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Sample records for class switch recombination

  1. Immunoglobulin class-switch recombination deficiencies.

    Science.gov (United States)

    Durandy, Anne; Kracker, Sven

    2012-01-01

    Immunoglobulin class-switch recombination deficiencies (Ig-CSR-Ds) are rare primary immunodeficiencies characterized by defective switched isotype (IgG/IgA/IgE) production. Depending on the molecular defect in question, the Ig-CSR-D may be combined with an impairment in somatic hypermutation (SHM). Some of the mechanisms underlying Ig-CSR and SHM have been described by studying natural mutants in humans. This approach has revealed that T cell-B cell interaction (resulting in CD40-mediated signaling), intrinsic B-cell mechanisms (activation-induced cytidine deaminase-induced DNA damage), and complex DNA repair machineries (including uracil-N-glycosylase and mismatch repair pathways) are all involved in class-switch recombination and SHM. However, several of the mechanisms required for full antibody maturation have yet to be defined. Elucidation of the molecular defects underlying the diverse set of Ig-CSR-Ds is essential for understanding Ig diversification and has prompted better definition of the clinical spectrum of diseases and the development of increasingly accurate diagnostic and therapeutic approaches. PMID:22894609

  2. Ig heavy chain class switch recombination: mechanism and regulation

    OpenAIRE

    Stavnezer, Janet; Schrader, Carol E.

    2014-01-01

    Ig heavy chain class switching occurs rapidly after activation of mature naïve B cells, resulting in a switch from expressing IgM and IgD to expression of IgG, IgE, or IgA; this switch improves the ability of antibodies to remove the pathogen that induces the humoral immune response. Class switching occurs by a deletional recombination between two different switch (S) regions, each of which is associated with a heavy chain constant (CH) region gene. Class switch recombination (CSR) is instiga...

  3. Interallelic class switch recombination contributes significantly to class switching in mouse B cells.

    Science.gov (United States)

    Reynaud, Stéphane; Delpy, Laurent; Fleury, Laurence; Dougier, Hei-Lanne; Sirac, Christophe; Cogné, Michel

    2005-05-15

    Except for the expression of IgM and IgD, DNA recombination is constantly needed for the expression of other Ig classes and subclasses. The predominant path of class switch recombination (CSR) is intrachromosomal, and the looping-out and deletion model has been abundantly documented. However, switch regions also occasionally constitute convenient substrates for interchromosomal recombination, since it is noticeably the case in a number of chromosomal translocations causing oncogene deregulation in the course of lymphoma and myeloma. Although asymmetric accessibility of Ig alleles should theoretically limit its occurrence, interallelic CSR was shown to occur at low levels during IgA switching in rabbit, where the definition of allotypes within both V and C regions helped identify interchromosomally derived Ig. Thus, we wished to evaluate precisely interallelic CSR frequency in mouse B cells, by using a system in which only one allele (of b allotype) could express a functional VDJ region, whereas only interallelic CSR could restore expression of an excluded (a allotype) allele. In our study, we show that interchromosomal recombination of V(H) and Cgamma or Calpha occurs in vivo in B cells at a frequency that makes a significant contribution to physiological class switching: trans-association of V(H) and C(H) genes accounted for 7% of all alpha mRNA, and this frequency was about twice higher for the gamma3 transcripts, despite the much shorter distance between the J(H) region and the Cgamma3 gene, thus confirming that this phenomenon corresponded to site-specific switching and not to random recombination between long homologous loci. PMID:15879114

  4. IgH chain class switch recombination: mechanism and regulation.

    Science.gov (United States)

    Stavnezer, Janet; Schrader, Carol E

    2014-12-01

    IgH class switching occurs rapidly after activation of mature naive B cells, resulting in a switch from expression of IgM and IgD to expression of IgG, IgE, or IgA; this switch improves the ability of Abs to remove the pathogen that induces the humoral immune response. Class switching occurs by a deletional recombination between two switch regions, each of which is associated with a H chain constant region gene. Class switch recombination (CSR) is instigated by activation-induced cytidine deaminase, which converts cytosines in switch regions to uracils. The uracils are subsequently removed by two DNA-repair pathways, resulting in mutations, single-strand DNA breaks, and the double-strand breaks required for CSR. We discuss several aspects of CSR, including how CSR is induced, CSR in B cell progenitors, the roles of transcription and chromosomal looping in CSR, and the roles of certain DNA-repair enzymes in CSR. PMID:25411432

  5. Parp3 negatively regulates immunoglobulin class switch recombination.

    Science.gov (United States)

    Robert, Isabelle; Gaudot, Léa; Rogier, Mélanie; Heyer, Vincent; Noll, Aurélia; Dantzer, Françoise; Reina-San-Martin, Bernardo

    2015-05-01

    To generate highly specific and adapted immune responses, B cells diversify their antibody repertoire through mechanisms involving the generation of programmed DNA damage. Somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by the recruitment of activation-induced cytidine deaminase (AID) to immunoglobulin loci and by the subsequent generation of DNA lesions, which are differentially processed to mutations during SHM or to double-stranded DNA break intermediates during CSR. The latter activate the DNA damage response and mobilize multiple DNA repair factors, including Parp1 and Parp2, to promote DNA repair and long-range recombination. We examined the contribution of Parp3 in CSR and SHM. We find that deficiency in Parp3 results in enhanced CSR, while SHM remains unaffected. Mechanistically, this is due to increased occupancy of AID at the donor (Sμ) switch region. We also find evidence of increased levels of DNA damage at switch region junctions and a bias towards alternative end joining in the absence of Parp3. We propose that Parp3 plays a CSR-specific role by controlling AID levels at switch regions during CSR. PMID:26000965

  6. IGH switch breakpoints in Burkitt lymphoma : Exclusive involvement of noncanonical class switch recombination

    NARCIS (Netherlands)

    Guikema, Jeroen E. J.; de Boer, Conny; Haralambieva, Eugenia; Smit, Laura A.; van Noesel, Carel J. M.; Schuuring, Ed; Kluin, Philip M.

    2006-01-01

    Most chromosomal t(8;14) translocations in sporadic Burkitt lymphomas (BL) are mediated by immunoglobulin class switch, recombination (CSR), yet all tumors express IgM, suggesting an incomplete or exclusively monoallelic CSR event. We studied the exact configuration of both the nontranslocated IGH a

  7. IGH switch breakpoints in Burkitt lymphoma: Exclusive involvement of noncanonical class switch recombination

    NARCIS (Netherlands)

    J.E.J. Guikema; C. de Boer; E. Haralambieva; L.A. Smit; C.J.M. van Noesel; E. Schuuring; P.M. Kluin

    2006-01-01

    Most chromosomal t(8;14) translocations in sporadic Burkitt lymphomas (BL) are mediated by immunoglobulin class switch, recombination (CSR), yet all tumors express IgM, suggesting an incomplete or exclusively monoallelic CSR event. We studied the exact configuration of both the nontranslocated IGH a

  8. IGH switch breakpoints in Burkitt lymphoma: exclusive involvement of noncanonical class switch recombination.

    Science.gov (United States)

    Guikema, Jeroen E J; de Boer, Conny; Haralambieva, Eugenia; Smit, Laura A; van Noesel, Carel J M; Schuuring, Ed; Kluin, Philip M

    2006-09-01

    Most chromosomal t(8;14) translocations in sporadic Burkitt lymphomas (BL) are mediated by immunoglobulin class switch recombination (CSR), yet all tumors express IgM, suggesting an incomplete or exclusively monoallelic CSR event. We studied the exact configuration of both the nontranslocated IGH allele and the MYC/IGH breakpoint by applying a combination of low- and high-resolution methods (interphase FISH, DNA fiber FISH, long-distance PCR, and Southern blotting) on 16 BL. IGH class switch events involving the nontranslocated IGH allele were not observed. Thirteen cases had MYC/IGH breakpoints in or nearby IGH switch (S) sites, including five at Smu, three at Sgamma and five at Salpha. All eight translocations with a breakpoint at Sgamma or Salpha were perfectly reciprocal, without deletion of Cmu-Cdelta or other CH elements. Internal Smu deletions claimed to be a marker for CSR activity and implicated in stabilization of IgM expression were found in BL but did not correlate with downstream translocation events. This study shows that switch breakpoints in sporadic BL are exclusively resolved by a noncanonical recombination mechanism involving only one switch region.

  9. Efficient AID targeting of switch regions is not sufficient for optimal class switch recombination.

    Science.gov (United States)

    Bonaud, Amélie; Lechouane, Fabien; Le Noir, Sandrine; Monestier, Olivier; Cogné, Michel; Sirac, Christophe

    2015-07-06

    Antibody affinity maturation relies on activation-induced cytidine deaminase (AID)-dependent somatic hypermutation (SHM) of immunoglobulin (Ig) loci. Class switch recombination (CSR) can in parallel occur between AID-targeted, transcribed, spliced and repetitive switch (S) regions. AID thus initiates not only mutations but also double-strand breaks (DSBs). What governs the choice between those two outcomes remains uncertain. Here we explore whether insertion of transcribed intronic S regions in a locus (Igκ) strongly recruiting AID is sufficient for efficient CSR. Although strongly targeted by AID and carrying internal deletions, the knocked-in S regions only undergo rare CSR-like events. This model confirms S regions as exquisite SHM targets, extending AID activity far from transcription initiation sites, and shows that such spliced and repetitive AID targets are not sufficient by themselves for CSR. Beyond transcription and AID recruitment, additional IgH elements are thus needed for CSR, restricting this hazardous gene remodelling to IgH loci.

  10. Constraints contributed by chromatin looping limit recombination targeting during Ig class switch recombination.

    Science.gov (United States)

    Feldman, Scott; Achour, Ikbel; Wuerffel, Robert; Kumar, Satyendra; Gerasimova, Tatiana; Sen, Ranjan; Kenter, Amy L

    2015-03-01

    Engagement of promoters with distal elements in long-range looping interactions has been implicated in regulation of Ig class switch recombination (CSR). The principles determining the spatial and regulatory relationships among Igh transcriptional elements remain poorly defined. We examined the chromosome conformation of C region (CH) loci that are targeted for CSR in a cytokine-dependent fashion in mature B lymphocytes. Germline transcription (GLT) of the γ1 and ε CH loci is controlled by two transcription factors, IL-4-inducible STAT6 and LPS-activated NF-κB. We showed that although STAT6 deficiency triggered loss of GLT, deletion of NF-κB p50 abolished both GLT and γ1 locus:enhancer looping. Thus, chromatin looping between CH loci and Igh enhancers is independent of GLT production and STAT6, whereas the establishment and maintenance of these chromatin contacts requires NF-κB p50. Comparative analysis of the endogenous γ1 locus and a knock-in heterologous promoter in mice identified the promoter per se as the interactive looping element and showed that transcription elongation is dispensable for promoter/enhancer interactions. Interposition of the LPS-responsive heterologous promoter between the LPS-inducible γ3 and γ2b loci altered GLT expression and essentially abolished direct IgG2b switching while maintaining a sequential μ→γ3→γ2b format. Our study provides evidence that promoter/enhancer looping interactions can introduce negative constraints on distal promoters and affect their ability to engage in germline transcription and determine CSR targeting.

  11. Constraints contributed by chromatin looping limit recombination targeting during Ig class switch recombination.

    Science.gov (United States)

    Feldman, Scott; Achour, Ikbel; Wuerffel, Robert; Kumar, Satyendra; Gerasimova, Tatiana; Sen, Ranjan; Kenter, Amy L

    2015-03-01

    Engagement of promoters with distal elements in long-range looping interactions has been implicated in regulation of Ig class switch recombination (CSR). The principles determining the spatial and regulatory relationships among Igh transcriptional elements remain poorly defined. We examined the chromosome conformation of C region (CH) loci that are targeted for CSR in a cytokine-dependent fashion in mature B lymphocytes. Germline transcription (GLT) of the γ1 and ε CH loci is controlled by two transcription factors, IL-4-inducible STAT6 and LPS-activated NF-κB. We showed that although STAT6 deficiency triggered loss of GLT, deletion of NF-κB p50 abolished both GLT and γ1 locus:enhancer looping. Thus, chromatin looping between CH loci and Igh enhancers is independent of GLT production and STAT6, whereas the establishment and maintenance of these chromatin contacts requires NF-κB p50. Comparative analysis of the endogenous γ1 locus and a knock-in heterologous promoter in mice identified the promoter per se as the interactive looping element and showed that transcription elongation is dispensable for promoter/enhancer interactions. Interposition of the LPS-responsive heterologous promoter between the LPS-inducible γ3 and γ2b loci altered GLT expression and essentially abolished direct IgG2b switching while maintaining a sequential μ→γ3→γ2b format. Our study provides evidence that promoter/enhancer looping interactions can introduce negative constraints on distal promoters and affect their ability to engage in germline transcription and determine CSR targeting. PMID:25624452

  12. ALKBH1 is dispensable for abasic site cleavage during base excision repair and class switch recombination.

    Science.gov (United States)

    Müller, Tina A; Yu, Kefei; Hausinger, Robert P; Meek, Katheryn

    2013-01-01

    Potential roles of the abasic site lyase activity associated with AlkB homolog 1 (ALKBH1) were assessed by studies focusing on the two cellular processes that create abasic sites as intermediates: base excision repair and class switch recombination. Alkbh1(-/-) pups (lacking exon 3) were born at a lower than expected frequency from heterozygous parents, suggesting a reduced survival rate and non-Mendelian inheritance, and they exhibited a gender bias in favor of males (70% males and 30% females). To study ALKBH1's potential involvement in DNA repair, fibroblasts were isolated from Alkbh1(-/-) mice, spontaneously immortalized and tested for resistance to DNA damaging agents. Alkbh1(-/-) and isogenic cells expressing hALKBH1 showed no difference in survival to the DNA damaging agents methyl-methionine sulfate or H2O2. This result indicates that ALKBH1 does not play a major role in the base excision repair pathway. To assess ALKBH1's role in class switch recombination, splenic B cells were isolated from Alkbh1(-/-) and Alkbh1(+/+) mice and subjected to switching from IgM to IgG1. No differences were found in IgG1 switching, suggesting that Alkbh1 is not involved in class switch recombination of the immunoglobulin heavy chain during B lymphocyte activation. PMID:23825659

  13. ALKBH1 is dispensable for abasic site cleavage during base excision repair and class switch recombination.

    Directory of Open Access Journals (Sweden)

    Tina A Müller

    Full Text Available Potential roles of the abasic site lyase activity associated with AlkB homolog 1 (ALKBH1 were assessed by studies focusing on the two cellular processes that create abasic sites as intermediates: base excision repair and class switch recombination. Alkbh1(-/- pups (lacking exon 3 were born at a lower than expected frequency from heterozygous parents, suggesting a reduced survival rate and non-Mendelian inheritance, and they exhibited a gender bias in favor of males (70% males and 30% females. To study ALKBH1's potential involvement in DNA repair, fibroblasts were isolated from Alkbh1(-/- mice, spontaneously immortalized and tested for resistance to DNA damaging agents. Alkbh1(-/- and isogenic cells expressing hALKBH1 showed no difference in survival to the DNA damaging agents methyl-methionine sulfate or H2O2. This result indicates that ALKBH1 does not play a major role in the base excision repair pathway. To assess ALKBH1's role in class switch recombination, splenic B cells were isolated from Alkbh1(-/- and Alkbh1(+/+ mice and subjected to switching from IgM to IgG1. No differences were found in IgG1 switching, suggesting that Alkbh1 is not involved in class switch recombination of the immunoglobulin heavy chain during B lymphocyte activation.

