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Sample records for multiple immediate-early gene-deleted

  1. Properties of a herpes simplex virus multiple immediate-early gene-deleted recombinant as a vaccine vector

    SciTech Connect

    Watanabe, Daisuke; Brockman, Mark A.; Ndung'u, Thumbi; Mathews, Lydia; Lucas, William T.; Murphy, Cynthia G.; Felber, Barbara K.; Pavlakis, George N.; Deluca, Neal A.; Knipe, David M. . E-mail: david_knipe@hms.harvard.edu

    2007-01-20

    Herpes simplex virus (HSV) recombinants induce durable immune responses in rhesus macaques and mice and have induced partial protection in rhesus macaques against mucosal challenge with virulent simian immunodeficiency virus (SIV). In this study, we evaluated the properties of a new generation HSV vaccine vector, an HSV-1 multiple immediate-early (IE) gene deletion mutant virus, d106, which contains deletions in the ICP4, ICP27, ICP22, and ICP47 genes. Because several of the HSV IE genes have been implicated in immune evasion, inactivation of the genes encoding these proteins was expected to result in enhanced immunogenicity. The d106 virus expresses few HSV gene products and shows minimal cytopathic effect in cultured cells. When d106 was inoculated into mice, viral DNA accumulated at high levels in draining lymph nodes, consistent with an ability to transduce dendritic cells and activate their maturation and movement to lymph nodes. A d106 recombinant expressing Escherichia coli {beta}-galactosidase induced durable {beta}-gal-specific IgG and CD8{sup +} T cell responses in naive and HSV-immune mice. Finally, d106-based recombinants have been constructed that express simian immunodeficiency virus (SIV) gag, env, or a rev-tat-nef fusion protein for several days in cultured cells. Thus, d106 shows many of the properties desirable in a vaccine vector: limited expression of HSV gene products and cytopathogenicity, high level expression of transgenes, ability to induce durable immune responses, and an ability to transduce dendritic cells and induce their maturation and migration to lymph nodes.

  2. Assessment of the Toxicity of CuO Nanoparticles by Using Saccharomyces cerevisiae Mutants with Multiple Genes Deleted.

    PubMed

    Bao, Shaopan; Lu, Qicong; Fang, Tao; Dai, Heping; Zhang, Chao

    2015-12-01

    To develop applicable and susceptible models to evaluate the toxicity of nanoparticles, the antimicrobial effects of CuO nanoparticles (CuO-NPs) on various Saccharomyces cerevisiae (S. cerevisiae) strains (wild type, single-gene-deleted mutants, and multiple-gene-deleted mutants) were determined and compared. Further experiments were also conducted to analyze the mechanisms associated with toxicity using copper salt, bulk CuO (bCuO), carbon-shelled copper nanoparticles (C/Cu-NPs), and carbon nanoparticles (C-NPs) for comparisons. The results indicated that the growth inhibition rates of CuO-NPs for the wild-type and the single-gene-deleted strains were comparable, while for the multiple-gene deletion mutant, significantly higher toxicity was observed (P < 0.05). When the toxicity of the CuO-NPs to yeast cells was compared with the toxicities of copper salt and bCuO, we concluded that the toxicity of CuO-NPs should be attributed to soluble copper rather than to the nanoparticles. The striking difference in adverse effects of C-NPs and C/Cu-NPs with equivalent surface areas also proved this. A toxicity assay revealed that the multiple-gene-deleted mutant was significantly more sensitive to CuO-NPs than the wild type. Specifically, compared with the wild-type strain, copper was readily taken up by mutant strains when cell permeability genes were knocked out, and the mutants with deletions of genes regulated under oxidative stress (OS) were likely producing more reactive oxygen species (ROS). Hence, as mechanism-based gene inactivation could increase the susceptibility of yeast, the multiple-gene-deleted mutants should be improved model organisms to investigate the toxicity of nanoparticles. PMID:26386067

  3. The green monster process for the generation of yeast strains carrying multiple gene deletions.

    PubMed

    Suzuki, Yo; Stam, Jason; Novotny, Mark; Yachie, Nozomu; Lasken, Roger S; Roth, Frederick P

    2012-01-01

    Phenotypes for a gene deletion are often revealed only when the mutation is tested in a particular genetic background or environmental condition(1,2). There are examples where many genes need to be deleted to unmask hidden gene functions(3,4). Despite the potential for important discoveries, genetic interactions involving three or more genes are largely unexplored. Exhaustive searches of multi-mutant interactions would be impractical due to the sheer number of possible combinations of deletions. However, studies of selected sets of genes, such as sets of paralogs with a greater a priori chance of sharing a common function, would be informative. In the yeast Saccharomyces cerevisiae, gene knockout is accomplished by replacing a gene with a selectable marker via homologous recombination. Because the number of markers is limited, methods have been developed for removing and reusing the same marker(5,6,7,8,9,10). However, sequentially engineering multiple mutations using these methods is time-consuming because the time required scales linearly with the number of deletions to be generated. Here we describe the Green Monster method for routinely engineering multiple deletions in yeast(11). In this method, a green fluorescent protein (GFP) reporter integrated into deletions is used to quantitatively label strains according to the number of deletions contained in each strain (Figure 1). Repeated rounds of assortment of GFP-marked deletions via yeast mating and meiosis coupled with flow-cytometric enrichment of strains carrying more of these deletions lead to the accumulation of deletions in strains (Figure 2). Performing multiple processes in parallel, with each process incorporating one or more deletions per round, reduces the time required for strain construction. The first step is to prepare haploid single-mutants termed 'ProMonsters,' each of which carries a GFP reporter in a deleted locus and one of the 'toolkit' loci-either Green Monster GMToolkit-a or GMToolkit-? at the can1? locus (Figure 3). Using strains from the yeast deletion collection(12), GFP-marked deletions can be conveniently generated by replacing the common KanMX4 cassette existing in these strains with a universal GFP-URA3 fragment. Each GMToolkit contains: either the a- or ?-mating-type-specific haploid selection marker(1) and exactly one of the two markers that, when both GMToolkits are present, collectively allow for selection of diploids. The second step is to carry out the sexual cycling through which deletion loci can be combined within a single cell by the random assortment and/or meiotic recombination that accompanies each cycle of mating and sporulation. PMID:23271437

  4. Multiple tandemly repeated binding sites for cellular nuclear factor 1 that surround the major immediate-early promoters of simian and human cytomegalovirus.

    PubMed Central

    Jeang, K T; Rawlins, D R; Rosenfeld, P J; Shero, J H; Kelly, T J; Hayward, G S

    1987-01-01

    We show that the large DNA genomes of human and simian cytomegaloviruses (HCMV and SCMV, respectively) each contain multiple binding sites for purified cellular nuclear factor 1 (NF1) protein. Examination of the major immediate-early (IE) gene region in the HindIII H fragment of SCMV (Colburn) by filter binding assays showed that it competed 45-fold better than the single adenovirus type 2 binding site for NF1 protein and that it contained at least two distinct binding loci. Direct DNase I footprinting analyses of the 5' upstream locus detected at least 20 adjacent NF1-binding sites located between positions -600 and -1300 relative to the IE94 mRNA start site. DNA sequence analysis of the region revealed a conserved consensus NF1 recognition element (T)TGG(C/A)N5GCCAA embedded within each of 23 highly diverged 30-base-pair tandem repeats, together with a second downstream cluster of five consensus NF1-binding sites between positions +470 and +570 in the large first intron. Two separate NF1-binding loci were also found in the equivalent IE68 gene of HCMV(Towne) DNA, but in this case the DNA sequence and competition filter binding experiments indicated a maximum of only four to five consensus binding sites encompassing the promoter-enhancer region. In transient expression assays, neither the isolated upstream IE94 tandem repeats nor a synthetic single-copy consensus NF1-binding site acted as transcriptional cis activators or enhancers when placed adjacent to the simian virus 40 minimal early region promoter. We conclude that the large and complex 5' upstream promoter-regulatory region for the SCMV IE94 gene comprises two distinct domains. The previously described four sets of 13- to 18-base-pair interspersed repeat elements between -55 and -580 provide most of the high basal transcriptional strength, whereas the arrangement of further upstream tandemly repeated NF1-binding sites may contribute significantly to the expanded biological host range for expression of SCMV IE94 compared with HCMV IE68. Images PMID:3033283

  5. Activation of the inducible orphan receptor gene nur77 by serum growth factors: dissociation of immediate-early and delayed-early responses.

    PubMed Central

    Williams, G T; Lau, L F

    1993-01-01

    We have characterized the genetic elements that mediate the transcriptional activation of nur77, a growth factor-inducible gene encoding a member of the steroid/thyroid hormone receptor superfamily. Although initially identified as a serum-inducible immediate-early gene with expression kinetics similar to those of c-fos, we found that transcriptional activation of nur77 by serum growth factors in fibroblasts is in fact composed of two components: an immediate-early component, which can occur in the absence of de novo protein synthesis, and a delayed-early component, which is dependent on de novo protein synthesis. The expression of nur77 following serum stimulation reflects the superimposition of immediate-early and delayed-early expression. Immediate-early and delayed-early expression can be dissociated from one another by deletion or base substitution mutations of the nur77 promoter. Immediate-early expression of nur77 is mediated primarily by sequences located between nucleotides -86 and -126 upstream of the transcription start site. This region includes a sequence that resembles but differs from the CArG element found in other serum-inducible promoters. Upstream of the CArG-like element is a potential binding site for a transcription factor of the Ets family; the presence of this site is required for significant transcriptional induction. Delayed-early expression of nur77 is mediated by multiple AP-1-like and GC-rich elements, which can interact with products of immediate-early genes such as Fos/Jun and Zif268, respectively. Furthermore, we show that Zif268 can activate transcription of the nur77 promoter, suggesting that it may play a role in the delayed-early expression of nur77. Images PMID:8413214

  6. Direct cellobiose production from cellulose using sextuple beta-glucosidase gene deletion Neurospora crassa mutants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Direct cellobiose production from cellulose by a genetically modified fungus—Neurospora crassa, was explored in this study. A library of N. crassa sextuple beta-glucosidase (bgl) gene deletion strains was constructed. Various concentrations of cellobiose were detected in the culture broth of the N. ...

  7. Simple Method for Markerless Gene Deletion in Multidrug-Resistant Acinetobacter baumannii.

    PubMed

    Oh, Man Hwan; Lee, Je Chul; Kim, Jungmin; Choi, Chul Hee; Han, Kyudong

    2015-05-15

    The traditional markerless gene deletion technique based on overlap extension PCR has been used for generating gene deletions in multidrug-resistant Acinetobacter baumannii. However, the method is time-consuming because it requires restriction digestion of the PCR products in DNA cloning and the construction of new vectors containing a suitable antibiotic resistance cassette for the selection of A. baumannii merodiploids. Moreover, the availability of restriction sites and the selection of recombinant bacteria harboring the desired chimeric plasmid are limited, making the construction of a chimeric plasmid more difficult. We describe a rapid and easy cloning method for markerless gene deletion in A. baumannii, which has no limitation in the availability of restriction sites and allows for easy selection of the clones carrying the desired chimeric plasmid. Notably, it is not necessary to construct new vectors in our method. This method utilizes direct cloning of blunt-end DNA fragments, in which upstream and downstream regions of the target gene are fused with an antibiotic resistance cassette via overlap extension PCR and are inserted into a blunt-end suicide vector developed for blunt-end cloning. Importantly, the antibiotic resistance cassette is placed outside the downstream region in order to enable easy selection of the recombinants carrying the desired plasmid, to eliminate the antibiotic resistance cassette via homologous recombination, and to avoid the necessity of constructing new vectors. This strategy was successfully applied to functional analysis of the genes associated with iron acquisition by A. baumannii ATCC 19606 and to ompA gene deletion in other A. baumannii strains. Consequently, the proposed method is invaluable for markerless gene deletion in multidrug-resistant A. baumannii. PMID:25746991

  8. Negative elongation factor NELF controls transcription of immediate early genes in a stimulus-specific manner

    SciTech Connect

    Fujita, Toshitsugu; Piuz, Isabelle; Schlegel, Werner

    2009-01-15

    The transcription rate of immediate early genes (IEGs) is controlled directly by transcription elongation factors at the transcription elongation step. Negative elongation factor (NELF) and 5,6-dichloro-1-{beta}-D-ribofuranosylbenzimidazole (DRB) sensitivity-inducing factor (DSIF) stall RNA polymerase II (pol II) soon after transcription initiation. Upon induction of IEG transcription, DSIF is converted into an accelerator for pol II elongation. To address whether and how NELF as well as DSIF controls overall IEG transcription, its expression was reduced using stable RNA interference in GH4C1 cells. NELF knock-down reduced thyrotropin-releasing hormone (TRH)-induced transcription of the IEGs c-fos, MKP-1, and junB. In contrast, epidermal growth factor (EGF)-induced transcription of these IEGs was unaltered or even slightly increased by NELF knock-down. Thus, stable knock-down of NELF affects IEG transcription stimulation-specifically. Conversely, DSIF knock-down reduced both TRH- and EGF-induced transcription of the three IEGs. Interestingly, TRH-induced activation of the MAP kinase pathway, a pathway essential for transcription of the three IEGs, was down-regulated by NELF knock-down. Thus, stable knock-down of NELF, by modulating intracellular signaling pathways, caused stimulation-specific loss of IEG transcription. These observations indicate that NELF controls overall IEG transcription via multiple mechanisms both directly and indirectly.

  9. Characterization of synthetic DNA bar codes in Saccharomyces cerevisiae gene-deletion strains

    PubMed Central

    Eason, Robert G.; Pourmand, Nader; Tongprasit, Waraporn; Herman, Zelek S.; Anthony, Kevin; Jejelowo, Olufisayo; Davis, Ronald W.; Stolc, Viktor

    2004-01-01

    Incorporation of strain-specific synthetic DNA tags into yeast Saccharomyces cerevisiae gene-deletion strains has enabled identification of gene functions by massively parallel growth rate analysis. However, it is important to confirm the sequences of these tags, because mutations introduced during construction could lead to significant errors in hybridization performance. To validate this experimental system, we sequenced 11,812 synthetic 20-mer molecular bar codes and adjacent sequences (>1.8 megabases synthetic DNA) by pyrosequencing and Sanger methods. At least 31% of the genome-integrated 20-mer tags contain differences from those originally synthesized. However, these mutations result in anomalous hybridization in only a small subset of strains, and the sequence information enables redesign of hybridization probes for arrays. The robust performance of the yeast gene-deletion dual oligonucleotide bar-code design in array hybridization validates the use of molecular bar codes in living cells for tracking their growth phenotype. PMID:15258289

  10. Enhanced Hydrogen Production in Escherichia coli Through Chemical Mutagenesis, Gene Deletion, and Transposon Mutagenesis 

    E-print Network

    Garzon Sanabria, Andrea Juliana

    2011-08-08

    be increased by random mutagenesis using N-methyl-N?-nitro-N-nitrosoguanidine (MNNG) and that hydrogen production can be further increased in the chemically-mutagenized strain by targeted gene deletion and overexpression of genes related to formate...), from chemical mutagen 3/86 increased hydrogen production 188 ? 0.50-fold (relative to the unmutagenized strain), and deletion of hycA, which encodes the repressor of formate hydrogen lyase (FHL), increased hydrogen production 232 ? 0.50-fold...

  11. Systematic gene deletions evidences that laccases are involved in several stages of wood degradation in the filamentous fungus Podospora anserina.

    PubMed

    Xie, Ning; Chapeland-Leclerc, Florence; Silar, Philippe; Ruprich-Robert, Gwenaël

    2014-01-01

    Transformation of plant biomass into biofuels may supply environmentally friendly alternative biological sources of energy. Laccases are supposed to be involved in the lysis of lignin, a prerequisite step for efficient breakdown of cellulose into fermentable sugars. The role in development and plant biomass degradation of the nine canonical laccases belonging to three different subfamilies and one related multicopper oxidase of the Ascomycota fungus Podospora anserina was investigated by targeted gene deletion. The 10 genes were inactivated singly, and multiple mutants were constructed by genetic crosses. lac6(?), lac8(?) and mco(?) mutants were significantly reduced in their ability to grow on lignin-containing materials, but also on cellulose and plastic. Furthermore, lac8(?), lac7(?), mco(?) and lac6(?) mutants were defective towards resistance to phenolic substrates and H2 O2 , which may also impact lignocellulose breakdown. Double and multiple mutants were generally more affected than single mutants, evidencing redundancy of function among laccases. Our study provides the first genetic evidences that laccases are major actors of wood utilization in a fungus and that they have multiple roles during this process apart from participation in lignin lysis. PMID:24102726

  12. Effects of G-gene Deletion and Replacement on Rabies Virus Vector Gene Expression

    PubMed Central

    Sato, Sho; Ohara, Shinya; Tsutsui, Ken-Ichiro; Iijima, Toshio

    2015-01-01

    The glycoprotein-gene (G gene) -deleted rabies virus (RV) vector is a powerful tool to examine the function and structure of neural circuits. We previously reported that the deletion of the G gene enhances the transgene expression level of the RV vector. However, the mechanism of this enhancement remains to be clarified. We presume that there are two possible factors for this enhancement. The first factor is the glycoprotein of RV, which shows cytotoxicity; thus, may cause a dysfunction in the translation process of infected cells. The second possible factor is the enhanced expression of the L gene, which encodes viral RNA polymerase. In the RV, it is known that the gene expression level is altered depending on the position of the gene. Since G-gene deletion displaces the L gene in the genome, the expression of the L gene and viral transcription may be enhanced. In this study, we compared the transgene expression level and viral transcription of three recombinant RV vectors. The effect of glycoprotein was examined by comparing the viral gene expression of G-gene-intact RV and G-gene-replaced RV. Despite the fact that the L-gene transcription level of these two RV vectors was similar, the G-gene-replaced RV vector showed higher viral transcription and transgene expression level than the G-gene-intact RV vector. To examine the effect of the position of the L gene, we compared the viral gene expression of the G-gene-deleted RV and G-gene-replaced RV. The G-gene-deleted RV vector showed higher L-gene transcription, viral transcription, and transgene expression level than the G-gene-replaced RV vector. These results indicate that G-gene deletion enhances the transgene expression level through at least two factors, the absence of glycoprotein and enhancement of L-gene expression. These findings enable investigators to design a useful viral vector that shows a controlled desirable transgene expression level in applications. PMID:26023771

  13. Human Cytomegalovirus pUL97 Regulates the Viral Major Immediate Early Promoter by Phosphorylation-Mediated Disruption of Histone Deacetylase 1 Binding

    PubMed Central

    Bigley, Tarin M.; Reitsma, Justin M.; Mirza, Shama P.

    2013-01-01

    Human cytomegalovirus (HCMV) is a common agent of congenital infection and causes severe disease in immunocompromised patients. Current approved therapies focus on inhibiting viral DNA replication. The HCMV kinase pUL97 contributes to multiple stages of viral infection including DNA replication, controlling the cell cycle, and virion maturation. Our studies demonstrate that pUL97 also functions by influencing immediate early (IE) gene expression during the initial stages of infection. Inhibition of kinase activity using the antiviral compound maribavir or deletion of the UL97 gene resulted in decreased expression of viral immediate early genes during infection. Expression of pUL97 was sufficient to transactivate IE1 gene expression from the viral genome, which was dependent on viral kinase activity. We observed that pUL97 associates with histone deacetylase 1 (HDAC1). HDAC1 is a transcriptional corepressor that acts to silence expression of viral genes. We observed that inhibition or deletion of pUL97 kinase resulted in increased HDAC1 and decreased histone H3 lysine 9 acetylation associating with the viral major immediate early (MIE) promoter. IE expression during pUL97 inhibition or deletion was rescued following inhibition of deacetylase activity. HDAC1 associates with chromatin by protein-protein interactions. Expression of active but not inactive pUL97 kinase decreased HDAC1 interaction with the transcriptional repressor protein DAXX. Finally, using mass spectrometry, we found that HDAC1 is uniquely phosphorylated upon expression of pUL97. Our results support the conclusion that HCMV pUL97 kinase regulates viral immediate early gene expression by phosphorylation-mediated disruption of HDAC1 binding to the MIE promoter. PMID:23616659

  14. Gene Deletion Strategy To Examine the Involvement of the Two Chondroitin Lyases in Flavobacterium columnare Virulence.

    PubMed

    Li, Nan; Qin, Ting; Zhang, Xiao Lin; Huang, Bei; Liu, Zhi Xin; Xie, Hai Xia; Zhang, Jin; McBride, Mark J; Nie, Pin

    2015-11-01

    Flavobacterium columnare is an important bacterial pathogen of freshwater fish that causes high mortality of infected fish and heavy economic losses in aquaculture. The pathogenesis of this bacterium is poorly understood, in part due to the lack of efficient methods for genetic manipulation. In this study, a gene deletion strategy was developed and used to determine the relationship between the production of chondroitin lyases and virulence. The F. johnsoniae ompA promoter (PompA) was fused to sacB to construct a counterselectable marker for F. columnare. F. columnare carrying PompA-sacB failed to grow on media containing 10% sucrose. A suicide vector carrying PompA-sacB was constructed, and a gene deletion strategy was developed. Using this approach, the chondroitin lyase-encoding genes, cslA and cslB, were deleted. The ?cslA and ?cslB mutants were both partially deficient in digestion of chondroitin sulfate A, whereas a double mutant (?cslA ?cslB) was completely deficient in chondroitin lyase activity. Cells of F. columnare wild-type strain G4 and of the chondroitin lyase-deficient ?cslA ?cslB mutant exhibited similar levels of virulence toward grass carp in single-strain infections. Coinfections, however, revealed a competitive advantage for the wild type over the chondroitin lyase mutant. The results indicate that chondroitin lyases are not essential virulence factors of F. columnare but may contribute to the ability of the pathogen to compete and cause disease in natural infections. The gene deletion method developed in this study may be employed to investigate the virulence factors of this bacterium and may have wide application in many other members of the phylum Bacteroidetes. PMID:26253667

  15. A Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Aging.

    PubMed

    McCormick, Mark A; Delaney, Joe R; Tsuchiya, Mitsuhiro; Tsuchiyama, Scott; Shemorry, Anna; Sim, Sylvia; Chou, Annie Chia-Zong; Ahmed, Umema; Carr, Daniel; Murakami, Christopher J; Schleit, Jennifer; Sutphin, George L; Wasko, Brian M; Bennett, Christopher F; Wang, Adrienne M; Olsen, Brady; Beyer, Richard P; Bammler, Theodor K; Prunkard, Donna; Johnson, Simon C; Pennypacker, Juniper K; An, Elroy; Anies, Arieanna; Castanza, Anthony S; Choi, Eunice; Dang, Nick; Enerio, Shiena; Fletcher, Marissa; Fox, Lindsay; Goswami, Sarani; Higgins, Sean A; Holmberg, Molly A; Hu, Di; Hui, Jessica; Jelic, Monika; Jeong, Ki-Soo; Johnston, Elijah; Kerr, Emily O; Kim, Jin; Kim, Diana; Kirkland, Katie; Klum, Shannon; Kotireddy, Soumya; Liao, Eric; Lim, Michael; Lin, Michael S; Lo, Winston C; Lockshon, Dan; Miller, Hillary A; Moller, Richard M; Muller, Brian; Oakes, Jonathan; Pak, Diana N; Peng, Zhao Jun; Pham, Kim M; Pollard, Tom G; Pradeep, Prarthana; Pruett, Dillon; Rai, Dilreet; Robison, Brett; Rodriguez, Ariana A; Ros, Bopharoth; Sage, Michael; Singh, Manpreet K; Smith, Erica D; Snead, Katie; Solanky, Amrita; Spector, Benjamin L; Steffen, Kristan K; Tchao, Bie Nga; Ting, Marc K; Vander Wende, Helen; Wang, Dennis; Welton, K Linnea; Westman, Eric A; Brem, Rachel B; Liu, Xin-Guang; Suh, Yousin; Zhou, Zhongjun; Kaeberlein, Matt; Kennedy, Brian K

    2015-11-01

    Many genes that affect replicative lifespan (RLS) in the budding yeast Saccharomyces cerevisiae also affect aging in other organisms such as C. elegans and M. musculus. We performed a systematic analysis of yeast RLS in a set of 4,698 viable single-gene deletion strains. Multiple functional gene clusters were identified, and full genome-to-genome comparison demonstrated a significant conservation in longevity pathways between yeast and C. elegans. Among the mechanisms of aging identified, deletion of tRNA exporter LOS1 robustly extended lifespan. Dietary restriction (DR) and inhibition of mechanistic Target of Rapamycin (mTOR) exclude Los1 from the nucleus in a Rad53-dependent manner. Moreover, lifespan extension from deletion of LOS1 is nonadditive with DR or mTOR inhibition, and results in Gcn4 transcription factor activation. Thus, the DNA damage response and mTOR converge on Los1-mediated nuclear tRNA export to regulate Gcn4 activity and aging. PMID:26456335

  16. Recovery of Replication-Competent and G-Gene-Deleted Rabies Viruses from cDNA.

    PubMed

    Hagendorf, Nadin; Conzelmann, Karl-Klaus

    2015-01-01

    This protocol describes the recovery of replication-competent rabies viruses (RV) such as SAD L16 or SAD L16-eGFP. It is suggested that at least three parallel transfection experiments are performed to increase the success rate (in three 3.5-cm(2) dishes or in three wells in a six-well plate). The entire protocol takes 10 d, and successful rescue can be obtained after 6 d. An additional procedure for the recovery of G-gene-deleted viruses is also included. Please note that appropriate biosafety measures are needed. PMID:26631127

  17. Constitutional and mosaic large NF1 gene deletions in neurofibromatosis type 1.

    PubMed Central

    Rasmussen, S A; Colman, S D; Ho, V T; Abernathy, C R; Arn, P H; Weiss, L; Schwartz, C; Saul, R A; Wallace, M R

    1998-01-01

    A set of neurofibromatosis type 1 (NF1) patients was screened for large NF1 gene deletions by comparing patient and parent genotypes at 10 intragenic polymorphic loci. Of 67 patient/parent sets (47 new mutation patients and 20 familial cases), five (7.5%) showed loss of heterozygosity (LOH), indicative of NF1 gene deletion. These five patients did not have severe NF1 manifestations, mental retardation, or dysmorphic features, in contrast to previous reports of large NF1 deletions. All five deletions were de novo and occurred on the maternal chromosome. However, two patients showed partial LOH, consistent with somatic mosaicism for the deletion, suggesting that mosaicism may be more frequent in NF1 than previously recognised (and may have bearing on clinical severity). We suggest that large NF1 deletions (1) are not always associated with unusual clinical features, (2) tend to occur more frequently on maternal alleles, and (3) are an important mechanism for constitutional and somatic mutations in NF1 patients. Images PMID:9643287

  18. Rb and p53 gene deletions in lung adenocarcinomas from irradiated and control mice

    SciTech Connect

    Zhang, Y.; Woloschak, G.E.

    1997-08-01

    This study was conducted on mouse lung adenocarcinoma tissues that were formalin-treated and paraffin-embedded 25 years ago to investigate the large gene deletions of mRb and p53 in B6CF{sub 1} male mice. A total of 80 lung tissue samples from irradiated mice and 40 lung samples from nonirradiated controls were randomly selected and examined in the mRb portion of this study. The results showed a significant (P < 0.05) higher percentage of mRb deletions in lung adenocarcinomas from mice exposed to 60 once-weekly {gamma}-ray doses than those from mice receiving 24 once-weekly {gamma}-ray doses at low doses and low dose rates; however, the percentage was not significantly different (P > 0.05) from that for spontaneous lung adenocarcinomas or lung adenocarcinomas from mice exposed to single-dose {gamma} irradiation at a similar total dose. mRb fragments 3 (71%) and 5 (67%), the parts of the gene that encoded the pocket binding region of Rb protein to adenovirus E1A and SV40 T-antigen, were the most frequently deleted fragments. p53 gene deletion analysis was carried out on normal lungs and lung adenocarcinomas that were initially found to bear mRb deletions. Exons 1,4,5,6, and 9 were chosen to be analyzed.

  19. Transcriptional Dynamics Reveal Critical Roles for Non-coding RNAs in the Immediate-Early Response

    PubMed Central

    Aitken, Stuart; Magi, Shigeyuki; Alhendi, Ahmad M. N.; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Daub, Carsten O.; Arner, Erik; Carninci, Piero; Forrest, Alistair R. R.; Hayashizaki, Yoshihide; Khachigian, Levon M.; Okada-Hatakeyama, Mariko; Semple, Colin A.

    2015-01-01

    The immediate-early response mediates cell fate in response to a variety of extracellular stimuli and is dysregulated in many cancers. However, the specificity of the response across stimuli and cell types, and the roles of non-coding RNAs are not well understood. Using a large collection of densely-sampled time series expression data we have examined the induction of the immediate-early response in unparalleled detail, across cell types and stimuli. We exploit cap analysis of gene expression (CAGE) time series datasets to directly measure promoter activities over time. Using a novel analysis method for time series data we identify transcripts with expression patterns that closely resemble the dynamics of known immediate-early genes (IEGs) and this enables a comprehensive comparative study of these genes and their chromatin state. Surprisingly, these data suggest that the earliest transcriptional responses often involve promoters generating non-coding RNAs, many of which are produced in advance of canonical protein-coding IEGs. IEGs are known to be capable of induction without de novo protein synthesis. Consistent with this, we find that the response of both protein-coding and non-coding RNA IEGs can be explained by their transcriptionally poised, permissive chromatin state prior to stimulation. We also explore the function of non-coding RNAs in the attenuation of the immediate early response in a small RNA sequencing dataset matched to the CAGE data: We identify a novel set of microRNAs responsible for the attenuation of the IEG response in an estrogen receptor positive cancer cell line. Our computational statistical method is well suited to meta-analyses as there is no requirement for transcripts to pass thresholds for significant differential expression between time points, and it is agnostic to the number of time points per dataset. PMID:25885578

  20. Soluble epoxide hydrolase gene deletion improves blood flow and reduces infarct size after cerebral ischemia in reproductively senescent female mice

    PubMed Central

    Zuloaga, Kristen L.; Zhang, Wenri; Roese, Natalie E.; Alkayed, Nabil J.

    2015-01-01

    Soluble epoxide hydrolase (sEH), a key enzyme in the metabolism of vasodilatory epoxyeicosatrienoic acids (EETs), is sexually dimorphic, suppressed by estrogen, and contributes to underlying sex differences in cerebral blood flow and injury after cerebral ischemia. We tested the hypothesis that sEH inhibition or gene deletion in reproductively senescent (RS) female mice would increase cerebral perfusion and decrease infarct size following stroke. RS (15–18 month old) and young (3–4 month old) female sEH knockout (sEHKO) mice and wild type (WT) mice were subjected to 45 min middle cerebral artery occlusion (MCAO) with laser Doppler perfusion monitoring. WT mice were treated with vehicle or a sEH inhibitor t-AUCB at the time of reperfusion and every 24 h thereafter for 3 days. Differences in regional cerebral blood flow were measured in vivo using optical microangiography (OMAG). Infarct size was measured 3 days after reperfusion. Infarct size and cerebral perfusion 24 h after MCAO were not altered by age. Both sEH gene deletion and sEH inhibition increased cortical perfusion 24 h after MCAO. Neither sEH gene deletion nor sEH inhibition reduced infarct size in young mice. However, sEH gene deletion, but not sEH inhibition of the hydrolase domain of the enzyme, decreased infarct size in RS mice. Results of these studies show that sEH gene deletion and sEH inhibition enhance cortical perfusion following MCAO and sEH gene deletion reduces damage after ischemia in RS female mice; however this neuroprotection in absent is young mice. PMID:25642188

  1. Evidence of Selection for the ?-Globin Gene Deletions and Triplications in a Southern Chinese Population.

    PubMed

    Xie, Xing-Mei; Wu, Man-Yu; Li, Dong-Zhi

    2015-12-01

    ?(+)-Thalassemia (?(+)-thal) is common in Southern China. The high frequency could be due to over dominant selection through malaria. Two molecular mechanisms that produce ?(+)-thal have been defined; one results in the -?(3.7) (rightward) deletion and reciprocal ???(anti 3.7) triplication, and the other one results in the -?(4.2) (leftward) deletion and reciprocal ???(anti 4.2) triplication. Considering that each de novo event produced a chromosome with an ? gene deletion and a chromosome with an ? triplication, if there is no favorable allele, one would expected to find the same allelic frequencies. We found a favorable selection for the -?(3.7) deletion in the Chinese population, and we also found that the ? triplication is not as rare as was first thought, especially for the ???(anti 3.7) triplication. PMID:26290492

  2. Biochemical activities of T-antigen proteins encoded by simian virus 40 A gene deletion mutants.

    PubMed Central

    Clark, R; Peden, K; Pipas, J M; Nathans, D; Tjian, R

    1983-01-01

    We have analyzed T antigens produced by a set of simian virus 40 (SV40) A gene deletion mutants for ATPase activity and for binding to the SV40 origin of DNA replication. Virus stocks of nonviable SV40 A gene deletion mutants were established in SV40-transformed monkey COS cells. Mutant T antigens were produced in mutant virus-infected CV1 cells. The structures of the mutant T antigens were characterized by immunoprecipitation with monoclonal antibodies directed against distinct regions of the T-antigen molecule. T antigens in crude extracts prepared from cells infected with 10 different mutants were immobilized on polyacrylamide beads with monoclonal antibodies, quantified by Coomassie blue staining, and then assayed directly for T antigen-specific ATPase activity and for binding to the SV40 origin of DNA replication. Our results indicate that the T antigen coding sequences required for origin binding map between 0.54 and 0.35 map units on the SV40 genome. In contrast, sequences closer to the C terminus of T antigen (between 0.24 and 0.20 map units) are required for ATPase activity. The presence of the ATPase activity correlated closely with the ability of the mutant viruses to replicate and to transform nonpermissive cells. The origin binding activity was retained, however, by three mutants that lacked these two functions, indicating that this activity is not sufficient to support either cellular transformation or viral replication. Neither the ATPase activity nor the origin binding activity correlated with the ability of the mutant DNA to activate silent rRNA genes or host cell DNA synthesis. Images PMID:6300658

  3. Effects of Bax Gene Deletion on Social Behaviors and Neural Response to Olfactory Cues in Mice

    PubMed Central

    Holmes, Melissa M.; Niel, Lee; Anyan, Jeff J.; Griffith, Andrew T.; Monks, D. Ashley; Forger, Nancy G.

    2011-01-01

    Bax is a pro-death protein that plays a crucial role in developmental neuronal cell death. Bax?/? mice exhibit increased neuron number and the elimination of several neural sex differences. Here we examined the effects of Bax gene deletion on social behaviors (olfactory preference, social recognition, social approach, and aggression) and the neural processing of olfactory cues. Bax deletion eliminated the normal sex difference in olfactory preference behavior. In the social recognition test, both genotypes discriminated a novel conspecific, but wildtype males and Bax?/? animals of both sexes spent much more time than wildtype females investigating stimulus animals. Similarly, Bax?/? mice were more sociable than wildtype mice in a social approach test. Bax deletion had no effect on aggression in a resident/intruder paradigm where males, regardless of genotype, exhibited a shorter latency to attack. Thus, the prevention of neuronal cell death by Bax gene deletion results in greater sociability as well as the elimination of sex differences in some social behaviors. To examine olfactory processing of socially relevant cues, we counted c-Fos immunoreactive (Fos-ir) cells in several nodes of the accessory olfactory pathway after exposure to male-soiled or control bedding. In both genotypes, exposure to male-soiled bedding increased Fos-ir cells in the posterodorsal medial amygdala, principal nucleus of the bed nucleus of the stria terminalis, and medial preoptic nucleus (MPN), and the response in the MPN was greater in females than in males. However, a reduction in Fos-ir cells was seen in the anteroventral periventricular nucleus of Bax?/? mice. PMID:22034980

  4. Stress-induced hematopoietic failure in the absence of immediate early response gene X-1 (IEX-1, IER3)

    E-print Network

    Ramsey, Haley

    Expression of the immediate early response gene X-1 (IEX-1, IER3) is diminished significantly in hematopoietic stem cells in a subgroup of patients with early stage myelodysplastic syndromes, but it is not clear whether ...

  5. A self-excising beta-recombinase/six cassette for repetitive gene deletion and homokaryon purification in Neurospora crassa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In a previous study we developed a cassette employing a bacterial beta-recombinase acting on six recognition sequences (beta-rec/six), which allowed repetitive site-specific gene deletion and marker recycling in Neurospora crassa. However, only one positive selection marker was used in the cassette...

  6. Herpes Simplex Virus Immediate-Early Protein ICP0 Is Targeted by SIAH-1 for Proteasomal Degradation?†?

    PubMed Central

    Nagel, Claus-Henning; Albrecht, Nina; Milovic-Holm, Kristijana; Mariyanna, Lakshmikanth; Keyser, Britta; Abel, Bettina; Weseloh, Britta; Hofmann, Thomas G.; Eibl, Martha M.; Hauber, Joachim

    2011-01-01

    Herpes simplex virus (HSV) immediate-early protein ICP0 is a transcriptional activator with E3 ubiquitin ligase activity that induces the degradation of ND10 proteins, including the promyelocytic leukemia protein (PML) and Sp100. Moreover, ICP0 has a role in the derepression of viral genomes and in the modulation of the host interferon response to virus infection. Here, we report that ICP0 interacts with SIAH-1, a cellular E3 ubiquitin ligase that is involved in multiple cellular pathways and is itself capable of mediating PML degradation. This novel virus-host interaction profoundly stabilized SIAH-1 and recruited this cellular E3 ligase into ICP0-containing nuclear bodies. Moreover, SIAH-1 mediated the polyubiquitination of HSV ICP0 in vitro and in vivo. After infection of SIAH-1 knockdown cells with HSV, higher levels of ICP0 were produced, ICP0 was less ubiquitinated, and the half-life of this multifunctional viral regulatory protein was increased. These results indicate an inhibitory role of SIAH-1 during lytic infection by targeting ICP0 for proteasomal degradation. PMID:21632771

  7. A Diverse Repertoire of CD4 T Cells Targets the Immediate-Early 1 Protein of Human Cytomegalovirus

    PubMed Central

    Ameres, Stefanie; Liang, Xiaoling; Wiesner, Martina; Mautner, Josef; Moosmann, Andreas

    2015-01-01

    T-cell responses to the immediate-early 1 (IE-1) protein of human cytomegalovirus (HCMV) are associated with protection from viral disease. Thus, IE-1 is a promising target for immunotherapy. CD8 T-cell responses to IE-1 are generally strong. In contrast, CD4 T-cell responses to IE-1 were described to be comparatively infrequent or undetectable in HCMV carriers, and information on their target epitopes and their function has been limited. To analyze the repertoire of IE-1-specific CD4 T cells, we expanded them from healthy donors with autologous IE-1-expressing mini-Epstein–Barr virus-transformed B-cell lines and established IE-1-specific CD4 T-cell clones. Clones from seven out of seven HCMV-positive donors recognized endogenously processed IE-1 epitopes restricted through HLA-DR, DQ, or DP. Three to seven IE-1 epitopes were recognized per donor. Cumulatively, about 27 different HLA/peptide class II complexes were recognized by 117 IE-1-specific clones. Our results suggest that a highly diversified repertoire of IE-1-specific CD4 T cells targeting multiple epitopes is usually present in healthy HCMV carriers. Therefore, multiepitope approaches to immunomonitoring and immunotherapy will make optimal use of this potentially important class of HCMV-specific effector cells. PMID:26635812

  8. Inflammatory responses to pneumovirus infection in IFN-alpha beta R gene-deleted mice.

    PubMed

    Garvey, Tara L; Dyer, Kimberly D; Ellis, John A; Bonville, Cynthia A; Foster, Barbara; Prussin, Calman; Easton, Andrew J; Domachowske, Joseph B; Rosenberg, Helene F

    2005-10-01

    Pneumonia virus of mice (PVM; family Paramyxoviridae) is a natural pathogen of rodents that reproduces important clinical features of severe respiratory syncytial virus infection in humans. As anticipated, PVM infection induces transcription of IFN antiviral response genes preferentially in wild-type over IFN-alphabetaR gene-deleted (IFN-alphabetaR-/-) mice. However, we demonstrate that PVM infection results in enhanced expression of eotaxin-2 (CCL24), thymus and activation-regulated chemokine (CCL17), and the proinflammatory RNase mouse eosinophil-associated RNase (mEar) 11, and decreased expression of monocyte chemotactic protein-5, IFN-gamma-inducible protein-10, and TLR-3 in lung tissue of IFN-alphabetaR-/- mice when compared with wild type. No differential expression of chemokines MIP-1alpha or MIP-2 or Th2 cytokines IL-4 or IL-5 was observed. Differential expression of proinflammatory mediators was associated with distinct patterns of lung pathology. The widespread granulocytic infiltration and intra-alveolar edema observed in PVM-infected, wild-type mice are replaced with patchy, dense inflammatory foci localized to the periphery of the larger blood vessels. Bronchoalveolar lavage fluid from IFN-alphabetaR-/- mice yielded 7- to 8-fold fewer leukocytes overall, with increased percentages of eosinophils, monocytes, and CD4+ T cells, and decreased percentage of CD8+ T cells. Differential pathology is associated with prolonged survival of the IFN-alphabetaR-/- mice (50% survival at 10.8 +/- 0.6 days vs the wild type at 9.0 +/- 0.3 days; p < 0.02) despite increased virus titers. Overall, our findings serve to identify novel transcripts that are differentially expressed in the presence or absence of IFN-alphabetaR-mediated signaling, further elucidating interactions between the IFN and antiviral inflammatory responses in vivo. PMID:16177121

  9. Functional profiling in Streptococcus mutans: construction and examination of a genomic collection of gene deletion mutants.

    PubMed

    Quivey, R G; Grayhack, E J; Faustoferri, R C; Hubbard, C J; Baldeck, J D; Wolf, A S; MacGilvray, M E; Rosalen, P L; Scott-Anne, K; Santiago, B; Gopal, S; Payne, J; Marquis, R E

    2015-12-01

    A collection of tagged deletion mutant strains was created in Streptococcus mutans UA159 to facilitate investigation of the aciduric capability of this oral pathogen. Gene-specific barcoded deletions were attempted in 1432 open reading frames (representing 73% of the genome), and resulted in the isolation of 1112 strains (56% coverage) carrying deletions in distinct non-essential genes. As S. mutans virulence is predicated upon the ability of the organism to survive an acidic pH environment, form biofilms on tooth surfaces, and out-compete other oral microflora, we assayed individual mutant strains for the relative fitness of the deletion strain, compared with the parent strain, under acidic and oxidative stress conditions, as well as for their ability to form biofilms in glucose- or sucrose-containing medium. Our studies revealed a total of 51 deletion strains with defects in both aciduricity and biofilm formation. We have also identified 49 strains whose gene deletion confers sensitivity to oxidative damage and deficiencies in biofilm formation. We demonstrate the ability to examine competitive fitness of mutant organisms using the barcode tags incorporated into each deletion strain to examine the representation of a particular strain in a population. Co-cultures of deletion strains were grown either in vitro in a chemostat to steady-state values of pH 7 and pH 5 or in vivo in an animal model for oral infection. Taken together, these data represent a mechanism for assessing the virulence capacity of this pathogenic microorganism and a resource for identifying future targets for drug intervention to promote healthy oral microflora. PMID:25973955

  10. A Form of Perforant Path LTP Can Occur without ERK1/2 Phosphorylation or Immediate Early Gene Induction

    ERIC Educational Resources Information Center

    Steward, Oswald; Huang, Fen; Guzowski, John F.

    2007-01-01

    Stimulation paradigms that induce perforant path long-term potentiation (LTP) initiate phosphorylation of ERK1/2 and induce expression of a variety of immediate early genes (IEGs). These events are thought to be critical components of the mechanism for establishing the changes in synaptic efficacy that endure for hours or longer. Here we show that…

  11. A new role for downstream Toll-like receptor signaling in mediating immediate early gene expression during focal cerebral ischemia.

    PubMed

    Famakin, Bolanle M; Mou, Yongshan; Johnson, Kory; Spatz, Maria; Hallenbeck, John

    2014-02-01

    To better understand the role of downstream Toll-like receptor (TLR) signaling during acute cerebral ischemia, we performed cDNA microarrays, on brain RNA, and cytokine arrays, on serum, from wild type (WT), MyD88-/- and TRIF-mutant mice, at baseline and following permanent middle cerebral artery occlusion (pMCAO). The acute stress response pathway was among the top pathways identified by Ingenuity Pathway Analysis of microarray data. We used real-time polymerase chain reaction to confirm the expression of four immediate early genes; EGR1, EGR2, ARC, Nurr77, in this pathway, and insulin degrading enzyme (IDE). Compared to WT, baseline immediate early gene expression was increased up to10-fold in MyD88-/- and TRIF-mutant mice. However, following pMCAO, immediate early gene expression remained unchanged, from this elevated baseline in these mice, but increased up to 12-fold in WT. Furthermore, expression of IDE, which also degrades ?-amyloid, decreased significantly only in TRIF-mutant mice. Finally, sE-Selectin, sICAM, sVCAM-1, and MMP-9 levels were significantly decreased only in MyD88-/- compared with WT mice. We thus report a new role for downstream TLR signaling in immediate early gene expression during acute cerebral ischemia. We also show that the TRIF pathway regulates IDE expression; a major enzyme that clears ?-amyloid from the brain. PMID:24301291

  12. Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus

    SciTech Connect

    Davis, M.G.; Kenney, S.C.; Kamine, J.; Pagano, J.S.; Huang, E.S.

    1987-12-01

    Almost all homosexual patients with acquired immunodeficiency syndrome are also actively infected with human cytomegalovirus (HCMV). The authors have hypothesized that an interaction between HCMV and human immunodeficiency virus (HIV), the agent that causes acquired immunodeficiency syndrome, may exist at a molecular level and contribute to the manifestations of HIV infection. In this report, they demonstrate that the immediate-early gene region of HCMV, in particular immediate-early region 2, trans-activates the expression of the bacterial gene chloramphenicol acetyltransferase that is fused to the HIV long terminal repeat and carried by plasmid pHIV-CAT. The HCMV immediate-early trans-activator increases the level of mRNA from the plamid pHIV-CAT. The sequences of HIV that are responsive to trans-activation by the HDMV immediate-early region are distinct from HIV sequences that are required for response to the HIV tat. The stimulation of HIV gene expression by HDMV gene functions could enhance the consequences of HIV infection in persons with previous or concurrent HCMV infection.

  13. TISSUE-PLASMINOGEN ACTIVATOR IS INDUCED AS AN IMMEDIATE-EARLY GENE DURING SEIZURE, KINDLING, AND LONG-TERM POTENTIATION

    EPA Science Inventory

    Activity-dependent genes in brain have been identified using differential screening of hippocampal cDNA library from rats exposed to metrazol seizures under conditions of superconduction. Five immediate early genes whose expression is elevated by neural activity were identified. ...

  14. Expression of the Immediate-Early Gene-Encoded Protein Egr-1 ("zif268") during in Vitro Classical Conditioning

    ERIC Educational Resources Information Center

    Mokin, Maxim; Keifer, Joyce

    2005-01-01

    Expression of the immediate-early genes (IEGs) has been shown to be induced by activity-dependent synaptic plasticity or behavioral training and is thought to play an important role in long-term memory. In the present study, we examined the induction and expression of the IEG-encoded protein Egr-1 during an in vitro neural correlate of eyeblink…

  15. Novelty-Induced Increased Expression of Immediate-Early Genes c-fos and arg 3.1

    E-print Network

    Kuhl, Dietmar

    ; amygdala; limbic system In nature, animals are constantly confronted with new situations. They continuously memory formation. To determine the involvement of limbic and neocortical brain structures in novelty: novelty; learning; memory; gustatory system; immediate-early genes; c-fos; arg 3.1; cingulate cortex

  16. Salicylate-induced changes in immediate-early genes in the hippocampal CA1 area

    PubMed Central

    WU, HAO; XU, FENG-LEI; YIN, YONG; DA, PENG; YOU, XIAO-DONG; XU, HUI-MIN; TANG, YAN

    2015-01-01

    Studies have suggested that salicylate affects neuronal function via interactions with specific membrane channels/receptors. However, the effect of salicylate on activity and synaptic morphology of the hippocampal Cornu Ammonis (CA) 1 area remains to be elucidated. The activation of immediate-early genes (IEGs) was reported to correlate with neuronal activity, in particular activity-regulated cytoskeleton-associated protein and early growth response gene 1. The aim of the present study was to evaluate the expression of these IEGs, as well that of N-methyl D-aspartate (NMDA) receptor subunit 2B in rats following acute and chronic salicylate treatment. Protein and messenger RNA levels of all three genes were increased in rats following chronic administration of salicylate (300 mg/kg for 10 days), returning to baseline levels 14 days post-cessation of treatment. The transient upregulation of gene expression following treatment was accompanied by ultrastructural alterations in hippocampal CA1 area synapses. An increase in synaptic interface curvature was observed as well as an increased number of presynaptic vesicles; in addition, postsynaptic densities thickened and lengthened. In conclusion, the results of the present study indicated that chronic exposure to salicylate may lead to structural alteration of hippocampal CA1 neurons, and it was suggested that this process occurs through induced expression of IEGs via NMDA receptor activation. PMID:25873216

  17. Modeling the Kinetics of a Memory-Associated Immediate Early Gene's Compartmental Expression After Sensory Experience

    NASA Astrophysics Data System (ADS)

    Willats, Adam; Ivanova, Tamara; Prinz, Astrid; Liu, Robert

    2015-03-01

    Immediate Early Genes (IEGs) are rapidly and transiently transcribed in neurons after a sensory experience. Some of these genes act as effector IEGs, which mediate specific effects on cellular function. Arc is one such effector IEG that is essential for synaptic plasticity and memory consolidation in hippocampus and cortex. The expression of Arc in neurons has previously been examined using an imaging method known as Compartmental Analysis of Temporal Fluorescent In-Situ Hybridization. Previous work found that the time course of Arc expression within the nuclear and perinuclear cytoplasmic compartments of a neuron is altered by prior sensory experience. We explore a simple model of the kinetics of IEG transcription and nuclear export, with the aim of eventually uncovering possible mechanisms for how experience alters expression kinetics. Thus far, we characterize our compartmental model using phase-plane analysis and validate it against several IEG expression data sets, including one where prior experience with vocalizing mice alters the time course of call-induced Arc expression in the auditory cortex of a listening mouse. Our model provides a framework to explore why Arc expression may change depending on a receiver's past sound experience and internal state. Adam Willats was supported by NIH Training Grant 5T90DA032466. This research was also supported by NIDCD R01 DC8343.

  18. Total beta-globin gene deletion has high frequency in Filipinos

    SciTech Connect

    Patrick, N.; Miyakawa, F.; Hunt, J.A.

    1994-09-01

    The distribution of {beta}-thalassemia [{beta}{sup Th}] mutations is unique to each ethnic group. Most mutations affect one or a few bases; large deletions have been rare. Among families screened in Hawaii, [{beta}{sup Th}] heterozygotes were diagnosed by microcytosis, absence of abnormal hemoglobins on isoelectric focusing, and raised Hb A{sub 2} by chromatography. Gene frequency for {beta}{sup Th} was 0.02 in Filipinos. In Filipinos, polymerase chain reaction [PCR] with denaturing gradient gel electrophoresis for {beta}{sup Th} mutations detected a mutation in only 6 of 42 {beta}{sup Th} heterozygotes; an IVS2-666 C/T polymorphism showed non-heterozygosity in 37 and heterozygosity in only 5 of these {beta}{sup Th} heterozygotes. One {beta}{sup Th}/{beta}{sup Th} major patient and his mother had no mutation detected by allele-specific oligomer hybridization; PCR failed to amplify any DNA from his {beta}-globin gene. After a total {beta}-globin gene deletion [{beta}{sup Del}] was found in a Filipino family in Ontario, specific PCR amplification for {beta}{sup Del} detected this in 43 of 53 {beta}{sup Th} Filipino samples tested; the above {beta}{sup Th}/{beta}{sup Th} patient was a ({beta}{sup Del}/{beta}{sup Del}) homozygote. The {beta}{sup Del} may account for over 60% of all {beta}{sup Th} alleles in Filipinos; this is the highest proportion of a deletion {beta}{sup Th} mutation reported from any population. Most but not all {beta}{sup Del} heterozygotes had high Hb F [5.13 {plus_minus} 3.94 mean {plus_minus} 1 s.d.] compared to the codon 41/42 four base deletion common in Chinese [2.30 {plus_minus} 0.86], or to {beta}{sup Th} heterozygotes with normal {alpha}-globin genes [2.23 {plus_minus} 0.80].

  19. Inducible nitric oxide synthase gene deletion exaggerates MAPK-mediated cyclooxygenase-2 induction by inflammatory stimuli

    PubMed Central

    Upmacis, Rita K.; Deeb, Ruba S.; Koyuncu, Hilal; Hajjar, David P.

    2010-01-01

    Cyclooxygenase (COX)-2 and inducible nitric oxide (NO) synthase (iNOS) are responsive to a wide array of inflammatory stimuli, have been localized to vascular smooth muscle cells (SMCs), and are intimately linked to the progression of vascular disease, including atherosclerotic lesion formation. We and others have shown that the production and subsequent impact of COX products appear to be correlative with the status of NO synthesis. This study examined the impact of inflammation-driven NO production on COX-2 expression in SMCs. Concurrent stimulation of quiescent rat aortic SMCs with lipopolysaccharide (LPS) and interferon (IFN)-? increased COX-2, iNOS, and nitrite production. Pharmacological inhibition of NO synthase (NG-monomethyl-l-arginine) concentration- and time-dependently magnified LPS + IFN-?-mediated COX-2 mRNA and protein induction in a cGMP-independent manner. COX-2 induction was associated with activation of the ERK, p38, and JNK mitogen-activated protein kinase (MAPK) pathways. Interestingly, NO synthase inhibition enhanced ERK, p38, and to a lesser extent JNK phosphorylation but suppressed MAPK phosphatase (MKP)-1 induction in response to LPS + IFN-?. Similarly, the exposure of SMCs from iNOS?/? mice to LPS + IFN-? produced an enhancement of COX-2 induction, p38, and JNK phosphorylation and an attenuated upregulation of MKP-1 versus their wild-type counterparts. Taken together, our data indicate that NO, in part derived from iNOS, negatively regulates the immediate early induction of COX-2 in response to inflammatory stimuli. PMID:20543082

  20. Inducible nitric oxide synthase gene deletion exaggerates MAPK-mediated cyclooxygenase-2 induction by inflammatory stimuli.

    PubMed

    Lamon, Brian D; Upmacis, Rita K; Deeb, Ruba S; Koyuncu, Hilal; Hajjar, David P

    2010-09-01

    Cyclooxygenase (COX)-2 and inducible nitric oxide (NO) synthase (iNOS) are responsive to a wide array of inflammatory stimuli, have been localized to vascular smooth muscle cells (SMCs), and are intimately linked to the progression of vascular disease, including atherosclerotic lesion formation. We and others have shown that the production and subsequent impact of COX products appear to be correlative with the status of NO synthesis. This study examined the impact of inflammation-driven NO production on COX-2 expression in SMCs. Concurrent stimulation of quiescent rat aortic SMCs with lipopolysaccharide (LPS) and interferon (IFN)-gamma increased COX-2, iNOS, and nitrite production. Pharmacological inhibition of NO synthase (N(G)-monomethyl-l-arginine) concentration- and time-dependently magnified LPS + IFN-gamma-mediated COX-2 mRNA and protein induction in a cGMP-independent manner. COX-2 induction was associated with activation of the ERK, p38, and JNK mitogen-activated protein kinase (MAPK) pathways. Interestingly, NO synthase inhibition enhanced ERK, p38, and to a lesser extent JNK phosphorylation but suppressed MAPK phosphatase (MKP)-1 induction in response to LPS + IFN-gamma. Similarly, the exposure of SMCs from iNOS(-/-) mice to LPS + IFN-gamma produced an enhancement of COX-2 induction, p38, and JNK phosphorylation and an attenuated upregulation of MKP-1 versus their wild-type counterparts. Taken together, our data indicate that NO, in part derived from iNOS, negatively regulates the immediate early induction of COX-2 in response to inflammatory stimuli. PMID:20543082

  1. Temporal regulation of expression of immediate early and second phase transcripts by endothelin-1 in cardiomyocytes

    PubMed Central

    Cullingford, Timothy E; Markou, Thomais; Fuller, Stephen J; Giraldo, Alejandro; Pikkarainen, Sampsa; Zoumpoulidou, Georgia; Alsafi, Ali; Ekere, Collins; Kemp, Timothy J; Dennis, Jayne L; Game, Laurence; Sugden, Peter H; Clerk, Angela

    2008-01-01

    Background Endothelin-1 stimulates Gq protein-coupled receptors to promote proliferation in dividing cells or hypertrophy in terminally differentiated cardiomyocytes. In cardiomyocytes, endothelin-1 rapidly (within minutes) stimulates protein kinase signaling, including extracellular-signal regulated kinases 1/2 (ERK1/2; though not ERK5), with phenotypic/physiological changes developing from approximately 12 h. Hypertrophy is associated with changes in mRNA/protein expression, presumably consequent to protein kinase signaling, but the connections between early, transient signaling events and developed hypertrophy are unknown. Results Using microarrays, we defined the early transcriptional responses of neonatal rat cardiomyocytes to endothelin-1 over 4 h, differentiating between immediate early gene (IEG) and second phase RNAs with cycloheximide. IEGs exhibited differential temporal and transient regulation, with expression of second phase RNAs within 1 h. Of transcripts upregulated at 30 minutes encoding established proteins, 28 were inhibited >50% by U0126 (which inhibits ERK1/2/5 signaling), with 9 inhibited 25-50%. Expression of only four transcripts was not inhibited. At 1 h, most RNAs (approximately 67%) were equally changed in total and polysomal RNA with approximately 17% of transcripts increased to a greater extent in polysomes. Thus, changes in expression of most protein-coding RNAs should be reflected in protein synthesis. However, approximately 16% of transcripts were essentially excluded from the polysomes, including some protein-coding mRNAs, presumably inefficiently translated. Conclusion The phasic, temporal regulation of early transcriptional responses induced by endothelin-1 in cardiomyocytes indicates that, even in terminally differentiated cells, signals are propagated beyond the primary signaling pathways through transcriptional networks leading to phenotypic changes (that is, hypertrophy). Furthermore, ERK1/2 signaling plays a major role in this response. PMID:18275597

  2. HVC lesions modify immediate early gene expression in auditory forebrain regions of female songbirds.

    PubMed

    Lynch, Kathleen S; Kleitz-Nelson, Hayley K; Ball, Gregory F

    2013-04-01

    It is well established that auditory forebrain regions of oscine birds are essential for the encoding of species-typical songs and are, therefore, vital for recognition of song during sociosexual interactions. Regions such as the caudal medial nidopallium (NCM) and the caudal medial mesopallium (CMM) are involved in perceptual processing of song and the formation of auditory memories. There is an additional telencephalic nucleus, however, that has also been implicated in species recognition. This nucleus is HVC, a prominent nucleus that sits at the apex of the song system, and is well known for its critical role in song learning and song production in male songbirds. Here, we explore the functional relationship between auditory forebrain regions (i.e., NCM and CMM) and HVC in female canaries (Serinus canaria). We lesion HVC and examine immediate early gene responses to conspecific song presentation within CMM and NCM to explore whether HVC can modulate auditory responses within these forebrain regions. Our results reveal robust deficits in ZENK-ir in CMM and NCM of HVC-lesioned females when compared with control- and sham-lesioned females, indicating that functional connections exists between HVC and NCM/CMM. Although these connected regions have been implicated in song learning and production in males, they likely serve distinct functions in female songbirds that face the task of song recognition rather than song production. Identifying functional connections between HVC and auditory regions involved in song perception is an essential step toward developing a comprehensive understanding of the neural basis of song recognition. PMID:23076815

  3. Splitting Hares and Tortoises: A Classification of Neuronal Immediate Early Gene Transcription Based on Poised RNA Polymerase II

    PubMed Central

    Saha, Ramendra N.; Dudek, Serena M.

