胡业丰; 姚刚

    2012-01-01

    目的 探讨纳米羟基磷灰石/聚酰胺66(n-HA/PA66)复合人工椎体在颈椎前路次全切除术中应用的短中期临床疗效.方法 自2008年5月~2009年6月对44例脊髓型颈椎病行前路椎体次全切除、椎管减压、n-HA/PA66复合人工椎体植骨融合+钢板内固定术治疗,以JOA评分改善率评价神经功能恢复情况,并依据X线片判断椎间稳定性和融合情况.结果 本组无术中并发症,伤口均一期愈合.患者获随访12~26个月,平均18个月,症状均明显改善,JOA评分由术前(6.4±1.8)分提高到术后(15.2±1.5)分,JOA改善率83.0%,优良率86.4%,问卷调查满意度97.6%.X线检查证实无人工椎体移位、下沉,融合率100%.结论 n-HA/PA66复合人工椎体具有良好的生物相容性及安全性,是一种较理想的骨移植材料,适用于颈椎病前路次全切除术中.%Objective To evaluate the short and mid-term clinical effect of anterior cervical subtotal corpectomy and fusion with n-HA/PA66 composite artificial vertebral body for cervical spondylosis. Methods From may 2008 to June 2009, 44 patients with cervical spondylosis received anterior cervical subtotal corpectomy,spinal canal decompression and reconstruction by n-HA/PA66 composite artificial vertebral body combined with plate instrumentation. Neurological function was assessed by improvement rate of JOA score, and roentgenograms was analyzed to identify the stability of the fused level. Results In all patients, no complications occurred during operation. Wounds were normally healed without acute or chronic infection. All patients were followed up for 12 to 26 months, with an average of 18 months. Preoperative symptoms were all improved in patients, the mean JOA scores was (6.4±1.8) preoperatively and improved to (15.2±1.5) at final follow-up, JOA improvement rate was 83.0%, the excellent and good rate was 85.7%, patients of 97.6% were satisfied with this procedure. The X-ray films demonstrated that no

  6. LDL receptor-GFP fusion proteins: new tools for the characterization of disease-causing mutations in the LDL receptor gene

    DEFF Research Database (Denmark)

    Holst, Henrik Uffe; Dagnæs-Hansen, Frederik; Corydon, Thomas Juhl;

    2001-01-01

    The function of a series of LDL receptor GFP fusion proteins with different, flexible, unstructured spacer regions was analysed. An optimised version of the fusion protein was used to analyse the effect of a LDL receptor mutation (W556S) found in FH patients and characterized as transport defective....... In cultured liver cells this mutation was found to inhibit the transport of LDL receptor GFP fusion protein to the cell surface, thus leading to impaired internalisation of fluorescent labelled LDL. Co-locallisation studies confirmed the retention of the mutant protein in the endoplasmic reticulum....

  7. Magnetic fusion; La fusion magnetique

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-07-01

    This document is a detailed lecture on thermonuclear fusion. The basic physics principles are recalled and the technological choices that have led to tokamaks or stellarators are exposed. Different aspects concerning thermonuclear reactors such as safety, economy and feasibility are discussed. Tore-supra is described in details as well as the ITER project.

  8. 人源载体介导的minidystrophin-EGFP融合基因在Cos-7细胞中的表达%A minidystrophin-EGFP fusion gene expressed in Cos-7 cells mediated by human source vector

    Institute of Scientific and Technical Information of China (English)

    梁羽; 梁德生; 薛志刚; 龙志高; 邬玲仟; 潘乾; 胡艺俏; 戴和平; 夏昆; 夏家辉

    2005-01-01

    目的构建微小肌营养不良蛋白(minidystrophin)和增强绿色荧光蛋白(enhanced green fluoresce protein, EGFP)融合基因的人源载体,观察该载体在Cos-7细胞中的表达.方法以正常人肌营养不良基因cDNA(GenBank NM004006)为模板,通过PCR克隆的方法构建minidystrophin基因,融合EGFP基因后连接到人源载体pHrneo,大量提取重组质粒,转染Cos-7细胞,通过逆转录聚合酶链反应、荧光显微镜观察等方法检测该载体在细胞内的表达.结果成功构建pHrnDysG载体,转染Cos-7后,逆转录聚合酶链反应可扩增出735 bp特异条带,荧光显微镜观察可见表达蛋白分布于细胞膜上.结论 pHrn载体介导的minidystrophin基因可以在真核细胞表达,并被有效地转运至细胞膜,可望用于杜氏肌营养不良基因治疗的研究.%Objective To construct a human source vector containing minidystrophin-EGFP fusion gene and investigate its expression in Cos-7 cells. Methods The recombinant human source vector named pHrnDysG was constructed with PCR-clone methods. Three fragments of dystrophin gene were PCR amplified from normal human dystrophin gene cDNA (GenBank NM04006). These three fragments were ligated to generate a minidystrophin gene. The enhanced green fluorescent protein (EGFP) gene was fused to the C terminal of the minidystrophin gene, and then the pHrnDysG was finally obtained by cloning the fusion gene to pHrneo. Fluorescence microscope and RT-PCR were used to detect the expression of minidystrophin-EGFP fusion gene after the recombinant construct was transfected into Cos-7 cells by lipofectamine. Results Restrictive enzyme digestion analysis and sequencing confirmed that pHrnDysG vector was constructed successfully. After the recombinant pHrnDysG was transfected to Cos-7 cells, RT-PCR demonstrated that the fusion gene was successfully transcribed, and the green fluorescence was observed at the cell membrane. Conclusion The minidystrophin-EGFP fusion gene

  9. Tame Fusion

    Institute of Scientific and Technical Information of China (English)

    S.D. Scott

    2003-01-01

    The first section of this paper covers preliminaries. Essentially, the next four cover units. It is shown that a compatible nearring with DCCR is Nnilpotent if and only if every maximal right N-subgroup is a right ideal. The last five sections relate to fusion (I.e., N-groups minimal for being generated by Nsubgroups, where each is N-isomorphic to a given N-group). Right N-subgroups of a tame nearring N with DCCR, minimal for not annihilating a minimal ideal from the left, are self monogenic and N-isomorphic. That this holds for any collection of minimal ideals is significant. Here, the right N-subgroup involved is a 'fusion product' of the 'components'.

  10. Fusion rules of equivariantizations of fusion categories

    OpenAIRE

    Burciu, Sebastian; Natale, Sonia

    2012-01-01

    We determine the fusion rules of the equivariantization of a fusion category $\\mathcal{C}$ under the action of a finite group $G$ in terms of the fusion rules of $\\mathcal{C}$ and group-theoretical data associated to the group action. As an application we obtain a formula for the fusion rules in an equivariantization of a pointed fusion category in terms of group-theoretical data. This entails a description of the fusion rules in any braided group-theoretical fusion category.

  11. Cold Fusion

    OpenAIRE

    Zhang, Chu; Yue, Manyu; Yu, Huanzhang; Chen, Cheng

    2006-01-01

    Science can often result in technologies which can solve energy problems in societies. On March 23, 1989, two scientists Stanley Pons and Martin Fleischmann claimed at a press conference that they had been able to perform nuclear fusion at room temperature. Their claim was quickly investigated and checked by many scientists around the world. Their discovery generated a heated debate in the scientific literature and magazines in the next few years, and their work was criticized for being unsci...

  12. Carpal Fusion

    OpenAIRE

    Jalal Jalalshokouhi; Mohammad Hossein Herischi; Shahyar Pashaei; Ali Akbar Ameri

    2012-01-01

    Carpal fusion may be seen in hereditary and nonhereditary conditions such as acrocallosal syndrome,acromegaly, Apert syndrome, arthrogryposis, Carpenter syndrome, chromosomal abnormalities, ectrodactyly-ectodermal dysplasia-cleft (EEC) syndrome, the F form of acropectorovertebral dysgenesis or the F syndrome, fetal alcohol syndrome, Holt-Oram syndrome, Leopard syndrome, multiple synostosis syndrome, oligosyndactyly syndrome, Pfeiffer-like syndrome, scleroderma, split hand and foot malformatio...

  13. Artificial Economy

    Directory of Open Access Journals (Sweden)

    Alexandru JIVAN

    2011-08-01

    Full Text Available This paper proposes to eliminate, a routine in the economic thinking, claimed to be responsible for the negative essence of economic developments, from the point of view, of the ecological implications (employment in the planetary ecosystem. The methodological foundations start from the natural origins of the functionality of the human economic society according to the originary physiocrat liberalism, and from specific natural characteristics of the humankind. This paper begins with a comment-analysis of the difference between natural and artificial within the economy, and then explains some of the most serious diversions from the natural essence of economic liberalism. It shall be explained the original (heterodox interpretation of the Classical political economy (economics, by making calls to the Romanian economic thinking from aggravating past century. Highlighting the destructive impact of the economy - which, under the invoked doctrines, we call unnatural - allows an intuitive presentation of a logical extension of Marshall's market price, based on previous research. Besides the doctrinal arguments presented, the economic realities inventoried along the way (major deficiencies and effects, determined demonstrate the validity of the hypothesis of the unnatural character and therefore necessarily to be corrected, of the concept and of the mechanisms of the current economy.The results of this paper consist of original heterodox methodspresented, intuitive or developed that can be found conclusively within the key proposals for education and regulation.

  14. Next Level of Data Fusion for Human Face Recognition

    CERN Document Server

    Bhowmik, Mrinal Kanti; Bhattacharjee, Debotosh; Basu, Dipak Kumar; Nasipuri, Mita

    2011-01-01

    This paper demonstrates two different fusion techniques at two different levels of a human face recognition process. The first one is called data fusion at lower level and the second one is the decision fusion towards the end of the recognition process. At first a data fusion is applied on visual and corresponding thermal images to generate fused image. Data fusion is implemented in the wavelet domain after decomposing the images through Daubechies wavelet coefficients (db2). During the data fusion maximum of approximate and other three details coefficients are merged together. After that Principle Component Analysis (PCA) is applied over the fused coefficients and finally two different artificial neural networks namely Multilayer Perceptron(MLP) and Radial Basis Function(RBF) networks have been used separately to classify the images. After that, for decision fusion based decisions from both the classifiers are combined together using Bayesian formulation. For experiments, IRIS thermal/visible Face Database h...

  15. Application of data fusion in computer facial recognition

    Directory of Open Access Journals (Sweden)

    Wang Ai Qiang

    2013-11-01

    Full Text Available The recognition rate of single recognition method is inefficiency in computer facial recognition. We proposed a new confluent facial recognition method using data fusion technology, a variety of recognition algorithm are combined to form the fusion-based face recognition system to improve the recognition rate in many ways. Data fusion considers three levels of data fusion, feature level fusion and decision level fusion. And the data layer uses a simple weighted average algorithm, which is easy to implement. Artificial neural network algorithm was selected in feature layer and fuzzy reasoning algorithm was used in decision layer. Finally, we compared with the BP neural network algorithm in the MATLAB experimental platform. The result shows that the recognition rate has been greatly improved after adopting data fusion technology in computer facial recognition.

  16. KIF5B-RET fusion gene and non-small cell lung cancer%KIF5B-RET融合基因与非小细胞肺癌

    Institute of Scientific and Technical Information of China (English)

    韩英; 成志勇

    2013-01-01

    Lung cancer is the leading cause of mortality in cancer worldwide. Molecular targeted therapy is the hotpot of lung cancer study in recent years. In 2012, a novel fusion gene KIF5B-RET was identified in non-small cell lung cancer. This fusion gene is more frequently detected in the lung adenocarcinoma, with no or little history of cigarette smoking. The mutually exclusive nature of the RET fusions and other oncogenic alterations such as EGFR,K-Ras,ALK,etc. .suggests that the KIF5B-RET fusion is a new driver mutation. It could be a promising molecular target for the personalized diagnosis and treatment of non-small cell lung cancer.%肺癌是全世界范围死亡率最高的肿瘤.近年来,靶向治疗成为肺癌研究的热点.2012年研究发现肺癌中存在一种新的融合基因KIF5B-RET,其阳性患者多为不吸烟或很少吸烟的腺癌患者.其存在与其他已知的基因改变如EGFR、K-Ras、ALK等相互排斥,提示KIF5B-RET是一种新的致癌驱动突变,有可能成为非小细胞肺癌个体化诊断与治疗的一个分子靶点.

  17. Artifically inserting a reticuloendotheliosis virus long terminal repeat into a bacterial artificial chromosome clone of Marek's disease virus (MDV) alters expression of nearby MDV genes

    Science.gov (United States)

    The long terminal repeat (LTR) sequence of reticuloendotheliosis virus (REV) was inserted into the very virulent Marek’s disease virus (MDV) Md5 bacterial artificial chromosome clone. The insertion site was nearly identical to the REV LTR that was naturally inserted into the JM/102W strain of MDV fo...

  18. Discover颈人工椎间盘置换术联合颈椎前路减压融合术治疗颈椎病的临床疗效%The clinic effect of discover cervical artificial disc replacement combined with anterior cervical decompression and fusion in treatment of cervical spondylosis

    Institute of Scientific and Technical Information of China (English)

    吴兴林

    2014-01-01

    Objective To explore the clinic effect of discover cervical artificial disc replacement combined with anterior cervical decompression and fusion in treatment of cervical spondylosis. Methods 96 patients were selected from our hospital,and the they were evenly divied into two group by random,experimental group patients were treated with discover cervical artificial disc replacement combined with anterior cervical decompression,the control group patients were treated with anterior cervical decompression and fusion.Compared and analyzed the two groups'cervical spine,the average hospital stay,postoperative cervical fixation time,normal activity recovery time and clinical effect after treatment. Results The experimental group's cervical average activity was (44.6±4.7) degree which was higher than control group,and the difference was significantly(P < 0.05);The experimental group was shorter than control group in average hospital stay,postoperative cervical fixation time,normal activity recovery time,and the difference was significantly(P < 0.05);Experimental group's total effective rate was 97.9% which was higher than the control group(87.5%),and the difference was significantly(P<0.05). Conclusion Discover cervical artificial disc replacement combined with anterior cervical decompression and fusion can reduce the average hospital stay,postoperative cervical fixation time,normal activity recovery time,can ensure the patients's cervical average activity to recover normal,and can improve the clinical effect.%目的:探讨分析Discover颈人工椎间盘置换术联合颈椎前路减压融合术的临床疗效。方法选择我院96例患者,将其随机均分为两组,实验组行Discover颈人工椎间盘置换术联和颈椎前路减压融合术治疗;对照组行颈椎前路减压融合术治疗,比较患者术后颈椎活动度、平均住院时间、术后颈椎固定时间、恢复正常活动时间以及患者临床疗效,并进行统计学分析。

  19. Cloning and expression of truncated HBcAg gene,whole-length HBcAg gene and HBc-HBsAg fusion gene in vitro%截短序列和全序列HBcAg基因以及HBV C-S融合基因的克隆与表达

    Institute of Scientific and Technical Information of China (English)

    朱翔; 路文明; 丁宁玲; 叶建中; 王锋; 沙莉; 李扬; 高胜兰

    2015-01-01

    目的:构建截短序列和全序列HBcAg基因和HBc-HBsAg融合基因原核表达质粒,研究目的蛋白在大肠杆菌中的表达及其免疫原性。方法利用HBV全基因(adr亚型)质粒pUCmT-HBV分别扩增HBsAg截短基因、HBcAg截短基因和HBcAg全基因,构建成重组质粒pSK-HBs、pSK-HBc和pKS-HBV C,经DNA序列测定鉴定后,分别将HBcAg截短基因、HBcAg全基因及HBc-HBsAg融合基因亚克隆至表达质粒PET-30a,在大肠杆菌BL21(DE3)中进行表达HBcAg截短基因、HBcAg全基因和HBc-HBsAg融合基因产物,采用PAGE-SDS和免疫印迹法对表达产物进行鉴定。结果成功构建了含HBcAg截短基因、HBcAg全基因和HBc-HBsAg融合基因的原核表达质粒;成功构建的质粒在大肠杆菌BL21(DE3)中能大量表达HBcAg蛋白和HBc-HBsAg融合蛋白,免疫印迹分析结果显示表达产物具有免疫原性。结论成功构建的原核表达载体在大肠杆菌BL21(DE3)中能顺利表达HBcAg蛋白和HBc-HBsAg融合蛋白,表达产物具有免疫原性,为慢性乙型肝炎特异性免疫治疗研究提供了实验基础。%Objective To construct the prokaryotic recombinant plasmids carring truncated HBcAg gene, whole-length HBcAg gene and HBc-HBsAg fusion gene,and to observe the expression of target proteins in E.coli and their immunogenicity in vitro. Methods Truncated HBcAg gene,whole-length HBcAg gene and HBc-HBsAg fusion gene were obtained from plasmid pUCmT-HBV containing whole-length HBV gene (subtype adr)and con-struct recombinant plasmids of pSK-HBs,pSK-HBc and pKS-HBV C. Truncated HBcAg gene,whole-length HBcAg gene and HBc-HBsAg fusion gene which were obtained by fusing truncated HBsAg and truncated HBcAg gene,were subcloned into a expression vector pET-30a respectively after confirmed by DNA sequencing. The gene products were expressed in E.coli BL21 (DE3) and identified by SDS-PAGE and Western blot. Results The prokaryotic expression plasmids

  20. 人工椎间盘置换加颈前路椎体次全切减压植骨融合术治疗多节段颈椎病%Artificial Disc Replacement Combined with Anterior Cervical Decompression and Autograft Bone Fusion for the Treatment of Multi-segment Cervical Spondylosis

    Institute of Scientific and Technical Information of China (English)

    廖维峰; 肖晟; 黄象望; 刘向阳; 张毅; 向铁城

    2014-01-01

    [目的]探讨人工椎间盘置换加颈前路椎体次全切减压植骨融合术治疗多节段颈椎病的临床疗效。[方法]湖南省人民医院2008年2月至2012年6月收治的12例多节段颈椎病手术病例,均行人工椎间盘置换加颈前路椎体次全切减压植骨融合术,随访时间为12~18个月,平均随访15.5个月,均摄术前、术后及末次随访时的颈椎正侧位及颈椎过伸过屈位X线片及磁共振检查,观察植骨融合、内固定及人工椎间盘的情况,以JO A评分评价神经功能改善情况。[结果]所有病例内置物无松动、移位,植骨融合时间在3~6个月,平均4.9个月。置换间隙活动度术后1年时为12.5°±5.0°,与术前(12.3°±4.9°)比较无统计学差异(P>0.05)。术前JOA 评分平均为9.3分,术后6个月时平均为16.1分,平均改善率为91.2%。[结论]人工椎间盘置换加颈前路椎体次全切减压植骨融合术治疗多节段颈椎病近期疗效满意,是治疗多节段颈椎病的一种可行方法。%[Objective]To explore the clinical efficacy of cervical artificial disc replacement combined with anterior cervical decompression and autograft bone fusion for the treatment of multi -segment cervical spon-dylosis .[Methods]Twelve patients with multi- segment cervical spondylosis operated in Hunan provincial people's hospital from Feb .2008 to June 2012 underwent cervical artificial disc replacement combined with an-terior cervical decompression and autograft bone fusion .The follow up time was 12~18 months(average 15 .5 months) .Cervical MRI and X-ray films of cervical normal lateral position ,hyperextension and hyperflexion position were performed before and after operation and at the last time of follow up .Bone fusion ,internal fixa-tion and artificial disc were observed .JOA score was used to evaluate the improvement of neurological func-tion .[Results]No loosening and displacement of

  1. Seismic data fusion anomaly detection

    Science.gov (United States)

    Harrity, Kyle; Blasch, Erik; Alford, Mark; Ezekiel, Soundararajan; Ferris, David

    2014-06-01

    Detecting anomalies in non-stationary signals has valuable applications in many fields including medicine and meteorology. These include uses such as identifying possible heart conditions from an Electrocardiography (ECG) signals or predicting earthquakes via seismographic data. Over the many choices of anomaly detection algorithms, it is important to compare possible methods. In this paper, we examine and compare two approaches to anomaly detection and see how data fusion methods may improve performance. The first approach involves using an artificial neural network (ANN) to detect anomalies in a wavelet de-noised signal. The other method uses a perspective neural network (PNN) to analyze an arbitrary number of "perspectives" or transformations of the observed signal for anomalies. Possible perspectives may include wavelet de-noising, Fourier transform, peak-filtering, etc.. In order to evaluate these techniques via signal fusion metrics, we must apply signal preprocessing techniques such as de-noising methods to the original signal and then use a neural network to find anomalies in the generated signal. From this secondary result it is possible to use data fusion techniques that can be evaluated via existing data fusion metrics for single and multiple perspectives. The result will show which anomaly detection method, according to the metrics, is better suited overall for anomaly detection applications. The method used in this study could be applied to compare other signal processing algorithms.

  2. Multi-slice spiral CT findings of renal cell carcinoma associated with XP11.2 translocation-TFE gene fusion

    International Nuclear Information System (INIS)

    Objective: To investigate the MSCT features of the renal cell carcinoma associated with XP11.2 translocation-TFE gene fusion (XP11.2-TFE Ca). Methods: The MSCT features of XP11.2-TFE Ca in six patients were retrospectively analyzed,which were confirmed by postoperative histopathology. All the tumor features were recorded and compared to the histopathological findings. Variance test analysis was performed to compare the CT values among tumor, normal renal cortex and normal renal medulla.Results XP11.2-TFE Ca appeared as a solitary lesion in all the 6 patients, which limited in the medulla in 3 patients and infiltrated both medulla and renal pelvis in other 3 patients. The tumor diameter ranged from 3.8 to 5.2 cm [mean diameter, (4.2 ± 1.3) cm], And the adjacent renal cortex was compressed or involved. Four lesions were oval, 2 lesions were irregular shape. Tumor capsule showed in all lesions in the six patients. Cystic component and retroperitoneal lymph node metastasis respectively occurred in one patient. In all lesions, calcification was not detected. On unenhanced CT scan phase, the CT values of the normal cortex, normal medulla and XP11.2-TFE Ca were (42 ±5), (38 ±4) and (48 ±4) HU respectively, with no significant statistical difference (F=1.267, P>0.05); on cortical nephrographic phase after contrast injection, they were (174 ± 10), (72 ± 8) and (100 ± 9) HU respectively, with significant statistical difference among the three groups (F=6.588, P<0.01); on parenchymal nephrographic phase,they were (207±12), (109±8) and (121±11) HU respectively, with significant statistical difference (F=7.172, P<0.01); and on the excretory phase,they were (148 ± 12), (67 ±8) and (83 ±7) HU respectively, with significant statistical difference (F=2.678, P<0.05). On each phase of contrast-enhanced MSCT scan,the enhancement of XP11.2-TFE Ca was higher than that of the medulla and lower than that of the cortex. Conclusions: XP11.2-TFE Ca had some characteristic MSCT

  3. Preparation, characterization, and in ovo vaccination of dextran-spermine nanoparticle DNA vaccine coexpressing the fusion and hemagglutinin genes against Newcastle disease

    Directory of Open Access Journals (Sweden)

    Firouzamandi M

    2016-01-01

    to the chickens from lethal viral challenge. In addition, vaccination with pDNA/D-SPM complex did not induce high antibody titer when compared with naked pDNA. Therefore, it was concluded that DNA vaccination with plasmid internal ribosome entry site-HN/F can be suitable for in ovo application against ND, whereas D-SPM is not recommended for in ovo gene delivery. Keywords: Newcastle disease, DNA vaccine, in ovo vaccination, Newcastle disease virus, dextran-spermine nanoparticle, hemagglutinin and fusion

  4. FUSION WORLD

    Institute of Scientific and Technical Information of China (English)

    Caroline; 黄颖(翻译)

    2009-01-01

    Fusion World”科技展示体验中心是英国设计公司MET Studio为新加坡科技研究局(A*Star)的科学工程委员会(SERC)所设计的,位于启汇城的办公地点,用于展示该委员会的精选技术作品,以吸引潜在的客户和启汇城内的学生购买群体。

  5. Carpal Fusion

    Directory of Open Access Journals (Sweden)

    Jalal Jalalshokouhi*

    2012-05-01

    Full Text Available Carpal fusion may be seen in hereditary and nonhereditary conditions such as acrocallosal syndrome,acromegaly, Apert syndrome, arthrogryposis, Carpenter syndrome, chromosomal abnormalities, ectrodactyly-ectodermal dysplasia-cleft (EEC syndrome, the F form of acropectorovertebral dysgenesis or the F syndrome, fetal alcohol syndrome, Holt-Oram syndrome, Leopard syndrome, multiple synostosis syndrome, oligosyndactyly syndrome, Pfeiffer-like syndrome, scleroderma, split hand and foot malformation, Stickler syndrome, thalidomide embryopathy, Turner syndrome and many other conditions as mentioned in Rubinstein-Taybi's book. Sometimes there is no known causative disease.Diagnosis is usually made by plain X-ray during studying a syndrome or congenital disease or could be an incidental finding like our patients. Hand bone anomalies are more common in syndromes or other congenital or non-hereditary conditions, but polydactyly, syndactyly or oligodactyly and carpal fusions are interesting. X-ray is the modality of choice, but MRI and X-ray CT with multiplanar reconstructions may be used for diagnosis.