  14. p53 Represses Class Switch Recombination to IgG2a through its Antioxidant Function1

    OpenAIRE

    Guikema, Jeroen E. J.; Schrader, Carol E.; Brodsky, Michael H.; Linehan, Erin K.; Richards, Adam; El Falaky, Nahla; Li, Daniel H.; Sluss, Hayla K.; Szomolanyi-Tsuda, Eva; Stavnezer, Janet

    2010-01-01

    Immunoglobulin class switch recombination (CSR) occurs in activated mature B cells, and causes an exchange of the IgM isotype for IgG, IgE or IgA isotypes, which increases the effectiveness of the humoral immune response. DNA double-stranded breaks (DSBs) in recombining switch (S) regions, where CSR occurs, are required for recombination. Activation-induced cytidine deaminase (AID) initiates DSB formation by deamination of cytosines in S regions. This reaction requires reactive oxygen species...

  15. Three-dimensional architecture of the IgH locus facilitates class switch recombination.

    Science.gov (United States)

    Kenter, Amy L; Feldman, Scott; Wuerffel, Robert; Achour, Ikbel; Wang, Lili; Kumar, Satyendra

    2012-09-01

    Immunoglobulin (Ig) class switch recombination (CSR) is responsible for diversification of antibody effector function during an immune response. This region-specific recombination event, between repetitive switch (S) DNA elements, is unique to B lymphocytes and is induced by activationinduced deaminase (AID). CSR is critically dependent on transcription of noncoding RNAs across S regions. However, mechanistic insight regarding this process has remained unclear. New studies indicate that long-range intrachromosomal interactions among IgH transcriptional elements organize the formation of the S/S synaptosome, as a prerequisite for CSR. This three-dimensional chromatin architecture simultaneously brings promoters and enhancers into close proximity to facilitate transcription. Here, we recount how transcription across S DNA promotes accumulation of RNA polymerase II, leading to the introduction of activating chromatin modifications and hyperaccessible chromatin that is amenable to AID activity.

  16. DNA-PKcs Is Involved in Ig Class Switch Recombination in Human B Cells.

    Science.gov (United States)

    Björkman, Andrea; Du, Likun; Felgentreff, Kerstin; Rosner, Cornelia; Pankaj Kamdar, Radhika; Kokaraki, Georgia; Matsumoto, Yoshihisa; Davies, E Graham; van der Burg, Mirjam; Notarangelo, Luigi D; Hammarström, Lennart; Pan-Hammarström, Qiang

    2015-12-15

    Nonhomologous end-joining (NHEJ) is one of the major DNA double-strand break repair pathways in mammalian cells and is required for both V(D)J recombination and class switch recombination (CSR), two Ig gene-diversification processes occurring during B cell development. DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) is a component of the classical NHEJ machinery and has a critical function during V(D)J recombination. However, its role in CSR has been controversial. In this study, we examined the pattern of recombination junctions from in vivo-switched B cells from two DNA-PKcs-deficient patients. One of them harbored mutations that did not affect DNA-PKcs kinase activity but caused impaired Artemis activation; the second patient had mutations resulting in diminished DNA-PKcs protein expression and kinase activity. These results were compared with those from DNA-PKcs-deficient mouse B cells. A shift toward the microhomology-based alternative end-joining at the recombination junctions was observed in both human and mouse B cells, suggesting that the classical NHEJ pathway is impaired during CSR when DNA-PKcs is defective. Furthermore, cells from the second patient showed additional or more severe alterations in CSR and/or NHEJ, which may suggest that DNA-PKcs and/or its kinase activity have additional, Artemis-independent functions during these processes. PMID:26546606

  17. Imbalanced PTEN and PI3K Signaling Impairs Class Switch Recombination.

    Science.gov (United States)

    Chen, Zhangguo; Getahun, Andrew; Chen, Xiaomi; Dollin, Yonatan; Cambier, John C; Wang, Jing H

    2015-12-01

    Class switch recombination (CSR) generates isotype-switched Abs with distinct effector functions. B cells express phosphatase and tensin homolog (PTEN) and multiple isoforms of class IA PI3K catalytic subunits, including p110α and p110δ, whose roles in CSR remain unknown or controversial. In this article, we demonstrate a direct effect of PTEN on CSR signaling by acute deletion of Pten specifically in mature B cells, thereby excluding the developmental impact of Pten deletion. We show that mature B cell-specific PTEN overexpression enhances CSR. More importantly, we establish a critical role for p110α in CSR. Furthermore, we identify a cooperative role for p110α and p110δ in suppressing CSR. Mechanistically, dysregulation of p110α or PTEN inversely affects activation-induced deaminase expression via modulating AKT activity. Thus, our study reveals that a signaling balance between PTEN and PI3K isoforms is essential to maintain normal CSR. PMID:26500350

  18. Evolution of class switch recombination function in fish activation-induced cytidine deaminase, AID.

    Science.gov (United States)

    Wakae, Koshou; Magor, Brad G; Saunders, Holly; Nagaoka, Hitoshi; Kawamura, Akemi; Kinoshita, Kazuo; Honjo, Tasuku; Muramatsu, Masamichi

    2006-01-01

    Following activation of mammalian B cells, class switch recombination (CSR) and somatic hypermutation (SHM) of the Ig heavy chain (IgH) gene can improve the functions of the expressed antibodies. Activation-induced cytidine deaminase (AID) is the only known B cell-specific protein required for inducing CSR and SHM in mammals. Lower vertebrates have an AID homologue, and there is some evidence of SHM in vivo. However there is no evidence of CSR in the cartilaginous or bony fishes, and this may be due in part to a lack of cis-elements in the IgH gene that are the normal targets of AID-mediated recombination. We have tested whether bony fish (zebrafish and catfish) AID can mediate CSR and SHM in mammalian cells. As expected, ectopic expression of fish AID in mouse fibroblasts resulted in mutations in an introduced SHM reporter gene, indicating that fish AID can mediate SHM. Unexpectedly, expression of fish AID in mouse AID-/- B cells induced surface IgG expression as well as switched transcripts from Ig gene loci, clearly indicating that the fish AID protein can mediate CSR, at least in mouse cells. These results suggest that the AID protein acquired the ability to mediate CSR before the IgH locus evolved the additional exon clusters and switch regions that are the targets of recombination. We discuss how pleiotropic functions of specific domains within the AID protein may have facilitated the early evolution of CSR in lower vertebrates.

  19. Sense transcription through the S region is essential for immunoglobulin class switch recombination.

    Science.gov (United States)

    Haddad, Dania; Oruc, Zéliha; Puget, Nadine; Laviolette-Malirat, Nathalie; Philippe, Magali; Carrion, Claire; Le Bert, Marc; Khamlichi, Ahmed Amine

    2011-04-20

    Class switch recombination (CSR) occurs between highly repetitive sequences called switch (S) regions and is initiated by activation-induced cytidine deaminase (AID). CSR is preceded by a bidirectional transcription of S regions but the relative importance of sense and antisense transcription for CSR in vivo is unknown. We generated three mouse lines in which we attempted a premature termination of transcriptional elongation by inserting bidirectional transcription terminators upstream of Sμ, upstream of Sγ3 or downstream of Sγ3 sequences. The data show, at least for Sγ3, that sense transcriptional elongation across S region is absolutely required for CSR whereas its antisense counterpart is largely dispensable, strongly suggesting that sense transcription is sufficient for AID targeting to both DNA strands. PMID:21378751

  20. Ongoing in vivo immunoglobulin class switch DNA recombination in chronic lymphocytic leukemia B cells.

    Science.gov (United States)

    Cerutti, Andrea; Zan, Hong; Kim, Edmund C; Shah, Shefali; Schattner, Elaine J; Schaffer, András; Casali, Paolo

    2002-12-01

    Chronic lymphocytic leukemia (CLL) results from the expansion of malignant CD5(+) B cells that usually express IgD and IgM. These leukemic cells can give rise in vivo to clonally related IgG(+) or IgA(+) elements. The requirements and modalities of this process remain elusive. Here we show that leukemic B cells from 14 of 20 CLLs contain the hallmarks of ongoing Ig class switch DNA recombination (CSR), including extrachromosomal switch circular DNAs and circle transcripts generated by direct S micro -->Sgamma, S micro -->Salpha, and S micro -->Sepsilon as well as sequential Sgamma-->Salpha and Sgamma-->Sepsilon CSR. Similar CLL B cells express transcripts for activation-induced cytidine deaminase, a critical component of the CSR machinery, and contain germline I(H)-C(H) and mature V(H)DJ(H)-C(H) transcripts encoded by multiple Cgamma, Calpha, and Cepsilon genes. Ongoing CSR occurs in only a fraction of the CLL clone, as only small proportions of CD5(+)CD19(+) cells express surface IgG or IgA and lack IgM and IgD. In vivo class-switching CLL B cells down-regulate switch circles and circle transcripts in vitro unless exposed to exogenous CD40 ligand and IL-4. In addition, CLL B cells that do not class switch in vivo activate the CSR machinery and secrete IgG, IgA, or IgE upon in vitro exposure to CD40 ligand and IL-4. These findings indicate that in CLL at least some members of the malignant clone actively differentiate in vivo along a pathway that induces CSR. They also suggest that this process is elicited by external stimuli, including CD40 ligand and IL-4, provided by bystander immune cells.

  1. Interaction between HIV-1 Tat and DNA-PKcs modulates HIV transcription and class switch recombination.

    Science.gov (United States)

    Zhang, Shi-Meng; Zhang, He; Yang, Tian-Yi; Ying, Tian-Yi; Yang, Pei-Xiang; Liu, Xiao-Dan; Tang, Sheng-Jian; Zhou, Ping-Kun

    2014-01-01

    HIV-1 tat targets a variety of host cell proteins to facilitate viral transcription and disrupts host cellular immunity by inducing lymphocyte apoptosis, but whether it influences humoral immunity remains unclear. Previously, our group demonstrated that tat depresses expression of DNA-PKcs, a critical component of the non-homologous end joining pathway (NHEJ) of DNA double-strand breaks repair, immunoglobulin class switch recombination (CSR) and V(D)J recombination, and sensitizes cells to ionizing radiation. In this study, we demonstrated that HIV-1 Tat down-regulates DNA-PKcs expression by directly binding to the core promoter sequence. In addition, Tat interacts with and activates the kinase activity of DNA-PKcs in a dose-dependent and DNA independent manner. Furthermore, Tat inhibits class switch recombination (CSR) at low concentrations (≤ 4 µg/ml) and stimulates CSR at high concentrations (≥ 8 µg/ml). On the other hand, low protein level and high kinase activity of DNA-PKcs promotes HIV-1 transcription, while high protein level and low kinase activity inhibit HIV-1 transcription. Co-immunoprecipitation results revealed that DNA-PKcs forms a large complex comprised of Cyclin T1, CDK9 and Tat via direct interacting with CDK9 and Tat but not Cyclin T1. Taken together, our results provide new clues that Tat regulates host humoral immunity via both transcriptional depression and kinase activation of DNA-PKcs. We also raise the possibility that inhibitors and interventions directed towards DNA-PKcs may inhibit HIV-1 transcription in AIDS patients. PMID:25332688

  2. CtIP promotes microhomology-mediated alternative end joining during class-switch recombination.

    Science.gov (United States)

    Lee-Theilen, Mieun; Matthews, Allysia J; Kelly, Dierdre; Zheng, Simin; Chaudhuri, Jayanta

    2011-01-01

    Immunoglobulin heavy chain (Igh locus) class-switch recombination (CSR) requires targeted introduction of DNA double strand breaks (DSBs) into repetitive 'switch'-region DNA elements in the Igh locus and subsequent ligation between distal DSBs. Both canonical nonhomologous end joining (C-NHEJ) that seals DNA ends with little or no homology and a poorly defined alternative end joining (A-NHEJ, also known as alt-NHEJ) process that requires microhomology ends for ligation have been implicated in CSR. Here, we show that the DNA end-processing factor CtIP is required for microhomology-directed A-NHEJ during CSR. Additionally, we demonstrate that microhomology joins that are enriched upon depletion of the C-NHEJ component Ku70 require CtIP. Finally, we show that CtIP binds to switch-region DNA in a fashion dependent on activation-induced cytidine deaminase. Our results establish CtIP as a bona fide component of microhomology-dependent A-NHEJ and unmask a hitherto unrecognized physiological role of microhomology-mediated end joining in a C-NHEJ-proficient environment.

  3. Complex biallelic IGH rearrangements in IgM-expressing Z-138 cell line : Involvement of downstream immunoglobulin class switch recombination

    NARCIS (Netherlands)

    Guikema, JEJ; Fenton, JAL; de Boer, C; Kleiverda, K; Brink, AATP; Raap, AK; Estrov, Z; Schuuring, E; Kluin, PM

    2005-01-01

    Chromosomal translocations involving the immunoglobulin (Ig) receptor loci usually disrupt and silence these loci. On the basis of observations in follicular lymphoma (FL) with downstream Ig heavy chain (IGH) class switch recombination (CSR), we hypothesized that downstream CSR-mediated chromosomal

  4. Pathophysiology of B-cell intrinsic immunoglobulin class switch recombination deficiencies.

    Science.gov (United States)

    Durandy, Anne; Taubenheim, Nadine; Peron, Sophie; Fischer, Alain

    2007-01-01

    B-cell intrinsic immunoglobulin class switch recombination (Ig-CSR) deficiencies, previously termed hyper-IgM syndromes, are genetically determined conditions characterized by normal or elevated serum IgM levels and an absence or very low levels of IgG, IgA, and IgE. As a function of the molecular mechanism, the defective CSR is variably associated to a defect in the generation of somatic hypermutations (SHMs) in the Ig variable region. The study of Ig-CSR deficiencies contributed to a better delineation of the mechanisms underlying CSR and SHM, the major events of antigen-triggered antibody maturation. Four Ig-CSR deficiency phenotypes have been so far reported: the description of the activation-induced cytidine deaminase (AID) deficiency (Ig-CSR deficiency 1), caused by recessive mutations of AICDA gene, characterized by a defect in CSR and SHM, clearly established the role of AID in the induction of the Ig gene rearrangements underlying CSR and SHM. A CSR-specific function of AID has, however, been detected by the observation of a selective CSR defect caused by mutations affecting the C-terminus of AID. Ig-CSR deficiency 2 is the consequence of uracil-N-glycosylase (UNG) deficiency. Because UNG, a molecule of the base excision repair machinery, removes uracils from DNA and AID deaminates cytosines into uracils, that observation indicates that the AID-UNG pathway directly targets DNA of switch regions from the Ig heavy-chain locus to induce the CSR process. Ig-CSR deficiencies 3 and 4 are characterized by a selective CSR defect resulting from blocks at distinct steps of CSR. A further understanding of the CSR machinery is expected from their molecular definition. PMID:17560278

  5. The Fanconi anemia core complex is dispensable during somatic hypermutation and class switch recombination.

    Directory of Open Access Journals (Sweden)

    Peter H L Krijger

    Full Text Available To generate high affinity antibodies during an immune response, B cells undergo somatic hypermutation (SHM of their immunoglobulin genes. Error-prone translesion synthesis (TLS DNA polymerases have been reported to be responsible for all mutations at template A/T and at least a fraction of G/C transversions. In contrast to A/T mutations which depend on PCNA ubiquitination, it remains unclear how G/C transversions are regulated during SHM. Several lines of evidence indicate a mechanistic link between the Fanconi Anemia (FA pathway and TLS. To investigate the contribution of the FA pathway in SHM we analyzed FancG-deficient B cells. B cells deficient for FancG, an essential member of the FA core complex, were hypersensitive to treatment with cross-linking agents. However, the frequencies and nucleotide exchange spectra of SHM remained comparable between wild-type and FancG-deficient B cells. These data indicate that the FA pathway is not involved in regulating the outcome of SHM in mammals. In addition, the FA pathway appears dispensable for class switch recombination.