    2013-01-01

    Immediate early transcription is an integral part of the neuronal response to environmental stimulation and serves many brain processes including development, learning, triggers of programmed cell death, and reaction to injury and drugs. Following a stimulus, neurons express a select few genes within a short period of time without undergoing de novo protein translation. Referred to as the ‘gateway to genetic response’, these immediate early genes (IEGs) are either expressed within a few minutes of stimulation or later within the hour. In neuronal IEGs that are expressed rapidly, productive elongation in response to neuronal activity is jump-started by constitutive transcription initiation together with RNA polymerase II stalling in the vicinity of the promoter. IEGs expressed later in the hour do not depend on this mechanism. On the basis of this Polymerase II poising, we propose that the immediate early genes can be grouped in two distinct classes: the rapid and the delayed IEGs. The possible biological relevance of these classes in neurons is discussed. PMID:23711585

  4. Structure and transcription of an immediate-early region in the human herpesvirus 6 genome.

    PubMed Central

    Schiewe, U; Neipel, F; Schreiner, D; Fleckenstein, B

    1994-01-01

    The unique segment of the human herpesvirus 6 (HHV-6) genome is essentially collinear to the unique long DNA segment of another betaherpesvirus, the human cytomegalovirus (HCMV). However, the HHV-6 genomic section that is analogous in position to the major immediate-early (IE) locus of HCMV does not exhibit recognizable sequence homologies. The respective HHV-6 region of 5.5 kbp is flanked on one side by 25 to 28 incomplete tandem repeats of 105 to 110 bp that contain, with one exception, a single KpnI restriction site (KpnI repeats). About 250 reiterations of the sequence motif CACATA are located on the other end. We identified two open reading frames of 375 and 2,595 nucleotides, respectively, on one strand. Strand-specific Northern blot analyses with RNA harvested from HHV-6 (strain U1102)-infected HSB-2 cells or cord blood lymphocytes revealed two transcripts of about 3.5 and 4.7 kb in the corresponding orientation. Sequence analyses of the respective cDNA clones and primer extension experiments were used to map the mRNAs. The two transcripts are coterminal and multiply spliced and code for the same putative 104.6-kDa protein, but they are initiated from different promoters. Characterization of smaller cDNA clones and Northern blotting with other strand-specific probes showed that singly spliced mRNAs of 1.0 and 1.5 kb are transcribed from the opposite strand; they could code for a 17.2-kDa polypeptide. Blocking experiments with cycloheximide led to the conclusion that only the 3.5-kb mRNA is synthesized in the absence of protein biosynthesis upon infection with cell-free virus. This identifies a single IE gene of HHV-6 at the genomic position corresponding to the major IE region of HCMV, although the coding content and transcriptional regulation are quite different for these two herpesvirus IE regions. Images PMID:8151768

  5. A novel 7-nucleotide motif located in 3' untranslated sequences of the immediate-early gene set mediates platelet-derived growth factor induction of the JE gene.

    PubMed Central

    Freter, R R; Irminger, J C; Porter, J A; Jones, S D; Stiles, C D

    1992-01-01

    A cohort of the serum and growth factor regulated immediate-early gene set is induced with slower kinetics than c-fos. Two of the first immediate-early genes characterized as such, c-myc and JE, are contained within this subset. cis-acting genomic elements mediating induction of the slower responding subset of immediate-early genes have never been characterized. Herein we characterize two widely separated genomic elements which are together essential for induction of the murine JE gene by platelet-derived growth factor, serum, interleukin-1, and double-stranded RNA. One of these elements is novel in several regards. It is a 7-mer, TTTTGTA, found in the proximal 3' sequences downstream of the JE stop codon. The 3' element is position dependent and orientation independent. It does not function in polyadenylation, splicing, or destabilization of the JE transcript. Copies of the 7-mer or its inverse are found at comparable 3' sites in 25 immediate-early genes that encode transcription factors or cytokines. Given its general occurrence, the 7-mer may be a required cis-acting control element mediating induction of the immediate-early gene set. Images PMID:1448065

  6. In-Frame and Unmarked Gene Deletions in Burkholderia cenocepacia via an Allelic Exchange System Compatible with Gateway Technology.

    PubMed

    Fazli, Mustafa; Harrison, Joe J; Gambino, Michela; Givskov, Michael; Tolker-Nielsen, Tim

    2015-06-01

    Burkholderia cenocepacia is an emerging opportunistic pathogen causing life-threatening infections in immunocompromised individuals and in patients with cystic fibrosis, which are often difficult, if not impossible, to treat. Understanding the genetic basis of virulence in this emerging pathogen is important for the development of novel treatment regimes. Generation of deletion mutations in genes predicted to encode virulence determinants is fundamental to investigating the mechanisms of pathogenesis. However, there is a lack of appropriate selectable and counterselectable markers for use in B. cenocepacia, making its genetic manipulation problematic. Here we describe a Gateway-compatible allelic exchange system based on the counterselectable pheS gene and the I-SceI homing endonuclease. This system provides efficiency in cloning homology regions of target genes and allows the generation of precise and unmarked gene deletions in B. cenocepacia. As a proof of concept, we demonstrate its utility by deleting the Bcam1349 gene, encoding a cyclic di-GMP (c-di-GMP)-responsive regulator protein important for biofilm formation. PMID:25795676

  7. RCSD1-ABL1 Translocation Associated with IKZF1 Gene Deletion in B-Cell Acute Lymphoblastic Leukemia

    PubMed Central

    Kamran, Shawana; Raca, Gordana; Nazir, Kamran

    2015-01-01

    The RCSD1 gene has recently been identified as a novel gene fusion partner of the ABL1 gene in cases of B-cell Acute Lymphoblastic Leukemia (B-ALL). The RCSD1 gene is located at 1q23 and ABL1 is located at 9q34, so that the RCSD1-ABL1 fusion typically arises through a rare reciprocal translocation t(1;9)(q23;q34). Only a small number of RCSD1-ABL1 positive cases of B-ALL have been described in the literature, and the full spectrum of clinical, morphological, immunophenotypic, and molecular features associated with this genetic abnormality has not been defined. We describe extensive genetic characterization of a case of B-ALL with RCSD1-ABL1 fusion, by using conventional cytogenetic analysis, Fluorescence In Situ Hybridization (FISH) studies, and Chromosomal Microarray Analysis (CMA). The use of CMA resulted in detection of an approximately 70?kb deletion at 7p12.2, which caused a disruption of the IKZF1 gene. Deletions and mutations of IKZF1 are recurring abnormalities in B-ALL and are associated with a poor prognosis. Our findings highlight the association of the deletion of IKZF1 gene with the t(1;9)(q24;q34) and illustrate the importance of comprehensive cytogenetic and molecular evaluation for accurate prediction of prognosis in patients with B-cell ALL. PMID:26600955

  8. Genotype-phenotype correlation of contiguous gene deletions of SLC6A8, BCAP31 and ABCD1.

    PubMed

    van de Kamp, J M; Errami, A; Howidi, M; Anselm, I; Winter, S; Phalin-Roque, J; Osaka, H; van Dooren, S J M; Mancini, G M; Steinberg, S J; Salomons, G S

    2015-02-01

    The BCAP31 gene is located between SLC6A8, associated with X-linked creatine transporter deficiency, and ABCD1, associated with X-linked adrenoleukodystrophy. Recently, loss-of-function mutations in BCAP31 were reported in association with severe developmental delay, deafness and dystonia. We characterized the break points in eight patients with deletions of SLC6A8, BCAP31 and/or ABCD1 and studied the genotype-phenotype correlations. The phenotype in patients with contiguous gene deletions involving BCAP31 overlaps with the phenotype of isolated BCAP31 deficiency. Only deletions involving both BCAP31 and ABCD1 were associated with hepatic cholestasis and death before 1?year, which might be explained by a synergistic effect. Remarkably, a patient with an isolated deletion at the 3'-end of SLC6A8 had a similar severe phenotype as seen in BCAP31 deficiency but without deafness. This might be caused by the disturbance of a regulatory element between SLC6A8 and BCAP31. PMID:24597975

  9. Double gene deletion reveals the lack of cooperation between PPAR{alpha} and PPAR{beta} in skeletal muscle

    SciTech Connect

    Bedu, E.; Desplanches, D.; Pequignot, J.; Bordier, B.; Desvergne, B. . E-mail: beatrice.desvergne@unil.ch

    2007-06-15

    The peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of most of the pathways linked to lipid metabolism. PPAR{alpha} and PPAR{beta} isotypes are known to regulate muscle fatty acid oxidation and a reciprocal compensation of their function has been proposed. Herein, we investigated muscle contractile and metabolic phenotypes in PPAR{alpha}-/-, PPAR{beta}-/-, and double PPAR{alpha}-/- {beta}-/- mice. Heart and soleus muscle analyses show that the deletion of PPAR{alpha} induces a decrease of the HAD activity ({beta}-oxidation) while soleus contractile phenotype remains unchanged. A PPAR{beta} deletion alone has no effect. However, these mild phenotypes are not due to a reciprocal compensation of PPAR{beta} and PPAR{alpha} functions since double gene deletion PPAR{alpha}-PPAR{beta} mostly reproduces the null PPAR{alpha}-mediated reduced {beta}-oxidation, in addition to a shift from fast to slow fibers. In conclusion, PPAR{beta} is not required for maintaining skeletal muscle metabolic activity and does not compensate the lack of PPAR{alpha} in PPAR{alpha} null mice.

  10. A new variant of self-excising ?-recombinase/six cassette for repetitive gene deletion and homokaryon purification in Neurospora crassa.

    PubMed

    Szewczyk, Edyta; Kasuga, Takao; Fan, Zhiliang

    2014-05-01

    In a previous study, we developed a cassette employing a bacterial ?-recombinase acting on six recognition sequences (?-rec/six), which allowed repetitive site-specific gene deletion and marker recycling in Neurospora crassa. However, only one positive selection marker was used in the cassette. A tedious subsequent procedure was needed to purify homokaryons due to the lack of a negative selection after cassette eviction. Additionally, the endoxylanase xylP promoter from Penicillium chrysogenum used in the construct was not strongly regulated in N. crassa, which led to low efficiency in cassette eviction. Herein we report an improved variant of the self-excising ?-recombinase/six cassette for repetitive gene deletions in N. crassa using a native endoxylanase gh10-2 promoter from N. crassa, plus the introduction of a bidirectional selection marker to facilitate homokaryon selection using a thymidine kinase (tk) gene (negative selection) in addition to the phosphinothricin resistance gene (bar(r)) (positive selection). PMID:24556286

  11. Characterization of a Replication-Incompetent Pseudorabies Virus Mutant Lacking the Sole Immediate Early Gene IE180

    PubMed Central

    Wu, Brendan W.

    2014-01-01

    ABSTRACT The alphaherpesvirus pseudorabies virus (PRV) encodes a single immediate early gene called IE180. The IE180 protein is a potent transcriptional activator of viral genes involved in DNA replication and RNA transcription. A PRV mutant with both copies of IE180 deleted was constructed 20 years ago (S. Yamada and M. Shimizu, Virology 199:366–375, 1994, doi:10.1006/viro.1994.1134), but propagation of the mutant depended on complementing cell lines that expressed the toxic IE180 protein constitutively. Recently, Oyibo et al. constructed a novel set of PRV IE180 mutants and a stable cell line with inducible IE180 expression (H. Oyibo, P. Znamenskiy, H. V. Oviedo, L. W. Enquist, A. Zador, Front. Neuroanat. 8:86, 2014, doi:10.3389/fnana.2014.00086), which we characterized further here. These mutants failed to replicate new viral genomes, synthesize immediate early, early, or late viral proteins, and assemble infectious virions. The PRV IE180-null mutant did not form plaques in epithelial cell monolayers and could not spread from primary infected neurons to second-order neurons in culture. PRV IE180-null mutants lacked the property of superinfection exclusion. When PRV IE180-null mutants infected cells first, subsequent superinfecting viruses were not blocked in cell entry and formed replication compartments in epithelial cells, fibroblasts, and neurons. Cells infected with PRV IE180-null mutants survived as long as uninfected cells in culture while expressing a fluorescent reporter gene. Transcomplementation with IE180 in epithelial cells restored all mutant phenotypes to wild type. The conditional expression of PRV IE180 protein enables the propagation of replication-incompetent PRV IE180-null mutants and will facilitate construction of long-term single-cell-infecting PRV mutants for precise neural circuit tracing and high-capacity gene delivery vectors. PMID:25389174

  12. Epstein-Barr Virus Immediate-Early Protein BZLF1 Is SUMO-1 Modified and Disrupts Promyelocytic Leukemia Bodies

    PubMed Central

    Adamson, Amy L.; Kenney, Shannon

    2001-01-01

    Although the immediate-early proteins of both herpes simplex virus (HSV) and cytomegalovirus (CMV) are known to modify promyelocytic leukemia (PML) (ND10) bodies in the nucleus of the host cell, it has been unclear whether lytic infection with gamma herpesviruses induces a similar effect. The PML protein is induced by interferon, involved in major histocompatibility complex class I presentation, and necessary for certain types of apoptosis. Therefore, it is likely that PML bodies function in an antiviral capacity. SUMO-1 modification of PML is known to be required for the formation of PML bodies. To examine whether Epstein-Barr virus (EBV) lytic replication interferes with PML bodies, we expressed the EBV immediate-early genes BZLF1 (Z) and BRLF1 (R) in EBV-positive cell lines and examined PML localization. Both Z and R expression resulted in PML dispersion in EBV-positive cells. Z but not R expression is sufficient to disrupt PML bodies in EBV-negative cell lines. We show that dispersion of PML bodies by Z requires a portion of the transcriptional activation domain of Z but not the DNA-binding function. As was previously reported for the HSV-1 ICP0 and CMV IE1 proteins, Z reduces the amount of SUMO-1-modified PML. We also found that Z itself is SUMO-1 modified (through amino acid 12) and that Z competes with PML for limiting amounts of SUMO-1. These results suggest that disruption of PML bodies is important for efficient lytic replication of EBV. Furthermore, Z may potentially alter the function of a variety of cellular proteins by inhibiting SUMO-1 modification. PMID:11160742

  13. Is NF-1 gene deletion the molecular mechanism of neurofibromatosis type 1 with destinctive facies?

    SciTech Connect

    Leppig, K.A.; Stephens, K.G.; Viskochill, D.; Kaplan, P.

    1994-09-01

    We have studied a patient with neurofibromatosis type 1 and unusual facial features using fluorescence in situ hybridization (FISH) and found that the patient had a deletion that minimially encompasses exon 2-11 of the NF-1 gene. The patient was one of two individuals initially described by Kaplan and Rosenblatt who suggested that another condition aside from neurofibromatosis type 1 may account for the unusual facial features observed in these patients with neurofibromatosis type 1. FISH studies were performed using a P1 clone probe, P1-9, which contains exons 2-11 of the NF-1 gene on chromosomes prepared from the patients. In all 20 metaphase cells analyzed, one of the chromosome 17 homologues was deleted for the P1-9 probe. Therefore, this patient had neurofibromatosis type 1 and unusual facial features as the result of a deletion which minimally includes exons 2-11 of the NF-1 gene. The extent of the deletion is being mapped by FISH and somatic cell hybrid analysis. The patient studied was a 7-year-old male with mild developmental delays, normal growth parameters, and physical findings consistent with neurofibromatosis type 1, including multiple cafe au lait spots, several curaneous neurofibroma, and speckling of the irises. In addition, his unusual facial features consisted of telecanthus, antimongoloid slant of the palpebral fissures, a broad base of the nose, low set and mildly posteriorly rotated ears, thick helices, high arched palate, short and pointed chin, and low posterior hairline. We propose that deletions of the NF-1 gene and/or contiguous genes are the etiology of neurofibromatosis type 1 and unusual facial features. This particular facial appearance was inherited from the patient`s mother and has been described in other individuals with neurofibromatosis type 1. We are using FISH to rapidly screen patients with this phenotype for large deletions involving the NF-1 gene and flanking DNA sequences.

  14. A new method for simultaneous gene deletion and down-regulation in Brucella melitensis Rev.1.

    PubMed

    Saeedinia, Ali Reza; Zeinoddini, Mehdi; Soleimani, Masoud; Sadeghizadeh, Majid

    2015-01-01

    In this study, our aim was to integrate an antisense expression cassette in bacterial chromosome for providing a long-term expression down-regulation in a bid to develop a new approach for simultaneous deletion and down-regulation of target genes in bacterial system. Therefore, we were used this approach for simultaneous deletion of the perosamine synthetase (per) gene and down-regulation of the virB1 expression in Brucella melitensis Rev.1. The per gene, which is one of the LPS O-chain coding genes, was replaced by homologous recombination with an antisense virB1 expression cassette together with kanamycin resistance cassette (kan(R)). Deletion of the per gene was characterized by PCR analysis and DNA sequencing. The expression of antisense virB1 cassette was confirmed by RT-PCR. Down-regulation of the virB1 mRNA expression was quantified by real-time RT-PCR using virB1 specific primers relative to the groEL reference gene. The survival rate of mutant strain was evaluated by CFU count in the BALB/c mice. The virB1 mRNA expression was down-regulated on average 10-fold in mutant strain as compared to parental strain. The loss of per gene function and decrease of the virB1 mRNA expression resulted in reduced entry and survival of the mutant Rev.1 strain in BALB/c mice splenocytes. We propose that this method can be used for simultaneous regulation of multiple genes expression. PMID:25249309

  15. Time Course of Immediate Early Gene Protein Expression in the Spinal Cord following Conditioning Stimulation of the Sciatic Nerve in Rats

    PubMed Central

    Bojovic, Ognjen; Panja, Debabrata; Bittins, Margarethe; Bramham, Clive R.; Tjølsen, Arne

    2015-01-01

    Long-term potentiation induced by conditioning electrical stimulation of afferent fibers is a widely studied form of synaptic plasticity in the brain and the spinal cord. In the spinal cord dorsal horn, long-term potentiation is induced by a series of high-frequency trains applied to primary afferent fibers. Conditioning stimulation (CS) of sciatic nerve primary afferent fibers also induces expression of immediate early gene proteins in the lumbar spinal cord. However, the time course of immediate early gene expression and the rostral-caudal distribution of expression in the spinal cord have not been systematically studied. Here, we examined the effects of sciatic nerve conditioning stimulation (10 stimulus trains, 0.5 ms stimuli, 7.2 mA, 100 Hz, train duration 2 s, 8 s intervals between trains) on cellular expression of immediate early genes, Arc, c-Fos and Zif268, in anesthetized rats. Immunohistochemical analysis was performed on sagittal sections obtained from Th13- L5 segments of the spinal cord at 1, 2, 3, 6 and 12 h post-CS. Strikingly, all immediate early genes exhibited a monophasic increase in expression with peak increases detected in dorsal horn neurons at 2 hours post-CS. Regional analysis showed peak increases at the location between the L3 and L4 spinal segments. Both Arc, c-Fos and Zif268 remained significantly elevated at 2 hours, followed by a sharp decrease in immediate early gene expression between 2 and 3 hours post-CS. Colocalization analysis performed at 2 hours post-CS showed that all c-Fos and Zif268 neurons were positive for Arc, while 30% and 43% of Arc positive neurons were positive for c-Fos and Zif268, respectively. The present study identifies the spinal cord level and time course of immediate early gene (IEGP) expression of relevance for analysis of IEGPs function in neuronal plasticity and nociception. PMID:25860146

  16. Development of a markerless gene deletion system for Bacillus subtilis based on the mannose phosphoenolpyruvate-dependent phosphotransferase system.

    PubMed

    Wenzel, Marian; Altenbuchner, Josef

    2015-10-01

    To optimize Bacillus subtilis as a production strain for proteins and low molecular substances by genome engineering, we developed a markerless gene deletion system. We took advantage of a general property of the phosphoenolpyruvate-dependent phosphotransferase system (PTS), in particular the mannose PTS. Mannose is phosphorylated during uptake by its specific transporter (ManP) to mannose 6-phosphate, which is further converted to fructose 6-phosphate by the mannose-6-phosphate isomerase (ManA). When ManA is missing, accumulation of the phosphorylated mannose inhibits cell growth. This system was constructed by deletion of manP and manA in B. subtilis ?6, a 168 derivative strain with six large deletions of prophages and antibiotic biosynthesis genes. The manP gene was inserted into an Escherichia coli plasmid together with a spectinomycin resistance gene for selection in B. subtilis. To delete a specific region, its up- and downstream flanking sites (each of approximately 700?bp) were inserted into the vector. After transformation, integration of the plasmid into the chromosome of B. subtilis by single cross-over was selected by spectinomycin. In the second step, excision of the plasmid was selected by growth on mannose. Finally, excision and concomitant deletion of the target region were verified by colony PCR. In this way, all nine prophages, seven antibiotic biosynthesis gene clusters and two sigma factors for sporulation were deleted and the B. subtilis genome was reduced from 4215 to 3640?kb. Despite these extensive deletions, growth rate and cell morphology remained similar to the B. subtilis 168 parental strain. PMID:26238998

  17. Tph2 gene deletion enhances amphetamine-induced hypermotility: effect of 5-HT restoration and role of striatal noradrenaline release.

    PubMed

    Carli, Mirjana; Kostoula, Chrysaugi; Sacchetti, Giuseppina; Mainolfi, Pierangela; Anastasia, Alessia; Villani, Claudia; Invernizzi, Roberto William

    2015-11-01

    Variants of tryptophan hydroxylase-2 (Tph2), the gene encoding enzyme responsible for the synthesis of brain serotonin (5-HT), have been associated with neuropsychiatric disorders, substance abuse and addiction. This study assessed the effect of Tph2 gene deletion on motor behavior and found that motor activity induced by 2.5 and 5 mg/kg amphetamine was enhanced in Tph2(-/-) mice. Using the in vivo microdialysis technique we found that the ability of amphetamine to stimulate noradrenaline (NA) release in the striatum was reduced by about 50% in Tph2(-/-) mice while the release of dopamine (DA) was not affected. Tph2 deletion did not affect the release of NA and DA in the prefrontal cortex. The role of endogenous 5-HT in enhancing the effect of amphetamine was confirmed showing that treatment with the 5-HT precursor 5-hydroxytryptophan (10 mg/kg) restored tissue and extracellular levels of brain 5-HT and the effects of amphetamine on striatal NA release and motor activity in Tph2(-/-) mice. Treatment with the NA precursor dihydroxyphenylserine (400 mg/kg) was sufficient to restore the effect of amphetamine on striatal NA release and motor activity in Tph2(-/-) mice. These findings indicate that amphetamine-induced hyperactivity is attenuated by endogenous 5-HT through the inhibition of striatal NA release. Tph2(-/-) mice may be a useful preclinical model to assess the role of 5-HT-dependent mechanisms in the action of psychostimulants. Acute sensitivity to the motor effects of amphetamine has been associated to increased risk of psychostimulant abuse. Here, we show that deletion of Tph2, the gene responsible for brain 5-HT synthesis, enhances the motor effect of amphetamine in mice through the inhibition of striatal NA release. This suggests that Tph2(-/-) mice is a useful preclinical model to assess the role of 5-HT-dependent mechanisms in psychostimulants action. Tph2, tryptophan hydroxylase-2. PMID:26259827

  18. MK-801 Impairs Cognitive Coordination on a Rotating Arena (Carousel) and Contextual Specificity of Hippocampal Immediate-Early Gene Expression in a Rat Model of Psychosis

    PubMed Central

    Kubík, Št?pán; Buchtová, Helena; Valeš, Karel; Stuchlík, Aleš

    2014-01-01

    Flexible behavior in dynamic, real-world environments requires more than static spatial learning and memory. Discordant and unstable cues must be organized in coherent subsets to give rise to meaningful spatial representations. We model this form of cognitive coordination on a rotating arena – Carousel where arena- and room-bound spatial cues are dissociated. Hippocampal neuronal ensemble activity can repeatedly switch between multiple representations of such an environment. Injection of tetrodotoxin into one hippocampus prevents cognitive coordination during avoidance of a stationary room-defined place on the Carousel and increases coactivity of previously unrelated neurons in the uninjected hippocampus. Place avoidance on the Carousel is impaired after systemic administration of non-competitive NMDAr blockers (MK-801) used to model schizophrenia in animals and people. We tested if this effect is due to cognitive disorganization or other effect of NMDAr antagonism such as hyperlocomotion, spatial memory impairment, or general learning deficit. We also examined if the same dose of MK-801 alters patterns of immediate-early gene (IEG) expression in the hippocampus. IEG expression is triggered in neuronal nuclei in a context-specific manner after behavioral exploration and it is used to map activity in neuronal populations. IEG expression is critical for maintenance of synaptic plasticity and memory consolidation. We show that the same dose of MK-801 that impairs spatial coordination of rats on the Carousel also eliminates contextual specificity of IEG expression in hippocampal CA1 ensembles. This effect is due to increased similarity between ensembles activated in different environments, consistent with the idea that it is caused by increased coactivity between neurons, which did not previously fire together. Our data support the proposition of the Hypersynchrony theory that cognitive disorganization in psychosis is due to increased coactivity between unrelated neurons. PMID:24659959

  19. POLY I:C INHIBITS THE EXPRESSION OF CHANNEL CATFISH VIRUS IMMEDIATE-EARLY GENE ORF 1 AT EARLY TIMES AFTER INFECTION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Channel catfish virus (CCV) is a herpes virus that infects channel catfish fry and fingerlings. Previous research has demonstrated that Type I interferons inhibit the expression of immediate-early (IE) genes of some mammalian herpesviruses. However, CCV is distantly related to the mammalian herpesvi...

  20. Immediate-Early Gene Transcriptional Activation in Hippocampus Ca1 and Ca3 Does Not Accurately Reflect Rapid, Pattern Completion-Based Retrieval of Context Memory

    ERIC Educational Resources Information Center

    Pevzner, Aleksandr; Guzowski, John F.

    2015-01-01

    No studies to date have examined whether immediate-early gene (IEG) activation is driven by context memory recall. To address this question, we utilized the context preexposure facilitation effect (CPFE) paradigm. In CPFE, animals acquire contextual fear conditioning through hippocampus-dependent rapid retrieval of a previously formed contextual…

  1. Activation of immediate-early response gene c-Fos protein in the rat paralimbic cortices after myocardial infarction

    PubMed Central

    Ahn, Ji Yun; Tae, Hyun-Jin; Cho, Jeong-Hwi; Kim, In Hye; Ahn, Ji Hyeon; Park, Joon Ha; Kim, Dong Won; Cho, Jun Hwi; Won, Moo-Ho; Hong, Seongkweon; Lee, Jae-Chul; Seo, Jeong Yeol

    2015-01-01

    c-Fos is a good biological marker for detecting the pathogenesis of central nervous system disorders. Few studies are reported on the change in myocardial infarction-induced c-Fos expression in the paralimbic regions. Thus, in this study, we investigated the changes in c-Fos expression in the rat cingulate and piriform cortices after myocardial infarction. Neuronal degeneration in cingulate and piriform cortices after myocardial infarction was detected using cresyl violet staining, NeuN immunohistochemistry and Fluoro-Jade B histofluorescence staining. c-Fos-immunoreactive cells were observed in cingulate and piriform cortices at 3 days after myocardial infarction and peaked at 7 and 14 days after myocardial infarction. But they were hardly observed at 56 days after myocardial infarction. The chronological change of c-Fos expression determined by western blot analysis was basically the same as that of c-Fos immunoreactivity. These results indicate that myocardial infarction can cause the chronological change of immediate-early response gene c-Fos protein expression, which might be associated with the neural activity induced by myocardial infarction. PMID:26487852

  2. Expression of immediate-early genes in the inferior colliculus and auditory cortex in salicylate-induced tinnitus in rat.

    PubMed

    Hu, S S; Mei, L; Chen, J Y; Huang, Z W; Wu, H

    2014-01-01

    Tinnitus could be associated with neuronal hyperactivity in the auditory center. As a neuronal activity marker, immediate-early gene (IEG) expression is considered part of a general neuronal response to natural stimuli. Some IEGs, especially the activity-dependent cytoskeletal protein (Arc) and the early growth response gene-1 (Egr-1), appear to be highly correlated with sensory-evoked neuronal activity. We hypothesize, therefore, an increase of Arc and Egr-1 will be observed in a tinnitus model. In our study, we used the gap prepulse inhibition of acoustic startle (GPIAS) paradigm to confirm that salicylate induces tinnitus-like behavior in rats. However, expression of the Arc gene and Egr-1 gene were decreased in the inferior colliculus (IC) and auditory cortex (AC), in contradiction of our hypothesis. Expression of N-methyl d-aspartate receptor subunit 2B (NR2B) was increased and all of these changes returned to normal 14 days after treatment with salicylate ceased. These data revealed long-time administration of salicylate induced tinnitus markedly but reversibly and caused neural plasticity changes in the IC and the AC. Decreased expression of Arc and Egr-1 might be involved with instability of synaptic plasticity in tinnitus. PMID:24704997

  3. Expression of Immediate-Early Genes in the Inferior Colliculus and Auditory Cortex in Salicylate-Induced Tinnitus in Rat

    PubMed Central

    Hu, S.S.; Mei, L.; Chen, J.Y.; Huang, Z.W.; Wu, H.

    2014-01-01

    Tinnitus could be associated with neuronal hyperactivity in the auditory center. As a neuronal activity marker, immediate-early gene (IEG) expression is considered part of a general neuronal response to natural stimuli. Some IEGs, especially the activity-dependent cytoskeletal protein (Arc) and the early growth response gene-1 (Egr-1), appear to be highly correlated with sensory-evoked neuronal activity. We hypothesize, therefore, an increase of Arc and Egr-1 will be observed in a tinnitus model. In our study, we used the gap prepulse inhibition of acoustic startle (GPIAS) paradigm to confirm that salicylate induces tinnitus-like behavior in rats. However, expression of the Arc gene and Egr-1 gene were decreased in the inferior colliculus (IC) and auditory cortex (AC), in contradiction of our hypothesis. Expression of N-methyl D-aspartate receptor subunit 2B (NR2B) was increased and all of these changes returned to normal 14 days after treatment with salicylate ceased. These data revealed long-time administration of salicylate induced tinnitus markedly but reversibly and caused neural plasticity changes in the IC and the AC. Decreased expression of Arc and Egr-1 might be involved with instability of synaptic plasticity in tinnitus. PMID:24704997

  4. Microarray and RT-PCR screening for white spot syndrome virus immediate-early genes in cycloheximide-treated shrimp

    SciTech Connect

    Liu Wangjing; Chang Yunshiang; Wang Chunghsiung; Kou, Guang-Hsiung; Lo Chufang . E-mail: gracelow@ntu.edu.tw

    2005-04-10

    Here, we report for the first time the successful use of cycloheximide (CHX) as an inhibitor to block de novo viral protein synthesis during WSSV (white spot syndrome virus) infection. Sixty candidate IE (immediate-early) genes were identified using a global analysis microarray technique. RT-PCR showed that the genes corresponding to ORF126, ORF242 and ORF418 in the Taiwan isolate were consistently CHX-insensitive, and these genes were designated ie1, ie2 and ie3, respectively. The sequences for these IE genes also appear in the two other WSSV isolates that have been sequenced. Three corresponding ORFs were identified in the China WSSV isolate, but only an ORF corresponding to ie1 was predicted in the Thailand isolate. In a promoter activity assay in Sf9 insect cells using EGFP (enhanced green fluorescence protein) as a reporter, ie1 showed very strong promoter activity, producing higher EGFP signals than the insect Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus (OpMNPV) ie2 promoter.

  5. Tightly regulated expression of Autographa californica multicapsid nucleopolyhedrovirus immediate early genes emerges from their interactions and possible collective behaviors.

    PubMed

    Ono, Chikako; Sato, Masanao; Taka, Hitomi; Asano, Shin-ichiro; Matsuura, Yoshiharu; Bando, Hisanori

    2015-01-01

    To infect their hosts, DNA viruses must successfully initiate the expression of viral genes that control subsequent viral gene expression and manipulate the host environment. Viral genes that are immediately expressed upon infection play critical roles in the early infection process. In this study, we investigated the expression and regulation of five canonical regulatory immediate-early (IE) genes of Autographa californica multicapsid nucleopolyhedrovirus: ie0, ie1, ie2, me53, and pe38. A systematic transient gene-expression analysis revealed that these IE genes are generally transactivators, suggesting the existence of a highly interactive regulatory network. A genetic analysis using gene knockout viruses demonstrated that the expression of these IE genes was tolerant to the single deletions of activator IE genes in the early stage of infection. A network graph analysis on the regulatory relationships observed in the transient expression analysis suggested that the robustness of IE gene expression is due to the organization of the IE gene regulatory network and how each IE gene is activated. However, some regulatory relationships detected by the genetic analysis were contradictory to those observed in the transient expression analysis, especially for IE0-mediated regulation. Statistical modeling, combined with genetic analysis using knockout alleles for ie0 and ie1, showed that the repressor function of ie0 was due to the interaction between ie0 and ie1, not ie0 itself. Taken together, these systematic approaches provided insight into the topology and nature of the IE gene regulatory network. PMID:25816136

  6. Saccule contribution to immediate early gene induction in the gerbil brainstem with posterior canal galvanic or hypergravity stimulation

    NASA Technical Reports Server (NTRS)

    Marshburn, T. H.; Kaufman, G. D.; Purcell, I. M.; Perachio, A. A.

    1997-01-01

    Immunolabeling patterns of the immediate early gene-related protein Fos in the gerbil brainstem were studied following stimulation of the sacculus by both hypergravity and galvanic stimulation. Head-restrained, alert animals were exposed to a prolonged (1 h) inertial vector of 2 G (19.6 m/s2) head acceleration directed in a dorso-ventral head axis to maximally stimulate the sacculus. Fos-defined immunoreactivity was quantified, and the results compared to a control group. The hypergravity stimulus produced Fos immunolabeling in the dorsomedial cell column (dmcc) of the inferior olive independently of other subnuclei. Similar dmcc labeling was induced by a 30 min galvanic stimulus of up to -100 microA applied through a stimulating electrode placed unilaterally on the bony labyrinth overlying the posterior canal (PC). The pattern of vestibular afferent firing activity induced by this galvanic stimulus was quantified in anesthetized gerbils by simultaneously recording from Scarpa's ganglion. Only saccular and PC afferent neurons exhibited increases in average firing rates of 200-300%, suggesting a pattern of current spread involving only PC and saccular afferent neurons at this level of stimulation. These results suggest that alteration in saccular afferent firing rates are sufficient to induce Fos-defined genomic activation of the dmcc, and lend further evidence to the existence of a functional vestibulo-olivary-cerebellar pathway of adaptation to novel gravito-inertial environments.

  7. Na+ dependent acid-base transporters in the choroid plexus; insights from slc4 and slc9 gene deletion studies

    PubMed Central

    Christensen, Henriette L.; Nguyen, An T.; Pedersen, Fredrik D.; Damkier, Helle H.

    2013-01-01

    The choroid plexus epithelium (CPE) is located in the ventricular system of the brain, where it secretes the majority of the cerebrospinal fluid (CSF) that fills the ventricular system and surrounds the central nervous system. The CPE is a highly vascularized single layer of cuboidal cells with an unsurpassed transepithelial water and solute transport rate. Several members of the slc4a family of bicarbonate transporters are expressed in the CPE. In the basolateral membrane the electroneutral Na+ dependent Cl?/HCO3? exchanger, NCBE (slc4a10) is expressed. In the luminal membrane, the electrogenic Na+:HCO3? cotransporter, NBCe2 (slc4a5) is expressed. The electroneutral Na+:HCO3? cotransporter, NBCn1 (slc4a7), has been located in both membranes. In addition to the bicarbonate transporters, the Na+/H+ exchanger, NHE1 (slc9a1), is located in the luminal membrane of the CPE. Genetically modified mice targeting slc4a2, slc4a5, slc4a7, slc4a10, and slc9a1 have been generated. Deletion of slc4a5, 7 or 10, or slc9a1 has numerous impacts on CP function and structure in these mice. Removal of the transporters affects brain ventricle size (slc4a5 and slc4a10) and intracellular pH regulation (slc4a7 and slc4a10). In some instances, removal of the proteins from the CPE (slc4a5, 7, and 10) causes changes in abundance and localization of non-target transporters known to be involved in pH regulation and CSF secretion. The focus of this review is to combine the insights gathered from these knockout mice to highlight the impact of slc4 gene deletion on the CSF production and intracellular pH regulation resulting from the deletion of slc4a5, 7 and 10, and slc9a1. Furthermore, the review contains a comparison of the described human mutations of these genes to the findings in the knockout studies. Finally, the future perspective of utilizing these proteins as potential targets for the treatment of CSF disorders will be discussed. PMID:24155723

  8. Distinct Mechanisms for Induction and Tolerance Regulate the Immediate Early Genes Encoding Interleukin 1? and Tumor Necrosis Factor ?

    PubMed Central

    Adamik, Juraj; Wang, Kent Z. Q.; Unlu, Sebnem; Su, An-Jey A.; Tannahill, Gillian M.; Galson, Deborah L.; O’Neill, Luke A.; Auron, Philip E.

    2013-01-01

    Interleukin-1? and Tumor Necrosis Factor ? play related, but distinct, roles in immunity and disease. Our study revealed major mechanistic distinctions in the Toll-like receptor (TLR) signaling-dependent induction for the rapidly expressed genes (IL1B and TNF) coding for these two cytokines. Prior to induction, TNF exhibited pre-bound TATA Binding Protein (TBP) and paused RNA Polymerase II (Pol II), hallmarks of poised immediate-early (IE) genes. In contrast, unstimulated IL1B displayed very low levels of both TBP and paused Pol II, requiring the lineage-specific Spi-1/PU.1 (Spi1) transcription factor as an anchor for induction-dependent interaction with two TLR-activated transcription factors, C/EBP? and NF-?B. Activation and DNA binding of these two pre-expressed factors resulted in de novo recruitment of TBP and Pol II to IL1B in concert with a permissive state for elongation mediated by the recruitment of elongation factor P-TEFb. This Spi1-dependent mechanism for IL1B transcription, which is unique for a rapidly-induced/poised IE gene, was more dependent upon P-TEFb than was the case for the TNF gene. Furthermore, the dependence on phosphoinositide 3-kinase for P-TEFb recruitment to IL1B paralleled a greater sensitivity to the metabolic state of the cell and a lower sensitivity to the phenomenon of endotoxin tolerance than was evident for TNF. Such differences in induction mechanisms argue against the prevailing paradigm that all IE genes possess paused Pol II and may further delineate the specific roles played by each of these rapidly expressed immune modulators. PMID:23936458

  9. Small-molecule inhibitors of ERK-mediated immediate early gene expression and proliferation of melanoma cells expressing mutated BRaf.

    PubMed

    Samadani, Ramin; Zhang, Jun; Brophy, Amanda; Oashi, Taiji; Priyakumar, U Deva; Raman, E Prabhu; St John, Franz J; Jung, Kwan-Young; Fletcher, Steven; Pozharski, Edwin; MacKerell, Alexander D; Shapiro, Paul

    2015-05-01

    Constitutive activation of the extracellular-signal-regulated kinases 1 and 2 (ERK1/2) are central to regulating the proliferation and survival of many cancer cells. The current inhibitors of ERK1/2 target ATP binding or the catalytic site and are therefore limited in their utility for elucidating the complex biological roles of ERK1/2 through its phosphorylation and regulation of over 100 substrate proteins. To overcome this limitation, a combination of computational and experimental methods was used to identify low-molecular-mass inhibitors that are intended to target ERK1/2 substrate-docking domains and selectively interfere with ERK1/2 regulation of substrate proteins. In the present study, we report the identification and characterization of compounds with a thienyl benzenesulfonate scaffold that were designed to inhibit ERK1/2 substrates containing an F-site or DEF (docking site for ERK, FXF) motif. Experimental evidence shows the compounds inhibit the expression of F-site containing immediate early genes (IEGs) of the Fos family, including c-Fos and Fra1, and transcriptional regulation of the activator protein-1 (AP-1) complex. Moreover, this class of compounds selectively induces apoptosis in melanoma cells containing mutated BRaf and constitutively active ERK1/2 signalling, including melanoma cells that are inherently resistant to clinically relevant kinase inhibitors. These findings represent the identification and initial characterization of a novel class of compounds that inhibit ERK1/2 signalling functions and their potential utility for elucidating ERK1/2 and other signalling events that control the growth and survival of cancer cells containing elevated ERK1/2 activity. PMID:25695333

  10. Inhibition of transcription of the beta interferon gene by the human herpesvirus 6 immediate-early 1 protein.

    PubMed

    Jaworska, Joanna; Gravel, Annie; Fink, Karin; Grandvaux, Nathalie; Flamand, Louis

    2007-06-01

    Human herpesviruses (HHV) are stealth pathogens possessing several decoy or immune system evasion mechanisms favoring their persistence within the infected host. Of these viruses, HHV-6 is among the most successful human parasites, establishing lifelong infections in nearly 100% of individuals around the world. To better understand this host-pathogen relationship, we determined whether HHV-6 could interfere with the development of the innate antiviral response by affecting interferon (IFN) biosynthesis. Using inducible cell lines and transient transfection assays, we have identified the immediate-early 1 (IE1) protein as a potent inhibitor of IFN-beta gene expression. IE1 proteins from both HHV-6 variants were capable of suppressing IFN-beta gene induction. IE1 prevents IFN-beta gene expression triggered by Sendai virus infection, double-stranded RNA (dsRNA) and dsDNA transfection, or the ectopic expression of IFN-beta gene activators such as retinoic inducible gene I protein, mitochondrial antiviral signaling protein, TBK-1, IkappaB kinase epsilon (IKKepsilon), and IFN regulatory factor 3 (IRF3). While the stability of IFN-beta mRNA is not affected, IE1-expressing cells have reduced levels of dimerized IRF3 and nucleus-translocated IRF3 in response to activation by TBK-1 or IKKepsilon. Using nuclear extracts and gel shift experiments, we could demonstrate that in the presence of IE1, IRF3 does not bind efficiently to the IFN-beta promoter sequence. Overall, these results indicate that the IE1 protein of HHV-6, one of the first viral proteins synthesized upon viral entry, is a potent suppressor of IFN-beta gene induction and likely contributes to favor the establishment of and successful infection of cells with this virus. PMID:17376932

  11. Small-molecule inhibitors of ERK-mediated immediate early gene expression and proliferation of melanoma cells expressing mutated BRaf

    PubMed Central

    Samadani, Ramin; Zhang, Jun; Brophy, Amanda; Oashi, Taiji; Priyakumar, U. Deva; Raman, E. Prabhu; St John, Franz J.; Jung, Kwan-Young; Fletcher, Steven; Pozharski, Edwin; MacKerell, Alexander D.; Shapiro, Paul

    2015-01-01

    Constitutive activation of the extracellular-signal-regulated kinases 1 and 2 (ERK1/2) are central to regulating the proliferation and survival of many cancer cells. The current inhibitors of ERK1/2 target ATP binding or the catalytic site and are therefore limited in their utility for elucidating the complex biological roles of ERK1/2 through its phosphorylation and regulation of over 100 substrate proteins. To overcome this limitation, a combination of computational and experimental methods was used to identify low-molecular-mass inhibitors that are intended to target ERK1/2 substrate-docking domains and selectively interfere with ERK1/2 regulation of substrate proteins. In the present study, we report the identification and characterization of compounds with a thienyl benzenesulfonate scaffold that were designed to inhibit ERK1/2 substrates containing an F-site or DEF (docking site for ERK, FXF) motif. Experimental evidence shows the compounds inhibit the expression of F-site containing immediate early genes (IEGs) of the Fos family, including c-Fos and Fra1, and transcriptional regulation of the activator protein-1 (AP-1) complex. Moreover, this class of compounds selectively induces apoptosis in melanoma cells containing mutated BRaf and constitutively active ERK1/2 signalling, including melanoma cells that are inherently resistant to clinically relevant kinase inhibitors. These findings represent the identification and initial characterization of a novel class of compounds that inhibit ERK1/2 signalling functions and their potential utility for elucidating ERK1/2 and other signalling events that control the growth and survival of cancer cells containing elevated ERK1/2 activity. PMID:25695333

  12. Construction of a triple gene-deleted Chinese Pseudorabies virus variant and its efficacy study as a vaccine candidate on suckling piglets.

    PubMed

    Zhang, Chaolin; Guo, Linghua; Jia, Xiangrui; Wang, Tongyan; Wang, Juan; Sun, Zhe; Wang, Lilin; Li, Xiangdong; Tan, Feifei; Tian, Kegong

    2015-05-15

    New-emerging variants of Pseudorabies virus (PRV) compromise the protection provided by current vaccines and cause the death of all ages of vaccinated pigs since 2011. New vaccines based on current circulating PRV strain are needed to control the spread of disease since the variants are antigenically different from classical strains of virus. In this study, a TK/gE/gI triple gene-deleted PRV derived from current circulating field isolate was generated by using bacterial artificial chromosome techniques, and the rescued virus showed similar growth properties in vitro to its parent strain but reduced plaque size. To evaluate it as vaccine candidate, 9 day-old pigs were vaccinated and challenged with a virulent PRV variant. The results showed that vaccination can generate high level of protective gB-specific antibodies after vaccination and provide complete protection to the viral challenge. By contrast, the unvaccinated piglets all died within 6 days after viral challenge. Therefore, the TK/gE/gI triple gene-deleted PRV could be a promising vaccine candidate to control the wide spreading of PR variants in China. PMID:25865469

  13. Impact of alg3 gene deletion on growth, development, pigment production, protein secretion, and functions of recombinant Trichoderma reesei cellobiohydrolases in Aspergillus niger

    SciTech Connect

    Dai, Ziyu; Aryal, Uma K.; Shukla, Anil K.; Qian, Weijun; Smith, Richard D.; Magnuson, Jon K.; Adney, William S.; Beckham, Gregg T.; Brunecky, Roman; Himmel, Michael E.; Decker, Stephen R.; Ju, Xiaohui; Zhang, Xiao; Baker, Scott E.

    2013-09-25

    ALG3 is a Family 58 glycosyltransferase enzyme involved in early N-linked glycan synthesis. Here, we investigated the effect of the alg3 gene disruption on growth, development, metabolism, and protein secretion in Aspergillus niger. The alg3 gene deletion resulted in a significant reduction of growth on complete (CM) and potato dextrose agar (PDA) media and a substantial reduction of spore production on CM. It also delayed spore germination in the liquid cultures of both CM and PDA media, but led to a significant accumulation of red pigment on both CM and liquid modified minimal medium (MM) supplemented with yeast extract. The relative abundance of 55 proteins of the total 190 proteins identified in the secretome was significantly different as a result of alg3 gene deletion. Comparison of a Trichoderma reesei cellobiohydrolase (Cel7A) heterologously expressed in A. niger parental and ?alg3 strains showed that the recombinant Cel7A expressed in the mutant background was smaller in size than that from the parental strains. This study suggests that ALG3 is critical for growth and development, pigment production, and protein secretion in A. niger. Functional analysis of recombinant Cel7A with aberrant glycosylation demonstrates the feasibility of this alternative approach to evaluate the role of N-linked glycosylation in glycoprotein secretion and function.

  14. Negative and positive regulation by a short segment in the 5'-flanking region of the human cytomegalovirus major immediate-early gene

    SciTech Connect

    Nelson, J.A.; Reynolds-Kohler, C.; Smith, B.A.

    1987-11-01

    To analyze the significance of inducible DNase I-hypersensitive sites occurring in the 5'-flanking sequence of the major immediate-early gene of human cytomegalovirus (HCMV), various deleted portions of the HCMV immediate-early promoter regulatory region were attached to the chloramphenicol acetyltransferase (CAT) gene and assayed for activity in transiently transfected undifferentiated and differentiated human teratocarcinoma cells, Tera-2. Assays of progressive deletions in the promoter regulatory region indicated that removal of a 395-base-pair portion of this element (nucleotides -750 to -1145) containing two inducible DNase I sites which correlate with gene expression resulted in a 7.5-fold increase in CAT activity in undifferentiated cells. However, in permissive differentiated Tera-2, human foreskin fibroblast, and HeLa cells, removal of this regulatory region resulted in decreased activity. In addition, attachment of this HCMV upstream element to a homologous or heterologous promoter increased activity three-to fivefold in permissive cells. Therefore, a cis regulatory element exists 5' to the enhancer of the major immediate-early gene of HCMV. This element negatively modulates expression in nonpermissive cells but positively influences expression in permissive cells.

  15. Social contact elicits immediate-early gene expression in dopaminergic cells of the male prairie vole extended olfactory amygdala

    PubMed Central

    Northcutt, Katharine V.; Lonstein, Joseph S.

    2010-01-01

    Male prairie voles (Microtus ochrogaster) are a valuable model in which to study the neurobiology of sociality because, unlike most mammals, they pair bond after mating and display paternal behaviors. Research on the regulation of these social behaviors has highlighted dopamine (DA) neurotransmission in both pair bonding and parenting. We recently described large numbers of dopaminergic cells in the male prairie vole principal nucleus of the bed nucleus of the stria terminalis (pBST) and posterodorsal medial amygdala (MeApd), but such cells were very few in number or absent in the non-monogamous species we examined, including meadow voles. This suggests that DA cells in these sites may be important for sociosexual behaviors in male prairie voles. To gain some insight into the function of these DAergic neurons in male prairie voles, we examined expression of the immediate-early genes (IEGs) Fos and Egr-1 in TH-immunoreactive (TH-ir) cells of the pBST and MeApd after males interacted or not with one of several social stimuli. We found that IEGs were constitutively expressed in some TH-ir neurons under any social condition, and that IEG expression in these cells decreased after a 3.5-hr social isolation. Thirty-min mating bouts (but not 6- or 24-hr bouts) that included ejaculation elicited greater IEG expression in TH-ir cells than did non-ejaculatory mating, interactions with a familiar female sibling, or interactions with pups. Furthermore, Fos expression in TH-ir cells was positively correlated with the display of copulatory, but not parental, behaviors. These effects of mating were not found in other DA-rich sites of the forebrain (including the anteroventral periventricular preoptic area, periventricular anterior hypothalamus, zona incerta, and arcuate nucleus). Thus, activity in DAergic cells of the male prairie vole pBST and MeApd is influenced by their social environment, and may be particularly involved in mating and its consequences, including pair bonding. PMID:19524021

  16. Herpes simplex virus type 1 immediate-early protein Vmw110 reactivates latent herpes simplex virus type 2 in an in vitro latency system.

    PubMed Central

    Harris, R A; Everett, R D; Zhu, X X; Silverstein, S; Preston, C M

    1989-01-01

    Reactivation of latent herpes simplex virus type 2 (HSV-2) by the immediate-early protein Vmw110 was studied by using an in vitro latency system. Adenovirus recombinants that express Vmw110 reactivated latent HSV-2. An HSV-1 mutant possessing a deletion in a carboxy-terminal region of Vmw110 reactivated latent HSV-2, whereas mutant FXE, which has a deletion in the second exon, did not. Therefore, Vmw110 alone is required to reactivate latent HSV-2 in vitro, and the region of Vmw110 defined by the deletion in FXE is important for this process. Images PMID:2545921

  17. Repression of adenovirus early gene expression by coinfection with a temperature-sensitive mutant in the immediate-early gene of pseudorabies virus.

    PubMed Central

    Feldman, L T; Ahlers, S E

    1986-01-01

    Wild-type adenovirus was coinfected with a mutant temperature sensitive for the immediate-early gene of pseudorabies virus. At the nonpermissive temperature, this mutant, tsG, strongly inhibited the transcription of all adenovirus early genes, including E1A. This inhibition was not observed with wild-type pseudorabies virus coinfection or with tsG coinfection at the permissive temperature. The level of repression was dependent upon the ratio of tsG to adenovirus in the infection. The results suggest that the temperature-sensitive protein may be interacting with transcription factors on the viral DNA or with the DNA itself to inhibit adenovirus transcription. Images PMID:3001339

  18. Toll-like Receptor 2 is Dispensable for an Immediate-early Microglial Reaction to Two-photon Laser-induced Cortical Injury In vivo

    PubMed Central

    Yoon, Heera; Jang, Yong Ho

    2015-01-01

    Microglia, the resident macrophages in the central nervous system, can rapidly respond to pathological insults. Toll-like receptor 2 (TLR2) is a pattern recognition receptor that plays a fundamental role in pathogen recognition and activation of innate immunity. Although many previous studies have suggested that TLR2 contributes to microglial activation and subsequent pathogenesis following brain tissue injury, it is still unclear whether TLR2 has a role in microglia dynamics in the resting state or in immediate-early reaction to the injury in vivo. By using in vivo two-photon microscopy imaging and Cx3cr1GFP/+ mouse line, we first monitored the motility of microglial processes (i.e. the rate of extension and retraction) in the somatosensory cortex of living TLR2-KO and WT mice; Microglial processes in TLR2-KO mice show the similar motility to that of WT mice. We further found that microglia rapidly extend their processes to the site of local tissue injury induced by a two-photon laser ablation and that such microglial response to the brain injury was similar between WT and TLR2-KO mice. These results indicate that there are no differences in the behavior of microglial processes between TLR2-KO mice and WT mice when microglia is in the resting state or encounters local injury. Thus, TLR2 might not be essential for immediate-early microglial response to brain tissue injury in vivo. PMID:26330759

  19. Seven gene deletions in seven days: Fast generation of Escherichia coli strains tolerant to acetate and osmotic stress.

    PubMed

    Jensen, Sheila I; Lennen, Rebecca M; Herrgård, Markus J; Nielsen, Alex T

    2015-01-01

    Generation of multiple genomic alterations is currently a time consuming process. Here, a method was established that enables highly efficient and simultaneous deletion of multiple genes in Escherichia coli. A temperature sensitive plasmid containing arabinose inducible lambda Red recombineering genes and a rhamnose inducible flippase recombinase was constructed to facilitate fast marker-free deletions. To further speed up the procedure, we integrated the arabinose inducible lambda Red recombineering genes and the rhamnose inducible FLP into the genome of E. coli K-12?MG1655. This system enables growth at 37?°C, thereby facilitating removal of integrated antibiotic cassettes and deletion of additional genes in the same day. Phosphorothioated primers were demonstrated to enable simultaneous deletions during one round of electroporation. Utilizing these methods, we constructed strains in which four to seven genes were deleted in E. coli W and E. coli K-12. The growth rate of an E. coli K-12 quintuple deletion strain was significantly improved in the presence of high concentrations of acetate and NaCl. In conclusion, we have generated a method that enables efficient and simultaneous deletion of multiple genes in several E. coli variants. The method enables deletion of up to seven genes in as little as seven days. PMID:26643270

  20. Seven gene deletions in seven days: Fast generation of Escherichia coli strains tolerant to acetate and osmotic stress

    PubMed Central

    Jensen, Sheila I.; Lennen, Rebecca M.; Herrgård, Markus J.; Nielsen, Alex T.