  6. Catalysed fusion

    CERN Document Server

    Farley, Francis

    2012-01-01

    A sizzling romance and a romp with subatomic particles at CERN. Love, discovery and adventure in the city where nations meet and beams collide. Life in a large laboratory. As always, the challenges are the same. Who leads? Who follows? Who succeeds? Who gets the credit? Who gets the women or the men? Young Jeremy arrives in CERN and joins the quest for green energy. Coping with baffling jargon and manifold dangers, he is distracted by radioactive rats, lovely ladies and an unscrupulous rival. Full of doubts and hesitations, he falls for a dazzling Danish girl, who leads him astray. His brilliant idea leads to a discovery and a new route to cold fusion. But his personal life is scrambled. Does it bring fame or failure? Tragedy or triumph?

  7. 人工全踝关节置换与传统的踝关节融合术治疗踝关节骨关节炎的临床效果对比%Comparison of clinical effects of artificial total ankle replacement and traditional ankle fusion in treating ankle osteoarthritis

    Institute of Scientific and Technical Information of China (English)

    周伟; 黄松; 陈敬有; 李贺伟

    2016-01-01

    Objective To study the clinical effect of artificial total ankle replacement and traditional ankle fusion in the treatment of ankle osteoarthritis .Methods Eighty‐five patients with ankle osteoarthritis in our hospital from January 2012 to December 2015 were selected as the research subjects and randomly divided into observation group and control group .The two groups were respec‐tively treated by conducting the artificial total ankle replacement and traditional ankle fusion .The VAS ,AOFAS ,modified Mazur and McGuire scores before and after operation and therapeutic efficacies were compared between the two groups .Results The post‐operative VAS score in the two groups was significantly decreased ,moreover the VAS score in the observation group was signifi‐cantly lower than that in the control group;the postoperative AOFAS ,modified Mazur and McGuire scores in the two groups were significantly increased ,moreover which in the observation group were significantly higher than those in the control group;the AO‐FAS score excellent rates in the observation group and control group were 93 .33% and 77 .78% respectively ,which in the observa‐tion group was significantly higher than that in the control group ,moreover the differences were statistically significant (P<0 .05) . Conclusion Using the artificial total ankle arthroplasty for treating ankle osteoarthritis has significant advantages in the aspects of reducing pain and improving the ankle function and treatment efficacy .%目的:探究人工全踝关节置换与传统的踝关节融合术治疗踝关节骨关节炎的疗效。方法将2012年1月至2015年12月的85例踝关节骨关节炎患者作为研究对象,将其随机分成观察组与对照组,并分别进行人工全踝关节置换与传统的踝关节融合术治疗,比较两组手术前后的视觉模拟评分法(VAS )评分、美国足踝外科协会踝‐后足评分系统(AOFAS )评分、改良McGuir和Mazur评分以及治

  8. TMPRSS2-ERG gene fusion in metastatic prostate cancers: a study of fine needle aspiration specimens%TMPRSS2-ERG融合基因在转移性前列腺癌中的表达

    Institute of Scientific and Technical Information of China (English)

    肖立; 朱雄增; WANG Yan; GONG Yun; GUO C Charles

    2011-01-01

    目的 检测转移性前列腺癌中TMPRSS2-ERG基因融合的发生率,探讨ERG基因重排在前列腺癌进展中的作用.方法 收集32例由细针穿刺诊断的转移性前列腺癌,穿刺部位包括盆腔及远处淋巴结、肝、骨、甲状腺等,回顾相关临床病理学资料.免疫组织化学采用EnVision法标记前列腺特异性抗原、突触素和嗜铬粒素A.运用ERG分离断裂探针荧光原位杂交(FISH)方法,检测细胞学蜡块中转移性前列腺癌的TMPRSS2-ERG基因融合.结果 患者平均年龄67岁,26例有经治疗的前列腺癌病史,其余6例以转移性病灶为首发症状.11例转移灶形态上提示为前列腺小细胞癌,免疫组织化学突触素(9/9)、嗜铬粒素A(7/8)阳性,前列腺特异性抗原(7/7)阴性.FISH分析显示,共有31.3%(10/32)转移性前列腺癌存在TMPRSS2-ERG基因融合,其中6例为ERG基因5′端缺失性重排;8例ERG基因重排伴拷贝数增加.11例转移性前列腺小细胞癌中,5例显示TMPRSS2-ERG基因融合,3例为5′端缺失性重排伴拷贝数增加.结论 细胞学细针穿刺标本可用于检测TMPRSS2-ERG融合基因状态;转移性前列腺癌常表达多拷贝ERG重排基因;即使发生小细胞癌转变后,仍然保持融合基因状态;TMPRSS2-ERG融合基因可用于区分前列腺来源的小细胞癌.%Objective To investigate diagnostic values of the detection of TMPRSS2-ERG gene fusion in metastatic prostate cancer. Methods A total of 32 fine needle aspiration (FNA) specimens of metastatic prostate carcinomas were retrieved from the pathology files at MD Anderson Cancer Center. The metastatic sites included the pelvic and remote lymph nodes, liver, bone, and thyroid gland. Immunohistochemical staining for PSA, PAP, synaptophysin, chromogranin A was performed. TMPRSS2-ERG gene fusion was evaluated on sections of cell blocks by fluorescence in situ hybridization (FISH) using ERG gene break-apart probes. Results The mean age of the patients was 67

  9. Molecular cytogenetic findings in a three-way novel variant of t(1;8;21)(p35;q22;q22): a unique relocation of the AML1/ETO fusion gene 1p35 in AML-M2.

    Science.gov (United States)

    Ahmad, Firoz; Kokate, Prajakta; Chheda, Pratiksha; Dalvi, Rupa; Das, Bibhu Ranjan; Mandava, Swarna

    2008-01-15

    Acute myeloid leukemia (AML) is a malignant neoplasm of hematopoietic stem cells characterized by an abnormal proliferation of myeloid precursors, a reduced rate of apoptosis, and an arrest in cellular differentiation. The present report deals with the results of hematologic, immunophenotypic, cytogenetic, fluorescence in situ hybridization (FISH), and molecular analyses of a 53-year-old female patient diagnosed with AML-M2. Cytogenetic and FISH analysis revealed a complex translocation involving three chromosomes showing t(1;8;21)(p35;q22;q22). The observation of breakpoints at 8q22 and 21q22 suggests a rearrangement of the ETO and AML1 genes, respectively. Using a dual-color FISH test with ETO and AML1 probes, an AML1/ETO fusion signal on the derivative 1p35 instead of der(8) was demonstrated. To the best of our knowledge, this is the first report about the relocation of the AML1/ETO fusion gene to the 1p35 rather than der(8), suggesting the presence of a novel variant of t(8;21)(q22;q22) in the observed patient. PMID:18206543

  10. Construction and verification of a plant vector carrying an eGfp/Gus fusion reporter gene%eGfp/Gus融合基因植物表达载体的构建和转化验证

    Institute of Scientific and Technical Information of China (English)

    吴学龙; 何海燕; 刘智宏; 黄锐之

    2011-01-01

    绿色荧光蛋白(Gfp)基因和葡萄糖醛酸糖苷酶(Gus)基因是广泛应用的2个报告基因,在定性和定量研究基因表达和启动子功能等方面各有优劣.为联合使用这2个报告基因,根据报告基因序列设计2对带有特异限制性内切酶位点的引物,PCR法分别扩增增强型Gfp(eGfp)和Gus基因,连接到植物表达载体pFGC5941中,构建含CaMV35S启动子驱动的eGfp/Gus基因融合表达载体,命名为pFGC-DR.注射农杆菌法转化烟草叶片,以及花器官农杆菌浸泡法转化拟南芥,发现融合基因成功地在烟草叶片中瞬时表达和在拟南芥中稳定表达,表明融合报告基因在烟草和拟南芥中都能高效表达.%Green fluorescent protein(Gfp) and beta-glucuronidase( Gus) are two widely used reporter genes, which have advantages and disadvantages for qualitative analysis and quantitative determination of gene expression and promoter activity in molecular studies. A vector carrying an enhanced GJp/Gus (eGfp/Gus) dual reporter gene was constructed to establish an efficient and convenient screening system for gene and promoter studies in plants. Primers with specific restriction endonuclease sites were designed according to sequences of the reporter genes. The eGJp and Gus genes were amplified respectively by PCR method. With corresponding endonucleases, the genes and the primary vector pFGC5941 were digested, and then these three fragments were ligated in one reaction to make a final vector. The vector, designated pFGC-DR, is characterized with a strong constitutive promoter CamV35S driving the eGfp/Gus fusion gene. Transient expression in tobacco leaves and transgenic expression studies in Arabidopsis showed that this fusion reporter protein retains functional activity for both eGJp and Gus. These results demonstrated the utility of the eGfp/Gus dual reporter system for studying of plant promoters.

  11. A bacterial artificial chromosome transgenic mouse model for visualization of neurite growth.

    Science.gov (United States)

    Tao, Tao; Chen, Chen; Sun, Jie; Peng, YaJing; Zhu, MinSheng

    2015-04-01

    Class III β-tubulin (Tubb3) is a component of the microtubules in neurons and contributes to microtubule dynamics that are required for axon outgrowth and guidance during neuronal development. We here report a novel bacterial artificial chromosome (BAC) transgenic mouse line that expresses Class III β-tubulin fused to mCherry, an improved monomeric red fluorescent protein, for the visualization of microtubules during neuronal development. A BAC containing Tubb3 gene was modified by insertion of mCherry complementary DNA downstream of Tubb3 coding sequence via homologous recombination. mCherry fusion protein was expressed in the nervous system and testis of the transgenic animal, and the fluorescent signal was observed in the neurons that located in the olfactory bulb, cerebral cortex, hippocampal formation, cerebellum, as well as the retina. Besides, Tubb3-mCherry fusion protein mainly distributed in neurites and colocalized with endogenous Class III β-tubulin. The fusion protein labels Purkinje cell dendrites during cerebellar circuit formation. Therefore, this transgenic line might be a novel tool for scientific community to study neuronal development both in vitro and in vivo.

  12. Trends in Artificial Intelligence.

    Science.gov (United States)

    Hayes, Patrick

    1978-01-01

    Discusses the foundations of artificial intelligence as a science and the types of answers that may be given to the question, "What is intelligence?" The paradigms of artificial intelligence and general systems theory are compared. (Author/VT)

  13. Artificial Inteligence and Law

    OpenAIRE

    Fuková, Kateřina

    2012-01-01

    Submitted diploma work Artificial Intelligence and Law deals with the rule of law and its position in the process of new advanced technologies in computer cybernetics and further scientific disciplines related with artificial intelligence and its creation. The first part of the work introduces the history of the first imagines about artificial intelligence and concerns with its birth. This chapter presents main theoretical knowledge and hypotheses defined artificial intelligence and progre...

  14. Cloning and molecular characterization of a novel lectin gene from Pinellia ternata

    Institute of Scientific and Technical Information of China (English)

    JIAN HONG YAO; XIU YUN ZHAO; ZHI HUA LIAO; JUAN LIN; ZHONG HAI CHEN; FEI CHEN; JUN SONG; XIAO FEN SUN; KE XUAN TANG

    2003-01-01

    The full-length cDNA of Pinellia ternata agglutinin (PTA) was cloned from inflorescences using RACE-PCR. Through comparative analysis of PTA gene (pta) and its deduced amino acid sequence with those of other Araceae species, pta was found to encode a precursor lectin with signal peptide and to have extensive homology with those of other Araceae species. PTA was a heterotetrameric mannose-binding lectin with three mannose-binding boxes like lectins from other Araceae and Amaryllidaceae species. Southern blot analysis of the genomic DNA revealed that pta belonged to a low-copy gene family. Northern blot analysis demonstrated that pta constitutively expressed in various plant tissues including root, leaf, stem and inflorescence. The pta cDNA sequence encoding for mature PTA protein was cloned into pET-32a plasmid and the resulting plasmid, pET-32a-PTA containing Trx-PTA fusion protein, was investigated for the expression in E. coli BL21. SDS-PAGE gel analysis showed that the Trx-PTA fusion protein was successfully expressed in E. coli BL21 when induced by IPTG. Artificial diet assay revealed that PTA fusion protein had significant levels of resistance against peach potato aphids when incorporated into artificial diet at 0.1% (w/v). The cloning of the pta gene will enable us to further test its effect in depth on aphids by transferring the gene into crop plants.

  15. Fusion energy

    International Nuclear Information System (INIS)

    The main purpose of the International Thermonuclear Experimental Reactor (ITER) is to develop an experimental fusion reactor through the united efforts of many technologically advanced countries. The ITER terms of reference, issued jointly by the European Community, Japan, the USSR, and the United States, call for an integrated international design activity and constitute the basis of current activities. Joint work on ITER is carried out under the auspices of the International Atomic Energy Agency (IAEA), according to the terms of quadripartite agreement reached between the European Community, Japan, the USSR, and the United States. The site for joint technical work sessions is at the MaxPlanck Institute of Plasma Physics. Garching, Federal Republic of Germany. The ITER activities have two phases: a definition phase performed in 1988 and the present design phase (1989--1990). During the definition phase, a set of ITER technical characteristics and supporting research and development (R ampersand D) activities were developed and reported. The present conceptual design phase of ITER lasts until the end of 1990. The objectives of this phase are to develop the design of ITER, perform a safety and environmental analysis, develop site requirements, define future R ampersand D needs, and estimate cost, manpower, and schedule for construction and operation. A final report will be submitted at the end of 1990. This paper summarizes progress in the ITER program during the 1989 design phase

  16. Bacterial Artificial Chromosome Mutagenesis Using Recombineering

    OpenAIRE

    Kumaran Narayanan; Qingwen Chen

    2011-01-01

    Gene expression from bacterial artificial chromosome (BAC) clones has been demonstrated to facilitate physiologically relevant levels compared to viral and nonviral cDNA vectors. BACs are large enough to transfer intact genes in their native chromosomal setting together with flanking regulatory elements to provide all the signals for correct spatiotemporal gene expression. Until recently, the use of BACs for functional studies has been limited because their large size has inherently presented...

  17. Bemerkungen zur "kalten Fusion"

    CERN Document Server

    Kuehne, R W

    2006-01-01

    Steven Jones et al. reported to have observed nuclear fusion at room temperature. They observed this "cold fusion" by electrolyzing heavy water. Later experiments confirmed these observations. These experiments confirmed the generation of strong electric fields within the deuterided metals. These electric fields accelerate the deuterons to keV energies and allow the observed nuclear fusion. Roman Sioda and I suggested a theoretical description of this nuclear fusion. Our "extended micro hot fusion" scenario explains how nuclear fusion can be generated over a long time within deuterided metals. Moreover we predicted the explosion of large pieces of deuterided metals. This article reviews the "cold fusion" work of Steven Jones et al. and discusses the fracto-fusion scenario. I show that the extended micro hot fusion scenario can explain the observed neutron emissions, neutron bursts, and heat bursts.

  18. Artificial synthesis and cloning of human obese gene%人肥胖(obese)基因的人工合成及克隆

    Institute of Scientific and Technical Information of China (English)

    杨林; 吴无畏

    2000-01-01

    根据人肥胖基因的cDNA序列,通过合理的引物设计、链延伸反应、PCR反应以及分子克隆等步骤,成功地合成出编码瘦蛋白(Leptin)的肥胖基因(ob基因)全长片段,并将其克隆至pUC18载体质粒上.序列分析和酶切鉴定显示肥胖基因得到了正确合成和克隆.%According to the known sequence of human ob gene cDNA,the gene coding the leptin was synthesized and cloned into pUC18 vector after reasonable primer designing,DNA strain extending,PCR reaction and molecular cloning.Sequence analysis and RE digest results showed the ob gene was synthesized and cloned correctly.

  19. Review of fusion synfuels

    International Nuclear Information System (INIS)

    Thermonuclear fusion offers an inexhaustible source of energy for the production of hydrogen from water. Depending on design, electric generation efficiencies of approx. 40 to 60% and hydrogen production efficiencies by high-temperature electrolysis of approx. 50 to 65% are projected for fusion reactors using high-temperatures blankets. Fusion/coal symbiotic systems appear economically promising for the first generation of commercial fusion synfuels plants. Coal production requirements and the environmental effects of large-scale coal usage would be greatly reduced by a fusion/coal system. In the long term, there could be a gradual transition to an inexhaustible energy system based solely on fusion

  20. Artificial neural network-based exploration of gene-nutrient interactions in folate and xenobiotic metabolic pathways that modulate susceptibility to breast cancer.

    Science.gov (United States)

    Naushad, Shaik Mohammad; Ramaiah, M Janaki; Pavithrakumari, Manickam; Jayapriya, Jaganathan; Hussain, Tajamul; Alrokayan, Salman A; Gottumukkala, Suryanarayana Raju; Digumarti, Raghunadharao; Kutala, Vijay Kumar

    2016-04-15

    In the current study, an artificial neural network (ANN)-based breast cancer prediction model was developed from the data of folate and xenobiotic pathway genetic polymorphisms along with the nutritional and demographic variables to investigate how micronutrients modulate susceptibility to breast cancer. The developed ANN model explained 94.2% variability in breast cancer prediction. Fixed effect models of folate (400 μg/day) and B12 (6 μg/day) showed 33.3% and 11.3% risk reduction, respectively. Multifactor dimensionality reduction analysis showed the following interactions in responders to folate: RFC1 G80A × MTHFR C677T (primary), COMT H108L × CYP1A1 m2 (secondary), MTR A2756G (tertiary). The interactions among responders to B12 were RFC1G80A × cSHMT C1420T and CYP1A1 m2 × CYP1A1 m4. ANN simulations revealed that increased folate might restore ER and PR expression and reduce the promoter CpG island methylation of extra cellular superoxide dismutase and BRCA1. Dietary intake of folate appears to confer protection against breast cancer through its modulating effects on ER and PR expression and methylation of EC-SOD and BRCA1. PMID:26784656

  1. Nucleotide sequence of a region of the herpes simplex virus type 1 gB glycoprotein gene: mutations affecting rate of virus entry and cell fusion.

    Science.gov (United States)

    Bzik, D J; Fox, B A; DeLuca, N A; Person, S

    1984-08-01

    The tsB5 isolate of herpes simplex virus type I (HSV-1) enters host cells more rapidly than does KOS, an independent isolate of HSV-1, and this rate-of-entry determinant is located between prototypic map coordinates 0.350 and 0.360 (1). The nucleotide sequence of strain tsB5 has now been determined between prototypic map coordinates 0.347 and 0.360. Comparison of the tsB5 sequence to the homologous KOS sequence revealed that the rate-of-entry difference between these two HSV-1 strains may be due to the single amino acid difference observed within these sequences (0.350 to 0.360). A cell fusion determinant in tsB5 is located between coordinates 0.345 and 0.355 and to the left of the rate-of-entry determinant (1). Nucleotide sequence analysis revealed a second amino acid difference between tsB5 and KOS at coordinate 0.349. The cell fusion determinant was tentatively assigned to this location. PMID:6089415

  2. Responses of Endoplasmic Reticulum Stress-Related Genes in Maize Embryo to Artificial Aging Treatment%玉米种胚内质网胁迫相关基因对人工老化处理的响应

    Institute of Scientific and Technical Information of China (English)

    曹广灿; 林一欣; 薛梅真; 邢芦蔓; 吕伟增; 杨伟飞; 陈军营

    2016-01-01

    [Objective] Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are involved in plant responses to environmental stresses. However, the expression of ER stress-related genes during maize seed aging has not been reported. In this study, the expression of ER stress-related genes during maize seed aging was investigated by Digital Gene Expression Profile (DGE) to provide theoretical support for clarifying the molecular mechanism of seed deterioration.[Method] Hybrid maize (Zea mays L.) cultivar Zhengdan 958 seeds were used as experimental material and treated by artificial aging treatment (45℃, 100% relative humidity). DGE analysis was carried out on the Illumina Hiseq 2000 platform using total RNA extracted from 3 d artificial aging treatment and the untreated embryos (CK) of maize seeds. The reads with adaptor and ambiguous sequences, and the low-quality reads were filtered out to obtain the high quality clean reads. Clean reads were mapped to the maize reference genome and genes database using SOAPaligner/SOAP2. The gene expression level was calculated by the RPKM (Reads Per kb per million reads) method. A combination of FDR<0.001 and the absolute value of |log2 ratio (T/CK)|≥1 was used as the threshold to determine the significance of gene expression difference. All differentially expressed genes (DEGs) were assigned to the pathways in KEGG (Kyoto Encyclopedia of Genes and Genomes) database and searched for the differentially expressed genes related to ER stress. Quantitative real-time PCR was performed to analyze the expression patterns of ER stress-related genes in the different artificial aging times.[Result] Analysis of the DEG revealed that 104 DEGs were relevant to the protein processing in ER during the process of artificial aging treatment. A total of 97 DEGs related to ER stress including 81 and 16 genes respectively up- and down-regulated were screened out. The expression levels of ER stress markerBiP gene, as well as ER chaperones

  3. 玉米种胚内质网胁迫相关基因对人工老化处理的响应%Responses of Endoplasmic Reticulum Stress-Related Genes in Maize Embryo to Artificial Aging Treatment

    Institute of Scientific and Technical Information of China (English)

    曹广灿; 林一欣; 薛梅真; 邢芦蔓; 吕伟增; 杨伟飞; 陈军营

    2016-01-01

    ERAD)途径的有83个差异表达基因(70个上调,13个下调),其中启动ERAD途径的关键酶基因EDEM(ER degradation enhancing mannosidase I-like protein)下调,参与蛋白泛素化的E2泛素结合酶基因UbcH5、E3泛素连接酶基因Hrd1和Doa10等也发生显著的表达变化。qRT-PCR结果表明,内质网胁迫相关基因在不同人工老化时间内表现表达多样性和复杂性。【结论】人工老化处理能造成玉米种胚细胞发生内质网胁迫。细胞通过上调分子伴侣基因表达和诱导ERAD途径响应内质网胁迫,但ERAD途径受阻可能引起错误折叠蛋白聚集,从而进一步加剧细胞损伤,最终导致种子活力降低甚至丧失。%[Objective] Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are involved in plant responses to environmental stresses. However, the expression of ER stress-related genes during maize seed aging has not been reported. In this study, the expression of ER stress-related genes during maize seed aging was investigated by Digital Gene Expression Profile (DGE) to provide theoretical support for clarifying the molecular mechanism of seed deterioration.[Method] Hybrid maize (Zea mays L.) cultivar Zhengdan 958 seeds were used as experimental material and treated by artificial aging treatment (45℃, 100% relative humidity). DGE analysis was carried out on the Illumina Hiseq 2000 platform using total RNA extracted from 3 d artificial aging treatment and the untreated embryos (CK) of maize seeds. The reads with adaptor and ambiguous sequences, and the low-quality reads were filtered out to obtain the high quality clean reads. Clean reads were mapped to the maize reference genome and genes database using SOAPaligner/SOAP2. The gene expression level was calculated by the RPKM (Reads Per kb per million reads) method. A combination of FDR<0.001 and the absolute value of |log2 ratio (T/CK)|≥1 was used as the threshold to determine the

  4. Promoter hypermethylation of the retinoic acid receptor beta2 gene is frequent in acute myeloid leukaemia and associated with the presence of CBFβ-MYH11 fusion transcripts

    DEFF Research Database (Denmark)

    Rethmeier, Anita; Aggerholm, Anni; Olesen, Lene Hyldahl;

    2006-01-01

    was unmethylated in 10/10 bone marrow and 7/7 blood samples from healthy individuals, the gene was hypermethylated in 43% of the AML patients. The RARbeta2 degree of promoter methylation differed between and within individuals, and the mRNA transcription levels of the gene varied inter-individually by a factor...