  6. Phenotypic and Functional Comparison of Class Switch Recombination Deficiencies with a Subgroup of Common Variable Immunodeficiencies.

    Science.gov (United States)

    Aan de Kerk, Daan J; Jansen, Machiel H; Jolles, Stephen; Warnatz, Klaus; Seneviratne, Suranjith L; Ten Berge, Ineke J M; van Leeuwen, Ester M M; Kuijpers, Taco W

    2016-10-01

    Primary antibody deficiencies (PADs) are the most common immunodeficiency in humans, characterized by low levels of immunoglobulins and inadequate antibody responses upon immunization. These PADs may result from an early block in B cell development with a complete absence of peripheral B cells and lack of immunoglobulins. In the presence of circulating B cells, some PADs are genetically caused by a class switch recombination (CSR) defect, but in the most common PAD, common variable immunodeficiency (CVID), very few gene defects have as yet been characterized despite various phenotypic classifications. Using a functional read-out, we previously identified a functional subgroup of CVID patients with plasmablasts (PBs) producing IgM only. We have now further characterized such CVID patients by a direct functional comparison with patients having genetically well-characterized CSR defects in CD40L, activation-induced cytidine deaminase (AID) and uracil N-glycosylase activity (UNG). The CSR-like CVID patients showed a failure in B cell activation patterns similar to the classical AID/UNG defects in three out of five CVID patients and distinct more individual defects in the two other CVID cases when tested for cellular activation and PB differentiation. Thus, functional categorization of B cell activation and differentiation pathways extends the expected variation in CVID to CSR-like defects of as yet unknown genetic etiology. PMID:27484504

  7. Class-Switch Recombination in the Absence of the IgH 3' Regulatory Region.

    Science.gov (United States)

    Kim, Ahrom; Han, Li; Santiago, Gabriel E; Verdun, Ramiro E; Yu, Kefei

    2016-10-01

    The ∼28-kb 3' regulatory region (3'RR), which is located at the most distal 3' region of the Ig H chain locus, has multiple regulatory functions that control IgH expression, class-switch recombination (CSR), and somatic hypermutation. In this article, we report that deletion of the entire 3'RR in a mouse B cell line that is capable of robust cytokine-dependent CSR to IgA results in reduced, but not abolished, CSR. These data suggest that 3'RR is not absolutely required for CSR and, thus, is not essential for targeting activation-induced cytidine deaminase to S regions, as was suggested. Moreover, replacing 3'RR with a DNA fragment including only its four DNase I hypersensitive sites (lacking the large spacer regions) restores CSR to a level equivalent to or even higher than in wild-type cells, suggesting that the four hypersensitive sites contain most of the CSR-promoting functions of 3'RR. Stimulated cells express abundant germline transcripts, with the presence or absence of 3'RR, providing evidence that 3'RR has a role in promoting CSR that is unique from enhancing S region transcription. PMID:27559052

  8. Scaffold functions of 14-3-3 adaptors in B cell immunoglobulin class switch DNA recombination.

    Directory of Open Access Journals (Sweden)

    Tonika Lam

    Full Text Available Class switch DNA recombination (CSR of the immunoglobulin heavy chain (IgH locus crucially diversifies antibody biological effector functions. CSR involves the induction of activation-induced cytidine deaminase (AID expression and AID targeting to switch (S regions by 14-3-3 adaptors. 14-3-3 adaptors specifically bind to 5'-AGCT-3' repeats, which make up for the core of all IgH locus S regions. They selectively target the upstream and downstream S regions that are set to undergo S-S DNA recombination. We hypothesized that 14-3-3 adaptors function as scaffolds to stabilize CSR enzymatic elements on S regions. Here we demonstrate that all seven 14-3-3β, 14-3-3ε, 14-3-3γ, 14-3-3η, 14-3-3σ, 14-3-3τ and 14-3-3ζ adaptors directly interacted with AID, PKA-Cα (catalytic subunit and PKA-RIα (regulatory inhibitory subunit and uracil DNA glycosylase (Ung. 14-3-3 adaptors, however, did not interact with AID C-terminal truncation mutant AIDΔ(180-198 or AIDF193A and AIDL196A point-mutants (which have been shown not to bind to S region DNA and fail to mediate CSR. 14-3-3 adaptors colocalized with AID and replication protein A (RPA in B cells undergoing CSR. 14-3-3 and AID binding to S region DNA was disrupted by viral protein R (Vpr, an accessory protein of human immunodeficiency virus type-1 (HIV-1, which inhibited CSR without altering AID expression or germline IH-CH transcription. Accordingly, we demonstrated that 14-3-3 directly interact with Vpr, which in turn, also interact with AID, PKA-Cα and Ung. Altogether, our findings suggest that 14-3-3 adaptors play important scaffold functions and nucleate the assembly of multiple CSR factors on S regions. They also show that such assembly can be disrupted by a viral protein, thereby allowing us to hypothesize that small molecule compounds that specifically block 14-3-3 interactions with AID, PKA and/or Ung can be used to inhibit unwanted CSR.

  9. Scaffold functions of 14-3-3 adaptors in B cell immunoglobulin class switch DNA recombination.

    Science.gov (United States)

    Lam, Tonika; Thomas, Lisa M; White, Clayton A; Li, Guideng; Pone, Egest J; Xu, Zhenming; Casali, Paolo

    2013-01-01

    Class switch DNA recombination (CSR) of the immunoglobulin heavy chain (IgH) locus crucially diversifies antibody biological effector functions. CSR involves the induction of activation-induced cytidine deaminase (AID) expression and AID targeting to switch (S) regions by 14-3-3 adaptors. 14-3-3 adaptors specifically bind to 5'-AGCT-3' repeats, which make up for the core of all IgH locus S regions. They selectively target the upstream and downstream S regions that are set to undergo S-S DNA recombination. We hypothesized that 14-3-3 adaptors function as scaffolds to stabilize CSR enzymatic elements on S regions. Here we demonstrate that all seven 14-3-3β, 14-3-3ε, 14-3-3γ, 14-3-3η, 14-3-3σ, 14-3-3τ and 14-3-3ζ adaptors directly interacted with AID, PKA-Cα (catalytic subunit) and PKA-RIα (regulatory inhibitory subunit) and uracil DNA glycosylase (Ung). 14-3-3 adaptors, however, did not interact with AID C-terminal truncation mutant AIDΔ(180-198) or AIDF193A and AIDL196A point-mutants (which have been shown not to bind to S region DNA and fail to mediate CSR). 14-3-3 adaptors colocalized with AID and replication protein A (RPA) in B cells undergoing CSR. 14-3-3 and AID binding to S region DNA was disrupted by viral protein R (Vpr), an accessory protein of human immunodeficiency virus type-1 (HIV-1), which inhibited CSR without altering AID expression or germline IH-CH transcription. Accordingly, we demonstrated that 14-3-3 directly interact with Vpr, which in turn, also interact with AID, PKA-Cα and Ung. Altogether, our findings suggest that 14-3-3 adaptors play important scaffold functions and nucleate the assembly of multiple CSR factors on S regions. They also show that such assembly can be disrupted by a viral protein, thereby allowing us to hypothesize that small molecule compounds that specifically block 14-3-3 interactions with AID, PKA and/or Ung can be used to inhibit unwanted CSR.

  10. PP4 is essential for germinal center formation and class switch recombination in mice.

    Directory of Open Access Journals (Sweden)

    Ming-Yu Chen

    Full Text Available PP4 is a serine/threonine phosphatase required for immunoglobulin (Ig VDJ recombination and pro-B/pre-B cell development in mice. To elucidate the role of PP4 in mature B cells, we ablated the catalytic subunit of murine PP4 in vivo utilizing the CD23 promoter and cre-loxP recombination and generated CD23(crePP4(F/F mice. The development of follicular and marginal zone B cells was unaffected in these mutants, but the proliferation of mature PP4-deficient B cells stimulated by in vitro treatment with either anti-IgM antibody (Ab or LPS was partially impaired. Interestingly, the induction of CD80 and CD86 expression on these stimulated B cells was normal. Basal levels of serum Igs of all isotypes were strongly reduced in CD23(crePP4(F/F mice, and their B cells showed a reduced efficiency of class switch recombination (CSR in vitro upon stimulation by LPS or LPS plus IL-4. When CD23(crePP4(F/F mice were challenged with either the T cell-dependent antigen TNP-KLH or the T cell-independent antigen TNP-Ficoll, or by H1N1 virus infection, the mutant animals failed to form germinal centers (GCs in the spleen and the draining mediastinal lymph nodes, and did not efficiently mount antigen-specific humoral responses. In the resting state, PP4-deficient B cells exhibited pre-existing DNA fragmentation. Upon stimulation by DNA-damaging drug etoposide in vitro, mutant B cells showed increased cleavage of caspase 3. In addition, the mutant B cells displayed impaired CD40-mediated MAPK activation, abnormal IgM-mediated NF-κB activation, and reduced S phase entry upon IgM/CD40-stimulation. Taken together, our results establish a novel role for PP4 in CSR, and reveal crucial functions for PP4 in the maintenance of genomic stability, GC formation, and B cell-mediated immune responses.

  11. A Damage-Independent Role for 53BP1 that Impacts Break Order and Igh Architecture during Class Switch Recombination

    Directory of Open Access Journals (Sweden)

    Pedro P. Rocha

    2016-06-01

    Full Text Available During class switch recombination (CSR, B cells replace the Igh Cμ or δ exons with another downstream constant region exon (CH, altering the antibody isotype. CSR occurs through the introduction of AID-mediated double-strand breaks (DSBs in switch regions and subsequent ligation of broken ends. Here, we developed an assay to investigate the dynamics of DSB formation in individual cells. We demonstrate that the upstream switch region Sμ is first targeted during recombination and that the mechanism underlying this control relies on 53BP1. Surprisingly, regulation of break order occurs through residual binding of 53BP1 to chromatin before the introduction of damage and independent of its established role in DNA repair. Using chromosome conformation capture, we show that 53BP1 mediates changes in chromatin architecture that affect break order. Finally, our results explain how changes in Igh architecture in the absence of 53BP1 could promote inversional rearrangements that compromise CSR.

  12. A Damage-Independent Role for 53BP1 that Impacts Break Order and Igh Architecture during Class Switch Recombination.

    Science.gov (United States)

    Rocha, Pedro P; Raviram, Ramya; Fu, Yi; Kim, JungHyun; Luo, Vincent M; Aljoufi, Arafat; Swanzey, Emily; Pasquarella, Alessandra; Balestrini, Alessia; Miraldi, Emily R; Bonneau, Richard; Petrini, John; Schotta, Gunnar; Skok, Jane A

    2016-06-28

    During class switch recombination (CSR), B cells replace the Igh Cμ or δ exons with another downstream constant region exon (CH), altering the antibody isotype. CSR occurs through the introduction of AID-mediated double-strand breaks (DSBs) in switch regions and subsequent ligation of broken ends. Here, we developed an assay to investigate the dynamics of DSB formation in individual cells. We demonstrate that the upstream switch region Sμ is first targeted during recombination and that the mechanism underlying this control relies on 53BP1. Surprisingly, regulation of break order occurs through residual binding of 53BP1 to chromatin before the introduction of damage and independent of its established role in DNA repair. Using chromosome conformation capture, we show that 53BP1 mediates changes in chromatin architecture that affect break order. Finally, our results explain how changes in Igh architecture in the absence of 53BP1 could promote inversional rearrangements that compromise CSR. PMID:27320916

  13. Differential regulation of S-region hypermutation and class-switch recombination by noncanonical functions of uracil DNA glycosylase

    OpenAIRE

    Yousif, Ashraf S.; Stanlie, Andre; Mondal, Samiran; Honjo, Tasuku; Begum, Nasim A.

    2014-01-01

    Uracil DNA glycosylase (UNG) has been known as a critical base excision repair protein required for class switch recombination (CSR) and somatic hypermutation (SHM). On the other hand, its precise function in both CSR and SHM is extremely debatable and elusive. Here, we showed that UNG suppresses S region SHM (s-SHM) by recruiting the faithful DNA repair complex and, in the absence of UNG, the error-prone repair complex that induces s-SHM overrides. Moreover, UNG promotes activation-induced c...

  14. APE1 is dispensable for S-region cleavage but required for its repair in class switch recombination

    OpenAIRE

    Xu, Jianliang; Husain, Afzal; Hu, Wenjun; Honjo, Tasuku; Kobayashi, Maki

    2014-01-01

    Apurinic/apyrimidinic endonuclease 1 (APE1) has been shown to be a critical endonuclease required for class switch recombination (CSR). Here we show that APE1’s endonuclease activity, but not its redox regulation or transcriptional regulation activity, is important for CSR. Conversely, APE1 is dispensable for activation-induced cytidine deaminase (AID)-induced somatic hypermutation (SHM) as well as IgH/c-myc translocation. Moreover, during CSR, APE1 is not required for AID-induced S-region br...

  15. AID expression increased by TNF-α is associated with class switch recombination of Igα gene in cancers.

    Science.gov (United States)

    Duan, Zhi; Zheng, Hui; Liu, Haidan; Li, Ming; Tang, Min; Weng, Xinxian; Yi, Wei; Bode, Ann M; Cao, Ya

    2016-07-01

    Recently, immunoglobulins (Igs) were unexpectedly found to be expressed in epithelial cancers. Immunoglobulin class switching or class switch recombination (CSR) is a natural biological process that alters a B cell's production of antibodies (immunoglobulins) from one class to another. However, the mechanism of CSR of Ig genes in cancer is still unknown. Here, we confirmed by detecting the hallmark of CSR that the Igα gene in cancer underwent CSR. Then we focused on activation-induced cytidine deaminase (AID), a crucial factor for initiating CSR. Further studies using tumor necrosis factor (TNF)-α stimulation and specific inhibitor of NF-κB revealed that TNF-α could increase AID expression through NF-κB signaling. Finally, we demonstrated that AID could co-localize with protein kinase A and bind to the switching (Sα) region of the Igα gene. Overexpression of AID obviously enhanced Igα heavy chain expression and its binding ability to the Sα region. These findings indicated that TNF-α-induced AID expression is involved with CSR in cancer. PMID:25849121

  16. ATM increases activation-induced cytidine deaminase activity at downstream S regions during class-switch recombination.

    Science.gov (United States)

    Khair, Lyne; Guikema, Jeroen E J; Linehan, Erin K; Ucher, Anna J; Leus, Niek G J; Ogilvie, Colin; Lou, Zhenkun; Schrader, Carol E; Stavnezer, Janet

    2014-05-15

    Activation-induced cytidine deaminase (AID) initiates Ab class-switch recombination (CSR) in activated B cells resulting in exchanging the IgH C region and improved Ab effector function. During CSR, AID instigates DNA double-strand break (DSB) formation in switch (S) regions located upstream of C region genes. DSBs are necessary for CSR, but improper regulation of DSBs can lead to chromosomal translocations that can result in B cell lymphoma. The protein kinase ataxia telangiectasia mutated (ATM) is an important proximal regulator of the DNA damage response (DDR), and translocations involving S regions are increased in its absence. ATM phosphorylates H2AX, which recruits other DNA damage response (DDR) proteins, including mediator of DNA damage checkpoint 1 (Mdc1) and p53 binding protein 1 (53BP1), to sites of DNA damage. As these DDR proteins all function to promote repair and recombination of DSBs during CSR, we examined whether mouse splenic B cells deficient in these proteins would show alterations in S region DSBs when undergoing CSR. We find that in atm(-/-) cells Sμ DSBs are increased, whereas DSBs in downstream Sγ regions are decreased. We also find that mutations in the unrearranged Sγ3 segment are reduced in atm(-/-) cells. Our data suggest that ATM increases AID targeting and activity at downstream acceptor S regions during CSR and that in atm(-/-) cells Sμ DSBs accumulate as they lack a recombination partner. PMID:24729610

  17. Redundant function of DNA ligase 1 and 3 in alternative end-joining during immunoglobulin class switch recombination.