    2015-01-01

    Generation of multiple genomic alterations is currently a time consuming process. Here, a method was established that enables highly efficient and simultaneous deletion of multiple genes in Escherichia coli. A temperature sensitive plasmid containing arabinose inducible lambda Red recombineering genes and a rhamnose inducible flippase recombinase was constructed to facilitate fast marker-free deletions. To further speed up the procedure, we integrated the arabinose inducible lambda Red recombineering genes and the rhamnose inducible FLP into the genome of E. coli K-12?MG1655. This system enables growth at 37?°C, thereby facilitating removal of integrated antibiotic cassettes and deletion of additional genes in the same day. Phosphorothioated primers were demonstrated to enable simultaneous deletions during one round of electroporation. Utilizing these methods, we constructed strains in which four to seven genes were deleted in E. coli W and E. coli K-12. The growth rate of an E. coli K-12 quintuple deletion strain was significantly improved in the presence of high concentrations of acetate and NaCl. In conclusion, we have generated a method that enables efficient and simultaneous deletion of multiple genes in several E. coli variants. The method enables deletion of up to seven genes in as little as seven days. PMID:26643270

  1. PU.1 is a suppressor of myeloid leukemia, inactivated in mice by gene deletion and mutation of its DNA binding domain.

    PubMed

    Cook, Wendy D; McCaw, Benjamin J; Herring, Christopher; John, Deborah L; Foote, Simon J; Nutt, Stephen L; Adams, Jerry M

    2004-12-01

    In most myeloid leukemias induced in mice by gamma-radiation, one copy of chromosome 2 has suffered a deletion. To search for a potential tumor suppressor gene in that region, we have delineated the deletions in a panel of these tumors. A commonly deleted region of 2 megabase pairs (Mbp) includes the gene encoding the PU.1 transcription factor, a powerful inducer of granulocytic/monocytic differentiation. Significantly, in 87% of these tumors the remaining PU.1 allele exhibited point mutations in the PU.1 DNA binding domain. Surprisingly, 86% of these mutations altered a single CpG, implicating deamination of deoxycytidine, a common mutational mechanism, as the origin of this lesion. The "hot spot" resides in the codon for a contact residue essential for DNA binding by PU.1. In keeping with a tumor suppressor role for PU.1, enforced expression of wild-type PU.1 in the promyelocytic leukemia cells inhibited their clonogenic growth, induced monocytic differentiation, and elicited apoptosis. The mutant PU.1 found in tumors retained only minimal growth suppressive function. The results suggest that PU.1 normally suppresses development of myeloid leukemia by promoting differentiation and that the combination of gene deletion and a point mutation that impairs its ability to bind DNA is particularly leukemogenic. PMID:15304397

  2. Immediate-early response 5 (IER5) interacts with protein phosphatase 2A and regulates the phosphorylation of ribosomal protein S6 kinase and heat shock factor 1.

    PubMed

    Kawabata, Shotaro; Ishita, Yuichiro; Ishikawa, Yukio; Sakurai, Hiroshi

    2015-11-30

    Immediate-early response 5 (IER5) is a growth factor-inducible protein with homology to the N-terminus of IER2. Deletion analysis shows that a large region of IER5, including the N-terminal region, is involved in cell growth and stress resistance. The N-terminal region mediates IER5 oligomerization and binding to the B55 regulatory subunit of protein phosphatase 2A (PP2A). IER5 physically interacts with the PP2A target proteins ribosomal protein S6 kinase (S6K) and heat shock factor 1 (HSF1), and the interactions are essential for the reduced phosphorylation of S6K and HSF1. Our data indicate that oligomeric IER5 regulates PP2A activity and cell growth. PMID:26496226

  3. Characterization of xylan utilization and discovery of a new endoxylanase in Thermoanaerobacterium saccharolyticum through targeted gene deletions

    SciTech Connect

    Podkaminer, Kara K; Guss, Adam M; McKenzie, Heather; Hogsett, David; Lynd, Lee R

    2012-01-01

    The economical production of fuels and commodity chemicals from lignocellulose requires the utilization of both the cellulose and hemicellulose fractions. Xylanase enzymes allow greater utilization of hemicellulose while also increasing cellulose hydrolysis. Recent metabolic engineering efforts have resulted in a strain of Thermoanaerobacterium saccharolyticum that can convert C(5) and C(6) sugars, as well as insoluble xylan, into ethanol at high yield. To better understand the process of xylan solubilization in this organism, a series of targeted deletions were constructed in the homoethanologenic T. saccharolyticum strain M0355 to characterize xylan hydrolysis and xylose utilization in this organism. While the deletion of -xylosidase xylD slowed the growth of T. saccharolyticum on birchwood xylan and led to an accumulation of short-chain xylo-oligomers, no other single deletion, including the deletion of the previously characterized endoxylanase XynA, had a phenotype distinct from that of the wild type. This result indicates a multiplicity of xylanase enzymes which facilitate xylan degradation in T. saccharolyticum. Growth on xylan was prevented only when a previously uncharacterized endoxylanase encoded by xynC was also deleted in conjunction with xynA. Sequence analysis of xynC indicates that this enzyme, a low-molecular-weight endoxylanase with homology to glycoside hydrolase family 11 enzymes, is secreted yet untethered to the cell wall. Together, these observations expand our understanding of the enzymatic basis of xylan hydrolysis by T. saccharolyticum.

  4. CuZnSOD gene deletion targeted to skeletal muscle leads to loss of contractile force but does not cause muscle atrophy in adult mice

    PubMed Central

    Zhang, Yiqiang; Davis, Carol; Sakellariou, George K.; Shi, Yun; Kayani, Anna C.; Pulliam, Daniel; Bhattacharya, Arunabh; Richardson, Arlan; Jackson, Malcolm J.; McArdle, Anne; Brooks, Susan V.; Van Remmen, Holly

    2013-01-01

    We have previously shown that deletion of CuZnSOD in mice (Sod1?/? mice) leads to accelerated loss of muscle mass and contractile force during aging. To dissect the relative roles of skeletal muscle and motor neurons in this process, we used a Cre-Lox targeted approach to establish a skeletal muscle-specific Sod1-knockout (mKO) mouse to determine whether muscle-specific CuZnSOD deletion is sufficient to cause muscle atrophy. Surprisingly, mKO mice maintain muscle masses at or above those of wild-type control mice up to 18 mo of age. In contrast, maximum isometric specific force measured in gastrocnemius muscle is significantly reduced in the mKO mice. We found no detectable increases in global measures of oxidative stress or ROS production, no reduction in mitochondrial ATP production, and no induction of adaptive stress responses in muscle from mKO mice. However, Akt-mTOR signaling is elevated and the number of muscle fibers with centrally located nuclei is increased in skeletal muscle from mKO mice, which suggests elevated regenerative pathways. Our data demonstrate that lack of CuZnSOD restricted to skeletal muscle does not lead to muscle atrophy but does cause muscle weakness in adult mice and suggest loss of CuZnSOD may potentiate muscle regenerative pathways.—Zhang, Y., Davis, C., Sakellariou, G.K., Shi, Y., Kayani, A.C., Pulliam, D., Bhattacharya, A., Richardson, A., Jackson, M.J., McArdle, A., Brooks, S.V., Van Remmen, H. CuZnSOD gene deletion targeted to skeletal muscle leads to loss of contractile force but does not cause muscle atrophy in adult mice. PMID:23729587

  5. CDKN2 Gene Deletion as Poor Prognosis Predictor Involved in the Progression of Adult B-Lineage Acute Lymphoblastic Leukemia Patients

    PubMed Central

    Xu, Na; Li, Yu-ling; Zhou, Xuan; Cao, Rui; Li, Huan; Lu, Qi-si; Li, Lin; Lu, Zi-yuan; Huang, Ji-xian; Sun, Jing; Liu, Qi-fa; Du, Qing-feng; Liu, Xiao-li

    2015-01-01

    Deletion of cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) is well known in many hematologic malignancies, but only few reports have investigated this deletion effect on clinical prognosis. This study performed analysis of the CDKN2 deletion in 215 adult B- lineage acute lymphoblastic leukemia (B-ALL) patients, and related cytogenetic prognostic factors (BCR/ABL; E2A/PBXl; TEL/AML1; Mixed Lineage Leukemia (MLL) rearrangement; MYC, Immunoglobulin heavy locus (IGH) translocation). The prevalence of CDKN2 deletions in all study populations was 28.4%. There is no difference between patients with CDKN2 deletion and wild-type patients in sex, age, white blood cells (WBC) count, BM blast percentage, extra infiltration and induction complete remission (CR) rate. Analysis in relapse patients revealed that the distribution of CDKN2 deletion is higher in relapse patients (44.6%) than all patients (28.4%, P=0.006). Deletion of CDKN2 was significantly associated with poor outcomes including decreased overall survival (OS) (P<0.001), lower disease free-survival (DFS) (P<0.001), and increased cumulative incidence of relapse (P=0.002); Also, CDKN2 deletion was strongly associated with IGH translocation (P=0.021); and had an adverse effect on patients with BCR-ABL fusion gene or with MLL rearrangement. Patients with CDKN2 gene deletion benefited from allogenic hematopoietic stem cell transplantation (Allo-HSCT). Deletion of CDKN2 gene was commonly observed through leukemia progression and was poor prognostic marker in long-term outcomes. PMID:26516359

  6. Microcephaly, Intellectual Impairment, Bilateral Vesicoureteral Reflux, Distichiasis and Glomuvenous Malformations Associated with a 16q24.3 Contiguous Gene Deletion and a Glomulin Mutation

    PubMed Central

    Butler, Matthew G.; Dagenais, Susan L.; Garcia-Perez, José L.; Brouillard, Pascal; Vikkula, Miikka; Strouse, Peter; Innis, Jeffrey W.; Glover, Thomas W.

    2012-01-01

    Two hereditary syndromes, lymphedema-distichiasis syndrome (LD) and blepharo-chelio-dontic (BCD) syndrome include the aberrant growth of eyelashes from the meibomian glands, known as distichiasis. LD is an autosomal dominant syndrome primarily characterized by distichiasis and the onset of lymphedema usually during puberty. Mutations in the forkhead transcription factor FOXC2 are the only known cause of LD. BCD syndrome consists of autosomal dominant abnormalities of the eyelid, lip, and teeth, and the etiology remains unknown. In this report, we describe a proband that presented with distichiasis, microcephaly, bilateral grade IV vesicoureteral reflux requiring ureteral re-implantation, mild intellectual impairment and apparent glomuvenous malformations. Distichiasis was present in three generations of the proband’s maternal side of the family. The glomuvenous malformations were severe in the proband, and maternal family members exhibited lower extremity varicosities of variable degree. A GLMN (glomulin) gene mutation was identified in the proband that accounts for the observed glomuvenous malformations; no other family member could be tested. TIE2 sequencing revealed no mutations. In the proband, an additional submicroscopic 265 kb contiguous gene deletion was identified in 16q24.3, located 609 kb distal to the FOXC2 locus, which was inherited from the proband’s mother. The deletion includes the C16ORF95, FBXO31, MAP1LC3B, and ZCCHC14 loci and 115 kb of a gene desert distal to FOXC2 and FOXL1. Thus, it is likely that the microcephaly, distichiasis, vesicoureteral and intellectual impairment in this family may be caused by the deletion of one or more of these genes and/or deletion of distant cis-regulatory elements of FOXC2 expression. PMID:22407726

  7. Identification of immediate-early-type cis-response elements in the promoter for the ribonucleotide reductase large subunit from herpes simplex virus type 2.

    PubMed Central

    Wymer, J P; Chung, T D; Chang, Y N; Hayward, G S; Aurelian, L

    1989-01-01

    Regulation of the expression of the herpes simplex virus (HSV) type 2 large subunit of ribonucleotide reductase (ICP10) gene was studied directly by immunofluorescence or by chloramphenicol acetyltransferase analysis with hybrid ICP10 promoter constructions. In Vero cells, cotransfection with DNA encoding HSV IE110 or Vmw65 proteins or HCMV IE2 enhanced expression at least 10-fold. In contrast, expression was minimally enhanced by DNA encoding IE175 at low doses and slightly reduced at high doses. IE110-mediated trans-activation was minimal in primary astrocytes and cells from line 293. However, Vmw65 enhanced expression 20-fold in all cell types. cis-Response elements in the ICP10 promoter include a TAATGARAT-like element and other sequences associated with regulation of IE gene expression and potential SP-1, consensus AP-1, and octamer transcription factor 1 binding elements. Factors that bind to the ICP10 promoter were identified in mock and HSV-infected cell extracts. DNA-protein complex formation, presumably involving Vmw65, was demonstrated by gel retardation analysis with mixtures of uninfected cell nuclear extracts and virion lysates. The octamer transcription factor 1 motif (ATGCAAAT) was necessary for optimal Vmw65 binding to the ICP10 promoter as evidenced by competition experiments with oligonucleotides overlapping the consensus IE110 promoter virion response element. The data suggest that ICP10 can be regulated as an immediate-early gene. Images PMID:2542589

  8. CAMKII-conditional deletion of histone deacetylase 2 potentiates acute methamphetamine-induced expression of immediate early genes in the mouse nucleus accumbens

    PubMed Central

    Torres, Oscar V.; McCoy, Michael T.; Ladenheim, Bruce; Jayanthi, Subramaniam; Brannock, Christie; Tulloch, Ingrid; Krasnova, Irina N.; Cadet, Jean Lud

    2015-01-01

    Methamphetamine (METH) produces increases in the expression of immediate early genes (IEGs) and of histone deacetylase 2 (HDAC2) in the rat nucleus accumbens (NAc). Here, we tested whether HDAC2 deletion influenced the effects of METH on IEG expression in the NAc. Microarray analyses showed no baseline differences in IEG expression between wild-type (WT) and HDAC2 knockout (KO) mice. Quantitative-PCR analysis shows that an acute METH injection produced time-dependent increases in mRNA levels of several IEGs in both genotypes. Interestingly, HDAC2KO mice displayed greater METH-induced increases in Egr1 and Egr2 mRNA levels measured at one hour post-injection. The levels of Fosb, Fra2, Egr1, and Egr3 mRNAs stayed elevated in the HDAC2KO mice 2 hours after the METH injection whereas these mRNAs had normalized in the WT mice. In WT mice, METH caused increased HDAC2 recruitment to the promoters some IEGs at 2 hours post injection. METH-induced prolonged increases in Fosb, Fra2, Egr1, and Egr3 mRNA levels in HDAC2KO mice were associated with increased enrichment of phosphorylated CREB (pCREB) on the promoters of these genes. Based on our observations, we hypothesize that HDAC2 may regulate the expression of these genes, in part, by prolonging the actions of pCREB in the mouse NAc. PMID:26300473

  9. Activity-dependent expression of miR-132 regulates immediate-early gene induction during olfactory learning in the greater short-nosed fruit bat, Cynopterus sphinx.

    PubMed

    Mukilan, Murugan; Ragu Varman, Durairaj; Sudhakar, Sivasubramaniam; Rajan, Koilmani Emmanuvel

    2015-04-01

    The activity-dependent expression of immediate-early genes (IEGs) and microRNA (miR)-132 has been implicated in synaptic plasticity and the formation of long-term memory (LTM). In the present study, we show that olfactory training induces the expression of IEGs (EGR-1, C-fos, C-jun) and miR-132 at similar time scale in olfactory bulb (OB) of Cynopterus sphinx. We examined the role of miR-132 in the OB using antisense oligodeoxynucleotide (AS-ODN) and demonstrated that a local infusion of AS-ODN in the OB 2h prior to training impaired olfactory memory formation in C. sphinx. However, the infusion of AS-ODN post-training did not cause a deficit in memory formation. Furthermore, the inhibition of miR-132 reduced the olfactory training-induced expression of IEGs and post synaptic density protein-95 (PSD-95) in the OB. Additionally, we show that miR-132 regulates the activation of calcium/calmodulin-dependent protein kinase-II (CaMKII) and cAMP response element binding protein (CREB), possibly through miR-148a. These data suggest that olfactory training induces the expression of miR-132 and IEGs, which in turn activates post-synaptic proteins that regulate olfactory memory formation. PMID:25725166

  10. Full trans-activation mediated by the immediate-early protein of equine herpesvirus 1 requires a consensus TATA box, but not its cognate binding sequence.

    PubMed

    Kim, Seong K; Shakya, Akhalesh K; O'Callaghan, Dennis J

    2016-01-01

    The immediate-early protein (IEP) of equine herpesvirus 1 (EHV-1) has extensive homology to the IEP of alphaherpesviruses and possesses domains essential for trans-activation, including an acidic trans-activation domain (TAD) and binding domains for DNA, TFIIB, and TBP. Our data showed that the IEP directly interacted with transcription factor TFIIA, which is known to stabilize the binding of TBP and TFIID to the TATA box of core promoters. When the TATA box of the EICP0 promoter was mutated to a nonfunctional TATA box, IEP-mediated trans-activation was reduced from 22-fold to 7-fold. The IEP trans-activated the viral promoters in a TATA motif-dependent manner. Our previous data showed that the IEP is able to repress its own promoter when the IEP-binding sequence (IEBS) is located within 26-bp from the TATA box. When the IEBS was located at 100bp upstream of the TATA box, IEP-mediated trans-activation was very similar to that of the minimal IE(nt -89 to +73) promoter lacking the IEBS. As the distance from the IEBS to the TATA box decreased, IEP-mediated trans-activation progressively decreased, indicating that the IEBS located within 100bp from the TATA box sequence functions as a distance-dependent repressive element. These results indicated that IEP-mediated full trans-activation requires a consensus TATA box of core promoters, but not its binding to the cognate sequence (IEBS). PMID:26541315

  11. Immediate-early protein of equid herpesvirus type 1 as a target for cytotoxic T-lymphocytes in the Thoroughbred horse.

    PubMed

    Kydd, Julia H; Case, Ruth; Minke, Julius; Audonnet, Jean-Christophe; Wagner, Bettina; Antczak, Douglas F

    2014-08-01

    Cytotoxic T-lymphocytes (CTLs) are associated with protective immunity against disease caused by equid herpesvirus type 1 (EHV-1). However, the EHV-1 target proteins for CTLs are poorly defined. This limits the development of vaccine candidates designed to stimulate strong CTL immunity. Here, classical CTL assays using lymphocytes from horses of three defined MHC class I types that experienced natural infection with EHV-1 and a modified vaccinia virus construct containing an EHV-1 gene encoding the immediate-early (IE) protein are reported. Horses homozygous for the equine leukocyte antigen (ELA)-A2 haplotype, but not the ELA-A5 haplotype, produced MHC-restricted CTL responses against the IE protein. Previously, horses homozygous for the ELA-A3 haplotype also mounted CTL responses against the IE protein. Both haplotypes are common in major horse breeds, including the Thoroughbred. Thus, the IE protein is an attractive candidate molecule for future studies of T-cell immunity to EHV-1 in the horse. PMID:24836672

  12. Barrier-to-Autointegration Factor 1 (BAF/BANF1) Promotes Association of the SETD1A Histone Methyltransferase with Herpes Simplex Virus Immediate-Early Gene Promoters

    PubMed Central

    Oh, Hyung Suk; Traktman, Paula

    2015-01-01

    ABSTRACT We have shown previously that A-type lamins and intranuclear localization of the herpes simplex virus (HSV) genome are critical for the formation of the VP16 activator complex on HSV immediate-early (IE) gene promoters in murine cells, which implies a critical role for lamin A and its associated proteins in HSV gene expression. Because barrier-to-autointegration factor 1 (BAF/BANF1) has been thought to bridge chromosomes to the nuclear lamina, we hypothesized that BAF might mediate viral genome targeting to the nuclear lamina. We found that overexpression of BAF enhances HSV-1 replication and knockdown of BAF decreases HSV gene expression, delays the kinetics of viral early replication compartment formation, and reduces viral yield compared to those in control small interfering RNA-transfected cells. However, BAF depletion did not affect genome complex targeting to the nuclear periphery. Instead, we found that the levels of a histone-modifying enzyme, SETD1A methyltransferase, and histone H3 lysine 4 trimethylation were reduced on IE and early (E) gene promoters in BAF-depleted cells during HSV lytic infection. Our results demonstrate a novel function of BAF as an epigenetic regulator of HSV lytic infection. We hypothesize that BAF facilitates IE and E gene expression by recruiting the SETD1A methyltransferase to viral IE and E gene promoters. PMID:26015494

  13. Matrix Metalloproteinase-2 (MMP-2) Gene Deletion Enhances MMP-9 Activity, Impairs PARP-1 Degradation, and Exacerbates Hepatic Ischemia and Reperfusion Injury in Mice

    PubMed Central

    Kato, Hiroyuki; Duarte, Sergio; Liu, Daniel; Busuttil, Ronald W.; Coito, Ana J.

    2015-01-01

    Hepatic ischemia and reperfusion injury (IRI) is an inflammatory condition and a significant cause of morbidity and mortality after surgery. Matrix metalloproteinases (MMPs) have been widely implicated in the pathogenesis of inflammatory diseases. Among the different MMPs, gelatinases (MMP-2 and MMP-9) are within the most prominent MMPs detected during liver IRI. While the role of MMP-9 in liver damage has been fairly documented, direct evidence of the role for MMP-2 activity in hepatic IRI remains to be established. Due to the lack of suitable inhibitors to target individual MMPs in vivo, gene manipulation is as an essential tool to assess MMP direct contribution to liver injury. Hence, we used MMP-2-/- deficient mice and MMP-2+/+ wild-type littermates to examine the function of MMP-2 activity in hepatic IRI. MMP-2 expression was detected along the sinusoids of wild-type livers before and after surgery and in a small population of leukocytes post-IRI. Compared to MMP-2+/+ mice, MMP-2 null (MMP-2-/-) mice showed exacerbated liver damage at 6, 24, and 48 hours post-reperfusion, which was fatal in some cases. MMP-2 deficiency resulted in upregulation of MMP-9 activity, spontaneous leukocyte infiltration in naïve livers, and amplified MMP-9-dependent transmigration of leukocytes in vitro and after hepatic IRI. Moreover, complete loss of MMP-2 activity impaired the degradation of poly (ADP-ribose) polymerase (PARP-1) in extensively damaged livers post-reperfusion. However, the administration of a PARP-1 inhibitor to MMP-2 null mice restored liver preservation to almost comparable levels of MMP-2+/+ mice post-IRI. Deficient PARP-1 degradation in MMP-2-null sinusoidal endothelial cells correlated with their increased cytotoxicity, evaluated by the measurement of LDH efflux in the medium. In conclusion, our results show for the first time that MMP-2 gene deletion exacerbates liver IRI. Moreover, they offer new insights into the MMP-2 modulation of inflammatory responses, which could be relevant for the design of new pharmacological MMP-targeted agents to treat hepatic IRI. PMID:26355684

  14. Immediate early gene expression and delayed cell death in limbic areas of the rat brain after kainic acid treatment and recovery in the cold.

    PubMed

    Goodenough, S; Davidson, M; Chen, W; Beckmann, A; Pujic, Z; Otsuki, M; Matsumoto, I; Wilce, P

    1997-06-01

    Systemic injection of kainic acid (KA) results in characteristic behaviors and programmed cell death in some regions of the rat brain. We used KA followed by recovery at 4 degrees C to restrict damage to limbic structures and compared patterns of immediate early gene (IEG) expression and associated DNA binding activity in these damaged areas with that in spared brain regions. Male Wistar rats were injected with KA (12 mg/kg, i.p.) and kept at 4 degrees C for 5 h. This treatment reduced the severity of behaviors and restricted damage (observed by Nissl staining) to the CA1 and CA3 regions of the hippocampus and an area including the entorhinal cortex. DNA laddering, characteristic of apoptosis, was first evident in the hippocampus and the entorhinal cortex 18 and 22 h after KA, respectively. The pattern of IEG mRNA induction fell into three classes: IEGs that were induced in both damaged and spared areas (c-fos, fos B, jun B, and egr-1), IEGs that were induced specifically in the damaged areas (fra-2 and c-jun), and an IEG that was significantly induced by saline injection and/or the cold treatment (jun D). The pattern of immunoreactivity closely followed that of mRNA expression. Binding to the AP-1 and EGR DNA consensus sequences increased in all three regions studied. This study describes a unique modification of the animal model of KA-induced neurotoxicity which may prove a useful tool for dissecting the molecular cascade that ultimately results in programmed cell death. PMID:9217081

  15. The Murine Gammaherpesvirus Immediate-Early Rta Synergizes with IRF4, Targeting Expression of the Viral M1 Superantigen to Plasma Cells

    PubMed Central

    O'Flaherty, Brigid M.; Soni, Tanushree; Wakeman, Brian S.; Speck, Samuel H.

    2014-01-01

    MHV68 is a murine gammaherpesvirus that infects laboratory mice and thus provides a tractable small animal model for characterizing critical aspects of gammaherpesvirus pathogenesis. Having evolved with their natural host, herpesviruses encode numerous gene products that are involved in modulating host immune responses to facilitate the establishment and maintenance of lifelong chronic infection. One such protein, MHV68 M1, is a secreted protein that has no known homologs, but has been shown to play a critical role in controlling virus reactivation from latently infected macrophages. We have previous demonstrated that M1 drives the activation and expansion of V?4+ CD8+ T cells, which are thought to be involved in controlling MHV68 reactivation through the secretion of interferon gamma. The mechanism of action and regulation of M1 expression are poorly understood. To gain insights into the function of M1, we set out to evaluate the site of expression and transcriptional regulation of the M1 gene. Here, using a recombinant virus expressing a fluorescent protein driven by the M1 gene promoter, we identify plasma cells as the major cell type expressing M1 at the peak of infection in the spleen. In addition, we show that M1 gene transcription is regulated by both the essential viral immediate-early transcriptional activator Rta and cellular interferon regulatory factor 4 (IRF4), which together potently synergize to drive M1 gene expression. Finally, we show that IRF4, a cellular transcription factor essential for plasma cell differentiation, can directly interact with Rta. The latter observation raises the possibility that the interaction of Rta and IRF4 may be involved in regulating a number of viral and cellular genes during MHV68 reactivation linked to plasma cell differentiation. PMID:25101696

  16. Contrasting role of phospholipase C-{gamma}1 in the expression of immediate early genes induced by epidermal or platelet-derived growth factors

    SciTech Connect

    Liao Hongjun; Santos, Josue de los; Carpenter, Graham . E-mail: graham.carpenter@vanderbilt.edu

    2006-04-01

    While significant progress has been achieved in identifying the signal transduction elements that operate downstream of activated receptor tyrosine kinases, it remains unclear how different receptors utilize these signaling elements to achieve a common response. This study compares the capacity of epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) to elicit the induction of immediate early gene (IEG) mRNAs in the presence or absence of phospholipase C-{gamma}1 (PLC-{gamma}1). The results show that while PDGF induction of nearly all IEG mRNAs is abrogated in plcg1 null cells, EGF induction of the same genes is variable in the null cells and exhibits three distinct responses. Five IEG mRNAs (Nup475, Cyr61, TF, Gly, TS7) are completely inducible by EGF in the presence or absence of PLC-{gamma}1, while three others (JE, KC, FIC) exhibit a stringent requirement for the presence of PLC-{gamma}1. The third type of response is exhibited by c-fos and COX-2. While these mRNAs are completely induced by EGF in the absence of PLC-{gamma}1, the time course of their accumulation is significantly delayed. No IEG was identified as completely inducible by EGF and PDGF in the absence of PLC-{gamma}1. Electrophoretic mobility shift assays (EMSA) demonstrate that PLC-{gamma}1 is necessary for nuclear extracts from PDGF-treated cells, but not EGF-treated cells, to interact with probes for AP-1 or NF-{kappa}B.

  17. Motor-Coordination-Dependent Learning, More than Others, Is Impaired in Transgenic Mice Expressing Pseudorabies Virus Immediate-Early Protein IE180

    PubMed Central

    López-Ramos, Juan C.; Tomioka, Yukiko; Morimatsu, Masami; Yamamoto, Sayo; Ozaki, Kinuyo; Ono, Etsuro; Delgado-García, José M.

    2010-01-01

    The cerebellum in transgenic mice expressing pseudorabies virus immediate-early protein IE180 (TgIE96) was substantially diminished in size, and its histoarchitecture was severely disorganized, resulting in severe ataxia. TgIE96 mice can therefore be used as an experimental model to study the involvement of cerebellar circuits in different learning tasks. The performance of three-month-old TgIE96 mice was studied in various behavioral tests, including associative learning (classical eyeblink conditioning), object recognition, spatial orientation (water maze), startle response and prepulse inhibition, and passive avoidance, and compared with that of wild-type mice. Wild-type and TgIE96 mice presented similar reflexively evoked eyeblinks, and acquired classical conditioned eyelid responses with similar learning curves for both trace and delay conditioning paradigms. The two groups of mice also had similar performances during the object recognition test. However, they showed significant differences for the other three tests included in this study. Although both groups of animals were capable of swimming, TgIE96 mice failed to learn the water maze task during the allowed time. The startle response to a severe tone was similar in both control and TgIE96 mice, but the latter were unable to produce a significant prepulse inhibition. TgIE96 mice also presented evident deficits for the proper accomplishment of a passive avoidance test. These results suggest that the cerebellum is not indispensable for the performance of classical eyeblink conditioning and for object recognition tasks, but seems to be necessary for the proper performance of water maze, prepulse inhibition, and passive avoidance tests. PMID:20711341

  18. Expression pattern of immediate early genes in the cerebellum of D1R KO, D2R KO, and wild type mice under vestibular-controlled activity

    PubMed Central

    Nakamura, Toru; Sato, Asako; Kitsukawa, Takashi; Sasaoka, Toshikuni; Yamamori, Tetsuo

    2015-01-01

    We previously reported the different motor abilities of D1R knockout (KO), D2R KO and wild-type (WT) mice. To understand the interaction between the cerebellum and the striatal direct and indirect pathways, we examined the expression patterns of immediate early genes (IEG) in the cerebellum of these three genotypes of mice. In the WT naive mice, there was little IEG expression. However, we observed a robust expression of c-fos mRNA in the vermis and hemisphere after running rota-rod tasks. In the vermis, c-fos was expressed throughout the lobules except lobule 7, and also in crus 1 of the ansiform lobule (Crus1), copula of the pyramis (Cop) and most significantly in the flocculus in the hemisphere. jun-B was much less expressed but more preferentially expressed in Purkinje cells. In addition, we observed significant levels of c-fos and jun-B expressions after handling mice, and after the stationary rota-rod task in naive mice. Surprisingly, we observed significant expression of c-fos and jun-B even 30 min after single weighing. Nonetheless, certain additional c-fos and jun-B expressions were observed in three genotypes of the mice that experienced several sessions of motor tasks 24 h after stationary rota-rod task and on days 1 and 5 after rota-rod tasks, but no significant differences in expressions after the running rota-rod tasks were observed among the three genotypes. In addition, there may be some differences 24 h after the stationary rota-rod task between the naive mice and the mice that experienced several sessions of motor tasks. PMID:26137459

  19. The Varicella-Zoster Virus Immediate-Early 63 protein affects chromatin controlled gene transcription in a cell-type dependent manner

    PubMed Central

    Habran, Lionel; El Mjiyad, Nadia; Di Valentin, Emmanuel; Sadzot-Delvaux, Catherine; Bontems, Sébastien; Piette, Jacques

    2007-01-01

    Background Varicella Zoster Virus Immediate Early 63 protein (IE63) has been shown to be essential for VZV replication, and critical for latency establishment. The activity of the protein as a transcriptional regulator is not fully clear yet. Using transient transfection assays, IE63 has been shown to repress viral and cellular promoters containing typical TATA boxes by interacting with general transcription factors. Results In this paper, IE63 regulation properties on endogenous gene expression were evaluated using an oligonucleotide-based micro-array approach. We found that IE63 modulates the transcription of only a few genes in HeLa cells including genes implicated in transcription or immunity. Furthermore, we showed that this effect is mediated by a modification of RNA POL II binding on the promoters tested and that IE63 phosphorylation was essential for these effects. In MeWo cells, the number of genes whose transcription was modified by IE63 was somewhat higher, including genes implicated in signal transduction, transcription, immunity, and heat-shock signalling. While IE63 did not modify the basal expression of several NF-?B dependent genes such as IL-8, ICAM-1, and I?B?, it modulates transcription of these genes upon TNF? induction. This effect was obviously correlated with the amount of p65 binding to the promoter of these genes and with histone H3 acetylation and HDAC-3 removal. Conclusion While IE63 only affected transcription of a small number of cellular genes, it interfered with the TNF-inducibility of several NF-?B dependent genes by the accelerated resynthesis of the inhibitor I?B?. PMID:17971236

  20. Analysis of human cytomegalovirus-encoded SUMO targets and temporal regulation of SUMOylation of the immediate-early proteins IE1 and IE2 during infection.

    PubMed

    Kim, Eui Tae; Kim, Young-Eui; Kim, Ye Ji; Lee, Myoung Kyu; Hayward, Gary S; Ahn, Jin-Hyun

    2014-01-01

    Post-translational modification of proteins by members of the small ubiquitin-like modifier (SUMO) is involved in diverse cellular functions. Many viral proteins are SUMO targets and also interact with the cellular SUMOylation system. During human cytomegalovirus (HCMV) infection, the immediate-early (IE) proteins IE1 and IE2 are covalently modified by SUMO. IE2 SUMOylation promotes its transactivation activity, whereas the role of IE1 SUMOylation is not clear. We performed in silico, genome-wide analysis to identify possible SUMOylation sites in HCMV-encoded proteins and evaluated their modification using the E. coli SUMOylation system and in vitro assays. We found that only IE1 and IE2 are substantially modified by SUMO in E. coli, although US34A was also identified as a possible SUMO target in vitro. We also found that SUMOylation of IE1 and IE2 is temporally regulated during viral infection. Levels of SUMO-modified form of IE1 were increased during the early phase of infection, but decreased in the late phase when IE2 and its SUMO-modified forms were expressed at high levels. IE2 expression inhibited IE1 SUMOylation in cotransfection assays. As in IE2 SUMOylation, PIAS1, a SUMO E3 ligase, interacted with IE1 and enhanced IE1 SUMOylation. In in vitro assays, an IE2 fragment that lacked covalent and non-covalent SUMO attachment sites, but was sufficient for PIAS1 binding, effectively inhibited PIAS1-mediated SUMOylation of IE1, indicating that IE2 expression negatively regulates IE1 SUMOylation. We also found that the IE2-mediated downregulation of IE1 SUMOylation correlates with the IE1 activity to repress the promoter containing the interferon stimulated response elements. Taken together, our data demonstrate that IE1 and IE2 are the main viral SUMO targets in HCMV infection and that temporal regulation of their SUMOylation may be important in the progression of this infection. PMID:25050850

  1. Combinatorial Strategies for Improving Multiple-Stress Resistance in Industrially Relevant Escherichia coli Strains

    PubMed Central

    Herrgård, Markus J.

    2014-01-01

    High-cell-density fermentation for industrial production of chemicals can impose numerous stresses on cells due to high substrate, product, and by-product concentrations; high osmolarity; reactive oxygen species; and elevated temperatures. There is a need to develop platform strains of industrial microorganisms that are more tolerant toward these typical processing conditions. In this study, the growth of six industrially relevant strains of Escherichia coli was characterized under eight stress conditions representative of fed-batch fermentation, and strains W and BL21(DE3) were selected as platforms for transposon (Tn) mutagenesis due to favorable resistance characteristics. Selection experiments, followed by either targeted or genome-wide next-generation-sequencing-based Tn insertion site determination, were performed to identify mutants with improved growth properties under a subset of three stress conditions and two combinations of individual stresses. A subset of the identified loss-of-function mutants were selected for a combinatorial approach, where strains with combinations of two and three gene deletions were systematically constructed and tested for single and multistress resistance. These approaches allowed identification of (i) strain-background-specific stress resistance phenotypes, (ii) novel gene deletion mutants in E. coli that confer single and multistress resistance in a strain-background-dependent manner, and (iii) synergistic effects of multiple gene deletions that confer improved resistance over single deletions. The results of this study underscore the suboptimality and strain-specific variability of the genetic network regulating growth under stressful conditions and suggest that further exploration of the combinatorial gene deletion space in multiple strain backgrounds is needed for optimizing strains for microbial bioprocessing applications. PMID:25085490

  2. The palindromic series I repeats in the simian cytomegalovirus major immediate-early promoter behave as both strong basal enhancers and cyclic AMP response elements.

    PubMed Central

    Chang, Y N; Crawford, S; Stall, J; Rawlins, D R; Jeang, K T; Hayward, G S

    1990-01-01

    A 600-base-pair (bp) enhancer region upstream from the major IE94 gene of simian cytomegalovirus (SCMV) produces very strong basal expression of associated gene products. This domain consists of multiple sets of interspersed repetitive elements, including 11 copies of a conserved 16-bp palindromic sequence with the consensus CCATTGACGTCAATGG. These series I repeats contain an 8-bp core TGACGTCA that resembles the cyclic AMP (cAMP) response element (CRE) of cellular genes. In transient chloramphenicol acetyltransferase assays in K562 human erythroleukemia cells, a set of deleted variants of the IE94 promoter all responded up to 15-fold to induction by cAMP. However, successive removal of most of the SCMV 16-bp motifs reduced basal expression over 20-fold. The cAMP stimulation was also manifested at the steady-state RNA level after SCMV infection of K562 cells and was detectable within 1.5 h after treatment of DNA-transfected cells. Addition of a single 30-bp oligonucleotide encompassing the 16-bp palindrome conveyed up to 10-fold cAMP responsiveness onto a heterologous weak promoter but had no effect on basal expression. In contrast, two or more adjacent copies produced 20- to 40-fold increases in basal expression and provided greater than 200-fold activation in the presence of cAMP. Similar effects were obtained when the oligonucleotides were placed in a downstream location relative to the reporter gene. Studies with mutant oligonucleotides revealed that both the core CRE and the flanking sequence portions of the 16-bp elements were essential for enhancer function. Both components were also important for maximum cAMP responsiveness. Band shift assays with fractionated nuclear extracts from Raji lymphocytes revealed multiple competable complexes with cellular DNA-binding factors that recognized the series I elements. Three distinct CREB-like factors were detected that required only the core 8-bp elements for binding. We conclude that the 16-bp series I repeats provide a major contribution to the constitutive enhancer properties of the IE94 promoter and also act as functional CREs. The cAMP response properties appear likely to play a key role in reactivation of the virus from a latent state in appropriately differentiating cell types. Images PMID:2152815

  3. Detection of phase-dependent transcriptomic changes and Rubisco-mediated CO2 fixation into poly (3-hydroxybutyrate) under heterotrophic condition in Ralstonia eutropha H16 based on RNA-seq and gene deletion analyses

    PubMed Central

    2013-01-01

    Background Ralstonia eutropha H16 is well known to produce polyhydroxyalkanoates (PHAs), which are potential bio-based biodegradable plastics, in an efficient manner as an energy storage material under unbalanced growth conditions. To obtain further knowledge of PHA biosynthesis, this study performed a quantitative transcriptome analysis based on deep sequencing of the complementary DNA generated from the RNA (RNA-seq) of R. eutropha H16. Results Total RNAs were extracted from R. eutropha cells in growth, PHA production, and stationary phases on fructose. rRNAs in the preparation were removed by repeated treatments with magnetic beads specific to bacterial rRNAs, and then the 36 bp sequences were determined using an Illumina high-throughput sequencer. The RNA-seq results indicated the induction of gene expression for transcription, translation, cell division, peptidoglycan biosynthesis, pilus and flagella assembly, energy conservation, and fatty acid biosynthesis in the growth phase; and the repression trends of genes involved in central metabolisms in the PHA production phase. Interestingly, the transcription of genes for Calvin-Benson-Bassham (CBB) cycle and several genes for ?-oxidation were significantly induced in the PHA production phase even when the cells were grown on fructose. Moreover, incorporation of 13C was observed in poly(3-hydroxybutyrate) synthesized by R. eutropha H16 from fructose in the presence of NaH13CO3, and further gene deletion analyses revealed that both of the two ribulose 1,5-bisphosphate carboxylase (Rubiscos) in CBB cycle were actually functional in CO2 fixation under the heterotrophic condition. Conclusions The results revealed the phase-dependent transcriptomic changes and a CO2 fixation capability under heterotrophic conditions by PHA-producing R. eutropha. PMID:23879744

  4. PERK (eIF2? kinase) is required to activate the stress-activated MAPKs and induce the expression of immediate-early genes upon disruption of ER calcium homoeostasis

    PubMed Central

    Liang, Shun-Hsin; Zhang, Wei; Mcgrath, Barbara C.; Zhang, Peichuan; Cavener, Douglas R.

    2005-01-01

    The eIF2? (eukaryotic initiation factor-2?) kinase PERK (doublestranded RNA-activated protein kinase-like ER kinase) is essential for the normal function of highly secretory cells in the pancreas and skeletal system, as well as the UPR (unfolded protein response) in mammalian cells. To delineate the regulatory machinery underlying PERK-dependent stress-responses, gene profiling was employed to assess global changes in gene expression in PERK-deficient MEFs (mouse embryonic fibroblasts). Several IE (immediate-early) genes, including c-myc, c-jun, egr-1 (early growth response factor-1), and fra-1 (fos-related antigen-1), displayed PERK-dependent expression in MEFs upon disruption of calcium homoeostasis by inhibiting the ER (endoplasmic reticulum) transmembrane SERCA (sarcoplasmic/ER Ca2+-ATPase) calcium pump. Induction of c-myc and egr-1 by other reagents that elicit the UPR, however, showed variable dependence upon PERK. Induction of c-myc expression by thapsigargin was shown to be linked to key signalling enzymes including PLC (phospholipase C), PI3K (phosphatidylinositol 3-kinase) and p38 MAPK (mitogen-activated protein kinase). Analysis of the phosphorylated status of major components in MAPK signalling pathways indicated that thapsigargin and DTT (dithiothreitol) but not tunicamycin could trigger the PERK-dependent activation of JNK (c-Jun N-terminal kinase) and p38 MAPK. However, activation of JNK and p38 MAPK by non-ER stress stimuli including UV irradiation, anisomycin, and TNF-? (tumour necrosis factor-?) was found to be independent of PERK. PERK plays a particularly important role in mediating the global cellular response to ER stress that is elicited by the depletion of calcium from the ER. We suggest that this specificity of PERK function in the UPR is an extension of the normal physiological function of PERK to act as a calcium sensor in the ER. PMID:16124869

  5. Inhibition of iridovirus protein synthesis and virus replication by antisense morpholino oligonucleotides targeted to the major capsid protein, the 18 kDa immediate-early protein, and a viral homolog of RNA polymerase II

    SciTech Connect

    Sample, Robert; Bryan, Locke; Long, Scott; Majji, Sai; Hoskins, Glenn; Sinning, Allan; Olivier, Jake; Chinchar, V. Gregory . E-mail: vchinchar@microbio.umsmed.edu

    2007-02-20

    Frog virus 3 (FV3) is a large DNA virus that encodes {approx} 100 proteins. Although the general features of FV3 replication are known, the specific roles that most viral proteins play in the virus life cycle have not yet been elucidated. To address the question of viral gene function, antisense morpholino oligonucleotides (asMOs) were used to transiently knock-down expression of specific viral genes and thus infer their role in virus replication. We designed asMOs directed against the major capsid protein (MCP), an 18 kDa immediate-early protein (18K) that was thought to be a viral regulatory protein, and the viral homologue of the largest subunit of RNA polymerase II (vPol-II{alpha}). All three asMOs successfully inhibited translation of the targeted protein, and two of the three asMOs resulted in marked phenotypic changes. Knock-down of the MCP resulted in a marked reduction in viral titer without a corresponding drop in the synthesis of other late viral proteins. Transmission electron microscopy (TEM) showed that in cells treated with the anti-MCP MO assembly sites were devoid of viral particles and contained numerous aberrant structures. In contrast, inhibition of 18K synthesis did not block virion formation, suggesting that the 18K protein was not essential for replication of FV3 in fathead minnow (FHM) cells. Finally, consistent with the view that late viral gene expression is catalyzed by a virus-encoded or virus-modified Pol-II-like protein, knock-down of vPol-II{alpha} triggered a global decline in late gene expression and virus yields without affecting the synthesis of early viral genes. Collectively, these results demonstrate the utility of using asMOs to elucidate the function of FV3 proteins.

  6. The equine herpesvirus-1 IR3 gene that lies antisense to the sole immediate-early (IE) gene is trans-activated by the IE protein, and is poorly expressed to a protein

    SciTech Connect

    Ahn, Byung Chul; Breitenbach, Jonathan E.; Kim, Seong K.; O'Callaghan, Dennis J. . E-mail: docall@lsuhsc.edu

    2007-06-20

    The unique IR3 gene of equine herpesvirus 1 (EHV-1) is expressed as a late 1.0-kb transcript. Previous studies confirmed the IR3 transcription initiation site and tentatively identified other cis-acting elements specific to IR3 such as a TATA box, a 443 base pair 5'untranslated region (UTR), a 285 base pair open reading frame (ORF), and a poly adenylation (A) signal [Holden, V.R., Harty, R.N., Yalamanchili, R.R., O'Callaghan, D.J., 1992. The IR3 gene of equine herpesvirus type 1: a unique gene regulated by sequences within the intron of the immediate-early gene. DNA Seq. 3, 143-152]. Transient transfection assays revealed that the IR3 promoter is strongly trans-activated by the IE protein (IEP) and that coexpression of the IEP with the early EICP0 and IR4 regulatory proteins results in maximal trans-activation of the IR3 promoter. Gel shift assays revealed that the IEP directly binds to the IR3 promoter region. Western blot analysis showed that the IR3 protein produced in E. coli was detected by antibodies to IR3 synthetic peptides; however, the IR3 protein was not detected in EHV-1 infected cell extracts by these same anti-IR3 antibodies, even though the IR3 transcript was detected by northern blot. These findings suggest that the IR3 may not be expressed to a protein. Expression of an IR3/GFP fusion gene was not observed, but expression of a GFP/IR3 fusion gene was detected by fluorescent microscopy. In further attempts to detect the IR3/GFP fusion protein using anti-GFP antibody, western blot analysis showed that the IR3/GFP fusion protein was not detected in vivo. Interestingly, a truncated form of the GFP/IR3 protein was synthesized from the GFP/IR3 fusion gene. However, GFP/IR3 and IR3/GFP fusion proteins of the predicted sizes were synthesized by in vitro coupled transcription and translation of the fusion genes, suggesting poor expression of the IR3 protein in vivo. The possible role of the IR3 transcript in EHV-1 infection is discussed.

  7. 3-Hydroxy-3-methylglutaryl CoA lyase (HL): Mouse and human HL gene (HMGCL) cloning and detection of large gene deletions in two unrelated HL-deficient patients

    SciTech Connect

    Wang, S.P.; Robert, M.F.; Mitchell, G.A.

    1996-04-01

    3-hydroxy-3-methylglutaryl CoA lyase (HL, EC 4.1.3.4) catalyzes the cleavage of 3-hydroxy-3-methylglutaryl CoA to acetoacetic acid and acetyl CoA, the final reaction of both ketogenesis and leucine catabolism. Autosomal-recessive HL deficiency in humans results in episodes of hypoketotic hypoglycemia and coma. Using a mouse HL cDNA as a probe, we isolated a clone containing the full-length mouse HL gene that spans about 15 kb of mouse chromosome 4 and contains nine exons. The promoter region of the mouse HL gene contains elements characteristic of a housekeeping gene: a CpG island containing multiple Sp1 binding sites surrounds exon 1, and neither a TATA nor a CAAT box are present. We identified multiple transcription start sites in the mouse HL gene, 35 to 9 bases upstream of the translation start codon. We also isolated two human HL genomic clones that include HL exons 2 to 9 within 18 kb. The mouse and human HL genes (HGMW-approved symbol HMGCL) are highly homologous, with identical locations of intron-exon junctions. By genomic Southern blot analysis and exonic PCR, was found 2 of 33 HL-deficient probands to be homozygous for large deletions in the HL gene. 26 refs., 4 figs., 2 tabs.

  8. Trehalose-related Gene Deletions in Fusarium verticillioides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fusarium verticillioides is a widespread corn pathogen that causes root, stalk and ear rot and produces fumonisins, toxic secondary metabolites associated with disease in livestock and humans. Our goal is to assess the feasibility of exploiting trehalose metabolism as a target for F. verticillioides...

  9. Trehalose-related gene deletions in Fusarium verticillioides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fusarium verticillioides is a widespread corn pathogen that causes root, stalk, and ear rot and produces fumonisins, toxic secondary metabolites associated with disease in livestock and humans. Our goal is to assess the feasibility of exploiting trehalose metabolism as a target for F. verticillioide...

  10. Ornithine Decarboxylase Gene Deletion Mutants of Leishmania donovani*

    E-print Network

    Schnaufer, Achim

    ). The ODC enzyme of protozoan parasites is a novel therapeutic target, because D,L- -difluoromethylor on the avail- ability of cloned genes and their flanking sequences, and mo- lecular clones encoding ODC have

  11. Gene Deletion and Functional Analysis of Fusarium verticillioides Trehalose Metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fusarium verticillioides is a species of fungus that causes stalk, ear, and kernel rot of corn and produces fumonisins, a group of mycotoxins that have dangerous health effects. We have observed previously that the intracellular concentration of trehalose, a disaccharide involved in resistance to st...

  12. Frequent gene deletions in potentially malignant oral lesions.

    PubMed Central

    Emilion, G.; Langdon, J. D.; Speight, P.; Partridge, M.

    1996-01-01

    Some oral cancers are preceded by premalignant lesions which include leucoplakia and erythroplakia. At present there are no reliable markers to identify lesions that may progress to malignancy. We have analysed 30 potentially malignant oral lesions for deletions at chromosomal regions that harbour tumour-suppressor genes for oral cancer. A total of 16 of 30 cases (53%) showed loss of heterozygosity (LOH) or allele imbalance at TP53, DCC, 3p21.3-22.1 or 3p12.1-13. These genetic alterations were detected in dysplastic lesions but not in histologically normal mucosa and may be early events in the carcinogenic process. A total of 64% of dysplastic lesions that recurred during the study showed LOH or allele imbalance in the initial biopsy and the number of genetic abnormalities increased in the tumours that developed. This type of molecular profiling may help to identify patients with lesions that may recur or acquire additional genetic events and progress to malignancy. Images Figure 2 PMID:8611386

  13. CHARACTERIZING FUMONISIN BIOSYNTHESIS THROUGH ANALYSIS OF FUM GENE DELETION MUTANTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fumonisins are produced by Gibberella moniliformis, a causal agent of maize ear and stalk rot, and pose a health risk to humans and livestock alike. Recently, a fumonisin biosynthetic gene cluster was described in G. moniliformis. The cluster consists of 15 co-regulated genes (FUM1 and FUM6 throug...

  14. PHLPP1 gene deletion protects the brain from ischemic injury

    PubMed Central

    Chen, Bo; Van Winkle, Jessica A; Lyden, Patrick D; Brown, Joan H; Purcell, Nicole H

    2013-01-01

    A recently discovered protein phosphatase PHLPP (PH domain Leucine-rich repeat Protein Phosphatase) has been shown to dephosphorylate Akt on its hydrophobic motif (Ser473) thereby decreasing Akt kinase activity. We generated PHLPP1 knockout (KO) mice and used them to explore the ability of enhanced in vivo Akt signaling to protect the brain against ischemic insult. Brains from KO mice subjected to middle cerebral artery occlusion (MCAO) for 2?hours showed significantly greater increases in Akt activity and less neurovascular damage after reperfusion than wild-type (WT) mice. Remarkably, infarct volume in the PHLPP1 KO was significantly reduced compared with WT (12.7±2.7% versus 22.9±3.1%) and this was prevented by Akt inhibition. Astrocytes from KO mice and neurons in which PHLPP1 was downregulated showed enhanced Akt activation and diminished cell death in response to oxygen-glucose deprivation. Thus, deletion of PHLPP1 can enhance Akt activation in neurons and astrocytes, and can significantly increase cell survival and diminish infarct size after MCAO. Inhibition of PHLPP could be a therapeutic approach to minimize damage after focal ischemia. PMID:23072745

  15. The first Korean patient with Potocki-Shaffer syndrome: a rare cause of multiple exostoses.

    PubMed

    Sohn, Young Bae; Yim, Shin-Young; Cho, Eun-Hae; Kim, Ok-Hwa

    2015-02-01

    Potocki-Shaffer syndrome (PSS, OMIM #601224) is a rare contiguous gene deletion syndrome caused by haploinsufficiency of genes located on the 11p11.2p12. Affected individuals have a number of characteristic features including multiple exostoses, biparietal foramina, abnormalities of genitourinary system, hypotonia, developmental delay, and intellectual disability. We report here on the first Korean case of an 8-yr-old boy with PSS diagnosed by high resolution microarray. Initial evaluation was done at age 6 months because of a history of developmental delay, hypotonia, and dysmorphic face. Coronal craniosynostosis and enlarged parietal foramina were found on skull radiographs. At age 6 yr, he had severe global developmental delay. Multiple exostoses of long bones were detected during a radiological check-up. Based on the clinical and radiological features, PSS was highly suspected. Subsequently, chromosomal microarray analysis identified an 8.6 Mb deletion at 11p11.2 [arr 11p12p11.2 (Chr11:39,204,770-47,791,278)×1]. The patient continued rehabilitation therapy for profound developmental delay. The progression of multiple exostosis has being monitored. This case confirms and extends data on the genetic basis of PSS. In clinical and radiologic aspect, a patient with multiple exostoses accompanying with syndromic features, including craniofacial abnormalities and mental retardation, the diagnosis of PSS should be considered. PMID:25653495

  16. Multiple Sclerosis

    MedlinePLUS

    MENU Return to Web version Multiple Sclerosis Overview What is multiple sclerosis (MS)? Multiple sclerosis is an autoimmune disease that affects the nervous system. Normally, antibodies produced by ...

  17. Multiple Sclerosis

    MedlinePLUS

    ... Awards Enhancing Diversity Find People About NINDS NINDS Multiple Sclerosis Information Page Condensed from Multiple Sclerosis: Hope Through ... en Español Additional resources from MedlinePlus What is Multiple Sclerosis? An unpredictable disease of the central nervous system, ...

  18. Multiple Sclerosis

    MedlinePLUS

    Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the ... attacks healthy cells in your body by mistake. Multiple sclerosis affects women more than men. It often begins ...

  19. Finger Multiplication

    ERIC Educational Resources Information Center

    Simanihuruk, Mudin

    2011-01-01

    Multiplication facts are difficult to teach. Therefore many researchers have put a great deal of effort into finding multiplication strategies. Sherin and Fuson (2005) provided a good survey paper on the multiplication strategies research area. Kolpas (2002), Rendtorff (1908), Dabell (2001), Musser (1966) and Markarian (2009) proposed the finger…

  20. SAMSN1 Is a Tumor Suppressor Gene in Multiple Myeloma12

    PubMed Central

    Noll, Jacqueline E.; Hewett, Duncan R.; Williams, Sharon A.; Vandyke, Kate; Kok, Chung; To, Luen B.; Zannettino, Andrew C.W.

    2014-01-01

    Multiple myeloma (MM), a hematological malignancy characterized by the clonal growth of malignant plasma cells (PCs) in the bone marrow, is preceded by the benign asymptomatic condition, monoclonal gammopathy of undetermined significance (MGUS). Several genetic abnormalities have been identified as critical for the development of MM; however, a number of these abnormalities are also found in patients with MGUS, indicating that there are other, as yet unidentified, factors that contribute to the onset of MM disease. In this study, we identify a Samsn1 gene deletion in the 5TGM1/C57BL/KaLwRij murine model of myeloma. In addition, SAMSN1 expression is reduced in the malignant CD138 + PCs of patients with MM and this reduced expression correlates to total PC burden. We identify promoter methylation as a potential mechanism through which SAMSN1 expression is modulated in human myeloma cell lines. Notably, re-expression of Samsn1 in the 5TGM1 murine PC line resulted in complete inhibition of MM disease development in vivo and decreased proliferation in stromal cell–PC co-cultures in vitro. This is the first study to identify deletion of a key gene in the C57BL/KaLwRij mice that also displays reduced gene expression in patients with MM and is therefore likely to play an integral role in MM disease development. PMID:25117979

  1. CRISPR/Cas9: a molecular Swiss army knife for simultaneous introduction of multiple genetic modifications in Saccharomyces cerevisiae.

    PubMed

    Mans, Robert; van Rossum, Harmen M; Wijsman, Melanie; Backx, Antoon; Kuijpers, Niels G A; van den Broek, Marcel; Daran-Lapujade, Pascale; Pronk, Jack T; van Maris, Antonius J A; Daran, Jean-Marc G

    2015-03-01

    A variety of techniques for strain engineering in Saccharomyces cerevisiae have recently been developed. However, especially when multiple genetic manipulations are required, strain construction is still a time-consuming process. This study describes new CRISPR/Cas9-based approaches for easy, fast strain construction in yeast and explores their potential for simultaneous introduction of multiple genetic modifications. An open-source tool (http://yeastriction.tnw.tudelft.nl) is presented for identification of suitable Cas9 target sites in S. cerevisiae strains. A transformation strategy, using in vivo assembly of a guideRNA plasmid and subsequent genetic modification, was successfully implemented with high accuracies. An alternative strategy, using in vitro assembled plasmids containing two gRNAs, was used to simultaneously introduce up to six genetic modifications in a single transformation step with high efficiencies. Where previous studies mainly focused on the use of CRISPR/Cas9 for gene inactivation, we demonstrate the versatility of CRISPR/Cas9-based engineering of yeast by achieving simultaneous integration of a multigene construct combined with gene deletion and the simultaneous introduction of two single-nucleotide mutations at different loci. Sets of standardized plasmids, as well as the web-based Yeastriction target-sequence identifier and primer-design tool, are made available to the yeast research community to facilitate fast, standardized and efficient application of the CRISPR/Cas9 system. PMID:25743786

  2. CRISPR/Cas9: a molecular Swiss army knife for simultaneous introduction of multiple genetic modifications in Saccharomyces cerevisiae

    PubMed Central

    Mans, Robert; van Rossum, Harmen M.; Wijsman, Melanie; Backx, Antoon; Kuijpers, Niels G.A.; van den Broek, Marcel; Daran-Lapujade, Pascale; Pronk, Jack T.; van Maris, Antonius J.A.; Daran, Jean-Marc G.