  5. Development and Evolution of Neural Networks in an Artificial Chemistry

    OpenAIRE

    Astor, Jens C.; Adami, Christoph

    1998-01-01

    We present a model of decentralized growth for Artificial Neural Networks (ANNs) inspired by the development and the physiology of real nervous systems. In this model, each individual artificial neuron is an autonomous unit whose behavior is determined only by the genetic information it harbors and local concentrations of substrates modeled by a simple artificial chemistry. Gene expression is manifested as axon and dendrite growth, cell division and differentiation, substrate production and c...

  6. Fusion Canada issue 23

    International Nuclear Information System (INIS)

    A short bulletin from the National Fusion Program highlighting in this issue TdeV tokamak updates, fusion research in Korea, CCFM program review, TdeV divertor plasma, and CFFTP program review. 4 figs

  7. Fusion Canada issue 20

    International Nuclear Information System (INIS)

    Fusion Canada's publication of the National Fusion Program. Included in this issue is the CFFTP Industrial Impact Study, CCFM/TdeV Update:helium pumping, research funds, and deuterium in beryllium - high temperature behaviour. 3 figs

  8. Anticipatory Artificial Autopoiesis

    OpenAIRE

    DuBois, Daniel; Holmberg, Stig C.

    2010-01-01

    In examining relationships between autopoiesis and anticipation in artificial life (Alife) systems it is demonstrated that anticipation may increase efficiency and viability in artificial autopoietic living systems. This paper, firstly, gives a review of the Varela et al [1974] automata algorithm of an autopoietic living cell. Some problems in this algorithm must be corrected. Secondly, a new and original anticipatory artificial autopoiesis algorithm for automata is presented. ...

  9. Inteligencia artificial en vehiculo

    OpenAIRE

    Amador Díaz, Pedro

    2012-01-01

    Desarrollo de un robot seguidor de líneas, en el que se implementan diversas soluciones de las áreas de sistemas embebidos e inteligencia artificial. Desenvolupament d'un robot seguidor de línies, en el qual s'implementen diverses solucions de les àrees de sistemes encastats i intel·ligència artificial. Follower robot development of lines, in which various solutions are implemented in the areas of artificial intelligence embedded systems.

  10. Artificial cognition architectures

    CERN Document Server

    Crowder, James A; Friess, Shelli A

    2013-01-01

    The goal of this book is to establish the foundation, principles, theory, and concepts that are the backbone of real, autonomous Artificial Intelligence. Presented here are some basic human intelligence concepts framed for Artificial Intelligence systems. These include concepts like Metacognition and Metamemory, along with architectural constructs for Artificial Intelligence versions of human brain functions like the prefrontal cortex. Also presented are possible hardware and software architectures that lend themselves to learning, reasoning, and self-evolution

  11. Combining Heavy Ion Radiation and Artificial MicroRNAs to Target the Homologous Recombination Repair Gene Efficiently Kills Human Tumor Cells

    International Nuclear Information System (INIS)

    Purpose: Previously, we demonstrated that heavy ions kill more cells at the same dose than X-rays because DNA-clustered lesions produced by heavy ions affect nonhomologous end-joining (NHEJ) repair but not homologous recombination repair (HRR). We have also shown that our designed artificial microRNAs (amiRs) could efficiently target XRCC4 (an essential factor for NHEJ) or XRCC2 (an essential factor for HRR) and sensitize human tumor cells to X-rays. Based on these data, we were interested in testing the hypothesis that combining heavy ions and amiRs to target HRR but not NHEJ should more efficiently kill human tumor cells. Methods and Materials: Human tumor cell lines (U87MG, a brain tumor cell line, and A549, a lung cancer cell line) and their counterparts, overexpressed with amiR to target XRCC2, XRCC4 or both, were used in this study. Survival sensitivities were examined using a clonogenic assay after these cells were exposed to X-rays or heavy ions. In addition, these cell lines were subcutaneously injected into nude mice to form xenografts and the tumor size was compared after the tumor areas were exposed to X-rays or heavy ions. Results: Although targeting either XRCC4 (NHEJ factor) or XRCC2 (HRR factor) sensitized the human tumor cells to X-rays, in vitro and the xenograft animal model, targeting only XRCC2 but not XRCC4 sensitized the human tumor cells to heavy ions in vitro and in the xenograft animal model. Conclusions: Combining heavy ions with targeting the HRR pathway, but not the NHEJ pathway, could significantly improve the efficiency of tumor cell death.

  12. Combining Heavy Ion Radiation and Artificial MicroRNAs to Target the Homologous Recombination Repair Gene Efficiently Kills Human Tumor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Zheng Zhiming [Department of Neurosurgery, Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan (China); Department of Radiation Oncology, School of Medicine, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Wang Ping; Wang Hongyan; Zhang Xiangming [Department of Radiation Oncology, School of Medicine, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Wang Minli [Division of Life Sciences, Universities Space Research Association, Houston, Texas (United States); Cucinotta, Francis A. [National Aeronautics and Space Administration, Lyndon B. Johnson Space Center, Houston, Texas (United States); Wang Ya, E-mail: ywang94@emory.edu [Department of Radiation Oncology, School of Medicine, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2013-02-01

    Purpose: Previously, we demonstrated that heavy ions kill more cells at the same dose than X-rays because DNA-clustered lesions produced by heavy ions affect nonhomologous end-joining (NHEJ) repair but not homologous recombination repair (HRR). We have also shown that our designed artificial microRNAs (amiRs) could efficiently target XRCC4 (an essential factor for NHEJ) or XRCC2 (an essential factor for HRR) and sensitize human tumor cells to X-rays. Based on these data, we were interested in testing the hypothesis that combining heavy ions and amiRs to target HRR but not NHEJ should more efficiently kill human tumor cells. Methods and Materials: Human tumor cell lines (U87MG, a brain tumor cell line, and A549, a lung cancer cell line) and their counterparts, overexpressed with amiR to target XRCC2, XRCC4 or both, were used in this study. Survival sensitivities were examined using a clonogenic assay after these cells were exposed to X-rays or heavy ions. In addition, these cell lines were subcutaneously injected into nude mice to form xenografts and the tumor size was compared after the tumor areas were exposed to X-rays or heavy ions. Results: Although targeting either XRCC4 (NHEJ factor) or XRCC2 (HRR factor) sensitized the human tumor cells to X-rays, in vitro and the xenograft animal model, targeting only XRCC2 but not XRCC4 sensitized the human tumor cells to heavy ions in vitro and in the xenograft animal model. Conclusions: Combining heavy ions with targeting the HRR pathway, but not the NHEJ pathway, could significantly improve the efficiency of tumor cell death.

  13. Bemerkungen zur "kalten Fusion"

    OpenAIRE

    Kuehne, Rainer W.

    2006-01-01

    Steven Jones et al. reported to have observed nuclear fusion at room temperature. They observed this "cold fusion" by electrolyzing heavy water. Later experiments confirmed these observations. These experiments confirmed the generation of strong electric fields within the deuterided metals. These electric fields accelerate the deuterons to keV energies and allow the observed nuclear fusion. Roman Sioda and I suggested a theoretical description of this nuclear fusion. Our "extended micro hot f...

  14. HIV-1 vif基因人工miRNA的构建和功能分析%Construction and Function Analysis of Artificial miRNA Targeting to HIV-1 Vif Gene

    Institute of Scientific and Technical Information of China (English)

    王芳宇; 周云; 何丽芳; 滕涛; 杨海; 陈小卫

    2013-01-01

    Objective To construct artificial miR-vif and study their effects on HIV-1 infection. Methods To replace the stem sequence in the stem-loop structure of the well-characterized native miR-155 with siRNA sequences targeting to HIV-1 vif gene, and construct four artificial miR-vif. To detect the vif gene silence efficiency and the expression of IFN-β gene by qPCR; to test the cell toxicity through MTT assays and analyze the HIV-1 infection by using HIV-1 pseudotyped virus experiment. Results The qPCR results showed that four miR-vif could downregulate vif gene expression, and miR-vif-1 presented the highest gene silence efficiency, reached 68%. The further experiments confirmed that miR-vif-1 had neither effect on the viability of the transfected cells nor interference the expression of IFN-β gene. In addition, the results verified that miR-vif-1 has inhibition effect of 66. 5% on HIV-1 replication. Conclusion The miR-vif-1 could efficiently suppress HIV-1 replication and would be a useful candidate for further study on anti-HIV-1 infection.%目的 构建人工miR-vif,并研究其对HIV-1感染宿主细胞的影响.方法 以miR-155为基础骨架,根据HIV-1 vif基因序列设计并合成4对miRNA寡聚单链DNA,构建4个人工miR-vif.采用qPCR技术检测其对vif基因的沉默效率和对干扰素表达的影响;MTT法测定其对被转染细胞的毒性;HIV-1假病毒实验技术检测其对感染的抑制作用.结果 qPCR结果显示,4个人工miR-vif对vif基因都具有一定的沉默效果,其中miR-vif-1的沉默效率最高,达68%.且不会对细胞干扰素的表达产生影响.MTT实验证实miR-vif-1不会影响被转染细胞的活性,此外,HIV-1假病毒实验显示,miR-vif-1对HIV-1 p24的抑制作用达66.5%,效果明显.结论 所获得的miR-vif-1对HIV-1的复制具有良好的抑制作用,可为进一步的抗HIV-1感染研究提供基础.

  15. Induction of cell-cell fusion by ectromelia virus is not inhibited by its fusion inhibitory complex

    Directory of Open Access Journals (Sweden)

    Fuchs Pinhas

    2009-09-01

    Full Text Available Abstract Background Ectromelia virus, a member of the Orthopox genus, is the causative agent of the highly infectious mousepox disease. Previous studies have shown that different poxviruses induce cell-cell fusion which is manifested by the formation of multinucleated-giant cells (polykaryocytes. This phenomenon has been widely studied with vaccinia virus in conditions which require artificial acidification of the medium. Results We show that Ectromelia virus induces cell-cell fusion under neutral pH conditions and requires the presence of a sufficient amount of viral particles on the plasma membrane of infected cells. This could be achieved by infection with a replicating virus and its propagation in infected cells (fusion "from within" or by infection with a high amount of virus particles per cell (fusion "from without". Inhibition of virus maturation or inhibition of virus transport on microtubules towards the plasma membrane resulted in a complete inhibition of syncytia formation. We show that in contrast to vaccinia virus, Ectromelia virus induces cell-cell fusion irrespectively of its hemagglutination properties and cell-surface expression of the orthologs of the fusion inhibitory complex, A56 and K2. Additionally, cell-cell fusion was also detected in mice lungs following lethal respiratory infection. Conclusion Ectromelia virus induces spontaneous cell-cell fusion in-vitro and in-vivo although expressing an A56/K2 fusion inhibitory complex. This syncytia formation property cannot be attributed to the 37 amino acid deletion in ECTV A56.

  16. Cold fusion research

    International Nuclear Information System (INIS)

    I am pleased to forward to you the Final Report of the Cold Fusion Panel. This report reviews the current status of cold fusion and includes major chapters on Calorimetry and Excess Heat, Fusion Products and Materials Characterization. In addition, the report makes a number of conclusions and recommendations, as requested by the Secretary of Energy

  17. Towards cognitive image fusion

    NARCIS (Netherlands)

    Toet, A.; Hogervorst, M.A.; Nikolov, S.G.; Lewis, J.J.; Dixon, T.D.; Bull, D.R.; Canagarajah, C.N.

    2010-01-01

    The increasing availability and deployment of imaging sensors operating in multiple spectral bands has led to a large research effort in image fusion, resulting in a plethora of pixel-level image fusion algorithms. However, the cognitive aspects of multisensor image fusion have not received much att

  18. Towards cognitive image fusion

    NARCIS (Netherlands)

    Toet, A.; Hogervorst, M.A.; Nikolov, S.G.; Lewis, J.; Dixon, T.; Bull, D.; Canagarajah, N.

    2007-01-01

    The increasing availability and deployment of imaging sensors operating in multiple spectral bands has led to a large research effort in image fusion, resulting in a plethora of pixel-level image fusion algorithms. However, the cognitive aspects of multisensor image fusion have not received much att

  19. Fusion technology program

    International Nuclear Information System (INIS)

    The report summarizes work performed in the following areas: system and safety studies for fusion reactors; nuclear data for fusion reactors; neutronics calculations for fusion reactors; radiation damage of vanadium alloys and stainless steel 316; facility for in-pile crack growth measurement; niobium tin magnet for Sultan - stage II; development of NET conductor; and development of ceramic tritium breeding materials

  20. Magneto-Inertial Fusion

    International Nuclear Information System (INIS)

    In this community white paper, we describe an approach to achieving fusion which employs a hybrid of elements from the traditional magnetic and inertial fusion concepts, called magneto-inertial fusion (MIF). The status of MIF research in North America at multiple institutions is summarized including recent progress, research opportunities, and future plans

  1. Fusion Canada issue 18

    International Nuclear Information System (INIS)

    A short bulletin from the National Fusion Program. Included in this issue is a report on the ITER agreement signed with the EDA, the robotic maintenance for NET, the CFFTP Fusion Pilot Study, the new IEA joint programs on environment, safety and economic aspects of fusion power, and a review by the CCFM advisory committee. 3 figs

  2. 检测循环前列腺癌细胞中TMPRSS2:ERG融合基因%Detection of TMPRSS2:ERG fusion gene in circulating prostate cancer cells

    Institute of Scientific and Technical Information of China (English)

    Xueying Mao; Dan Berney; David M. Prowse; Yong-Jie Lu; Greg Shaw; Sharon Y. James; Patraicia Purkis; Sakunthala C. Kudahetti; Theodora Tsigani; Saname Kia; Bryan D. Young; R. Tim D. Oliver

    2008-01-01

    目的:研究前列腺癌病人的循环癌细胞(CTC)中TMPRSS2:ERG融合基因的存在及其与肿瘤转移之间的潜在关系.方法:利用RT-PCR,在27例前列腺切除术中得到的前列腺癌活检标本中检测TMPRSS2:ERG和TMPRSS2:ETV1转录子出现的频率,在15名晚期雄激素非依赖病人的循环癌细胞中检测TMPRSS2:ERGG转录子出现的频率.利用荧光原位杂交技术(FISH)分析10个CTC样本(取自15个CTC样本)中导致TMPRSS2:ERG融合的ERG基因组截短情况.结果:在44%的样本中发现了TMPRSS2:ERGG转录子,但是没有检测到TMPRSS2:ETV1转录子的表达.FISH分析结果显示在10例CTC样本的6例中发现染色体重组影响了ERG基因,包括一例在原癌位置上发生了TMPRSS2:ERG融合.可是,在15例CTC样本中没有检测到TMPRSS2:ERG转录子,包括用FISH检测的10例.结论:虽然需要进一步研究来确认TMPRSS2:ERG融合与前列腺癌转移之间的关系,但是通过FISH分析ERG基因基因组截短是一种有效的监测CTC的出现和前列腺癌潜在转移的方法.%Aim: To investigate the existence of TMPRSS2:ERG fusion gene in circulating tumor cells (CTC) from prostate cancer patients and its potential in monitoring tumor metastasis. Methods: We analyzed the frequency of TMPRSS2:ERG and TMPRSS2:ETV1 transcripts in 27 prostate cancer biopsies from prostatectomies, and TMPRSS2:ERG transcripts in CTC isolated from 15 patients with advanced androgen independent disease using reverse transcription polymerase chain reaction (RT-PCR). Fluorescence in situ hybridization (FISH) was applied to analyze the genomic truncation of ERG, which is the result of TMPRSS2:ERG fusion in 10 of the 15 CTC samples. Results: TMPRSS2:ERG transcripts were found in 44% of our samples, but we did not detect expression of TMPRSS2:ETV1. Using FISH analysis we detected chromosomal rearrangements affecting the ERG gene in 6 of 10 CTC samples, including 1 case with associated TMPRSS2:ERG fusion at the

  3. Novel ZEB2-BCL11B Fusion Gene Identified by RNA-Sequencing in Acute Myeloid Leukemia with t(2;14(q22;q32.

    Directory of Open Access Journals (Sweden)

    Synne Torkildsen

    Full Text Available RNA-sequencing of a case of acute myeloid leukemia with the bone marrow karyotype 46,XY,t(2;14(q22;q32[5]/47,XY,idem,+?4,del(6(q13q21[cp6]/46,XY[4] showed that the t(2;14 generated a ZEB2-BCL11B chimera in which exon 2 of ZEB2 (nucleotide 595 in the sequence with accession number NM_014795.3 was fused to exon 2 of BCL11B (nucleotide 554 in the sequence with accession number NM_022898.2. RT-PCR together with Sanger sequencing verified the presence of the above-mentioned fusion transcript. All functional domains of BCL11B are retained in the chimeric protein. Abnormal expression of BCL11B coding regions subjected to control by the ZEB2 promoter seems to be the leukemogenic mechanism behind the translocation.

  4. Fusion expression of mutated cecropin CMIV in E. coli

    Institute of Scientific and Technical Information of China (English)

    谢维; 邱奇峰; 董雪吟; 华子春; 徐贤秀

    1997-01-01

    A cDNA coding mutated cecropin CMIV from Bombyx mori was synthesized according to its amino acid sequense using E .coli biased codons .The gene was cloned into the fusion expression vector pEZZ318 and was expressed in E .coli HB101.The fusion protein produced was purified by affinity chromatography to yield 26 mg/L fusion product .The anti-bacterial activities of recombinant cecropin CMIV were recovered after cleavage by chemical method.

  5. Protein-protein fusion catalyzed by sortase A.

    Science.gov (United States)

    Levary, David A; Parthasarathy, Ranganath; Boder, Eric T; Ackerman, Margaret E

    2011-04-06

    Chimeric proteins boast widespread use in areas ranging from cell biology to drug delivery. Post-translational protein fusion using the bacterial transpeptidase sortase A provides an attractive alternative when traditional gene fusion fails. We describe use of this enzyme for in vitro protein ligation and report the successful fusion of 10 pairs of protein domains with preserved functionality--demonstrating the robust and facile nature of this reaction.

  6. Protein-protein fusion catalyzed by sortase A.

    Directory of Open Access Journals (Sweden)

    David A Levary

    Full Text Available Chimeric proteins boast widespread use in areas ranging from cell biology to drug delivery. Post-translational protein fusion using the bacterial transpeptidase sortase A provides an attractive alternative when traditional gene fusion fails. We describe use of this enzyme for in vitro protein ligation and report the successful fusion of 10 pairs of protein domains with preserved functionality--demonstrating the robust and facile nature of this reaction.

  7. Artificial life and life artificialization in Tron

    Directory of Open Access Journals (Sweden)

    Carolina Dantas Figueiredo

    2012-12-01

    Full Text Available Cinema constantly shows the struggle between the men and artificial intelligences. Fiction, and more specifically fiction films, lends itself to explore possibilities asking “what if?”. “What if”, in this case, is related to the eventual rebellion of artificial intelligences, theme explored in the movies Tron (1982 and Tron Legacy (2010 trat portray the conflict between programs and users. The present paper examines these films, observing particularly the possibility programs empowering. Finally, is briefly mentioned the concept of cyborg as a possibility of response to human concerns.

  8. Analysis artefacts of the INS-IGF2 fusion transcript

    DEFF Research Database (Denmark)

    Wernersson, Rasmus; Frogne, Thomas; Rescan, Claude;

    2015-01-01

    Background: In gene expression analysis, overlapping genes, splice variants, and fusion transcripts are potential sources of data analysis artefacts, depending on how the observed intensity is assigned to one, or more genes. We here exemplify this by an in-depth analysis of the INS-IGF2 fusion...... proteomics analysis we could not demonstrate INS-IGF2 protein in samples of human islets nor in EndoC-βH1. Conclusions: Sequence features, such as fusion transcripts spanning multiple genes can lead to unexpected results in gene expression analysis, and care must be taken in generating and interpreting...... the results. For the specific case of INS-IGF2 we conclude that the abundance of the fusion transcript/protein is exceedingly lower than previously reported, and that current immuno-reagents available for detecting INS-IGF2 protein have a strong cross-reaction to native human proinsulin. Finally, we were...

  9. 人工选育浆蜂与原种意大利蜜蜂csd基因多态性比较%Comparison of csd gene polymorphism between artificially bred high royal jelly producing honeybee and native Italy honeybee

    Institute of Scientific and Technical Information of China (English)

    刘志勇; 曾志将; 吴小波; 颜伟玉; 王子龙

    2015-01-01

    In this study,artificially bred high jelly producing honeybees were used as the experimental mate⁃rial.Genome DNA was extracted from each honeybee sample for PCR amplification of the csd region 3,PCR prod⁃ucts were cloned and sequenced.Finally 13 csd haplotypes were obtained.The difference in the polymorphism of csd gene between high royal jelly producing honeybee and native Italy honeybee was compared. The results showed that the nucleotide diversity (π) values of csd in these two strains are 0.057 85±0.004 92 and 0.043 80 ±0.005 75,respectively.Z test indicated that there is no significant difference between the πvalues of these two strains.Phylogenetic tree showed that csd haplotypes do not form two branches reflecting the two strains.Rather, they are well mixed among each other.The Fst distance between high royal jelly producing honeybee and native Italy honeybee is 0.036 9,indicating a weak genetic differentiation between these two strains.These results indica⁃ted that artificial selection has no effect on the polymorphism of csd gene in high royal jelly producing honeybees.%以人工选育的浆蜂为材料,提取每个工蜂样品的基因组DNA,对csd 基因3区进行PCR扩增、克隆和测序,最终获得了13个浆蜂csd基因单倍型。对浆蜂与原种意大利蜜蜂csd基因的多态性进行比较。结果表明浆蜂和原种意大利蜜蜂的核苷酸多样度(π)分别为0.05785±0.00492和0.04380±0.00575,两者之间没有显著差异。系统进化树表明来自浆蜂和原种意大利蜜蜂的单倍型混杂在一起,没有形成完全独立的2个分支。群体分析表明浆蜂和原种意大利蜜蜂之间的Fst 距离是0.0369,两者之间的遗传分化很弱。这些结果说明人工选育对浆蜂csd基因的多态性没有产生显著影响。

  10. Magnetized target fusion and fusion propulsion.

    Energy Technology Data Exchange (ETDEWEB)

    Kirkpatrick, R. C. (Ronald C.)