    Science.gov (United States)

    Masani, Shahnaz; Han, Li; Meek, Katheryn; Yu, Kefei

    2016-02-01

    Nonhomologous end-joining (NHEJ) is the major DNA double-strand break (DSB) repair pathway in mammals and resolves the DSBs generated during both V(D)J recombination in developing lymphocytes and class switch recombination (CSR) in antigen-stimulated B cells. In contrast to the absolute requirement for NHEJ to resolve DSBs associated with V(D)J recombination, DSBs associated with CSR can be resolved in NHEJ-deficient cells (albeit at a reduced level) by a poorly defined alternative end-joining (A-EJ) pathway. Deletion of DNA ligase IV (Lig4), a core component of the NHEJ pathway, reduces CSR efficiency in a mouse B-cell line capable of robust cytokine-stimulated CSR in cell culture. Here, we report that CSR levels are not further reduced by deletion of either of the two remaining DNA ligases (Lig1 and nuclear Lig3) in Lig4(-/-) cells. We conclude that in the absence of Lig4, Lig1, and Lig3 function in a redundant manner in resolving switch region DSBs during CSR. PMID:26787901

  18. 53BP1 regulates DNA resection and the choice between classical and alternative end joining during class switch recombination.

    Science.gov (United States)

    Bothmer, Anne; Robbiani, Davide F; Feldhahn, Niklas; Gazumyan, Anna; Nussenzweig, Andre; Nussenzweig, Michel C

    2010-04-12

    Class switch recombination (CSR) diversifies antibodies by joining highly repetitive DNA elements, which are separated by 60-200 kbp. CSR is initiated by activation-induced cytidine deaminase, an enzyme that produces multiple DNA double-strand breaks (DSBs) in switch regions. Switch regions are joined by a mechanism that requires an intact DNA damage response and classical or alternative nonhomologous end joining (A-NHEJ). Among the DNA damage response factors, 53BP1 has the most profound effect on CSR. We explore the role of 53BP1 in intrachromosomal DNA repair using I-SceI to introduce paired DSBs in the IgH locus. We find that the absence of 53BP1 results in an ataxia telangiectasia mutated-dependent increase in DNA end resection and that resected DNA is preferentially repaired by microhomology-mediated A-NHEJ. We propose that 53BP1 favors long-range CSR in part by protecting DNA ends against resection, which prevents A-NHEJ-dependent short-range rejoining of intra-switch region DSBs.

  19. Opinion: uracil DNA glycosylase (UNG) plays distinct and non-canonical roles in somatic hypermutation and class switch recombination.

    Science.gov (United States)

    Yousif, Ashraf S; Stanlie, Andre; Begum, Nasim A; Honjo, Tasuku

    2014-10-01

    Activation-induced cytidine deaminase (AID) is essential to class switch recombination (CSR) and somatic hypermutation (SHM). Uracil DNA glycosylase (UNG), a member of the base excision repair complex, is required for CSR. The role of UNG in CSR and SHM is extremely controversial. AID deficiency in mice abolishes both CSR and SHM, while UNG-deficient mice have drastically reduced CSR but augmented SHM raising a possibility of differential functions of UNG in CSR and SHM. Interestingly, UNG has been associated with a CSR-specific repair adapter protein Brd4, which interacts with acetyl histone 4, γH2AX and 53BP1 to promote non-homologous end joining during CSR. A non-canonical scaffold function of UNG, but not the catalytic activity, can be attributed to the recruitment of essential repair proteins associated with the error-free repair during SHM, and the end joining during CSR. PMID:24994819

  20. Mediator facilitates transcriptional activation and dynamic long-range contacts at the IgH locus during class switch recombination.

    Science.gov (United States)

    Thomas-Claudepierre, Anne-Sophie; Robert, Isabelle; Rocha, Pedro P; Raviram, Ramya; Schiavo, Ebe; Heyer, Vincent; Bonneau, Richard; Luo, Vincent M; Reddy, Janardan K; Borggrefe, Tilman; Skok, Jane A; Reina-San-Martin, Bernardo

    2016-03-01

    Immunoglobulin (Ig) class switch recombination (CSR) is initiated by the transcription-coupled recruitment of activation-induced cytidine deaminase (AID) to Ig switch regions (S regions). During CSR, the IgH locus undergoes dynamic three-dimensional structural changes in which promoters, enhancers, and S regions are brought to close proximity. Nevertheless, little is known about the underlying mechanisms. In this study, we show that Med1 and Med12, two subunits of the mediator complex implicated in transcription initiation and long-range enhancer/promoter loop formation, are dynamically recruited to the IgH locus enhancers and the acceptor regions during CSR and that their knockdown in CH12 cells results in impaired CSR. Furthermore, we show that conditional inactivation of Med1 in B cells results in defective CSR and reduced acceptor S region transcription. Finally, we show that in B cells undergoing CSR, the dynamic long-range contacts between the IgH enhancers and the acceptor regions correlate with Med1 and Med12 binding and that they happen at a reduced frequency in Med1-deficient B cells. Our results implicate the mediator complex in the mechanism of CSR and are consistent with a model in which mediator facilitates the long-range contacts between S regions and the IgH locus enhancers during CSR and their transcriptional activation.

  1. Mediator facilitates transcriptional activation and dynamic long-range contacts at the IgH locus during class switch recombination

    Science.gov (United States)

    Thomas-Claudepierre, Anne-Sophie; Robert, Isabelle; Rocha, Pedro P.; Raviram, Ramya; Schiavo, Ebe; Heyer, Vincent; Bonneau, Richard; Luo, Vincent M.; Reddy, Janardan K.; Borggrefe, Tilman; Skok, Jane A.

    2016-01-01

    Immunoglobulin (Ig) class switch recombination (CSR) is initiated by the transcription-coupled recruitment of activation-induced cytidine deaminase (AID) to Ig switch regions (S regions). During CSR, the IgH locus undergoes dynamic three-dimensional structural changes in which promoters, enhancers, and S regions are brought to close proximity. Nevertheless, little is known about the underlying mechanisms. In this study, we show that Med1 and Med12, two subunits of the mediator complex implicated in transcription initiation and long-range enhancer/promoter loop formation, are dynamically recruited to the IgH locus enhancers and the acceptor regions during CSR and that their knockdown in CH12 cells results in impaired CSR. Furthermore, we show that conditional inactivation of Med1 in B cells results in defective CSR and reduced acceptor S region transcription. Finally, we show that in B cells undergoing CSR, the dynamic long-range contacts between the IgH enhancers and the acceptor regions correlate with Med1 and Med12 binding and that they happen at a reduced frequency in Med1-deficient B cells. Our results implicate the mediator complex in the mechanism of CSR and are consistent with a model in which mediator facilitates the long-range contacts between S regions and the IgH locus enhancers during CSR and their transcriptional activation. PMID:26903242

  2. Mediator facilitates transcriptional activation and dynamic long-range contacts at the IgH locus during class switch recombination.

    Science.gov (United States)

    Thomas-Claudepierre, Anne-Sophie; Robert, Isabelle; Rocha, Pedro P; Raviram, Ramya; Schiavo, Ebe; Heyer, Vincent; Bonneau, Richard; Luo, Vincent M; Reddy, Janardan K; Borggrefe, Tilman; Skok, Jane A; Reina-San-Martin, Bernardo

    2016-03-01

    Immunoglobulin (Ig) class switch recombination (CSR) is initiated by the transcription-coupled recruitment of activation-induced cytidine deaminase (AID) to Ig switch regions (S regions). During CSR, the IgH locus undergoes dynamic three-dimensional structural changes in which promoters, enhancers, and S regions are brought to close proximity. Nevertheless, little is known about the underlying mechanisms. In this study, we show that Med1 and Med12, two subunits of the mediator complex implicated in transcription initiation and long-range enhancer/promoter loop formation, are dynamically recruited to the IgH locus enhancers and the acceptor regions during CSR and that their knockdown in CH12 cells results in impaired CSR. Furthermore, we show that conditional inactivation of Med1 in B cells results in defective CSR and reduced acceptor S region transcription. Finally, we show that in B cells undergoing CSR, the dynamic long-range contacts between the IgH enhancers and the acceptor regions correlate with Med1 and Med12 binding and that they happen at a reduced frequency in Med1-deficient B cells. Our results implicate the mediator complex in the mechanism of CSR and are consistent with a model in which mediator facilitates the long-range contacts between S regions and the IgH locus enhancers during CSR and their transcriptional activation. PMID:26903242

  3. Fanca deficiency reduces A/T transitions in somatic hypermutation and alters class switch recombination junctions in mouse B cells.

    Science.gov (United States)

    Nguyen, Thuy Vy; Riou, Lydia; Aoufouchi, Saïd; Rosselli, Filippo

    2014-06-01

    Fanconi anemia is a rare genetic disorder that can lead to bone marrow failure, congenital abnormalities, and increased risk for leukemia and cancer. Cells with loss-of-function mutations in the FANC pathway are characterized by chromosome fragility, altered mutability, and abnormal regulation of the nonhomologous end-joining (NHEJ) pathway. Somatic hypermutation (SHM) and immunoglobulin (Ig) class switch recombination (CSR) enable B cells to produce high-affinity antibodies of various isotypes. Both processes are initiated after the generation of dG:dU mismatches by activation-induced cytidine deaminase. Whereas SHM involves an error-prone repair process that introduces novel point mutations into the Ig gene, the mismatches generated during CSR are processed to create double-stranded breaks (DSBs) in DNA, which are then repaired by the NHEJ pathway. As several lines of evidence suggest a possible role for the FANC pathway in SHM and CSR, we analyzed both processes in B cells derived from Fanca(-/-) mice. Here we show that Fanca is required for the induction of transition mutations at A/T residues during SHM and that despite globally normal CSR function in splenic B cells, Fanca is required during CSR to stabilize duplexes between pairs of short microhomology regions, thereby impeding short-range recombination downstream of DSB formation. PMID:24799500

  4. Regulation of immunoglobulin class-switch recombination: choreography of noncoding transcription, targeted DNA deamination, and long-range DNA repair.

    Science.gov (United States)

    Matthews, Allysia J; Zheng, Simin; DiMenna, Lauren J; Chaudhuri, Jayanta

    2014-01-01

    Upon encountering antigens, mature IgM-positive B lymphocytes undergo class-switch recombination (CSR) wherein exons encoding the default Cμ constant coding gene segment of the immunoglobulin (Ig) heavy-chain (Igh) locus are excised and replaced with a new constant gene segment (referred to as "Ch genes", e.g., Cγ, Cɛ, or Cα). The B cell thereby changes from expressing IgM to one producing IgG, IgE, or IgA, with each antibody isotype having a different effector function during an immune reaction. CSR is a DNA deletional-recombination reaction that proceeds through the generation of DNA double-strand breaks (DSBs) in repetitive switch (S) sequences preceding each Ch gene and is completed by end-joining between donor Sμ and acceptor S regions. CSR is a multistep reaction requiring transcription through S regions, the DNA cytidine deaminase AID, and the participation of several general DNA repair pathways including base excision repair, mismatch repair, and classical nonhomologous end-joining. In this review, we discuss our current understanding of how transcription through S regions generates substrates for AID-mediated deamination and how AID participates not only in the initiation of CSR but also in the conversion of deaminated residues into DSBs. Additionally, we review the multiple processes that regulate AID expression and facilitate its recruitment specifically to the Ig loci, and how deregulation of AID specificity leads to oncogenic translocations. Finally, we summarize recent data on the potential role of AID in the maintenance of the pluripotent stem cell state during epigenetic reprogramming. PMID:24507154

  5. Aberrant recombination and repair during immunoglobulin class switching in BRCA1-deficient human B cells

    DEFF Research Database (Denmark)

    Björkman, Andrea; Qvist, Per; Du, Likun;

    2015-01-01

    machinery. A shift to the use of microhomology-based, alternative end-joining (A-EJ) and increased frequencies of intra-S region deletions as well as insertions of inverted S sequences were observed at the recombination junctions amplified from BRCA1-deficient human B cells. Furthermore, increased use of...... underlying BRCA1’s function in maintaining genome stability and tumor suppression but may also point to a previously unrecognized role of BRCA1 in B-cell lymphomagenesis....

  6. S-S synapsis during class switch recombination is promoted by distantly located transcriptional elements and activation-induced deaminase.

    Science.gov (United States)

    Wuerffel, Robert; Wang, Lili; Grigera, Fernando; Manis, John; Selsing, Erik; Perlot, Thomas; Alt, Frederick W; Cogne, Michel; Pinaud, Eric; Kenter, Amy L

    2007-11-01

    Molecular mechanisms underlying synapsis of activation-induced deaminase (AID)-targeted S regions during class switch recombination (CSR) are poorly understood. By using chromosome conformation capture techniques, we found that in B cells, the Emicro and 3'Ealpha enhancers were in close spatial proximity, forming a unique chromosomal loop configuration. B cell activation led to recruitment of the germline transcript (GLT) promoters to the Emicro:3'Ealpha complex in a cytokine-dependent fashion. This structure facilitated S-S synapsis because Smicro was proximal to Emicro and a downstream S region was corecruited with the targeted GLT promoter to Emicro:3'Ealpha. We propose that GLT promoter association with the Emicro:3'Ealpha complex creates an architectural scaffolding that promotes S-S synapsis during CSR and that these interactions are stabilized by AID. Thus, the S-S synaptosome is formed as a result of the self-organizing transcription system that regulates GLT expression and may serve to guard against spurious chromosomal translocations.

  7. Differential regulation of S-region hypermutation and class-switch recombination by noncanonical functions of uracil DNA glycosylase

    Science.gov (United States)

    Yousif, Ashraf S.; Stanlie, Andre; Mondal, Samiran; Honjo, Tasuku; Begum, Nasim A.

    2014-01-01

    Activation-induced cytidine deaminase (AID) is essential to class-switch recombination (CSR) and somatic hypermutation (SHM) in both V region SHM and S region SHM (s-SHM). Uracil DNA glycosylase (UNG), a member of the base excision repair (BER) complex, is required for CSR. Strikingly, however, UNG deficiency causes augmentation of SHM, suggesting involvement of distinct functions of UNG in SHM and CSR. Here, we show that noncanonical scaffold functions of UNG regulate s-SHM negatively and CSR positively. The s-SHM suppressive function of UNG is attributed to the recruitment of faithful BER components at the cleaved DNA locus, with competition against error-prone polymerases. By contrast, the CSR-promoting function of UNG enhances AID-dependent S-S synapse formation by recruiting p53-binding protein 1 and DNA-dependent protein kinase, catalytic subunit. Several loss-of-catalysis mutants of UNG discriminated CSR-promoting activity from s-SHM suppressive activity. Taken together, the noncanonical function of UNG regulates the steps after AID-induced DNA cleavage: error-prone repair suppression in s-SHM and end-joining promotion in CSR. PMID:24591630

  8. p21 is dispensable for AID-mediated class switch recombination and mutagenesis of immunoglobulin genes during somatic hypermutation.