    2015-01-01

    A variety of techniques for strain engineering in Saccharomyces cerevisiae have recently been developed. However, especially when multiple genetic manipulations are required, strain construction is still a time-consuming process. This study describes new CRISPR/Cas9-based approaches for easy, fast strain construction in yeast and explores their potential for simultaneous introduction of multiple genetic modifications. An open-source tool (http://yeastriction.tnw.tudelft.nl) is presented for identification of suitable Cas9 target sites in S. cerevisiae strains. A transformation strategy, using in vivo assembly of a guideRNA plasmid and subsequent genetic modification, was successfully implemented with high accuracies. An alternative strategy, using in vitro assembled plasmids containing two gRNAs, was used to simultaneously introduce up to six genetic modifications in a single transformation step with high efficiencies. Where previous studies mainly focused on the use of CRISPR/Cas9 for gene inactivation, we demonstrate the versatility of CRISPR/Cas9-based engineering of yeast by achieving simultaneous integration of a multigene construct combined with gene deletion and the simultaneous introduction of two single-nucleotide mutations at different loci. Sets of standardized plasmids, as well as the web-based Yeastriction target-sequence identifier and primer-design tool, are made available to the yeast research community to facilitate fast, standardized and efficient application of the CRISPR/Cas9 system. PMID:25743786

  3. Characterization of Multiple Bistratified Retinal Ganglion Cells in A Purkinje Cell Protein 2-Cre Transgenic Mouse Line

    PubMed Central

    Ivanova, Elena; Lee, Patrick; Pan, Zhuo-Hua

    2012-01-01

    Retinal ganglion cells are categorized into multiple classes, including multiple types of bistratified ganglion cells (BGCs). The recent use of transgenic mouse lines with specific type(s) of ganglion cells that are labeled by fluorescent markers has facilitated the morphological and physiological studies of BGCs, particularly the directional-selective BGCs. The most important benefit from using transgenic animals is the capability to perform in vivo gene manipulation. In particular, the Cre/LoxP recombination system has become a powerful tool, allowing gene deletion, over-expression, and ectopic expression in a cell type-specific and temporally controlled fashion. The key to this tool is the availability of Cre mouse lines with cell or tissue type-specific expression of Cre recombinase. In this study, we characterized the Cre-positive retinal ganglion cells in a PCP2 (Purkinje cell protein 2)-cre mouse line. We found that all of the Cre-positive retinal ganglion cells were BGCs. Based on morphological criteria, we determined that they can be grouped into five types. The On- and Off-dendrites of three of these types stratified outside of the cholinergic bands and differed from directional selective ganglion cells (DSGCs) morphologically. These cells were negative for Brn-3b and positive for both calretinin and CART retina markers. The remaining two types were identified as putative On-Off and On-DSGCs. This Cre mouse line could be useful for further studies of the molecular and functional properties of BGCs in mice. PMID:23224947

  4. Multiple Trichofolliculomas Mimicking Multiple Trichoepitheliomas

    PubMed Central

    Nayak, Sudhir UK; Shenoi, Shrutakirthi D; Geetha, V; Prabhu, Smitha; Nagel, Bhawna

    2015-01-01

    Trichofolliculomas are benign hair follicle hamartomas which were initially considered as hair follicle tumors. Usually presenting as a solitary lesion associated with a tuft of vellus hairs, multiple trichofolliculomas are rare. Trichofolliculomas are characterized by a histopathological feature of dermal keratin cyst with cyst wall showing radiating hair follicles. We report this case for the rare presentation of multiple trichofolliculomas on the face which clinically mimicked multiple trichoepitheliomas. PMID:25814743

  5. Multiple myeloma

    MedlinePLUS

    Plasma cell dyscrasia; Plasma cell myeloma; Malignant plasmacytoma; Plasmacytoma of bone; Myeloma - multiple ... myeloma most commonly causes a low red blood cell count ( anemia ), which can lead to fatigue and ...

  6. Multiple Pregnancy

    MedlinePLUS

    ... is fertilized by a sperm, more than one embryo may implant and grow in your uterus . This ... fertilized egg splits, it results in multiple identical embryos. This type of pregnancy results in identical twins ( ...

  7. Multiple Nuclear Localization Signals Mediate Nuclear Localization of the GATA Transcription Factor AreA

    PubMed Central

    Hunter, Cameron C.; Siebert, Kendra S.; Downes, Damien J.; Wong, Koon Ho; Kreutzberger, Sara D.; Fraser, James A.; Clarke, David F.; Hynes, Michael J.; Davis, Meryl A.

    2014-01-01

    The Aspergillus nidulans GATA transcription factor AreA activates transcription of nitrogen metabolic genes in response to nitrogen limitation and is known to accumulate in the nucleus during nitrogen starvation. Sequence analysis of AreA revealed multiple nuclear localization signals (NLSs), five putative classical NLSs conserved in fungal AreA orthologs but not in the Saccharomyces cerevisiae functional orthologs Gln3p and Gat1p, and one putative noncanonical RRX33RXR bipartite NLS within the DNA-binding domain. In order to identify the functional NLSs in AreA, we constructed areA mutants with mutations in individual putative NLSs or combinations of putative NLSs and strains expressing green fluorescent protein (GFP)-AreA NLS fusion genes. Deletion of all five classical NLSs individually or collectively did not affect utilization of nitrogen sources or AreA-dependent gene expression and did not prevent AreA nuclear localization. Mutation of the bipartite NLS conferred the inability to utilize alternative nitrogen sources and abolished AreA-dependent gene expression likely due to effects on DNA binding but did not prevent AreA nuclear localization. Mutation of all six NLSs simultaneously prevented AreA nuclear accumulation. The bipartite NLS alone strongly directed GFP to the nucleus, whereas the classical NLSs collaborated to direct GFP to the nucleus. Therefore, AreA contains multiple conserved NLSs, which show redundancy and together function to mediate nuclear import. The noncanonical bipartite NLS is conserved in GATA factors from Aspergillus, yeast, and mammals, indicating an ancient origin. PMID:24562911

  8. Screening of point mutations by multiple SSCP analysis in the dystrophin gene

    SciTech Connect

    Lasa, A.; Baiget, M.; Gallano, P.

    1994-09-01

    Duchenne muscular dystrophy (DMD) is a lethal, X-linked neuromuscular disorder. The population frequency of DMD is one in approximately 3500 boys, of which one third is thought to be a new mutant. The DMD gene is the largest known to date, spanning over 2,3 Mb in band Xp21.2; 79 exons are transcribed into a 14 Kb mRNA coding for a protein of 427 kD which has been named dystrophin. It has been shown that about 65% of affected boys have a gene deletion with a wide variation in localization and size. The remaining affected individuals who have no detectable deletions or duplications would probably carry more subtle mutations that are difficult to detect. These mutations occur in several different exons and seem to be unique to single patients. Their identification represents a formidable goal because of the large size and complexity of the dystrophin gene. SSCP is a very efficient method for the detection of point mutations if the parameters that affect the separation of the strands are optimized for a particular DNA fragment. The multiple SSCP allows the simultaneous study of several exons, and implies the use of different conditions because no single set of conditions will be optimal for all fragments. Seventy-eight DMD patients with no deletion or duplication in the dystrophin gene were selected for the multiple SSCP analysis. Genomic DNA from these patients was amplified using the primers described for the diagnosis procedure (muscle promoter and exons 3, 8, 12, 16, 17, 19, 32, 45, 48 and 51). We have observed different mobility shifts in bands corresponding to exons 8, 12, 43 and 51. In exons 17 and 45, altered electrophoretic patterns were found in different samples identifying polymorphisms already described.

  9. Multiple Sclerosis.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on multiple sclerosis is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  10. Myeloma (multiple)

    PubMed Central

    2006-01-01

    Introduction Multiple myeloma is the most common primary cancer of the bones in adults, representing about 1% of all cancers diagnosed in the US in 2004, and 14% of all haematological malignancies. In the UK, multiple myeloma accounts for 1% of all new cases of cancer diagnosed each year. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatment in people with asymptomatic early stage multiple myeloma (stage I)? What are the effects of first-line treatments in people with advanced stage multiple myeloma (stages II and III)? What are the effect of salvage treatments, or supportive therapy, in people with advanced stage multiple myeloma (stages II and III)? We searched: Medline, Embase, The Cochrane Library and other important databases up to November 2004 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 71 systematic reviews, RCTs, or observational studies that met our inclusion criteria. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: allogenic transplant (non-myeloablative), autologous stem cell transplant (early or late transplantation, double or single, purging of), bisphosphonates, bone marrow stem cells, bortezomib, chemotherapy (combination, conventional dose, intermediate dose plus stem cell rescue, high-dose plus stem cell rescue), combination chemotherapy plus corticosteroids, deferred treatment (in stage I disease), early chemotherapy plus corticosteroids (in stage I disease), epoetin alpha, first-line treatments, infection prophylaxis, interferon, maintenance therapy (in advanced multiple myeloma), melphalan (normal dose, high dose before autologous stem cell transplantation, plus total body irradiation), optimum priming regimen, peripheral blood stem cells, plasmapheresis, salvage therapy regimens, single-agent chemotherapy (adding prednisolone), single-agent chemotherapy (bendamustine, melphalan, cyclophosphamide, lomustine, carmustine) with or without corticosteroid (prednisolone, dexamethasone), syngeneic transplantation, and thalidomide (and derivatives).

  11. Multiple myeloma

    PubMed Central

    Rajkumar, S. Vincent

    2008-01-01

    Multiple myeloma is a clonal plasma cell malignancy that accounts for slightly more than 10% of all hematologic cancers. In this paper, we present a historically focused review of the disease, from the description of the first case in 1844 to the present. The evolution of drug therapy and stem-cell transplantation for the treatment of myeloma, as well as the development of new agents, is discussed. We also provide an update on current concepts of diagnosis and therapy, with an emphasis on how treatments have emerged from a historical perspective after certain important discoveries and the results of experimental studies. PMID:18332230

  12. Multiple sclerosis.

    PubMed

    Files, Daniel Kane; Jausurawong, Tani; Katrajian, Ruba; Danoff, Robert

    2015-06-01

    Multiple sclerosis (MS) is a chronic, debilitating disease that can have devastating effects. Presentation varies widely in symptoms, pace, and progression. In addition to a thorough history and physical examination, diagnostic tools required to diagnose MS and exclude other diagnoses include MRI, evoked potential testing, and cerebrospinal fluid analysis. Although the disease is not curable presently, quality of life can be improved by minimizing the frequency and severity of disease burden. Disease modification, symptom management, preservation of function, and treatment of psychosocial issues are paramount to enhance the quality of life for the patient affected with MS. PMID:25979578

  13. Gene Deletions Resulting in Increased Nitrogen Release by Azotobacter vinelandii: Application of a Novel Nitrogen Biosensor

    PubMed Central

    Eberhart, Lauren J.; Ohlert, Janet M.; Knutson, Carolann M.; Plunkett, Mary H.

    2015-01-01

    Azotobacter vinelandii is a widely studied model diazotrophic (nitrogen-fixing) bacterium and also an obligate aerobe, differentiating it from many other diazotrophs that require environments low in oxygen for the function of the nitrogenase. As a free-living bacterium, A. vinelandii has evolved enzymes and transporters to minimize the loss of fixed nitrogen to the surrounding environment. In this study, we pursued efforts to target specific enzymes and further developed screens to identify individual colonies of A. vinelandii producing elevated levels of extracellular nitrogen. Targeted deletions were done to convert urea into a terminal product by disrupting the urease genes that influence the ability of A. vinelandii to recycle the urea nitrogen within the cell. Construction of a nitrogen biosensor strain was done to rapidly screen several thousand colonies disrupted by transposon insertional mutagenesis to identify strains with increased extracellular nitrogen production. Several disruptions were identified in the ammonium transporter gene amtB that resulted in the production of sufficient levels of extracellular nitrogen to support the growth of the biosensor strain. Further studies substituting the biosensor strain with the green alga Chlorella sorokiniana confirmed that levels of nitrogen produced were sufficient to support the growth of this organism when the medium was supplemented with sufficient sucrose to support the growth of the A. vinelandii in coculture. The nature and quantities of nitrogen released by urease and amtB disruptions were further compared to strains reported in previous efforts that altered the nifLA regulatory system to produce elevated levels of ammonium. These results reveal alternative approaches that can be used in various combinations to yield new strains that might have further application in biofertilizer schemes. PMID:25888177

  14. TIM2 Gene Deletion Results in Susceptibility to Cisplatin-Induced Kidney Toxicity

    PubMed Central

    Krishnamoorthy, Aparna; Clement, Matthew E.; O'leary, Eileen; Bonventre, Joseph V.; Vaidya, Vishal S.

    2010-01-01

    T-cell Immunoglobulin and Mucin domain 2 (TIM2) belongs to the receptor family of cell surface molecules expressed on kidney, liver, and T cells. Previous studies have revealed that TIM2-deficient mice (TIM2?/?) are more susceptible to the Th2-mediated immune response in an airway inflammation model. Here, we investigated the phenotypic response of TIM2?/? mice to cisplatin-induced kidney toxicity. A lethality study in male BALB/c wild-type (TIM2+/+) and TIM2?/? mice, administered with 20 mg/kg cisplatin ip, resulted in 80% mortality of TIM2?/? mice as compared with 30% mortality in the TIM2+/+ group by day 5. The TIM2?/? mice showed approximately fivefold higher injury as estimated by blood urea nitrogen and serum creatinine at 48 h that was confirmed by significantly increased proximal tubular damage assessed histologically (H & E staining). A significantly higher expression of Th2-associated cytokines, TNF-?, IL-1?, IL-6, and TGF?, with a significant reduction of Th1-associated cytokines, RANTES and MCP-1, by 72 h was observed in the TIM2?/? mice as compared with TIM2+/+ mice. A higher baseline protein expression of caspase-3 (approximately twofold) coupled with an early onset of p53 protein activation by 48 h resulted in an increased apoptosis by 48–72 h in TIM2?/? compared with TIM2+/+. In conclusion, the increased expression of the proinflammatory and proapoptotic genes, with a higher number of apoptotic cells, and a pronounced increase in injury and mortality of the TIM2-deficient mice collectively suggest a protective role of TIM2 in cisplatin-induced nephrotoxicity. PMID:20702592

  15. Relatively low proportion of dystrophin gene deletions in Israeili Duchenne and Becker muscular dystrophy patients

    SciTech Connect

    Shomrat, R.; Gluck, E.; Legum, C.; Shiloh, Y.

    1994-02-15

    Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic disorders caused by mutations in the X-linked dystrophin gene. The most common mutations in western populations are deletions that are spread non-randomly throughout the gene. Molecular analysis of the dystrophin gene structure by hybridization of the full length cDNA to Southern blots and by PCR in 62 unrelated Israeli male DMD/BMD patients showed deletions in 23 (37%). This proportion is significantly lower than that found in European and North American populations (55-65%). Seventy-eight percent of the deletions were confined to exons 44-52, half of these exons 44-45, and the remaining 22% to exons 1 and 19. There was no correlation between the size of the deletion and the severity of the disease. All the deletions causing frameshift resulted in the DMD phenotypes. 43 refs., 1 fig., 1 tab.

  16. Prevalence of the Prefoldin Subunit 5 Gene Deletion in Canine Mammary Tumors

    PubMed Central

    Bornemann-Kolatzki, Kirsten; Neumann, Stephan; Escobar, Hugo Murua; Nolte, Ingo; Hammer, Susanne Conradine; Hewicker-Trautwein, Marion; Junginger, Johannes; Kaup, Franz-Josef; Brenig, Bertram; Schütz, Ekkehard

    2015-01-01

    Background A somatic deletion at the proximal end of canine chromosome 27 (CFA27) was recently reported in 50% of malignant mammary tumors. This region harbours the tumor suppressor gene prefoldin subunit 5 (PFDN5) and the deletion correlated with a higher Ki-67 score. PFDN5 has been described to repress c-MYC and is, therefore, a candidate tumor-suppressor and cancer-driver gene in canine mammary cancer. Aim of this study was to confirm the recurrent deletion in a larger number of tumors. Methods Droplet digital PCR for PFDN5 was performed in DNA from 102 malignant, 40 benign mammary tumors/dysplasias, 11 non-neoplastic mammary tissues and each corresponding genomic DNA from leukocytes. The copy number of PFDN5 was normalized to a reference amplicon on canine chromosome 32 (CFA32). Z-scores were calculated, based on Gaussian distributed normalized PFDN5 copy numbers of the leukocyte DNA. Z-scores ? -3.0 in tissue were considered as being indicative of the PFDN5 deletion and called as such. The Ki-67 proliferation index was assessed in a subset of 79 tissue samples by immunohistochemistry. Results The deletion was confirmed in 24% of all malignant tumors, detected in only 7.5% of the benign tumors and was not present in any normal mammary tissue sample. The subgroup of solid carcinomas (n = 9) showed the highest frequency of the deletion (67%) and those malignomas without microscopical high fraction of benign tissue (n = 71) had a 32% frequency (p<0.01 vs. benign samples). The Ki-67 score was found to be significantly higher (p<0.05) in the PFDN5-deleted group compared to malignant tumors without the deletion. Conclusions A somatic deletion of the PFDN5 gene is recurrently present in canine mammary cancer, supporting a potential role in carcinogenesis. The association of this deletion with higher Ki-67 indicates an increased proliferation rate and thus a link to tumor aggressiveness can be hypothesized. The confirmation of earlier results warrants further studies on PFDN5 as cancer-driver gene. PMID:26132936

  17. 5S RRNA GENE DELETIONS CAUSE AN UNEXPECTEDLY HIGH FITNESS LOSS IN ESCHERICHIA COLI. (R825354)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  18. Proteomics and bioinformatics analysis of mouse hypothalamic neurogenesis with or without EPHX2 gene deletion

    PubMed Central

    Zhong, Lijun; Zhou, Juntuo; Wang, Dawei; Zou, Xiajuan; Lou, Yaxin; Liu, Dan; Yang, Bin; Zhu, Yi; Li, Xiaoxia

    2015-01-01

    The aim of this study was to identify differently expressed proteins in the presence and absence of EPHX2 gene in mouse hypothalamus using proteomics profiling and bioinformatics analysis. This study was performed on 3 wild type (WT) and 3 EPHX2 gene global knockout (KO) mice (EPHX2 -/-). Using the nano- electrospray ionization (ESI)-LC-MS/MS detector, we identified 31 over-expressed proteins in WT mouse hypothalamus compared to the KO counterparts. Gene Ontology (GO) annotation in terms of the protein-protein interaction network indicated that cellular metabolic process, protein metabolic process, signaling transduction and protein post-translation biological processes involved in EPHX2 -/- regulatory network. In addition, signaling pathway enrichment analysis also highlighted chronic neurodegenerative diseases and some other signaling pathways, such as TGF-beta signaling pathway, T cell receptor signaling pathway, ErbB signaling pathway, Neurotrophin signaling pathway and MAPK signaling pathway, were strongly coupled with EPHX2 gene knockout. Further studies into the molecular functions of EPHX2 gene in hypothalamus will help to provide new perspective in neurogenesis. PMID:26722453

  19. Gene Deletion of VIP Leads to Increased Mortality Associated with Progressive Right Ventricular Hypertrophy

    PubMed Central

    Szema, Anthony M.; Hamidi, Sayyed A.

    2014-01-01

    Vasoactive Intestinal Peptide (VIP) knockout mice exhibit asthma, pulmonary hypertension, and left ventricular wall thinning. Humans with these disorders have premature death. We show here that VIP KO mice have reduced survival (100% mortality at 20 months), vs. 100% survival among WT C57BL/6 mice. Moreover, the ratios of weights of right ventricle divided by left ventricle plus septum were progressively increased in VIP KO mice with age. Core temperatures were lower in VIP KO mice when compared to WT littermates, with an associated pro-inflammatory cytokine milieu. Overall, our results indicate that VIP is important for survival in mice. Its absence leads to increased mortality, with progressive right ventricular hypertrophy as a surrogate of pulmonary hypertension, lower body weight, hypothermia, and pro-inflammatory milieu. These studies support VIP as a novel therapeutic agent in pulmonary hypertension. PMID:24860842

  20. A glycoprotein E gene-deleted bovine herpesvirus 1 as a candidate vaccine strain

    PubMed Central

    Weiss, M.; Brum, M.C.S.; Anziliero, D.; Weiblen, R.; Flores, E.F.

    2015-01-01

    A bovine herpesvirus 1 (BoHV-1) defective in glycoprotein E (gE) was constructed from a Brazilian genital BoHV-1 isolate, by replacing the full gE coding region with the green fluorescent protein (GFP) gene for selection. Upon co-transfection of MDBK cells with genomic viral DNA plus the GFP-bearing gE-deletion plasmid, three fluorescent recombinant clones were obtained out of approximately 5000 viral plaques. Deletion of the gE gene and the presence of the GFP marker in the genome of recombinant viruses were confirmed by PCR. Despite forming smaller plaques, the BoHV-1?gE recombinants replicated in MDBK cells with similar kinetics and to similar titers to that of the parental virus (SV56/90), demonstrating that the gE deletion had no deleterious effects on replication efficacy in vitro. Thirteen calves inoculated intramuscularly with BoHV-1?gE developed virus neutralizing antibodies at day 42 post-infection (titers from 2 to 16), demonstrating the ability of the recombinant to replicate and to induce a serological response in vivo. Furthermore, the serological response induced by recombinant BoHV-1?gE could be differentiated from that induced by wild-type BoHV-1 by the use of an anti-gE antibody ELISA kit. Taken together, these results indicated the potential application of recombinant BoHV-1 ?gE in vaccine formulations to prevent the losses caused by BoHV-1 infections while allowing for differentiation of vaccinated from naturally infected animals. PMID:26200229

  1. A glycoprotein E gene-deleted bovine herpesvirus 1 as a candidate vaccine strain.

    PubMed

    Weiss, M; Brum, M C S; Anziliero, D; Weiblen, R; Flores, E F

    2015-09-01

    A bovine herpesvirus 1 (BoHV-1) defective in glycoprotein E (gE) was constructed from a Brazilian genital BoHV-1 isolate, by replacing the full gE coding region with the green fluorescent protein (GFP) gene for selection. Upon co-transfection of MDBK cells with genomic viral DNA plus the GFP-bearing gE-deletion plasmid, three fluorescent recombinant clones were obtained out of approximately 5000 viral plaques. Deletion of the gE gene and the presence of the GFP marker in the genome of recombinant viruses were confirmed by PCR. Despite forming smaller plaques, the BoHV-1?gE recombinants replicated in MDBK cells with similar kinetics and to similar titers to that of the parental virus (SV56/90), demonstrating that the gE deletion had no deleterious effects on replication efficacy in vitro. Thirteen calves inoculated intramuscularly with BoHV-1?gE developed virus neutralizing antibodies at day 42 post-infection (titers from 2 to 16), demonstrating the ability of the recombinant to replicate and to induce a serological response in vivo. Furthermore, the serological response induced by recombinant BoHV-1?gE could be differentiated from that induced by wild-type BoHV-1 by the use of an anti-gE antibody ELISA kit. Taken together, these results indicated the potential application of recombinant BoHV-1 ?gE in vaccine formulations to prevent the losses caused by BoHV-1 infections while allowing for differentiation of vaccinated from naturally infected animals. PMID:26200229

  2. Novel human CYP2A6 alleles confound gene deletion analysis.

    PubMed

    Nakajima, Miki; Yoshida, Ryoko; Fukami, Tatsuki; McLeod, Howard L; Yokoi, Tsuyoshi

    2004-07-01

    Cytochrome P450 (CYP) 2A6 metabolizes a number of drugs and a variety of procarcinogens. CYP2A6 also catalyzes nicotine C-oxidation leading to cotinine formation, a major metabolic pathway of nicotine in humans. There are genetic polymorphisms in the human CYP2A6 gene and a relationship between the CYP2A6 genotype and smoking habits as well as the incidence of lung cancer has been indicated. CYP2A6*4 alleles are the whole deleted type and are completely deficient in the enzymatic activity. An unequal crossover junction is located in the 3'-flanking region in the CYP2A6*4A allele, whereas the junction is located in either intron 8 or exon 9 in the CYP2A6*4D allele. In the present study, a novel genotyping method to distinguish between two different whole deleted alleles of CYP2A6*4A and CYP2A6*4D was established. In the process, two novel alleles, CYP2A6*1F and CYP2A6*1G, were found. The CYP2A6*1F has a single nucleotide polymorphism (SNP) of C5717T in exon 8, and the CYP2A6*1G has two SNPs, C5717T in exon 8 and A5825G in intron 8. The SNP of C5717T corresponds to C1224T on the cDNA sequence and is a synonymous mutation. Since the CYP2A6*1F produces a recognition site of the restriction enzymes that is the same as CYP2A6*4D, the presence of the CYP2A6*1F allele could cause a mistyping as the CYP2A6*4D allele. According to an improved genotyping method, the allele frequencies of CYP2A6*4A, CYP2A6*4D, CYP2A6*1F, and CYP2A6*1G in 165 Caucasians were 3.0%, 0%, 1.8%, and 1.2%, respectively. The allele frequencies of CYP2A6*4A, CYP2A6*4D, CYP2A6*1F, and CYP2A6*1G in 94 African-Americans were 0%, 0.5%, 0%, and 13.3%, respectively. This is the first report of a method that can distinguish between CYP2A6*4A, CYP2A6*4D, and CYP2A6*1F which could otherwise cause a mistyping as CYP2A6*4D. PMID:15225612

  3. Partial gene deletion in LEC rat: An animal model for Wilson disease

    SciTech Connect

    Wu, J.; Forbes, J.R.; Cox, D.W.

    1994-09-01

    Wilson disease is an inherited disorder of copper transport in which incorporation of copper into ceruloplasmin and excretion of copper into bile are greatly reduced. Copper accumulates to a toxic level in the liver and also in the brain and kidney, causing a spectrum of hepatic and neurological abnormalities. We have recently cloned the gene for Wilson disease (designated ATP7B), which encodes a putative copper-transporting P-type ATPase. The inbred mutant Long-Evans Cinnamon (LEC) rat strain shows similarity to Wilson disease in many clinical and biochemical features. We have cloned cDNAs for the rat homologue (Atp7b) of the human Wilson disease gene (ATP7B) and have shown that the two genes have {approximately}82% identity at the amino acid sequence level. Rat cDNA sequences were used to identify a partial deletion in the Atp7b gene in the LEC rat. The deletion removes at least 750 bp of the coding region at the 3{prime} end, which includes the crucial ATP binding domain and extends downstream of the gene. The proximal breakpoint has been precisely localized at the cDNA level. Our results provide convincing evidence that the LEC rat is an animal model for Wilson disease. This model will be important for studying liver pathophysiology, for developing therapy for Wilson disease, and for studying the pathway of copper transport and its possible interaction with other heavy metals.

  4. PCR detection of retinoblastoma gene deletions in radiation-induced mouse lung adenocarcinomas

    SciTech Connect

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1994-05-01

    From 1971--1986, Argonne National Laboratory conducted a series of large-scale studies of tumor incidence in 40,000 BCF{sub 1} mice irradiated with {sup 60}Co {gamma}-rays or JANUS fission-spectrum neutrons. Polymerase chain reaction (PCR) technique was used to detect deletions in the mouse retinoblastoma (mRb) gene. Six mRb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. Absence of any of these fragments on a Southern blot indicated a deletion of that portion of the mRb gene. Tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death in post-mortem analyses. Spontaneous tumors as well as those from irradiated mice were analyzed for mRb deletions. In all normal mouse tissues studies all six mRb exon fragments were present on Southern blots. Tumors in six neutron-irradiated mice also had no mRb deletions. However, 1 of 6 tumors from {gamma}-irradiated mice and 6 of 18 spontaneous tumors from unirradiated mice showed a deletion in one or both mRb alleles. All deletions detected were in the 5{prime} region of the mRb gene.

  5. Forebrain glucocorticoid receptor gene deletion attenuates behavioral changes and antidepressant responsiveness during chronic stress

    PubMed Central

    Jacobson, Lauren

    2014-01-01

    Stress is an important risk factor for mood disorders. Stress also stimulates the secretion of glucocorticoids, which have been found to influence mood. To determine the role of forebrain glucocorticoid receptors (GR) in behavioral responses to chronic stress, the present experiments compared behavioral effects of repeated social defeat in mice with forebrain GR deletion and in floxed GR littermate controls. Repeated defeat produced alterations in forced swim and tail suspension immobility in floxed GR mice that did not occur in mice with forebrain GR deletion. Defeat-induced changes in immobility in floxed GR mice were prevented by chronic antidepressant treatment, indicating that these behaviors were dysphoria-related. In contrast, although mice with forebrain GR deletion exhibited antidepressant-induced decreases in tail suspension immobility in the absence of stress, this response did not occur in mice with forebrain GR deletion after defeat. There were no marked differences in plasma corticosterone between genotypes, suggesting that behavioral differences depended on forebrain GR rather than on abnormal glucocorticoid secretion. Defeat-induced gene expression of the neuronal activity marker c-fos in the ventral hippocampus, paraventricular thalamus and lateral septum correlated with genotype-related differences in behavioral effects of defeat, whereas c-fos induction in the nucleus accumbens and central and basolateral amygdala correlated with genotype-related differences in behavioral responses to antidepressant treatment. The dependence of both negative (dysphoria-related) and positive (antidepressant-induced) behaviors on forebrain GR is consistent with the contradictory effects of glucocorticoids on mood, and implicates these or other forebrain regions in these effects. PMID:25168761

  6. SPC-Cre-ERT2 transgenic mouse for temporal gene deletion in alveolar epithelial cells.

    PubMed

    Gui, Yao-Song; Wang, Lianmei; Tian, Xinlun; Feng, Ruie; Ma, Aiping; Cai, Baiqiang; Zhang, Hongbing; Xu, Kai-Feng

    2012-01-01

    Although several Cre-loxP-based gene knockout mouse models have been generated for the study of gene function in alveolar epithelia in the lung, their applications are still limited. In this study, we developed a SPC-Cre-ER(T2) mouse model, in which a tamoxifen-inducible Cre recombinase (Cre-ER(T2)) is under the control of the human surfactant protein C (SPC) promoter. The specificity and efficiency of Cre-ER(T2) activity was first evaluated by crossing SPC-Cre-ER(T2) mouse with ROSA26R mouse, a ?-galactosidase reporter strain. We found that Cre-ER(T2) was expressed in 30.7% type II alveolar epithelial cells of SPC-Cre-ER(T2)/ROSA26R mouse lung tissues in the presence of tamoxifen. We then tested the tamoxifen-inducible recombinase activity of Cre-ER(T2) in a mouse strain bearing TSC1 conditional knockout alleles (TSC1(fx/fx)). TSC1 deletion was detected in the lungs of tamoxifen treated SPC-Cre-ER(T2)/TSC1(fx/fx) mice. Therefore this SPC-Cre-ER(T2) mouse model may be a valuable tool to investigate functions of genes in lung development, physiology and disease. PMID:23049940

  7. Current aspects of therapeutic reduction mammaplasty for immediate early breast cancer management: An update

    PubMed Central

    Munhoz, Alexandre Mendonça; Montag, Eduardo; Gemperli, Rolf

    2014-01-01

    Breast-conservation surgery (BCS) is established as a safe surgical treatment for most patients with early breast cancer. Recently, advances in oncoplastic techniques are capable of preserving the breast form and quality of life. Although most BCS defects can be managed with primary closure, the aesthetic outcome may be unpredictable. Among technical options, therapeutic reduction mammaplasty (TRM) remains a useful procedure since the BCS defect can be repaired and the preoperative appearance can be improved, resulting in more proportional breasts. As a consequence of rich breast tissue vascularization, the greater part of reduction techniques have based their planning on preserving the pedicle of the nipple-areola complex after tumor removal. Reliable circulation and improvement of a conical shape to the breast are commonly described in TRM reconstructions. With an immediate approach, the surgical process is smooth since both procedures can be carried out in one operative setting. Additionally, it permits wider excision of the tumor, with a superior mean volume of the specimen and potentially reduces the incidence of margin involvement. Regardless of the fact that there is no consensus concerning the best TRM technique, the criteria is determined by the surgeon’s experience, the extent/location of glandular tissue resection and the size of the defect in relation to the size of the remaining breast. The main advantages of the technique utilized should include reproducibility, low interference with the oncological treatment and long-term results. The success of the procedure depends on patient selection, coordinated planning and careful intra-operative management. PMID:24527398

  8. Current aspects of therapeutic reduction mammaplasty for immediate early breast cancer management: An update.

    PubMed

    Munhoz, Alexandre Mendonça; Montag, Eduardo; Gemperli, Rolf

    2014-02-10

    Breast-conservation surgery (BCS) is established as a safe surgical treatment for most patients with early breast cancer. Recently, advances in oncoplastic techniques are capable of preserving the breast form and quality of life. Although most BCS defects can be managed with primary closure, the aesthetic outcome may be unpredictable. Among technical options, therapeutic reduction mammaplasty (TRM) remains a useful procedure since the BCS defect can be repaired and the preoperative appearance can be improved, resulting in more proportional breasts. As a consequence of rich breast tissue vascularization, the greater part of reduction techniques have based their planning on preserving the pedicle of the nipple-areola complex after tumor removal. Reliable circulation and improvement of a conical shape to the breast are commonly described in TRM reconstructions. With an immediate approach, the surgical process is smooth since both procedures can be carried out in one operative setting. Additionally, it permits wider excision of the tumor, with a superior mean volume of the specimen and potentially reduces the incidence of margin involvement. Regardless of the fact that there is no consensus concerning the best TRM technique, the criteria is determined by the surgeon's experience, the extent/location of glandular tissue resection and the size of the defect in relation to the size of the remaining breast. The main advantages of the technique utilized should include reproducibility, low interference with the oncological treatment and long-term results. The success of the procedure depends on patient selection, coordinated planning and careful intra-operative management. PMID:24527398

  9. Immediate, Early, and Conventional Implant Placement in a Patient with History of Periodontitis

    PubMed Central

    Lanza, Alessandro; Scognamiglio, Fabio; Femiano, Felice; Lanza, Michele

    2015-01-01

    The aim of this paper is to describe a case of implant-prosthetic rehabilitation in a patient with periodontitis, focusing on the different timing of implant placement. After initial periodontal treatment, teeth with advanced mobility degree and severe bone resorption were extracted. At different healing time oral implants were placed in a prosthetic-guided position. After osseointegration period the implants were loaded and the results at one year of follow-up are presented. PMID:25949833

  10. Immediate early responses of avian tracheal epithelial cells to infection with highly pathogenic avian influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic (HP) avian influenza viruses (AIV) present an on going threat to the U.S. poultry industry. In order to develop new AIV control strategies it is necessary to understand the underlying mechanism of viral infection. Because the early events of AIV infection can occur on tracheal ep...

  11. Water deprivation-induced sodium appetite: humoral and cardiovascular mediators and immediate early genes

    NASA Technical Reports Server (NTRS)

    De Luca, Laurival A Jr; Xu, Zhice; Schoorlemmer, Guus H M.; Thunhorst, Robert L.; Beltz, Terry G.; Menani, Jose V.; Johnson, Alan Kim

    2002-01-01

    Adult rats deprived of water for 24-30 h were allowed to rehydrate by ingesting only water for 1-2 h. Rats were then given access to both water and 1.8% NaCl. This procedure induced a sodium appetite defined by the operational criteria of a significant increase in 1.8% NaCl intake (3.8 +/- 0.8 ml/2 h; n = 6). Expression of Fos (as assessed by immunohistochemistry) was increased in the organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus (MnPO), subfornical organ (SFO), and supraoptic nucleus (SON) after water deprivation. After rehydration with water but before consumption of 1.8% NaCl, Fos expression in the SON disappeared and was partially reduced in the OVLT and MnPO. However, Fos expression did not change in the SFO. Water deprivation also 1) increased plasma renin activity (PRA), osmolality, and plasma Na+; 2) decreased blood volume; and 3) reduced total body Na+; but 4) did not alter arterial blood pressure. Rehydration with water alone caused only plasma osmolality and plasma Na+ concentration to revert to euhydrated levels. The changes in Fos expression and PRA are consistent with a proposed role for ANG II in the control of the sodium appetite produced by water deprivation followed by rehydration with only water.

  12. Immediate early responses of avian tracheal epithelial cells to infection with highly pathogenic avian invluenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic (HP) avian influenza viruses (AIV) present an ongoing threat to the world poultry industry. In order to develop new AIV control strategies it is necessary to understand the underlying mechanism of viral infection at mucosal respiratory sites. Chicken and duck tracheal epithelial ...

  13. Pretransplant immediately early-1-specific T cell responses provide protection for CMV infection after kidney transplantation.

    PubMed

    Bestard, O; Lucia, M; Crespo, E; Van Liempt, B; Palacio, D; Melilli, E; Torras, J; Llaudó, I; Cerezo, G; Taco, O; Gil-Vernet, S; Grinyó, J M; Cruzado, J M

    2013-07-01

    Cytomegalovirus (CMV) infection is still a major complication after kidney transplantation. Although cytotoxic CMV-specific T cells play a crucial role controlling CMV survival and replication, current pretransplant risk assessment for CMV infection is only based on donor/recipient (IgG)-serostatus. Here, we evaluated the usefulness of monitoring pre- and 6-month CMV-specific T cell responses against two dominant CMV antigens (IE-1 and pp65) and a CMV lysate, using an IFN-? Elispot, for predicting the advent of CMV infection in two cohorts of 137 kidney transplant recipients either receiving routine prophylaxis (n = 39) or preemptive treatment (n = 98). Incidence of CMV antigenemia/disease within the prophylaxis and preemptive group was 28%/20% and 22%/12%, respectively. Patients developing CMV infection showed significantly lower anti-IE-1-specific T cell responses than those that did not in both groups (p < 0.05). In a ROC curve analysis, low pretransplant anti-IE-1-specific T cell responses predicted the risk of both primary and late-onset CMV infection with high sensitivity and specificity (AUC > 0.70). Furthermore, when using most sensitive and specific Elispot cut-off values, a higher than 80% and 90% sensitivity and negative predictive value was obtained, respectively. Monitoring IE-1-specific T cell responses before transplantation may be useful for predicting posttransplant risk of CMV infection, thus potentially guiding decision-making regarding CMV preventive treatment. PMID:23711167

  14. Immediate early gene activation in hippocampus and dorsal striatum: Effects of explicit place and response training

    E-print Network

    , Department of Psychology, Box 351525, Guthrie Hall, Seattle, WA 98195, USA Received 11 September 2006 of performance during post-testing probe trials. Quantification of Zif268-IR in both hippocampus and striatum, but not 90 min, post-testing. The synthesis of c-Fos early in testing could reflect the recruitment of key

  15. Multiple Myeloma Symptoms

    MedlinePLUS

    ... ET. CALL NOW Home » About Multiple Myeloma » Symptoms Multiple Myeloma Symptoms Multiple myeloma symptoms may vary by patient, ... to be managed or prevented. The most common multiple myeloma symptoms may include: • Bone pain or bone fractures • ...

  16. Multiple osteochondromas.

    PubMed

    Bovée, Judith V M G

    2008-01-01

    Multiple osteochondromas (MO) is characterised by development of two or more cartilage capped bony outgrowths (osteochondromas) of the long bones. The prevalence is estimated at 1:50,000, and it seems to be higher in males (male-to-female ratio 1.5:1). Osteochondromas develop and increase in size in the first decade of life, ceasing to grow when the growth plates close at puberty. They are pedunculated or sessile (broad base) and can vary widely in size. The number of osteochondromas may vary significantly within and between families, the mean number of locations is 15-18. The majority are asymptomatic and located in bones that develop from cartilage, especially the long bones of the extremities, predominantly around the knee. The facial bones are not affected. Osteochondromas may cause pain, functional problems and deformities, especially of the forearm, that may be reason for surgical removal. The most important complication is malignant transformation of osteochondroma towards secondary peripheral chondrosarcoma, which is estimated to occur in 0.5-5%. MO is an autosomal dominant disorder and is genetically heterogeneous. In almost 90% of MO patients germline mutations in the tumour suppressor genes EXT1 or EXT2 are found. The EXT genes encode glycosyltransferases, catalyzing heparan sulphate polymerization. The diagnosis is based on radiological and clinical documentation, supplemented with, if available, histological evaluation of osteochondromas. If the exact mutation is known antenatal diagnosis is technically possible. MO should be distinguished from metachondromatosis, dysplasia epiphysealis hemimelica and Ollier disease. Osteochondromas are benign lesions and do not affect life expectancy. Management includes removal of osteochondromas when they give complaints. Removed osteochondromas should be examined for malignant transformation towards secondary peripheral chondrosarcoma. Patients should be well instructed and regular follow-up for early detection of malignancy seems justified. For secondary peripheral chondrosarcoma, en-bloc resection of the lesion and its pseudocapsule with tumour-free margins, preferably in a bone tumour referral centre, should be performed. PMID:18271966

  17. Multiple alcohol dehydrogenases but no functional acetaldehyde dehydrogenase causing excessive acetaldehyde production from ethanol by oral streptococci

    PubMed Central

    Pavlova, Sylvia I.; Jin, Ling; Gasparovich, Stephen R.

    2013-01-01

    Ethanol consumption and poor oral hygiene are risk factors for oral and oesophageal cancers. Although oral streptococci have been found to produce excessive acetaldehyde from ethanol, little is known about the mechanism by which this carcinogen is produced. By screening 52 strains of diverse oral streptococcal species, we identified Streptococcus gordonii V2016 that produced the most acetaldehyde from ethanol. We then constructed gene deletion mutants in this strain and analysed them for alcohol and acetaldehyde dehydrogenases by zymograms. The results showed that S. gordonii V2016 expressed three primary alcohol dehydrogenases, AdhA, AdhB and AdhE, which all oxidize ethanol to acetaldehyde, but their preferred substrates were 1-propanol, 1-butanol and ethanol, respectively. Two additional dehydrogenases, S-AdhA and TdhA, were identified with specificities to the secondary alcohol 2-propanol and threonine, respectively, but not to ethanol. S. gordonii V2016 did not show a detectable acetaldehyde dehydrogenase even though its adhE gene encodes a putative bifunctional acetaldehyde/alcohol dehydrogenase. Mutants with adhE deletion showed greater tolerance to ethanol in comparison with the wild-type and mutant with adhA or adhB deletion, indicating that AdhE is the major alcohol dehydrogenase in S. gordonii. Analysis of 19 additional strains of S. gordonii, S. mitis, S. oralis, S. salivarius and S. sanguinis showed expressions of up to three alcohol dehydrogenases, but none showed detectable acetaldehyde dehydrogenase, except one strain that showed a novel ALDH. Therefore, expression of multiple alcohol dehydrogenases but no functional acetaldehyde dehydrogenase may contribute to excessive production of acetaldehyde from ethanol by certain oral streptococci. PMID:23637459

  18. Multiple alcohol dehydrogenases but no functional acetaldehyde dehydrogenase causing excessive acetaldehyde production from ethanol by oral streptococci.

    PubMed

    Pavlova, Sylvia I; Jin, Ling; Gasparovich, Stephen R; Tao, Lin

    2013-07-01

    Ethanol consumption and poor oral hygiene are risk factors for oral and oesophageal cancers. Although oral streptococci have been found to produce excessive acetaldehyde from ethanol, little is known about the mechanism by which this carcinogen is produced. By screening 52 strains of diverse oral streptococcal species, we identified Streptococcus gordonii V2016 that produced the most acetaldehyde from ethanol. We then constructed gene deletion mutants in this strain and analysed them for alcohol and acetaldehyde dehydrogenases by zymograms. The results showed that S. gordonii V2016 expressed three primary alcohol dehydrogenases, AdhA, AdhB and AdhE, which all oxidize ethanol to acetaldehyde, but their preferred substrates were 1-propanol, 1-butanol and ethanol, respectively. Two additional dehydrogenases, S-AdhA and TdhA, were identified with specificities to the secondary alcohol 2-propanol and threonine, respectively, but not to ethanol. S. gordonii V2016 did not show a detectable acetaldehyde dehydrogenase even though its adhE gene encodes a putative bifunctional acetaldehyde/alcohol dehydrogenase. Mutants with adhE deletion showed greater tolerance to ethanol in comparison with the wild-type and mutant with adhA or adhB deletion, indicating that AdhE is the major alcohol dehydrogenase in S. gordonii. Analysis of 19 additional strains of S. gordonii, S. mitis, S. oralis, S. salivarius and S. sanguinis showed expressions of up to three alcohol dehydrogenases, but none showed detectable acetaldehyde dehydrogenase, except one strain that showed a novel ALDH. Therefore, expression of multiple alcohol dehydrogenases but no functional acetaldehyde dehydrogenase may contribute to excessive production of acetaldehyde from ethanol by certain oral streptococci. PMID:23637459

  19. MultipleColposcopyJCO

    Cancer.gov

    Performing multiple biopsies during a procedure known as colposcopy—visual inspection of the cervix—is more effective than performing only a single biopsy of the worst-appearing area for detecting cervical cancer precursors. This multiple biopsy approach

  20. Depression and Multiple Sclerosis

    MedlinePLUS

    Depression - National Multiple Sclerosis Society Skip to navigation Skip to content Menu Navigation National Multiple Sclerosis Society ... Twitter Email Home Symptoms & Diagnosis MS Symptoms Depression Depression Share Smaller Text Larger Text Print In this ...

  1. Multiple sclerosis - discharge

    MedlinePLUS

    Your doctor has told you that you have multiple sclerosis. This disease affects the brain and spinal cord ( ... your doctor may prescribe medicine. Some people with multiple sclerosis need to use a urinary catheter . This is ...

  2. Multiple Myeloma Section

    Cancer.gov

    The Multiple Myeloma Section currently has several ongoing and upcoming protocols related to the molecular Natural History and novel treatments for Multiple Myeloma and its precursors - Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smolder

  3. Multiple Sclerosis International Federation

    MedlinePLUS

    ... MS support organisation Find support What is MS? Multiple sclerosis (MS) is a progressive disease of the nervous ... and mental health professionals Learn more Contact us Multiple Sclerosis International Federation 3rd Floor Skyline House 200 Union ...

  4. Characterization of baculovirus Autographa californica multiple nuclear polyhedrosis virus infection in mammalian cells

    SciTech Connect

    Kitajima, Masayuki; Hamazaki, Hiroyuki; Miyano-Kurosaki, Naoko; Takaku, Hiroshi . E-mail: hiroshi.takaku@it-chiba.ac.jp

    2006-05-05

    The baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) is used as a vector in many gene therapy studies. Wild-type AcMNPV infects many mammalian cell types in vitro, but does not replicate. We investigated the dynamics of AcMNPV genomic DNA in infected mammalian cells and used flow cytometric analysis to demonstrate that recombinant baculovirus containing a cytomegalovirus immediate early promoter/enhancer with green fluorescent protein (GFP) expressed high levels of GFP in Huh-7 cells, but not B16, Raw264.7, or YAC-1 cells. The addition of butyrate, a deacetylase inhibitor, markedly enhanced the percentage of GFP-expressing Huh-7 and B16 cells, but not Raw264.7 and YAC-1 cells. The addition of 5-aza-2'-deoxycytidine, a DNA methylation inhibitor, had no enhancing effect. Polymerase chain reaction analysis using AcMNPV-gp64-specific primers indicated that AcMNPV infected not only Huh-7 and B16 cells, but also Raw264.7 and YAC-1 cells in vitro. The genomic DNA was detected in Huh-7 and B16 cells 96 h after infection. Genomic AcMNPV DNA in YAC-1 cells was not transported to the nucleus. Luciferase assay indicated that AcMNPV p35 gene mRNA and p35 promoter activity were clearly expressed only in Huh-7 and B16 cells. These results suggest that viral genomic DNA expression is restricted by different host cell factors, such as degradation, deacetylation, and inhibition of nuclear transport, depending on the mammalian cell type.

  5. Reference genes for quantitative gene expression studies in multiple avian species.

    PubMed

    Olias, Philipp; Adam, Iris; Meyer, Anne; Scharff, Constance; Gruber, Achim D

    2014-01-01

    Quantitative real-time PCR (qPCR) rapidly and reliably quantifies gene expression levels across different experimental conditions. Selection of suitable reference genes is essential for meaningful normalization and thus correct interpretation of data. In recent years, an increasing number of avian species other than the chicken has been investigated molecularly, highlighting the need for an experimentally validated pan-avian primer set for reference genes. Here we report testing a set for 14 candidate reference genes (18S, ABL, GAPDH, GUSB, HMBS, HPRT, PGK1, RPL13, RPL19, RPS7, SDHA, TFRC, VIM, YWHAZ) on different tissues of the mallard (Anas platyrhynchos), domestic chicken (Gallus gallus domesticus), common crane (Grus grus), white-tailed eagle (Haliaeetus albicilla), domestic turkey (Meleagris gallopavo f. domestica), cockatiel (Nymphicus hollandicus), Humboldt penguin (Sphenicus humboldti), ostrich (Struthio camelus) and zebra finch (Taeniopygia guttata), spanning a broad range of the phylogenetic tree of birds. Primer pairs for six to 11 genes were successfully established for each of the nine species. As a proof of principle, we analyzed expression levels of 10 candidate reference genes as well as FOXP2 and the immediate early genes, EGR1 and CFOS, known to be rapidly induced by singing in the avian basal ganglia. We extracted RNA from microbiopsies of the striatal song nucleus Area X of adult male zebra finches after they had sang or remained silent. Using three different statistical algorithms, we identified five genes (18S, PGK1, RPS7, TFRC, YWHAZ) that were stably expressed within each group and also between the singing and silent conditions, establishing them as suitable reference genes. In conclusion, the newly developed pan-avian primer set allows accurate normalization and quantification of gene expression levels in multiple avian species. PMID:24926893

  6. Multiple Myeloma Section

    Cancer.gov

    The Multiple Myeloma Section The mission of the Multiple Myeloma Section of the NCI is to... Ola Landgren, M.D., Ph.D. Dr. Landgren is the director of the Clinical Program in the Multiple Myeloma Research Section.  He received his M.D. in 1995 and Ph.D. i

  7. The role of the PI3K-Akt signal transduction pathway in Autographa californica multiple nucleopolyhedrovirus infection of Spodoptera frugiperda cells

    SciTech Connect

    Xiao Wei; Yang Yi; Weng Qingbei; Lin Tiehao; Yuan Meijin; Yang Kai; Pang Yi

    2009-08-15

    Many viruses activate the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway, thereby modulating diverse downstream signaling pathways associated with antiapoptosis, proliferation, cell cycling, protein synthesis and glucose metabolism, in order to augment their replication. To date, the role of the PI3K-Akt pathway in Baculovirus replication has not been defined. In the present study, we demonstrate that infection of Sf9 cells with Autographa californica multiple nucleopolyhedrovirus (AcMNPV) elevated cellular Akt phosphorylation at 1 h post-infection. The maximum Akt phosphorylation occurred at 6 h post-infection and remained unchanged until 18 h post-infection. The PI3K-specific inhibitor, LY294002, suppressed Akt phosphorylation in a dose-dependent manner, suggesting that AcMNPV-induced Akt phosphorylation is PI3K-dependent. The inhibition of PI3K-Akt activation by LY294002 significantly reduced the viral yield, including a reduction in budded viruses and occlusion bodies. The virus production was reduced only when the inhibitor was added within 24 h of infection, implying that activation of PI3K occurred early in infection. Correspondingly, both viral DNA replication and late (VP39) and very late (POLH) viral protein expression were impaired by LY294002 treatment; LY294002 had no effect on immediate-early (IE1) and early-late (GP64) protein expression. These results demonstrate that the PI3K-Akt pathway is required for efficient Baculovirus replication.

  8. Multiple Scattering Tomography

    NASA Astrophysics Data System (ADS)

    Modregger, Peter; Kagias, Matias; Peter, Silvia; Abis, Matteo; Guzenko, Vitaliy A.; David, Christian; Stampanoni, Marco

    2014-07-01

    Multiple scattering represents a challenge for numerous modern tomographic imaging techniques. In this Letter, we derive an appropriate line integral that allows for the tomographic reconstruction of angular resolved scattering distributions, even in the presence of multiple scattering. The line integral is applicable to a wide range of imaging techniques utilizing various kinds of probes. Here, we use x-ray grating interferometry to experimentally validate the framework and to demonstrate additional structural sensitivity, which exemplifies the impact of multiple scattering tomography.

  9. Complex Multiplicative Calculus

    E-print Network

    Bashirov, Agamirza

    2011-01-01

    In the present paper we extend the concepts of multiplicative de- rivative and integral to complex-valued functions of complex variable. Some drawbacks, arising with these concepts in the real case, are explained satis- factorily. Properties of complex multiplicative derivatives and integrals are studied. In particular, the fundamental theorem of complex multiplicative calculus, relating these concepts, is proved. It is shown that complex multi- plicative calculus is not just another realization of the ordinary calculus. In particular, the Cauchy formula of complex calculus disappears in multiplicative complex calculus.

  10. Multiple density layered insulator

    DOEpatents

    Alger, Terry W. (Tracy, CA)

    1994-01-01

    A multiple density layered insulator for use with a laser is disclosed wh provides at least two different insulation materials for a laser discharge tube, where the two insulation materials have different thermoconductivities. The multiple layer insulation materials provide for improved thermoconductivity capability for improved laser operation.

  11. Multiple density layered insulator

    DOEpatents

    Alger, T.W.

    1994-09-06

    A multiple density layered insulator for use with a laser is disclosed which provides at least two different insulation materials for a laser discharge tube, where the two insulation materials have different thermoconductivities. The multiple layer insulation materials provide for improved thermoconductivity capability for improved laser operation. 4 figs.

  12. Constraining Multiple Grammars

    ERIC Educational Resources Information Center

    Hopp, Holger

    2014-01-01

    This article offers the author's commentary on the Multiple Grammars (MG) language acquisition theory proposed by Luiz Amaral and Tom Roeper in the present issue. Multiple Grammars advances the claim that optionality is a constitutive characteristic of any one grammar, with interlanguage grammars being perhaps the clearest examples of a…

  13. Applying Multiple Intelligences

    ERIC Educational Resources Information Center

    Christodoulou, Joanna A.

    2009-01-01

    The ideas of multiple intelligences introduced by Howard Gardner of Harvard University more than 25 years ago have taken form in many ways, both in schools and in other sometimes-surprising settings. The silver anniversary of Gardner's learning theory provides an opportunity to reflect on the ways multiple intelligences theory has taken form and…

  14. Multiple Myeloma Research Foundation

    MedlinePLUS

    ... extended lives that would have been lost to multiple myeloma yesterday. And it is accelerating all the time. Learn how ... approved 1998 MMRF established The MMRF changed the multiple myeloma treatment landscape by removing obstacles and injecting speed at each step of the research ...

  15. Multiple personality: diagnostic considerations.

    PubMed

    Coons, P M

    1980-10-01

    Multiple personality is a syndrome characterized by 2 or more alternating personality states and amnesia. Multiple personality must be differentiated from fugue, possession syndromes, mediumships, hysterical personality, schizophrenia, hypnotic states, organic brain syndrome and simulation. A review of the literature, discussion of diagnosis, and 4 illustrative cases are presented. PMID:7430076

  16. A Tailored galK Counterselection System for Efficient Markerless Gene Deletion and Chromosomal Tagging in Magnetospirillum gryphiswaldense

    PubMed Central

    Raschdorf, Oliver; Plitzko, Jürgen M.; Schüler, Dirk

    2014-01-01

    Magnetotactic bacteria have emerged as excellent model systems to study bacterial cell biology, biomineralization, vesicle formation, and protein targeting because of their ability to synthesize single-domain magnetite crystals within unique organelles (magnetosomes). However, only few species are amenable to genetic manipulation, and the limited methods for site-specific mutagenesis are tedious and time-consuming. Here, we report the adaptation and application of a fast and convenient technique for markerless chromosomal manipulation of Magnetospirillum gryphiswaldense using a single antibiotic resistance cassette and galK-based counterselection for marker recycling. We demonstrate the potential of this technique by genomic excision of the phbCAB operon, encoding enzymes for polyhydroxyalkanoate (PHA) synthesis, followed by chromosomal fusion of magnetosome-associated proteins to fluorescent proteins. Because of the absence of interfering PHA particles, these engineered strains are particularly suitable for microscopic analyses of cell biology and magnetosome biosynthesis. PMID:24814778

  17. Combined cardiomyocyte PKC? and PKC? gene deletion uncovers their central role in restraining developmental and reactive heart growth

    PubMed Central

    Song, Moshi; Matkovich, Scot J.; Zhang, Yan; Hammer, Daniel J.; Dorn, Gerald W.