    2001-01-01

    Magnetized target fusion (MTF) is a thermonuclear fusion concept that is intermediate between the two mainline approaches, magnetic confinement and inertial confinement fusion (MCF and ICF). MTF incorporates some aspects of each and offers advantages over each of the mainline approaches. First, it provides a means of reducing the driver power requirements, thereby admitting a wider range of drivers than ICF. Second, the magnetic field is only used for insulation, not confinement, and the plasma is wall confined, so that plasma instabilities are traded in for hydrodynamic instabilities. However, the degree of compression required to reach fusion conditions is lower than for ICF, so that hydrodynamic instabilities are much less threatening. The standoff driver innovation proposes to dynamically form the target plasma and a gaseous shell that compresses and confines the target plasma. Therefore, fusion target fabrication is traded in for a multiplicity of plasma guns, which must work in synchrony. The standoff driver embodiment of MTF leads to a fusion propulsion system concept that is potentially compact and lightweight. We will discuss the underlying physics of MTF and some of the details of the fusion propulsion concept using the standoff driver approach. We discuss here the optimization of an MTF target design for space propulsion.

  11. Thermal Resonance Fusion

    OpenAIRE

    Dong, Bao-Guo

    2015-01-01

    We first show a possible mechanism to create a new type of nuclear fusion, thermal resonance fusion, i.e. low energy nuclear fusion with thermal resonance of light nuclei or atoms, such as deuterium or tritium. The fusion of two light nuclei has to overcome the Coulomb barrier between these two nuclei to reach up to the interacting region of nuclear force. We found nuclear fusion could be realized with thermal vibrations of crystal lattice atoms coupling with light atoms at low energy by reso...

  12. Fusion applications study: FAME

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, K.R.

    1986-01-01

    Fusion has a wide spectrum of applications that appear technically possible and may become economically feasible. Near-term (approx. 2000) application for production of nuclear fuels and useful radioisotopes is an economically attractive possibility as soon as fusion is ready. Electricity production will remain a prime, large-scale application of fusion. In the longer term, as fossil fuels dwindle, production of hydrogen could become a major application. Additional applications some of which have not even been conceived of yet, will add to this potential richness and diversity of fusion. It is the purpose of the fusion applications study - FMAE - to innovate, investigate, and evaluate these potential applications.

  13. Artificial insemination in poultry

    Science.gov (United States)

    Artificial insemination is a relative simple yet powerful tool geneticists can employ for the propagation of economically important traits in livestock and poultry. In this chapter, we address the fundamental methods of the artificial insemination of poultry, including semen collection, semen evalu...

  14. Viral membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, Stephen C., E-mail: harrison@crystal.harvard.edu

    2015-05-15

    Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a “fusion loop” or “fusion peptide”) engages the target-cell membrane and collapse of the bridging intermediate thus formed draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics. - Highlights: • Viral fusion proteins overcome the high energy barrier to lipid bilayer merger. • Different molecular structures but the same catalytic mechanism. • Review describes properties of three known fusion-protein structural classes. • Single-virion fusion experiments elucidate mechanism.

  15. Viral membrane fusion

    International Nuclear Information System (INIS)

    Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a “fusion loop” or “fusion peptide”) engages the target-cell membrane and collapse of the bridging intermediate thus formed draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics. - Highlights: • Viral fusion proteins overcome the high energy barrier to lipid bilayer merger. • Different molecular structures but the same catalytic mechanism. • Review describes properties of three known fusion-protein structural classes. • Single-virion fusion experiments elucidate mechanism

  16. Onion artificial muscles

    Science.gov (United States)

    Chen, Chien-Chun; Shih, Wen-Pin; Chang, Pei-Zen; Lai, Hsi-Mei; Chang, Shing-Yun; Huang, Pin-Chun; Jeng, Huai-An

    2015-05-01

    Artificial muscles are soft actuators with the capability of either bending or contraction/elongation subjected to external stimulation. However, there are currently no artificial muscles that can accomplish these actions simultaneously. We found that the single layered, latticed microstructure of onion epidermal cells after acid treatment became elastic and could simultaneously stretch and bend when an electric field was applied. By modulating the magnitude of the voltage, the artificial muscle made of onion epidermal cells would deflect in opposing directions while either contracting or elongating. At voltages of 0-50 V, the artificial muscle elongated and had a maximum deflection of -30 μm; at voltages of 50-1000 V, the artificial muscle contracted and deflected 1.0 mm. The maximum force response is 20 μN at 1000 V.

  17. EML4-ALK融合基因在非小细胞肺癌中的研究进展%Research Progress of EML4-ALK Fusion Gene in Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    赵腾; 夏凡; 王晓红

    2012-01-01

    肺癌是发病率和死亡率最高的恶性肿瘤,分子靶向治疗以其特异性高、副反应轻的特点正日益受到关注.近年来临床研究发现EML4-ALK融合基因是除EGFR突变及KRAS突变之外的另-个重要的酪氨酸激酶抑制剂的作用靶点,该融合基因在年轻、不吸烟或少吸烟、腺癌、无EGFR和KRAS突变的非小细胞肺癌患者中发生率较高,且该融合基因阳性者对酪氨酸激酶抑制剂耐药,对于ALK抑制剂(如克唑替尼)则有良好的治疗反应,关于该药的临床试验表明:总有效率达57%(46例确定为部分缓解,1例确定为完全缓解),估计6个月无进展生存概率为72%,常见的副反应是1、2级胃肠道反应.该基因及该药的发现为非小细胞肺癌患者带来了希望.%The morbidity and mortality of lung cancer is currently the highest in all the malignant tumors. Because of its higher specificity and milder side-effects, molecule target therapy in non-small cell lung cancer (NSCLC) is drawing concern at present Recently clinical studies have found that EML4-ALK fusion gene is another important molecular target of tyrosine kinase inhibitors in addition to EGFR mutations and KRAS mutations. The fusion gene has higher morbidity in NSCLC patients who are young, never or light smoking history, adenocarcinomas, without EGFR and KRAS mutation. Although patients who harbor this mutation do not benefit from EGFR TKIs , they have shown good response to ALK inhibitor (for example: Crizotinib). Clinical trials about the drug have shown: the Overall response rate was 57% (with 46 confirmed partial responses and 1 confirmed complete response), and the estimated probability of 6-month progression-free survival was 72%, grade 1 or 2 mild gastrointestinal effects are the common side effects. Discovery of the gene and the drug may bring new hope for the patients with NSCLC.

  18. 融合基因VH-mms13的构建及其蛋白表达鉴定%Construction of fusion gene VH-mms13 and identification of its protein

    Institute of Scientific and Technical Information of China (English)

    杨柳青; 孔登; 王雪耘; 王晓红; 孟丽; 王小柯

    2015-01-01

    Objective To construct the prokaryotic expression vector pET30a( +)-VH-mms13 and identification of its protein after induced with IPTG.Method Heavy chain variable region VH gene of typeⅣcollagenase monoclonal antibody and magnetosome membrane protein gene mms13 were amplified separately,the fusion gene VH-linker-mms13 were synthesized by SOE-PCR technique and inserted into pET30a ( +) plasmid, which was confirmed by restriction enzyme digest and sequencing.Then the recombinant plasmid pET30a ( +)-VH-mms13 was transform into E.coli DE3 and induced with 0.4 mmol/L IPTG.The fused protein was identified by SDS-PAGE and Western blot.Results The length of fusion gene VH-mms13 was 738 bp,and the sequence was correct.After induced with IPTG,the fused protein was found in the inclusion body and Western blot results suggested that the fused protein can bind with His-tag antibody specifically.Conclusion Expression vector pET30a ( +)-VH-mms13 is successfully constructed and the fusion protein has good immunogenicity,which lay the foundation for the development of biomagnetism-targeted drug.%目的:构建原核表达载体pET30a(+)-VH-mms13,诱导表达后鉴定融合蛋白表达。方法分别扩增单克隆抗体基因的重链可变区VH基因和细菌磁小体膜蛋白基因mms13基因,采用重叠延伸PCR技术(splicing by overlap extension ,SOE-PCR)构建融合基因VH-linker-mms13,并将融合基因插入pET30a(+)载体,酶切、测序验证;将重组质粒导入大肠杆菌DE3中,0.4 mmol/L异丙基疏代半乳糖苷( Isopropyl β-D-thiogalactoside ,IPTG)诱导表达,产物经SDS-PAGE电泳和Western blot 双重鉴定。结果 PCR鉴定构建的融合基因VH-mms13大小为738 bp,与理论值相符,测序结果表明序列无误;转入DE3经IPTG诱导,在包含体中检测到融合蛋白表达;Western blot结果显示该表达蛋白可与His-tag抗体特异性结合,蛋白大小符合融合

  19. Incidence and clinical relevance of TEL/AML1 fusion genes in children with acute lymphoblastic leukemia enrolled in the German and Italian multicenter therapy trials. Associazione Italiana Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Münster Study Group.

    Science.gov (United States)

    Borkhardt, A; Cazzaniga, G; Viehmann, S; Valsecchi, M G; Ludwig, W D; Burci, L; Mangioni, S; Schrappe, M; Riehm, H; Lampert, F; Basso, G; Masera, G; Harbott, J; Biondi, A

    1997-07-15

    The molecular approach for the analysis of leukemia associated chromosomal translocations has led to the identification of prognostic relevant subgroups. In pediatric acute lymphoblastic leukemia (ALL), the most common translocations, t(9;22) and t(4;11), have been associated with a poorer clinical outcome. Recently the TEL gene at chromosome 12p13 and the AML1 gene at chromosome 21q22 were found to be involved in the translocation t(12;21)(p13;q22). By conventional cytogenetics, however, this chromosomal abnormality is barely detectable and occurs in less than 0.05% of childhood ALL. To investigate the frequency of the molecular equivalent of the t(12;21), the TEL/AML1 gene fusion, we have undertaken a prospective screening in the running German Berlin-Frankfurt-Münster (BFM) and Italian Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) multicenter ALL therapy trials. We have analyzed 334 unselected cases of pediatric ALL patients consecutively referred over a period of 5 and 9 months, respectively. The overall incidence of the t(12;21) in pediatric ALL is 18.9%. The 63 cases positive for the TEL/AML1 chimeric products ranged in age between 1 and 12 years, and all but one showed CD10 and pre-B immunophenotype. Interestingly, one case displayed a pre-pre-B immunophenotype. Among the B-lineage subgroup, the t(12;21) occurs in 22.0% of the cases. Fifteen of 61 (24.6%) cases coexpressed at least two myeloid antigens (CD13, CD33, or CDw65) in more than 20% of the gated blast cells. DNA index was available for 59 of the 63 TEL/AML1 positive cases; a hyperdiploid DNA content (> or = 1.16) was detected in only four patients, being nonhyperdiploid in the remaining 55. Based on this prospective analysis, we retrospectively evaluated the impact of TEL/AML1 in prognosis by identifying the subset of B-lineage ALL children enrolled in the closed German ALL-BFM-90 and Italian ALL-AIEOP-91 protocols who had sufficient material for analysis. A total of 342 children

  20. The fusion breeder

    International Nuclear Information System (INIS)

    The fusion breeder is a fusion reactor designed with special blankets to maximize the transmutation by 14 MeV neutrons of uranium-238 to plutonium or thorium to uranium-233 for use as a fuel for fission reactors. Breeding fissile fuels has not been a goal of the U.S. fusion energy program. This paper suggests it is time for a policy change to make the fusion breeder a goal of the U.S. fusion program and the U.S. nuclear energy program. There is wide agreement that many approaches will work and will produce fuel for five equal-sized LWRs, and some approach as many as 20 LWRs at electricity costs within 20% of those at today's price of uranium ($30/lb of U3O8). The blankets designed to suppress fissioning, called symbiotes, fusion fuel factories, or just fusion breeders, will have safety characteristics more like pure fusion reactors and will support as many as 15 equal power LWRs. The blankets designed to maximize fast fission of fertile material will have safety characteristics more like fission reactors and will support 5 LWRs. This author strongly recommends development of the fission suppressed blanket type, a point of view not agreed upon by everyone. There is, however, wide agreement that, to meet the market price for uranium which would result in LWR electricity within 20% of today's cost with either blanket type, fusion components can cost severalfold more than would be allowed for pure fusion to meet the goal of making electricity alone at 20% over today's fission costs. Also widely agreed is that the critical-pathitem for the fusion breeder is fusion development itself; however, development of fusion breeder specific items (blankets, fuel cycle) should be started now in order to have the fusion breeder by the time the rise in uranium prices forces other more costly choices

  1. Genetic recombination in Actinoplanes brasiliensis by protoplast fusion.

    OpenAIRE

    Palleroni, N. J.

    1983-01-01

    Protoplast formation, fusion, and cell regeneration have been achieved with mutant strains of Actinoplanes brasiliensis. Three-, four-, and five-factor crosses have shown genetic recombination among the markers, and a five-factor cross is analyzed and discussed. Possibilities of using protoplast fusion for gene mapping and strain improvement are suggested.

  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. Fusion of a viral antigen to invariant chain leads to augmented T-cell immunity and improved protection in gene-gun DNA-vaccinated mice

    DEFF Research Database (Denmark)

    Grujic, Mirjana; Holst, Peter J; Christensen, Jan P;

    2009-01-01

    against lethal peripheral challenge. The current study questioned whether the same strategy, i.e. linkage of GP to an Ii chain, could be applied to a naked DNA vaccine. Following gene-gun immunization with the linked construct (DNA-IiGP), GP-specific CD4(+) T cells could not be detected by flow cytometry...

  4. Materials research for fusion

    Science.gov (United States)

    Knaster, J.; Moeslang, A.; Muroga, T.

    2016-05-01

    Fusion materials research started in the early 1970s following the observation of the degradation of irradiated materials used in the first commercial fission reactors. The technological challenges of fusion energy are intimately linked with the availability of suitable materials capable of reliably withstanding the extremely severe operational conditions of fusion reactors. Although fission and fusion materials exhibit common features, fusion materials research is broader. The harder mono-energetic spectrum associated with the deuterium-tritium fusion neutrons (14.1 MeV compared to average for fission neutrons) releases significant amounts of hydrogen and helium as transmutation products that might lead to a (at present undetermined) degradation of structural materials after a few years of operation. Overcoming the historical lack of a fusion-relevant neutron source for materials testing is an essential pending step in fusion roadmaps. Structural materials development, together with research on functional materials capable of sustaining unprecedented power densities during plasma operation in a fusion reactor, have been the subject of decades of worldwide research efforts underpinning the present maturity of the fusion materials research programme.

  5. Economics of fusion research

    International Nuclear Information System (INIS)

    This report provides the results of a study of methods of economic analysis applied to the evaluation of fusion research. The study recognizes that a hierarchy of economic analyses of research programs exists: standard benefit-cost analysis, expected value of R and D information, and expected utility analysis. It is shown that standard benefit-cost analysis, as commonly applied to research programs, is inadequate for the evaluation of a high technology research effort such as fusion research. A methodology for performing an expected value analysis is developed and demonstrated and an overview of an approach to perform an expected utility analysis of fusion research is presented. In addition, a potential benefit of fusion research, not previously identified, is discussed and rough estimates of its magnitude are presented. This benefit deals with the effect of a fusion research program on optimal fossil fuel consumption patterns. The results of this study indicate that it is both appropriate and possible to perform an expected value analysis of fusion research in order to assess the economics of a fusion research program. The results indicate further that the major area of benefits of fusion research is likely due to the impact of a fusion research program on optimal fossil fuel consumption patterns and it is recommended that this benefit be included in future assessments of fusion research economics

  6. Economics of fusion research

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    1977-10-15

    This report provides the results of a study of methods of economic analysis applied to the evaluation of fusion research. The study recognizes that a hierarchy of economic analyses of research programs exists: standard benefit-cost analysis, expected value of R and D information, and expected utility analysis. It is shown that standard benefit-cost analysis, as commonly applied to research programs, is inadequate for the evaluation of a high technology research effort such as fusion research. A methodology for performing an expected value analysis is developed and demonstrated and an overview of an approach to perform an expected utility analysis of fusion research is presented. In addition, a potential benefit of fusion research, not previously identified, is discussed and rough estimates of its magnitude are presented. This benefit deals with the effect of a fusion research program on optimal fossil fuel consumption patterns. The results of this study indicate that it is both appropriate and possible to perform an expected value analysis of fusion research in order to assess the economics of a fusion research program. The results indicate further that the major area of benefits of fusion research is likely due to the impact of a fusion research program on optimal fossil fuel consumption patterns and it is recommended that this benefit be included in future assessments of fusion research economics.

  7. Artificial intelligence in medicine.

    Science.gov (United States)

    Ramesh, A. N.; Kambhampati, C.; Monson, J. R. T.; Drew, P. J.

    2004-01-01

    INTRODUCTION: Artificial intelligence is a branch of computer science capable of analysing complex medical data. Their potential to exploit meaningful relationship with in a data set can be used in the diagnosis, treatment and predicting outcome in many clinical scenarios. METHODS: Medline and internet searches were carried out using the keywords 'artificial intelligence' and 'neural networks (computer)'. Further references were obtained by cross-referencing from key articles. An overview of different artificial intelligent techniques is presented in this paper along with the review of important clinical applications. RESULTS: The proficiency of artificial intelligent techniques has been explored in almost every field of medicine. Artificial neural network was the most commonly used analytical tool whilst other artificial intelligent techniques such as fuzzy expert systems, evolutionary computation and hybrid intelligent systems have all been used in different clinical settings. DISCUSSION: Artificial intelligence techniques have the potential to be applied in almost every field of medicine. There is need for further clinical trials which are appropriately designed before these emergent techniques find application in the real clinical setting. PMID:15333167

  8. ALK protein expression and gene fusion in bronchoscopic specimens of lung adenocarcinoma%检测肺腺癌活检标本间变性淋巴瘤激酶蛋白表达和基因融合

    Institute of Scientific and Technical Information of China (English)

    梁小龙; 王孟昭; 张静; 罗玉凤; 张淑英; 武莎斐; 刘媛媛; 曾瑄

    2014-01-01

    Objective To explore ALK protein expression and gene fusion in formalin-fixed and paraffin-embedded (FFPE) specimens obtained from lung cancer by bronchoscopy,and to investigate the relationship between ALK status and clinicopathological characteristics of the patients.Methods Seventyfour FFPE samples obtained from lung adenocarcinoma by bronchoscopy were tested for ALK protein expression and gene fusion respectively by immunohistochemistry (IHC) using Ventana D5F3 antibody and fluorescence in situ hybridization (FISH) using ALK break apart probe.Results sixty-five of the 74 samples were successfully tested by FISH (87.8%,65/74).There were 5 FISH-positive cases (7.7%,5/65),all with advanced stage carcinoma.Among these five FISH-positive cases,3 were IHC-positive (4.1%,3/74) and 2 IHC-negative cases.All the other 69 samples were IHC-negative,including nine FISH-uninformative samples (7 samples were less than 50 tumor cells and 2 samples with weak FISH signal).Both ALK IHC and FISH results were not correlated with age,sex,history of smoking,histological classification,differentiation and lymph node metastasis.Conclusions Bronchoscopic specimens of lung cancer can be used to detect ALK expression and gene fusion.Inmunohistochemistry in combination with FISH test may be more favorable for ALK test.%目的 探讨采用肺腺癌支气管镜活检标本检测间变性淋巴瘤激酶(ALK)蛋白表达和基因融合的可行性,及其与临床病理特征的关系.方法 74例福尔马林固定石蜡包埋的肺腺癌支气管镜活检标本,采用Bench Mark全自动免疫组化染色机和D5F3抗体试剂盒,以免疫组化法检测ALK蛋白的表达,采用Abbott ALK分离探针,以荧光原位杂交(FISH)法检测ALK基因融合.结果 74例标本中,65例成功地进行了FISH检测,成功检测率为87.8% (65/74);FISH阳性5例,阳性率为7.7%(5/65),均为中晚期低分化腺癌;其中免疫组化阳性3例,阳性率为4.1% (3/74);另2

  9. Conditions Favorable for the Somatic Embryogenesis in Carrot Cell Culture Enhance Expression of the roIC Promoter-GUS Fusion Gene 1

    Science.gov (United States)

    Fujii, Nobuharu; Uchimiya, Hirofumi

    1991-01-01

    We obtained carrot (Daucus carota) cells possessing the 5′-noncoding sequence of the ORF12 gene (roIC) of TL-DNA of the Ri plasmid and a structural gene of bacterial β-glucuronidase by Agrobacterium-mediated transformation. When such cells were cultured in medium containing 2,4-dichlorophenoxyacetic acid, substantial reduction in β-glucuronidase activity was observed. Upon transferring the cells from a 2,4-D-containing medium to one devoid of 2,4-dichlorophenoxyacetic acid, enhanced expression of β-glucuronidase in somatic embryo development was recorded. Activation by gibberillic acid and suppression by abscisic acid of β-glucuronidase activities, in concord with embryogenesis, were also noted. Images Figure 2 PMID:16667958

  10. Conditions Favorable for the Somatic Embryogenesis in Carrot Cell Culture Enhance Expression of the roIC Promoter-GUS Fusion Gene.

    Science.gov (United States)

    Fujii, N; Uchimiya, H

    1991-01-01

    We obtained carrot (Daucus carota) cells possessing the 5'-noncoding sequence of the ORF12 gene (roIC) of TL-DNA of the Ri plasmid and a structural gene of bacterial beta-glucuronidase by Agrobacterium-mediated transformation. When such cells were cultured in medium containing 2,4-dichlorophenoxyacetic acid, substantial reduction in beta-glucuronidase activity was observed. Upon transferring the cells from a 2,4-D-containing medium to one devoid of 2,4-dichlorophenoxyacetic acid, enhanced expression of beta-glucuronidase in somatic embryo development was recorded. Activation by gibberillic acid and suppression by abscisic acid of beta-glucuronidase activities, in concord with embryogenesis, were also noted. PMID:16667958

  11. The artificial disc: theory, design and materials.

    Science.gov (United States)

    Bao, Q B; McCullen, G M; Higham, P A; Dumbleton, J H; Yuan, H A

    1996-06-01

    Low back pain is one of the most common medical conditions in the Western world. Disc degeneration, an inevitable process of aging, of variable rate and degree, is one of the major causes of low back pain. Currently, there are two major surgical interventions for treating conditions related to the degenerative disc: discectomy and fusion. Although discectomy and fusion produce a relatively good short-term clinical result in relieving pain, both these surgical treatments alter the biomechanics of the spine, possibly leading to further degeneration of the surrounding tissues and the discs at adjacent levels. Over the past 35 years, a tremendous effort has been made to develop an artificial disc to replace the degenerated disc. The goal is the restoration of the natural biomechanics of the segment after disc excision, thus relieving pain and preventing further degeneration at adjacent segments. However, the artificial disc faces a complex biomechanical environment which makes replication of the biomechanics difficult and long-term survival challenging to designs and materials. The purpose of this article is to examine the factors of importance in designing a disc replacement. Topics covered include the structure and function of the natural disc, the changes that occur with disc degeneration and existing methods of treatment for the degenerative spine. The progress in achieving a functional, long-lasting disc replacement is outlined.

  12. Genetic variability of attachment (G and Fusion (F protein genes of human metapneumovirus strains circulating during 2006-2009 in Kolkata, Eastern India

    Directory of Open Access Journals (Sweden)

    Chawla-Sarkar Mamta

    2011-02-01

    Full Text Available Abstract Background Human metapneumovirus (hMPV is associated with the acute respiratory tract infection (ARTI in all the age groups. However, there is limited information on prevalence and genetic diversity of human metapneumovirus (hMPV strains circulating in India. Objective To study prevalence and genomic diversity of hMPV strains among ARTI patients reporting in outpatient departments of hospitals in Kolkata, Eastern India. Methods Nasal and/or throat swabs from 2309 patients during January 2006 to December 2009, were screened for the presence of hMPV by RT-PCR of nucleocapsid (N gene. The G and F genes of representative hMPV positive samples were sequenced. Results 118 of 2309 (5.11% clinical samples were positive for hMPV. The majority (≈80% of the positive cases were detected during July−November all through the study period. Genetic analysis revealed that 77% strains belong to A2 subgroup whereas rest clustered in B1 subgroup. G sequences showed higher diversity at the nucleotide and amino acid level. In contrast, less than 10% variation was observed in F gene of representative strains of all four years. Sequence analysis also revealed changes in the position of stop codon in G protein, which resulted in variable length (217-231 aa polypeptides. Conclusion The study suggests that approximately 5% of ARTI in the region were caused by hMPV. This is the first report on the genetic variability of G and F gene of hMPV strains from India which clearly shows that the G protein of hMPV is continuously evolving. Though the study partially fulfills lacunae of information, further studies from other regions are necessary for better understanding of prevalence, epidemiology and virus evolution in Indian subcontinent.