    Science.gov (United States)

    Shansab, Maryam; Selsing, Erik

    2011-03-01

    In B cells, activation-induced cytidine deaminase (AID) induces somatic hypermutation (SHM) at rearranged immunoglobulin (Ig) variable (V) regions. Previous studies have shown that both monoubiquitination of proliferating cell nuclear antigen (PCNA) and translesional DNA polymerase activity are important for inducing mutagenesis during SHM. Regulation of PCNA ubiquitination by p21, also known as Cdkn1a and p21(Cip1/Waf1), is an important mechanism that controls mutation loads in mammalian cells. In this study, we have assessed whether p21 has an in vivo function in regulating mutagenesis in B cells by analyzing SHM frequency in p21-deficient mice. Our results show that p21 is dispensable for SHM. This suggests that, during SHM of Ig genes, p21 does not act to regulate mutagenesis load. We also show that p21 transcript levels are the same in both wildtype and AID-deficient B cells during B cell activation, and that AID-mediated class switch recombination (CSR) is not affected by p21 deficiency; thereby indicating that p21 regulation in B cells is not altered by AID-induced DNA damage and that p21 has no affect on AID-dependent Ig gene diversification. Our results suggest that regulation of p21 in activated B cells is probably more important for maintaining proper cell cycle progression as opposed to promoting SHM of Ig genes.

  9. Differential regulation of S-region hypermutation and class-switch recombination by noncanonical functions of uracil DNA glycosylase.

    Science.gov (United States)

    Yousif, Ashraf S; Stanlie, Andre; Mondal, Samiran; Honjo, Tasuku; Begum, Nasim A

    2014-03-18

    Activation-induced cytidine deaminase (AID) is essential to class-switch recombination (CSR) and somatic hypermutation (SHM) in both V region SHM and S region SHM (s-SHM). Uracil DNA glycosylase (UNG), a member of the base excision repair (BER) complex, is required for CSR. Strikingly, however, UNG deficiency causes augmentation of SHM, suggesting involvement of distinct functions of UNG in SHM and CSR. Here, we show that noncanonical scaffold functions of UNG regulate s-SHM negatively and CSR positively. The s-SHM suppressive function of UNG is attributed to the recruitment of faithful BER components at the cleaved DNA locus, with competition against error-prone polymerases. By contrast, the CSR-promoting function of UNG enhances AID-dependent S-S synapse formation by recruiting p53-binding protein 1 and DNA-dependent protein kinase, catalytic subunit. Several loss-of-catalysis mutants of UNG discriminated CSR-promoting activity from s-SHM suppressive activity. Taken together, the noncanonical function of UNG regulates the steps after AID-induced DNA cleavage: error-prone repair suppression in s-SHM and end-joining promotion in CSR. PMID:24591630

  10. Elucidation of the enigmatic IgD class-switch recombination via germline deletion of the IgH 3′ regulatory region

    OpenAIRE

    Rouaud, Pauline; Saintamand, Alexis; Saad, Faten; Carrion, Claire; Lecardeur, Sandrine; Cogné, Michel; Denizot, Yves

    2014-01-01

    Classical class-switch recombination (cCSR) substitutes the Cμ gene with Cγ, Cε, or Cα, thereby generating IgG, IgE, or IgA classes, respectively. This activation-induced deaminase (AID)–driven process is controlled by the IgH 3′ regulatory region (3′RR). Regulation of rare IgD CSR events has been enigmatic. We show that μδCSR occurs in mouse mesenteric lymph node (MLN) B cells and is AID-dependent. AID attacks differ from those in cCSR because they are not accompanied by extensive somatic hy...

  11. Non-canonical uracil processing in DNA gives rise to double-strand breaks and deletions: relevance to class switch recombination.

    Science.gov (United States)

    Bregenhorn, Stephanie; Kallenberger, Lia; Artola-Borán, Mariela; Peña-Diaz, Javier; Jiricny, Josef

    2016-04-01

    During class switch recombination (CSR), antigen-stimulated B-cells rearrange their immunoglobulin constant heavy chain (CH) loci to generate antibodies with different effector functions. CSR is initiated by activation-induced deaminase (AID), which converts cytosines in switch (S) regions, repetitive sequences flanking the CH loci, to uracils. Although U/G mispairs arising in this way are generally efficiently repaired to C/Gs by uracil DNA glycosylase (UNG)-initiated base excision repair (BER), uracil processing in S-regions of activated B-cells occasionally gives rise to double strand breaks (DSBs), which trigger CSR. Surprisingly, genetic experiments revealed that CSR is dependent not only on AID and UNG, but also on mismatch repair (MMR). To elucidate the role of MMR in CSR, we studied the processing of uracil-containing DNA substrates in extracts of MMR-proficient and -deficient human cells, as well as in a system reconstituted from recombinant BER and MMR proteins. Here, we show that the interplay of these repair systems gives rise to DSBs in vitro and to genomic deletions and mutations in vivo, particularly in an S-region sequence. Our findings further suggest that MMR affects pathway choice in DSB repair. Given its amenability to manipulation, our system represents a powerful tool for the molecular dissection of CSR.

  12. Non-canonical uracil processing in DNA gives rise to double-strand breaks and deletions: relevance to class switch recombination.

    Science.gov (United States)

    Bregenhorn, Stephanie; Kallenberger, Lia; Artola-Borán, Mariela; Peña-Diaz, Javier; Jiricny, Josef

    2016-04-01

    During class switch recombination (CSR), antigen-stimulated B-cells rearrange their immunoglobulin constant heavy chain (CH) loci to generate antibodies with different effector functions. CSR is initiated by activation-induced deaminase (AID), which converts cytosines in switch (S) regions, repetitive sequences flanking the CH loci, to uracils. Although U/G mispairs arising in this way are generally efficiently repaired to C/Gs by uracil DNA glycosylase (UNG)-initiated base excision repair (BER), uracil processing in S-regions of activated B-cells occasionally gives rise to double strand breaks (DSBs), which trigger CSR. Surprisingly, genetic experiments revealed that CSR is dependent not only on AID and UNG, but also on mismatch repair (MMR). To elucidate the role of MMR in CSR, we studied the processing of uracil-containing DNA substrates in extracts of MMR-proficient and -deficient human cells, as well as in a system reconstituted from recombinant BER and MMR proteins. Here, we show that the interplay of these repair systems gives rise to DSBs in vitro and to genomic deletions and mutations in vivo, particularly in an S-region sequence. Our findings further suggest that MMR affects pathway choice in DSB repair. Given its amenability to manipulation, our system represents a powerful tool for the molecular dissection of CSR. PMID:26743004

  13. Microbiota regulate the ability of lung dendritic cells to induce IgA class-switch recombination and generate protective gastrointestinal immune responses.

    Science.gov (United States)

    Ruane, Darren; Chorny, Alejo; Lee, Haekyung; Faith, Jeremiah; Pandey, Gaurav; Shan, Meimei; Simchoni, Noa; Rahman, Adeeb; Garg, Aakash; Weinstein, Erica G; Oropallo, Michael; Gaylord, Michelle; Ungaro, Ryan; Cunningham-Rundles, Charlotte; Alexandropoulos, Konstantina; Mucida, Daniel; Merad, Miriam; Cerutti, Andrea; Mehandru, Saurabh

    2016-01-11

    Protective immunoglobulin A (IgA) responses to oral antigens are usually orchestrated by gut dendritic cells (DCs). Here, we show that lung CD103(+) and CD24(+)CD11b(+) DCs induced IgA class-switch recombination (CSR) by activating B cells through T cell-dependent or -independent pathways. Compared with lung DCs (LDC), lung CD64(+) macrophages had decreased expression of B cell activation genes and induced significantly less IgA production. Microbial stimuli, acting through Toll-like receptors, induced transforming growth factor-β (TGF-β) production by LDCs and exerted a profound influence on LDC-mediated IgA CSR. After intranasal immunization with inactive cholera toxin (CT), LDCs stimulated retinoic acid-dependent up-regulation of α4β7 and CCR9 gut-homing receptors on local IgA-expressing B cells. Migration of these B cells to the gut resulted in IgA-mediated protection against an oral challenge with active CT. However, in germ-free mice, the levels of LDC-induced, CT-specific IgA in the gut are significantly reduced. Herein, we demonstrate an unexpected role of the microbiota in modulating the protective efficacy of intranasal vaccination through their effect on the IgA class-switching function of LDCs. PMID:26712806

  14. Murine germinal center B cells require functional Fms-like tyrosine kinase 3 signaling for IgG1 class-switch recombination.

    Science.gov (United States)

    Svensson, Mattias N D; Andersson, Karin M E; Wasén, Caroline; Erlandsson, Malin C; Nurkkala-Karlsson, Merja; Jonsson, Ing-Marie; Brisslert, Mikael; Bemark, Mats; Bokarewa, Maria I

    2015-12-01

    Switched antibody classes are important for efficient immune responses. Aberrant antibody production to otherwise harmless antigens may result in autoimmunity. The protein kinase fms-like tyrosine kinase 3 receptor (Flt3) has an important role during early B-cell development, but the role of Flt3 in peripheral B cells has not been assessed before. Herein we describe a previously unappreciated role for Flt3 in IgG1 class-switch recombination (CSR) and production. We show that Flt3 is reexpressed on B-cell lymphoma 6(+) germinal center B cells in vivo and following LPS activation of peripheral B cells in vitro. Absence of Flt3 signaling in Flt3 ligand-deficient mice results in impaired IgG1 CSR and accumulation of IgM-secreting plasma cells. On activated B cells, Flt3 is coexpressed and functions in synergy with the common-gamma chain receptor family. B cells from Flt3 ligand-deficient mice have impaired IL-4R signaling, with reduced phosphorylation of signal transducer and activator of transcription (Stat) 6, and demonstrate a failure to initiate CSR to IgG1 with low expression of γ1 germ-line transcripts, resulting in impaired IgG1 production. Thus, functional synergy between Flt3 and IL-4R signaling is critical for Stat-mediated regulation of sterile γ1 germ-line transcripts and CSR to IgG1. PMID:26627255

  15. Immunoglobulin genes undergo legitimate repair in human B cells not only after cis- but also frequent trans-class switch recombination.

    Science.gov (United States)

    Laffleur, B; Bardet, S M; Garot, A; Brousse, M; Baylet, A; Cogné, M

    2014-01-01

    Immunoglobulin (Ig) genes specifically recruit activation-induced deaminase (AID) for 'on-target' DNA deamination, initiating either variable (V) region somatic hypermutation, or double-strand break intermediates of class switch recombination (CSR). Such breaks overwhelmingly undergo legitimate intra-Ig repair rather than rare illegitimate and potentially oncogenic junctions outside of Ig loci. We show that in human B cells, legitimate synapsis and repair efficiently join Ig genes whether physically linked on one chromosome or located apart on both alleles. This indicates mechanisms faithfully recognizing and/or pairing loci with homology in structure and accessibility, thus licensing interchromosomal trans-CSR junctions while usually preventing illegitimate interchromosomal recombination with AID off-target genes. Physical linkage of IgH genes in cis on the same allele just increases the likelihood of legitimate repair by another fourfold. The strongest force driving CSR might thus be recognition of legitimate target genes. Formation of IgH intra-allelic loops along this process would then constitute a consequence rather than a pre-requisite of this gene-pairing process.

  16. Elucidation of the enigmatic IgD class-switch recombination via germline deletion of the IgH 3' regulatory region.

    Science.gov (United States)

    Rouaud, Pauline; Saintamand, Alexis; Saad, Faten; Carrion, Claire; Lecardeur, Sandrine; Cogné, Michel; Denizot, Yves

    2014-05-01

    Classical class-switch recombination (cCSR) substitutes the Cμ gene with Cγ, Cε, or Cα, thereby generating IgG, IgE, or IgA classes, respectively. This activation-induced deaminase (AID)-driven process is controlled by the IgH 3' regulatory region (3'RR). Regulation of rare IgD CSR events has been enigmatic. We show that μδCSR occurs in mouse mesenteric lymph node (MLN) B cells and is AID-dependent. AID attacks differ from those in cCSR because they are not accompanied by extensive somatic hypermutation (SHM) of targeted regions and because repaired junctions exhibit features of the alternative end-joining (A-EJ) pathway. In contrast to cCSR and SHM, μδCSR is 3'RR-independent, as its absence affects neither breakpoint locations in Sμ- and Sδ-like (σ(δ)) nor mutation patterns at Sμ-σ(δ) junctions. Although mutations occur in the immediate proximity of the μδ junctions, SHM is absent distal to the junctions within both Sμ and rearranged VDJ regions. In conclusion, μδCSR is active in MLNs, occurs independently of 3'RR-driven assembly, and is even dramatically increased in 3'RR-deficient mice, further showing that its regulation differs from cCSR. PMID:24752300

  17. Requirement of 8-mercaptoguanosine as a costimulus for IL-4-dependent μ to γ1 class switch recombination in CD38-activated B cells

    International Nuclear Information System (INIS)

    Mature B-2 cells expressing surface IgM and IgD proliferate upon stimulation by CD38, CD40 or lipopolysaccharide (LPS) and differentiate into IgG1-producing plasma cells in the presence of cytokines. The process of class switch recombination (CSR) from IgM to other isotypes is highly regulated by cytokines and activation-induced cytidine deaminase (AID). Blimp-1 and XBP-1 play an essential role in the terminal differentiation of switched B-2 cells to Ig-producing plasma cells. IL-5 induces AID and Blimp-1 expression in CD38- and CD40-activated B-2 cells, leading to μ to γ1 CSR at DNA level and IgG1 production. IL-4, a well-known IgG1-inducing factor, does not induce μ to γ1 CSR in CD38-activated B-2 cells or Blimp-1, while IL-4 induces μ to γ1 CSR, XBP-1 expression, and IgG1 production expression in CD40-activated B-2 cells. Interestingly, the addition of 8-mercaptoguanosine (8-SGuo) with IL-4 to the culture of CD38-activated B cells can induce μ to γ1 CSR, Blimp-1 expression, and IgG1 production. Intriguingly, 8-SGuo by itself induces AID expression in CD38-activated B cells. However, it does not induce μ to γ1 CSR. These results imply that the mode of B-cell activation for extracellular stimulation affects the outcome of cytokine stimulation with respect to the efficiency and direction of CSR, and the requirements of the transcriptional regulator and the generation of antibody-secreting cells. Furthermore, our data suggest the requirement of additional molecules in addition to AID for CSR

  18. High expression of AID and active class switch recombination might account for a more aggressive disease in unmutated CLL patients: link with an activated microenvironment in CLL disease.

    Science.gov (United States)

    Palacios, Florencia; Moreno, Pilar; Morande, Pablo; Abreu, Cecilia; Correa, Agustín; Porro, Valentina; Landoni, Ana Ines; Gabus, Raul; Giordano, Mirta; Dighiero, Guillermo; Pritsch, Otto; Oppezzo, Pablo

    2010-06-01

    Interaction of chronic lymphocytic leukemia (CLL) B cells with tissue microenvironment has been suggested to favor disease progression by promoting malignant B-cell growth. Previous work has shown expression in peripheral blood (PB) of CLL B cells of activation-induced cytidine deaminase (AID) among CLL patients with an unmutated (UM) profile of immunoglobulin genes and with ongoing class switch recombination (CSR) process. Because AID expression results from interaction with activated tissue microenvironment, we speculated whether the small subset with ongoing CSR is responsible for high levels of AID expression and could be derived from this particular microenvironment. In this work, we quantified AID expression and ongoing CSR in PB of 50 CLL patients and characterized the expression of different molecules related to microenvironment interaction. Our results show that among UM patients (1) high AID expression is restricted to the subpopulation of tumoral cells ongoing CSR; (2) this small subset expresses high levels of proliferation, antiapoptotic and progression markers (Ki-67, c-myc, Bcl-2, CD49d, and CCL3/4 chemokines). Overall, this work outlines the importance of a cellular subset in PB of UM CLL patients with a poor clinical outcome, high AID levels, and ongoing CSR, whose presence might be a hallmark of a recent contact with the microenvironment. PMID:20233972

  19. The SAGA Deubiquitination Module Promotes DNA Repair and Class Switch Recombination through ATM and DNAPK-Mediated γH2AX Formation.