    2015-01-01

    Cell growth is orchestrated by changes in gene expression that respond to developmental and environmental cues. Among the signaling pathways that direct growth are enzymes of the protein kinase C (PKC) family, which are ubiquitous proteins belonging to three distinct subclasses: conventional PKCs, novel PKCs, and atypical PKCs. Functional overlap makes determining the physiological actions of different PKC isoforms difficult. We showed that two novel PKC isoforms, PKC? and PKC?, redundantly govern stress-reactive and developmental heart growth by modulating the expression of cardiac genes central to stress-activated protein kinase and periostin signaling. Mice with combined postnatal cardiomyocyte-specific genetic ablation of PKC? and germline deletion of PKC? (DCKO) had normally sized hearts, but their hearts had transcriptional changes typical of pathological hypertrophy. Cardiac hypertrophy and dysfunction induced by hemodynamic overloading were greater in DCKO mice than in mice with a single deletion of either PKC? or PKC?. Furthermore, gene expression analysis of the hearts of DCKO mice revealed transcriptional derepression of the genes encoding the kinase ERK (extracellular signal–regulated kinase) and periostin. Mice with combined embryonic ablation of PKC? and PKC? showed enhanced growth and cardiomyocyte hyperplasia that induced pathological ventricular stiffening and early lethality, phenotypes absent in mice with a single deletion of PKC? or PKC?. Our results indicate that novel PKCs provide retrograde feedback inhibition of growth signaling pathways central to cardiac development and stress adaptation. These growth-suppressing effects of novel PKCs have implications for therapeutic inhibition of PKCs in cancer, heart, and other diseases. PMID:25900833

  18. Impaired cell division and sporulation of a Bacillus subtilis strain with the ftsA gene deleted.

    PubMed Central

    Beall, B; Lutkenhaus, J

    1992-01-01

    The ftsZ and ftsA genes of Bacillus subtilis are organized in a simple operon expressed from promoter sequences immediately upstream of ftsA. The promoter-distal ftsZ gene is an essential septation gene. In this report, it is shown that the promoter-proximal ftsA gene can be deleted in a previously constructed strain in which the essential gene, ftsZ, is under the control of the inducible spac promoter. Absence of the ftsA gene product resulted in a very filamentous morphology indicating an important role for ftsA in cell division. Also, growth was severely impaired, and viability and sporulation were reduced. The defective sporulation phenotype correlated with a deficiency in the processing of pro-sigma E to its active form. Images PMID:1551857

  19. Targeted Gene Deletion and In Vivo Analysis of Putative Virulence Gene Function in the Pathogenic Dermatophyte Arthroderma benhamiae?

    PubMed Central

    Grumbt, Maria; Defaweux, Valérie; Mignon, Bernard; Monod, Michel; Burmester, Anke; Wöstemeyer, Johannes; Staib, Peter

    2011-01-01

    Dermatophytes cause the majority of superficial mycoses in humans and animals. However, little is known about the pathogenicity of this specialized group of filamentous fungi, for which molecular research has been limited thus far. During experimental infection of guinea pigs by the human pathogenic dermatophyte Arthroderma benhamiae, we recently detected the activation of the fungal gene encoding malate synthase AcuE, a key enzyme of the glyoxylate cycle. By the establishment of the first genetic system for A. benhamiae, specific ?acuE mutants were constructed in a wild-type strain and, in addition, in a derivative in which we inactivated the nonhomologous end-joining pathway by deletion of the A. benhamiae KU70 gene. The absence of AbenKU70 resulted in an increased frequency of the targeted insertion of linear DNA by homologous recombination, without notably altering the monitored in vitro growth abilities of the fungus or its virulence in a guinea pig infection model. Phenotypic analyses of ?acuE mutants and complemented strains depicted that malate synthase is required for the growth of A. benhamiae on lipids, major constituents of the skin. However, mutant analysis did not reveal a pathogenic role of the A. benhamiae enzyme in guinea pig dermatophytosis or during epidermal invasion of the fungus in an in vitro model of reconstituted human epidermis. The presented efficient system for targeted genetic manipulation in A. benhamiae, paired with the analyzed infection models, will advance the functional characterization of putative virulence determinants in medically important dermatophytes. PMID:21478433

  20. Targeted Gene Deletion Demonstrates that Cell Adhesion MoleculeICAM-4 is Critical for Erythroblastic Island Formation

    SciTech Connect

    Lee, Gloria; Lo, Annie; Short, Sarah A.; Mankelow, Tosti J.; Spring, Frances; Parsons, Stephen F.; Mohandas, Narla; Anstee, David J.; Chasis, Joel Anne

    2006-02-15

    Erythroid progenitors differentiate in erythroblastic islands, bone marrow niches composed of erythroblasts surrounding a central macrophage. Evidence suggests that within islands adhesive interactions regulate erythropoiesis and apoptosis. We are exploring whether erythroid intercellular adhesion molecule-4 (ICAM-4), animmunoglobulin superfamily member, participates in island formation. Earlier, we identified alpha V integrins as ICAM-4 counter receptors. Since macrophages express alpha V, ICAM-4 potentially mediates island attachments. To test this, we generated ICAM-4 knockout mice and developed quantitative, live cell techniques for harvesting intact islands and for reforming islands in vitro. We observed a 47 percent decrease in islands reconstituted from ICAM-4 null marrow compared to wild type. We also found a striking decrease in islands formed in vivo in knockout mice. Further, peptides that block ICAM-4 alpha V adhesion produced a 53-57 percent decrease in reconstituted islands, strongly suggesting that ICAM-4 binding to macrophage alpha V functions in island integrity. Importantly, we documented that alpha V integrin is expressed in macrophages isolated from erythro blastic islands. Collectively, these data provide convincing evidence that ICAM-4 is critical in erythroblastic island formation via ICAM-4/alpha V adhesion and also demonstrate that the novel experimental strategies we developed will be valuable in exploring molecular mechanisms of erythroblastic island formation and their functional role in regulating erythropoiesis.

  1. Single Gene Deletions of Orexin, Leptin, Neuropeptide Y, and Ghrelin Do Not Appreciably Alter Food Anticipatory Activity in Mice

    PubMed Central

    Gunapala, Keith M.; Gallardo, Christian M.; Hsu, Cynthia T.; Steele, Andrew D.

    2011-01-01

    Timing activity to match resource availability is a widely conserved ability in nature. Scheduled feeding of a limited amount of food induces increased activity prior to feeding time in animals as diverse as fish and rodents. Typically, food anticipatory activity (FAA) involves temporally restricting unlimited food access (RF) to several hours in the middle of the light cycle, which is a time of day when rodents are not normally active. We compared this model to calorie restriction (CR), giving the mice 60% of their normal daily calorie intake at the same time each day. Measurement of body temperature and home cage behaviors suggests that the RF and CR models are very similar but CR has the advantage of a clearly defined food intake and more stable mean body temperature. Using the CR model, we then attempted to verify the published result that orexin deletion diminishes food anticipatory activity (FAA) but observed little to no diminution in the response to CR and, surprisingly, that orexin KO mice are refractory to body weight loss on a CR diet. Next we tested the orexigenic neuropeptide Y (NPY) and ghrelin and the anorexigenic hormone, leptin, using mouse mutants. NPY deletion did not alter the behavior or physiological response to CR. Leptin deletion impaired FAA in terms of some activity measures, such as walking and rearing, but did not substantially diminish hanging behavior preceding feeding time, suggesting that leptin knockout mice do anticipate daily meal time but do not manifest the full spectrum of activities that typify FAA. Ghrelin knockout mice do not have impaired FAA on a CR diet. Collectively, these results suggest that the individual hormones and neuropepetides tested do not regulate FAA by acting individually but this does not rule out the possibility of their concerted action in mediating FAA. PMID:21464907

  2. Exploiting gene deletion fitness effects in yeast to understand the modular architecture of protein complexes under different growth conditions

    E-print Network

    Pache, Roland A.; Babu, M. Madan; Aloy, Patrick

    2009-07-18

    , Weissman JS, Ingles CJ, Hughes TR, Parkinson J, Gerstein M, Wodak SJ, Emili A, Greenblatt JF: Global landscape of protein complexes in the yeast Saccharomyces cerevisiae. Nature 2006, 440(7084):637–643. 3. Bader GD, Hogue CWV: Analyzing yeast protein...

  3. Comparison of interval timing behaviour in mice following dorsal or ventral hippocampal lesions with mice having ?-opioid receptor gene deletion

    PubMed Central

    Yin, Bin; Meck, Warren H.

    2014-01-01

    Mice with cytotoxic lesions of the dorsal hippocampus (DH) underestimated 15 s and 45 s target durations in a bi-peak procedure as evidenced by proportional leftward shifts of the peak functions that emerged during training as a result of decreases in both ‘start’ and ‘stop’ times. In contrast, mice with lesions of the ventral hippocampus (VH) displayed rightward shifts that were immediately present and were largely limited to increases in the ‘stop’ time for the 45 s target duration. Moreover, the effects of the DH lesions were congruent with the scalar property of interval timing in that the 15 s and 45 s functions superimposed when plotted on a relative timescale, whereas the effects of the VH lesions violated the scalar property. Mice with DH lesions also showed enhanced reversal learning in comparison to control and VH lesioned mice. These results are compared with the timing distortions observed in mice lacking ?-opioid receptors (Oprd1?/?) which were similar to mice with DH lesions. Taken together, these results suggest a balance between hippocampal–striatal interactions for interval timing and demonstrate possible functional dissociations along the septotemporal axis of the hippocampus in terms of motivation, timed response thresholds and encoding in temporal memory. PMID:24446500

  4. Systematic gene deletion and functional characterization of histidine kinase phosphorelay receptors (HKRs) in the human pathogenic fungus Aspergillus fumigatus.

    PubMed

    Chapeland-Leclerc, F; Dilmaghani, A; Ez-Zaki, L; Boisnard, S; Da Silva, B; Gaslonde, T; Porée, F H; Ruprich-Robert, G

    2015-11-01

    Histidine kinase receptors (HKRs) appear to be a common strategy for model and pathogenic fungi to sense and respond to environmental stresses. In the human pathogen Aspergillus fumigatus, which is responsible for invasive aspergillosis, 13 genes potentially encoding HKRs have been identified. Until now, only three HKRs have been functionally characterized. The aim of this study was to perform the systematic invalidation of A. fumigatus HKR genes and the careful phenotypic characterization of the relevant mutants. This study notably allowed to gain new important insights into the role of HKRs in physiology of A. fumigatus. Actually, we showed that (i) NikA/TcsC could be involved in the cell wall integrity pathway, (ii) Fhk6 and PhkA were involved in the regulation of the "fluffy" developmental program, (iii) PhkB could participate in the regulation of conidiation and (iv) PhkA was implied in the resistance of oxidative stresses. PMID:26365385

  5. Safety and Serological Response to a Matrix Gene-deleted Rabies Virus-based Vaccine Vector in Dogs

    PubMed Central

    McGettigan, James P.; David, Frederic; Figueiredo, Monica Dias; Minke, Jules; Mebatsion, Teshome; Schnell, Matthias J.

    2014-01-01

    Dogs account for the majority of human exposures and deaths due to rabies virus (RABV) worldwide. In this report, we show that a replication-deficient RABV-based vaccine in which the matrix gene is deleted (RABV- M) is safe and induces rapid and potent VNA titers after a single inoculation in dogs. Average VNA titers peaked at 3.02 or 5.11 International Units (IU/ml) by 14 days post-immunization with a single dose of 106 or 107 focus forming units (ffu), respectively, of RABV- M. By day 70 post immunization, all dogs immunized with either dose of vaccine showed VNA titers >0.5 IU/ml, the level indicative of a satisfactory immunization. Importantly, no systemic or local reactions were noted in any dog immunized with RABV- M. The elimination of dog rabies through mass vaccination is hindered by limited resources, requirement for repeat vaccinations often for the life of a dog, and in some parts of the world, inferior vaccine quality. Our preliminary safety and immunogenicity data in dogs suggest that RABV- M might complement currently used inactivated RABV-based vaccines in vaccination campaigns by helping to obtain 100% response in vaccinated dogs, thereby increasing overall vaccination coverage. PMID:24508037

  6. Oculo-facio-cardio-dental (OFCD) syndrome: the first Italian case of BCOR and co-occurring OTC gene deletion.

    PubMed

    Di Stefano, C; Lombardo, B; Fabbricatore, C; Munno, C; Caliendo, I; Gallo, F; Pastore, L

    2015-04-01

    Oculo-facio-cardio-dental (OFCD) syndrome is a rare genetic disorder affecting ocular, facial, dental and cardiac systems. The syndrome is an X-linked dominant trait and it might be lethal in males. This syndrome is usually caused by mutations in the BCL6 interacting co-repressor gene (BCOR). We described a female child with mild phenotype of oculo-facio-cardio-dental syndrome. Array-comparative genomic hybridization (a-CGH) analysis revealed a de novo heterozygous deletion in the Xp11.4 region of approximately 2.3 Mb, involving BCOR and ornithine carbamoyl-transferase (OTC) genes. The deletion observed was subsequently confirmed by real time PCR. In this study we report a first case with co-occurrence of BCOR and OTC genes completely deleted in OFCD syndrome. PMID:25620158

  7. CONSTRUCTION AND CHARACTERIZATION OF PTA GENE DELETED MUTANT OF C CLOSTRIDIUM TYROBUTYRICUM FOR BUTYRIC ACID FERMENTATION. (R829479C016)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  8. Discoidin domain receptor 2 germline gene deletion leads to altered heart structure and function in the mouse

    PubMed Central

    Yeo, Seon Ju; Kim, In Jai; Park, Joong Il; Gu, Yusu; Dalton, Nancy D.; Peterson, Kirk L.; Greenberg, Barry H.

    2014-01-01

    Discoidin domain receptor 2 (DDR2) is a fibrillar collagen receptor that is expressed in mesenchymal cells throughout the body. In the heart, DDR2 is selectively expressed on cardiac fibroblasts. We generated a germline DDR2 knockout mouse and used this mouse to examine the role of DDR2 deletion on heart structure and function. Echocardiographic measurements from null mice were consistent with those from a smaller heart, with reduced left ventricular chamber dimensions and little change in wall thickness. Fractional shortening appeared normal. Left ventricular pressure measurements revealed mild inotropic and lusitropic abnormalities that were accentuated by dobutamine infusion. Both body and heart weights from 10-wk-old male mice were ?20% smaller in null mice. The reduced heart size was not simply due to reduced body weight, since cardiomyocyte lengths were atypically shorter in null mice. Although normalized cardiac collagen mass (assayed by hydroxyproline content) was not different in null mice, the collagen area fraction was statistically higher, suggesting a reduced collagen density from altered collagen deposition and cross-linking. Cultured cardiac fibroblasts from null mice deposited collagen at a slower rate than wild-type littermates, possibly due to the expression of lower prolyl 4-hydroxylase ?-isoform 1 enzyme levels. We conclude that genetic deletion of the DDR2 collagen receptor alters cardiac fibroblast function. The resulting perturbations in collagen deposition can influence the structure and function of mature cardiomyocytes. PMID:24993042

  9. Efficacy of a novel virulence gene-deleted Salmonella Typhimurium vaccine for protection against Salmonella infections in growing piglets.

    PubMed

    Hur, Jin; Song, Suck Oh; Lim, Jae Sam; Chung, In Kie; Lee, John Hwa

    2011-02-15

    We have previously developed a novel attenuated Salmonella Typhimurium (S. Typhimurium) ?cpxR ?lon vaccine. This study was carried out to examine whether this vaccine could effectively protect growing piglets against Salmonella infection. Attenuated S. Typhimurium secreting the B subunit of Escherichia coli heat-labile enterotoxin was also used as a mucosal adjuvant. Pregnant sows in groups A and B were primed and boosted with the vaccine and mucosal adjuvant, whereas sows in groups C, D and E received PBS. Piglets in groups A and C were intramuscularly primed with formalin-inactivated vaccine and orally boosted with live vaccine, while piglets in groups B, D and E received PBS. Piglets in groups A, B, C, and D were challenged with a wild type virulent S. Typhimurium at the 11th weeks of age. Colostrum sIgA and IgG titers in vaccinated groups A and B sows were approximately 50 and 40 times higher than those of non-vaccinated groups C, D and E sows (P<0.001). Serum IgG titers of group A piglets were also significantly higher than those of groups D and E piglets during the study (P<0.001). Furthermore, no clinical signs were observed in group A piglets during the entire experimental period after the challenge, while diarrhea was observed in many of the piglets in groups B, C, and D. No Salmonella was isolated from fecal samples of the groups A and C piglets on day 14 after challenge, whereas the challenge strain was isolated from several piglets in groups B and D. These results indicate that vaccination of the piglets with the vaccine and mucosal adjuvant in addition to vaccination of their sows induced effective protection against Salmonella infections in the growing piglets. PMID:20869776

  10. Correlations between long inverted repeat (LIR) features, deletion size and distance from breakpoint in human gross gene deletions

    PubMed Central

    Aygun, Nevim

    2015-01-01

    Long inverted repeats (LIRs) have been shown to induce genomic deletions in yeast. In this study, LIRs were investigated within ±10?kb spanning each breakpoint from 109 human gross deletions, using Inverted Repeat Finder (IRF) software. LIR number was significantly higher at the breakpoint regions, than in control segments (P < 0.001). In addition, it was found that strong correlation between 5? and 3? LIR numbers, suggesting contribution to DNA sequence evolution (r = 0.85, P < 0.001). 138 LIR features at ±3?kb breakpoints in 89 (81%) of 109 gross deletions were evaluated. Significant correlations were found between distance from breakpoint and loop length (r = ?0.18, P < 0.05) and stem length (r = ?0.18, P < 0.05), suggesting DNA strands are potentially broken in locations closer to bigger LIRs. In addition, bigger loops cause larger deletions (r = 0.19, P < 0.05). Moreover, loop length (r = 0.29, P < 0.02) and identity between stem copies (r = 0.30, P < 0.05) of 3? LIRs were more important in larger deletions. Consequently, DNA breaks may form via LIR-induced cruciform structure during replication. DNA ends may be later repaired by non-homologous end-joining (NHEJ), with following deletion. PMID:25657065

  11. Unexpected effects of gene deletion on mercury interactions with the methylation-deficient mutant hgcAB

    SciTech Connect

    Lin, Hui; Hurt, Jr., Richard Ashley; Johs, Alexander; Parks, Jerry M; Morrell-Falvey, Jennifer L; Liang, Liyuan; Elias, Dwayne A; Gu, Baohua

    2014-01-01

    The hgcA and hgcB gene pair is essential for mercury (Hg) methylation by certain anaerobic bacteria,1 but little is known about how deletion of hgcAB affects cell surface interactions and intracellular uptake of Hg. Here, we compare hgcAB mutants with the wild-type (WT) strains of both Geobacter sulfurreducens PCA and Desulfovibrio desulfuricans ND132 and observe differences in Hg redox transformations, adsorption, and uptake in laboratory incubation studies. In both strains, deletion of hgcAB increased the reduction of Hg(II) but decreased the oxidation of Hg(0) under anaerobic conditions. The measured cellular thiol content in hgcAB mutants was lower than the WT, accounting for decreased adsorption and uptake of Hg. Despite the lack of methylation activity, Hg uptake by the hgcAB continued, albeit at a slower rate than the WT. These findings demonstrate that deletion of the hgcAB gene not only eliminates Hg methylation but also alters cell physiology, resulting in changes to Hg redox reactions, sorption, and uptake by cells.

  12. GJB1/Connexin 32 whole gene deletions in patients with X-linked Charcot-Marie-Tooth disease.

    PubMed

    Gonzaga-Jauregui, Claudia; Zhang, Feng; Towne, Charles F; Batish, Sat Dev; Lupski, James R

    2010-10-01

    The X-linked form of Charcot-Marie-Tooth disease (CMTX) is the second most common form of this genetically heterogeneous inherited peripheral neuropathy. CMT1X is caused by mutations in the GJB1 gene. Most of the mutations causative for CMT1X are missense mutations. In addition, a few disease causative nonsense mutations and frameshift deletions that lead to truncated forms of the protein have also been reported to be associated with CMT1X. Previously, there have been reports of patients with deletions of the coding sequence of GJB1; however, the size and breakpoints of these deletions were not assessed. Here, we report five patients with deletions that range in size from 12.2 to 48.3 kb and that completely eliminate the entire coding sequence of the GJB1 gene, resulting in a null allele for this locus. Analyses of the breakpoints of these deletions showed that they are nonrecurrent and that they can be generated by different mechanisms. In addition to PMP22, GJB1 is the second CMT gene for which both point mutations and genomic rearrangements can cause a neuropathy phenotype, stressing the importance of CMT as a genomic disorder. PMID:20532933

  13. Col2CreERT2, A MOUSE MODEL FOR A CHONDROCYTE-SPECIFIC AND INDUCIBLE GENE DELETION

    PubMed Central

    Chen, M.; Li, S.; Xie, W.; Wang, B.; Chen, D.

    2014-01-01

    In 2007 and 2008, we published two articles reporting a tamoxifen (TM)-inducible, chondrocyte-specific gene-targeting mouse model in which the expression of CreERT2 is driven by the type II collagen promoter (Col2CreERT2). The fusion protein is specifically expressed and translocated into the nucleus upon TM administration, which in turn triggers gene recombination. Since then, this animal model has become a powerful tool to study the molecular mechanism of skeletal development and degenerative cartilage diseases, including knee joint osteoarthritis (OA), temporomandibular joint (TMJ) OA, and intervertebral disc (IVD) degeneration. In this review article, we summarise the application of Col2CreERT2 mice and discuss the potential usage of this animal model in a broad spectrum of cartilage development and molecular pathology studies. PMID:25340803

  14. Characterization and cross-protection evaluation of M949_1603 gene deletion Riemerella anatipestifer mutant RA-M1.

    PubMed

    Zou, Jiechi; Wang, Xiaolan; Ding, Chan; Tian, Mingxing; Han, Xiangan; Wang, Shaohui; Yu, Shengqing

    2015-12-01

    Riemerella anatipestifer infection causes high mortality for ducks which results in major economic losses in the duck industry. In this study, we identified a mutant strain RA-M1 by Tn4351 transposon mutagenesis, in which the M949_1603 gene encoding glycosyl transferase was inactivated. PCR analysis revealed that M949_1603 gene is specifically existed in R. anatipestifer serotype 1 strains. RA-M1 presented no reactivity to the anti-lipopolysaccharide (LPS) MAb in an indirect ELISA. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western blotting demonstrated that RA-M1 LPS had a deficiency in ladder-like binding pattern to rabbit antiserum against R. anatipestifer serotype 1 strain CH3, indicating that the O-antigen structure of RA-M1 was changed. RA-M1 showed significant attenuated virulence in ducks and higher sensitivity to normal duck serum, compared with its parent strain CH3. Furthermore, cross-protection of RA-M1 for R. anatipestifer serotypes 1, 2, and 10 strains was evaluated. Ducks that received two immunizations with inactivated RA-M1 vaccine were 100 % protected from challenge with R. anatipestifer serotype 1 strain WJ4, serotype 2 strain Yb2, and serotype 10 strain HXb2. No changes were observed in the liver, heart, or spleen samples from the protected ducks during autopsy and histological examination. Furthermore, vaccination generated high antibody titers of 1:12,800 against serotypes 1, 2, and 10 strains and enhanced production of interleukin 2 (IL-2) and IL-4 in ducks. These results suggested that M949_1603 gene is associated with serotype 1 O-antigen biosynthesis, and mutant RA-M1 could be used as a novel cross-protection vaccine candidate to protect ducks against R. anatipestifer infection. PMID:26266750

  15. Multiple sclerosis and pregnancy.

    PubMed

    Bodiguel, E; Bensa, C; Brassat, D; Laplaud, D; Le Page, E; Ouallet, J-C; Zephir, H; De Seze, J

    2014-04-01

    The question of pregnancy in patients with multiple sclerosis is regularly raised due to the prevalence of the disease in middle age women. The multiple sclerosis think tank (Groupe de Réflexion sur la Sclérose en Plaques [GRESEP]) decided to develop recommendations on this issue, with consideration to both the impact of multiple sclerosis on pregnancy, and that of pregnancy on the disease. As with topics of previous works, the formal expert consensus method was used. The working group was composed of hospital-based and private practice neurologists. The reading group was composed of neurologists, anaesthetists and obstetricians. Each recommendation is presented with the relevant level of consensus. PMID:24684929

  16. Molecular characterisation and computational modelling of macrophage heterogeneity of major immediate early gene expression during a murine cytomegalovirus infection 

    E-print Network

    Hassim, Muhamad Fairus Bin Noor

    2013-11-29

    Human cytomegalovirus (HCMV) is a major cause of morbidity and mortality amongst immuno-compromised individuals and is the leading cause of congenital diseases amongst newborn infants. Mouse CMV (MCMV) infection of inbred mice has been extensively...

  17. Group 2 coronaviruses prevent immediate early interferon induction by protection of viral RNA from host cell recognition

    SciTech Connect

    Versteeg, Gijs A.; Bredenbeek, Peter J.; Worm, Sjoerd H.E. van den; Spaan, Willy J.M. . E-mail: w.j.m.spaan@lumc.nl

    2007-04-25

    Many viruses encode antagonists to prevent interferon (IFN) induction. Infection of fibroblasts with the murine hepatitis coronavirus (MHV) and SARS-coronavirus (SARS-CoV) did not result in nuclear translocation of interferon-regulatory factor 3 (IRF3), a key transcription factor involved in IFN induction, and induction of IFN mRNA transcription. Furthermore, MHV and SARS-CoV infection could not prevent IFN induction by poly (I:C) or Sendai virus, suggesting that these CoVs do not inactivate IRF3-mediated transcription regulation, but apparently prevent detection of replicative RNA by cellular sensory molecules. Our data indicate that shielding of viral RNA to host cell sensors might be the main general mechanism for coronaviruses to prevent IFN induction.

  18. Transcription Mapping and Expression Patterns of Genes in the Major Immediate-Early Region of Kaposi's Sarcoma-Associated Herpesvirus

    E-print Network

    Ronquist, Fredrik

    of Kaposi's Sarcoma-Associated Herpesvirus Alexei K. Saveliev, Fan Xiu Zhu, and Yan Yuan1 Department and a delayed-early mRNA of 1.3 kb. © 2002 Elsevier Science (USA) INTRODUCTION Kaposi's sarcoma that this virus is an etio- logic agent of Kaposi's sarcoma (KS) (Ambroziak et al., 1995). KSHV is also associated

  19. Multiple sclerosis (image)

    MedlinePLUS

    Multiple sclerosis is a central nervous system disorder marked by decreased nerve function with initial inflammation of the protective myelin nerve covering and eventual scarring. Symptoms and severity of ...

  20. Challenges of Parenting Multiples

    MedlinePLUS

    ... tell them apart by their individual characteristics and personalities. depending on the personalities of the parents and children and the nature ... multiples. You can also work with your children’s teachers to provide the best environment for your children. • ...

  1. What Is Multiple Myeloma?

    MedlinePLUS

    ... Multiple myeloma is a cancer formed by malignant plasma cells. Normal plasma cells are found in the bone marrow and ... to an infection, they mature and change into plasma cells. Plasma cells make the antibodies (also called ...

  2. Photovoltaics: Separating Multiple Excitons

    SciTech Connect

    Nozik, A. J.

    2012-05-01

    Scientists have demonstrated an efficient process for generating multiple excitons in adjacent silicon nanocrystals from a single high-energy photon. Their findings could prove useful for a wide range of photovoltaic applications.

  3. Communicating with Multiple Impairments 

    E-print Network

    Dunlop, Catherine

    2007-01-01

    The aim of the study was to ascertain the effect of multiple special needs on the communication interactions between students and their carers in residential units of a special school. In particular, staff control, student ...

  4. Multiple Turbo Codes

    NASA Technical Reports Server (NTRS)

    Divsalar, D.; Pollara, F.

    1995-01-01

    A description is given of multiple turbo codes and a suitable decoder structure derived from an approximation to the maximum a posteriori probability (MAP) decision rule, which is substantially different from the decoder for two-code-based encoders.

  5. Pomalidomide for Multiple Myeloma

    Cancer.gov

    A summary of results from a phase III trial that compared the combination of pomalidomide (Pomalyst®) and low-dose dexamethasone versus high-dose dexamethasone alone in patients with multiple myeloma that has progressed despite other treatments.

  6. Mobile multiple access study

    NASA Technical Reports Server (NTRS)

    1977-01-01

    Multiple access techniques (FDMA, CDMA, TDMA) for the mobile user and attempts to identify the current best technique are discussed. Traffic loading is considered as well as voice and data modulation and spacecraft and system design. Emphasis is placed on developing mobile terminal cost estimates for the selected design. In addition, design examples are presented for the alternative techniques of multiple access in order to compare with the selected technique.

  7. Multiple stage multiple filter hydrate store

    DOEpatents

    Bjorkman, H.K. Jr.

    1983-05-31

    An improved hydrate store for a metal halogen battery system is disclosed which employs a multiple stage, multiple filter means for separating the halogen hydrate from the liquid used in forming the hydrate. The filter means is constructed in the form of three separate sections which combine to substantially cover the interior surface of the store container. Exit conduit means is provided in association with the filter means for transmitting liquid passing through the filter means to a hydrate former subsystem. The hydrate former subsystem combines the halogen gas generated during the charging of the battery system with the liquid to form the hydrate in association with the store. Relief valve means is interposed in the exit conduit means for controlling the operation of the separate sections of the filter means, such that the liquid flow through the exit conduit means from each of the separate sections is controlled in a predetermined sequence. The three separate sections of the filter means operate in three discrete stages to provide a substantially uniform liquid flow to the hydrate former subsystem during the charging of the battery system. The separation of the liquid from the hydrate causes an increase in the density of the hydrate by concentrating the hydrate along the filter means. 7 figs.

  8. Multiple Indicators, Multiple Causes Measurement Error Models

    PubMed Central

    Tekwe, Carmen D.; Carter, Randy L.; Cullings, Harry M.; Carroll, Raymond J.

    2014-01-01

    Multiple Indicators, Multiple Causes Models (MIMIC) are often employed by researchers studying the effects of an unobservable latent variable on a set of outcomes, when causes of the latent variable are observed. There are times however when the causes of the latent variable are not observed because measurements of the causal variable are contaminated by measurement error. The objectives of this paper are: (1) to develop a novel model by extending the classical linear MIMIC model to allow both Berkson and classical measurement errors, defining the MIMIC measurement error (MIMIC ME) model, (2) to develop likelihood based estimation methods for the MIMIC ME model, (3) to apply the newly defined MIMIC ME model to atomic bomb survivor data to study the impact of dyslipidemia and radiation dose on the physical manifestations of dyslipidemia. As a by-product of our work, we also obtain a data-driven estimate of the variance of the classical measurement error associated with an estimate of the amount of radiation dose received by atomic bomb survivors at the time of their exposure. PMID:24962535

  9. Multiple sclerosis and glutamate.

    PubMed

    Groom, Anthony J; Smith, Terence; Turski, Lechoslaw

    2003-05-01

    Experimental autoimmune encephalomyelitis reproduces in rodents the features of multiple sclerosis, an immune-mediated, disabling disorder of the human nervous system. No adequate therapy is available for multiple sclerosis, despite anti-inflammatory, immunosuppressive, and immunomodulatory measures. Increasingly glutamate is implicated in the pathogenesis of neurodegenerative diseases. Here we (1) review changes in the glutamatergic system in multiple sclerosis and (2) reveal the effects of glutamate AMPA antagonists in acute and chronic rodent models of multiple sclerosis. Administration of structurally diverse competitive and non-competitive AMPA antagonists reduces neurologic disability in rodents subjected to acute experimental autoimmune encephalomyelitis. In addition, AMPA antagonists are active in both the adoptive transfer and in chronic models of experimental autoimmune encephalomyelitis in rats and mice and affect both the acute and chronic relapsing phases. Moreover, short-term therapy with AMPA antagonists leads to sustained benefit well into the progressive phases. These results imply that therapeutic strategies for multiple sclerosis should be complemented by glutamate AMPA antagonists to reduce neurologic disability. PMID:12853317

  10. Multiple origins of life

    NASA Technical Reports Server (NTRS)

    Raup, D. M.; Valentine, J. W.

    1983-01-01

    There is some indication that life may have originated readily under primitive earth conditions. If there were multiple origins of life, the result could have been a polyphyletic biota today. Using simple stochastic models for diversification and extinction, we conclude: (1) the probability of survival of life is low unless there are multiple origins, and (2) given survival of life and given as many as 10 independent origins of life, the odds are that all but one would have gone extinct, yielding the monophyletic biota we have now. The fact of the survival of our particular form of life does not imply that it was unique or superior.

  11. Multiple sort flow cytometer

    DOEpatents

    Engh, G. van den; Esposito, R.J.

    1996-01-09

    A flow cytometer utilizes multiple lasers for excitation and respective fluorescence of identified dyes bonded to specific cells or events to identify and verify multiple events to be sorted from a sheath flow and droplet stream. Once identified, verified and timed in the sheath flow, each event is independently tagged upon separation from the flow by an electrical charge of +60, +120, or +180 volts and passed through oppositely charged deflection plates with ground planes to yield a focused six way deflection of at least six events in a narrow plane. 8 figs.

  12. Multiplicative Calculus and Student Projects.

    ERIC Educational Resources Information Center

    Campbell, Duff

    1999-01-01

    Multiplicative calculus is based on a multiplicative rate of change whereas the usual calculus is based on an additive rate of change. Describes some student investigations into multiplicative calculus, including an original student idea about multiplicative Euler's Method. (Author/ASK)

  13. Multiple Access Trade Study

    NASA Technical Reports Server (NTRS)

    Motamedi, Masoud

    1990-01-01

    The Personal Access Satellite System (PASS) strawman design uses a hybrid Time Division Multiple Access (TDMA)/Frequency Division Multiple Access (FDMA) implementation. TDMA is used for the forward direction (from Suppliers to Users), and FDMA for the return direction (from Users to Suppliers). An alternative architecture is proposed that will require minimal real time coordination and yet provide a fast access method by using random access Code Division Multiple Access (CDMA). The CDMA system issues are addressed such as connecting suppliers and users, both of whom may be located anywhere in the CONUS, when the user terminals are constrained in size and weight; and providing efficient traffic routing under highly variable traffic requirements. It is assumed that bandwidth efficiency is not of paramount importance. CDMA or Spread Spectrum Multiple Access (SSMA) communication is a method in which a group of carriers operate at the same nominal center frequency but are separable from each other by the low cross correlation of the spreading codes used. Interference and multipath rejection capability, ease of selective addressing and message screening, low density power spectra for signal hiding and security, and high resolution ranging are among the benefits of spread spectrum communications.

  14. Multiple access trade study

    NASA Astrophysics Data System (ADS)

    Motamedi, Masoud

    1990-09-01

    The Personal Access Satellite System (PASS) strawman design uses a hybrid Time Division Multiple Access (TDMA)/Frequency Division Multiple Access (FDMA) implementation. TDMA is used for the forward direction (from Suppliers to Users), and FDMA for the return direction (from Users to Suppliers). An alternative architecture is proposed that will require minimal real time coordination and yet provide a fast access method by using random access Code Division Multiple Access (CDMA). The CDMA system issues are addressed such as connecting suppliers and users, both of whom may be located anywhere in the CONUS, when the user terminals are constrained in size and weight; and providing efficient traffic routing under highly variable traffic requirements. It is assumed that bandwidth efficiency is not of paramount importance. CDMA or Spread Spectrum Multiple Access (SSMA) communication is a method in which a group of carriers operate at the same nominal center frequency but are separable from each other by the low cross correlation of the spreading codes used. Interference and multipath rejection capability, ease of selective addressing and message screening, low density power spectra for signal hiding and security, and high resolution ranging are among the benefits of spread spectrum communications.

  15. Managing advanced multiple sclerosis.

    PubMed Central

    Teasell, R. W.

    1993-01-01

    Multiple sclerosis is one of the most common neurologic conditions in Canada. Many individuals with MS eventually develop the progressive form of the disease. The neurologic and psychosocial manifestations of the later stages of MS are numerous. Family physicians ought to have some understanding of patients with advanced MS and some knowledge of how to manage them. PMID:8499793

  16. Unfolding Fraction Multiplication

    ERIC Educational Resources Information Center

    Wyberg, Terry; Whitney, Stephanie R.; Cramer, Kathleen A.; Monson, Debra S.; Leavitt, Seth

    2011-01-01

    Students often have difficulty understanding fractions, in general, and understanding how to multiply fractions, in particular. To move past this potential problem area, students need to develop a deeper understanding of multiplication and connect the ideas to fractions. In this article, the authors share their insights into teaching fraction…

  17. Theories for multiple resonances

    E-print Network

    D. Klakow; M. Weber; P. -G. Reinhard

    1995-02-09

    Two microscopic theories for multiple resonances in nuclei are compared, n-particle-hole RPA and quantized Time-Dependent Hartree-Fock (TDHF). The Lipkin-Meshkov-Glick model is used as test case. We find that quantized TDHF is superior in many respects, except for very small systems.

  18. The Multiple Mirror Telescope

    NASA Astrophysics Data System (ADS)

    Beckers, J. M.; Ulich, B. L.; Shannon, R. R.; Carleton, N. P.; Geary, J. C.; Latham, D. W.; Angel, J. R. P.; Hoffmann, W. F.; Low, F. J.; Weymann, R. J.

    The Multiple Mirror Telescope (MMT), located on top of Mount Hopkins (2600 m) in Arizona, consists of six main telescope systems, each of which is a classical Cassegrain with a 1.8 m diameter parabolic primary with focal ratio f/2.7, and a hyperbolic secondary producing a final f/31.6 for each of the individual telescopes. The most significant departures of the MMT from conventional optical telescope technology are (1) the use of light-weight 'egg-crate' mirrors, which reduced the telescope weight, (2) the use of an alt-azimuth mount, which simplifies the gravitational effects on the structure, (3) the use of a ball-bearing support rather than hydrostatic bearings, resulting in cost savings and less maintenance, (4) the use of spur gear drives rather than worm gears, and (5) the use of multiple coaligned light collectors rather than a single monolithic mirror. Early multiple objective telescopes are discussed, and the early history of the MMT project is given. The design and performance of the telescope are explained, and MMT instrumentation (spectrograph, optical design, detector, infrared photometer, SAO CCD camera) is given. Astronomical research with the telescope is discussed, along with plans for future multiple objective telescopes.

  19. Mastering the Multiplication Facts

    ERIC Educational Resources Information Center

    D'Ettorre, Jenna

    2009-01-01

    The purpose of this paper is to share the results of a six-week research project (after baseline data was collected) that focused on three different strategies (flashcards, interactive games, and music) and their effectiveness in helping fifth grade students memorize the basic multiplication facts. Many teachers face a serious problem when their…

  20. Automatic multiple applicator electrophoresis

    NASA Technical Reports Server (NTRS)

    Grunbaum, B. W.

    1977-01-01

    Easy-to-use, economical device permits electrophoresis on all known supporting media. System includes automatic multiple-sample applicator, sample holder, and electrophoresis apparatus. System has potential applicability to fields of taxonomy, immunology, and genetics. Apparatus is also used for electrofocusing.

  1. Multiple Grammars and MOGUL

    ERIC Educational Resources Information Center

    Truscott, John

    2014-01-01

    Optionality is a central phenomenon in second language acquisition (SLA), for which any adequate theory must account. Amaral and Roeper (this issue; henceforth A&R) offer an appealing approach to it, using Roeper's Multiple Grammars Theory, which was created with first language in mind but which extends very naturally to SLA. They include…

  2. Marsh Geomorphology: Multiple methods

    E-print Network

    Savidge, Dana

    Marsh Geomorphology: Multiple methods: · RTK GPS pedestrian surveys · Single beam echo soundingIO Measurement Clark Alexander, SkIO Geomorphology Julie Amft, SkIO Measurement Trent Moore, SkIO Measurement Mike Robinson, SkIO, Geomorphology Al Garrett, SRNL Model Dave Hayes, SRNL Dye Dana Savidge, SkIO Radar

  3. Multiple Primary Cancer Monograph

    Cancer.gov

    To identify groups of cancer survivors that are at increased risk for multiple primary cancers, investigators led an effort to provide the first comprehensive population-based analysis of the risk of subsequent cancer in the U.S., resulting in a monograph.

  4. Managing Multiple Measures

    ERIC Educational Resources Information Center

    DePascale, Charles A.

    2012-01-01

    Regardless of how one might feel about the recent developments in teacher evaluation systems, No Child Left Behind (NCLB) and adequate yearly progress (AYP), or student assessments for high-stakes promotion decisions, educators overwhelmingly agree that use of multiple measures is better than reliance on a single measure such as a large-scale,…

  5. Portable multiplicity counter

    DOEpatents

    Newell, Matthew R. (Los Alamos, NM); Jones, David Carl (Los Alamos, NM)

    2009-09-01

    A portable multiplicity counter has signal input circuitry, processing circuitry and a user/computer interface disposed in a housing. The processing circuitry, which can comprise a microcontroller integrated circuit operably coupled to shift register circuitry implemented in a field programmable gate array, is configured to be operable via the user/computer interface to count input signal pluses receivable at said signal input circuitry and record time correlations thereof in a total counting mode, coincidence counting mode and/or a multiplicity counting mode. The user/computer interface can be for example an LCD display/keypad and/or a USB interface. The counter can include a battery pack for powering the counter and low/high voltage power supplies for biasing external detectors so that the counter can be configured as a hand-held device for counting neutron events.

  6. Interference multiple access communications

    NASA Astrophysics Data System (ADS)

    Brothers, L. Reggie; DeBardelaben, James A.; Niedzwiecki, Joshua; Learned, Rachel E.; Eisenberg, Yiftach; Cooper, David M.

    2007-04-01

    The implementation of network centric warfare on the battlefield has driven the growing demand for high capacity warfighter communication systems. Although new high capacity SATCOM systems such as WGS are being introduced in the near term, these systems use the interference avoidance paradigm, which fundamentally limits overall network performance. This paper introduces a new wireless networking paradigm called Interference Multiple Access (IMA), developed under the auspices of DARPA. The interference multiple access paradigm exploits multi-access interference to enable revolutionary improvements in wireless communication capacity and latency without the need for infrastructure, coordination, or spectrum preplanning. Simulation and over-the-air test results suggest that greater than 3X increases in network throughput (especially in low SNR scenarios) can be achieved over traditional contention and scheduled-based spectrum access approaches when applied to WIN-T NCW terminals communicating in a mesh topology over the WGS constellation.

  7. [Multiple food allergy].

    PubMed

    Pinheiro, Adriana; Prates, Sara

    2011-01-01

    Multiple food allergy is an adverse immune response to more than one food. When a child is allergic to a great number of foods, the clinical picture can be serious and the eviction of the implied allergens leads to important dietary restrictions. We describe the case of a 4-year-old child with serious atopic eczema and multiple food allergy. At 8 months she presented positive specific Imunoglobulin (Ig)E for milk, wheat, rye, barley, gluten, soy, egg (yolk and white) and initiated eviction of these foods. At 20 months she tried to introduce wheat but suspended after aggravation of atopic eczema. At 3 years old, she had anaphylaxis after contact with cheese. At 4 years old she keeps eviction of milk, egg, wheat, gluten, barley and rye. Food restrictions in these patients are high, demanding a rigorous control of foods ingested to prevent both adverse reactions and nutricional deficits. Multidisciplinary approach is important. PMID:22015034

  8. Multiple zeros of polynomials

    NASA Technical Reports Server (NTRS)

    Wood, C. A.

    1974-01-01

    For polynomials of higher degree, iterative numerical methods must be used. Four iterative methods are presented for approximating the zeros of a polynomial using a digital computer. Newton's method and Muller's method are two well known iterative methods which are presented. They extract the zeros of a polynomial by generating a sequence of approximations converging to each zero. However, both of these methods are very unstable when used on a polynomial which has multiple zeros. That is, either they fail to converge to some or all of the zeros, or they converge to very bad approximations of the polynomial's zeros. This material introduces two new methods, the greatest common divisor (G.C.D.) method and the repeated greatest common divisor (repeated G.C.D.) method, which are superior methods for numerically approximating the zeros of a polynomial having multiple zeros. These methods were programmed in FORTRAN 4 and comparisons in time and accuracy are given.

  9. Universality of particle multiplicities

    SciTech Connect

    Goulianos, K. |

    1994-09-01

    We discuss the scaling properties and universality aspects of the rapidity and multiplicity distributions of particles produced in high energy hadronic and e{sup +}e{sup {minus}} interactions. This paper is based on material presented in three lectures on pomeron phenomenology, which included a review of traditional soft pomeron physics and selected topics on hard diffraction processes probing the structure function of the pomeron.

  10. Multiple membrane cavity optomechanics

    E-print Network

    M. Bhattacharya; P. Meystre

    2008-04-08

    We investigate theoretically the extension of cavity optomechanics to multiple membrane systems. We describe such a system in terms of the coupling of the collective normal modes of the membrane array to the light fields. We show these modes can be optically addressed individually and be cooled, trapped and characterized, e.g. via quantum nondemolition measurements. Analogies between this system and a linear chain of trapped ions or dipolar molecules imply the possibility of related applications in the quantum regime.

  11. Multiple lymphomatous polyposis.

    PubMed

    Kadayifçi, A; Benekli, M; Sava?, M C; Arslan, S; Uzunalimo?lu, B; Bari?ta, I; Güllü, I H; Tekuzman, G

    1997-04-01

    Multiple lymphomatous polyposis (MLP) is a distinctive and particularly rare clinical type of malignant gastrointestinal lymphoma, which is classified as B-cell centrocytic non-Hodgkin's lymphoma. this rare entity has been recently reclassified as mantle cell lymphoma. We herein report three additional cases of MLP involving various segments of the gastrointestinal tract. MLP has an aggressive biologic behavior and a relatively poor prognosis and must be treated accordingly as a high-grade lymphoma with systemic chemotherapy. PMID:9142193

  12. Multiple muons in MACRO

    NASA Technical Reports Server (NTRS)

    Heinz, R.

    1985-01-01

    An analysis of the multiple muon events in the Monopole Astrophysics and Cosmic Ray Observatory detector was conducted to determine the cosmic ray composition. Particular emphasis is placed on the interesting primary cosmic ray energy region above 2000 TeV/nucleus. An extensive study of muon production in cosmic ray showers has been done. Results were used to parameterize the characteristics of muon penetration into the Earth to the location of a detector.

  13. MULTIPLE OSCILLATION STABILIZING CONTROL.

    SciTech Connect

    YUE,M.; SCHLUETER,R.; AZARM,M.; BARI,R.

    2004-07-23

    This paper presents a strategy that may be used to guide stabilizing control design for multiple oscillations, which are difficult to control using conventional control design procedures. A multiple oscillation phenomena is observed in an example power system. A local bifurcation and an interarea bifurcation develop in an example power system due to multiple bifurcation parameter variations. The dynamic behaviors of the bifurcating system are complex due to the overlapping of the two different bifurcation subsystems and are shown to be difficult to control. The double bifurcations are studied in this paper and in order to stabilize them, three kind of {mu}-synthesis robust controls are designed, (a) {mu}-synthesis power system stabilizer (MPSS); (b) {mu}-synthesis SVC control (MSVC); and (c) a mixed MPSS/MSVC control. Based on the bifurcation subsystem analysis, the measurement signals and locations of the controls are selected. The control performances of three kind of controls are evaluated and compared. The conclusions are given according to the analysis and time simulation results.

  14. Strongly Multiplicative and 3-Multiplicative Linear Secret Sharing Schemes

    E-print Network

    Chee, Yeow Meng

    the intermediate results secretly shared among the players with the underlying LSSS. Due to the nature of linearityStrongly Multiplicative and 3-Multiplicative Linear Secret Sharing Schemes Zhifang Zhang1 , Mulan. Strongly multiplicative linear secret sharing schemes (LSSS) have been a powerful tool for constructing

  15. Multiple emulsions High-Order Multiple Emulsions Formed in

    E-print Network

    Multiple emulsions High-Order Multiple Emulsions Formed in Poly(dimethylsiloxane) Microfluidics** A. R. Abate and D. A. Weitz* Multiple emulsions are nested sets of drops.[1,2] Drops of one kind of yet another fluid. Such ``emulsions within emulsions'' are very useful for many applications

  16. Ninlaro Approved for Multiple Myeloma

    MedlinePLUS

    ... medlineplus/news/fullstory_155844.html Ninlaro Approved for Multiple Myeloma Blocks certain enzymes, hindering cancer-cell growth To ... Food and Drug Administration to treat people with multiple myeloma who have had at least one prior treatment ...

  17. Empliciti Approved for Multiple Myeloma

    MedlinePLUS

    ... medlineplus/news/fullstory_155973.html Empliciti Approved for Multiple Myeloma Drug boosts immune system to destroy cancer cells ... and Drug Administration to treat the blood cancer multiple myeloma. The drug is only approved for patients who ...

  18. The Functions of Multiple Representations.

    ERIC Educational Resources Information Center

    Ainsworth, Shaaron

    1999-01-01

    Discusses multiple representations and multimedia learning environments; describes a functional taxonomy of MERs (multiple external representations); and considers how MERs are used to support cognitive processes in learning and problem solving with computers. (Contains 41 references.) (Author/LRW)

  19. Modeling Multiple Information Seeking Episodes.

    ERIC Educational Resources Information Center

    Lin, Shin-jeng; Belkin, Nicholas J.

    2000-01-01

    Discussion of information retrieval and information seeking behavior focuses on a multi-dimensional conceptual model called MISE (multiple information-seeking episodes). Identifies eight different reasons why people engage in multiple information-seeking episodes, characterizes them in terms of traits of Multiple Information Seeking Episode…

  20. Multiple Sparse Representations Classification

    PubMed Central

    Plenge, Esben; Klein, Stefan S.; Niessen, Wiro J.; Meijering, Erik

    2015-01-01

    Sparse representations classification (SRC) is a powerful technique for pixelwise classification of images and it is increasingly being used for a wide variety of image analysis tasks. The method uses sparse representation and learned redundant dictionaries to classify image pixels. In this empirical study we propose to further leverage the redundancy of the learned dictionaries to achieve a more accurate classifier. In conventional SRC, each image pixel is associated with a small patch surrounding it. Using these patches, a dictionary is trained for each class in a supervised fashion. Commonly, redundant/overcomplete dictionaries are trained and image patches are sparsely represented by a linear combination of only a few of the dictionary elements. Given a set of trained dictionaries, a new patch is sparse coded using each of them, and subsequently assigned to the class whose dictionary yields the minimum residual energy. We propose a generalization of this scheme. The method, which we call multiple sparse representations classification (mSRC), is based on the observation that an overcomplete, class specific dictionary is capable of generating multiple accurate and independent estimates of a patch belonging to the class. So instead of finding a single sparse representation of a patch for each dictionary, we find multiple, and the corresponding residual energies provides an enhanced statistic which is used to improve classification. We demonstrate the efficacy of mSRC for three example applications: pixelwise classification of texture images, lumen segmentation in carotid artery magnetic resonance imaging (MRI), and bifurcation point detection in carotid artery MRI. We compare our method with conventional SRC, K-nearest neighbor, and support vector machine classifiers. The results show that mSRC outperforms SRC and the other reference methods. In addition, we present an extensive evaluation of the effect of the main mSRC parameters: patch size, dictionary size, and sparsity level. PMID:26177106

  1. Multiple thymic carcinoids.

    PubMed

    Kawaguchi, Koji; Usami, Noriyasu; Okasaka, Toshiki; Yokoi, Kohei

    2011-06-01

    We present a very rare case of simultaneous thymic carcinoids with similar size, one of which showed spontaneous regression. A 68-year-old man was admitted to the hospital because of two similar abnormal masses at his anterior mediastinum on chest computed tomography, one of which had decreased from 25 to 16 mm in diameter. A total thymectomy was performed and the pathologic examinations revealed that both tumors were atypical carcinoids. There have been seldom reports of multiple thymic carcinoids, and this case might suggest that total thymectomy is the best way to treat thymic carcinoid because of the possibility of multicentric origins. PMID:21619996

  2. Complex Gaussian multiplicative chaos

    E-print Network

    Hubert Lacoin; Rémi Rhodes; Vincent Vargas

    2015-02-15

    In this article, we study complex Gaussian multiplicative chaos. More precisely, we study the renormalization theory and the limit of the exponential of a complex log-correlated Gaussian field in all dimensions (including Gaussian Free Fields in dimension 2). Our main working assumption is that the real part and the imaginary part are independent. We also discuss applications in 2D string theory; in particular we give a rigorous mathematical definition of the so-called Tachyon fields, the conformally invariant operators in critical Liouville Quantum Gravity with a c=1 central charge, and derive the original KPZ formula for these fields.

  3. Phase-multiplication holography

    SciTech Connect

    Collins, H.D.; Prince, J.M.; Davis, T.J.

    1982-01-25

    This disclosure relates generally to nondestructive testing for identifying structural characteristics of an object by scanned holographic techniques using a known source of radiation, such as electromagnetic or acoustical radiation. It is an object of this invention to provide an apparatus and method for synthetic aperture expansion in holographic imaging applications to construct fringe patterns capable of holographic reproduction where aperture restrictions in nondestructive testing applications would conventionally make such imaging techniques impossible. The apparatus and method result in the production of a sharply defined frontal image of structural characteristics which could not otherwise be imaged because they occur either near the surface of the object or are confined by geometry restricting aperture dimensions available for scanning purposes. The depth of the structural characteristic below the surface of the object can also be determined by the reconstruction parameters which produce the sharpest focus. Lateral resolution is established by simulated reduction in the radiation wavelength and may easily be an order of magnitude less than the electromagnetic wavelength in the material or 2 times the standard depth of penetration. Since the phase multiplication technique is performed on the detected data, the penetration depth available due to the longer wavelength signals applied to the test object remains unchanged. The phase multiplication technique can also be applied to low frequency acoustic holography, resulting in a test which combines excellent penetration of difficult materials with high resolution images.

  4. Smoldering multiple myeloma.

    PubMed

    Rajkumar, S Vincent; Landgren, Ola; Mateos, María-Victoria

    2015-05-14

    Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder. SMM is distinguished from monoclonal gammopathy of undetermined significance by a much higher risk of progression to multiple myeloma (MM). There have been major advances in the diagnosis, prognosis, and management of SMM in the last few years. These include a revised disease definition, identification of several new prognostic factors, a classification based on underlying cytogenetic changes, and new treatment options. Importantly, a subset of patients previously considered SMM is now reclassified as MM on the basis of biomarkers identifying patients with an ?80% risk of progression within 2 years. SMM has assumed greater significance on the basis of recent trials showing that early therapy can be potentially beneficial to patients. As a result, there is a need to accurately diagnose and risk-stratify patients with SMM, including routine incorporation of modern imaging and laboratory techniques. In this review, we outline current concepts in diagnosis and risk stratification of SMM, and provide specific recommendations on the management of SMM. PMID:25838344

  5. Multiple capillary biochemical analyzer

    DOEpatents

    Dovichi, Norman J. (Edmonton, CA); Zhang, Jian Z. (Edmonton, CA)

    1995-01-01

    A multiple capillary analyzer allows detection of light from multiple capillaries with a reduced number of interfaces through which light must pass in detecting light emitted from a sample being analyzed, using a modified sheath flow cuvette. A linear or rectangular array of capillaries is introduced into a rectangular flow chamber. Sheath fluid draws individual sample streams through the cuvette. The capillaries are closely and evenly spaced and held by a transparent retainer in a fixed position in relation to an optical detection system. Collimated sample excitation radiation is applied simultaneously across the ends of the capillaries in the retainer. Light emitted from the excited sample is detected by the optical detection system. The retainer is provided by a transparent chamber having inward slanting end walls. The capillaries are wedged into the chamber. One sideways dimension of the chamber is equal to the diameter of the capillaries and one end to end dimension varies from, at the top of the chamber, slightly greater than the sum of the diameters of the capillaries to, at the bottom of the chamber, slightly smaller than the sum of the diameters of the capillaries. The optical system utilizes optic fibres to deliver light to individual photodetectors, one for each capillary tube. A filter or wavelength division demultiplexer may be used for isolating fluorescence at particular bands.

  6. Multiple capillary biochemical analyzer

    DOEpatents

    Dovichi, N.J.; Zhang, J.Z.

    1995-08-08

    A multiple capillary analyzer allows detection of light from multiple capillaries with a reduced number of interfaces through which light must pass in detecting light emitted from a sample being analyzed, using a modified sheath flow cuvette. A linear or rectangular array of capillaries is introduced into a rectangular flow chamber. Sheath fluid draws individual sample streams through the cuvette. The capillaries are closely and evenly spaced and held by a transparent retainer in a fixed position in relation to an optical detection system. Collimated sample excitation radiation is applied simultaneously across the ends of the capillaries in the retainer. Light emitted from the excited sample is detected by the optical detection system. The retainer is provided by a transparent chamber having inward slanting end walls. The capillaries are wedged into the chamber. One sideways dimension of the chamber is equal to the diameter of the capillaries and one end to end dimension varies from, at the top of the chamber, slightly greater than the sum of the diameters of the capillaries to, at the bottom of the chamber, slightly smaller than the sum of the diameters of the capillaries. The optical system utilizes optic fibers to deliver light to individual photodetectors, one for each capillary tube. A filter or wavelength division demultiplexer may be used for isolating fluorescence at particular bands. 21 figs.

  7. Neutron-multiplication measurement instrument

    SciTech Connect

    Nixon, K.V.; Dowdy, E.J.; France, S.W.; Millegan, D.R.; Robba, A.A.

    1982-01-01

    The Advanced Nuclear Technology Group of the Los Alamos National Laboratory is now using intelligent data-acquisition and analysis instrumentation for determining the multiplication of nuclear material. Earlier instrumentation, such as the large NIM-crate systems, depended on house power and required additional computation to determine multiplication or to estimate error. The portable, battery-powered multiplication measurement unit, with advanced computational power, acquires data, calculates multiplication, and completes error analysis automatically. Thus, the multiplication is determined easily and an available error estimate enables the user to judge the significance of results.