  13. Robust expression and secretion of Xylanase1 in Chlamydomonas reinhardtii by fusion to a selection gene and processing with the FMDV 2A peptide.

    Directory of Open Access Journals (Sweden)

    Beth A Rasala

    Full Text Available Microalgae have recently received attention as a potential low-cost host for the production of recombinant proteins and novel metabolites. However, a major obstacle to the development of algae as an industrial platform has been the poor expression of heterologous genes from the nuclear genome. Here we describe a nuclear expression strategy using the foot-and-mouth-disease-virus 2A self-cleavage peptide to transcriptionally fuse heterologous gene expression to antibiotic resistance in Chlamydomonas reinhardtii. We demonstrate that strains transformed with ble-2A-GFP are zeocin-resistant and accumulate high levels of GFP that is properly 'cleaved' at the FMDV 2A peptide resulting in monomeric, cytosolic GFP that is easily detectable by in-gel fluorescence analysis or fluorescent microscopy. Furthermore, we used our ble2A nuclear expression vector to engineer the heterologous expression of the industrial enzyme, xylanase. We demonstrate that linking xyn1 expression to ble2A expression on the same open reading frame led to a dramatic (~100-fold increase in xylanase activity in cells lysates compared to the unlinked construct. Finally, by inserting an endogenous secretion signal between the ble2A and xyn1 coding regions, we were able to target monomeric xylanase for secretion. The novel microalgae nuclear expression strategy described here enables the selection of transgenic lines that are efficiently expressing the heterologous gene-of-interest and should prove valuable for basic research as well as algal biotechnology.

  14. Robust expression and secretion of Xylanase1 in Chlamydomonas reinhardtii by fusion to a selection gene and processing with the FMDV 2A peptide.

    Science.gov (United States)

    Rasala, Beth A; Lee, Philip A; Shen, Zhouxin; Briggs, Steven P; Mendez, Michael; Mayfield, Stephen P

    2012-01-01

    Microalgae have recently received attention as a potential low-cost host for the production of recombinant proteins and novel metabolites. However, a major obstacle to the development of algae as an industrial platform has been the poor expression of heterologous genes from the nuclear genome. Here we describe a nuclear expression strategy using the foot-and-mouth-disease-virus 2A self-cleavage peptide to transcriptionally fuse heterologous gene expression to antibiotic resistance in Chlamydomonas reinhardtii. We demonstrate that strains transformed with ble-2A-GFP are zeocin-resistant and accumulate high levels of GFP that is properly 'cleaved' at the FMDV 2A peptide resulting in monomeric, cytosolic GFP that is easily detectable by in-gel fluorescence analysis or fluorescent microscopy. Furthermore, we used our ble2A nuclear expression vector to engineer the heterologous expression of the industrial enzyme, xylanase. We demonstrate that linking xyn1 expression to ble2A expression on the same open reading frame led to a dramatic (~100-fold) increase in xylanase activity in cells lysates compared to the unlinked construct. Finally, by inserting an endogenous secretion signal between the ble2A and xyn1 coding regions, we were able to target monomeric xylanase for secretion. The novel microalgae nuclear expression strategy described here enables the selection of transgenic lines that are efficiently expressing the heterologous gene-of-interest and should prove valuable for basic research as well as algal biotechnology. PMID:22937037

  15. Prokaryotic Expression of the p23-IL-18 Fusion Gene of Theileria sergenti%牛瑟氏泰勒虫p23-IL-18融合基因的原核表达

    Institute of Scientific and Technical Information of China (English)

    白杨; 许应天; 吴艳丽; 于志云

    2014-01-01

    In order to prepare the genetically engineering subunit vaccine of brovine Theileria sergenti, the p23-IL-18 fusion gene was cloned into prokaryotic pET-28a expression vector in this experiment. It can construct recombinant prokaryotic expression plasmid pET-28a-p23-IL-18 which induced expression by IPTG. The expression products were examined by SDS-PAGE and Western-blotting. The results showed that the prokaryotic expression plasmid pET-28a-p23-IL-18 was built successfully and the objective gene was successfully expressed in Escherichia coli. The molecular weight of fusion protein was 48 kDa and could react with Theileria sergenti positive serum with good antigencity. The results of this research laid the foundations for genetically engineering subunit vaccine of brovine Theileria sergenti.%为探索牛瑟氏泰勒虫病基因工程亚单位疫苗的可行性,以p23-IL-18融合基因克隆到原核表达载体pET-28a,构建原核重组质粒pET-28a-p23-IL-18,用IPTG诱导表达,对表达产物进行SDS-PAGE和Western-blotting分析。结果表明,构建牛瑟氏泰勒虫pET-28a-p23-IL-18原核表达质粒,目的基因在大肠杆菌中获得表达,融合蛋白的分子量约为48 kDa,并被牛瑟氏泰勒虫阳性血清所识别,具有良好的反应原性。此结果为牛瑟氏泰勒虫病基因工程亚单位疫苗的制备提供了理论依据。

  16. Fusion of Nonionic Vesicles

    DEFF Research Database (Denmark)

    Bulut, Sanja; Oskolkova, M. Z.; Schweins, R.;

    2010-01-01

    We present an experimental study of vesicle fusion using light and neutron scattering to monitor fusion events. Vesicles are reproducibly formed with an extrusion procedure using an single amphiphile triethylene glycol mono-n-decyl ether in water. They show long-term stability for temperatures...... around 20 C, but at temperatures above 26 C we observe an increase in the scattered intensity due to fusion. The system is unusually well suited for the study of basic mechanisms of vesicle fusion. The vesicles are flexible with a bending rigidity of only a few k(H)T. The monolayer spontaneous curvature......, Ho, depends strongly on temperature in a known way and is thus tunable. For temperatures where H-0 > 0 vesicles tyre long-term stable, while in the range H-0 fusion rate increases the more negative the Spontaneous curvature Through a quantitative;analysis of the fusion rate we arrive tit...

  17. Muon Catalyzed Fusion

    Science.gov (United States)

    Armour, Edward A.G.

    2007-01-01

    Muon catalyzed fusion is a process in which a negatively charged muon combines with two nuclei of isotopes of hydrogen, e.g, a proton and a deuteron or a deuteron and a triton, to form a muonic molecular ion in which the binding is so tight that nuclear fusion occurs. The muon is normally released after fusion has taken place and so can catalyze further fusions. As the muon has a mean lifetime of 2.2 microseconds, this is the maximum period over which a muon can participate in this process. This article gives an outline of the history of muon catalyzed fusion from 1947, when it was first realised that such a process might occur, to the present day. It includes a description of the contribution that Drachrnan has made to the theory of muon catalyzed fusion and the influence this has had on the author's research.

  18. Fusion research principles

    CERN Document Server

    Dolan, Thomas James

    2013-01-01

    Fusion Research, Volume I: Principles provides a general description of the methods and problems of fusion research. The book contains three main parts: Principles, Experiments, and Technology. The Principles part describes the conditions necessary for a fusion reaction, as well as the fundamentals of plasma confinement, heating, and diagnostics. The Experiments part details about forty plasma confinement schemes and experiments. The last part explores various engineering problems associated with reactor design, vacuum and magnet systems, materials, plasma purity, fueling, blankets, neutronics

  19. Magnetic fusion technology

    CERN Document Server

    Dolan, Thomas J

    2014-01-01

    Magnetic Fusion Technology describes the technologies that are required for successful development of nuclear fusion power plants using strong magnetic fields. These technologies include: ? magnet systems, ? plasma heating systems, ? control systems, ? energy conversion systems, ? advanced materials development, ? vacuum systems, ? cryogenic systems, ? plasma diagnostics, ? safety systems, and ? power plant design studies. Magnetic Fusion Technology will be useful to students and to specialists working in energy research.

  20. Status of fusion maintenance

    International Nuclear Information System (INIS)

    Effective maintenance will be an essential ingredient in determining fusion system productivity. This level of productivity will result only after close attention is paid to the entire system as an entity and appropriate integration of the elements is made. The status of fusion maintenance is reviewed in the context of the entire system. While there are many challenging developmental tasks ahead in fusion maintenance, the required technologies are available in several high-technology industries, including nuclear fission

  1. Filter Bank Fusion frames

    OpenAIRE

    Chebira, Amina; Fickus, Matthew; Mixon, Dustin G.

    2011-01-01

    In this paper we characterize and construct novel oversampled filter banks implementing fusion frames. A fusion frame is a sequence of orthogonal projection operators whose sum can be inverted in a numerically stable way. When properly designed, fusion frames can provide redundant encodings of signals which are optimally robust against certain types of noise and erasures. However, up to this point, few implementable constructions of such frames were known; we show how to construct them using ...

  2. Fusion facility siting considerations

    International Nuclear Information System (INIS)

    Inherent in the fusion program's transition from hydrogen devices to commercial power machines is a general increase in the size and scope of succeeding projects. This growth will lead to increased emphasis on safety, environmental impact, and the external effects of fusion in general, and of each new device in particular. A critically important consideration in this regard is site selection. The purpose of this paper is to examine major siting issues that may affect the economics, safety, and environmental impact of fusion

  3. Fusion facility siting considerations

    Science.gov (United States)

    Bussell, G. T.

    1985-02-01

    Inherent in the fusion program's transition from hydrogen devices to commercial power machines is a general increase in the size and scope of succeeding projects. This growth will lead to increased emphasis on safety, environmental impact, and the external effects of fusion in general, and of each new device in particular. An important consideration in this regard is site selection. Major siting issues that may affect the economics, safety, and environmental impact of fusion are examined.

  4. 2A self-cleaving peptide-based multi-gene expression system in the silkworm Bombyx mori

    Science.gov (United States)

    Wang, Yuancheng; Wang, Feng; Wang, Riyuan; Zhao, Ping; Xia, Qingyou

    2015-01-01

    Fundamental and applied studies of silkworms have entered the functional genomics era. Here, we report a multi-gene expression system (MGES) based on 2A self-cleaving peptide (2A), which regulates the simultaneous expression and cleavage of multiple gene targets in the silk gland of transgenic silkworms. First, a glycine-serine-glycine spacer (GSG) was found to significantly improve the cleavage efficiency of 2A. Then, the cleavage efficiency of six types of 2As with GSG was analyzed. The shortest porcine teschovirus-1 2A (P2A-GSG) exhibited the highest cleavage efficiency in all insect cell lines that we tested. Next, P2A-GSG successfully cleaved the artificial human serum albumin (66 kDa) linked with human acidic fibroblast growth factor (20.2 kDa) fusion genes and vitellogenin receptor fragment (196 kD) of silkworm linked with EGFP fusion genes, importantly, vitellogenin receptor protein was secreted to the outside of cells. Furthermore, P2A-GSG successfully mediated the simultaneous expression and cleavage of a DsRed and EGFP fusion gene in silk glands and caused secretion into the cocoon of transgenic silkworms using our sericin1 expression system. We predicted that the MGES would be an efficient tool for gene function research and innovative research on various functional silk materials in medicine, cosmetics, and other biomedical areas. PMID:26537835

  5. Development of lung adenocarcinomas with exclusive dependence on oncogene fusions.

    Science.gov (United States)

    Saito, Motonobu; Shimada, Yoko; Shiraishi, Kouya; Sakamoto, Hiromi; Tsuta, Koji; Totsuka, Hirohiko; Chiku, Suenori; Ichikawa, Hitoshi; Kato, Mamoru; Watanabe, Shun-Ichi; Yoshida, Teruhiko; Yokota, Jun; Kohno, Takashi

    2015-06-01

    This report delivers a comprehensive genetic alteration profile of lung adenocarcinomas (LADC) driven by ALK, RET, and ROS1 oncogene fusions. These tumors are difficult to study because of their rarity. Each drives only a low percentage of LADCs. Whole-exome sequencing and copy-number variation analyses were performed on a Japanese LADC cohort (n = 200) enriched in patients with fusions (n = 31, 15.5%), followed by deep resequencing for validation. The driver fusion cases showed a distinct profile with smaller numbers of nonsynonymous mutations in cancer-related genes or truncating mutations in SWI/SNF chromatin remodeling complex genes than in other LADCs (P < 0.0001). This lower mutation rate was independent of age, gender, smoking status, pathologic stage, and tumor differentiation (P < 0.0001) and was validated in nine fusion-positive cases from a U.S. LADCs cohort (n = 230). In conclusion, our findings indicate that LADCs with ALK, RET, and ROS1 fusions develop exclusively via their dependence on these oncogene fusions. The presence of such few alterations beyond the fusions supports the use of monotherapy with tyrosine kinase inhibitors targeting the fusion products in fusion-positive LADCs. PMID:25855381

  6. Approach to multisensor/multilook information fusion

    Science.gov (United States)

    Myler, Harley R.; Patton, Ronald

    1997-07-01

    We are developing a multi-sensor, multi-look Artificial Intelligence Enhanced Information Processor (AIEIP) that combines classification elements of geometric hashing, neural networks and evolutionary algorithms in a synergistic combination. The fusion is coordinated using a piecewise level fusion algorithm that operates on probability data from statistics of the individual classifiers. Further, the AIEIP incorporates a knowledge-based system to aid a user in evaluating target data dynamically. The AIEIP is intended as a semi-autonomous system that not only fuses information from electronic data sources, but also has the capability to include human input derived from battlefield awareness and intelligence sources. The system would be useful in either advanced reconnaissance information fusion tasks where multiple fixed sensors and human observer inputs must be combined or for a dynamic fusion scenario incorporating an unmanned vehicle swarm with dynamic, multiple sensor data inputs. This paper represents our initial results from experiments and data analysis using the individual components of the AIEIP on FLIR target sets of ground vehicles.

  7. Frontiers in fusion research

    CERN Document Server

    Kikuchi, Mitsuru

    2011-01-01

    Frontiers in Fusion Research provides a systematic overview of the latest physical principles of fusion and plasma confinement. It is primarily devoted to the principle of magnetic plasma confinement, that has been systematized through 50 years of fusion research. Frontiers in Fusion Research begins with an introduction to the study of plasma, discussing the astronomical birth of hydrogen energy and the beginnings of human attempts to harness the Sun's energy for use on Earth. It moves on to chapters that cover a variety of topics such as: * charged particle motion, * plasma kinetic theory, *

  8. Fusion reactor safety

    International Nuclear Information System (INIS)

    Nuclear fusion could soon become a viable energy source. Work in plasma physics, fusion technology and fusion safety is progressing rapidly in a number of Member States and international collaboration continues on work aiming at the demonstration of fusion power generation. Safety of fusion reactors and technological and radiological aspects of waste management are important aspects in the development and design of fusion machines. In order to provide an international forum to review and discuss the status and the progress made since 1983 in programmes related to operational safety aspects of fusion reactors, their waste management and decommissioning concepts, the IAEA had organized the Technical Committee on ''Fusion Reactor Safety'' in Culham, 3-7 November 1986. All presentations of this meeting were divided into four sessions: 1. Statements on National-International Fusion Safety Programmes (5 papers); 2. Operation and System Safety (15 papers); 3. Waste Management and Decommissioning (5 papers); 4. Environmental Impacts (6 papers). A separate abstract was prepared for each of these 31 papers. Refs, figs, tabs

  9. Magnetic-confinement fusion

    Science.gov (United States)

    Ongena, J.; Koch, R.; Wolf, R.; Zohm, H.

    2016-05-01

    Our modern society requires environmentally friendly solutions for energy production. Energy can be released not only from the fission of heavy nuclei but also from the fusion of light nuclei. Nuclear fusion is an important option for a clean and safe solution for our long-term energy needs. The extremely high temperatures required for the fusion reaction are routinely realized in several magnetic-fusion machines. Since the early 1990s, up to 16 MW of fusion power has been released in pulses of a few seconds, corresponding to a power multiplication close to break-even. Our understanding of the very complex behaviour of a magnetized plasma at temperatures between 150 and 200 million °C surrounded by cold walls has also advanced substantially. This steady progress has resulted in the construction of ITER, a fusion device with a planned fusion power output of 500 MW in pulses of 400 s. ITER should provide answers to remaining important questions on the integration of physics and technology, through a full-size demonstration of a tenfold power multiplication, and on nuclear safety aspects. Here we review the basic physics underlying magnetic fusion: past achievements, present efforts and the prospects for future production of electrical energy. We also discuss questions related to the safety, waste management and decommissioning of a future fusion power plant.

  10. Laser fusion program overview

    International Nuclear Information System (INIS)

    This program is structured to proceed through a series of well defined fusion milestones to proof of the scientific feasibility, of laser fusion with the Shiva Nova system. Concurrently, those key technical areas, such as advanced lasers, which are required to progress beyond proof of feasibility, are being studied. We have identified and quantified the opportunities and key technical issues in military applications, such as weapons effects simulations, and in civilian applications, such as central-station electric power production. We summarize the current status and future plans for the laser fusion program at LLL, emphasizing the civilian applications of laser fusion

  11. Principles of artificial intelligence

    CERN Document Server

    Nilsson, Nils J

    1980-01-01

    A classic introduction to artificial intelligence intended to bridge the gap between theory and practice, Principles of Artificial Intelligence describes fundamental AI ideas that underlie applications such as natural language processing, automatic programming, robotics, machine vision, automatic theorem proving, and intelligent data retrieval. Rather than focusing on the subject matter of the applications, the book is organized around general computational concepts involving the kinds of data structures used, the types of operations performed on the data structures, and the properties of th

  12. The Artificial Anal Sphincter

    OpenAIRE

    Christiansen, John

    2000-01-01

    The artificial anal sphincter as treatment for end stage anal incontinence was first described in 1987. Published series concern a total of 42 patients, with a success rate of approximately 80%. Infection has been the most serious complication, but a number of technical complications related to the device have also occurred and required revisional procedures in 40% to 60% of the patients. The artificial anal sphincter may be used for the same indications as dynamic graciloplasty except in pat...

  13. RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas

    OpenAIRE

    Bao, Zhao-Shi; Chen, Hui-min; Yang, Ming-Yu; Zhang, Chuan-Bao; Yu, Kai; Ye, Wan-Lu; Hu, Bo-Qiang; Yan, Wei; Zhang, Wei; Akers, Johnny; Ramakrishnan, Valya; Li, Jie; Carter, Bob; Liu, Yan-Wei; HU, HUI-MIN

    2014-01-01

    Studies of gene rearrangements and the consequent oncogenic fusion proteins have laid the foundation for targeted cancer therapy. To identify oncogenic fusions associated with glioma progression, we catalogued fusion transcripts by RNA-seq of 272 gliomas. Fusion transcripts were more frequently found in high-grade gliomas, in the classical subtype of gliomas, and in gliomas treated with radiation/temozolomide. Sixty-seven in-frame fusion transcripts were identified, including three recurrent ...

  14. Construction of Eukaryotic Expression Vector with mBD1-mBD3 Fusion Genes and Exploring Its Activity against Influenza A Virus

    Directory of Open Access Journals (Sweden)

    Wanyi Li

    2014-03-01

    Full Text Available Influenza (flu pandemics have exhibited a great threat to human health throughout history. With the emergence of drug-resistant strains of influenza A virus (IAV, it is necessary to look for new agents for treatment and transmission prevention of the flu. Defensins are small (2–6 kDa cationic peptides known for their broad-spectrum antimicrobial activity. Beta-defensins (β-defensins are mainly produced by barrier epithelial cells and play an important role in attacking microbe invasion by epithelium. In this study, we focused on the anti-influenza A virus activity of mouse β-defensin 1 (mBD1 and β defensin-3 (mBD3 by synthesizing their fusion peptide with standard recombinant methods. The eukaryotic expression vectors pcDNA3.1(+/mBD1-mBD3 were constructed successfully by overlap-PCR and transfected into Madin-Darby canine kidney (MDCK cells. The MDCK cells transfected by pcDNA3.1(+/mBD1-mBD3 were obtained by G418 screening, and the mBD1-mBD3 stable expression pattern was confirmed in MDCK cells by RT-PCR and immunofluorescence assay. The acquired stable transfected MDCK cells were infected with IAV (A/PR/8/34, H1N1, 0.1 MOI subsequently and the virus titers in cell culture supernatants were analyzed by TCID50 72 h later. The TCID50 titer of the experimental group was clearly lower than that of the control group (p < 0.001. Furthermore, BALB/C mice were injected with liposome-encapsulated pcDNA3.1(+/mBD1-mBD3 through muscle and then challenged with the A/PR/8/34 virus. Results showed the survival rate of 100% and lung index inhibitory rate of 32.6% in pcDNA3.1(+/mBD1-mBD3group; the TCID50 titer of lung homogenates was clearly lower than that of the control group (p < 0.001. This study demonstrates that mBD1-mBD3 expressed by the recombinant plasmid pcDNA3.1(+/mBD1-mBD3 could inhibit influenza A virus replication both in vitro and in vivo. These observations suggested that the recombinant mBD1-mBD3 might be developed into an agent for

  15. KAR5 Encodes a Novel Pheromone-inducible Protein Required for Homotypic Nuclear Fusion

    OpenAIRE

    Beh, Christopher T.; Brizzio, Valeria; Rose, Mark D.

    1997-01-01

    KAR5 is required for membrane fusion during karyogamy, the process of nuclear fusion during yeast mating. To investigate the molecular mechanism of nuclear fusion, we cloned and characterized the KAR5 gene and its product. KAR5 is a nonessential gene, and deletion mutations produce a bilateral defect in the homotypic fusion of yeast nuclei. KAR5 encodes a novel protein that shares similarity with a protein in Schizosaccharomyces pombe that may play a similar role in nuclear fusion. Kar5p is i...

  16. Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia.

    OpenAIRE

    Mitani, K; Ogawa, S.; Tanaka, T; Miyoshi, H; Kurokawa, M; Mano, H.; Yazaki, Y; Ohki, M; Hirai, H

    1994-01-01

    The t(3;21)(q26;q22) translocation, which is one of the consistent chromosomal abnormalities found in blastic crisis of chronic myelocytic leukemia (CML), is thought to play an important role in the leukemic progression of CML to an acute blastic crisis phase. The AML1 gene, which is located at the translocation breakpoint of the t(8;21)(q22;q22) translocation found in acute myelocytic leukemia, was also rearranged by the t(3;21)(q26;q22) translocation. Screening of a cDNA library of the t(3;...

  17. Chorioallantoic Fusion Defects and Embryonic Lethality Resulting from Disruption of Zfp36L1, a Gene Encoding a CCCH Tandem Zinc Finger Protein of the Tristetraprolin Family

    OpenAIRE

    Stumpo, Deborah J.; Byrd, Noah A.; Phillips, Ruth S.; Ghosh, Sanjukta; Maronpot, Robert R.; Castranio, Trisha; Meyers, Erik N.; Mishina, Yuji; Blackshear, Perry J.

    2004-01-01

    The mouse gene Zfp36L1 encodes zinc finger protein 36-like 1 (Zfp36L1), a member of the tristetraprolin (TTP) family of tandem CCCH finger proteins. TTP can bind to AU-rich elements within the 3′-untranslated regions of the mRNAs encoding tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), leading to accelerated mRNA degradation. TTP knockout mice exhibit an inflammatory phenotype that is largely due to increased TNF secretion. Zfp36L1 has activities sim...