    Science.gov (United States)

    Ramachandran, Shaliny; Haddad, Dania; Li, Conglei; Le, Michael X; Ling, Alexanda K; So, Clare C; Nepal, Rajeev M; Gommerman, Jennifer L; Yu, Kefei; Ketela, Troy; Moffat, Jason; Martin, Alberto

    2016-05-17

    Class switch recombination (CSR) requires activation-induced deaminase (AID) to instigate double-stranded DNA breaks at the immunoglobulin locus. DNA breaks activate the DNA damage response (DDR) by inducing phosphorylation of histone H2AX followed by non-homologous end joining (NHEJ) repair. We carried out a genome-wide screen to identify CSR factors. We found that Usp22, Eny2, and Atxn7, members of the Spt-Ada-Gcn5-acetyltransferase (SAGA) deubiquitination module, are required for deubiquitination of H2BK120ub following DNA damage, are critical for CSR, and function downstream of AID. The SAGA deubiquitinase activity was required for optimal irradiation-induced γH2AX formation, and failure to remove H2BK120ub inhibits ATM- and DNAPK-induced γH2AX formation. Consistent with this effect, these proteins were found to function upstream of various double-stranded DNA repair pathways. This report demonstrates that deubiquitination of histone H2B impacts the early stages of the DDR and is required for the DNA repair phase of CSR. PMID:27160905

  20. Comparison of identical and functional Igh alleles reveals a nonessential role for Eμ in somatic hypermutation and class-switch recombination.

    Science.gov (United States)

    Li, Fubin; Yan, Yi; Pieretti, Joyce; Feldman, Danielle A; Eckhardt, Laurel A

    2010-11-15

    Somatic hypermutation (SHM), coupled with Ag selection, provides a mechanism for generating Abs with high affinity for invading pathogens. Class-switch recombination (CSR) ensures that these Abs attain pathogen-appropriate effector functions. Although the enzyme critical to both processes, activation-induced cytidine deaminase, has been identified, it remains unclear which cis-elements within the Ig loci are responsible for recruiting activation-induced cytidine deaminase and promoting its activity. Studies showed that Ig gene-transcription levels are positively correlated with the frequency of SHM and CSR, making the intronic, transcriptional enhancer Eμ a likely contributor to both processes. Tests of this hypothesis yielded mixed results arising, in part, from the difficulty in studying B cell function in mice devoid of Eμ. In Eμ's absence, V(H) gene assembly is dramatically impaired, arresting B cell development. The current study circumvented this problem by modifying the murine Igh locus through simultaneous insertion of a fully assembled V(H) gene and deletion of Eμ. The behavior of this allele was compared with that of a matched allele carrying the same V(H) gene but with Eμ intact. Although IgH transcription was as great or greater on the Eμ-deficient allele, CSR and SHM were consistently, but modestly, reduced relative to the allele in which Eμ remained intact. We conclude that Eμ contributes to, but is not essential for, these complex processes and that its contribution is not as a transcriptional enhancer but, rather, is at the level of recruitment and/or activation of the SHM/CSR machinery.

  1. B cell TLR1/2, TLR4, TLR7 and TLR9 interact in induction of class switch DNA recombination: modulation by BCR and CD40, and relevance to T-independent antibody responses

    OpenAIRE

    Pone, Egest J; Lou, Zheng; Lam, Tonika; Greenberg, Milton L.; Wang, Rui; Xu, Zhenming; Casali, Paolo

    2015-01-01

    Ig class switch DNA recombination (CSR) in B cells is crucial to the maturation of antibody responses. It requires IgH germline IH-CH transcription and expression of AID, both of which are induced by engagement of CD40 or dual engagement of a Toll-like receptor (TLR) and B cell receptor (BCR). Here, we have addressed cross-regulation between two different TLRs or between a TLR and CD40 in CSR induction by using a B cell stimulation system involving lipopolysaccharides (LPS). LPS mediated long...

  2. Lineage tracing of human B cells reveals the in vivo landscape of human antibody class switching.

    Science.gov (United States)

    Horns, Felix; Vollmers, Christopher; Croote, Derek; Mackey, Sally F; Swan, Gary E; Dekker, Cornelia L; Davis, Mark M; Quake, Stephen R

    2016-01-01

    Antibody class switching is a feature of the adaptive immune system which enables diversification of the effector properties of antibodies. Even though class switching is essential for mounting a protective response to pathogens, the in vivo patterns and lineage characteristics of antibody class switching have remained uncharacterized in living humans. Here we comprehensively measured the landscape of antibody class switching in human adult twins using antibody repertoire sequencing. The map identifies how antibodies of every class are created and delineates a two-tiered hierarchy of class switch pathways. Using somatic hypermutations as a molecular clock, we discovered that closely related B cells often switch to the same class, but lose coherence as somatic mutations accumulate. Such correlations between closely related cells exist when purified B cells class switch in vitro, suggesting that class switch recombination is directed toward specific isotypes by a cell-autonomous imprinted state. PMID:27481325

  3. B cell TLR1/2, TLR4, TLR7 and TLR9 interact in induction of class switch DNA recombination: modulation by BCR and CD40, and relevance to T-independent antibody responses.

    Science.gov (United States)

    Pone, Egest J; Lou, Zheng; Lam, Tonika; Greenberg, Milton L; Wang, Rui; Xu, Zhenming; Casali, Paolo

    2015-02-01

    Ig class switch DNA recombination (CSR) in B cells is crucial to the maturation of antibody responses. It requires IgH germline IH-CH transcription and expression of AID, both of which are induced by engagement of CD40 or dual engagement of a Toll-like receptor (TLR) and B cell receptor (BCR). Here, we have addressed cross-regulation between two different TLRs or between a TLR and CD40 in CSR induction by using a B cell stimulation system involving lipopolysaccharides (LPS). LPS-mediated long-term primary class-switched antibody responses and memory-like antibody responses in vivo and induced generation of class-switched B cells and plasma cells in vitro. Consistent with the requirement for dual TLR and BCR engagement in CSR induction, LPS, which engages TLR4 through its lipid A moiety, triggered cytosolic Ca2+ flux in B cells through its BCR-engaging polysaccharidic moiety. In the presence of BCR crosslinking, LPS synergized with a TLR1/2 ligand (Pam3CSK4) in CSR induction, but much less efficiently with a TLR7 (R-848) or TLR9 (CpG) ligand. In the absence of BCR crosslinking, R-848 and CpG, which per se induced marginal CSR, virtually abrogated CSR to IgG1, IgG2a, IgG2b, IgG3 and/or IgA, as induced by LPS or CD154 (CD40 ligand) plus IL-4, IFN-γ or TGF-β, and reduced secretion of class-switched Igs, without affecting B cell proliferation or IgM expression. The CSR inhibition by TLR9 was associated with the reduction in AID expression and/or IgH germline IH-S-CH transcription, and required co-stimulation of B cells by CpG with LPS or CD154. Unexpectedly, B cells also failed to undergo CSR or plasma cell differentiation when co-stimulated by LPS and CD154. Overall, by addressing the interaction of TLR1/2, TLR4, TLR7 and TLR9 in the induction of CSR and modulation of TLR-dependent CSR by BCR and CD40, our study suggests the complexity of how different stimuli cross-regulate an important B cell differentiation process and an important role of TLRs in inducing

  4. Homologous elements hs3a and hs3b in the 3' regulatory region of the murine immunoglobulin heavy chain (Igh) locus are both dispensable for class-switch recombination.

    Science.gov (United States)

    Yan, Yi; Pieretti, Joyce; Ju, Zhongliang; Wei, Shiniu; Christin, John R; Bah, Fatmata; Birshtein, Barbara K; Eckhardt, Laurel A

    2011-08-01

    Immunoglobulin heavy chain (IgH) genes are formed, tested, and modified to yield diverse, specific, and high affinity antibody responses to antigen. The processes involved must be regulated, however, to avoid unintended damage to chromosomes. The 3' regulatory region of the Igh locus plays a major role in regulating class-switch recombination (CSR), the process by which antibody effector functions are modified during an immune response. Loss of all known enhancer-like elements in this region dramatically impairs CSR, but individual element deletions have no effect on this process. In the present study, we explored the hypothesis that an underlying functional redundancy in the homologous elements hs3a and hs3b was masking the importance of either element to CSR. Several transgenic mouse lines were generated, each carrying a bacterial artificial chromosome transgene that mimicked Igh locus structure but in which hs3a was missing and hs3b was flanked by loxP sites. Matings to Cyclization Recombination Enzyme-expressing mice established "pairs" of lines that differed only in the presence or absence of hs3b. Remarkably, CSR remained robust in the absence of both hs3a and hs3b, suggesting that the remaining two elements of the 3' regulatory region, hs1.2 and hs4, although individually dispensable for CSR, are, together, sufficient to support CSR.

  5. Homologous elements hs3a and hs3b in the 3' regulatory region of the murine immunoglobulin heavy chain (Igh) locus are both dispensable for class-switch recombination.

    Science.gov (United States)

    Yan, Yi; Pieretti, Joyce; Ju, Zhongliang; Wei, Shiniu; Christin, John R; Bah, Fatmata; Birshtein, Barbara K; Eckhardt, Laurel A

    2011-08-01

    Immunoglobulin heavy chain (IgH) genes are formed, tested, and modified to yield diverse, specific, and high affinity antibody responses to antigen. The processes involved must be regulated, however, to avoid unintended damage to chromosomes. The 3' regulatory region of the Igh locus plays a major role in regulating class-switch recombination (CSR), the process by which antibody effector functions are modified during an immune response. Loss of all known enhancer-like elements in this region dramatically impairs CSR, but individual element deletions have no effect on this process. In the present study, we explored the hypothesis that an underlying functional redundancy in the homologous elements hs3a and hs3b was masking the importance of either element to CSR. Several transgenic mouse lines were generated, each carrying a bacterial artificial chromosome transgene that mimicked Igh locus structure but in which hs3a was missing and hs3b was flanked by loxP sites. Matings to Cyclization Recombination Enzyme-expressing mice established "pairs" of lines that differed only in the presence or absence of hs3b. Remarkably, CSR remained robust in the absence of both hs3a and hs3b, suggesting that the remaining two elements of the 3' regulatory region, hs1.2 and hs4, although individually dispensable for CSR, are, together, sufficient to support CSR. PMID:21673112

  6. Estrogen receptors bind to and activate the HOXC4/HoxC4 promoter to potentiate HoxC4-mediated activation-induced cytosine deaminase induction, immunoglobulin class switch DNA recombination, and somatic hypermutation.

    Science.gov (United States)

    Mai, Thach; Zan, Hong; Zhang, Jinsong; Hawkins, J Seth; Xu, Zhenming; Casali, Paolo

    2010-11-26

    Estrogen enhances antibody and autoantibody responses through yet to be defined mechanisms. It has been suggested that estrogen up-regulates the expression of activation-induced cytosine deaminase (AID), which is critical for antibody class switch DNA recombination (CSR) and somatic hypermutation (SHM), through direct activation of this gene. AID, as we have shown, is induced by the HoxC4 homeodomain transcription factor, which binds to a conserved HoxC4/Oct site in the AICDA/Aicda promoter. Here we show that estrogen-estrogen receptor (ER) complexes do not directly activate the AID gene promoter in B cells undergoing CSR. Rather, they bind to three evolutionarily conserved and cooperative estrogen response elements (EREs) we identified in the HOXC4/HoxC4 promoter. By binding to these EREs, ERs synergized with CD154 or LPS and IL-4 signaling to up-regulate HoxC4 expression, thereby inducing AID and CSR without affecting B cell proliferation or plasmacytoid differentiation. Estrogen administration in vivo significantly potentiated CSR and SHM in the specific antibody response to the 4-hydroxy-3-nitrophenylacetyl hapten conjugated with chicken γ-globulin. Ablation of HoxC4 (HoxC4(-/-)) abrogated the estrogen-mediated enhancement of AID gene expression and decreased CSR and SHM. Thus, estrogen enhances AID expression by activating the HOXC4/HoxC4 promoter and inducing the critical AID gene activator, HoxC4.

  7. Lineage tracing of human B cells reveals the in vivo landscape of human antibody class switching

    Science.gov (United States)

    Horns, Felix; Vollmers, Christopher; Croote, Derek; Mackey, Sally F; Swan, Gary E; Dekker, Cornelia L; Davis, Mark M; Quake, Stephen R

    2016-01-01

    Antibody class switching is a feature of the adaptive immune system which enables diversification of the effector properties of antibodies. Even though class switching is essential for mounting a protective response to pathogens, the in vivo patterns and lineage characteristics of antibody class switching have remained uncharacterized in living humans. Here we comprehensively measured the landscape of antibody class switching in human adult twins using antibody repertoire sequencing. The map identifies how antibodies of every class are created and delineates a two-tiered hierarchy of class switch pathways. Using somatic hypermutations as a molecular clock, we discovered that closely related B cells often switch to the same class, but lose coherence as somatic mutations accumulate. Such correlations between closely related cells exist when purified B cells class switch in vitro, suggesting that class switch recombination is directed toward specific isotypes by a cell-autonomous imprinted state. DOI: http://dx.doi.org/10.7554/eLife.16578.001 PMID:27481325

  8. Stabilization of a class of switched nonlinear systems

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The stabilization of a class of switched nonlinear systems is investigated in the paper. The systems concerned are of (generalized) switched Byrnes-Isidori canonical form, which has all switched models in (generalized) ByrnesIsidori canonical form. First, a stability result of switched systems is obtained. Then it is used to solve the stabilization problem of the switched nonlinear control systems. In addition, necessary and sufficient conditions are obtained for a switched affine nonlinear system to be feedback equivalent to (generalized) switched Byrnes-Isidori canonical systems are presented.Finally, as an application the stability of switched lorenz systems is investigated.

  9. Genome-wide analysis reveals selective modulation of microRNAs and mRNAs by histone deacetylase inhibitor in B cells induced to undergo class switch DNA recombination and plasma cell differentiation

    Directory of Open Access Journals (Sweden)

    Tian eShen

    2015-12-01

    Full Text Available As we have suggested, epigenetic factors, such as microRNAs (miRNAs, can interact with genetic programs to regulate B cell functions, thereby informing antibody and autoantibody responses. We have shown that histone deacetylase inhibitors (HDI inhibit the differentiation events critical to the maturation of the antibody response: class-switch DNA recombination (CSR, somatic hypermutation (SHM and plasma cell differentiation, by modulating intrinsic B cell mechanisms. HDI repress the expression of AID and Blimp-1, which are critical for CSR/SHM and plasma cell differentiation, respectively, in mouse and human B cells by upregulating selected miRNAs that silenced AICDA/Aicda and PRDM1/Prdm1 mRNAs, as demonstrated by multiple qRT-PCRs (J. Immunol. 193:5933-5950, 2014. To further define the selectivity of HDI-mediated modulation of miRNA and gene expression, we performed genome-wide miRNA-Seq and mRNA-Seq analysis in B cells stimulated by LPS plus IL-4 and treated with HDI or nil. Consistent with what we have shown using qRT-PCR, these HDI-treated B cells displayed reduced expression of Aicda and Prdm1, and increased expression of miR-155, miR-181b and miR-361, which target Aicda, and miR-23b, miR-30a and miR-125b, which target Prdm1. In B cells induced to undergo CSR and plasma cell differentiation, about 23% of over 22,000 mRNAs analyzed were expressed at a significantly high copy number (more than 20 copies/cell. Only 18 (0.36% of these highly expressed mRNAs, including Aicda, Prdm1 and Xbp1, were downregulated by HDI by 50% or more. Further, only 16 (0.30% of the highly expressed mRNAs were upregulated (more than twofold by HDI. The selectivity of HDI-mediated modulation of gene expression was emphasized by unchanged expression of the genes that are involved in regulation, targeting or DNA repair processes of CSR, as well as unchanged expression of the genes encoding epigenetic regulators and factors that are important for cell signaling or

  10. Genome-Wide Analysis Reveals Selective Modulation of microRNAs and mRNAs by Histone Deacetylase Inhibitor in B Cells Induced to Undergo Class-Switch DNA Recombination and Plasma Cell Differentiation.