  8. Swamp Works- Multiple Projects

    NASA Technical Reports Server (NTRS)

    Carelli, Jonathan M.; Schuler, Jason M.; Chandler, Meredith L.

    2013-01-01

    My Surface Systems internship over the summer 2013 session covered a broad range of projects that utilized multiple fields of engineering and technology. This internship included a project to create a command center for a 120 ton regolith bin, for the design and assembly of a blast shield to add further protection for the Surface Systems engineers, for the design and assembly of a portable four monitor hyper wall strip that could extend as large as needed, research and programming a nano drill that could be utilized on a next generation robot or rover, and social media tasks including the making of videos, posting to social networking websites and creation of a new outreach program to help spread the word about the Swamp Works laboratory.

  9. Multiple primary prostate cancer.

    PubMed

    Lanesky, J; Opipari, M I; McKenzie, M

    1979-06-01

    Although increasing reports are noted of apparent endometrial carcinoma of prostatic origin, the controversy is present of the actual existence of such an entity. The association of papillary prostatic cancer (endometrial or ductal) with the typical microacinar variety has also been previously presented. This report is an account of 2 cases of multiple prostatic primary tumors. The first case is the twelfth reported case of endometrial (utricular) carcinoma not only simultaneously associated with microacinar type carcinoma, but also with a previous transitional carcinoma of the urinary bladder. The second case is a papillary carcinoma and associated microacinar type with the papillary component responding dramatically to chemotherapy. Significant aspects of interest in this case include the site of papillary metastasis to the lungs, elevated estrogen levels with normalization after treatment, and finally response to chemotherapy. PMID:452201

  10. MULTIPLE GALAXY COLLISIONS

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Here is a sampling of 15 ultraluminous infrared galaxies viewed by NASA's Hubble Space Telescope. Hubble's sharp vision reveals more complexity within these galaxies, which astronomers are interpreting as evidence of a multiple-galaxy pileup. These images, taken by the Wide Field and Planetary Camera 2, are part of a three-year study of 123 galaxies within 3 billion light-years of Earth. The study was conducted in 1996, 1997, and 1999. False colors were assigned to these photos to enhance fine details within these coalescing galaxies. Credits: NASA, Kirk Borne (Raytheon and NASA Goddard Space Flight Center, Greenbelt, Md.), Luis Colina (Instituto de Fisica de Cantabria, Spain), and Howard Bushouse and Ray Lucas (Space Telescope Science Institute, Baltimore, Md.)

  11. Multiple Sclerosis in Children

    PubMed Central

    INALOO, Soroor; HAGHBIN, Saideh

    2013-01-01

    Multiple sclerosis (MS) is the most important immune-mediated demyelinated disease of human which is typically the disease of young adults. A total of 4% to 5% of MS population are pediatric. Pediatric MS is defined as the appearance of MS before the age of sixteen. About 80% of the pediatric cases and nearly all adolescent onset patients present with attacks typical to adult MS. Approximately 97% to 99% of the affected children have relapsing-remitting MS, while 85% to 95% of the adults experience such condition. MS in children is associated with more frequent and severe relapses. Treatment is the same as adults. We aimed to review the epidemiology, etiology, clinical manifestations, and treatment of MS in children. PMID:24665290

  12. On Multiple Einstein Rings

    E-print Network

    M. C. Werner; J. An; N. W. Evans

    2008-07-30

    A number of recent surveys for gravitational lenses have found examples of double Einstein rings. Here, we investigate analytically the occurrence of multiple Einstein rings. We prove, under very general assumptions, that at most one Einstein ring can arise from a mass distribution in a single plane lensing a single background source. Two or more Einstein rings can therefore only occur in multi-plane lensing. Surprisingly, we show that it is possible for a single source to produce more than one Einstein ring. If two point masses (or two isothermal spheres) in different planes are aligned with observer and source on the optical axis, we show that there are up to three Einstein rings. We also discuss the image morphologies for these two models if axisymmetry is broken, and give the first instances of magnification invariants in the case of two lens planes.

  13. Mixed Mode Matrix Multiplication

    SciTech Connect

    Meng-Shiou Wu; Srinivas Aluru; Ricky A. Kendall

    2004-09-30

    In modern clustering environments where the memory hierarchy has many layers (distributed memory, shared memory layer, cache,...), an important question is how to fully utilize all available resources and identify the most dominant layer in certain computations. When combining algorithms on all layers together, what would be the best method to get the best performance out of all the resources we have? Mixed mode programming model that uses thread programming on the shared memory layer and message passing programming on the distributed memory layer is a method that many researchers are using to utilize the memory resources. In this paper, they take an algorithmic approach that uses matrix multiplication as a tool to show how cache algorithms affect the performance of both shared memory and distributed memory algorithms. They show that with good underlying cache algorithm, overall performance is stable. When underlying cache algorithm is bad, superlinear speedup may occur, and an increasing number of threads may also improve performance.

  14. Multiple layer insulation cover

    DOEpatents

    Farrell, James J. (Livingston Manor, NY); Donohoe, Anthony J. (Ovid, NY)

    1981-11-03

    A multiple layer insulation cover for preventing heat loss in, for example, a greenhouse, is disclosed. The cover is comprised of spaced layers of thin foil covered fabric separated from each other by air spaces. The spacing is accomplished by the inflation of spaced air bladders which are integrally formed in the cover and to which the layers of the cover are secured. The bladders are inflated after the cover has been deployed in its intended use to separate the layers of the foil material. The sizes of the material layers are selected to compensate for sagging across the width of the cover so that the desired spacing is uniformly maintained when the cover has been deployed. The bladders are deflated as the cover is stored thereby expediting the storage process and reducing the amount of storage space required.

  15. Biomarkers in multiple sclerosis.

    PubMed

    Housley, William J; Pitt, David; Hafler, David A

    2015-11-01

    Substantial effort has been made over the last six decades to identify biomarkers for multiple sclerosis that can improve disease diagnosis, predict disease progression, and improve clinical outcomes. However, to date, few of these findings have proven clinically useful. In this review, we address the current state of MS biomarker research. We start by discussing biomarkers currently in clinical use including Oligoclonal bands, MRI, and JC viral titers. We go on to discuss other potential biomarkers from MS serum and cerebrospinal fluid including Markers of neurodegeneration including neurofilament and GFAP, the monocyte macrophage marker CD163, the glial activation marker YKL-40, the B cell chemoattractant CXCL13, miRNA and mRNA, myelin reactive t cells, Kir4.1 antibodies, osteopontin, and microbiome associated lipopeptides. Finally, we discuss the current state of MS genetic studies and how genetics may offer simple, reliable testing for MS susceptibility and progression. PMID:26143623

  16. Multiple Choice Learning: Learning to Produce Multiple Structured Outputs

    E-print Network

    Kohli, Pushmeet

    predictions: 1. Interactive Intelligent Systems. The goal of interactive machine-learning algorithmsMultiple Choice Learning: Learning to Produce Multiple Structured Outputs Abner Guzman for structured predic- tion tasks that involve interaction with users or successive components in a cas- caded

  17. “Undiagnosing” multiple sclerosis

    PubMed Central

    Klein, Eran P.; Bourdette, Dennis

    2012-01-01

    Objective: To describe the clinical characteristics of encounters with patients misdiagnosed with multiple sclerosis (MS). Methods: A cross-sectional Internet-based physician survey of MS specialists was performed. Results: The response rate for the survey was 50.4%. Of those who responded, the majority (95%) reported having evaluated 1 or more patients who had been diagnosed with MS, but who they strongly felt did not have MS, within the last year. The majority of respondents (>90%) also reported the use of disease-modifying therapy in a proportion of these patients. Most respondents (94%) found clinical encounters with these patients equally or more challenging than giving a new diagnosis of MS. Fourteen percent of respondents reported that they did not always inform such patients of their opinion that they did not have MS. Conclusions: The misdiagnosis of MS is common and has significant consequences for patient care and health care system costs. Caring for a patient with a misdiagnosis of MS is challenging, and at times honest disclosure of a misdiagnosis represents an important ethical concern for neurologists. More data are needed on this patient population to improve diagnostic acumen and the care of these patients. PMID:22581930

  18. Multiple stage railgun

    DOEpatents

    Hawke, Ronald S. (Livermore, CA); Scudder, Jonathan K. (Pleasanton, CA); Aaland, Kristian (Livermore, CA)

    1982-01-01

    A multiple stage magnetic railgun accelerator (10) for accelerating a projectile (15) by movement of a plasma arc (13) along the rails (11,12). The railgun (10) is divided into a plurality of successive rail stages (10a-n) which are sequentially energized by separate energy sources (14a-n) as the projectile (15) moves through the bore (17) of the railgun (10). Propagation of energy from an energized rail stage back towards the breech end (29) of the railgun (10) can be prevented by connection of the energy sources (14a-n) to the rails (11,12) through isolation diodes (34a-n). Propagation of energy from an energized rail stage back towards the breech end of the railgun can also be prevented by dividing the rails (11,12) into electrically isolated rail sections (11a-n, 12a-n). In such case means (55a-n) are used to extinguish the arc at the end of each energized stage and a fuse (31) or laser device (61) is used to initiate a new plasma arc in the next energized rail stage.

  19. Multiple Myeloma: An Update

    PubMed Central

    Al-Farsi, Khalil

    2013-01-01

    Multiple myeloma is a rare, largely incurable malignant disease of plasma cells. Patients usually present with hypercalcemia, renal insufficiency, anemia and/or lytic bony lesions along with a monoclonal protein in the serum and/or urine in addition to an increase in the number of clonal plasma cells in the bone marrow. Patients with myeloma live on an average for five to seven years, with their survival dependent on the presence or absence of different prognostic markers. Treatment of younger fit patients is with induction therapy consisting of steroids with one or more novel anti-myeloma agents followed by high dose melphalan and autologous stem cell transplantation, while older and less fit patients are treated with melphalan-based combination chemotherapy. Supportive care is of paramount importance and includes the use of bisphosphonates, prophylactic antibiotics, thrombosis prophylaxis and the use of hematopoietic growth factors along with the treatment of complications of disease and its therapy. As more progress is being made and deeper responses are being attained, the disease might turn into a potentially curable one in the near future. PMID:23386937

  20. Multiple trellis coded modulation

    NASA Technical Reports Server (NTRS)

    Simon, Marvin K. (Inventor); Divsalar, Dariush (Inventor)

    1990-01-01

    A technique for designing trellis codes to minimize bit error performance for a fading channel. The invention provides a criteria which may be used in the design of such codes which is significantly different from that used for average white Gaussian noise channels. The method of multiple trellis coded modulation of the present invention comprises the steps of: (a) coding b bits of input data into s intermediate outputs; (b) grouping said s intermediate outputs into k groups of s.sub.i intermediate outputs each where the summation of all s.sub.i,s is equal to s and k is equal to at least 2; (c) mapping each of said k groups of intermediate outputs into one of a plurality of symbols in accordance with a plurality of modulation schemes, one for each group such that the first group is mapped in accordance with a first modulation scheme and the second group is mapped in accordance with a second modulation scheme; and (d) outputting each of said symbols to provide k output symbols for each b bits of input data.

  1. Immunopathogenesis of multiple sclerosis.

    PubMed

    Brinar, Vesna

    2009-06-01

    Immunopathogenesis of multiple sclerosis is a complex process involving T cell mediated autoimmunity at initial stage of disease. A long standing view that Th1 cells are critical for early inflammatory development of lesions is challenging by recent findings that Th1 helper cells with Th17 phenotype are even more important. A complex autoimmunity of MS is further complicated with evidence that CD8 cells, regulatory T cells, clonal expansion of B cells, cells of myelin lineage, antibodies and complement, as well as process intrinsic to central nervous system contribute to the tissue destruction. Although there are a lot of evidences about inflammatory phase of MS, far less is known about mechanisms involved in degenerative phase of disease. It is not known weather quantitative, or qualitative differences in inflammatory response contributes to destruction of the tissue, or as it was shown experimentally demyelination may sometimes occur independent of T cells. Understanding of immunopathogenesis of MS especially regarding various stages of disease is necessary for clinicians in choosing optimal therapy of MS in individual patients. Influences of immunomodulatory treatment on various stages of MS immuno-pathogenesis are presented. PMID:25384860

  2. Multiple-Event Gully

    NASA Technical Reports Server (NTRS)

    2003-01-01

    MGS MOC Release No. MOC2-554, 24 November 2003

    Middle- and polar-latitude gullies are common on crater and trough walls in the martian southern hemisphere. Some also occur in the north. One of the controversies surrounding gullies is whether they involved fluid flow (such as liquid water) or were formed by dry landsliding processes. The occurrence of banked and leveed channels in many gullies argues that they formed by fluid flow. Another question centers on whether gullies are 'one-shot deals' or involved more than one episode of fluid flow. This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image, acquired in November 2003, shows a gully with an apron, near the center of the frame, that formed by multiple fluid flows. The apron of debris at the base of the gully near the center of the picture is not just one apron, it is three. Three separate aprons formed at three different times. First, the larger, left-most apron formed. Later, another event caused fluid to cut through that apron and create a new one (the middle of the three). Later, a third event cut both aprons and formed a small, third one. This image shows the wall of an impact crater located near 51.3oS, 326.6oW. The image covers an area 3 km (1.9 mi) wide, and is illuminated by sunlight from the upper left.

  3. Adult Multiple Intelligences and Math.

    ERIC Educational Resources Information Center

    Costanzo, Meg Ryback

    In the Adult Multiple Intelligences (AMI) study, 10 teachers of adults from the northeastern region of the United States explored for 18 months the ways that multiple intelligences (MI) theory could support instruction and assessment in various adult learning contexts. The results of this research were published in a book by Julie Viens called MI…

  4. The problem with multiple robots

    NASA Technical Reports Server (NTRS)

    Huber, Marcus J.; Kenny, Patrick G.

    1994-01-01

    The issues that can arise in research associated with multiple, robotic agents are discussed. Two particular multi-robot projects are presented as examples. This paper was written in the hope that it might ease the transition from single to multiple robot research.

  5. Multiple Intelligences for Differentiated Learning

    ERIC Educational Resources Information Center

    Williams, R. Bruce

    2007-01-01

    There is an intricate literacy to Gardner's multiple intelligences theory that unlocks key entry points for differentiated learning. Using a well-articulated framework, rich with graphic representations, Williams provides a comprehensive discussion of multiple intelligences. He moves the teacher and students from curiosity, to confidence, to…

  6. Multiple Intelligences and Lab Groups

    ERIC Educational Resources Information Center

    Colannino, Noreen M.; Hoyt, William L.; Murray, Ann

    2004-01-01

    Science teachers who are committed to excellence in the classroom continually seek ways to improve teaching and learning, and the concept of multiple intelligences holds promise as a method for accomplishing this. The essence of the theory of multiple intelligences is to understand the many differences among students, the variations in the ways…

  7. Multiple View Vision Kalle strm,

    E-print Network

    Lunds Universitet

    Multiple View Vision Kalle Åström, Centre for Mathematical Sciences, Lund University P O Box 118 historical overview of multiple view vision and in particular the es- timation of both camera geometry within the field of computer vision are their inverses in the mathematical sense, i.e. to calculate

  8. Multiple Regression Assumptions. ERIC Digest.

    ERIC Educational Resources Information Center

    Osborne, Jason W.; Waters, Elaine

    This Digest presents a discussion of the assumptions of multiple regression that is tailored to the practicing researcher. The focus is on the assumptions of multiple regression that are not robust to violation, and that researchers can deal with if violated. Assumptions of normality, linearity, reliability of measurement, and homoscedasticity are…

  9. Bent Bonds and Multiple Bonds.

    ERIC Educational Resources Information Center

    Robinson, Edward A.; Gillespie, Ronald J.

    1980-01-01

    Considers carbon-carbon multiple bonds in terms of Pauling's bent bond model, which allows direct calculation of double and triple bonds from the length of a CC single bond. Lengths of these multiple bonds are estimated from direct measurements on "bent-bond" models constructed of plastic tubing and standard kits. (CS)

  10. Multiple sclerosis update.

    PubMed

    Markowitz, Clyde E

    2013-11-01

    Multiple sclerosis (MS) is a chronic but incurable disease of the central nervous system (CNS) that is often diagnosed in the second or third decade of life. It is more common among women than men, significantly impairs patient quality of life, and is associated with substantial costs to patients, healthcare systems, and society. Of the approximately 2.3 million individuals worldwide that have MS, more than 400,000 reside in the United States. Although the etiology of MS is not completely understood, a great deal of evidence suggests a complex relationship between environmental and genetic factors. The pathophysiology of MS involves an aberrant attack by the host immune system on oligodendrocytes, which synthesize and maintain myelin sheaths in the CNS. There are 4 identified disease courses in MS, and approximately 85% of people with MS present with relapsing-remitting MS, which is characterized by discrete acute attacks followed by periods of remission. Signs and symptoms of MS are dependent on the demyelinated area(s) of the CNS and often involve sensory disturbances, limb weakness, fatigue, and increased body temperature. The criteria for a diagnosis of MS include evidence of damage in at least 2 separate areas of the CNS, evidence that the damage occurred at different time points, and the ruling out of other possible diagnoses. Diseasemodifying drugs (DMDs) that reduce the frequency of relapses, development of brain lesions, and progression of disability are the standard of care for relapsing forms of MS, and the use of DMDs should be initiated as early as possible. PMID:24494618

  11. Swamp Works- Multiple Projects

    NASA Technical Reports Server (NTRS)

    Carelli, Jonathan M.

    2013-01-01

    My Surface Systems internship over the summer 2013 session covered a broad range of projects that ranged multiple aspects and fields of engineering and technology. This internship included a project to create a command center for a 120 ton regolith bin, a design and build for a blast shield to add further protection for the Surface Systems engineers, a design for a portable four monitor hyper wall that can extend as large as needed, research and programming a nano drill for a next generation robot, and social media tasks including the making of videos, posting to social networking websites and implementation of a new weekly outreach program to help spread the word about the Swamp Works laboratory. The objectives for the command center were to create a central computer controlled area for the still in production lunar regolith bin. It needed to be easy to use and the operating systems had to be Linux. The objectives for the hyper wall were to build a mobile transport of monitors that could potentially attach to one another. It needed to be light but sturdy, and have the ability to last. The objectives for the blast shield included a robust design that could withstand a small equipment malfunction, while also being convenient for use. The objectives for the nano-drill included the research and implementation of programming for vertical and horizontal movement. The hyper wall and blasts shield project were designed by me in the Pro/Engineer/Creo2 software. Each project required a meeting with the Swamp Works engineers and was declared successful.

  12. On Multiple-Layered Vortices

    NASA Technical Reports Server (NTRS)

    Rossow, Vernon J.

    2011-01-01

    As part of an ongoing effort to find ways to make vortex flow fields decompose more quickly, photographs and observations are presented of vortex flow fields that indicate the presence of multiple layers of fluid rotating about a common axis. A survey of the literature indicates that multiple-layered vortices form in waterspouts, tornadoes and lift-generated vortices of aircraft. An explanation for the appearance of multiple-layered structures in vortices is suggested. The observations and data presented are intended to improve the understanding of the formation and persistence of vortex flow fields.

  13. Proton interactions with high multiplicity

    SciTech Connect

    Kokoulina, E. S. Nikitin, V. A.; Petukhov, Y. P.; Kutov, A. Ya.

    2012-06-15

    Project Thermalization is aimed to study the proton-proton interaction with high multiplicity of secondary particles. The region of high multiplicity is especially actual at present. We expect the manifestation of the secondary particle collective behavior at this region. The experimentally measured topological cross section was corrected for apparatus acceptance and detection efficiency. These data are in good agreement with gluon dominance model. The comparison with other models is also done and shows no essential deviations. There is evidence that Bose-Einstein condensation can formed at high total multiplicity region.

  14. Autonomic dysfunction in multiple sclerosis.

    PubMed

    Racosta, Juan Manuel; Kimpinski, Kurt; Morrow, Sarah Anne; Kremenchutzky, Marcelo

    2015-12-01

    Autonomic dysfunction is a prevalent and significant cause of disability among patients with multiple sclerosis. Autonomic dysfunction in multiple sclerosis is usually explained by lesions within central nervous system regions responsible for autonomic regulation, but novel evidence suggests that other factors may be involved as well. Additionally, the interactions between the autonomic nervous system and the immune system have generated increased interest about the role of autonomic dysfunction in the pathogenesis of multiple sclerosis. In this paper we analyze systematically the most relevant signs and symptoms of autonomic dysfunction in MS, considering separately their potential causes and implications. PMID:26070809

  15. Constraining multiple systems with GAIA

    E-print Network

    Beauvalet, L.

    GAIA will provide observations of some multiple asteroid and dwarf systems. These observations are a way to determine and improve the quantification of dynamical parameters, such as the masses and the gravity fields, in ...

  16. Lung Multiple Primary Rules Matrix

    Cancer.gov

    Lung Multiple Primary Rules – Matrix C340-C349 (Excludes lymphoma and leukemia M9590 – 9989 and Kaposi sarcoma M9140) * Prepare one abstract. Use the histology coding rules to assign the appropriate histology code. ** Prepare two or more abstracts.

  17. Multiplicities in high energy interactions

    SciTech Connect

    Derrick, M.

    1985-05-13

    This paper reviews the data on multiplicities in high energy interactions. Results from e/sup +/e/sup -/ annihilation, from neutrino interactions, and from hadronic collisions, both diffractive and nondiffractive, are compared and contrasted. The energy dependence of the mean charged multiplicity, , as well as the rapidity density at Y = 0 are presented. For hadronic collisions, the data on neutral pion production shows a strong correlation with . The heavy particle fractions increase with ..sqrt..s up to the highest energies. The charged particle multiplicity distributions for each type of reaction show a scaling behavior when expressed in terms of the mean. Attempts to understand this behavior, which was first predicted by Koba, Nielsen, and Olesen, are discussed. The multiplicity correlations and the energy variation of the shape of the KNO scaling distribution provide important constraints on models. Some extrapolations to the energies of the Superconducting Super Collider are made. 51 refs., 27 figs.

  18. MULTIPLE SCALES FOR SUSTAINABLE RESULTS

    EPA Science Inventory

    This session will highlight recent research that incorporates the use of multiple scales and innovative environmental accounting to better inform decisions that affect sustainability, resilience, and vulnerability at all scales. Effective decision-making involves assessment at mu...

  19. Jejunal morphology in multiple sclerosis.

    PubMed

    Bateson, M C; Hopwood, D; MacGillivray, J B

    1979-05-26

    In a prospective survey jejunal biopsy samples from 11 patients with multiple sclerosis on normal diets were compared with those from controls matched for age and sex. Quantitative histology, morphometry, and electron microscopy showed no difference between the two groups. Since there was no evidence that gluten sensitivity plays a role in the aetiology of multiple sclerosis, the wide adoption of gluten exclusion by patients seems unjustified. PMID:86833

  20. Interacting Multiple Model Kalman Filters (IMMKF) Interacting Multiple Model Kalman Filters

    E-print Network

    Williams, Brian C.

    Interacting Multiple Model Kalman Filters (IMMKF) Interacting Multiple Model Kalman Filters (IMMKF R.Q.A. Santana Interacting Multiple Model Kalman Filters (IMMKF) #12;Interacting Multiple Model Kalman Filters (IMMKF) Sumário 1 Introdução Abordagens de múltiplos modelos Introdução ao Interacting

  1. Multiplication of Fractions through Paper Folding.

    ERIC Educational Resources Information Center

    Sinicrope, Rose; Mick, Harold W.

    1992-01-01

    Presents an instructional approach that utilizes paper-folding activities to help students understand the concept of fractions. Utilizes an area model of multiplication to extend the concept of multiplication of whole numbers to multiplication of fractions. (MDH)

  2. Introduction Matrix multiplication based linear algebra

    E-print Network

    Pernet, Clément

    Introduction Matrix multiplication based linear algebra Computing the characteristic polynomial Conclusion and perspectives Matrix Multiplication Based Computations of the Characteristic Polynomial Clément Meeting ORCCA-SCG, February 9, 2007 Clément Pernet Matrix multiplication based Characteristic Polynomial

  3. Telerobotic management system: coordinating multiple human operators with multiple robots

    NASA Astrophysics Data System (ADS)

    King, Jamie W.; Pretty, Raymond; Brothers, Brendan; Gosine, Raymond G.

    2003-09-01

    This paper describes an application called the Tele-robotic management system (TMS) for coordinating multiple operators with multiple robots for applications such as underground mining. TMS utilizes several graphical interfaces to allow the user to define a partially ordered plan for multiple robots. This plan is then converted to a Petri net for execution and monitoring. TMS uses a distributed framework to allow robots and operators to easily integrate with the applications. This framework allows robots and operators to join the network and advertise their capabilities through services. TMS then decides whether tasks should be dispatched to a robot or a remote operator based on the services offered by the robots and operators.

  4. [Multiple myeloma with D immunoglobulin].

    PubMed

    Benchekroun, Laila; Ouzzif, Zohra; Bouabdillah, Mounya; Jaouhar, Nouzha; Aoufir, Fatiha; Aoufi, Farida; Chabraoui, Layachi

    2011-01-01

    The immunoglobulin D multiple myeloma is a rare form of multiple myeloma and affects a young population. It is characterized by its clinical severity and poor prognosis. We report four cases of multiple myeloma immunoglobulin D diagnosed and supported in the university hospital Center of Sale and Rabat-Morocco. We propose to study the epidemiological, clinical and biological characteristics of this rare type of monoclonal gammopathy. Through the observations reported, the clinical aspect of myeloma is characterized by the high frequency of extra-bone manifestations including impaired kidney function. The immunoglobulin D multiple myeloma is mainly type ?, the IgD ? is rare, the predominance of ? light chains could be explained by rearrangements at the immunoglobulin genes. Bence-Jones proteinuria is almost constant in the multiple myeloma immunoglobulin D, it is mainly type ?, reflecting excess production of light chains by plasma cells. The marrow is invaded by plasma cells in very different proportions of up to 95%. It's a clinical entity, difficult to diagnose, particularly when low homogeneous band on electrophoresis goes unnoticed for an eye inexperienced or when immune serum anti-IgD was not used during the immunotyping. PMID:22008139

  5. Biological auctions with multiple rewards.

    PubMed

    Reiter, Johannes G; Kanodia, Ayush; Gupta, Raghav; Nowak, Martin A; Chatterjee, Krishnendu

    2015-08-01

    The competition for resources among cells, individuals or species is a fundamental characteristic of evolution. Biological all-pay auctions have been used to model situations where multiple individuals compete for a single resource. However, in many situations multiple resources with various values exist and single reward auctions are not applicable. We generalize the model to multiple rewards and study the evolution of strategies. In biological all-pay auctions the bid of an individual corresponds to its strategy and is equivalent to its payment in the auction. The decreasingly ordered rewards are distributed according to the decreasingly ordered bids of the participating individuals. The reproductive success of an individual is proportional to its fitness given by the sum of the rewards won minus its payments. Hence, successful bidding strategies spread in the population. We find that the results for the multiple reward case are very different from the single reward case. While the mixed strategy equilibrium in the single reward case with more than two players consists of mostly low-bidding individuals, we show that the equilibrium can convert to many high-bidding individuals and a few low-bidding individuals in the multiple reward case. Some reward values lead to a specialization among the individuals where one subpopulation competes for the rewards and the other subpopulation largely avoids costly competitions. Whether the mixed strategy equilibrium is an evolutionarily stable strategy (ESS) depends on the specific values of the rewards. PMID:26180069

  6. Gasdynamic Multiple-Mirror Trap

    NASA Astrophysics Data System (ADS)

    Beklemishev, Alexei; Anikeev, Andrei; Bagryansky, Peter; Burdakov, Alexander; Gavrilenko, Dmitrii; Ivanov, Alexander; Polosatkin, Sergei; Sinitsky, Stanislav

    2013-10-01

    The new linear device for confinement of fusion plasmas, GDMT, is being developed at the Budker Institute of Nuclear Physics, Novosibirsk. The facility will combine features of existing GOL-3 and GDT devices: the central GDT-like cell with sloshing NBI ions, and the multiple-mirror plugs for suppression of axial losses. Such combination became feasible due to recent discoveries. In particular, the requirement of flute-mode stability can be relaxed by using vortex confinement, achieved by plasma biasing through open field lines. This allows the use of potentially destabilizing multiple-mirror sections. Another key effect is the enhanced multiple-mirror confinement at low densities, which is due to collective rather than coulomb scattering of ions. Hence the multiple-mirror plugs can work at pressures compatible with magnetic confinement. These two main technologies are supplemented by axial injection of pulsed electron beams. Besides additional plasma heating (like in GOL-3), such injection can be used for induced collective scattering in the multiple-mirror plugs and for plasma biasing. The new device is designed to be superconducting and modular. It will be built in stages, with the first stage, GDMT-T, intended for PMI studies. The work was financially supported by Ministry of Education and Science RF.

  7. Constraining multiple systems with GAIA

    NASA Astrophysics Data System (ADS)

    Beauvalet, L.; Lainey, V.; Arlot, J.-E.; Bancelin, D.; Binzel, R. P.; Marchis, F.

    2012-12-01

    GAIA will provide observations of some multiple asteroid and dwarf systems. These observations are a way to determine and improve the quantification of dynamical parameters, such as the masses and the gravity fields, in these multiple systems. Here we investigate this problem in the cases of Pluto's and Eugenia's system. We simulate observations reproducing an approximate planning of the GAIA observations for both systems, as well as the New Horizons observations of Pluto. We have developed a numerical model reproducing the specific behavior of multiple asteroid system around the Sun and fit it to the simulated observations using least-square method, giving the uncertainties on the fitted parameters. We found that GAIA will improve significantly the precision of Pluto's and Charon's mass, as well as Petit Prince's orbital elements and Eugenia's polar oblateness.

  8. Multiple smart weapons employment mechanism

    SciTech Connect

    McGlynn, M.P.; Meiklejohn, W.D.

    1993-07-20

    A digital communications armament network adaptor is described for carrying multiple smart weapons on a single wing pylon station of an aircraft, comprising: an aircraft having a weapons controller configured in compliance with MIL-STD 1553; multiple wing-mounted pylons on said aircraft, each providing a weapons station with communications and ejection and release mechanisms electrically connected to said controller for the airborne launch of smart weapons; a multiple ejector rack affixed to at least one pylon, said rack holding a plurality of smart weapons; and an electronic digital network connected between the controller and said rack-mounted smart weapons, said network located in said rack and including circuitry which receives coded digital communications from said controller and selectively rebroadcasts said communications to one of said smart weapons on said rack designated by said coded communications, thereby controlling all required functions of said designated smart weapon.

  9. Convergence and Discriminant: Assessing Multiple Traits Using Multiple Methods

    ERIC Educational Resources Information Center

    Pae, Hye K.

    2012-01-01

    Multiple traits of language proficiency as well as test method effects were concurrently analyzed to investigate interrelations of construct validity, convergent validity, and discriminant validity using multitrait-multimethod (MTMM) matrices. A total of 585 test takers' scores were derived from the field test of the "Pearson Test of English…

  10. Multiple Imputation Strategies for Multiple Group Structural Equation Models

    ERIC Educational Resources Information Center

    Enders, Craig K.; Gottschall, Amanda C.

    2011-01-01

    Although structural equation modeling software packages use maximum likelihood estimation by default, there are situations where one might prefer to use multiple imputation to handle missing data rather than maximum likelihood estimation (e.g., when incorporating auxiliary variables). The selection of variables is one of the nuances associated…

  11. Multiple resonant railgun power supply

    DOEpatents

    Honig, E.M.; Nunnally, W.C.

    1985-06-19

    A multiple repetitive resonant railgun power supply provides energy for repetitively propelling projectiles from a pair of parallel rails. A plurality of serially connected paired parallel rails are powered by similar power supplies. Each supply comprises an energy storage capacitor, a storage inductor to form a resonant circuit with the energy storage capacitor and a magnetic switch to transfer energy between the resonant circuit and the pair of parallel rails for the propelling of projectiles. The multiple serial operation permits relatively small energy components to deliver overall relatively large amounts of energy to the projectiles being propelled.

  12. Multiple resonant railgun power supply

    DOEpatents

    Honig, Emanuel M. (Los Alamos, NM); Nunnally, William C. (Los Alamos, NM)

    1988-01-01

    A multiple repetitive resonant railgun power supply provides energy for repetitively propelling projectiles from a pair of parallel rails. A plurality of serially connected paired parallel rails are powered by similar power supplies. Each supply comprises an energy storage capacitor, a storage inductor to form a resonant circuit with the energy storage capacitor and a magnetic switch to transfer energy between the resonant circuit and the pair of parallel rails for the propelling of projectiles. The multiple serial operation permits relatively small energy components to deliver overall relatively large amounts of energy to the projectiles being propelled.

  13. Multiple order common path spectrometer

    NASA Technical Reports Server (NTRS)

    Newbury, Amy B. (Inventor)

    2010-01-01

    The present invention relates to a dispersive spectrometer. The spectrometer allows detection of multiple orders of light on a single focal plane array by splitting the orders spatially using a dichroic assembly. A conventional dispersion mechanism such as a defraction grating disperses the light spectrally. As a result, multiple wavelength orders can be imaged on a single focal plane array of limited spectral extent, doubling (or more) the number of spectral channels as compared to a conventional spectrometer. In addition, this is achieved in a common path device.

  14. Multiplicative calculus and its applications

    NASA Astrophysics Data System (ADS)

    Bashirov, Agamirza E.; Kurpinar, Emine Misirli; Özyapici, Ali

    2008-01-01

    Two operations, differentiation and integration, are basic in calculus and analysis. In fact, they are the infinitesimal versions of the subtraction and addition operations on numbers, respectively. In the period from 1967 till 1970 Michael Grossman and Robert Katz gave definitions of a new kind of derivative and integral, moving the roles of subtraction and addition to division and multiplication, and thus established a new calculus, called multiplicative calculus. In the present paper our aim is to bring up this calculus to the attention of researchers and demonstrate its usefulness.

  15. Systematic imaging review: Multiple Sclerosis

    PubMed Central

    Katdare, Aparna; Ursekar, Meher

    2015-01-01

    Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system characterised by immune-mediated demyelination, and is a leading cause of neurological disability worldwide. It has a wide spectrum of clinical presentations which overlap with other neurological conditions many times. Further, the radiological array of findings in MS can also be confused for multiple other conditions, leading to the need to look for the more typical findings, and interpret these in close conjunction with the clinical picture including temporal evolution. This review aims to revisit the MRI findings in MS, including recent innovations in imaging, and to help distinguish MS from its mimics. PMID:26538845

  16. Effects of gene deletion of the tissue inhibitor of the matrix metalloproteinase-type 1 (TIMP-1) on left ventricular geometry and function in mice

    NASA Technical Reports Server (NTRS)

    Roten, L.; Nemoto, S.; Simsic, J.; Coker, M. L.; Rao, V.; Baicu, S.; Defreyte, G.; Soloway, P. J.; Zile, M. R.; Spinale, F. G.

    2000-01-01

    Alterations in the expression and activity of the matrix metalloproteinases (MMPs) and the tissue inhibitors of the MMPs (TIMPs) have been implicated in tissue remodeling in a number of disease states. One of the better characterized TIMPs, TIMP-1, has been shown to bind to active MMPs and to regulate the MMP activational process. The goal of this study was to determine whether deletion of the TIMP-1 gene in mice, which in turn would remove TIMP-1 expression in LV myocardium, would produce time-dependent effects on LV geometry and function. Age-matched sibling mice (129Sv) deficient in the TIMP-1 gene (TIMP-1 knock-out (TIMP-1 KO), n=10) and wild-type mice (n=10) underwent comparative echocardiographic studies at 1 and 4 months of age. LV catheterization studies were performed at 4 months and the LV harvested for histomorphometric studies. LV end-diastolic volume and mass increased (18+/-4 and 38+/-3%, respectively, P<0.05) at 4 months in the TIMP-1 KO group; a significant increase compared to wild-type controls (P<0.05). At 4 months, LV and end-diastolic wall stress was increased by over two-fold in the TIMP-1 KO compared to wild type (P<0.05). However, LV systolic pressure and ejection performance were unchanged in the two groups of mice. LV myocyte cross-sectional area was unchanged in the TIMP-1 KO mice compared to controls, but myocardial fibrillar collagen content was reduced. Changes in LV geometry occurred in TIMP-1 deficient mice and these results suggest that constitutive TIMP-1 expression participates in the maintenance of normal LV myocardial structure. Copyright 2000 Academic Press.

  17. One Step Construction of Agrobacterium Recombination-ready-plasmids (OSCAR), an efficient and robust tool for ATMT based gene deletion construction in fungi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing availability of genomic data and sophistication of analytical methodology in fungi has elevated the need for functional genomics tools in these organisms. Previously we reported a method called DelsGate for rapid preparation of deletion constructs for protoplast-mediated fungal transforma...

  18. Attenuation, transmission, and immunogenicity of an ORF-C gene deleted strain of infectious laryngotracheitis virus (ILTV) in specific pathogen free chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infectious laryngotracheitis (ILT) is a very serious and widespread respiratory disease of chickens caused by infectious laryngotracheitis virus (ILTV). Conventional attenuated ILT vaccines, obtained by continuous passages in chicken embryos and tissue culture, had been the main tools utilized by th...

  19. Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron-type dwarfism.

    PubMed Central

    Godowski, P J; Leung, D W; Meacham, L R; Galgani, J P; Hellmiss, R; Keret, R; Rotwein, P S; Parks, J S; Laron, Z; Wood, W I

    1989-01-01

    Laron-type dwarfism is an autosomal recessive genetic disorder that is characterized by high levels of growth hormone and low levels of insulin-like growth factor I in the circulation. Several lines of evidence suggest that this disease is caused by a defect in the growth hormone receptor. In order to analyze the receptor gene in patients with Laron-type dwarfism and with other growth disorders, we have first determined the gene structure in normal individuals. There are nine exons that encode the receptor and several additional exons in the 5' untranslated region. The coding exons span at least 87 kilobase pairs of chromosome 5. Characterization of the growth hormone receptor gene from nine patients with Laron-type dwarfism shows that two individuals have a deletion of a large portion of the extracellular, hormone binding domain of the receptor gene. Interestingly, this deletion includes nonconsecutive exons, suggesting that an unusual rearrangement may have occurred. Thus, we provide direct evidence that Laron-type dwarfism can result from a defect in the structural gene for the growth hormone receptor. Images PMID:2813379

  20. A gene deletion that up-regulates viral gene expression yields an attenuated RSV vaccine with improved antibody responses in children.

    PubMed

    Karron, Ruth A; Luongo, Cindy; Thumar, Bhagvanji; Loehr, Karen M; Englund, Janet A; Collins, Peter L; Buchholz, Ursula J

    2015-11-01

    Respiratory syncytial virus (RSV) is the leading viral cause of severe pediatric respiratory illness, and a safe and effective vaccine for use in infancy and early childhood is needed. We previously showed that deletion of the coding sequence for the viral M2-2 protein (?M2-2) down-regulated viral RNA replication and up-regulated gene transcription and antigen synthesis, raising the possibility of development of an attenuated vaccine with enhanced immunogenicity. RSV MEDI ?M2-2 was therefore evaluated as a live intranasal vaccine in adults, RSV-seropositive children, and RSV-seronegative children. When results in RSV-seronegative children were compared to those achieved with the previous leading live attenuated RSV candidate vaccine, vaccine virus shedding was significantly more restricted, yet the postvaccination RSV-neutralizing serum antibody achieved [geometric mean titer (GMT) = 1:97] was significantly greater. Surveillance during the subsequent RSV season showed that several seronegative RSV MEDI ?M2-2 recipients had substantial antibody rises without reported illness, suggesting that the vaccine was protective yet primed for anamnestic responses to RSV. Rational design appears to have yielded a candidate RSV vaccine that is intrinsically superior at eliciting protective antibody in RSV-naïve children and highlights an approach for the development of live attenuated RSV vaccines. PMID:26537255

  1. Delineation of the clinically recognizable 17q22 contiguous gene deletion syndrome in a patient carrying the smallest microdeletion known to date.

    PubMed

    Martínez-Fernández, María Luisa; Fernández-Toral, Joaquin; Llano-Rivas, Isabel; Bermejo-Sánchez, Eva; MacDonald, Alexandra; Martínez-Frías, María Luisa

    2015-09-01

    We describe a patient with a 1.34?Mb microdeletion at chromosome band 17q22, which is also present in his affected mother. To better delineate this microdeletion syndrome, we compare the clinical and molecular characteristics of 10 previously reported cases and our patient. Of these, the present patient has the smallest deletion which includes five genes: MMD, TMEM100, PCTP, ANKFN1, and NOG. We compare the clinical manifestations described in relation to NOG, since this is the only gene whose loss is shared by our patient and the other eight patients. Previously, the clinical patterns associated with NOG mutations have been included under the general term "NOG-related symphalangism spectrum disorder (NOG-SSD)." Based on our analyses, and considering that there is a clinical correlation observed in cases with a "17q22 microdeletion including NOG" of which the main characteristics can be contributed to loss of this gene, we propose that the clinical patterns observed in these patients should be named as NOG-spectrum disorder-contiguous gene syndrome (NOGSD-CGS). This designation is important for clinicians because when a patient has defects concordant with alterations of NOG but also presents other anomalies not related to this gene, they would be able to suspect the existence of a microdeletion affecting 17q22, therefore, allowing an early diagnosis. This will also enable the clinician to provide the family with adequate information about the prognosis and the risk of reoccurrence in future potential offspring. PMID:25899082

  2. Molecular cloning and chromosomal localization of the human cyclin C (CCNC) and cyclin E (CCNE) genes: Deletion of the CCNC gene in human tumors

    SciTech Connect

    Li, Haimin; Lahti, J.M.; Kidd, V.J.

    1996-03-01

    The human G1-phase cyclins are important regulators of cell cycle progression that interact with various cyclin-dependent kinases and facilitate entry into S-phase. We have confirmed the localization of the human cyclin C (CCNC) gene to chromosome 6q21 and of human cyclin E (CCNE to 19q12). The CCNC gene structure was also determined, and we have shown that it is deleted in a subset of acute lymphoblastic leukemias, including a patient sample containing a t(2;6)(p21;q15), with no apparent cytogenetic deletion. Single-strand conformational polymorphism analysis of the remaining CCNC allele from patients with a deletion of one allele established that there were no further mutations within the exons or the flanking intronic sequences. These results suggest either that haploinsufficiency of the cyclin C protein is sufficient to promote tumorigenesis or that the important tumor suppressor gene is linked to the CCNC locus. 48 refs., 4 figs., 1 tab.

  3. Whole-Genome Microarray and Gene Deletion Studies Reveal Regulation of the Polyhydroxyalkanoate Production Cycle by the Stringent Response in Ralstonia eutropha H16

    PubMed Central

    Brigham, Christopher J.; Speth, Daan R.; Rha, ChoKyun

    2012-01-01

    Poly(3-hydroxybutyrate) (PHB) production and mobilization in Ralstonia eutropha are well studied, but in only a few instances has PHB production been explored in relation to other cellular processes. We examined the global gene expression of wild-type R. eutropha throughout the PHB cycle: growth on fructose, PHB production using fructose following ammonium depletion, and PHB utilization in the absence of exogenous carbon after ammonium was resupplied. Our results confirm or lend support to previously reported results regarding the expression of PHB-related genes and enzymes. Additionally, genes for many different cellular processes, such as DNA replication, cell division, and translation, are selectively repressed during PHB production. In contrast, the expression levels of genes under the control of the alternative sigma factor ?54 increase sharply during PHB production and are repressed again during PHB utilization. Global gene regulation during PHB production is strongly reminiscent of the gene expression pattern observed during the stringent response in other species. Furthermore, a ppGpp synthase deletion mutant did not show an accumulation of PHB, and the chemical induction of the stringent response with dl-norvaline caused an increased accumulation of PHB in the presence of ammonium. These results indicate that the stringent response is required for PHB accumulation in R. eutropha, helping to elucidate a thus-far-unknown physiological basis for this process. PMID:22961894

  4. Cockayne Syndrome due to a maternally-inherited whole gene deletion of ERCC8 and a paternally-inherited ERCC8 exon 4 deletion.

    PubMed

    Ting, T W; Brett, M S; Tan, E S; Shen, Y; Lee, S P; Lim, E C; Vasanwala, R F; Lek, N; Thomas, T; Lim, K W; Tan, E C

    2015-11-10

    Cockayne Syndrome (CS) is an autosomal recessive disorder that causes neurological regression, growth failure and dysmorphic features. We describe a Chinese female child with CS caused by deletions of exon 4 of ERCC8 on one chromosome and exons 1-12 on the other chromosome. By using chromosomal microarray, multiplex ligation-dependant probe analysis and long range PCR, we showed that she inherited a 277 kb deletion affecting the whole ERCC8 gene from the mother and a complex rearrangement resulting in deletion of exon 4 together with a 1,656 bp inversion of intron 4 from the father. A similar complex rearrangement has been reported in four unrelated Japanese CS patients. Analysis of the deletion involving exon 4 identified LINE and other repeat elements that may predispose the region to deletions, insertions and inversions. The patient also had insulin-dependent diabetes mellitus, a rare co-existing feature in patients with CS. More research will be needed to further understand the endocrine manifestations in CS patients. PMID:26210811

  5. Neurofilament light gene deletion exacerbates amyloid, dystrophic neurite, and synaptic pathology in the APP/PS1 transgenic model of Alzheimer's disease.

    PubMed

    Fernandez-Martos, Carmen M; King, Anna E; Atkinson, Rachel A K; Woodhouse, Adele; Vickers, James C

    2015-10-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with the loss of cognitive function. Neurofilament (NF) triplet proteins, the major structural (intermediate filament) proteins of neurons, are expressed in a subset of pyramidal cells that show a high degree of vulnerability to degeneration in AD. Alterations in the NF triplet proteins in amyloid-beta (A?) plaque-associated dystrophic neurites (DNs) represent the first cytoskeletal aberration to occur in the neocortex in the earliest stages of AD. We generated transgenic APP/PS1 (APPswe/PSEN1dE9) mice on the neurofilament light knockout (NFL KO) background to explore the role of NFL deletion in the context of DN formation, synaptic changes, and other neuropathologic features. Our analysis demonstrated that NFL deficiency significantly increased neocortical DN pathology, A? deposition, synapse vulnerability, and microgliosis in APP/PS1 mice. Thus, NFs may have a role in protecting neurites from dystrophy and in regulating cellular pathways related to the generation of A? plaques. PMID:26344875

  6. Whole-Genome Microarray and Gene Deletion Studies Reveal Regulation of the Polyhydroxyalkanoate Production Cycle by the Stringent Response in Ralstonia eutropha H16

    SciTech Connect

    Brigham, CJ; Speth, DR; Rha, C; Sinskey, AJ

    2012-10-22

    Poly(3-hydroxybutyrate) (PHB) production and mobilization in Ralstonia eutropha are well studied, but in only a few instances has PHB production been explored in relation to other cellular processes. We examined the global gene expression of wild-type R. eutropha throughout the PHB cycle: growth on fructose, PHB production using fructose following ammonium depletion, and PHB utilization in the absence of exogenous carbon after ammonium was resupplied. Our results confirm or lend support to previously reported results regarding the expression of PHB-related genes and enzymes. Additionally, genes for many different cellular processes, such as DNA replication, cell division, and translation, are selectively repressed during PHB production. In contrast, the expression levels of genes under the control of the alternative sigma factor sigma(54) increase sharply during PHB production and are repressed again during PHB utilization. Global gene regulation during PHB production is strongly reminiscent of the gene expression pattern observed during the stringent response in other species. Furthermore, a ppGpp synthase deletion mutant did not show an accumulation of PHB, and the chemical induction of the stringent response with DL-norvaline caused an increased accumulation of PHB in the presence of ammonium. These results indicate that the stringent response is required for PHB accumulation in R. eutropha, helping to elucidate a thus-far-unknown physiological basis for this process.

  7. A Rhomboid Protease Gene Deletion Affects a Novel Oligosaccharide N-Linked to the S-layer Glycoprotein of Haloferax volcanii*

    PubMed Central

    Parente, Juliana; Casabuono, Adriana; Ferrari, María Celeste; Paggi, Roberto Alejandro; De Castro, Rosana Esther; Couto, Alicia Susana; Giménez, María Inés

    2014-01-01

    Rhomboid proteases occur in all domains of life; however, their physiological role is not completely understood, and nothing is known of the biology of these enzymes in Archaea. One of the two rhomboid homologs of Haloferax volcanii (RhoII) is fused to a zinc finger domain. Chromosomal deletion of rhoII was successful, indicating that this gene is not essential for this organism; however, the mutant strain (MIG1) showed reduced motility and increased sensitivity to novobiocin. Membrane preparations of MIG1 were enriched in two glycoproteins, identified as the S-layer glycoprotein and an ABC transporter component. The H. volcanii S-layer glycoprotein has been extensively used as a model to study haloarchaeal protein N-glycosylation. HPLC analysis of oligosaccharides released from the S-layer glycoprotein after PNGase treatment revealed that MIG1 was enriched in species with lower retention times than those derived from the parent strain. Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. A glycoproteomics approach of the wild type glycopeptide fraction revealed Asn-732 peptide fragments linked to the sulfoquinovose-containing oligosaccharide. This work describes a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated. Furthermore, this study provides the first insight on the biological role of rhomboid proteases in Archaea, suggesting a link between protein glycosylation and this protease family. PMID:24596091

  8. A rhomboid protease gene deletion affects a novel oligosaccharide N-linked to the S-layer glycoprotein of Haloferax volcanii.

    PubMed

    Parente, Juliana; Casabuono, Adriana; Ferrari, María Celeste; Paggi, Roberto Alejandro; De Castro, Rosana Esther; Couto, Alicia Susana; Giménez, María Inés

    2014-04-18

    Rhomboid proteases occur in all domains of life; however, their physiological role is not completely understood, and nothing is known of the biology of these enzymes in Archaea. One of the two rhomboid homologs of Haloferax volcanii (RhoII) is fused to a zinc finger domain. Chromosomal deletion of rhoII was successful, indicating that this gene is not essential for this organism; however, the mutant strain (MIG1) showed reduced motility and increased sensitivity to novobiocin. Membrane preparations of MIG1 were enriched in two glycoproteins, identified as the S-layer glycoprotein and an ABC transporter component. The H. volcanii S-layer glycoprotein has been extensively used as a model to study haloarchaeal protein N-glycosylation. HPLC analysis of oligosaccharides released from the S-layer glycoprotein after PNGase treatment revealed that MIG1 was enriched in species with lower retention times than those derived from the parent strain. Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. A glycoproteomics approach of the wild type glycopeptide fraction revealed Asn-732 peptide fragments linked to the sulfoquinovose-containing oligosaccharide. This work describes a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated. Furthermore, this study provides the first insight on the biological role of rhomboid proteases in Archaea, suggesting a link between protein glycosylation and this protease family. PMID:24596091

  9. Non-virulence of a recombinant shrimp nidovirus is associated with its non structural gene sequence and not a large structural gene deletion

    SciTech Connect

    Gangnonngiw, Warachin; Anantasomboon, Gun; Sang-oum, Wiwat; Sriurairatana, Siriporn; Sritunyalucksana, Kallaya; Flegel, Timothy W.

    2009-03-01

    RT-PCR using a commercial kit for yellow head virus (YHV) detection in growth-retarded shrimp yielded an unusual 777 bp amplicon instead of expected amplicons of 277 bp for YHV type-1 (YHV-1) or 406 bp for YHV type-2 (YHV-2). Cloning and sequencing (GenBank (EU170438)) revealed approximately 80% identity to non-structural (NS) ORF1b sequences of both YHV-1 (GenBank (AA083987)) and YHV-2 (GenBank (AF227196)), indicating an atypical YHV type (A-YHV) phylogenetically equidistant from both types. An RT-PCR test specifically designed for A-YHV revealed that it was uncommon and that its occurrence in shrimp culture ponds did not correlate with growth retardation or mortality. By immunohistochemistry with YHV-specific monoclonal antibodies, the A-YHV gave positive reactions for envelope protein gp64 and capsid protein p20, but not for envelope protein gp116, even though gp116 and gp64 originate from a polyprotein of ORF3. Lack of gp116 immunoreactivity correlated with a large ORF3 deletion (GenBank (EU123854)) in the region of the protein targeted by an MAb against gp116. Transmission electron microscopy of A-YHV-infected shrimp revealed only unenveloped pre-virions. During manuscript revision, information received revealed that typing of YHV isolates based on sequences of ORF1b and ORF3 had yielded several geographical types, including one virulent type (YHV-1b) with an ORF3 deletion sequence that matched the sequence of A-YHV. Using these sequences and an additional A-YHV sequence ( (EU853170)) from the ORF1b typing region, A-YHV potentially represents a recombinant between type 1b and type 5. SDS-PAGE and Western blot analysis revealed that type 1b produced a gp116 deletion protein that did not bind with the MAb or polyclonal Ab to normal gp116. Overall, the information suggested that lack of A-YHV virulence was associated with the NS gene sequence linked to ORF1b rather than the deletion in ORF3.

  10. Complementary expression and phosphorylation of Cx46 and Cx50 during development and following gene deletion in mouse and in normal and orchitic mink testes.

    PubMed

    Pelletier, R-Marc; Akpovi, Casimir D; Chen, Li; Kumar, Nalin M; Vitale, María L

    2015-08-01

    Gap junction-mediated communication helps synchronize interconnected Sertoli cell activities. Besides, coordination of germ cell and Sertoli cell activities depends on gap junction-mediated Sertoli cell-germ cell communication. This report assesses mechanisms underlying the regulation of connexin 46 (Cx46) and Cx50 in mouse testis and those accompanying a "natural" seasonal and a pathological arrest of spermatogenesis, resulting from autoimmune orchitis (AIO) in mink. Furthermore, the impact of deleting Cx46 or Cx50 on the expression, phosphorylation of junction proteins, and spermatogenesis is evaluated. Cx46 mRNA and protein expression increased, whereas Cx50 decreased with adulthood in normal mice and mink. Cx46 mRNA and protein expression increased, whereas Cx50 decreased with adulthood in normal mice and mink. During the mink active spermatogenic phase, Cx50 became phosphorylated and localized to the site of the blood-testis barrier. By contrast, Cx46 was dephosphorylated and associated with annular junctions, suggesting phosphorylation/dephosphorylation of Cx46 and Cx50 involvement in the barrier dynamics. Cx46-positive annular junctions in contact with lipid droplets were found. Cx46 and Cx50 expression and localization were altered in mink with AIO. The deletion of Cx46 or Cx50 impacted on other connexin expression and phosphorylation and differently affected tight and adhering junction protein expression. The level of apoptosis, determined by ELISA, and a number of Apostain-labeled spermatocytes and spermatids/tubules were higher in mice lacking Cx46 (Cx46-/-) than wild-type and Cx50-/- mice, arguing for life-sustaining Cx46 gap junction-mediated exchanges in late-stage germ cells secluded from the blood by the barrier. The data show that expression and phosphorylation of Cx46 and Cx50 are complementary in seminiferous tubules. PMID:26017495

  11. One step construction of agrobacterium recombination-ready plasmids (OSCAR), an efficient and robust tool for ATMT based gene deletion construction in fungi.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing availability of genomic data and sophistication of analytical methodology in fungi has elevated the need for functional genomics tools in these organisms. Previously we reported a method called DelsGate for rapid preparation of deletion constructs for protoplast-mediated fungal transforma...

  12. Dean's Great Discovery: Multiplication, Division and Fractions

    ERIC Educational Resources Information Center

    Vale, Colleen; Davies, Anne

    2007-01-01

    Multiplication, division and fractions are "hotspots" for students in the middle years with many students experiencing difficulty with these concepts. Arrays effectively model multiplication and help children develop multiplicative thinking and learn multiplication facts. In this article the authors show how an open-ended array problem enabled a…

  13. Multiple Pathways for All Students

    ERIC Educational Resources Information Center

    Stirling, Lee Anna

    2012-01-01

    Maine has been focusing on the importance of postsecondary training. Maine's Skowhegan Area High School (SAHS) and Somerset Career and Technical Center (SCTC) have partnered in a Multiple Pathways initiative (funded by the Nellie Mae Education Foundation) to increase students' high school completion rate and to increase enrollment in postsecondary…

  14. Introductory Lectures on Multiple Membranes

    E-print Network

    Copland, Neil B

    2010-01-01

    These lecture notes introduce the multiple membrane theories known as BLG and ABJM. We assume the reader is familiar with string theory, but not with M-theory, 11-dimensional supergravity or membranes. We therefore start with a background on M-theory and its extended objects before discussing BLG and ABJM. The link to string theory via dimensional reduction will be maintained throughout.

  15. Introductory Lectures on Multiple Membranes

    E-print Network

    Neil B. Copland

    2010-12-02

    These lecture notes introduce the multiple membrane theories known as BLG and ABJM. We assume the reader is familiar with string theory, but not with M-theory, 11-dimensional supergravity or membranes. We therefore start with a background on M-theory and its extended objects before discussing BLG and ABJM. The link to string theory via dimensional reduction will be maintained throughout.