  18. Membrane fusion machines of paramyxoviruses: capture of intermediates of fusion

    OpenAIRE

    Charles J Russell; Theodore S Jardetzky; Lamb, Robert A.

    2001-01-01

    Peptides derived from heptad repeat regions adjacent to the fusion peptide and transmembrane domains of many viral fusion proteins form stable helical bundles and inhibit fusion specifically. Paramyxovirus SV5 fusion (F) protein-mediated fusion and its inhibition by the peptides N-1 and C-1 were analyzed. The temperature dependence of fusion by F suggests that thermal energy, destabilizing proline residues and receptor binding by the hemagglutinin–neuraminidase (HN) protein collectively contr...

  19. [Cashmere goat bacterial artificial chromosome recombination and cell transfection system].

    Science.gov (United States)

    Huang, Tian; Cao, Zhongyang; Yang, Yaohui; Cao, Gengsheng

    2016-03-01

    The Cashmere goat is mainly used to produce cashmere, which is very popular for its delicate fiber, luscious softness and natural excellent warm property. Keratin associated protein (KAP) and bone morphogenetic protein (BMP) of the Cashmere goat play an important role in the proliferation and development of cashmere fiber follicle cells. Bacterial artificial chromosome containing kap6.3, kap8.1 and bmp4 genes were used to increase the production and quality of Cashmere. First, we constructed bacterial artificial chromosomes by homology recombination. Then Tol2 transposon was inserted into bacterial artificial chromosomes that were then transfected into Cashmere goat fibroblasts by Amaxa Nucleofector technology according to the manufacture's instructions. We successfully constructed the BAC-Tol2 vectors containing target genes. Each vector contained egfp report gene with UBC promoter, Neomycin resistant gene for cell screening and two loxp elements for resistance removing after transfected into cells. The bacterial artificial chromosome-Tol2 vectors showed a high efficiency of transfection that can reach 1% to 6% with a highest efficiency of 10%. We also obtained Cashmere goat fibroblasts integrated exogenous genes (kap6.3, kap8.1 and bmp4) preparing for the clone of Cashmere goat in the future. Our research demonstrates that the insertion of Tol2 transposons into bacterial artificial chromosomes improves the transfection efficiency and accuracy of bacterial artificial chromosome error-free recombination.

  20. [Cashmere goat bacterial artificial chromosome recombination and cell transfection system].

    Science.gov (United States)

    Huang, Tian; Cao, Zhongyang; Yang, Yaohui; Cao, Gengsheng

    2016-03-01

    The Cashmere goat is mainly used to produce cashmere, which is very popular for its delicate fiber, luscious softness and natural excellent warm property. Keratin associated protein (KAP) and bone morphogenetic protein (BMP) of the Cashmere goat play an important role in the proliferation and development of cashmere fiber follicle cells. Bacterial artificial chromosome containing kap6.3, kap8.1 and bmp4 genes were used to increase the production and quality of Cashmere. First, we constructed bacterial artificial chromosomes by homology recombination. Then Tol2 transposon was inserted into bacterial artificial chromosomes that were then transfected into Cashmere goat fibroblasts by Amaxa Nucleofector technology according to the manufacture's instructions. We successfully constructed the BAC-Tol2 vectors containing target genes. Each vector contained egfp report gene with UBC promoter, Neomycin resistant gene for cell screening and two loxp elements for resistance removing after transfected into cells. The bacterial artificial chromosome-Tol2 vectors showed a high efficiency of transfection that can reach 1% to 6% with a highest efficiency of 10%. We also obtained Cashmere goat fibroblasts integrated exogenous genes (kap6.3, kap8.1 and bmp4) preparing for the clone of Cashmere goat in the future. Our research demonstrates that the insertion of Tol2 transposons into bacterial artificial chromosomes improves the transfection efficiency and accuracy of bacterial artificial chromosome error-free recombination. PMID:27349114

  1. Induction of specific humoral and cellular immune responses in a mouse model following gene fusion of HSP70C and Hantaan virus Gn and S0.7 in an adenoviral vector.

    Directory of Open Access Journals (Sweden)

    Linfeng Cheng

    Full Text Available Heat shock proteins (HSPs display adjuvant functions when given as fusion proteins to enhance vaccination efficiency. To evaluate enhanced potency of Hantaan virus (HTNV glycoprotein (GP and nucleocapsid protein (NP immunogenicity by heat shock protein 70 (HSP70, a recombinant adenovirus rAd-GnS0.7-pCAG-HSP70C expression vector was developed by genetically linking the HSP70 C-terminal gene (HSP70 359-610 aa, HSP70C to the Gn and 0.7 kb fragment of the NP (aa1-274-S0.7. C57BL/6 mice were immunized with these recombinant adenoviral vectors. A series of immunological assays determined the immunogenicity of the recombinant adenoviral vectors. The results showed that rAd-GnS0.7-pCAG-HSP70C induced a stronger humoral and cellular immune response than other recombinant adenoviruses (rAd-GnS0.7-pCAG and rAd-GnS0.7 and the HFRS vaccine control. Animal protection experiments showed that rAd-GnS0.7-pCAG-HSP70C was effective at protecting C57BL/6 mice from HTNV infection. The results of the immunological experiments showed that HSP70C lead to enhanced vaccine potency, and suggested significant potential in the development of genetically engineered vaccines against HTNV.

  2. Frequent fusion and fission of plant mitochondria with unequal nucleoid distribution

    OpenAIRE

    Arimura, Shin-ichi; Yamamoto, Junko; Aida, Gen Paul; Nakazono, Mikio; Tsutsumi, Nobuhiro

    2004-01-01

    The balance between mitochondrial fusion and fission influences the reticular shape of mitochondria in yeasts. Little is known about whether mitochondria fusion occurs in plants. Plant mitochondria are usually more numerous and more grain-shaped than animal mitochondria. blast searches of the nuclear and mitochondrial genome sequences of Arabidopsis thaliana did not find any obvious homologue of mitochondrial fusion genes found in animals and yeasts. To determine whether mitochondrial fusion ...

  3. Recombination and Fusion Expression of Porcine Defensin Gene pBD-2 in E.Coli%猪防御素基因pBD-2在大肠杆菌中的重组和融合表达

    Institute of Scientific and Technical Information of China (English)

    徐海涛; 马立保; 何启盖; 廖冰麟; 任芬芬

    2011-01-01

    哺乳动物防御素是动物机体在抵御病原微生物的防御反应中产生的一类重要的抗菌肽物质,具有十分广泛的抗菌谱,在先天免疫上起重要作用.本研究根据已报道的pBD-2基因cDNA序列,合成了3条基因片段(1、2、3).片段1、2和片段2、3各有15个碱基互补配对,PCR扩增延伸得到pBD-2基因,将pBD-2基因克隆至原核表达载体pGEX-KG,成功地在大肠杆菌BL21(DE3)中表达出pBD-2融合蛋白.pBD-2基因的成功表达为进一步研究其抗菌活性打下了基础.%Defensin is an important antimicrobial peptide produced in the course of animals' defense against pathogens,which has a broad antibacterial spectrum and plays an important role in innate immunity. Based on cDNA sequence of porcine defensin βdefensin 2 gene reported in this study, three gene fragment (1,2,3) were synthesized in this experiment. Fragment 1,2 and fragment 2,3 had respectively 15 bases for complementary pair. pBD-2 gene was produced by PCR amplifing, and pBD-2 was inserted into expression vector (pGEX-KG) and recombinant vector transformed into E.coli, where recombinant vector produced fusion protein successfully. The expression of pBD-2 gene lays a foundation in research on antimicrobial activities of defensin.

  4. Nuclear fusion inside condense matters

    Institute of Scientific and Technical Information of China (English)

    HE Jing-tang

    2007-01-01

    This article describes in detail the nuclear fusion inside condense matters--the Fleischmann-Pons effect, the reproducibility of cold fusions, self-consistentcy of cold fusions and the possible applications.

  5. Fusion helps diversification

    NARCIS (Netherlands)

    S. Liang; Z. Ren; M. de Rijke

    2014-01-01

    A popular strategy for search result diversification is to first retrieve a set of documents utilizing a standard retrieval method and then rerank the results. We adopt a different perspective on the problem, based on data fusion. Starting from the hypothesis that data fusion can improve performance

  6. Controlled Nuclear Fusion.

    Science.gov (United States)

    Glasstone, Samuel

    This publication is one of a series of information booklets for the general public published by The United States Atomic Energy Commission. Among the topics discussed are: Importance of Fusion Energy; Conditions for Nuclear Fusion; Thermonuclear Reactions in Plasmas; Plasma Confinement by Magnetic Fields; Experiments With Plasmas; High-Temperature…

  7. Fusion product spectra

    International Nuclear Information System (INIS)

    Accurate fusion product data is required for most fusion plasma simulations. The energy broadening of reaction products is demonstrated to be more complicated than the usual Gaussian broadening. The accurate integrals are performed to obtain , , and for all binary reactions in the four- and five-nucleon systems. Reaction cross sections were developed using R-Matrix models that include most recent measurements

  8. Controlled thermonuclear fusion

    CERN Document Server

    Bobin, Jean Louis

    2014-01-01

    The book is a presentation of the basic principles and main achievements in the field of nuclear fusion. It encompasses both magnetic and inertial confinements plus a few exotic mechanisms for nuclear fusion. The state-of-the-art regarding thermonuclear reactions, hot plasmas, tokamaks, laser-driven compression and future reactors is given.

  9. Fusion reactor materials

    International Nuclear Information System (INIS)

    At the Belgian Nuclear Research Centre SCK-CEN, activities related to fusion focus on environmental tolerance of opto-electronic components. The objective of this program is to contribute to the knowledge on the behaviour, during and after neutron irradiation, of fusion-reactor materials and components. The main scientific activities for 1997 are summarized

  10. Nuclear fusion in Jupiter

    International Nuclear Information System (INIS)

    We study nuclear fusion occurring according to conventional wisdom in the planet Jupiter. In particular, we consider if in a standard evolutionary model of Jupiter a significant part of Jupiter's luminosity has been due to nuclear fusion at any time during its evolution. Nuclear rate equations in dense matter allowing for screening and pressure effects have been integrated in time

  11. FUSION03, Concluding Remarks

    OpenAIRE

    Balantekin, A. B.

    2004-01-01

    Fusion reactions below the Coulomb barrier provide new insights into multidimensional quantum tunneling, nuclear reaction dynamics and nuclear structure. These reactions are also of considerable interest to nuclear astrophysics. In this summary recent developments in the field are reviewed and open questions related to subbarrier fusion are presented.

  12. Two Horizons of Fusion

    Science.gov (United States)

    Lo, Mun Ling; Chik, Pakey Pui Man

    2016-01-01

    In this paper, we aim to differentiate the internal and external horizons of "fusion." "Fusion" in the internal horizon relates to the structure and meaning of the object of learning as experienced by the learner. It clarifies the interrelationships among an object's critical features and aspects. It also illuminates the…

  13. Thermal Resonance Fusion

    CERN Document Server

    Dong, Bao-Guo

    2015-01-01

    We first show a possible mechanism to create a new type of nuclear fusion, thermal resonance fusion, i.e. low energy nuclear fusion with thermal resonance of light nuclei or atoms, such as deuterium or tritium. The fusion of two light nuclei has to overcome the Coulomb barrier between these two nuclei to reach up to the interacting region of nuclear force. We found nuclear fusion could be realized with thermal vibrations of crystal lattice atoms coupling with light atoms at low energy by resonance to overcome this Coulomb barrier. Thermal resonances combining with tunnel effects can greatly enhance the probability of the deuterium fusion to the detectable level. Our low energy nuclear fusion mechanism research - thermal resonance fusion mechanism results demonstrate how these light nuclei or atoms, such as deuterium, can be fused in the crystal of metal, such as Ni or alloy, with synthetic thermal vibrations and resonances at different modes and energies experimentally. The probability of tunnel effect at dif...

  14. Magnetic fusion theory effort

    International Nuclear Information System (INIS)

    The present publication is a comprehensive listing of the magnetic fusion theory effort. It updates the last publication, ERDA 77-18, and gives data on the FY 1977 and FY 1978 budgets. There is a section devoted to the National Magnetic Fusion Computer Center

  15. Fusion of biological membranes

    Indian Academy of Sciences (India)

    K Katsov; M Müller; M Schick

    2005-06-01

    The process of membrane fusion has been examined by Monte Carlo simulation, and is found to be very different than the conventional picture. The differences in mechanism lead to several predictions, in particular that fusion is accompanied by transient leakage. This prediction has recently been verified. Self-consistent field theory is applied to examine the free energy barriers in the different scenarios.

  16. Fusion Power Deployment

    International Nuclear Information System (INIS)

    Fusion power plants could be part of a future portfolio of non-carbon dioxide producing energy supplies such as wind, solar, biomass, advanced fission power, and fossil energy with carbon dioxide sequestration. In this paper, we discuss key issues that could impact fusion energy deployment during the last half of this century. These include geographic issues such as resource availability, scale issues, energy storage requirements, and waste issues. The resource needs and waste production associated with fusion deployment in the U.S. should not pose serious problems. One important feature of fusion power is the fact that a fusion power plant should be locatable within most local or regional electrical distribution systems. For this reason, fusion power plants should not increase the burden of long distance power transmission to our distribution system. In contrast to fusion power, regional factors could play an important role in the deployment of renewable resources such as wind, solar and biomass or fossil energy with CO2 sequestration. We examine the role of these regional factors and their implications for fusion power deployment

  17. Fusion Canada issue 22

    International Nuclear Information System (INIS)

    A short bulletin from the National Fusion Program highlighting in this issue a bi-lateral meeting between Canada and Japan, water and hydrogen detritiation, in-situ tokamak surface analysis, an update of CCFM/TdeV and tritium accounting Industry guidance in Fusion, fast probe for plasma-surface interaction. 4 figs

  18. Magnetic Fusion Program Plan

    International Nuclear Information System (INIS)

    This Plan reflects the present conditions of the energy situation and is consistent with national priorities for the support of basic and applied research. It is realistic in taking advantage of the technical position that the United States has already established in fusion research to make cost-effective progress toward the development of fusion power as a future energy option

  19. Tight p-fusion frames

    OpenAIRE

    Bachoc, Christine; Ehler, Martin

    2012-01-01

    Fusion frames enable signal decompositions into weighted linear subspace components. For positive integers p, we introduce p-fusion frames, a sharpening of the notion of fusion frames. Tight p-fusion frames are closely related to the classical notions of designs and cubature formulas in Grassmann spaces and are analyzed with methods from harmonic analysis in the Grassmannians. We define the p-fusion frame potential, derive bounds for its value, and discuss the connections to tight p-fusion fr...

  20. A saturation screen for cis-acting regulatory DNA in the Hox genes of Ciona intestinalis

    Energy Technology Data Exchange (ETDEWEB)

    Keys, David N.; Lee, Byung-in; Di Gregorio, Anna; Harafuji, Naoe; Detter, Chris; Wang, Mei; Kahsai, Orsalem; Ahn, Sylvia; Arellano, Andre; Zhang, Quin; Trong, Stephan; Doyle, Sharon A.; Satoh, Noriyuki; Satou, Yutaka; Saiga, Hidetoshi; Christian, Allen; Rokhsar, Dan; Hawkins, Trevor L.; Levine, Mike; Richardson, Paul

    2005-01-05

    A screen for the systematic identification of cis-regulatory elements within large (>100 kb) genomic domains containing Hox genes was performed by using the basal chordate Ciona intestinalis. Randomly generated DNA fragments from bacterial artificial chromosomes containing two clusters of Hox genes were inserted into a vector upstream of a minimal promoter and lacZ reporter gene. A total of 222 resultant fusion genes were separately electroporated into fertilized eggs, and their regulatory activities were monitored in larvae. In sum, 21 separable cis-regulatory elements were found. These include eight Hox linked domains that drive expression in nested anterior-posterior domains of ectodermally derived tissues. In addition to vertebrate-like CNS regulation, the discovery of cis-regulatory domains that drive epidermal transcription suggests that C. intestinalis has arthropod-like Hox patterning in the epidermis.

  1. Compact fusion reactors

    CERN Document Server

    CERN. Geneva

    2015-01-01

    Fusion research is currently to a large extent focused on tokamak (ITER) and inertial confinement (NIF) research. In addition to these large international or national efforts there are private companies performing fusion research using much smaller devices than ITER or NIF. The attempt to achieve fusion energy production through relatively small and compact devices compared to tokamaks decreases the costs and building time of the reactors and this has allowed some private companies to enter the field, like EMC2, General Fusion, Helion Energy, Lawrenceville Plasma Physics and Lockheed Martin. Some of these companies are trying to demonstrate net energy production within the next few years. If they are successful their next step is to attempt to commercialize their technology. In this presentation an overview of compact fusion reactor concepts is given.

  2. FUSION OF MEDICAL IMAGES

    Directory of Open Access Journals (Sweden)

    ALINE APARECIDA DE OLIVEIRA

    2013-08-01

    Full Text Available The use of image multiple modalities to achieve medical diagnosis has been commom practice lately. Nowadays the most used practice is medical image fusion, that is integrating information from several different methods within the same image. This paper aims at showing aplication and functionality of medical image fusion process such as Computed Tomography, Magnetic Resonance Imaging, Positron Emission Tomography and Doppler U.S. Image fusion process can be perfomed by pixel to pixel, region to region as well as based on decision taking. Free softwares can be found in the internet and images can be obtained either in separated or conneceted equipments. The choice of processes depends on several factors and the purpose of fusion as well as characteristics and conditions of each method should be taken into consideration. Currently equipment manufacturers are investing at improving the quality and detection capacity of images aiming at upgrading the fusion process which makes image interpretation more evident and trustworthy.

  3. Some fusion perspectives

    International Nuclear Information System (INIS)

    Some of the concepts of nuclear fusion reactions, advanced fusion fuels, environmental impacts, etc., are explored using the following general outline: I. Principles of Fusion (Nuclear Fuels and Reactions, Lawson Condition, n tau vs T, Nuclear Burn Characteristics); II. Magnetic Mirror Possibilities (the Ion Layer and Electron Layer, Exponential Build-up at MeV energies, Lorentz trapping at GeV energies); III. Pellet Fuel Fusion Prospects (Advanced Pellet Fuel Fusion Prospects, Burn Characteristics and Applications, Excitation-heating Prospects for Runaway Ion Temperatures). Inasmuch as the outline is very skeletal, a significant research and development effort may be in order to evaluate these prospects in more detail and hopefully ''harness the H-bomb'' for peaceful applications, the author concludes. 28 references

  4. Filter Bank Fusion Frames

    CERN Document Server

    Chebira, Amina; Mixon, Dustin G

    2010-01-01

    In this paper we characterize and construct novel oversampled filter banks implementing fusion frames. A fusion frame is a sequence of orthogonal projection operators whose sum can be inverted in a numerically stable way. When properly designed, fusion frames can provide redundant encodings of signals which are optimally robust against certain types of noise and erasures. However, up to this point, few implementable constructions of such frames were known; we show how to construct them using oversampled filter banks. In this work, we first provide polyphase domain characterizations of filter bank fusion frames. We then use these characterizations to construct filter bank fusion frame versions of discrete wavelet and Gabor transforms, emphasizing those specific finite impulse response filters whose frequency responses are well-behaved.

  5. Industry's role in inertial fusion

    International Nuclear Information System (INIS)

    This paper is an address to the Tenth Symposium on Fusion Engineering. The speaker first addressed the subject of industry's role in inertial fusion three years earlier in 1980, outlining programs that included participation in the Shiva construction project, and the industrial participants' program set up in the laser fusion program to bring industrial scientists and engineers into the laboratory to work on laser fusion. The speaker is now the president of KMS Fusion, Inc., the primary industrial participant in the inertial fusion program. The outlook for fusion energy and the attitude of the federal government toward the fusion program is discussed

  6. Non-Fusion and Fusion Expression of β-Galactosidase from Lactobacillus bulgaricus in Lactococcus lactis

    Institute of Scientific and Technical Information of China (English)

    CHUAN WANG; CHAO-WU ZHANG; HENG-CHUAN LIU; QIAN YU; XIAO-FANG PEI

    2008-01-01

    Objective To construct four recombinant Lactococcus lactis strains exhibiting high β-galactosidase activity in fusion or non-fusion ways, and to study the influence factors for their protein expression and secretion. Methods The gene fragments encoding β-galactosidase from two strains of Lactobacillus bulgaricus, wch9901 isolated from yogurt and 1.1480 purchased from the Chinese Academy of Sciences, were amplified and inserted into lactococcal expression vector pMG36e. For fusion expression, the open reading frame of the β-galactosidase gene was amplified, while for non-fusion expression, the open reading frame of the β-galactosidase gene was amplified with its native Shine-Dalgarno sequence upstream. The start codon of the β-galactosidase gene partially overlapped with the stop codon of vector origin open reading frame. Then, the recombinant plasmids were transformed into Escherichia coli DH5α and Lactococcus lactis subsp, lactis MG1363 and confirmed by determining β-galactosidase activities. Results The non-fusion expression plasmids showed a significantly higher β-galactosidase activity in transformed strains than the fusion expression plasmids. The highest enzyme activity was observed in Lactococcus lactis transformed with the non-fusion expression plasmids which were inserted into the β-galactosidase gene from Lactobacillus bulgaricus wch9901. The β-galactosidase activity was 2.75 times as high as that of the native counterpart. In addition, β-galactosidase expressed by recombinant plasmids in Lactococcus lactis could be secreted into the culture medium. The highest secretion rate (27.1%) was observed when the culture medium contained 20 g/L of lactose. Conclusion Different properties of the native bacteria may have some effects on the protein expression of recombinant plasmids. Non-fusion expression shows a higher enzyme activity in host bacteria. There may be a ost-related weak secretion signal peptide gene within the structure gene of Lb

  7. Research on Application of Artificial Fish Swarm Algorithm in Gene Regulatory Network%人工鱼群算法在基因调控网络中的应用研究

    Institute of Scientific and Technical Information of China (English)

    田旺兰; 李加升

    2014-01-01

    在分析基因调控网络现状及优缺点的基础上,提出利用人工鱼群算法对阈值布尔网络模型构建下的基因调控网络进行研究。将阈值布尔网络模型应用于花发育形态模型,构建基于预定义吸引子和极限环的综合网络。比较人工鱼群算法与模拟退火算法在基因调控网络中的应用情况,分析网络节点更新机制变化时布尔网络保留吸引子的能力,发现在极限环长度为2和特定网络拓扑下网络才具有鲁棒性。实验结果表明,与模拟退火算法相比,人工鱼群算法在网络发现、鲁棒性方面具有更好的性能,因此利用人工鱼群算法学习布尔网络结构是有效可行的。%Based on the analysis of the advantages and disadvantages of the current appliance of swarm intelligence algorithm into Gene Regulatory Network ( GRN ) , this paper studies the gene regulatory network constructed under Boolean network model using Artificial Fish Swarm Algorithm ( AFSA ) . Especially, the comprehensive network of predefined attractors and limit cycle is formulated by applying Boolean network model into flower growth morphogenesis. After comparing AFSA with Simulated Annealing( SA) and analyzing the ability of the networks to preserve the attractors when the updating schemes is changed from parallel to sequential,the paper finds the network has robustness within the limit cycle length equal to two and specific network topologies. Experimental results show that the intelligence algorithm outperforms simulated annealing in network discovery and robustness. Therefore,it is feasible to learn Boolean network using AFSA.