    Science.gov (United States)

    Shen, Tian; Sanchez, Helia N; Zan, Hong; Casali, Paolo

    2015-01-01

    As we have suggested, epigenetic factors, such as microRNAs (miRNAs), can interact with genetic programs to regulate B cell functions, thereby informing antibody and autoantibody responses. We have shown that histone deacetylase (HDAC) inhibitors (HDI) inhibit the differentiation events critical to the maturation of the antibody response: class-switch DNA recombination (CSR), somatic hypermutation (SHM), and plasma cell differentiation, by modulating intrinsic B cell mechanisms. HDI repress the expression of AID and Blimp-1, which are critical for CSR/SHM and plasma cell differentiation, respectively, in mouse and human B cells by upregulating selected miRNAs that silenced AICDA/Aicda and PRDM1/Prdm1 mRNAs, as demonstrated by multiple qRT-PCRs (J Immunol 193:5933-5950, 2014). To further define the selectivity of HDI-mediated modulation of miRNA and gene expression, we performed genome-wide miRNA-Seq and mRNA-Seq analysis in B cells stimulated by LPS plus IL-4 and treated with HDI or nil. Consistent with what we have shown using qRT-PCR, these HDI-treated B cells displayed reduced expression of Aicda and Prdm1, and increased expression of miR-155, miR-181b, and miR-361, which target Aicda, and miR-23b, miR-30a, and miR-125b, which target Prdm1. In B cells induced to undergo CSR and plasma cell differentiation, about 23% of over 22,000 mRNAs analyzed were expressed at a significantly high copy number (more than 20 copies/cell). Only 18 (0.36%) of these highly expressed mRNAs, including Aicda, Prdm1, and Xbp1, were downregulated by HDI by 50% or more. Further, only 16 (0.30%) of the highly expressed mRNAs were upregulated (more than twofold) by HDI. The selectivity of HDI-mediated modulation of gene expression was emphasized by unchanged expression of the genes that are involved in regulation, targeting, or DNA repair processes of CSR, as well as unchanged expression of the genes encoding epigenetic regulators and factors that are important for cell signaling or

  11. 中药制剂毛萼乙素对免疫球蛋白类别转换的作用%Effects of Eriocalyxin B on immunoglobulin class switch recombination

    Institute of Scientific and Technical Information of China (English)

    任建婷; 张洪信; 陆顺元; 顾鸣敏; 王铸钢

    2013-01-01

    Objective To investigate the effects of Eriocalyxin B (EriB) on immunoglobulin class switch recombination (CSR).Methods B lymphocytes (1B4.B6) were treated with lipopolysaccharide (LPS) and different doses (0 μmol/L,0.75 μmol/L,1.5 μmol/L and 2.0 μmol/L) of EriB,the proliferation of these cells was analyzed by MTT and flow cytometry,the generation of immunoglobulin,efficiency of CSR and expression of relevant genes which play important roles in CSR were examined by ELISA,RT-PCR and Western blotting respectively,and the regulation of NF-κB transcription via EriB was determined by luciferase assay.Results With the increase of EriB concentration,the proliferation and CSR of B cells were defective.EriB inhibited the activation of NF-κB1 through blocking IκBα phosphorylation and degradation.It also directly repressed the transcription level of NF-κB1.Conclusion EriB could inhibit CSR through repressing the activation of NF-κB signaling pathway.%目的 研究中药制剂毛萼乙素(EriB)对免疫球蛋白类别转换(CSR)的作用.方法 以不同剂量的EriB(0、0.75、1.5和2.0 μmol/L)处理脂多糖(LPS)刺激下的B淋巴细胞系1B4.B6细胞,采用MTT和流式细胞术检测细胞的生长状态,并分别采用ELISA、RT-PCR和Western blotting方法检测免疫球蛋白的产生及其CSR的效率以及CSR相关基因的表达水平,采用报告基因法检测EriB对NF-κB的转录调控作用.结果 随着EriB浓度的升高,B细胞增殖及CSR均出现障碍.进一步实验证实EriB通过抑制IKKα的活性阻断IκB磷酸化,进而抑制NF-κB1活化入核;同时直接抑制NF-κB1的转录从而导致其表达水平降低.结论 EriB可通过NF-κB信号通路抑制CSR的发生.

  12. HIV-1 Diversity After a Class Switch Failure

    OpenAIRE

    Kolber, Michael A.; Buendia, Patricia; Degruttola, Victor; Moore, Richard D.

    2010-01-01

    The purpose of this study is to evaluate whether the choice of a PI- or an efavirenz (EFV)-based HAART initial regimen impacts on the viral diversity after failure from a second, class-switch salvage regimen. Sequential HAART failures after a class switch were identified for which the genotypes showed evidence of signature mutations at each failure. Each second failure was required to be from a viral burden

  13. Characterization of recombination in the HLA class II region

    Energy Technology Data Exchange (ETDEWEB)

    Cullen, M.; Carrington, M. [National Cancer Institute, Frederick, MD (United States); Noble, J. [Roche Molecular Systems, Almeda, CA (United States)] [and others

    1997-02-01

    Studies of linkage disequilibrium across the HLA class II region have been useful in predicting where recombination is most likely to occur. The strong associations between genes within the 85-kb region from DQB1 to DRB1 are consistent with low frequency of recombination in this segment of DNA. Conversely, a lack of association between alleles of TAP1 and TAP2 ({approximately}15 kb) has been observed, suggesting that recombination occurs here with relatively high frequency. Much of the HLA class II region has now been sequenced, providing the tools to undertake detailed analysis of recombination. Twenty-seven families containing one or two recombinant chromosomes within the 500-kb interval between the DPB1 and DRB1 genes were used to determine patterns of recombination across this region. SSCP analysis and microsatellite typing yielded identification of 127 novel polymorphic markers distributed throughout the class II region, allowing refinement of the site of crossover in 30 class II recombinant chromosomes. The three regions where recombination was observed most frequently are as follows: the 45-kb interval between HLA-DNA and RING3 (11 cases), the 50-kb interval between DQB3 and DQB1 (6 cases), and an 8.8-kb segment of the TAP2 gene (3 cases). Six of the 10 remaining recombinants await further characterization, pending identification of additional informative markers, while four recombinants were localized to other intervals (outliers). Analysis of association between markers flanking HLA-DNA to RING3 (45 kb), as well as TAP1 to TAP2 (15 kb), by use of independent CEPH haplotypes indicated little or no linkage disequilibrium, supporting the familial recombination data. A notable sequence motif located within a region associated with increased rates of recombination consisted of a (TGGA){sub 12} tandem repeat within the TAP2 gene. 74 refs., 3 figs., 2 tabs.

  14. T-bet regulates T-independent IgG2a class switching.

    Science.gov (United States)

    Gerth, Andrea J; Lin, Ling; Peng, Stanford L

    2003-08-01

    The IgG2a Ig subclass plays a critical role in the pathogenesis of humoral autoimmunity and protection against pathogens. The T-box transcription factor T-bet has been implicated as a critical mediator of class-switch recombination (CSR) to IgG2a, but its relative importance to this process in various immune contexts remains incompletely defined. We report here that, surprisingly, T-bet is selectively required for IgG2a class switching in response to T-independent, but not T-dependent, stimuli. Specifically, T-dependent signaling through CD40, in contrast to T-independent signaling via lipopolysaccharide, can bypass a requirement for T-bet in IgG2a germline transcription and subsequent isotype switching. In contrast, T-bet-deficient B cells undergo class switching to other IgG isotypes at least as well as wild-type counterparts. Thus, T-bet is a class-specific regulator of IgG CSR and represents a unique regulator of B cell differentiation by participating in a T-independent, but not a T-dependent, activation pathway. T-bet-deficient B cells therefore represent a novel paradigm by which to investigate the regulation of humoral immune responses. PMID:12882831

  15. Ultra-Low Voltage Class AB Switched Current Memory Cell

    DEFF Research Database (Denmark)

    Igor, Mucha

    1996-01-01

    This paper presents the theoretical basis for the design of class AB switched current memory cells employing floating-gate MOS transistors, suitable for ultra-low-voltage applications. To support the theoretical assumptions circuits based on these cells were designed using a CMOS process with...

  16. Pillar switchings and acyclic embedding in mapping class group

    CERN Document Server

    Jeong, Chan-Seok

    2012-01-01

    The braid group $B_g$ is embedded in the ribbon braid group that is defined to be the mapping class group $\\Gamma_{0,(g),1}$. By gluing two copies of surface $S_{0,g+2}$ along $g+1$ holes, we get surface $S_{g,1}$. A pillar switching is a self-homeomorphism of $S_{g,1}$ which switches two pillars of surfaces by $180{}^\\circ$ horizontal rotation. We analyze the actions of pillar switchings on $\\pi_1 S_{g,1}$ and then give concrete expressions of pillar switchings in terms of standard Dehn twists. The map $\\psi: B_g \\rightarrow \\Gamma_{g,1}$ sending the generators of $B_g$ to pillar switchings on $S_{g,1}$ is defined by extending the embedding $B_g \\hookrightarrow \\Gamma_{0,(g+1),1}$. We show that this map is injective by analyzing the actions of pillar switchings on $\\pi_1 S_{g,1}$. The second part of this paper is to prove that this map induces a trivial homology homomorphism in the stable range. For the proof we use the categorical delooping. We construct a suitable monoidal 2-functor from tile category to s...

  17. Efficiency of Iepsilon promoter-directed switch recombination in GFP expression-based switch constructs works synergistically with other promoter and/or enhancer elements but is not tightly linked to the strength of transcription.

    Science.gov (United States)

    Zhang, Ke; Zhang, Ling; Yamada, Takechiyo; Vu, Michael; Lee, Anna; Saxon, Andrew

    2002-02-01

    One key unresolved issue in immunoglobulin class switch recombination (CSR) is how the accessibility of the switch region for CSR is controlled. To better understand the nature of accessibility control for human Ig CSR, we developed a novel inducible switch recombination assay based on expression of green fluorescence protein (GFP) from switch constructs undergoing substrate switch recombination (SSR). Efficient SSR depends on the cytokine-inducible Iepsilon promoter and co-stimulation with IL-4+anti-CD40. Characterization of SSR reveals that both S-S deletional recombination and S-S inversion occur. We show that the IL-4-inducible Iepsilon promoter (pIepsilon) selectively determines the efficiency of the accessibility for SSR. However, the pIepsilon-induced transcription, by itself,is not sufficient to direct efficient SSR. For efficient SSR, both pIepsilon-driven transcriptional activity and an additional promoter/enhancer-derived activity are required. The efficiency of SSR is not tightly correlated with the strength of the combined transcriptional activity. Our results suggest that the mechanism(s) underlying the transcriptional activity, e.g. DNA modification is important for controlling the accessibility for efficient switch recombination.

  18. APPLICATION OF INCREASED BREAKDOWN VOLTAGE SWITCH TO CLASS-E AMPLIFIER

    Directory of Open Access Journals (Sweden)

    Mustafa SÖNMEZ

    1998-02-01

    Full Text Available Class-E amplifier consist of a switching device (BJT or FET and a rezonant circuit. The power of amplifier depends on current and supply voltage of the transistor. The breakdown voltage of the transistor is increased to the maximum level in order to increase the power of the amplifier. Because of increasing the current increases the reverse induction, the reverse voltage creates a problem for the transistor. In this work, the increased breakdown voltage transistor Configuration is applied to class-E power amplifiers. Therefore, the reverse voltage problem is solved and supply voltage.

  19. Class switch recombination in selective IgA-deficient subjects

    DEFF Research Database (Denmark)

    Jensen, Lone Hummelshøj; Ryder, L P; Nielsen, L K;

    2006-01-01

    -beta in combination, induced IgA production, albeit lower than found in B cells from controls. The B cells from the IgA-deficient subjects were less effective in differentiating into CD138(+) X-box binding protein 1 (XBP-1)(+) plasma cells when stimulated with TGF-beta, IFN-gamma or IL-10. Interestingly, when adding...

  20. Class switch recombination in selective IgA-deficient subjects

    DEFF Research Database (Denmark)

    Jensen, Lone Hummelshøj; Ryder, L P; Nielsen, L K;

    2006-01-01

    control donors, all Caucasians. Stimulation of B cells from IgA-deficient donors with the cytokines transforming growth factor (TGF)-beta, interferon (IFN)-gamma or interleukin (IL)-10 in the presence of anti-CD40 antibodies showed reduced expression of both activation-induced cytidine deaminase (AID) and...

  1. The roles of APE1, APE2, DNA polymerase β and mismatch repair in creating S region DNA breaks during antibody class switch

    OpenAIRE

    Schrader, Carol E.; Guikema, Jeroen E.J.; Wu, Xiaoming; Stavnezer, Janet

    2008-01-01

    Immunoglobulin class switch recombination (CSR) occurs by an intrachromosomal deletion requiring generation of double-stranded DNA breaks (DSBs) in immunoglobulin switch region DNA. The initial steps of DSB formation have been elucidated: cytosine deamination by activation-induced cytidine deaminase (AID) and the generation of abasic sites by uracil-DNA glycosylase (UNG). We show that abasic sites are converted into single-strand breaks (SSBs) by apurinic/apyrimidinic endonucleases (APE1 and ...

  2. Analytical Design Equations for Class-E Power Amplifiers with Finite DC-Feed Inductance and Switch On-Resistance

    NARCIS (Netherlands)

    Acar, Mustafa; Annema, Anne Johan; Nauta, Bram

    2007-01-01

    Many critical design trade-offs of the class-E power amplifier (e.g power efficiency) are influenced by the switch on-resistance and the value of dc-feed drain inductance. In literature, the time-domain mathematical analyses of the class-E power amplifier with finite dc-feed inductance assume zero s

  3. A PTIP-PA1 subcomplex promotes transcription for IgH class switching independently from the associated MLL3/MLL4 methyltransferase complex

    DEFF Research Database (Denmark)

    Starnes, Linda M; Su, Dan; Pikkupeura, Laura M;

    2016-01-01

    Class switch recombination (CSR) diversifies antibodies for productive immune responses while maintaining stability of the B-cell genome. Transcription at the immunoglobulin heavy chain (Igh) locus targets CSR-associated DNA damage and is promoted by the BRCT domain-containing PTIP (Pax transacti...

  4. Two-output Class E Isolated dc-dc Converter at 5 MHz Switching Frequency

    OpenAIRE

    Pavlovic, Zoran; Oliver Ramírez, Jesús Angel; Alou Cervera, Pedro; García Suárez, Oscar; Prieto López, Roberto; Cobos Márquez, José Antonio

    2010-01-01

    This paper presents a two output class-E isolated dcdc converter that regulates the output voltages at fixed switching frequency. The converter is simulated at operating frequency of 5 MHz. The converter output power is 40 W and the output voltages are 15 V and 5 V. All the switches operate at zero voltage switching (ZVS) conditions for the full load range. The circuit configuration is simple with small passive components which reduce the size of the converter. The circuit also has ...

  5. Stabilization for a Class of Switched Nonlinear Systems With Novel Average Dwell Time Switching by T-S Fuzzy Modeling.