  16. Multiple Intelligences and Business Diversity.

    ERIC Educational Resources Information Center

    Martin, Joyce

    2003-01-01

    Results from 97 business students with substantial work histories indicate that the Multiple Intelligence Preference Inventory gives a valid and reliable indication of their preferred intelligences. Awareness of these results is associated with assessments of self and others as knowledge sources. This information can help in recognizing,…

  17. Overhearing Single and Multiple Perspectives

    ERIC Educational Resources Information Center

    Fox Tree, Jean E.; Mayer, Sarah A.

    2008-01-01

    In 2 spontaneous speech experiments, this study found that multiple perspectives improved overhearers' abilities to select abstract shapes from an array, although single-perspective descriptions were more detailed. Prior findings that overhearers performed better when listening in on dialogues (Fox Tree, 1999) can best be understood as an…

  18. Fashion, Paper Dolls and Multiplicatives

    ERIC Educational Resources Information Center

    Ura, Suzana Kaori; Stein-Barana, Alzira C. M.; Munhoz, Deisy P.

    2011-01-01

    The multiplicative principle is the tool allowing the counting of groups that can be described by a sequence of events. An event is a subset of sample space, i.e. a collection of possible outcomes, which may be equal to or smaller than the sample space as a whole. It is important that students understand this basic principle early on and know how…

  19. Multiple venous aneurysms of neck

    PubMed Central

    Swaika, Sweta; Basu, Sudipta; Bhadra, Ram C.; Maitra, Sujay

    2013-01-01

    Venous aneurysm of neck is a rare anomaly, usually presenting as a painless mass which increases in size on valsalva maneuver. A child with multiple aneurysms of the right common facial and external jugular veins diagnosed on Doppler ultrasonography and magnetic resonance venography is reported. PMID:23599580

  20. Presentation 7: Multiple Primary Rules

    Cancer.gov

    MP Rules - Note 2 The registrar must recognize that during the diagnostic workup the physician may start with a non-specific diagnosis (NOS) and as testing is completed, a more specific histology is identified. These diagnoses are not multiple primaries; they represent steps in the diagnostic work-up. See rules M7-M12.

  1. Improving Inferences from Multiple Methods.

    ERIC Educational Resources Information Center

    Shotland, R. Lance; Mark, Melvin M.

    1987-01-01

    Multiple evaluation methods (MEMs) can cause an inferential challenge, although there are strategies to strengthen inferences. Practical and theoretical issues involved in the use by social scientists of MEMs, three potential problems in drawing inferences from MEMs, and short- and long-term strategies for alleviating these problems are outlined.…

  2. Characteristics of Multiple Comparison Procedures.

    ERIC Educational Resources Information Center

    Yusuf, Mian Muhammad; And Others

    Multiple comparison procedures (MCPs), in the context of analysis of variance, are becoming more popular than the overall F tests. An attempt is made to clarify confusion among the different MCPs by systematically comparing and contrasting the procedures in terms of their purposes, restrictions, robustness to assumptions, and other special…

  3. Assessment of Multiplication Fact Fluency

    ERIC Educational Resources Information Center

    Ford, Marilyn Sue; Usnick, Virginia

    2011-01-01

    This project had two major goals: to determine the usefulness of individually-administered interview process to access elementary students' fluency with basic multiplication facts, and to determine whether a developmental sequence found in Australian mathematics education literature applied to elementary students in the United States. Students in…

  4. Multiple Literacies Theory: Exploring Futures

    ERIC Educational Resources Information Center

    Masny, Diana

    2011-01-01

    This article focuses on the contributions of philosophy, art and science to education through the conceptual, theoretical, and methodological usefulness of a Deleuze-Guattarian conceptual framework that informs multiple literacies theory (MLT). Education lends itself to Deleuze's notion of connecting and creating through philosophy, art and…

  5. Childhood Multiple Sclerosis: A Review

    ERIC Educational Resources Information Center

    Waldman, Amy; O'Connor, Erin; Tennekoon, Gihan

    2006-01-01

    Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) that is increasingly recognized as a disease that affects children. Similar to adult-onset MS, children present with visual and sensory complaints, as well as weakness, spasticity, and ataxia. A lumbar puncture can be helpful in diagnosing MS when…

  6. Fungible Weights in Multiple Regression

    ERIC Educational Resources Information Center

    Waller, Niels G.

    2008-01-01

    Every set of alternate weights (i.e., nonleast squares weights) in a multiple regression analysis with three or more predictors is associated with an infinite class of weights. All members of a given class can be deemed "fungible" because they yield identical "SSE" (sum of squared errors) and R[superscript 2] values. Equations for generating…

  7. Viscoelastic waves and multiple scales

    SciTech Connect

    Hedstrom, G.

    1994-05-01

    A multiple-scales argument is used to obtain the speeds of the main shear and compressional waves in a general homogeneous viscoelastic medium. The rate of spreading by diffusion of these waves is also derived. These methods are also used to determine the speed of the main viscoelastic Rayleigh wave, as well as the rate of its energy decay.

  8. The STAR Photon Multiplicity Detector

    E-print Network

    M. M. Aggarwal; S. K. Badyal; P. Bhaskar; V. S. Bhatia; S. Chattopadhyay; S. Das; R. Datta; A. K. Dubey; M. R. DuttaMajumdar; M. S. Ganti; P. Ghosh; A. Gupta; M. Gupta; R. Gupta; I. Kaur; A. Kumar; S. Mahajan; D. P. Mahapatra; L. K. Mangotra; D. Mishra; B. Mohanty; S. K. Nayak; T. K. Nayak; S. K. Pal; S. C . Phatak; B. V. K. S. Potukuchi; R. Raniwala; S. Raniwala; R. Sahoo; A. Sharma; R. N. Singaraju; G. Sood; M. D. Trivedi; R. Varma; Y. P. Viyogi

    2002-12-07

    Details concerning the design, fabrication and performance of STAR Photon Multiplicity Detector (PMD) are presented. The PMD will cover the forward region, within the pseudorapidity range 2.3--3.5, behind the forward time projection chamber. It will measure the spatial distribution of photons in order to study collective flow, fluctuation and chiral symmetry restoration.

  9. Drugs Approved for Multiple Myeloma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for multiple myeloma and other plasma cell neoplasms. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  10. Enhancing Learning through Multiple Intelligences

    ERIC Educational Resources Information Center

    Ozdemir, Pinar; Guneysu, Sibel; Tekkaya, Ceren

    2006-01-01

    This study investigated whether there was a significant difference between multiple intelligence instruction (MII) and traditionally designed science instruction (TDSI) on fourth grade students' understanding of concepts associated with the "Diversity of Living Things" unit. Students' intelligence types were also examined. There were two…

  11. Dynamic Shifts in Corticostriatal Expression Patterns of the Immediate Early Genes "Homer 1a" and "Zif268" during Early and Late Phases of Instrumental Training

    ERIC Educational Resources Information Center

    Kelley, Ann E.; Hernandez, Pepe J.; Schiltz, Craig A.

    2006-01-01

    Adaptive motor actions require prior knowledge of instrumental contingencies. With practice, these actions can become highly automatic in nature. However, the molecular and anatomical substrates mediating these related forms of learning are not understood. In the present study, we used in situ hybridization to measure the mRNA levels of two…

  12. Connective tissue growth factor: a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10

    PubMed Central

    1991-01-01

    Human umbilical vein endothelial (HUVE) cells have been previously reported to express the genes for the A and B chains of PDGF and to secrete PDGF-related factors into culture media. Antihuman PDGF IgG affinity chromatography was used to purify PDGF-related activity from HUVE cell-conditioned media. Immunoblot analysis of the affinity- purified proteins with anti-PDGF IgG and antibodies specific for the A or B chain peptides of PDGF combined with chemotactic and mitogenic assays revealed that the major PDGF immunorelated molecule secreted by HUVE cells is a monomer of approximately 36-38 kD and that less than 10% of the purified biologically active molecules are PDGF A or B chain peptides. Screening of an HUVE cell cDNA library in the expression vector lambda gtl 1 with the anti-PDGF antibody resulted in the cloning and sequencing of a cDNA with an open reading frame encoding a 38-kD cysteine-rich secreted protein which we show to be the major PDGF- related mitogen secreted by human vascular endothelial cells. The protein has a 45% overall homology to the translation product of the v- src-induced CEF-10 mRNA from chick embryo fibroblasts. We have termed this new mitogen connective tissue growth factor. PMID:1654338

  13. An Indole Alkaloid from a Tribal Folklore Inhibits Immediate Early Event in HSV-2 Infected Cells with Therapeutic Efficacy in Vaginally Infected Mice

    PubMed Central

    Bag, Paromita; Ojha, Durbadal; Mukherjee, Hemanta; Halder, Umesh Chandra; Mondal, Supriya; Chandra, Nidhi S.; Nandi, Suman; Sharon, Ashoke; Sarkar, Mamta Chawla; Chakrabarti, Sekhar; Chattopadhyay, Debprasad

    2013-01-01

    Herpes genitalis, caused by HSV-2, is an incurable genital ulcerative disease transmitted by sexual intercourse. The virus establishes life-long latency in sacral root ganglia and reported to have synergistic relationship with HIV-1 transmission. Till date no effective vaccine is available, while the existing therapy frequently yielded drug resistance, toxicity and treatment failure. Thus, there is a pressing need for non-nucleotide antiviral agent from traditional source. Based on ethnomedicinal use we have isolated a compound 7-methoxy-1-methyl-4,9-dihydro-3H-pyrido[3,4-b]indole (HM) from the traditional herb Ophiorrhiza nicobarica Balkr, and evaluated its efficacy on isolates of HSV-2 in vitro and in vivo. The cytotoxicity (CC50), effective concentrations (EC50) and the mode of action of HM was determined by MTT, plaque reduction, time-of-addition, immunofluorescence (IFA), Western blot, qRT-PCR, EMSA, supershift and co-immunoprecipitation assays; while the in vivo toxicity and efficacy was evaluated in BALB/c mice. The results revealed that HM possesses significant anti-HSV-2 activity with EC50 of 1.1-2.8 µg/ml, and selectivity index of >20. The time kinetics and IFA demonstrated that HM dose dependently inhibited 50-99% of HSV-2 infection at 1.5-5.0 µg/ml at 2-4 h post-infection. Further, HM was unable to inhibit viral attachment or penetration and had no synergistic interaction with acyclovir. Moreover, Western blot and qRT-PCR assays demonstrated that HM suppressed viral IE gene expression, while the EMSA and co-immunoprecipitation studies showed that HM interfered with the recruitment of LSD-1 by HCF-1. The in vivo studies revealed that HM at its virucidal concentration was nontoxic and reduced virus yield in the brain of HSV-2 infected mice in a concentration dependent manner, compared to vaginal tissues. Thus, our results suggest that HM can serve as a prototype to develop non-nucleotide antiviral lead targeting the viral IE transcription for the management of HSV-2 infections. PMID:24167591

  14. Method for deploying multiple spacecraft

    NASA Technical Reports Server (NTRS)

    Sharer, Peter J. (Inventor)

    2007-01-01

    A method for deploying multiple spacecraft is disclosed. The method can be used in a situation where a first celestial body is being orbited by a second celestial body. The spacecraft are loaded onto a single spaceship that contains the multiple spacecraft and the spacecraft is launched from the second celestial body towards a third celestial body. The spacecraft are separated from each other while in route to the third celestial body. Each of the spacecraft is then subjected to the gravitational field of the third celestial body and each of the spacecraft assumes a different, independent orbit about the first celestial body. In those situations where the spacecraft are launched from Earth, the Sun can act as the first celestial body, the Earth can act as the second celestial body and the Moon can act as the third celestial body.

  15. Multiple Exciton Generation Solar Cells

    SciTech Connect

    Luther, J. M.; Semonin, O. E.; Beard, M. C.; Gao, J.; Nozik, A. J.

    2012-01-01

    Heat loss is the major factor limiting traditional single junction solar cells to a theoretical efficiency of 32%. Multiple Exciton Generation (MEG) enables efficient use of the solar spectrum yielding a theoretical power conversion efficiency of 44% in solar cells under 1-sun conditions. Quantum-confined semiconductors have demonstrated the ability to generate multiple carriers but present-day materials deliver efficiencies far below the SQ limit of 32%. Semiconductor quantum dots of PbSe and PbS provide an active testbed for developing high-efficiency, inexpensive solar cells benefitting from quantum confinement effects. Here, we will present recent work of solar cells employing MEG to yield external quantum efficiencies exceeding 100%.

  16. Computational Reasoning across Multiple Models

    PubMed Central

    Tsafnat, Guy; Coiera, Enrico W.

    2009-01-01

    Computational support of clinical decisions frequently requires the integration of data in a variety of formats and from multiple sources and domains. Some impressive multiscale computational models of biological phenomena have been developed as part of the study of disease and healthcare systems. One can now contemplate harnessing these models arising from computational biology and using highly interconnected clinical data to support clinical decision-making. Indeed, understanding how to build computational systems able to reason across heterogeneous models and datasets is one of the major and perhaps foundational challenges of translational biomedical informatics. In this paper, the authors examine the use of multimodels (models composed of several daughter models) and explore three major research challenges to reasoning across multiple models: model selection, model composition, and computer aided model construction. PMID:19717801

  17. Emerging therapies in multiple myeloma.

    PubMed

    El-Amm, Joelle; Tabbara, Imad A

    2015-06-01

    The treatment of multiple myeloma has evolved significantly over the past 2 decades due to the use of high-dose chemotherapy and autologous stem cell transplantation, and the subsequent introduction of the immunomodulatory agents (thalidomide and lenalidomide) and the proteasome inhibitor (bortezomib). The median overall survival of multiple myeloma patients has increased significantly with patients younger than age 50 years experiencing a 10-year survival rate of around 40%. However, despite the increased effectiveness of the first-line agents, the majority of patients will eventually relapse and become drug resistant. Promising novel therapies have recently emerged and are being used to treat relapsed and refractory patients. This review will cover the clinical data regarding these emergent therapies that include new generation of proteasome inhibitors (carfilzomib, ixazomib, oprozomib, and marizomib), immunomodulatory drugs (pomalidomide), monoclonal antibodies (elotuzumab and daratumumab), signal transduction modulator (perifosine), and histone deacetylase inhibitors (vorinostat and panobinostat). PMID:23934133

  18. Multiple idiopathic apical root resorption.

    PubMed

    Kanungo, Manish; Khandelwal, Vishal; Nayak, Ullal Anand; Nayak, Prathibha Anand

    2013-01-01

    Idiopathic external root resorption is a rarely reported condition which has been observed in single or multiple teeth. This is a rare case of multiple idiopathic apical root resorption (MIARR) in a 16-year-old boy. External root resorption of the permanent teeth is a multifactorial process. Well-recognised causes of apical root resorption in permanent teeth include orthodontic therapy, trauma, periapical or periodontal inflammation, tumours, cysts, occlusal stresses, impacted teeth, systemic conditions, endocrine imbalances and dietary habits. When none of these causes are present, it is termed idiopathic root resorption which may be either cervical or apical. MIARR is a rare condition which is usually detected as an incidental radiographic finding. However, it may cause pain and mobility in severe cases. PMID:23616336

  19. Melanoma Multiple Primary Rules Matrix

    Cancer.gov

    Cutaneous Melanoma Multiple Primary Rules – Matrix C440 – C449 (Excludes melanoma of any other site) * P r e p ar e o n e abs tr a c t. U s e t h e hi s t o lo g y c o di ng r u le s t o as s i gn th e ap pr o p r iat e h is to lo

  20. [Special cases of multiple sclerosis].

    PubMed

    Mendibe Bilbao, Mar

    2014-12-01

    Multiple sclerosis is a chronic disease that usually occurs in young people and affects them for the rest of their lives. Patients and their families usually have a series of doubts and questions on everyday matters and all types of situations that occur during the distinct stages of life and which can influence the course of the disease. The aim of this review is to provide specific answers to these questions. PMID:25732948

  1. Protocol for multiple node network

    NASA Technical Reports Server (NTRS)

    Kirkham, Harold (Inventor)

    1995-01-01

    The invention is a multiple interconnected network of intelligent message-repeating remote nodes which employs an antibody recognition message termination process performed by all remote nodes and a remote node polling process performed by other nodes which are master units controlling remote nodes in respective zones of the network assigned to respective master nodes. Each remote node repeats only those messages originated in the local zone, to provide isolation among the master nodes.

  2. Multiple-access bosonic communications

    SciTech Connect

    Yen, Brent J.; Shapiro, Jeffrey H.

    2005-12-15

    The maximum rates for reliably transmitting classical information over bosonic multiple-access channels (MACs) are derived when the transmitters are restricted to coherent-state encodings. Inner and outer bounds for the ultimate capacity region of the bosonic MAC are also presented. It is shown that the sum-rate upper bound is achievable with a coherent-state encoding and that the entire region is asymptotically achievable in the limit of large mean input photon numbers.

  3. The Complexity of Iterated Multiplication

    E-print Network

    Massachusetts at Amherst, University of

    Supported by NSF grants DMS-8807202 and CCR-8802835. 1 #12;FO = AC0 ThC0 NC1 L NL AC1 DET* ThC1 NC2 DSPACE log2 n surprising fact { reported in BCH, Rei] { is that iterated integer multiplication is in P-uniform ThC0 but not known to be in (uniform) ThC0 , or even in L. Usually, uniformity does not pose as a serious issue

  4. Blepharochalasis with multiple system involvement.

    PubMed Central

    Ghose, S; Kalra, B R; Dayal, Y

    1984-01-01

    A rare case of bilateral blepharochalasis of the upper eyelids is presented in a 10-year-old boy with several systemic abnormalities--unilateral agenesis of the left kidney, multiple skeletal anomalies of the vertebral column, and congenital heart disease with a left to right shunt. Such widespread congenital defects in association with blepharochalasis have not been described before. Blepharochalasis may represent a part of a more generalised disorder. Images PMID:6743619

  5. Kidney Multiple Primary Rules Matrix

    Cancer.gov

    Kidney Multiple Primary Rules – Matrix C649 (Excludes lymphoma and leukemia M9590 – 9989 and Kaposi sarcoma M9140) * P r e p ar e o n e abs tr a c t. U s e t h e hi s t o lo g y c o di ng r u le s t o as s i gn th e ap pr o p r iat

  6. Colon Multiple Primary Rules Matrix

    Cancer.gov

    Colon Multiple Primary Rules – Matrix C180-C189 (Excludes lymphoma and leukemia M9590 – 9989 and Kaposi sarcoma M9140) * P r e p ar e o n e abs tr a c t. U s e t h e hi s t o lo g y c o di ng r u le s t o as s i gn th e ap pr o p

  7. Protocol for multiple node network

    NASA Technical Reports Server (NTRS)

    Kirkham, Harold (Inventor)

    1994-01-01

    The invention is a multiple interconnected network of intelligent message-repeating remote nodes which employs an antibody recognition message termination process performed by all remote nodes and a remote node polling process performed by other nodes which are master units controlling remote nodes in respective zones of the network assigned to respective master nodes. Each remote node repeats only those messages originated in the local zone, to provide isolation among the master nodes.

  8. FRACTIONAL DYNAMICS AT MULTIPLE TIMES.

    PubMed

    Meerschaert, Mark M; Straka, Peter

    2012-11-01

    A continuous time random walk (CTRW) imposes a random waiting time between random particle jumps. CTRW limit densities solve a fractional Fokker-Planck equation, but since the CTRW limit is not Markovian, this is not sufficient to characterize the process. This paper applies continuum renewal theory to restore the Markov property on an expanded state space, and compute the joint CTRW limit density at multiple times. PMID:23378670

  9. Multiplicity of Solutions in Aerodynamics

    NASA Technical Reports Server (NTRS)

    Dupont, M

    1927-01-01

    One of the most striking phenomena which accompany the flow of fluids such as air and water about bodies, is that of changes in character. This phenomena is still very little understood. We will first discuss the nature of these changes and then show that pure theory leads to a multiplicity of characters of flow, among which we will endeavor to indicate those bearing some analogy to experimental results.

  10. Multiple target laser ablation system

    DOEpatents

    Mashburn, D.N.

    1996-01-09

    A laser ablation apparatus and method are provided in which multiple targets consisting of material to be ablated are mounted on a movable support. The material transfer rate is determined for each target material, and these rates are stored in a controller. A position detector determines which target material is in a position to be ablated, and then the controller controls the beam trigger timing and energy level to achieve a desired proportion of each constituent material in the resulting film. 3 figs.

  11. Learning to track multiple targets.

    PubMed

    Liu, Xiao; Tao, Dacheng; Song, Mingli; Zhang, Luming; Bu, Jiajun; Chen, Chun

    2015-05-01

    Monocular multiple-object tracking is a fundamental yet under-addressed computer vision problem. In this paper, we propose a novel learning framework for tracking multiple objects by detection. First, instead of heuristically defining a tracking algorithm, we learn that a discriminative structure prediction model from labeled video data captures the interdependence of multiple influence factors. Given the joint targets state from the last time step and the observation at the current frame, the joint targets state at the current time step can then be inferred by maximizing the joint probability score. Second, our detection results benefit from tracking cues. The traditional detection algorithms need a nonmaximal suppression postprocessing to select a subset from the total detection responses as the final output and a large number of selection mistakes are induced, especially under a congested circumstance. Our method integrates both detection and tracking cues. This integration helps to decrease the postprocessing mistake risk and to improve performance in tracking. Finally, we formulate the entire model training into a convex optimization problem and estimate its parameters using the cutting plane optimization. Experiments show that our method performs effectively in a large variety of scenarios, including pedestrian tracking in crowd scenes and vehicle tracking in congested traffic. PMID:25051561

  12. Immune tolerance in multiple sclerosis.

    PubMed

    Goverman, Joan M

    2011-05-01

    Multiple sclerosis is believed to be mediated by T cells specific for myelin antigens that circulate harmlessly in the periphery of healthy individuals until they are erroneously activated by an environmental stimulus. Upon activation, the T cells enter the central nervous system and orchestrate an immune response against myelin. To understand the initial steps in the pathogenesis of multiple sclerosis, it is important to identify the mechanisms that maintain T-cell tolerance to myelin antigens and to understand how some myelin-specific T cells escape tolerance and what conditions lead to their activation. Central tolerance strongly shapes the peripheral repertoire of myelin-specific T cells, as most myelin-specific T cells are eliminated by clonal deletion in the thymus. Self-reactive T cells that escape central tolerance are generally capable only of low-avidity interactions with antigen-presenting cells. Despite the low avidity of these interactions, peripheral tolerance mechanisms are required to prevent spontaneous autoimmunity. Multiple peripheral tolerance mechanisms for myelin-specific T cells have been identified, the most important of which appears to be regulatory T cells. While most studies have focused on CD4(+) myelin-specific T cells, interesting differences in tolerance mechanisms and the conditions that abrogate these mechanisms have recently been described for CD8(+) myelin-specific T cells. PMID:21488900

  13. Lecture 12: Chain Matrix Multiplication CLRS Section 15.2

    E-print Network

    Wu, Dekai

    Lecture 12: Chain Matrix Multiplication CLRS Section 15.2 Outline of this Lecture Recalling matrix multiplication. The chain matrix multiplication problem. A dynamic programming algorithm for chain ma- trix multiplication. 1 #12;Recalling Matrix Multiplication Matrix: An ¡ ¢ matrix

  14. Multiple memory systems as substrates for multiple decision systems.

    PubMed

    Doll, Bradley B; Shohamy, Daphna; Daw, Nathaniel D

    2015-01-01

    It has recently become widely appreciated that value-based decision making is supported by multiple computational strategies. In particular, animal and human behavior in learning tasks appears to include habitual responses described by prominent model-free reinforcement learning (RL) theories, but also more deliberative or goal-directed actions that can be characterized by a different class of theories, model-based RL. The latter theories evaluate actions by using a representation of the contingencies of the task (as with a learned map of a spatial maze), called an "internal model." Given the evidence of behavioral and neural dissociations between these approaches, they are often characterized as dissociable learning systems, though they likely interact and share common mechanisms. In many respects, this division parallels a longstanding dissociation in cognitive neuroscience between multiple memory systems, describing, at the broadest level, separate systems for declarative and procedural learning. Procedural learning has notable parallels with model-free RL: both involve learning of habits and both are known to depend on parts of the striatum. Declarative memory, by contrast, supports memory for single events or episodes and depends on the hippocampus. The hippocampus is thought to support declarative memory by encoding temporal and spatial relations among stimuli and thus is often referred to as a relational memory system. Such relational encoding is likely to play an important role in learning an internal model, the representation that is central to model-based RL. Thus, insofar as the memory systems represent more general-purpose cognitive mechanisms that might subserve performance on many sorts of tasks including decision making, these parallels raise the question whether the multiple decision systems are served by multiple memory systems, such that one dissociation is grounded in the other. Here we investigated the relationship between model-based RL and relational memory by comparing individual differences across behavioral tasks designed to measure either capacity. Human subjects performed two tasks, a learning and generalization task (acquired equivalence) which involves relational encoding and depends on the hippocampus; and a sequential RL task that could be solved by either a model-based or model-free strategy. We assessed the correlation between subjects' use of flexible, relational memory, as measured by generalization in the acquired equivalence task, and their differential reliance on either RL strategy in the decision task. We observed a significant positive relationship between generalization and model-based, but not model-free, choice strategies. These results are consistent with the hypothesis that model-based RL, like acquired equivalence, relies on a more general-purpose relational memory system. PMID:24846190

  15. Whooping Cough - Multiple Languages: MedlinePlus

    MedlinePLUS

    ... Are Here: Home ? Multiple Languages ? All Health Topics ? Whooping Cough URL of this page: https://www.nlm.nih. ... V W XYZ List of All Topics All Whooping Cough - Multiple Languages To use the sharing features on ...

  16. CZ: Multiple Inheritance Without Diamonds Donna Malayeri

    E-print Network

    Aldrich, Jonathan

    CZ: Multiple Inheritance Without Diamonds Donna Malayeri Carnegie Mellon University donna, such as mixins and traits. Instead, we ad- dress the diamond problem directly, considering two diffi- culties approach: supporting multiple inheritance but forbidding diamond inheritance. Expressiveness is retained

  17. Pressure Sores - Multiple Languages: MedlinePlus

    MedlinePLUS

    ... Are Here: Home ? Multiple Languages ? All Health Topics ? Pressure Sores URL of this page: https://www.nlm.nih. ... V W XYZ List of All Topics All Pressure Sores - Multiple Languages To use the sharing features on ...

  18. Refractive Errors - Multiple Languages: MedlinePlus

    MedlinePLUS

    ... Are Here: Home ? Multiple Languages ? All Health Topics ? Refractive Errors URL of this page: https://www.nlm.nih. ... V W XYZ List of All Topics All Refractive Errors - Multiple Languages To use the sharing features on ...

  19. Oil Spills - Multiple Languages: MedlinePlus

    MedlinePLUS

    ... Are Here: Home ? Multiple Languages ? All Health Topics ? Oil Spills URL of this page: https://www.nlm.nih. ... V W XYZ List of All Topics All Oil Spills - Multiple Languages To use the sharing features on ...

  20. Parasitic Diseases - Multiple Languages: MedlinePlus

    MedlinePLUS

    ... Are Here: Home ? Multiple Languages ? All Health Topics ? Parasitic Diseases URL of this page: https://www.nlm.nih. ... V W XYZ List of All Topics All Parasitic Diseases - Multiple Languages To use the sharing features on ...

  1. 42 CFR 102.45 - Multiple survivors.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages...45 Multiple survivors. Multiple survivors of the same smallpox vaccine recipient or vaccinia contact may file Request Forms...

  2. 42 CFR 102.45 - Multiple survivors.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages...45 Multiple survivors. Multiple survivors of the same smallpox vaccine recipient or vaccinia contact may file Request Forms...

  3. 42 CFR 102.45 - Multiple survivors.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages...45 Multiple survivors. Multiple survivors of the same smallpox vaccine recipient or vaccinia contact may file Request Forms...

  4. 42 CFR 102.45 - Multiple survivors.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages...45 Multiple survivors. Multiple survivors of the same smallpox vaccine recipient or vaccinia contact may file Request Forms...

  5. 42 CFR 102.45 - Multiple survivors.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages...45 Multiple survivors. Multiple survivors of the same smallpox vaccine recipient or vaccinia contact may file Request Forms...

  6. Breast Diseases - Multiple Languages: MedlinePlus

    MedlinePLUS

    ... Are Here: Home ? Multiple Languages ? All Health Topics ? Breast Diseases URL of this page: https://www.nlm.nih. ... V W XYZ List of All Topics All Breast Diseases - Multiple Languages To use the sharing features on ...

  7. 46 CFR 120.322 - Multiple generators.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 2010-10-01 false Multiple generators. 120.322 Section 120.322 ...Distribution Systems § 120.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service...

  8. 46 CFR 129.323 - Multiple generators.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...2011-10-01 2011-10-01 false Multiple generators. 129.323 Section 129.323 Shipping...Distribution Systems § 129.323 Multiple generators. If an OSV uses two or more generators to supply electricity for the...

  9. 46 CFR 183.322 - Multiple generators.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 2012-10-01 false Multiple generators. 183.322 Section 183.322 ...Distribution Systems § 183.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service...

  10. 46 CFR 120.322 - Multiple generators.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 2014-10-01 false Multiple generators. 120.322 Section 120.322 ...Distribution Systems § 120.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service...

  11. 46 CFR 183.322 - Multiple generators.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 2014-10-01 false Multiple generators. 183.322 Section 183.322 ...Distribution Systems § 183.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service...

  12. 46 CFR 120.322 - Multiple generators.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 2012-10-01 false Multiple generators. 120.322 Section 120.322 ...Distribution Systems § 120.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service...

  13. 46 CFR 120.322 - Multiple generators.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 2011-10-01 false Multiple generators. 120.322 Section 120.322 ...Distribution Systems § 120.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service...

  14. 46 CFR 129.323 - Multiple generators.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...2010-10-01 2010-10-01 false Multiple generators. 129.323 Section 129.323 Shipping...Distribution Systems § 129.323 Multiple generators. If an OSV uses two or more generators to supply electricity for the...

  15. 46 CFR 129.323 - Multiple generators.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...2014-10-01 2014-10-01 false Multiple generators. 129.323 Section 129.323 Shipping...Distribution Systems § 129.323 Multiple generators. If an OSV uses two or more generators to supply electricity for the...

  16. 46 CFR 183.322 - Multiple generators.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 2011-10-01 false Multiple generators. 183.322 Section 183.322 ...Distribution Systems § 183.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service...

  17. 46 CFR 129.323 - Multiple generators.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...2013-10-01 2013-10-01 false Multiple generators. 129.323 Section 129.323 Shipping...Distribution Systems § 129.323 Multiple generators. If an OSV uses two or more generators to supply electricity for the...

  18. 46 CFR 120.322 - Multiple generators.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 2013-10-01 false Multiple generators. 120.322 Section 120.322 ...Distribution Systems § 120.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service...

  19. 46 CFR 183.322 - Multiple generators.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 2013-10-01 false Multiple generators. 183.322 Section 183.322 ...Distribution Systems § 183.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service...

  20. 46 CFR 129.323 - Multiple generators.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...2012-10-01 2012-10-01 false Multiple generators. 129.323 Section 129.323 Shipping...Distribution Systems § 129.323 Multiple generators. If an OSV uses two or more generators to supply electricity for the...

  1. 46 CFR 183.322 - Multiple generators.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 2010-10-01 false Multiple generators. 183.322 Section 183.322 ...Distribution Systems § 183.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service...

  2. Complementary and Alternative Medicine for Multiple Sclerosis

    MedlinePLUS

    ... and their FAMILIES COMPLEMENTARY AND ALTERNATIVE MEDICINE FOR MULTIPLE SCLEROSIS This fact sheet is provided to help you ... complementary and alternative medicine (CAM) for treatment of multiple sclerosis (MS). The American Academy of Neurology (AAN) is ...

  3. Emotional Disorders in People with Multiple Sclerosis

    MedlinePLUS

    ... and their FAMILIES EMOTIONAL DISORDERS IN PEOPLE WITH MULTIPLE SCLEROSIS This fact sheet presents the current research on emotional disorders in multiple sclerosis (MS) and summarizes the main findings of a ...

  4. Aortic Aneurysm - Multiple Languages: MedlinePlus

    MedlinePLUS

    ... Are Here: Home ? Multiple Languages ? All Health Topics ? Aortic Aneurysm URL of this page: https://www.nlm.nih. ... V W XYZ List of All Topics All Aortic Aneurysm - Multiple Languages To use the sharing features on ...

  5. Some Simple Computational Formulas for Multiple Regression

    ERIC Educational Resources Information Center

    Aiken, Lewis R., Jr.

    1974-01-01

    Short-cut formulas are presented for direct computation of the beta weights, the standard errors of the beta weights, and the multiple correlation coefficient for multiple regression problems involving three independent variables and one dependent variable. (Author)

  6. Multiple-Valued Logic: An Implementation

    NASA Astrophysics Data System (ADS)

    Dao, T. T.; Campbell, D. M.

    1986-01-01

    The state of the art for multiple-valued electronic devices relying on integrated injection logic (I2L) is discussed. Applications and extension of multiple-valued I2L devices to quaternary logic technology are presented.

  7. Detection and Classification of Multiple Person Interaction 

    E-print Network

    Blunsden, Scott

    2009-01-01

    This thesis investigates the classification of the behaviour of multiple persons when viewed from a video camera. Work upon a constrained case of multiple person interaction in the form of team games is investigated. A ...

  8. Rotavirus Infections - Multiple Languages: MedlinePlus

    MedlinePLUS

    ... Are Here: Home ? Multiple Languages ? All Health Topics ? Rotavirus Infections URL of this page: https://www.nlm. ... V W XYZ List of All Topics All Rotavirus Infections - Multiple Languages To use the sharing features ...

  9. Child Abuse - Multiple Languages: MedlinePlus

    MedlinePLUS

    ... Are Here: Home ? Multiple Languages ? All Health Topics ? Child Abuse URL of this page: https://www.nlm.nih. ... V W XYZ List of All Topics All Child Abuse - Multiple Languages To use the sharing features on ...

  10. Tick Bites - Multiple Languages: MedlinePlus

    MedlinePLUS

    ... Are Here: Home ? Multiple Languages ? All Health Topics ? Tick Bites URL of this page: https://www.nlm.nih. ... V W XYZ List of All Topics All Tick Bites - Multiple Languages To use the sharing features on ...

  11. The Multiple Control of Verbal Behavior

    PubMed Central

    Michael, Jack; Palmer, David C; Sundberg, Mark L

    2011-01-01

    Amid the novel terms and original analyses in Skinner's Verbal Behavior, the importance of his discussion of multiple control is easily missed, but multiple control of verbal responses is the rule rather than the exception. In this paper we summarize and illustrate Skinner's analysis of multiple control and introduce the terms convergent multiple control and divergent multiple control. We point out some implications for applied work and discuss examples of the role of multiple control in humor, poetry, problem solving, and recall. Joint control and conditional discrimination are discussed as special cases of multiple control. We suggest that multiple control is a useful analytic tool for interpreting virtually all complex behavior, and we consider the concepts of derived relations and naming as cases in point. PMID:22532752

  12. Multiple Tries on Trial Gerd Kortemeyer

    E-print Network

    Multiple Tries on Trial Gerd Kortemeyer Michigan State University AAPT Conference July 2015 #12;The Accusation Online homework fosters unproductive behavior Too many multiple tries are at fault ... or maybe ... Too few tries are at fault #12;Typical Online Physics Problem Multiple tries Open- ended numerical #12

  13. Parallel MATLAB: Single Program Multiple Data

    E-print Network

    Crawford, T. Daniel

    : is Single Program, Multiple Data Lecture #3: SPMD - 18 February The SPMD command (today's lecture) is likeParallel MATLAB: Single Program Multiple Data John Burkardt (FSU) Gene Cliff (AOE/ICAM - ecliff Computing SPMD: Single Program, Multiple Data QUAD Example Distributed Arrays LBVP & FEM 2D HEAT Examples

  14. Identifying the Multiple Intelligences of Your Students

    ERIC Educational Resources Information Center

    McClellan, Joyce A.; Conti, Gary J.

    2008-01-01

    One way of addressing individual differences among adult learners is to identify the Multiple Intelligences of the learner. Multiple Intelligences refers to the concept developed by Howard Gardner that challenges the traditional view of intelligence and explains the presence of nine different Multiple Intelligences. The purpose of this study was…

  15. Breast feeding twins and high multiples

    PubMed Central

    Flidel?Rimon, O; Shinwell, E S

    2006-01-01

    Breast feeding offers major health advantages for all infants, whether born singleton or from multiple pregnancy. Adequate quantity and quality of milk production has been documented even for high multiples. Combined efforts of parents, close family, friends, and the medical team can help to make either full or partial breast feeding of multiples possible. PMID:16923939

  16. SPARSE MATRIX MULTIPLICATION ON AN ASSOCIATIVE PROCESSOR

    E-print Network

    Ginosar, Ran

    SPARSE MATRIX MULTIPLICATION ON AN ASSOCIATIVE PROCESSOR L. Yavits, A. Morad, R. Ginosar Abstract--Sparse matrix multiplication is an important component of linear algebra computations. Implementing sparse of vector dot product does not depend on the vector size. Four sparse matrix multiplication algorithms

  17. Fast sparse matrix multiplication Raphael Yuster

    E-print Network

    Yuster, Raphael

    Fast sparse matrix multiplication Raphael Yuster Uri Zwick Abstract Let A and B two n Ã? n.38 ) algebraic operations. Obtaining a fast sparse matrix multiplication algorithm that beats the naive method are extremely sparse. The naive matrix multiplication algorithm, on the other hand, can be used to multiply two

  18. The Multiple Control of Verbal Behavior

    ERIC Educational Resources Information Center

    Michael, Jack; Palmer, David C.; Sundberg, Mark L.

    2011-01-01

    Amid the novel terms and original analyses in Skinner's "Verbal Behavior", the importance of his discussion of multiple control is easily missed, but multiple control of verbal responses is the rule rather than the exception. In this paper we summarize and illustrate Skinner's analysis of multiple control and introduce the terms "convergent…

  19. ORIGINAL CONTRIBUTION Modification of Multiple Sclerosis Phenotypes

    E-print Network

    Reich, David

    ORIGINAL CONTRIBUTION Modification of Multiple Sclerosis Phenotypes by African Ancestry at HLA. Oksenberg, PhD Background: In those with multiple sclerosis (MS), Afri- can American individuals have a more ancestry at HLA correlated with dis- ability as measured by the Multiple Sclerosis Severity Score (P .001

  20. EFFICIENT DESIGNS OF MULTIPLE SCLEROSIS CLINICAL TRIALS

    E-print Network

    Brennand, Tracy

    EFFICIENT DESIGNS OF MULTIPLE SCLEROSIS CLINICAL TRIALS by Dean Emile Vrecko B.Sc., University of Science Title of project: Efficient Designs of Multiple Sclerosis Clinical Trials Examining Committee: Dr Multiple sclerosis (MS) is a debilitating disease that attacks the central nervous system. Much research

  1. http://msj.sagepub.com Multiple Sclerosis

    E-print Network

    Hamarneh, Ghassan

    http://msj.sagepub.com Multiple Sclerosis DOI: 10.1177/135248506071178 2006; 12; 1Mult Scler Oral://www.sagepublications.com can be found at:Multiple SclerosisAdditional services and information for http in multiple sclerosis (MS) patients at a faster rate ((/4.5% versus (/1%) than loss in whole brain volume

  2. Multiple Sclerosis Luminance Threshold and Measurements

    E-print Network

    Foster, David H.

    Multiple Sclerosis Luminance Threshold and Measurements of Temporal Characteristics of Vision indicates multiple sclerosis; ON, optic neuritis. Table 1.-Clinical Details of Patients Details of Eye In patient with multiple sclerosis (MS) and In normal control subjects. The Inten Itles of the tlmull used

  3. Functional Multiple-Set Canonical Correlation Analysis

    ERIC Educational Resources Information Center

    Hwang, Heungsun; Jung, Kwanghee; Takane, Yoshio; Woodward, Todd S.

    2012-01-01

    We propose functional multiple-set canonical correlation analysis for exploring associations among multiple sets of functions. The proposed method includes functional canonical correlation analysis as a special case when only two sets of functions are considered. As in classical multiple-set canonical correlation analysis, computationally, the…

  4. BAYESIAN MULTIPLE PERSON TRACKING USING PROBABILITY

    E-print Network

    Frean, Marcus

    BAYESIAN MULTIPLE PERSON TRACKING USING PROBABILITY HYPOTHESIS DENSITY SMOOTHING S. Hernandez or multiple cameras, the scope and availability of multiple target tracking techniques for crowd analysis has approximation to the posterior density. The PHD filter is a good alternative to standard multi-target tracking

  5. Dependent Multiple Cue Integration for Robust Tracking

    E-print Network

    Moreno-Noguer, Francesc

    and versatility of our method. Index Terms--Bayesian tracking, multiple cue integration. Ç 1 INTRODUCTION TRACKINGDependent Multiple Cue Integration for Robust Tracking Francesc Moreno-Noguer, Alberto Sanfeliu, Member, IEEE, and Dimitris Samaras, Member, IEEE Abstract--We propose a new technique for fusing multiple

  6. PARALLEL MATRIX MULTIPLICATION: A SYSTEMATIC JOURNEY

    E-print Network

    Batory, Don

    PARALLEL MATRIX MULTIPLICATION: A SYSTEMATIC JOURNEY MARTIN D. SCHATZ, ROBERT A. VAN DE GEIJN- trix matrix multiplication algorithms. The journey starts with a description of how matrices implementation of matrix-vector multiplication and rank-1 update, continues on to reveal a fam- ily of matrix-matrix

  7. The Many Meanings of "Multiple Measures"

    ERIC Educational Resources Information Center

    Brookhart, Susan M.

    2009-01-01

    Professional assessment organizations almost universally endorse the use of multiple measures for making education decisions. In practice, however, the concept of multiple measures is defined and applied in many different ways, depending on how we answer two questions--What counts as a "measure"? and How are the multiple measures combined?…

  8. Stator and multiple piece seal

    SciTech Connect

    Heldreth, M.A.; Buckert, S.R.

    1993-06-22

    A gas turbine engine is described comprising a compressor section, a combustor section and a turbine section arranged in flow series and defining an annular flow path extending axially from the compressor section through the turbine section, the engine further comprising a plurality of air passageways extending from the compressor section to a plenum in the turbine section so that the pressure in the plenum is greater than the pressure in a portion of the flow path disposed within the turbine section, the turbine section comprising a stator vane array upstream of a rotor blade array, the stator vane array having a plurality of vanes interposed in the turbine section flow path and mounted radially between a segmented outer end wall and a segmented inner end wall, each of the segments, of the inner and outer end walls, having a narrow gap there between, the gap being in fluid communication with the plenum and the turbine section flow path defining a pressure differential across the gap, the stator vane array further comprising a multiple piece seal inserted in each of the gaps, the multiple piece seal comprising a first sealing member having a thickness sufficiently small so that the first sealing member deforms into sealing contact across the gap when exposed to the pressure differential, and a second sealing member having a thickness sufficiently large to prevent both the first and second sealing members from buckling when the multiple piece seal is inserted into the gap the first and second sealing members being attached at one end.

  9. Sequence Factorization with Multiple References

    PubMed Central

    Wandelt, Sebastian; Leser, Ulf

    2015-01-01

    The success of high-throughput sequencing has lead to an increasing number of projects which sequence large populations of a species. Storage and analysis of sequence data is a key challenge in these projects, because of the sheer size of the datasets. Compression is one simple technology to deal with this challenge. Referential factorization and compression schemes, which store only the differences between input sequence and a reference sequence, gained lots of interest in this field. Highly-similar sequences, e.g., Human genomes, can be compressed with a compression ratio of 1,000:1 and more, up to two orders of magnitude better than with standard compression techniques. Recently, it was shown that the compression against multiple references from the same species can boost the compression ratio up to 4,000:1. However, a detailed analysis of using multiple references is lacking, e.g., for main memory consumption and optimality. In this paper, we describe one key technique for the referential compression against multiple references: The factorization of sequences. Based on the notion of an optimal factorization, we propose optimization heuristics and identify parameter settings which greatly influence 1) the size of the factorization, 2) the time for factorization, and 3) the required amount of main memory. We evaluate a total of 30 setups with a varying number of references on data from three different species. Our results show a wide range of factorization sizes (optimal to an overhead of up to 300%), factorization speed (0.01 MB/s to more than 600 MB/s), and main memory usage (few dozen MB to dozens of GB). Based on our evaluation, we identify the best configurations for common use cases. Our evaluation shows that multi-reference factorization is much better than single-reference factorization. PMID:26422374

  10. Macrodystrophia lipomatosa involving multiple nerves.

    PubMed

    Rohilla, Seema; Jain, Nitin; Sharma, Rambaksh; Dhaulakhandi, Dhara B

    2012-03-01

    Macrodystrophia lipomatosa (MDL), a rare congenital disorder, is considered by some to be a localized form of Proteus syndrome. The implication of the PTEN (phosphatase and tensin homolog deleted on chromosome 10) gene in both strengthens this belief. We present a case who had MDL in multiple nerve territories--all on the same side of the body--with hypertrophy of mainly fibroadipose tissue throughout their distribution, thus pointing to a form of localized hemihypertrophy; both hemihypertrophy and lipomatous tumors are components of Proteus syndrome. PMID:21948052

  11. Multiple channel programmable coincidence counter

    DOEpatents

    Arnone, Gaetano J. (Los Alamos, NM)

    1990-01-01

    A programmable digital coincidence counter having multiple channels and featuring minimal dead time. Neutron detectors supply electrical pulses to a synchronizing circuit which in turn inputs derandomized pulses to an adding circuit. A random access memory circuit connected as a programmable length shift register receives and shifts the sum of the pulses, and outputs to a serializer. A counter is input by the adding circuit and downcounted by the seralizer, one pulse at a time. The decoded contents of the counter after each decrement is output to scalers.

  12. Newer therapies for multiple sclerosis.

    PubMed

    Coles, Alasdair

    2015-09-01

    The newer immunotherapies for multiple sclerosis (fingolimod, natalizumab, dimethyl fumarate, teriflunomide, alemtuzumab) offer advantages of efficacy or tolerability over the injectable therapies of the 1990s. But they also have greater risks. As further treatments emerge (daclizumab and ocrelizumab are likely to be licensed in the next two years), the physician needs to be able to place them within a complex landscape of drugs and a specific treatment strategy, which may be an "escalation" or "induction" approach. Whilst on treatment, neurologist and patient need to be vigilant to signs of disease breakthrough or adverse effects. PMID:26538846

  13. Coordination of multiple robot arms

    NASA Technical Reports Server (NTRS)

    Barker, L. K.; Soloway, D.

    1987-01-01

    Kinematic resolved-rate control from one robot arm is extended to the coordinated control of multiple robot arms in the movement of an object. The structure supports the general movement of one axis system (moving reference frame) with respect to another axis system (control reference frame) by one or more robot arms. The grippers of the robot arms do not have to be parallel or at any pre-disposed positions on the object. For multiarm control, the operator chooses the same moving and control reference frames for each of the robot arms. Consequently, each arm then moves as though it were carrying out the commanded motions by itself.

  14. The GL 569 Multiple System

    E-print Network

    M. Simon; C. Bender; L. Prato

    2006-04-04

    We report the results of high spectral and angular resolution infrared observations of the multiple system GL 569 A and B that were intended to measure the dynamical masses of the brown dwarf binary believed to comprise GL 569 B. Our analysis did not yield this result but, instead, revealed two surprises. First, at age ~100 Myr, the system is younger than had been reported earlier. Second, our spectroscopic and photometric results provide support for earlier indications that GL 569 B is actually a hierarchical brown dwarf triple rather than a binary. Our results suggest that the three components of GL 569 B have roughly equal mass, ~0.04 Msun.

  15. Newer therapies for multiple sclerosis

    PubMed Central

    Coles, Alasdair

    2015-01-01

    The newer immunotherapies for multiple sclerosis (fingolimod, natalizumab, dimethyl fumarate, teriflunomide, alemtuzumab) offer advantages of efficacy or tolerability over the injectable therapies of the 1990s. But they also have greater risks. As further treatments emerge (daclizumab and ocrelizumab are likely to be licensed in the next two years), the physician needs to be able to place them within a complex landscape of drugs and a specific treatment strategy, which may be an “escalation” or “induction” approach. Whilst on treatment, neurologist and patient need to be vigilant to signs of disease breakthrough or adverse effects. PMID:26538846

  16. Symptomatic management in multiple sclerosis

    PubMed Central

    Shah, Pushkar

    2015-01-01

    Multiple sclerosis (MS) is the commonest cause of disability in young adults. While there is increasing choice and better treatments available for delaying disease progression, there are still, very few, effective symptomatic treatments. For many patients such as those with primary progressive MS (PPMS) and those that inevitably become secondary progressive, symptom management is the only treatment available. MS related symptoms are complex, interrelated, and can be interdependent. It requires good understanding of the condition, a holistic multidisciplinary approach, and above all, patient education and empowerment. PMID:26538847

  17. Smart card multiple function badge

    SciTech Connect

    Nelson, R.A.

    1993-06-01

    Smart cards are credit card-sized computers with integrated data storage, an operating system to manage the data, and built-in security features that protect the data. They are used to distribute information to remote sites, providing the same or greater reliability, data integrity, and information security than a network system. However, smart cards may provide greater functionality at a lower cost than network systems. The US Department of Energy Hanford Site is developing the smart card to be used as a multiple function identification badge that will service various data management requirements on the Site. This paper discusses smart card technology and the proposed Hanford Site applications.

  18. Multiple piece turbine rotor blade

    DOEpatents

    Jones, Russell B; Fedock, John A

    2013-05-21

    A multiple piece turbine rotor blade with a shell having an airfoil shape and secured between a spar and a platform with the spar including a tip end piece. a snap ring fits around the spar and abuts against the spar tip end piece on a top side and abuts against a shell on the bottom side so that the centrifugal loads from the shell is passed through the snap ring and into the spar and not through a tip cap dovetail slot and projection structure.

  19. Multiple memory systems and extinction 

    E-print Network

    Gabriele, Amanda

    2005-08-29

    stream_source_info etd-tamu-2005A-PSYC-Gabriele.pdf.txt stream_content_type text/plain stream_size 84839 Content-Encoding ISO-8859-1 stream_name etd-tamu-2005A-PSYC-Gabriele.pdf.txt Content-Type text/plain; charset=ISO-8859...-1 MULTIPLE MEMORY SYSTEMS AND EXTINCTION A Thesis by AMANDA GABRIELE Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE May 2005...

  20. Myelin peptides in multiple sclerosis.

    PubMed

    Grau-López, L; Raïch, D; Ramo-Tello, C; Naranjo-Gómez, M; Dàvalos, A; Pujol-Borrell, R; Borràs, F E; Martínez-Cáceres, E

    2009-07-01

    The development of specific therapies for organ-specific autoimmune diseases requires the identification of relevant immunogenic epitopes, recognized by both pathogenic T cells and autoantibodies. Here, we review the most relevant studies focused in the identification of peptides in multiple sclerosis (MS) and the distinct T cell reactivity induced in patients compared to controls. Only a few studies reported significant differences in terms of T cell reactivity to them. The current knowledge on this issue, and the diagnostic and therapeutic possibilities opened by the identification of pathogenic MS epitopes are discussed in this paper. PMID:19393199

  1. Recirculation in multiple wave conversions

    SciTech Connect

    Brizard, A. J.; Kaufman, A. N.; Tracy, E. R.

    2008-08-15

    A one-dimensional multiple wave-conversion model is constructed that allows energy recirculation in ray phase space. Using a modular eikonal approach, the connection coefficients for this model are calculated by ray phase-space methods. Analytical results (confirmed numerically) show that all connection coefficients exhibit interference effects that depend on an interference phase, calculated from the coupling constants and the area enclosed by the intersecting rays. This conceptual model, which focuses on the topology of intersecting rays in phase space, is used to investigate how mode conversion between primary and secondary waves is modified by the presence of a tertiary wave.

  2. Recirculation in multiple wave conversions

    SciTech Connect

    Kaufman, A. N.; Brizard, A.J.; Kaufman, A.N.; Tracy, E.R.

    2008-07-30

    A one-dimensional multiple wave-conversion model is constructed that allows energy recirculation in ray phase space. Using a modular eikonal approach, the connection coefficients for this model are calculated by ray phase-space methods. Analytical results (confirmed numerically) show that all connection coefficients exhibit interference effects that depend on an interference phase, calculated from the coupling constants and the area enclosed by the intersecting rays. This conceptual model, which focuses on the topology of intersecting rays in phase space, is used to investigate how mode conversion between primary and secondary waves is modified by the presence of a tertiary wave.

  3. Multiple $q$-zeta brackets

    E-print Network

    Wadim Zudilin

    2015-03-22

    The multiple zeta values (MZVs) possess a rich algebraic structure of algebraic relations, which is conjecturally determined by two different (shuffle and stuffle) products of a certain algebra of noncommutative words. In a recent work, Bachmann constructed a $q$-analogue of the MZVs -- the so-called bi-brackets -- for which the two products are dual to each other, in a very natural way. We overview Bachmann's construction and discuss the radial asymptotics of the bi-brackets, its links to the MZVs, and related linear (in)dependence questions of the $q$-analogue.

  4. Multiple sclerosis: living the reality.

    PubMed

    Fawcett, Tonks N; Lucas, Maree

    Multiple sclerosis (MS) is a highly variable and unpredictable disease and is considered one of the most life-altering diagnoses a person can receive (Holland and Madonna, 2005). The hallmark of this disorder is its unpredictability. This article explores the journey one individual (ML) takes from the time that seemingly trivial symptoms took on a new and disturbing meaning to the point where, as someone newly diagnosed with MS, the potential challenges of the journey ahead have to be viewed with realism, optimism, and meaning. PMID:16415749

  5. www.sciencemag.org/cgi/content/full/science.1220683/DC1 Supplementary Materials for

    E-print Network

    Lim, Wendell

    (8), which can integrate multiple copies. Yeast strains and plasmids used in this work are listed Yeast Strain Construction and Manipulation The parent yeast strain for all experiments was F1950 (1278b phenotype (2-4). Yeast knockout strains were prepared using PCR-mediated gene deletion (5, 6

  6. Multiple protocol fluorometer and method

    DOEpatents

    Kolber, Zbigniew S. (Shoreham, NY); Falkowski, Paul G. (Stony Brook, NY)

    2000-09-19

    A multiple protocol fluorometer measures photosynthetic parameters of phytoplankton and higher plants using actively stimulated fluorescence protocols. The measured parameters include spectrally-resolved functional and optical absorption cross sections of PSII, extent of energy transfer between reaction centers of PSII, F.sub.0 (minimal), F.sub.m (maximal) and F.sub.v (variable) components of PSII fluorescence, photochemical and non-photochemical quenching, size of the plastoquinone (PQ) pool, and the kinetics of electron transport between Q.sub.a and PQ pool and between PQ pool and PSI. The multiple protocol fluorometer, in one embodiment, is equipped with an excitation source having a controlled spectral output range between 420 nm and 555 nm and capable of generating flashlets having a duration of 0.125-32 .mu.s, an interval between 0.5 .mu.s and 2 seconds, and peak optical power of up to 2 W/cm.sup.2. The excitation source is also capable of generating, simultaneous with the flashlets, a controlled continuous, background illumination.

  7. Innovative Agents in Multiple Myeloma

    PubMed Central

    Faiman, Beth; Richards, Tiffany

    2014-01-01

    Multiple myeloma (MM) remains an incurable cancer of the bone marrow plasma cells. However, the overall survival of patients with MM has increased dramatically within the past decade. This is due, in part, to newer agents such as immunomodulatory drugs (lenalidomide, thalidomide, and pomalidomide) and proteasome inhibitors (bortezomib, carfilzomib, MLN9708). These and several other new classes of drugs have arisen from an improved understanding of the complex environment in which genetic changes occur. Improved understanding of genetic events will enable clinicians to better stratify risk before and during therapy, tailor treatment, and test the value of personalized interventions. The ultimate goal in this incurable disease setting is to reduce the impact of cancer- or chemotherapy-related side effects. Nurses and advanced practitioners are integral to the treatment team. Thus, each should be aware of changes to the current drug landscape. Targeted drugs with sophisticated mechanisms of action are currently under investigation. Patients gain access to newer drugs within the context of clinical trials. Awareness of such trials will help accrual and determine if therapeutic benefit exists. In this article, we will describe new agents with unique and targeted mechanisms of action that have activity in patients with relapsed and/or refractory multiple myeloma. PMID:25089218

  8. Multiple channel data acquisition system

    DOEpatents

    Crawley, H. Bert (Ames, IA); Rosenberg, Eli I. (Ames, IA); Meyer, W. Thomas (Ames, IA); Gorbics, Mark S. (Ames, IA); Thomas, William D. (Boone, IA); McKay, Roy L. (Ames, IA); Homer, Jr., John F. (Ames, IA)

    1990-05-22

    A multiple channel data acquisition system for the transfer of large amounts of data from a multiplicity of data channels has a plurality of modules which operate in parallel to convert analog signals to digital data and transfer that data to a communications host via a FASTBUS. Each module has a plurality of submodules which include a front end buffer (FEB) connected to input circuitry having an analog to digital converter with cache memory for each of a plurality of channels. The submodules are interfaced with the FASTBUS via a FASTBUS coupler which controls a module bus and a module memory. The system is triggered to effect rapid parallel data samplings which are stored to the cache memories. The cache memories are uploaded to the FEBs during which zero suppression occurs. The data in the FEBs is reformatted and compressed by a local processor during transfer to the module memory. The FASTBUS coupler is used by the communications host to upload the compressed and formatted data from the module memory. The local processor executes programs which are downloaded to the module memory through the FASTBUS coupler.