  8. Inhibitory effect of RNAi on AML1-ETO fusion gene expression in leukemia cells%RNA干扰对急性髓系白血病AML1-ETO融合基因表达的抑制作用

    Institute of Scientific and Technical Information of China (English)

    卫菊; 李肃; 王椿; 秦尤文; 马晓霞; 谢匡成; 颜式可; 高彦荣; 蔡琦

    2008-01-01

    目的 应用RNA干扰技术抑制Kasumi-1细胞AML1-ETO融合基因的表达,研究随后出现的细胞增殖和细胞周期变化.方法 体外化学合成针对AML1-ETO融合基因的小干扰RNA(siRNA),并用电穿孔方法将AML1-ETO siRNA转染Kasumi-1细胞,以非特异性的siRNA转染细胞作阴性对照;电转带有增强型绿色荧光蛋白(EGFP)的载体,流式细胞术检测其绿色荧光以确定电转效率;荧光染料实时定量PCR及Western blot检测AML1-ETO siRNA的抑制效应;并应用CCK-8实验法检测细胞增殖率;采用碘化丙锭(PI)法测定细胞周期DNA含量.结果 电转增强EGFP的转染效率可达44.5%;电转AML1-ETO siRNA可以有效抑制AML1-ETO融合基因在mRNA和蛋白水平的表达;电转AML1-ETO siRNA 72 h后细胞增殖率[(47.90±0.02)%]低于对照组[(66.90±0.08)%](P<0.05);PI染色显示AML1-ETO siRNA转染细胞72 h后,G1期细胞比例为38.3%,对照组为31.6%,而处于G2/M期细胞分别为1.8%和2.4%.结论 化学合成的特异性siRNA能抑制AML1-ETO融合基因的表达,siRNA介导的AML1-ETo融合蛋白表达减少阻滞Kasnmi-1细胞在G1期,进而抑制细胞增殖.%Objective By inhibiting AML1-ETO fusion gene expression in Kasumi-I cells with RNAi, to investigate the changes in cell proliferation and cell cycle. Methods The small interference RNAs (siRNAs) specifically targeting the AML1-ETO fusion gene were synthesized in vitro and transfected into Ka-sumi-1 cells by electroporation, the non-specific siRNAs transfected cells were taken as control. EGFP plas-mid was transfected into Kasumi-1 cell and the transfection efficiency was detected by FCM. Inhibitory effect of siRNAs were detected by real-time RT-PCR and Western blots. Cell proliferation was measured by CCK-8 assay. DNA content was detected by PI assay. Results The transfection efficiency was 44.5%. The AML1-ETO specific siRNAs inhibited AML1-ETO expression at both mRNA and protein levels. The cell proliferation rate in si

  9. Artificial Promoters for Metabolic Optimization

    DEFF Research Database (Denmark)

    Jensen, Peter Ruhdal; Hammer, Karin

    1998-01-01

    In this article, we review some of the expression systems that are available for Metabolic Control Analysis and Metabolic Engineering, and examine their advantages and disadvantages in different contexts. In a recent approach, artificial promoters for modulating gene expression in micro-organisms...... level is then, in principle, ready for use in the industrial fermentation process; another advantage is that the system can be used to optimize the expression of different enzymes within the same cell. (C) 1998 John Wiley & Sons, Inc....... of activity change. Promoter libraries generated by this approach allow for optimization of gene expression and for experimental control analysis in a wide range of biological systems by choosing from the promoter library promoters giving, e.g., 25%, 50%, 200%, and 400% of the normal expression level...... of the gene in question. If the relevant variable (e.g., the flux or yield) is then measured with each of these constructs, then one can calculate the control coefficient and determine the optimal expression level. One advantage of the method is that the construct which is found to have the optimal expression...

  10. Artificial muscles on heat

    Science.gov (United States)

    McKay, Thomas G.; Shin, Dong Ki; Percy, Steven; Knight, Chris; McGarry, Scott; Anderson, Iain A.

    2014-03-01

    Many devices and processes produce low grade waste heat. Some of these include combustion engines, electrical circuits, biological processes and industrial processes. To harvest this heat energy thermoelectric devices, using the Seebeck effect, are commonly used. However, these devices have limitations in efficiency, and usable voltage. This paper investigates the viability of a Stirling engine coupled to an artificial muscle energy harvester to efficiently convert heat energy into electrical energy. The results present the testing of the prototype generator which produced 200 μW when operating at 75°C. Pathways for improved performance are discussed which include optimising the electronic control of the artificial muscle, adjusting the mechanical properties of the artificial muscle to work optimally with the remainder of the system, good sealing, and tuning the resonance of the displacer to minimise the power required to drive it.

  11. Artificial intelligence in nanotechnology.

    Science.gov (United States)

    Sacha, G M; Varona, P

    2013-11-15

    During the last decade there has been increasing use of artificial intelligence tools in nanotechnology research. In this paper we review some of these efforts in the context of interpreting scanning probe microscopy, the study of biological nanosystems, the classification of material properties at the nanoscale, theoretical approaches and simulations in nanoscience, and generally in the design of nanodevices. Current trends and future perspectives in the development of nanocomputing hardware that can boost artificial-intelligence-based applications are also discussed. Convergence between artificial intelligence and nanotechnology can shape the path for many technological developments in the field of information sciences that will rely on new computer architectures and data representations, hybrid technologies that use biological entities and nanotechnological devices, bioengineering, neuroscience and a large variety of related disciplines.

  12. Artificial intelligence in nanotechnology

    International Nuclear Information System (INIS)

    During the last decade there has been increasing use of artificial intelligence tools in nanotechnology research. In this paper we review some of these efforts in the context of interpreting scanning probe microscopy, the study of biological nanosystems, the classification of material properties at the nanoscale, theoretical approaches and simulations in nanoscience, and generally in the design of nanodevices. Current trends and future perspectives in the development of nanocomputing hardware that can boost artificial-intelligence-based applications are also discussed. Convergence between artificial intelligence and nanotechnology can shape the path for many technological developments in the field of information sciences that will rely on new computer architectures and data representations, hybrid technologies that use biological entities and nanotechnological devices, bioengineering, neuroscience and a large variety of related disciplines. (topical review)

  13. Artificial intelligence in nanotechnology

    Science.gov (United States)

    Sacha, G. M.; Varona, P.

    2013-11-01

    During the last decade there has been increasing use of artificial intelligence tools in nanotechnology research. In this paper we review some of these efforts in the context of interpreting scanning probe microscopy, the study of biological nanosystems, the classification of material properties at the nanoscale, theoretical approaches and simulations in nanoscience, and generally in the design of nanodevices. Current trends and future perspectives in the development of nanocomputing hardware that can boost artificial-intelligence-based applications are also discussed. Convergence between artificial intelligence and nanotechnology can shape the path for many technological developments in the field of information sciences that will rely on new computer architectures and data representations, hybrid technologies that use biological entities and nanotechnological devices, bioengineering, neuroscience and a large variety of related disciplines.

  14. 猪白细胞介素6和α干扰素基因的融合及其原核表达%Fusion and prokaryotic expression of interleukin-6 and interferon-α genes in swine

    Institute of Scientific and Technical Information of China (English)

    霍海龙; 赵跃; 王锐; 李卫真; 张永云; 刘丽仙; 王配; 苗永旺; 钱林东

    2013-01-01

    To achieve the fusion of interleukin-6/interferon-a (IL6/IFNa) genes and to investigate the feasibility of fusion protein as an iramunoadjuvant, the coding sequences of 116 and IFNa were cloned. Based on the coding sequences and the sequence of prokaryotic expression vector pET32a, the mature peptide sequences of 116 and IFNa were amplified using the specific primers designed with restriction enzyme sites, linker sequences and His tag and then transfected into Escherichia coli DH5a after linked with pMD18, respectively. The plasmids were extracted and digested by restriction enzyme respectively, and were linked together to construct the recombinant plas-mid of pMD18-/L6-IFNa. The plasmid was tranformed into E. coli DH5a and Rosetta(DE3) , and then expressed by the induction of different concentrations of IPTG for different time. The results showed that the recombinant plasmid of pET32-IL6-IFNa was constructed successfully. SDS-PAGE revealed that recombinant fusion proteins were highly expressed in E. coli Rosetta ( DE3) , with the molecular weight of 44 960. The expression were made the greatest after induction by 1. 00 mmol/L IPTG for 7. 0 h. PET32a-IL6-IFNcx existed in inclusion body form.%为了获得猪白细胞介素6(IL6)和α干扰素(IFNα)双重活性的融合蛋白,研究其作为免疫佐剂的可行性,利用IL6和IFNα基因的编码区序列以及原核表达载体pET32a序列,设计了带有限制性内切酶位点、Linker序列以及His标签的特异性引物扩增出猪IL6和IFNα的成熟肽基因序列,并分别与克隆载体pMD18连接后转化Escherichiα coli DH5α,提取质粒酶切并连接构建重组质粒pMD 18-IL6-IFNα.将该重组质粒和表达载体pET32a同时酶切并连接构建pET32-IL6-IFNα重组质粒,依次转化E.coli DH5α和E.coli Rosetta (DE3)感受态细胞,并经不同终浓度的IPTG以及不同时间的诱导表达.结果成功构建了IL6和IFNα的融合表达载体,SDS-PAGE检测pET32-IL6-IFN

  15. Artificial human vision.

    Science.gov (United States)

    Dowling, Jason

    2005-01-01

    Can vision be restored to the blind? As early as 1929 it was discovered that stimulating the visual cortex of an individual led to the perception of spots of light, known as phosphenes [1] . The aim of artificial human vision systems is to attempt to utilize the perception of phosphenes to provide a useful substitute for normal vision. Currently, four locations for electrical stimulation are being investigated; behind the retina (subretinal), in front of the retina (epiretinal), the optic nerve and the visual cortex (using intra- and surface electrodes). This review discusses artificial human vision technology and requirements, and reviews the current development projects.

  16. Spatially Resolved Artificial Chemistry

    DEFF Research Database (Denmark)

    Fellermann, Harold

    2009-01-01

    Although spatial structures can play a crucial role in chemical systems and can drastically alter the outcome of reactions, the traditional framework of artificial chemistry is a well-stirred tank reactor with no spatial representation in mind. Advanced method development in physical chemistry has...... made a class of models accessible to the realms of artificial chemistry that represent reacting molecules in a coarse-grained fashion in continuous space. This chapter introduces the mathematical models of Brownian dynamics (BD) and dissipative particle dynamics (DPD) for molecular motion and reaction...

  17. Bayesian artificial intelligence

    CERN Document Server

    Korb, Kevin B

    2003-01-01

    As the power of Bayesian techniques has become more fully realized, the field of artificial intelligence has embraced Bayesian methodology and integrated it to the point where an introduction to Bayesian techniques is now a core course in many computer science programs. Unlike other books on the subject, Bayesian Artificial Intelligence keeps mathematical detail to a minimum and covers a broad range of topics. The authors integrate all of Bayesian net technology and learning Bayesian net technology and apply them both to knowledge engineering. They emphasize understanding and intuition but also provide the algorithms and technical background needed for applications. Software, exercises, and solutions are available on the authors' website.

  18. Fusion Studies in Japan

    Science.gov (United States)

    Ogawa, Yuichi

    2016-05-01

    A new strategic energy plan decided by the Japanese Cabinet in 2014 strongly supports the steady promotion of nuclear fusion development activities, including the ITER project and the Broader Approach activities from the long-term viewpoint. Atomic Energy Commission (AEC) in Japan formulated the Third Phase Basic Program so as to promote an experimental fusion reactor project. In 2005 AEC has reviewed this Program, and discussed on selection and concentration among many projects of fusion reactor development. In addition to the promotion of ITER project, advanced tokamak research by JT-60SA, helical plasma experiment by LHD, FIREX project in laser fusion research and fusion engineering by IFMIF were highly prioritized. Although the basic concept is quite different between tokamak, helical and laser fusion researches, there exist a lot of common features such as plasma physics on 3-D magnetic geometry, high power heat load on plasma facing component and so on. Therefore, a synergetic scenario on fusion reactor development among various plasma confinement concepts would be important.

  19. Impact of loss of BH3-only proteins on the development and treatment of MLL-fusion gene-driven AML in mice.

    Science.gov (United States)

    Bilardi, Rebecca A; Anstee, Natasha S; Glaser, Stefan P; Robati, Mikara; Vandenberg, Cassandra J; Cory, Suzanne

    2016-01-01

    Inhibition of the apoptosis pathway controlled by opposing members of the Bcl-2 protein family plays a central role in cancer development and resistance to therapy. To investigate how pro-apoptotic Bcl-2 homology domain 3 (BH3)-only proteins impact on acute myeloid leukemia (AML), we generated mixed lineage leukemia (MLL)-AF9 and MLL-ENL AMLs from BH3-only gene knockout mice. Disease development was not accelerated by loss of Bim, Puma, Noxa, Bmf, or combinations thereof; hence these BH3-only proteins are apparently ineffectual as tumor suppressors in this model. We tested the sensitivity of MLL-AF9 AMLs of each genotype in vitro to standard chemotherapeutic drugs and to the proteasome inhibitor bortezomib, with or without the BH3 mimetic ABT-737. Loss of Puma and/or Noxa increased resistance to cytarabine, daunorubicin and etoposide, while loss of Bim protected against cytarabine and loss of Bmf had no impact. ABT-737 increased sensitivity to the genotoxic drugs but was not dependent on any BH3-only protein tested. The AML lines were very sensitive to bortezomib and loss of Noxa conveyed significant resistance. In vivo, several MLL-AF9 AMLs responded well to daunorubicin and this response was highly dependent on Puma and Noxa but not Bim. Combination therapy with ABT-737 provided little added benefit at the daunorubicin dose trialed. Bortezomib also extended survival of AML-bearing mice, albeit less than daunorubicin. In summary, our genetic studies reveal the importance of Puma and Noxa for the action of genotoxics currently used to treat MLL-driven AML and suggest that, while addition of ABT-737-like BH3 mimetics might enhance their efficacy, new Noxa-like BH3 mimetics targeting Mcl-1 might have greater potential. PMID:27584789

  20. Impulsive Neural Networks Algorithm Based on the Artificial Genome Model

    Directory of Open Access Journals (Sweden)

    Yuan Gao

    2014-05-01

    Full Text Available To describe gene regulatory networks, this article takes the framework of the artificial genome model and proposes impulsive neural networks algorithm based on the artificial genome model. Firstly, the gene expression and the cell division tree are applied to generate spiking neurons with specific attributes, neural network structure, connection weights and specific learning rules of each neuron. Next, the gene segment duplications and divergence model are applied to design the evolutionary algorithm of impulsive neural networks at the level of the artificial genome. The dynamic changes of developmental gene regulatory networks are controlled during the whole evolutionary process. Finally, the behavior of collecting food for autonomous intelligent agent is simulated, which is driven by nerves. Experimental results demonstrate that the algorithm in this article has the evolutionary ability on large-scale impulsive neural networks

  1. AAAIC '88 - Aerospace Applications of Artificial Intelligence; Proceedings of the Fourth Annual Conference, Dayton, OH, Oct. 25-27, 1988. Volumes 1 ampersand 2

    International Nuclear Information System (INIS)

    Topics presented include integrating neural networks and expert systems, neural networks and signal processing, machine learning, cognition and avionics applications, artificial intelligence and man-machine interface issues, real time expert systems, artificial intelligence, and engineering applications. Also considered are advanced problem solving techniques, combinational optimization for scheduling and resource control, data fusion/sensor fusion, back propagation with momentum, shared weights and recurrency, automatic target recognition, cybernetics, optical neural networks

  2. Fusion research in Hungary

    International Nuclear Information System (INIS)

    Hungarian fusion research started in the 1970s, when the idea of installing a small tokamak experiment emerged. In return to computer equipment a soviet tokamak was indeed sent to Hungary and started to operate as MT-1 at the Central Research Institute for Physics (KFKI) in 1979. Major research topics included diagnostic development, edge plasma studies and investigation of disruptions. Following a major upgrade in 1992 (new vacuum vessel, active position control and PC network based data acquisition system) the MT-1M tokamak was used for the study of transport processes with trace impurity injection, micropellet ablation studies, X-ray tomography and laser blow-off diagnostic development. Although funding ceased in the middle of the 90's the group was held alive by collaborations with EU fusion labs: FZ -Juelich, IPP-Garching and CRPP-EPFL Lausanne. In 1998 the machine was dismantled due to reorganization of the Hungarian Academy of Sciences. New horizons opened to fusion research from 1999, when Hungary joined EURATOM and a fusion Association was formed. Since then fusion physics studies are done in collaboration with major EU fusion laboratories, Hungarian researchers also play an active role in JET diagnostics upgrade and ITER design. Major topics are pellet ablation studies, plasma turbulence diagnosis using Beam Emission Spectroscopy and other techniques, tomography and plasma diagnostics using various neutral beams. In fusion relevant technology R and D Hungary has less records. Before joining EURATOM some materials irradiation studies were done at the Budapest Research Reactor at KFKI-AEKI. The present day fusion technology programme focuses still on irradiation studies, nuclear material database and electromagnetic testing techniques. Increasing the fusion technology research activities is a difficult task, as the competition in Hungarian industry is very strong and the interest of organizations in long-term investments into R and D is rather weak and

  3. Control of Fusion and Solubility in Fusion Systems

    CERN Document Server

    Craven, David A

    2009-01-01

    In this article, we consider the control of fusion in fusion systems, proving three previously known, non-trivial results in a new, largely elementary way. We then reprove a result of Aschbacher, that the product of two strongly closed subgroups is strongly closed; to do this, we consolidate the theory of quotients of fusion systems into a consistent theory. We move on considering p-soluble fusion systems, and prove that they are constrained, allowing us to effectively characterize fusion systems of p-soluble groups. This leads us to recast Thompson Factorization for Qd(p)-free fusion systems, and consider Thompson Factorization for more general fusion systems.

  4. Remote sensing image fusion

    CERN Document Server

    Alparone, Luciano; Baronti, Stefano; Garzelli, Andrea

    2015-01-01

    A synthesis of more than ten years of experience, Remote Sensing Image Fusion covers methods specifically designed for remote sensing imagery. The authors supply a comprehensive classification system and rigorous mathematical description of advanced and state-of-the-art methods for pansharpening of multispectral images, fusion of hyperspectral and panchromatic images, and fusion of data from heterogeneous sensors such as optical and synthetic aperture radar (SAR) images and integration of thermal and visible/near-infrared images. They also explore new trends of signal/image processing, such as

  5. Fusion facility siting considerations

    Energy Technology Data Exchange (ETDEWEB)

    Bussell, G.T.

    1985-07-01

    Inherent in the fusion program's transition from hydrogen devices to commercial power machines is a general increase in the size and scope of succeeding projects. This growth will lead to increased emphasis on safety, environmental impact, and the external effects of fusion in general, and of each new device in particular. A critically important consideration in this regard is site selection. The purpose of this paper is to examine major siting issues that may affect the economics, safety, and environmental impact of fusion.

  6. Fusion facility siting considerations

    Energy Technology Data Exchange (ETDEWEB)

    Bussell, G.T.

    1985-01-01

    Inherent in the fusion program's transition from hydrogen devices to commercial power machines is a general increase in the size and scope of succeeding projects. This growth will lead to increased emphasis on safety, environmental impact, and the external effects of fusion in general, and of each new device in particular. A critically important consideration in this regard is site selection. The purpose of this paper is to examine major siting issues that may affect the economics, safety, and environmental impact of fusion.

  7. On Exotic Saturated Fusion Systems

    Institute of Scientific and Technical Information of China (English)

    Jun LIAO

    2016-01-01

    In this paper, we prove that a product F1 × F2 of saturated fusion systems is exotic if and only if at least one of the factors is exotic. This result provides a method to construct new exotic fusion systems by known exotic fusion systems. We also investigate central products of saturated fusion systems.

  8. Fusion Systems for Profinite Groups

    OpenAIRE

    Stancu, Radu; Symonds, Peter

    2012-01-01

    We introduce the notion of a pro-fusion system on a pro-p group, which generalizes the notion of a fusion system on a finite p-group. We also prove a version of Alperin's Fusion Theorem for pro-fusion systems.

  9. Mitochondrial Fusion Proteins and Human Diseases

    Directory of Open Access Journals (Sweden)

    Michela Ranieri

    2013-01-01

    Full Text Available Mitochondria are highly dynamic, complex organelles that continuously alter their shape, ranging between two opposite processes, fission and fusion, in response to several stimuli and the metabolic demands of the cell. Alterations in mitochondrial dynamics due to mutations in proteins involved in the fusion-fission machinery represent an important pathogenic mechanism of human diseases. The most relevant proteins involved in the mitochondrial fusion process are three GTPase dynamin-like proteins: mitofusin 1 (MFN1 and 2 (MFN2, located in the outer mitochondrial membrane, and optic atrophy protein 1 (OPA1, in the inner membrane. An expanding number of degenerative disorders are associated with mutations in the genes encoding MFN2 and OPA1, including Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. While these disorders can still be considered rare, defective mitochondrial dynamics seem to play a significant role in the molecular and cellular pathogenesis of more common neurodegenerative diseases, for example, Alzheimer’s and Parkinson’s diseases. This review provides an overview of the basic molecular mechanisms involved in mitochondrial fusion and focuses on the alteration in mitochondrial DNA amount resulting from impairment of mitochondrial dynamics. We also review the literature describing the main disorders associated with the disruption of mitochondrial fusion.

  10. Xp11.2易位/TFE3基因融合相关性肾癌CT表现%CT imaging findings of renal cell carcinoma associated with Xp 11 .2 translocation/TFE3 gene fusions

    Institute of Scientific and Technical Information of China (English)

    姜天娇; 杨青; 段崇锋; 林东亮

    2014-01-01

    Objective To investigate the clinical ,pathological and imaging features of the renal cell carcinoma associated with Xp11 .2 translocation /TFE3 gene fusions ,so as to help to diagnosis before surgery .Methods The clinical ,patho-logical and imaging features of five cases were retrospectively analyzed ,and the related literatures were reviewed .Results The mean age was 35 years(range ,10~61 years) .Four cases were women .ALL of the five cases were hypovascular on contrast-enhanced CT and comprised of solid lesion with focal necrosis and hemorrhage ,four cases were calcified ,two ca-ses were adrenal metastasis ,four cases were lymph node metastasis .Tumor cells had the nest structure and papillary structure ,eosinophilic granula cells and psammoma bodies can be seen .All of TFE3 was positive .Conclusion Renal car-cinoma associated with Xp11 .2 translocation /TFE3 gene fusions is rare ,the possibility of this tumor should be consid-ered a renal mass seen in a young patient ,which demonstrates hemorrhage or necrosis on unenhanced CT ,slight enbance-ment on contrast-enhanced CT ,lymph node and distant organ metastasis .%目的:探讨Xp11.2易位/T FE3基因融合相关性肾癌的临床、病理及影像学特点,以有助于术前诊断。方法回顾分析5例Xp11.2易位/T FE3基因融合相关性肾癌的临床、病理及影像学特点并复习相关文献。结果患者平均年龄35岁(10~61岁),4例女性。5例Xp11.2易位/TFE3基因融合相关性肾癌增强CT扫描轻度强化,5例均有坏死、出血,4例可见钙化灶,2例肾上腺转移,4可见多发淋巴结转移。肿瘤细胞呈巢状或乳头状结构,可见嗜酸性颗粒细胞及沙砾体形成,T FE3均为阳性。结论 Xp11.2易位/T FE3基因融合相关性肾癌临床罕见,儿童与年轻人发病率高,如果CT平扫肿瘤可见出血、坏死,增强CT轻度强化,伴多发淋巴结或远处器官转移时,有助于本病的诊断。

  11. Artificial intelligence within AFSC

    Science.gov (United States)

    Gersh, Mark A.

    1990-01-01

    Information on artificial intelligence research in the Air Force Systems Command is given in viewgraph form. Specific research that is being conducted at the Rome Air Development Center, the Space Technology Center, the Human Resources Laboratory, the Armstrong Aerospace Medical Research Laboratory, the Armamant Laboratory, and the Wright Research and Development Center is noted.

  12. Artificial Left Ventricle

    CERN Document Server

    Ranjbar, Saeed; Meybodi, Mahmood Emami

    2014-01-01

    This Artificial left ventricle is based on a simple conic assumption shape for left ventricle where its motion is made by attached compressed elastic tubes to its walls which are regarded to electrical points at each nodal .This compressed tubes are playing the role of myofibers in the myocardium of the left ventricle. These elastic tubes have helical shapes and are transacting on these helical bands dynamically. At this invention we give an algorithm of this artificial left ventricle construction that of course the effect of the blood flow in LV is observed with making beneficiary used of sensors to obtain this effecting, something like to lifegates problem. The main problem is to evaluate powers that are interacted between elastic body (left ventricle) and fluid (blood). The main goal of this invention is to show that artificial heart is not just a pump, but mechanical modeling of LV wall and its interaction with blood in it (blood movement modeling) can introduce an artificial heart closed to natural heart...

  13. Artificial Gravity Research Plan

    Science.gov (United States)

    Gilbert, Charlene

    2014-01-01

    This document describes the forward working plan to identify what countermeasure resources are needed for a vehicle with an artificial gravity module (intermittent centrifugation) and what Countermeasure Resources are needed for a rotating transit vehicle (continuous centrifugation) to minimize the effects of microgravity to Mars Exploration crewmembers.

  14. Micromachined Artificial Haircell

    Science.gov (United States)

    Liu, Chang (Inventor); Engel, Jonathan (Inventor); Chen, Nannan (Inventor); Chen, Jack (Inventor)

    2010-01-01

    A micromachined artificial sensor comprises a support coupled to and movable with respect to a substrate. A polymer, high-aspect ratio cilia-like structure is disposed on and extends out-of-plane from the support. A strain detector is disposed with respect to the support to detect movement of the support.

  15. Terahertz Artificial Dielectric Lens

    Science.gov (United States)

    Mendis, Rajind; Nagai, Masaya; Wang, Yiqiu; Karl, Nicholas; Mittleman, Daniel M.

    2016-03-01

    We have designed, fabricated, and experimentally characterized a lens for the THz regime based on artificial dielectrics. These are man-made media that mimic properties of naturally occurring dielectric media, or even manifest properties that cannot generally occur in nature. For example, the well-known dielectric property, the refractive index, which usually has a value greater than unity, can have a value less than unity in an artificial dielectric. For our lens, the artificial-dielectric medium is made up of a parallel stack of 100 μm thick metal plates that form an array of parallel-plate waveguides. The convergent lens has a plano-concave geometry, in contrast to conventional dielectric lenses. Our results demonstrate that this lens is capable of focusing a 2 cm diameter beam to a spot size of 4 mm, at the design frequency of 0.17 THz. The results further demonstrate that the overall power transmission of the lens can be better than certain conventional dielectric lenses commonly used in the THz regime. Intriguingly, we also observe that under certain conditions, the lens boundary demarcated by the discontinuous plate edges actually resembles a smooth continuous surface. These results highlight the importance of this artificial-dielectric technology for the development of future THz-wave devices.

  16. Observations of artificial satellites

    Directory of Open Access Journals (Sweden)

    A. MAMMANO

    1964-06-01

    Full Text Available The following publication gives the results of photographic
    observations of artificial satellites made at Asiago during the second
    and third year of this programme. The fixed camera technique and that
    with moving film (the latter still in its experimental stage have been used.

  17. Fusion technology programme

    International Nuclear Information System (INIS)

    KfK participates to the Fusion Technology Programme of the European Community. Most of the work in progress addresses the Next European Torus (NET) and the long term technology aspects as defined in the 82/86 programme. A minor part serves to preparation of future contributions and to design studies on fusion concepts in a wider perspective. The Fusion Technology Programme of Euratom covers mainly aspects of nuclear engineering. Plasma engineering, heating, refueling and vacuum technology are at present part of the Physics Programme. In view of NET, integration of the different areas of work will be mandatory. KfK is therefore prepared to address technical aspects beyond the actual scope of the physics experiments. The technology tasks are reported project wise under title and code of the Euratom programme. Most of the projects described here are shared with other European fusion laboratories as indicated in the table annexed to this report. (orig./GG)

  18. Cell fusions in mammals

    DEFF Research Database (Denmark)

    Larsson, Lars-Inge; Bjerregaard, Bolette; Talts, Jan Fredrik

    2008-01-01

    Cell fusions are important to fertilization, placentation, development of skeletal muscle and bone, calcium homeostasis and the immune defense system. Additionally, cell fusions participate in tissue repair and may be important to cancer development and progression. A large number of factors appear...... to regulate cell fusions, including receptors and ligands, membrane domain organizing proteins, proteases, signaling molecules and fusogenic proteins forming alpha-helical bundles that bring membranes close together. The syncytin family of proteins represent true fusogens and the founding member, syncytin-1......, has been documented to be involved in fusions between placental trophoblasts, between cancer cells and between cancer cells and host ells. We review the literature with emphasis on the syncytin family and propose that syncytins may represent universal fusogens in primates and rodents, which work...

  19. Label Fusion Strategy Selection

    Directory of Open Access Journals (Sweden)

    Nicolas Robitaille

    2012-01-01

    Full Text Available Label fusion is used in medical image segmentation to combine several different labels of the same entity into a single discrete label, potentially more accurate, with respect to the exact, sought segmentation, than the best input element. Using simulated data, we compared three existing label fusion techniques—STAPLE, Voting, and Shape-Based Averaging (SBA—and observed that none could be considered superior depending on the dissimilarity between the input elements. We thus developed an empirical, hybrid technique called SVS, which selects the most appropriate technique to apply based on this dissimilarity. We evaluated the label fusion strategies on two- and three-dimensional simulated data and showed that SVS is superior to any of the three existing methods examined. On real data, we used SVS to perform fusions of 10 segmentations of the hippocampus and amygdala in 78 subjects from the ICBM dataset. SVS selected SBA in almost all cases, which was the most appropriate method overall.

  20. Cold nuclear fusion

    Directory of Open Access Journals (Sweden)

    Huang Zhenqiang Huang Yuxiang

    2013-10-01

    Full Text Available In normal temperature condition, the nuclear force constraint inertial guidance method, realize the combination of deuterium and tritium, helium and lithium... And with a magnetic moment of light nuclei controlled cold nuclear collide fusion, belongs to the nuclear energy research and development in the field of applied technology "cold nuclear collide fusion". According to the similarity of the nuclear force constraint inertial guidance system, the different velocity and energy of the ion beam mixing control, developed ion speed dc transformer, it is cold nuclear fusion collide, issue of motivation and the nuclear power plant start-up fusion and power transfer system of the important equipment, so the merger to apply for a patent

  1. Optical Fiber Fusion Splicing

    CERN Document Server

    Yablon, Andrew D

    2005-01-01

    This book is an up-to-date treatment of optical fiber fusion splicing incorporating all the recent innovations in the field. It provides a toolbox of general strategies and specific techniques that the reader can apply when optimizing fusion splices between novel fibers. It specifically addresses considerations important for fusion splicing of contemporary specialty fibers including dispersion compensating fiber, erbium-doped gain fiber, polarization maintaining fiber, and microstructured fiber. Finally, it discusses the future of optical fiber fusion splicing including silica and non-silica based optical fibers as well as the trend toward increasing automation. Whilst serving as a self-contained reference work, abundant citations from the technical literature will enable readers to readily locate primary sources.

  2. Fusion Revisits CERN

    CERN Multimedia

    2001-01-01

    It's going to be a hot summer at CERN. At least in the Main Building, where from 13 July to 20 August an exhibition is being hosted on nuclear fusion, the energy of the Stars. Nuclear fusion is the engine driving the stars but also a potential source of energy for mankind. The exhibition shows the different nuclear fusion techniques and research carried out on the subject in Europe. Inaugurated at CERN in 1993, following collaboration between Lausanne's CRPP-EPFL and CERN, with input from Alessandro Pascolini of Italy's INFN, this exhibition has travelled round Europe before being revamped and returning to CERN. 'Fusion, Energy of the Stars', from 13 July onwards, Main Building

  3. Fusion plasma physics

    CERN Document Server

    Stacey, Weston M

    2012-01-01

    This revised and enlarged second edition of the popular textbook and reference contains comprehensive treatments of both the established foundations of magnetic fusion plasma physics and of the newly developing areas of active research. It concludes with a look ahead to fusion power reactors of the future. The well-established topics of fusion plasma physics -- basic plasma phenomena, Coulomb scattering, drifts of charged particles in magnetic and electric fields, plasma confinement by magnetic fields, kinetic and fluid collective plasma theories, plasma equilibria and flux surface geometry, plasma waves and instabilities, classical and neoclassical transport, plasma-materials interactions, radiation, etc. -- are fully developed from first principles through to the computational models employed in modern plasma physics. The new and emerging topics of fusion plasma physics research -- fluctuation-driven plasma transport and gyrokinetic/gyrofluid computational methodology, the physics of the divertor, neutral ...

  4. Fusion technology development

    International Nuclear Information System (INIS)

    This report includes information on the following chapters: (1) conceptual design studies, (2) magnetics, (3) plasma heating, fueling, and exhaust, (4) materials for fusion reactors, (5) alternate applications, and (6) environment and safety

  5. Fusion reactor materials

    International Nuclear Information System (INIS)

    This is the fifteenth in a series of semiannual technical progress reports on fusion reactor materials. This report combines research and development activities which were previously reported separately in the following progress reports: Alloy Development for Irradiation Performance; Damage Analysis and Fundamental Studies; Special purpose Materials. These activities are concerned principally with the effects of the neutronic and chemical environment on the properties and performance of reactor materials; together they form one element of the overall materials programs being conducted in support of the Magnetic Fusion Energy Program of the U.S. Department of Energy. The Fusion Reactor Materials Program is a national effort involving several national laboratories, universities, and industries. The purpose of this series of reports is to provide a working technical record for the use of the program participants, and to provide a means of communicating the efforts of materials scientists to the rest of the fusion community, both nationally and worldwide

  6. Fusion technology (FT)

    International Nuclear Information System (INIS)

    The annual report of tha fusion technology (FT) working group discusses the projects carried out by the participating institutes in the fields of 1) fuel injection and plasma heating, 2) magnetic field technology, and 3) systems investigations. (HK)

  7. The utility of artificially evolved sequences in protein threading and fold recognition.

    Science.gov (United States)

    Brylinski, Michal

    2013-07-01

    Template-based protein structure prediction plays an important role in Functional Genomics by providing structural models of gene products, which can be utilized by structure-based approaches to function inference. From a systems level perspective, the high structural coverage of gene products in a given organism is critical. Despite continuous efforts towards the development of more sensitive threading approaches, confident structural models cannot be constructed for a considerable fraction of proteins due to difficulties in recognizing low-sequence identity templates with a similar fold to the target. Here we introduce a new modeling stratagem, which employs a library of synthetic sequences to improve template ranking in fold recognition by sequence profile-based methods. We developed a new method for the optimization of generic protein-like amino acid sequences to stabilize the respective structures using a combined empirical scoring function, which is compatible with these commonly used in protein threading and fold recognition. We show that the artificially evolved sequences, whose average sequence identity to the wild-type sequences is as low as 13.8%, have significant capabilities to recognize the correct structures. Importantly, the quality of the corresponding threading alignments is comparable to these constructed using conventional wild-type approaches (the average TM-score is 0.48 and 0.54, respectively). Fold recognition that uses data fusion to combine ranks calculated for both wild-type and synthetic template libraries systematically improves the detection of structural analogs. Depending on the threading algorithm used, it yields on average 4-16% higher recognition rates than using the wild-type template library alone. Synthetic sequences artificially evolved for the template structures provide an orthogonal source of signal that could be exploited to detect these templates unrecognized by standard modeling techniques. It opens up new directions in

  8. Fusion research in India

    International Nuclear Information System (INIS)

    The economic growth of our country demands a rapid increase in the energy output. Fusion is one such alternate clean source of energy to contribute in the energy mix towards the second half of the century, with a virtually inexhaustible fuel supply. The environmental impact of fusion would be acceptable and relatively safe. These advantages have driven the world fusion research programme since its inception. Till a pure fusion energy source is available, it is worthwhile to develop it for the benefit of conventional fission fuel preparation and other various usages. Indian National Fusion Programme was initiated by indigenously developing the first Indian Tokamak, ADITYA, successfully commissioned in 1989 and has been generating interesting scientific results on various topics. The next major program at Institute for Plasma Research (IPR) has been to construct a Steady State Superconducting Tokamak (SST-1) by mix of import and indigenous development. After successful engineering validation of the subsystems in integrated operations, successful machine operation has been continued. Since then, the machine has been upgraded with a graphite first wall. As a strategy towards leapfrogging to save time, IPR and Department of Atomic Energy (DAE) decided on India’s participation in the International Thermonuclear Experimental Reactor (ITER) as a full partner, unique features of which will be its ability to operate for long durations and at power levels ∼500 MW sufficient to demonstrate the physics of burning plasma in a power plant like environment. It will also serve as a test-bed for additional fusion power plant technologies. To accelerate the domestic fusion research programme with integration of knowledge gained from ITER, we would embark upon design of a smaller fusion machine which will use already available technologies to produce controlled fusion reactions and use it as an energetic neutron source for test of materials developed for future fusion reactors

  9. Introduction to Artificial Neural Networks

    DEFF Research Database (Denmark)

    Larsen, Jan

    1999-01-01

    The note addresses introduction to signal analysis and classification based on artificial feed-forward neural networks.......The note addresses introduction to signal analysis and classification based on artificial feed-forward neural networks....

  10. Economically competitive fusion

    Directory of Open Access Journals (Sweden)

    David J. Ward

    2008-12-01

    Full Text Available Not since the oil crisis of the 1970s has the perception that energy is a crucial and precious resource been as strong as it is today. The need for a new approach to world energy supply, driven by concerns over resources, pollution, and security, is leading to a reappraisal of fusion. Fusion has enormous potential and major safety and environmental advantages, and hence could make a large difference to energy supplies.

  11. Cold nuclear fusion

    OpenAIRE

    Huang Zhenqiang Huang Yuxiang

    2013-01-01

    In normal temperature condition, the nuclear force constraint inertial guidance method, realize the combination of deuterium and tritium, helium and lithium... And with a magnetic moment of light nuclei controlled cold nuclear collide fusion, belongs to the nuclear energy research and development in the field of applied technology "cold nuclear collide fusion". According to the similarity of the nuclear force constraint inertial guidance system, the different velocity and energy of the ion be...

  12. Fusion Simulation Program

    International Nuclear Information System (INIS)

    Many others in the fusion energy and advanced scientific computing communities participated in the development of this plan. The core planning team is grateful for their important contributions. This summary is meant as a quick overview the Fusion Simulation Program's (FSP's) purpose and intentions. There are several additional documents referenced within this one and all are supplemental or flow down from this Program Plan. The overall science goal of the DOE Office of Fusion Energy Sciences (FES) Fusion Simulation Program (FSP) is to develop predictive simulation capability for magnetically confined fusion plasmas at an unprecedented level of integration and fidelity. This will directly support and enable effective U.S. participation in International Thermonuclear Experimental Reactor (ITER) research and the overall mission of delivering practical fusion energy. The FSP will address a rich set of scientific issues together with experimental programs, producing validated integrated physics results. This is very well aligned with the mission of the ITER Organization to coordinate with its members the integrated modeling and control of fusion plasmas, including benchmarking and validation activities. (1). Initial FSP research will focus on two critical Integrated Science Application (ISA) areas: ISA1, the plasma edge; and ISA2, whole device modeling (WDM) including disruption avoidance. The first of these problems involves the narrow plasma boundary layer and its complex interactions with the plasma core and the surrounding material wall. The second requires development of a computationally tractable, but comprehensive model that describes all equilibrium and dynamic processes at a sufficient level of detail to provide useful prediction of the temporal evolution of fusion plasma experiments. The initial driver for the whole device model will be prediction and avoidance of discharge-terminating disruptions, especially at high performance, which are a critical

  13. Economically competitive fusion

    OpenAIRE

    Ward, David J.; Dudarev, Sergei L.

    2008-01-01

    Not since the oil crisis of the 1970s has the perception that energy is a crucial and precious resource been as strong as it is today. The need for a new approach to world energy supply, driven by concerns over resources, pollution, and security, is leading to a reappraisal of fusion. Fusion has enormous potential and major safety and environmental advantages, and hence could make a large difference to energy supplies.

  14. Virosome engineering of colloidal particles and surfaces: bioinspired fusion to supported lipid layers

    Science.gov (United States)

    Fleddermann, J.; Diamanti, E.; Azinas, S.; Košutić, M.; Dähne, L.; Estrela-Lopis, I.; Amacker, M.; Donath, E.; Moya, S. E.

    2016-04-01

    Immunostimulating reconstituted influenza virosomes (IRIVs) are liposomes with functional viral envelope glycoproteins: influenza virus hemagglutinin (HA) and neuraminidase intercalated in the phospholipid bilayer. Here we address the fusion of IRIVs to artificial supported lipid membranes assembled on polyelectrolyte multilayers on both colloidal particles and planar substrates. The R18 assay is used to prove the IRIV fusion in dependence of pH, temperature and HA concentration. IRIVs display a pH-dependent fusion mechanism, fusing at low pH in analogy to the influenza virus. The pH dependence is confirmed by the Quartz Crystal Microbalance technique. Atomic Force Microscopy imaging shows that at low pH virosomes are integrated in the supported membrane displaying flattened features and a reduced vertical thickness. Virosome fusion offers a new strategy for transferring biological functions on artificial supported membranes with potential applications in targeted delivery and sensing.Immunostimulating reconstituted influenza virosomes (IRIVs) are liposomes with functional viral envelope glycoproteins: influenza virus hemagglutinin (HA) and neuraminidase intercalated in the phospholipid bilayer. Here we address the fusion of IRIVs to artificial supported lipid membranes assembled on polyelectrolyte multilayers on both colloidal particles and planar substrates. The R18 assay is used to prove the IRIV fusion in dependence of pH, temperature and HA concentration. IRIVs display a pH-dependent fusion mechanism, fusing at low pH in analogy to the influenza virus. The pH dependence is confirmed by the Quartz Crystal Microbalance technique. Atomic Force Microscopy imaging shows that at low pH virosomes are integrated in the supported membrane displaying flattened features and a reduced vertical thickness. Virosome fusion offers a new strategy for transferring biological functions on artificial supported membranes with potential applications in targeted delivery and sensing

  15. Simulation Techniques and Prosthetic Approach Towards Biologically Efficient Artificial Sense Organs- An Overview

    CERN Document Server

    Neogi, Biswarup; Mukherjee, Soumyajit; Das, Achintya; Tibarewala, D N

    2011-01-01

    An overview of the applications of control theory to prosthetic sense organs including the senses of vision, taste and odor is being presented in this paper. Simulation aspect nowadays has been the centre of research in the field of prosthesis. There have been various successful applications of prosthetic organs, in case of natural biological organs dis-functioning patients. Simulation aspects and control modeling are indispensible for knowing system performance, and to generate an original approach of artificial organs. This overview focuses mainly on control techniques, by far a theoretical overview and fusion of artificial sense organs trying to mimic the efficacies of biologically active sensory organs. Keywords: virtual reality, prosthetic vision, artificial

  16. Conference on Norwegian fusion research

    International Nuclear Information System (INIS)

    The question of instituting a systematic research programme in Norway on aspects of thermonuclear and plasma physics has been raised. The conference here reported was intended to provide basic information on the status of fusion research internationally and to discuss a possible Norwegian programme. The main contributions covered the present status of fusion research, international cooperation, fusion research in small countries and minor laboratories, fusion research in Denmark and Sweden, and a proposed fusion experiment in Bergen. (JIW)

  17. Perspectives of fusion power

    International Nuclear Information System (INIS)

    New and practically inexhaustible sources of energy must be developed for the period when oil, coal and uranium will become scarce and expensive. Nuclear fusion holds great promise as one of these practically inexhaustible energy sources. Based on the deuteriumtritium reaction with tritium obtained from naturally occuring lithium, which is also widely available in Europe, the accessible energy resources in the world are 3.1012 to 3.1016 toe; based on the deuterium-deuterium reaction, the deuterium content of the oceans corresponds to 1020 toe. It is presently envisaged that in order to establish fusion as a large-scale energy source, three major thresholds must be reached: - Scientific feasibility, - Technical feasibility, i.e. the proof that the basic technical problems of the fusion reactor can be solved. - Commercial feasibility, i.e. proof that fusion power reactors can be built on an industrial scale, can be operated reliably and produce usable energy at prices competitive with other energy sources. From the above it is clear that the route to commercial fusion will be long and costly and involve the solution of extremely difficult technical problems. In view of the many steps which have to be taken, it appears unlikely that commercial fusion power will be in general use within the next 50 years and by that time world-wide expenditure on research, development and demonstration may well have exceeded 100 Bio ECU. (author)

  18. Energy from inertial fusion

    International Nuclear Information System (INIS)

    This book contains 22 articles on inertial fusion energy (IFE) research and development written in the framework of an international collaboration of authors under the guidance of an advisory group on inertial fusion energy set up in 1991 to advise the IAEA. It describes the actual scientific, engineering and technological developments in the field of inertial confinement fusion (ICF). It also identifies ways in which international co-operation in ICF could be stimulated. The book is intended for a large audience and provides an introduction to inertial fusion energy and an overview of the various technologies needed for IFE power plants to be developed. It contains chapters on (i) the fundamentals of IFE; (ii) inertial confinement target physics; (iii) IFE power plant design principles (requirements for power plant drivers, solid state laser drivers, gas laser drivers, heavy ion drivers, and light ion drivers, target fabrication and positioning, reaction chamber systems, power generation and conditioning and radiation control, materials management and target materials recovery), (iv) special design issues (radiation damage in structural materials, induced radioactivity, laser driver- reaction chamber interfaces, ion beam driver-reaction chamber interfaces), (v) inertial fusion energy development strategy, (vi) safety and environmental impact, (vii) economics and other figures of merit; (viii) other uses of inertial fusion (both those involving and not involving implosions); and (ix) international activities. Refs, figs and tabs

  19. MOTION MODELLINGUSINGCONCEPTS OF FUZZY ARTIFICIAL POTENTIAL FIELDS

    Directory of Open Access Journals (Sweden)

    O. Motlagh

    2010-12-01

    Full Text Available Artificial potential fields (APF are well established for reactive navigation of mobile robots. This paper describes a fast and robust fuzzy-APF on an ActivMedia AmigoBot. Obstacle-related information is fuzzified by using sensory fusion, which results in a shorter runtime. In addition, the membership functions of obstacle direction and range have been merged into one function, obtaining a smaller block of rules. The system is tested in virtual environments with non-concave obstacles. Then, the paper describes a new approach to motion modelling where the motion of intelligent travellers is modelled by consecutive path segments. In previous work, the authors described a reliable motion modelling technique using causal inference of fuzzy cognitive maps (FCM which has been efficiently modified for the purpose of this contribution. Results and analysis are given to demonstrate the efficiency and accuracy of the proposed motion modelling algorithm.

  20. Artificial Intelligence-The Emerging Technology

    Directory of Open Access Journals (Sweden)

    R. P. Shenoy

    1985-04-01

    Full Text Available Artificial Intelligence (AI, once considered as an obscure branch of computer science, is now having a growing number of adherents in a wide variety of fields. AI is particularly useful for combat automation in defence. The combined works of computer scientists and technologists and cognitive scientists have brought out for intelligent information processing knowledge is the key factor. In the last few years, AI has been tried out with a high degree of success in certain areas such as the Expert Systems and the Computer Vision Systems. Both these have great potential in target classification and identification, information fusion, multiradar Air Defence Network, C2 (Command andControl operations etc. in defence.