  9. Multiple pure tone noise prediction

    NASA Astrophysics Data System (ADS)

    Han, Fei; Sharma, Anupam; Paliath, Umesh; Shieh, Chingwei

    2014-12-01

    This paper presents a fully numerical method for predicting multiple pure tones, also known as “Buzzsaw” noise. It consists of three steps that account for noise source generation, nonlinear acoustic propagation with hard as well as lined walls inside the nacelle, and linear acoustic propagation outside the engine. Noise generation is modeled by steady, part-annulus computational fluid dynamics (CFD) simulations. A linear superposition algorithm is used to construct full-annulus shock/pressure pattern just upstream of the fan from part-annulus CFD results. Nonlinear wave propagation is carried out inside the duct using a pseudo-two-dimensional solution of Burgers' equation. Scattering from nacelle lip as well as radiation to farfield is performed using the commercial solver ACTRAN/TM. The proposed prediction process is verified by comparing against full-annulus CFD simulations as well as against static engine test data for a typical high bypass ratio aircraft engine with hardwall as well as lined inlets. Comparisons are drawn against nacelle unsteady pressure transducer measurements at two axial locations as well as against near- and far-field microphone array measurements outside the duct. This is the first fully numerical approach (no experimental or empirical input is required) to predict multiple pure tone noise generation, in-duct propagation and far-field radiation. It uses measured blade coordinates to calculate MPT noise.

  10. Multiple channel data acquisition system

    DOEpatents

    Crawley, H.B.; Rosenberg, E.I.; Meyer, W.T.; Gorbics, M.S.; Thomas, W.D.; McKay, R.L.; Homer, J.F. Jr.

    1990-05-22

    A multiple channel data acquisition system for the transfer of large amounts of data from a multiplicity of data channels has a plurality of modules which operate in parallel to convert analog signals to digital data and transfer that data to a communications host via a FASTBUS. Each module has a plurality of submodules which include a front end buffer (FEB) connected to input circuitry having an analog to digital converter with cache memory for each of a plurality of channels. The submodules are interfaced with the FASTBUS via a FASTBUS coupler which controls a module bus and a module memory. The system is triggered to effect rapid parallel data samplings which are stored to the cache memories. The cache memories are uploaded to the FEBs during which zero suppression occurs. The data in the FEBs is reformatted and compressed by a local processor during transfer to the module memory. The FASTBUS coupler is used by the communications host to upload the compressed and formatted data from the module memory. The local processor executes programs which are downloaded to the module memory through the FASTBUS coupler. 25 figs.

  11. MULTIPLE ECH LAUNCHER CONTROL SYSTEM

    SciTech Connect

    GREEN,M.T; PONCE,D; GRUNLOH,H.J; ELLIS,R.A; GROSNICKLE,W.H; HUMPHREY,R.L

    2003-10-01

    OAK-B135 The addition of new, high power gyrotrons to the heating and current drive arsenal at DIII-D, required a system upgrade for control of fully steerable ECH Launchers. Each launcher contains two pointing mirrors with two degrees of mechanical freedom. The two flavors of motion are called facet and tilt. Therefore up to four channels of motion per launcher need to be controlled. The system utilizes absolute encoders to indicate mirror position and therefore direction of the microwave beam. The launcher movement is primarily controlled by PLC, but future iterations of design, may require this control to be accomplished by a CPU on fast bus such as Compact PCI. This will be necessary to accomplish real time position control. Safety of equipment and personnel is of primary importance when controlling a system of moving parts. Therefore multiple interlocks and fault status enunciators have been implemented. This paper addresses the design of a Multiple ECH Launcher Control System, and characterizes the flexibility needed to upgrade to a real time position control system in the future.

  12. Multiple Waveband Temperature Sensor (MWTS)

    NASA Technical Reports Server (NTRS)

    Bandara, Sumith V.; Gunapala, Sarath; Wilson, Daniel; Stirbl, Robert; Blea, Anthony; Harding, Gilbert

    2006-01-01

    This slide presentation reviews the development of Multiple Waveband Temperature Sensor (MWTS). The MWTS project will result in a highly stable, monolithically integrated, high resolution infrared detector array sensor that records registered thermal imagery in four infrared wavebands to infer dynamic temperature profiles on a laser-irradiated ground target. An accurate surface temperature measurement of a target in extreme environments in a non-intrusive manner is required. The development challenge is to: determine optimum wavebands (suitable for target temperatures, nature of the targets and environments) to measure accurate target surface temperature independent of the emissivity, integrate simultaneously readable multiband Quantum Well Infrared Photodetectors (QWIPs) in a single monolithic focal plane array (FPA) sensor and to integrate the hardware/software and system calibration for remote temperature measurements. The charge was therefore to develop and demonstrate a multiband infrared imaging camera with the detectors simultaneously sensitive to multiple distinct color bands for front surface temperature measurements Wavelength ( m) measurements. Amongst the requirements are: that the measurement system will not affect target dynamics or response to the laser irradiation and that the simplest criterion for spectral band selection is to choose those practically feasible spectral bands that create the most contrast between the objects or scenes of interest in the expected environmental conditions. There is in the presentation a review of the modeling and simulation of multi-wave infrared temperature measurement and also a review of the detector development and QWIP capacities.

  13. Time-resolved multiple scattering

    NASA Astrophysics Data System (ADS)

    Kunz, Gerard J.

    1995-09-01

    Time and range resolved multiple-scattered radiation from the aureole around a traveling radiation, using an additional off axis scanning lidar-receiver, on top of an existing lidar. This system can be considered as an analogue equivalent of Bissonnette's fixed multi-field-of-view lidar. Because multiple-scattering is effective over much larger volumes than the illuminating volume by the laser pulse itself; the variations in the signals due to atmospheric structures are reduced to a certain extent. A simple second-order scattering model has been developed to understand this volume averaging effect. It has been shown that this model can be used to estimate the extinction coefficient of clouds and the average diameters of the cloud droplets. Lidar waveforms, obtained during a field experiment, have been inverted with the proposed model. The results appear to be in reasonable agreement with the in situ measured extinction using a nephelometer mounted on a cable car which was moving up and down a mountain slope through the clouds.

  14. [Current immunotherapy of multiple sclerosis].

    PubMed

    Paul, F; Ruprecht, K

    2015-08-01

    Following the introduction of interferon beta 1b as the first immunomodulatory therapy for multiple sclerosis (MS) in 1993, there are currently nine substances or substance classes approved for the treatment of MS (i.e. alemtuzumab, azathioprine, dimethyl fumarate, fingolimod, glatiramer acetate, interferon beta, mitoxantrone, natalizumab and teriflunomide). Major developments during the last 5 years include the approval of orally administered medications (i.e. fingolimod, teriflunomide and dimethyl fumarate), a monoclonal antibody (alemtuzumab), as well as glatiramer acetate with an administration frequency three times a week and a pegylated formulation of interferon beta 1a. The broadened therapeutic options enable a more differentiated and individualized therapy of MS; however, evidence-based data for therapeutic decision-making relevant in clinical practice are not always available. Rare but potentially severe and even life-threatening side effects of immunotherapies for MS require continuous pharmacovigilance and adherence to risk management plans. PMID:26253589

  15. 2014 Multiple Sclerosis Therapeutic Update

    PubMed Central

    Cree, Bruce A. C.

    2014-01-01

    Rapid advances are occurring in multiple sclerosis disease modifying therapies. Recent therapeutic advances include modifications to improve tolerability of existing products (e.g. interferon beta and glatiramer acetate), development of novel anti-neuroinflammatory medications (e.g. fingolimod, teriflunomide and dimethyl fumarate, daclizumab, alemtuzumab, ocrelizumab) and investigation of treatments in progressive MS (e.g. natalizumab, mastinib, natalizumab, siponimod). The impact of vitamin D supplementation on the disease course in relapsing MS patients is also being studied in several clinical trials. This article reviews the current state of the field with a forward look to the next phase of MS research that could focus on strategies to promote remyelination and provide neuronal protection. PMID:24707333

  16. Multiple-stage integrating accelerometer

    DOEpatents

    Devaney, Howard F. (Cedar Crest, NM)

    1986-01-01

    An accelerometer assembly is provided for use in activating a switch in response to multiple acceleration pulses in series. The accelerometer includes a housing forming a chamber. An inertial mass or piston is slidably disposed in the chamber and spring biased toward a first or reset position. A damping system is also provided to damp piston movement in response to first and subsequent acceleration pulses. Additionally, a cam, including a Z-shaped slot, and cooperating follower pin slidably received therein are mounted to the piston and the housing. The middle or cross-over leg of the Z-shaped slot cooperates with the follower pin to block or limit piston movement and prevent switch activation in response to a lone acceleration pulse. The switch of the assembly is only activated after two or more separate acceleration pulses are sensed and the piston reaches the end of the chamber opposite the reset position.

  17. Autonomic Dysregulation in Multiple Sclerosis.

    PubMed

    Pintér, Alexandra; Cseh, Domonkos; Sárközi, Adrienn; Illigens, Ben M; Siepmann, Timo

    2015-01-01

    Multiple sclerosis (MS) is a chronic, progressive central neurological disease characterized by inflammation and demyelination. In patients with MS, dysregulation of the autonomic nervous system may present with various clinical symptoms including sweating abnormalities, urinary dysfunction, orthostatic dysregulation, gastrointestinal symptoms, and sexual dysfunction. These autonomic disturbances reduce the quality of life of affected patients and constitute a clinical challenge to the physician due to variability of clinical presentation and inconsistent data on diagnosis and treatment. Early diagnosis and initiation of individualized interdisciplinary and multimodal strategies is beneficial in the management of autonomic dysfunction in MS. This review summarizes the current literature on the most prevalent aspects of autonomic dysfunction in MS and provides reference to underlying pathophysiological mechanisms as well as means of diagnosis and treatment. PMID:26213927

  18. Multiple importance sampling for PET.

    PubMed

    Szirmay-Kalos, Laszló; Magdics, Milán; Tóth, Balázs

    2014-04-01

    This paper proposes the application of multiple importance sampling in fully 3-D positron emission tomography to speed up the iterative reconstruction process. The proposed method combines the results of lines of responses (LOR) driven and voxel driven projections keeping their advantages, like importance sampling, performance and parallel execution on graphics processing units. Voxel driven methods can focus on point like features while LOR driven approaches are efficient in reconstructing homogeneous regions. The theoretical basis of the combination is the application of the mixture of the samples generated by the individual importance sampling methods, emphasizing a particular method where it is better than others. The proposed algorithms are built into the Tera-tomo system. PMID:24710165

  19. Conformal Mapping for Multiple Terminals

    E-print Network

    Wang, Weimin; Wang, Qiang; Ren, Hao

    2015-01-01

    Conformal mapping is an important mathematical tool in many physical and engineering fields, especially in electrostatics, fluid mechanics, classical mechanics, and transformation optics. However in the existing textbooks and literatures, it is only adopted to solve the problems which have only two terminals. Two terminals with electric potential differences, pressure difference, optical path difference, etc., can be mapped conformally onto a solvable structure, e.g., a rectangle, where the two terminals are mapped onto two opposite edges of the rectangle. Here we show a conformal mapping method for multiple terminals, which is more common in practical applications. Through accurate analysis of the boundary conditions, additional terminals or boundaries are folded in the inner of the mapped rectangle. Then the solution will not be influenced. The method is described in several typical situations and two application examples are detailed. The first example is an electrostatic actuator with three electrodes. A ...

  20. Multiple-stage integrating accelerometer

    DOEpatents

    Devaney, H.F.

    1984-06-27

    An accelerometer assembly is provided for use in activating a switch in response to multiple acceleration pulses in series. The accelerometer includes a housing forming a chamber. An inertial mass or piston is slidably disposed in the chamber and spring biased toward a first or reset position. A damping system is also provided to damp piston movement in response to first and subsequent acceleration pulses. Additionally, a cam, including a Z-shaped slot, and cooperating follower pin slidably received therein are mounted to the piston and the housing. The middle or cross-over leg of the Z-shaped slot cooperates with the follower pin to block or limit piston movement and prevent switch activation in response to a lone acceleration pulse. The switch of the assembly is only activated after two or more separate acceleration pulses are sensed and the piston reaches the end of the chamber opposite the reset position.

  1. Candidate autoantigens in multiple sclerosis.

    PubMed

    Schmidt, S

    1999-06-01

    Multiple sclerosis is an inflammatory demyelinating CNS disease of putatively autoimmune origin. Novel models of experimental autoimmune encephalomyelitis (EAE) have demonstrated that T cells specific for various myelin and even nonmyelin proteins are potentially encephalitogenic. The encephalitogenic T cell response directed against different CNS antigens not only determines the lesional topography of CNS inflammation but also the composition of the inflammatory infiltrates. The heterogeneity of the lesional distribution seen in EAE might therefore be useful for the understanding of the various clinical subtypes seen in MS. In this review the possible candidate autoantigens in MS are discussed with special regard to the human T cell and B cell responses against various myelin and nonmyelin proteins. PMID:10408714

  2. [The epidemiology of multiple myeloma].

    PubMed

    Suzuki, Kenshi; Takahashi, Haruka

    2015-01-01

    We investigated epidemiology of multiple myeloma (MM), referring to recent papers. This article includes three points: 1) the progression rate of monoclonal gammopathy of undetermined significance (MGUS) to MM, 2) the effect of radiation to prevalence of MM, and 3) secondary malignancy after chemotherapy used to treat MM. The risk of progression from MGUS to MM is 1% per year. The researches of atomic bomb showed that there is no increase of risk of MM after radiation exposure. In contrast, studies investigating workers in nuclear power plants point out that radiation exposure over 50 mSv increases risk of MM. The incidence of secondary malignancy after chemotherapy used to treat MM was about 5%. This article will help to review recent researches about epidemiology of MM. PMID:25626296

  3. [Multiple myeloma and renal impairment].

    PubMed

    Takahashi, Naoto

    2015-01-01

    Renal impairment (RI) is a common complication and it impacts on a survival of patients with systemic multiple myeloma (MM). In a cohort study in Akita, about 20-26% patients with MM showed RI at diagnosis and it was independently associated with overall survival. Cast nephropathy, amyloidosis, and monoclonal immunoglobulin deposition disease (Randall type) are known as three pathological findings of kidney in MM patients with RI. Recently, the term monoclonal gammopathy of renal significance (MGRS) was proposed because of a causal relationship between the monoclonal gammopathy and the renal damage. Bortezomib-based regimens may improve renal function in the majority of MM patients with RI. We discussed an epidemiology, clinic-pathological findings and treatments of MM with RI in this review. PMID:25626301

  4. Hereditary Multiple Exostoses with Pseudoaneurysm

    SciTech Connect

    Al-Hadidy, Azmy M. Al-Smady, Moa'ath M.; Haroun, Azmi A.; Hamamy, Hanan A.; Ghoul, Suha M.; Shennak, Akram O.

    2007-06-15

    A 16-year-old male patient with hereditary multiple exostoses (HME) was found to have a pseudoaneurysm of the left popliteal artery caused by osteochondroma in the lower femur. The diagnosis was confirmed by ultrasound, magnetic resonance imaging and magnetic resonance angiography without the need to perform an angiogram. The osteochondroma was excised and the popliteal artery was repaired with a saphenous graft. Vascular complications are extremely rare in HME, pseudoaneurysm being the most common and mostly located in the popliteal artery. This complication should be considered in young HME patients with a mass at the knee region. The radiological spectrum of investigations allows the diagnosis of this complication with proper and less invasive management procedures for the patient.

  5. Standardized multiple output power supply

    NASA Technical Reports Server (NTRS)

    Ragusa, E. V.

    1975-01-01

    A comprehensive program to develop a prototype model of a standardized multiple output power supply for use in space flight applications is described. The prototype unit was tested and evaluated to assure that the design would provide near optimum performance for the planned application. The prototype design used a dc-to-dc converter incorporating reqenerative current feedback with a time-ratio controlled duty cycle to achieve high efficiency over a wide variation of input voltage and output loads. The packaging concept uses a mainframe capable of accommodating up to four inverter/regulator modules with one common input filter and housekeeping module. Each inverter/regulator module provides a maximum of 100 watts or 10 amperes. Each module is adaptable to operate at any voltage between 4.0 volts and 108 volts. The prototype unit contains +5, + or - 15 and +28 volt modules.

  6. Moral enhancement requires multiple virtues.

    PubMed

    Hughes, James J

    2015-01-01

    Some of the debates around the concept of moral enhancement have focused on whether the improvement of a single trait, such as empathy or intelligence, would be a good in general, or in all circumstances. All virtue theories, however, both secular and religious, have articulated multiple virtues that temper and inform one another in the development of a mature moral character. The project of moral enhancement requires a reengagement with virtue ethics and contemporary moral psychology to develop an empirically grounded model of the virtues and a fuller model of character development. Each of these virtues may be manipulable with electronic, psychopharmaceutical, and genetic interventions. A set of interdependent virtues is proposed, along with some of the research pointing to ways such virtues could be enhanced. PMID:25473861

  7. Pulmonary hypertension complicating multiple myeloma

    PubMed Central

    Mark, Tomer M.; Niesvizky, Ruben; Sobol, Irina

    2015-01-01

    Abstract Pulmonary hypertension (PH) is an infrequently reported complication of multiple myeloma (MM). PH has been more commonly associated with amyloidosis, myeloproliferative diseases, and the POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome. PH in MM is typically mild to moderate and may be secondary to a variety of conditions, which include left ventricular dysfunction, high-output cardiac failure, chronic kidney disease, treatment-related toxicities, and precapillary involvement. We describe 3 patients with MM and severe PH. Each patient underwent right heart catheterization. All patients demonstrated elevated pulmonary pressures, transpulmonary gradients, and pulmonary vascular resistance. Each patient was ultimately treated with pulmonary vasodilator therapy with improvement in cardiopulmonary symptoms. Additional studies are needed to define the prevalence, prognosis, and pathogenesis of PH in this complex population and to help clarify who may benefit from targeted PH therapy. PMID:26401262

  8. Autonomic Dysregulation in Multiple Sclerosis

    PubMed Central

    Pintér, Alexandra; Cseh, Domonkos; Sárközi, Adrienn; Illigens, Ben M.; Siepmann, Timo

    2015-01-01

    Multiple sclerosis (MS) is a chronic, progressive central neurological disease characterized by inflammation and demyelination. In patients with MS, dysregulation of the autonomic nervous system may present with various clinical symptoms including sweating abnormalities, urinary dysfunction, orthostatic dysregulation, gastrointestinal symptoms, and sexual dysfunction. These autonomic disturbances reduce the quality of life of affected patients and constitute a clinical challenge to the physician due to variability of clinical presentation and inconsistent data on diagnosis and treatment. Early diagnosis and initiation of individualized interdisciplinary and multimodal strategies is beneficial in the management of autonomic dysfunction in MS. This review summarizes the current literature on the most prevalent aspects of autonomic dysfunction in MS and provides reference to underlying pathophysiological mechanisms as well as means of diagnosis and treatment. PMID:26213927

  9. Hughes syndrome and multiple sclerosis.

    PubMed

    Uthman, I; Noureldine, M H A; Berjawi, A; Skaf, M; Haydar, A A; Merashli, M; Hughes, G R V

    2015-02-01

    Multiple sclerosis (MS) and antiphospholipid syndrome (APS) share common clinical, laboratory and radiological features. We reviewed all the English papers on MS and APS published in the literature from 1965 to 2014 using PubMed and Google Scholar. We found that APS can mimic antiphospholipid antibodies (aPL)-positive MS in many ways in its clinical presentation. Nevertheless, APS diagnosis, clinical manifestations and management differ from those of MS. aPL were found in MS patients with titers ranging from 2% to 88%. The distribution and volume of lesions on magnetic resonance imaging (MRI) may help to differentiate MS from primary APS. In addition, atypical MS presentation can guide physicians toward an alternative diagnosis, especially when features of thrombosis and/or history of connective tissue disease are present. In that case, an anticoagulation trial could be worthwhile. PMID:25326228

  10. Supervisory Control Of Multiple Vehicles

    NASA Astrophysics Data System (ADS)

    Brooks, Thurston L.

    1989-03-01

    Economically mandated force limitations combined with a steadily shrinking pool of candidates endowed with the requisite skill levels, dictates that modern military systems must multiply the individual soldier's performance. An optimal solution within the realm of current technology can be achieved by recognizing that (1) machines are more effective than humans when the task is routine and specified, and (2) humans process complex data sets and deal with the unpredictable better than machines. These observations lead naturally to a philosophy in which the human's role becomes a higher level function associated with planning, teaching, initiating, monitoring, and intervening when the machine gets into trouble, while the machine performs the codifiable tasks with deliberate efficiency. Martin Marietta is developing the capability for a single operator to simultaneously control multiple remote weapons platforms through the development of a supervisory controls testbed. This effort is described.

  11. Naming Game with Multiple Hearers

    NASA Astrophysics Data System (ADS)

    Li, Bing; Chen, Guanrong; Chow, Tommy W. S.

    2013-05-01

    A new model called Naming Game with Multiple Hearers (NGMH) is proposed in this paper. A naming game over a population of individuals aims to reach consensus on the name of an object through pair-wise local interactions among all the individuals. The proposed NGMH model describes the learning process of a new word, in a population with one speaker and multiple hearers, at each interaction towards convergence. The characteristics of NGMH are examined on three types of network topologies, namely ER random-graph network, WS small-world network, and BA scale-free network. Comparative analysis on the convergence time is performed, revealing that the topology with a larger average (node) degree can reach consensus faster than the others over the same population. It is found that, for a homogeneous network, the average degree is the limiting value of the number of hearers, which reduces the individual ability of learning new words, consequently decreasing the convergence time; for a scale-free network, this limiting value is the deviation of the average degree. It is also found that a network with a larger clustering coefficient takes longer time to converge; especially a small-word network with smallest rewiring possibility takes longest time to reach convergence. As more new nodes are being added to scale-free networks with different degree distributions, their convergence time appears to be robust against the network-size variation. Most new findings reported in this paper are different from that of the single-speaker/single-hearer naming games documented in the literature.

  12. Migraine: Multiple Processes, Complex Pathophysiology

    PubMed Central

    Noseda, Rodrigo; Borsook, David

    2015-01-01

    Migraine is a common, multifactorial, disabling, recurrent, hereditary neurovascular headache disorder. It usually strikes sufferers a few times per year in childhood and then progresses to a few times per week in adulthood, particularly in females. Attacks often begin with warning signs (prodromes) and aura (transient focal neurological symptoms) whose origin is thought to involve the hypothalamus, brainstem, and cortex. Once the headache develops, it typically throbs, intensifies with an increase in intracranial pressure, and presents itself in association with nausea, vomiting, and abnormal sensitivity to light, noise, and smell. It can also be accompanied by abnormal skin sensitivity (allodynia) and muscle tenderness. Collectively, the symptoms that accompany migraine from the prodromal stage through the headache phase suggest that multiple neuronal systems function abnormally. As a consequence of the disease itself or its genetic underpinnings, the migraine brain is altered structurally and functionally. These molecular, anatomical, and functional abnormalities provide a neuronal substrate for an extreme sensitivity to fluctuations in homeostasis, a decreased ability to adapt, and the recurrence of headache. Advances in understanding the genetic predisposition to migraine, and the discovery of multiple susceptible gene variants (many of which encode proteins that participate in the regulation of glutamate neurotransmission and proper formation of synaptic plasticity) define the most compelling hypothesis for the generalized neuronal hyperexcitability and the anatomical alterations seen in the migraine brain. Regarding the headache pain itself, attempts to understand its unique qualities point to activation of the trigeminovascular pathway as a prerequisite for explaining why the pain is restricted to the head, often affecting the periorbital area and the eye, and intensifies when intracranial pressure increases. PMID:25926442

  13. Care Partners and Multiple Sclerosis

    PubMed Central

    Quig, Mary Elizabeth; Tyry, Tuula; Marrie, Ruth Ann; Cutter, Gary; Shearin, Edward; Johnson, Kamau; Simsarian, James

    2015-01-01

    Background: Caring for someone with multiple sclerosis (MS) can be a stressful experience that requires clinical attention. We investigated the impact of caregiver stress on the emotional well-being and physical health of the MS care partner using the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. Methods: Care partners of NARCOMS participants were invited to complete an online questionnaire that captured demographic characteristics, health status, caregiver burden as measured by the Zarit Caregiver Burden Interview, and impact of caregiving on employment. Results: Of 1446 care partners who agreed to participate, 1333 had complete data. Most were men (n = 825, 61.9%), with a mean (SD) age of 51.1 (11.2) years. The mean (SD) Zarit total score was 24.6 (15.1), placing the overall group in the mild caregiver burden range. Compared with male care partners, female care partners reported higher levels of burden and stress and more medication use for stress/anxiety and mood disorders. Male care partners were more likely to report physical concerns. Care partners of people with primary progressive MS reported greater perceived burden than did partners of people with secondary progressive MS and relapsing-remitting MS. More than 40% of care partners (559 of 1288) had missed work during the past year owing to caregiving responsibilities. Conclusions: Care partners of people with MS have substantial physical and psychological health concerns and experience an adverse impact on employment. Future research should evaluate how to mitigate the adverse effects of caregiving and evaluate positive aspects of the role.

  14. Migraine: multiple processes, complex pathophysiology.

    PubMed

    Burstein, Rami; Noseda, Rodrigo; Borsook, David

    2015-04-29

    Migraine is a common, multifactorial, disabling, recurrent, hereditary neurovascular headache disorder. It usually strikes sufferers a few times per year in childhood and then progresses to a few times per week in adulthood, particularly in females. Attacks often begin with warning signs (prodromes) and aura (transient focal neurological symptoms) whose origin is thought to involve the hypothalamus, brainstem, and cortex. Once the headache develops, it typically throbs, intensifies with an increase in intracranial pressure, and presents itself in association with nausea, vomiting, and abnormal sensitivity to light, noise, and smell. It can also be accompanied by abnormal skin sensitivity (allodynia) and muscle tenderness. Collectively, the symptoms that accompany migraine from the prodromal stage through the headache phase suggest that multiple neuronal systems function abnormally. As a consequence of the disease itself or its genetic underpinnings, the migraine brain is altered structurally and functionally. These molecular, anatomical, and functional abnormalities provide a neuronal substrate for an extreme sensitivity to fluctuations in homeostasis, a decreased ability to adapt, and the recurrence of headache. Advances in understanding the genetic predisposition to migraine, and the discovery of multiple susceptible gene variants (many of which encode proteins that participate in the regulation of glutamate neurotransmission and proper formation of synaptic plasticity) define the most compelling hypothesis for the generalized neuronal hyperexcitability and the anatomical alterations seen in the migraine brain. Regarding the headache pain itself, attempts to understand its unique qualities point to activation of the trigeminovascular pathway as a prerequisite for explaining why the pain is restricted to the head, often affecting the periorbital area and the eye, and intensifies when intracranial pressure increases. PMID:25926442

  15. Improving Multiple Fault Diagnosability using Possible Conflicts

    NASA Technical Reports Server (NTRS)

    Daigle, Matthew J.; Bregon, Anibal; Biswas, Gautam; Koutsoukos, Xenofon; Pulido, Belarmino

    2012-01-01

    Multiple fault diagnosis is a difficult problem for dynamic systems. Due to fault masking, compensation, and relative time of fault occurrence, multiple faults can manifest in many different ways as observable fault signature sequences. This decreases diagnosability of multiple faults, and therefore leads to a loss in effectiveness of the fault isolation step. We develop a qualitative, event-based, multiple fault isolation framework, and derive several notions of multiple fault diagnosability. We show that using Possible Conflicts, a model decomposition technique that decouples faults from residuals, we can significantly improve the diagnosability of multiple faults compared to an approach using a single global model. We demonstrate these concepts and provide results using a multi-tank system as a case study.

  16. Multiple acousto-optic q-switch

    DOEpatents

    Deason, Vance A. (Idaho Falls, ID)

    1993-01-01

    An improved dynamic moire interferometer comprised of a lasing medium providing a plurality of beams of coherent light, a multiple q-switch producing multiple trains of 100,000 or more pulses per second, a combining means collimating multiple trains of pulses into substantially a single train and directing beams to specimen gratings affixed to a test material, and a controller, triggering and sequencing the emission of the pulses with the occurrence and recording of a dynamic loading event.

  17. Multiple acousto-optic q-switch

    DOEpatents

    Deason, Vance A.

    1993-12-07

    An improved dynamic moire interferometer comprised of a lasing medium providing a plurality of beams of coherent light, a multiple q-switch producing multiple trains of 100,000 or more pulses per second, a combining means collimating multiple trains of pulses into substantially a single train and directing beams to specimen gratings affixed to a test material, and a controller, triggering and sequencing the emission of the pulses with the occurrence and recording of a dynamic loading event.

  18. Evolution of multiple supernova remnants

    NASA Astrophysics Data System (ADS)

    Vasiliev, Evgenii O.; Nath, Biman B.; Shchekinov, Yuri

    2015-01-01

    Heating of the interstellar medium (ISM) by multiple supernova (SN) explosions is at the heart of producing galaxy-scale outflows in starburst galaxies. Standard models of outflows assume a high efficiency of SNe in heating the gas to X-ray emitting temperatures and filling the central region of starburst with hot gas, in order to launch vigorous outflows. We use hydrodynamical simulations to study the efficiency of multiple SNe in heating the ISM and filling the volume with gas of high temperatures. We argue that it is important for SN remnants to have a large filling factor and a large heating efficiency. For this, they have to be clustered in space and time, and keep exploding until the hot gas percolates through the whole region, in order to compensate for the radiative loss. In the case of a limited number of SNe, we find that although the filling factor can be large, the heating efficiency declines after reaching a large value. In the case of a continuous series of SNe, the hot gas (T ? 3 × 106 K) can percolate through the whole region after the total volume filling factor reaches a threshold of ˜0.3. The efficiency of heating the gas to X-ray temperatures can be ?0.1 after this percolation epoch, which occurs after a period of ?10 Myr for a typical starburst SN rate density of ?SN ? 10-9 pc-3 yr-1 and gas density of n ? 10 cm-3 in starburst nuclei regions. This matches the recent observations of a time delay of similar order between the onset of star formation and galactic outflows. The efficiency to heat gas up to X-ray temperatures (?106.5 K) roughly scales as ? _SN^{0.2} n^{-0.6}. For a typical SN rate density and gas density in starburst nuclei, the heating efficiency is ˜0.15, also consistent with previous interpretations from X-ray observations. We discuss the implications of our results with regard to observational diagnostics of ionic ratios and emission measures in starburst nuclei regions.

  19. Experimental verification of carrier multiplication in graphene.

    PubMed

    Plötzing, T; Winzer, T; Malic, E; Neumaier, D; Knorr, A; Kurz, H

    2014-09-10

    We report on the first direct experimental observation of carrier multiplication in graphene reaching a multiplication factor of up to 2 and persisting on a picoseconds time scale. Exploiting multicolor pump-probe measurement techniques, the excited nonequilibrium carrier distribution is retrieved on an ultrafast time scale. This provides access to the temporal evolution of the optically excited carrier density and thus allows quantitative conclusions on possible carrier multiplication. Microscopic time- and momentum-resolved calculations on the ultrafast relaxation dynamics of optically excited carriers confirm the observation of carrier multiplication under corresponding experimental conditions, suggesting graphene as a promising material for novel high-efficiency photodetection devices. PMID:25144320

  20. Can Multiple Myeloma Be Found Early?

    MedlinePLUS

    ... Article Close Push escape to close saved articles window. My Saved Articles » My ACS » Multiple Myeloma + - Text Size Download Printable Version [PDF] » Early Detection, Diagnosis, and Staging ...

  1. Radiation Exposure - Multiple Languages: MedlinePlus

    MedlinePLUS

    ... List of All Topics All Radiation Exposure - Multiple Languages To use the sharing features on this page, please enable JavaScript. Korean (???) Russian (???????) Spanish (español) Korean (???) Radiation ...

  2. Gender agreement and multiple referents.

    PubMed

    Finocchiaro, Chiara; Mahon, Bradford Z; Caramazza, Alfonso

    2008-01-01

    We report a new pattern of usage in current, spoken Italian that has implications for both psycholinguistic models of language production and linguistic theories of language change. In Italian, gender agreement is mandatory for both singular and plural nouns. However, when two or more nouns of different grammatical gender appear in a conjoined noun phrase (NP), masculine plural agreement is required. In this study, we combined on-line and off-line methodologies in order to assess the mechanisms involved in gender marking in the context of multiple referents. The results of two pronoun production tasks showed that plural feminine agreement was significantly more difficult than plural masculine agreement. In a separate study using offline judgements of acceptability, we found that agreement violations in Italian are tolerated more readily in the case of feminine conjoined noun phrases (e.g., la mela e la banana 'the:fem apple:fem and the: fem banana: fem') than masculine conjoined noun phrases (e.g., il fiore e il libro 'the:mas flower: mas and the:mas book:mas'). Implications of these results are discussed both at the level of functional architecture within the language production system and at the level of changes in language use. PMID:21037930

  3. Multiple pathways regulate shoot branching

    PubMed Central

    Rameau, Catherine; Bertheloot, Jessica; Leduc, Nathalie; Andrieu, Bruno; Foucher, Fabrice; Sakr, Soulaiman

    2015-01-01

    Shoot branching patterns result from the spatio-temporal regulation of axillary bud outgrowth. Numerous endogenous, developmental and environmental factors are integrated at the bud and plant levels to determine numbers of growing shoots. Multiple pathways that converge to common integrators are most probably involved. We propose several pathways involving not only the classical hormones auxin, cytokinins and strigolactones, but also other signals with a strong influence on shoot branching such as gibberellins, sugars or molecular actors of plant phase transition. We also deal with recent findings about the molecular mechanisms and the pathway involved in the response to shade as an example of an environmental signal controlling branching. We propose the TEOSINTE BRANCHED1, CYCLOIDEA, PCF transcription factor TB1/BRC1 and the polar auxin transport stream in the stem as possible integrators of these pathways. We finally discuss how modeling can help to represent this highly dynamic system by articulating knowledges and hypothesis and calculating the phenotype properties they imply. PMID:25628627

  4. Allogeneic transplantation in multiple myeloma.

    PubMed

    Gahrton, Gösta; Krishnan, Amrita

    2014-02-01

    Allogeneic transplantation has the potential to cure subgroups of patients with multiple myeloma, but its role is controversial due to high transplant-related mortality. Therefore, myeloablative allogeneic transplantation has fallen out of favor. Allogeneic transplantation using reduced-intensity conditioning (RICallo) has lower transplant-related mortality and may be an option for subgroups of patients. Upfront tandem autologous/RICallo (auto/RICallo) was shown to be superior to single auto or tandem auto/auto in both progression-free and overall survival in two studies with long-term follow-up, while four similarly designed studies with shorter follow-up did not show a significant advantage. All studies included patients less than 70 years of age. No study has shown that the auto/RICallo approach is inferior to auto or auto/auto. There have been indications that poor-risk cytogenetics may be overcome by the auto/RICallo approach. Encouraging results have also been seen in treatment of relapsed patients. Small studies indicate that combining allogeneic transplant with new proteasome inhibitors and immunomodulatory drugs may further improve results. Prospective studies including these drugs for induction, conditioning and post-allogeneic transplant maintenance are warranted and planned. New cell therapies, such as with natural killer cells have shown encouraging results in experimental animals and should be tried in combination with allotransplantation. PMID:24224804

  5. Mechanisms of multiple chemical sensitivity.

    PubMed

    Winder, Chris

    2002-03-10

    Sensitivity to chemicals is a toxicological concept, contained in the dose-response relationship. Sensitivity also includes the concept of hypersensitivity, although controversy surrounds the nature of effects from very low exposures. The term multiple chemical sensitivity has been used to describe individuals with a debilitating, multi-organ sensitivity following chemical exposures. Many aspects of this condition extend the nature of sensitivity to low levels of exposure to chemicals, and is a designation with medical, immunological, neuropsychological and toxicological perspectives. The basis of MCS is still to be identified, although a large number of hypersensitivity, immunological, psychological, neurological and toxicological mechanisms have been suggested, including: allergy; autosuggestion; cacosomia; conditioned response; immunological; impairment of biochemical pathways involved in energy production; impairment of neurochemical pathways; illness belief system; limbic kindling; olfactory threshold sensitivity; panic disorder; psychosomatic condition; malingering; neurogenic inflammation; overload of biotransformation pathways (also linked with free radical production); psychological or psychiatric illness; airway reactivity; sensitisation of the neurological system; time dependent sensitisation, toxicant induced loss of tolerance. Most of these theories tend to break down into concepts involving: (1) disruption in immunological/allergy processes; (2) alteration in nervous system function; (3) changes in biochemical or biotransformation capacity; (4) changes in psychological/neurobehavioural function. Research into the possible mechanisms of MCS is far from complete. However, a number of promising avenues of investigation indicate that the possibility of alteration of the sensitivity of nervous system cells (neurogenic inflammation, limbic kindling, cacosomia, neurogenic switching) are a possible mechanism for MCS. PMID:11869820

  6. Optical multiple access intersatellite links

    NASA Astrophysics Data System (ADS)

    Grant, M. A.; Matthews, N. F.; Robson, D.

    1988-03-01

    The feasibility of an optical implementation of a multiple access medium data rate data relay service on the timescale of Euro-DRS was assessed. The service requirements for the feasibility study are based on the service which, in existing or planned systems, is implemented at S band. The system should communicate simultaneously with up to 8 LEO users in orbits of radii up to 7400 km providing 8 independently agile links. On each link, it should communicate at up to 2Mb/sec, at bit error rates of 10 to the minus 6th power in the return direction (LEO to GEO). A design concept for the GEO central node was produced. Mass and power estimates were evaluated and a preliminary spacecraft accommodation study performed. The system weighs 130 kg and has a power consumption of 300 W. The optical subsystem occupies a 75 x 75 x 30 cm volume on the top floor of the spacecraft. A number of trade-offs were identified and performed in reaching the final system configuration. The system should have 1 telescope system per user, a periscope mirror configuration for coarse pointing, a single telescope for both transmit and receive, and the use of both 0.8 micron for the LEO-GEO link and 1.3 micron for GEO-LEO.

  7. Multiple-measurement beam probe

    SciTech Connect

    Gilpatrick, J.D.; Grant, D.L.

    1986-01-01

    Particle accelerators are becoming smaller and are producing more intense beams; therefore, it is critical that beam-diagnostic instrumentation provide accelerator operators and automated control systems with a complete set of beam information. Traditionally, these beam data were collected and processed using limited-bandwidth interceptive techniques. For the new-generation accelerators, we are developing a multiple-measurement microstrip probe to obtain broadband beam data from inside a drift tube without perturbing the beam. The cylindrical probe's dimensions are 6-cm OD by 1.0 m long, and the probe is mounted inside a drift tube. The probe (and its associated electronics) monitors bunched-beam current, energy, and transverse position by sensing the beam's electromagnetic fields through the annular opening in the drift tube. The electrical impedance is tightly controlled through the full length of the probe and transmission lines to maintain beam-induced signal fidelity. The probe's small, cylindrical structure is matched to beam-bunch characteristics at specific beamline locations so that signal-to-noise ratios are optimized. Surrounding the probe, a mechanical structure attaches to the drift-tube interior and the quadrupole magnets; thus, the entire assembly's mechanical and electrical centers can be aligned and calibrated with respect to the rest of the linac.

  8. Remyelination Therapy in Multiple Sclerosis

    PubMed Central

    Harlow, Danielle E.; Honce, Justin M.; Miravalle, Augusto A.

    2015-01-01

    Multiple sclerosis (MS) is an immune-mediated disorder of the central nervous system that results in destruction of the myelin sheath that surrounds axons and eventual neurodegeneration. Current treatments approved for the treatment of relapsing forms of MS target the aberrant immune response and successfully reduce the severity of attacks and frequency of relapses. Therapies are still needed that can repair damage particularly for the treatment of progressive forms of MS for which current therapies are relatively ineffective. Remyelination can restore neuronal function and prevent further neuronal loss and clinical disability. Recent advancements in our understanding of the molecular and cellular mechanisms regulating myelination, as well as the development of high-throughput screens to identify agents that enhance myelination, have lead to the identification of many potential remyelination therapies currently in preclinical and early clinical development. One problem that has plagued the development of treatments to promote remyelination is the difficulty in assessing remyelination in patients with current imaging techniques. Powerful new imaging technologies are making it easier to discern remyelination in patients, which is critical for the assessment of these new therapeutic strategies during clinical trials. This review will summarize what is currently known about remyelination failure in MS, strategies to overcome this failure, new therapeutic treatments in the pipeline for promoting remyelination in MS patients, and new imaging technologies for measuring remyelination in patients. PMID:26696956

  9. Evidence for Multiple Rhythmic Skills.

    PubMed

    Tierney, Adam; Kraus, Nina

    2015-01-01

    Rhythms, or patterns in time, play a vital role in both speech and music. Proficiency in a number of rhythm skills has been linked to language ability, suggesting that certain rhythmic processes in music and language rely on overlapping resources. However, a lack of understanding about how rhythm skills relate to each other has impeded progress in understanding how language relies on rhythm processing. In particular, it is unknown whether all rhythm skills are linked together, forming a single broad rhythmic competence, or whether there are multiple dissociable rhythm skills. We hypothesized that beat tapping and rhythm memory/sequencing form two separate clusters of rhythm skills. This hypothesis was tested with a battery of two beat tapping and two rhythm memory tests. Here we show that tapping to a metronome and the ability to adjust to a changing tempo while tapping to a metronome are related skills. The ability to remember rhythms and to drum along to repeating rhythmic sequences are also related. However, we found no relationship between beat tapping skills and rhythm memory skills. Thus, beat tapping and rhythm memory are dissociable rhythmic aptitudes. This discovery may inform future research disambiguating how distinct rhythm competencies track with specific language functions. PMID:26376489

  10. Multiple sclerosis: Prospects and promise.

    PubMed

    Hauser, Stephen L; Chan, Jonah R; Oksenberg, Jorge R

    2013-09-01

    We have entered a golden era in multiple sclerosis (MS) research. Two decades ago, our understanding of the disease was largely descriptive and there were no approved therapies to modify the natural history of MS. Today, delineation of immune pathways relevant to MS have been clarified; a comprehensive map of genes that influence risk compiled; clues to environmental triggers identified; noninvasive in vivo monitoring of the MS disease process has been revolutionized by high-field MRI; and many effective therapies for the early, relapsing, component of MS now exist. However, major challenges remain. We still have no useful treatment for progressive MS (the holy grail of MS research), no means to repair injured axons or protect neurons, and extremely limited evidence to guide treatment decisions. Recent advances have set in place a foundation for development of increasingly selective immunotherapy for patients; application of genetic and genomic discoveries to improve therapeutic options; development of remyelination or neuroprotection therapies for progressive MS; and integrating clinical, imaging and genomic data for personalized medicine. MS has now advanced from the backwaters of autoimmune disease research to the front-line, and definitive answers, including cures, are now realistic goals for the next decade. Many of the breakthrough discoveries in MS have also resulted from meaningful interactions across disciplines, and especially from translational and basic scientists working closely with clinicians, highlighting that the clinical value of discoveries are most often revealed when ideas developed in the laboratory are tested at the bedside. PMID:23955638

  11. The thalamus and multiple sclerosis

    PubMed Central

    Minagar, Alireza; Barnett, Michael H.; Benedict, Ralph H.B.; Pelletier, Daniel; Pirko, Istvan; Sahraian, Mohamad Ali; Frohman, Elliott

    2013-01-01

    The paired thalamic nuclei are gray matter (GM) structures on both sides of the third ventricle that play major roles in cortical activation, relaying sensory information to the higher cortical centers that influence cognition. Multiple sclerosis (MS) is an immune-mediated disease of the human CNS that affects both the white matter (WM) and GM. A number of clinical observations as well as recent neuropathologic and neuroimaging studies have clearly demonstrated extensive involvement of the thalamus, basal ganglia, and neocortex in patients with MS. Modern MRI techniques permit visualization of GM lesions and measurement of atrophy. These contemporary methods have fundamentally altered our understanding of the pathophysiologic nature of MS. Evidence confirms the contention that GM injury can be detected in the earliest phases of MS, and that iron deposition and atrophy of deep gray nuclei are closely related to the magnitude of inflammation. Extensive involvement of GM, and particularly of the thalamus, is associated with a wide range of clinical manifestations including cognitive decline, motor deficits, fatigue, painful syndromes, and ocular motility disturbances in patients with MS. In this review, we characterize the neuropathologic, neuroimaging, and clinical features of thalamic involvement in MS. Further, we underscore the contention that neuropathologic and neuroimaging correlative investigations of thalamic derangements in MS may elucidate not heretofore considered pathobiological underpinnings germane to understanding the ontogeny, magnitude, and progression of the disease process. PMID:23296131

  12. Visualizing multiple word similarity measures.

    PubMed

    Kievit-Kylar, Brent; Jones, Michael N

    2012-09-01

    Although many recent advances have taken place in corpus-based tools, the techniques used to guide exploration and evaluation of these systems have advanced little. Typically, the plausibility of a semantic space is explored by sampling the nearest neighbors to a target word and evaluating the neighborhood on the basis of the modeler's intuition. Tools for visualization of these large-scale similarity spaces are nearly nonexistent. We present a new open-source tool to plot and visualize semantic spaces, thereby allowing researchers to rapidly explore patterns in visual data that describe the statistical relations between words. Words are visualized as nodes, and word similarities are shown as directed edges of varying strengths. The "Word-2-Word" visualization environment allows for easy manipulation of graph data to test word similarity measures on their own or in comparisons between multiple similarity metrics. The system contains a large library of statistical relationship models, along with an interface to teach them from various language sources. The modularity of the visualization environment allows for quick insertion of new similarity measures so as to compare new corpus-based metrics against the current state of the art. The software is available at www.indiana.edu/~semantic/word2word/. PMID:22810803

  13. Rehabilitation challenges in multiple sclerosis

    PubMed Central

    Burks, Jack S.; Bigley, George Kim; Hill, Harry Haydon

    2009-01-01

    While current immunomodulating drugs aim to reduce multiple sclerosis (MS) exacerbations and slow disease progression, rehabilitation aims to improve and maintain the functional abilities of patients in the face of disease progression. An increasing number of journal articles are describing the value of the many rehabilitation interventions that can be used throughout the course of the disease, from the initial symptoms to the advanced stages. An integrated team of healthcare professionals is necessary to address a myriad of problems to reduce impairments, disabilities, and handicaps. The problems may be related to fatigue, weakness, spasticity, mobility, balance, pain, cognition, mood, relationships, bowel, bladder, sexual function, swallowing, speech, transportation, employment, recreation, and activities of daily living (ADL) such as dressing, eating, bathing, and household chores. The team can help prevent complications and secondary disabilities, while increasing patient safety. Improving neurologically related function, maintaining good relationships, and feeling productive and creative adds enormously to the quality of life of people with MS and their families. Rehabilitation is more than an ‘extra’ service that is given after medical therapies; it is an integral part of the management of the diverse set of problems encountered throughout the course of the disease. An interdisciplinary team may have many members, including physicians, nurses, physical therapists, occupational therapists, speech and language pathologists, psychotherapists, social workers, recreational therapists, vocational rehabilitation therapists, patients, families, and other caregivers. PMID:20182578

  14. Evidence for Multiple Rhythmic Skills

    PubMed Central

    Tierney, Adam; Kraus, Nina

    2015-01-01

    Rhythms, or patterns in time, play a vital role in both speech and music. Proficiency in a number of rhythm skills has been linked to language ability, suggesting that certain rhythmic processes in music and language rely on overlapping resources. However, a lack of understanding about how rhythm skills relate to each other has impeded progress in understanding how language relies on rhythm processing. In particular, it is unknown whether all rhythm skills are linked together, forming a single broad rhythmic competence, or whether there are multiple dissociable rhythm skills. We hypothesized that beat tapping and rhythm memory/sequencing form two separate clusters of rhythm skills. This hypothesis was tested with a battery of two beat tapping and two rhythm memory tests. Here we show that tapping to a metronome and the ability to adjust to a changing tempo while tapping to a metronome are related skills. The ability to remember rhythms and to drum along to repeating rhythmic sequences are also related. However, we found no relationship between beat tapping skills and rhythm memory skills. Thus, beat tapping and rhythm memory are dissociable rhythmic aptitudes. This discovery may inform future research disambiguating how distinct rhythm competencies track with specific language functions. PMID:26376489

  15. Emerging therapies for multiple myeloma

    PubMed Central

    Podar, Klaus; Tai, Yu-Tzu; Hideshima, Teru; Vallet, Sonia; Richardson, Paul G; Anderson, Kenneth C

    2011-01-01

    Multiple myeloma (MM) is a clonal plasma cell malignancy clinically characterized by osteolytic lesions, immunodeficiency, and renal disease. There are an estimated 750,000 people diagnosed with MM worldwide, with a median overall survival of 3 – 5 years. Besides chromosomal aberrations, translocations, and mutations in essential growth and tumor-suppressor genes, accumulating data strongly highlight the pathophysiologic role of the bone marrow (BM) microenvironment in MM pathogenesis. Based on this knowledge, several novel agents have been identified, and treatment options in MM have fundamentally changed during the last decade. Thalidomide, bortezomib, and lenalidomide have been incorporated into conventional cytotoxic and transplantation regimens, first in relapsed and refractory and now also in newly diagnosed MM. Despite these significant advances, there remains an urgent need for more efficacious and tolerable drugs. Indeed, a plethora of preclinical agents awaits translation from the bench to the bedside. This article reviews the scientific rationale of new therapy regimens and newly identified therapeutic agents – small molecules as well as therapeutic antibodies – that hold promise to further improve outcome in MM. PMID:19249983

  16. Skin segmentation using multiple thresholding

    NASA Astrophysics Data System (ADS)

    Gasparini, Francesca; Schettini, Raimondo

    2006-01-01

    The segmentation of skin regions in color images is a preliminary step in several applications. Many different methods for discriminating between skin and non-skin pixels are available in the literature. The simplest, and often applied, methods build what is called an "explicit skin cluster" classifier which expressly defines the boundaries of the skin cluster in certain color spaces. These binary methods are very popular as they are easy to implement and do not require a training phase. The main difficulty in achieving high skin recognition rates, and producing the smallest possible number of false positive pixels, is that of defining accurate cluster boundaries through simple, often heuristically chosen, decision rules. In this study we apply a genetic algorithm to determine the boundaries of the skin clusters in multiple color spaces. To quantify the performance of these skin detection methods, we use recall and precision scores. A good classifier should provide both high recall and high precision, but generally, as recall increases, precision decreases. Consequently, we adopt a weighted mean of precision and recall as the fitness function of the genetic algorithm. Keeping in mind that different applications may have sharply different requirements, the weighting coefficients can be chosen to favor either high recall or high precision, or to satisfy a reasonable tradeoff between the two, depending on application demands. To train the genetic algorithm (GA) and test the performance of the classifiers applying the GA suggested boundaries, we use the large and heterogeneous Compaq skin database.

  17. Code design for multiple-input multiple-output broadcast channels 

    E-print Network

    Uppal, Momin Ayub

    2009-06-02

    Recent information theoretical results indicate that dirty-paper coding (DPC) achieves the entire capacity region of the Gaussian multiple-input multiple-output (MIMO) broadcast channel (BC). This thesis presents practical code designs for Gaussian...

  18. Multiplicity associated to high p{sub T} events and multiplicity fluctuations

    SciTech Connect

    Cunqueiro, L.; Pajares, C.; Dias de Deus, J.

    2006-09-15

    It is shown that the difference between the multiplicity associated to high p{sub T} events and the unbiased multiplicity is given by the normalized variance of the multiplicity distribution, as a consequence of high p{sub T} events being self-shadowed. We discuss the possibility of checking the nonmonotonic behavior with centrality of the normalized variance by measuring the difference between multiplicities.

  19. Schooling Built on the Multiple Intelligences

    ERIC Educational Resources Information Center

    Kunkel, Christine D.

    2009-01-01

    This article features a school built on multiple intelligences. As the first multiple intelligences school in the world, the Key Learning Community shapes its students' days to include significant time in the musical, spatial and bodily-kinesthetic intelligences, as well as the more traditional areas of logical-mathematical and linguistics. In…

  20. 47 CFR 73.3555 - Multiple ownership.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 4 2012-10-01 2012-10-01 false Multiple ownership. 73.3555 Section 73.3555 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Rules Applicable to All Broadcast Stations § 73.3555 Multiple ownership. (a)(1) Local radio ownership rule. A person or single entity...

  1. 46 CFR 183.322 - Multiple generators.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Multiple generators. 183.322 Section 183.322 Shipping...) ELECTRICAL INSTALLATION Power Sources and Distribution Systems § 183.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service power, the following...

  2. 46 CFR 120.322 - Multiple generators.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Multiple generators. 120.322 Section 120.322 Shipping... and Distribution Systems § 120.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service power, the following requirements must be met: (a) Each generator...

  3. 46 CFR 120.322 - Multiple generators.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Multiple generators. 120.322 Section 120.322 Shipping... and Distribution Systems § 120.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service power, the following requirements must be met: (a) Each generator...

  4. 46 CFR 120.322 - Multiple generators.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Multiple generators. 120.322 Section 120.322 Shipping... and Distribution Systems § 120.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service power, the following requirements must be met: (a) Each generator...

  5. 46 CFR 183.322 - Multiple generators.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Multiple generators. 183.322 Section 183.322 Shipping...) ELECTRICAL INSTALLATION Power Sources and Distribution Systems § 183.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service power, the following...

  6. 46 CFR 183.322 - Multiple generators.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Multiple generators. 183.322 Section 183.322 Shipping...) ELECTRICAL INSTALLATION Power Sources and Distribution Systems § 183.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service power, the following...

  7. 46 CFR 129.323 - Multiple generators.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Multiple generators. 129.323 Section 129.323 Shipping... INSTALLATIONS Power Sources and Distribution Systems § 129.323 Multiple generators. If an OSV uses two or more generators to supply electricity for the ship's service loads, to comply with § 129.310(a) of this...

  8. 46 CFR 129.323 - Multiple generators.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Multiple generators. 129.323 Section 129.323 Shipping... INSTALLATIONS Power Sources and Distribution Systems § 129.323 Multiple generators. If an OSV uses two or more generators to supply electricity for the ship's service loads, to comply with § 129.310(a) of this...

  9. 46 CFR 129.323 - Multiple generators.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Multiple generators. 129.323 Section 129.323 Shipping... INSTALLATIONS Power Sources and Distribution Systems § 129.323 Multiple generators. If an OSV uses two or more generators to supply electricity for the ship's service loads, to comply with § 129.310(a) of this...

  10. 46 CFR 120.322 - Multiple generators.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Multiple generators. 120.322 Section 120.322 Shipping... and Distribution Systems § 120.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service power, the following requirements must be met: (a) Each generator...

  11. 46 CFR 120.322 - Multiple generators.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Multiple generators. 120.322 Section 120.322 Shipping... and Distribution Systems § 120.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service power, the following requirements must be met: (a) Each generator...

  12. 46 CFR 183.322 - Multiple generators.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Multiple generators. 183.322 Section 183.322 Shipping...) ELECTRICAL INSTALLATION Power Sources and Distribution Systems § 183.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service power, the following...

  13. 46 CFR 129.323 - Multiple generators.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Multiple generators. 129.323 Section 129.323 Shipping... INSTALLATIONS Power Sources and Distribution Systems § 129.323 Multiple generators. If an OSV uses two or more generators to supply electricity for the ship's service loads, to comply with § 129.310(a) of this...

  14. 46 CFR 183.322 - Multiple generators.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Multiple generators. 183.322 Section 183.322 Shipping...) ELECTRICAL INSTALLATION Power Sources and Distribution Systems § 183.322 Multiple generators. When a vessel is equipped with two or more generators to supply ship's service power, the following...

  15. 46 CFR 129.323 - Multiple generators.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Multiple generators. 129.323 Section 129.323 Shipping... INSTALLATIONS Power Sources and Distribution Systems § 129.323 Multiple generators. If an OSV uses two or more generators to supply electricity for the ship's service loads, to comply with § 129.310(a) of this...

  16. Integer Programming Duality in Multiple Objective Programming

    E-print Network

    Klamroth, Kathrin

    -weighted Tchebycheff programs, using a cutting planes approach and a branch and bound methodology, respectively. FromInteger Programming Duality in Multiple Objective Programming Kathrin Klamroth1 Jørgen Tind1 for multiple crite- ria integer programming. However, in this case one may apply the more general e

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    E-print Network

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    / 28 #12;modular design software cycle & quality 1 Modular Design multiple choice quiz bottom-up design to Computer Science (MCS 260) software cycle & quality L-22 4 March 2015 5 / 28 #12;modular design software cycle & quality 1 Modular Design multiple choice quiz bottom-up design 2 Python Implementation

  18. 43 CFR 3400.1 - Multiple development.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Multiple development. 3400.1 Section 3400... Multiple development. (a) The granting of an exploration license, a license to mine or a lease for the exploration, development, or production of coal deposits shall preclude neither the issuance of...

  19. 43 CFR 3400.1 - Multiple development.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Multiple development. 3400.1 Section 3400... Multiple development. (a) The granting of an exploration license, a license to mine or a lease for the exploration, development, or production of coal deposits shall preclude neither the issuance of...

  20. 43 CFR 3400.1 - Multiple development.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Multiple development. 3400.1 Section 3400... Multiple development. (a) The granting of an exploration license, a license to mine or a lease for the exploration, development, or production of coal deposits shall preclude neither the issuance of...