    Science.gov (United States)

    Zhao, Xudong; Yin, Yunfei; Niu, Ben; Zheng, Xiaolong

    2016-08-01

    In this paper, the problem of switching stabilization for a class of switched nonlinear systems is studied by using average dwell time (ADT) switching, where the subsystems are possibly all unstable. First, a new concept of ADT is given, which is different from the traditional definition of ADT. Based on the new proposed switching signals, a sufficient condition of stabilization for switched nonlinear systems with unstable subsystems is derived. Then, the T-S fuzzy modeling approach is applied to represent the underlying nonlinear system to make the obtained condition easily verified. A novel multiple quadratic Lyapunov function approach is also proposed, by which some conditions are provided in terms of a set of linear matrix inequalities to guarantee the derived T-S fuzzy system to be asymptotically stable. Finally, a numerical example is given to demonstrate the effectiveness of our developed results. PMID:26316288

  6. Optical packet switched design with relaxed maximum hardware parameters and high service-class granularity for flexible switch node dimensioning

    DEFF Research Database (Denmark)

    Nord, Martin

    2004-01-01

    This work proposes a quality of service differentiation algorithm, improving the service class granularity and isolation of our recently presented waveband plane based design. The design aims at overcoming potential hardware limitations and increasing the switch node dimensioning flexibility in c...

  7. A Class of Stochastic Hybrid Systems with State-Dependent Switching Noise

    DEFF Research Database (Denmark)

    Leth, John-Josef; Rasmussen, Jakob Gulddahl; Schiøler, Henrik;

    2012-01-01

    In this paper, we develop theoretical results based on a proposed method for modeling switching noise for a class of hybrid systems with piecewise linear partitioned state space, and state-depending switching. We devise a stochastic model of such systems, whose global dynamics is governed...

  8. Stabilization for a class of second-order switched systems with saturation constrains

    Institute of Scientific and Technical Information of China (English)

    SONG Yang; GU Yu-qi; FEI Min-rui

    2009-01-01

    This paper proposes a global stabilization method for a class of planar switched systems with input saturation constrains by using a state feedback and switching strategy.This method is proved to be effective by analyzing the characteristics of the trajectory of second-order linear systems with input saturation.

  9. Resolution by unassisted Top3 points to template switch recombination intermediates during DNA replication.

    Science.gov (United States)

    Glineburg, M Rebecca; Chavez, Alejandro; Agrawal, Vishesh; Brill, Steven J; Johnson, F Brad

    2013-11-15

    The evolutionarily conserved Sgs1/Top3/Rmi1 (STR) complex plays vital roles in DNA replication and repair. One crucial activity of the complex is dissolution of toxic X-shaped recombination intermediates that accumulate during replication of damaged DNA. However, despite several years of study the nature of these X-shaped molecules remains debated. Here we use genetic approaches and two-dimensional gel electrophoresis of genomic DNA to show that Top3, unassisted by Sgs1 and Rmi1, has modest capacities to provide resistance to MMS and to resolve recombination-dependent X-shaped molecules. The X-shaped molecules have structural properties consistent with hemicatenane-related template switch recombination intermediates (Rec-Xs) but not Holliday junction (HJ) intermediates. Consistent with these findings, we demonstrate that purified Top3 can resolve a synthetic Rec-X but not a synthetic double HJ in vitro. We also find that unassisted Top3 does not affect crossing over during double strand break repair, which is known to involve double HJ intermediates, confirming that unassisted Top3 activities are restricted to substrates that are distinct from HJs. These data help illuminate the nature of the X-shaped molecules that accumulate during replication of damaged DNA templates, and also clarify the roles played by Top3 and the STR complex as a whole during the resolution of replication-associated recombination intermediates.

  10. Triggers of IgE class switching and allergy development

    DEFF Research Database (Denmark)

    Poulsen, Lars K.; Hummelshoj, Lone

    2007-01-01

    type 2 (Th2) T cell subset are the actions of thymic stromal lymphopoietin (TSLP) on dendritic cells and the OX40 ligand on CD4+ T cells. In order for a B lymphocyte to switch to IgE production it needs two signals provided by a Th2 cell in the form of the cytokines interleukin (IL-) 4/IL-13...

  11. Investigation of switching frequency variations in self-oscillating class D amplifiers

    DEFF Research Database (Denmark)

    Nielsen, Dennis; Knott, Arnold; Pfaffinger, Gerhard;

    2009-01-01

    Class D audio amplifiers have gained significant influence in sound reproduction due to their high efficiency. One of the most commonly used control methods in class D amplifiers is known as self-oscillation. An parameter of key interest in self-oscillating class D amplifiers is the switching...... frequency, which can be directly related to the performance of the amplifier. This paper will clearify the myth of the switching frequency through investigation of its dependency on modulation index and reference frequency. Validation is done using simulations and an 50 W amplifier providing 0...

  12. Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium.

    Directory of Open Access Journals (Sweden)

    Frances Humby

    2009-01-01

    Full Text Available BACKGROUND: Follicular structures resembling germinal centres (GCs that are characterized by follicular dendritic cell (FDC networks have long been recognized in chronically inflamed tissues in autoimmune diseases, including the synovium of rheumatoid arthritis (RA. However, it is debated whether these ectopic structures promote autoimmunity and chronic inflammation driving the production of pathogenic autoantibodies. Anti-citrullinated protein/peptide antibodies (ACPA are highly specific markers of RA, predict a poor prognosis, and have been suggested to be pathogenic. Therefore, the main study objectives were to determine whether ectopic lymphoid structures in RA synovium: (i express activation-induced cytidine deaminase (AID, the enzyme required for somatic hypermutation and class-switch recombination (CSR of Ig genes; (ii support ongoing CSR and ACPA production; and (iii remain functional in a RA/severe combined immunodeficiency (SCID chimera model devoid of new immune cell influx into the synovium. METHODS AND FINDINGS: Using immunohistochemistry (IHC and quantitative Taqman real-time PCR (QT-PCR in synovial tissue from 55 patients with RA, we demonstrated that FDC+ structures invariably expressed AID with a distribution resembling secondary lymphoid organs. Further, AID+/CD21+ follicular structures were surrounded by ACPA+/CD138+ plasma cells, as demonstrated by immune reactivity to citrullinated fibrinogen. Moreover, we identified a novel subset of synovial AID+/CD20+ B cells outside GCs resembling interfollicular large B cells. In order to gain direct functional evidence that AID+ structures support CSR and in situ manufacturing of class-switched ACPA, 34 SCID mice were transplanted with RA synovium and humanely killed at 4 wk for harvesting of transplants and sera. Persistent expression of AID and Igamma-Cmu circular transcripts (identifying ongoing IgM-IgG class-switching was observed in synovial grafts expressing FDCs/CD21L

  13. A Reduced Switch Voltage Stress Class E Power Amplifier Using Harmonic Control Network

    Directory of Open Access Journals (Sweden)

    Ali Reza Zirak

    2016-05-01

    Full Text Available In this paper, a harmonic control network (HCN is presented to reduce the voltage stress (maximum MOSFET voltage of the class E power amplifier (PA. Effects of the HCN on the amplifier specifications are investigated. The results show that the proposed HCN affects several specifications of the amplifier, such as drain voltage, switch current, output power capability (Cp factor, and drain impedance. The output power capability of the presented amplifier is also improved, compared with the conventional class E structure. High-voltage stress limits the design specifications of the desired amplifier. Therefore, several limitations can be removed with the reduced switch voltage. According to the results, the maximum drain voltage for the presented amplifier is reduced and subsequently, the output power capability is increased about 25% using the presented structure. Zero-voltage switching condition (ZVS and zero-voltage derivative switching condition (ZVDS are assumed in the design procedure. These two conditions are essential for high efficiency achievement in various classes of switching amplifiers. A class E PA with operating frequency of 1 MHz is designed and simulated using advanced design system (ADS and PSpice software. The theory and simulated results are in good agreement.

  14. The DNA glycosylases Ogg1 and Nth1 do not contribute to Ig class switching in activated mouse splenic B cells.

    Directory of Open Access Journals (Sweden)

    Anna J Ucher

    Full Text Available During activation of B cells to undergo class switching, B cell metabolism is increased, and levels of reactive oxygen species (ROS are increased. ROS can oxidize DNA bases resulting in substrates for the DNA glycosylases Ogg1 and Nth1. Ogg1 and Nth1 excise oxidized bases, and nick the resulting abasic sites, forming single-strand DNA breaks (SSBs as intermediates during the repair process. In this study, we asked whether splenic B cells from mice deficient in these two enzymes would show altered class switching and decreased DNA breaks in comparison with wild-type mice. As the c-myc gene frequently recombines with the IgH S region in B cells induced to undergo class switching, we also analyzed the effect of deletion of these two glycosylases on DSBs in the c-myc gene. We did not detect a reduction in S region or c-myc DSBs or in class switching in splenic B cells from Ogg1- or Nth1-deficient mice or from mice deficient in both enzymes.

  15. Constant Switching Frequency Self-Oscillating Controlled Class-D Amplifiers

    DEFF Research Database (Denmark)

    Nguyen-Duy, Khiem; Knott, Arnold; Andersen, Michael A. E.

    2014-01-01

    varies with the ratio of the output voltage to the input rail voltage. In other words, the switching frequency varies with the duty cycle of the output. The drop in the frequency results in lower control bandwidth and higher output voltage ripple, which are undesirable. This paper proposes a new self......The self-oscillating control approach has been used extensively in class-D amplifiers. It has several advantages such as high bandwidth and high audio performance. However, one of the primary disadvantages in a self-oscillating controlled system is that the switching frequency of the amplifier......-oscillating control scheme that maintains a constant switching frequency over the full range of output voltage. The frequency difference is processed by a compensator whose output adjusts the total loop gain of the control system. It has been proven by simulation that a con-stant switching frequency self...

  16. A Study of Code-Switching in Students’Talk in College English Class

    Institute of Scientific and Technical Information of China (English)

    席红梅; 赵快

    2015-01-01

    Code-switching between English and Chinese usually occurs in students’talk when they are involved in taking com⁃municative language activities in college English class. This paper studies the situations in which students are likely to use code-switching and analyzes it from the perspective of the mental world in Verscheren ’s Adaptation Theory. It shows that inadequate mastery of English language, cultural differences and the improper adjustment to context may lead to students ’using of code-switching. It also shows that the use of code-switching in students’talk adapts to students’cognitive elements and emotive ele⁃ments as well.

  17. Investigation of switching frequency variations and EMI properties in self-oscillating class D amplifiers

    DEFF Research Database (Denmark)

    Nielsen, Dennis; Knott, Arnold; Pfaffinger, Gerhard;

    2009-01-01

    Class D audio amplifiers have gained significant influence in sound reproduction due to their high efficiency. One of the most commonly used control methods in these amplifiers is self-oscillation. A parameter of key interest in self-oscillating amplifiers is the switching frequency, which is kno...

  18. Ultra Low Voltage Class AB Switched Current Memory Cells Based on Floating Gate Transistors

    DEFF Research Database (Denmark)

    Mucha, Igor

    1999-01-01

    A proposal for a class AB switched current memory cell, suitable for ultra-low-voltage applications is presented. The proposal employs transistors with floating gates, allowing to build analog building blocks for ultralow supply voltage operation also in CMOS processes with high threshold voltages...

  19. S-band class-F power amplifier with integrated switched mode power supply

    NARCIS (Netherlands)

    Bent, G. van der; Hek, A.P. de; Geurts, S.; Brouzes, H.; Vliet, F.E. van

    2012-01-01

    An S-band radar transmitter MMIC is reported containing a class-F power amplifier and a switched mode power supply. The integration of the power supply offers the possibility to optimize the power amplifier bias voltage for each individual device in a AESA antenna. This has several advantages such a

  20. Constant Switching Frequency Self-Oscillating Controlled Class-D Amplifiers

    OpenAIRE

    Nguyen-Duy, Khiem; Knott, Arnold; Andersen, Michael A. E.

    2014-01-01

    The self-oscillating control approach has been used extensively in class-D amplifiers. It has several advantages such as high bandwidth and high audio performance. However, one of the primary disadvantages in a self-oscillating controlled system is that the switching frequency of the amplifier varies with the ratio of the output voltage to the input rail voltage. In other words, the switching frequency varies with the duty cycle of the output. The drop in the frequency results in lower contro...

  1. Passivity and Passification for a Class of Uncertain Switched Stochastic Time-Delay Systems.

    Science.gov (United States)

    Lian, Jie; Shi, Peng; Feng, Zhi

    2013-02-01

    This paper is concerned with the problems of passivity and passification for a class of uncertain switched systems subject to stochastic disturbance and time-varying delay. The passivity property is adopted to analyze the influence of the external disturbance on such systems to achieve prescribed attenuation levels. Based on average dwell time approach, free-weighting matrix method, and Jensen's integral inequality, delay-dependent sufficient conditions are obtained in terms of linear matrix inequalities, which ensure the uncertain switched stochastic time-delay system to be robustly mean-square exponentially stable and stochastically passive. Then, the switched passive controllers are synthesized by linearization techniques. Finally, two numerical examples are given to illustrate the effectiveness of the proposed methods.

  2. Dynamic changes in binding of immunoglobulin heavy chain 3' regulatory region to protein factors during class switching.

    Science.gov (United States)

    Chatterjee, Sanjukta; Ju, Zhongliang; Hassan, Rabih; Volpi, Sabrina A; Emelyanov, Alexander V; Birshtein, Barbara K

    2011-08-19

    The 3' regulatory region (3' RR) of the Igh locus works at long distances on variable region (V(H)) and switch region (I) region promoters to initiate germ line (non-coding) transcription (GT) and promote class switch recombination (CSR). The 3' RR contains multiple elements, including enhancers (hs3a, hs1.2, hs3b, and hs4) and a proposed insulator region containing CTCF (CCCTC-binding factor) binding sites, i.e. hs5/6/7 and the downstream region ("38"). Notably, deletion of each individual enhancer (hs3a-hs4) has no significant phenotypic consequence, suggesting that the 3' RR has considerable structural flexibility in its function. To better understand how the 3' RR functions, we identified transcription factor binding sites and used chromatin immunoprecipitation (ChIP) assays to monitor their occupancy in splenic B cells that initiate GT and undergo CSR (LPS±IL4), are deficient in GT and CSR (p50(-/-)), or do not undergo CSR despite efficient GT (anti-IgM+IL4). Like 3' RR enhancers, hs5-7 and the 38 region were observed to contain multiple Pax5 binding sites (in addition to multiple CTCF sites). We found that the Pax5 binding profile to the 3' RR dynamically changed during CSR independent of the specific isotype to which switching was induced, and binding focused on hs1.2, hs4, and hs7. CTCF-associated and CTCF-independent cohesin interactions were also identified. Our observations are consistent with a scaffold model in which a platform of active protein complexes capable of facilitating GT and CSR can be formed by varying constellations of 3' RR elements.

  3. Rules of donor preference in saccharomyces mating-type gene switching revealed by a competition assay involving two types of recombination.

    Science.gov (United States)

    Wu, X; Wu, C; Haber, J E

    1997-10-01

    Mating type (MAT) switching in Saccharomyces cerevisiae is initiated by a double-strand break (DSB) created at MAT by HO endonuclease. MATa cells activate the entire left arm of chromosome III; thus MATa preferentially recombines with the silent donor HML. In contrast, MAT alpha cells inactivate the left arm, including HML, and thus preferentially recombine with HMR, 100 kb to the right of MAT. We present a novel competition assay, in which the DSB at MAT can be repaired either by MAT switching or by single-strand annealing (SSA) between two URA3 genes flanking MAT. With preferred donors, MATa or MAT alpha switching occurs 65-70% of the time in competition with SSA. When HML is deleted, 40% of MATa cells recombine with the "wrong" donor HMR; however, when HMR is deleted, only 18% of MAT alpha cells recombine with HML. In interchromosomal switching, with donors on chromosome III and MAT on chromosome V, MATa retains its strong preference for HML and switching is efficient, when the chromosome III recombination enhancer is present. However, MAT alpha donor preference is lost and interchromosomal switching is very inefficient. These experiments demonstrate the utility of using competition between two outcomes to measure the relative efficiency of recombination.

  4. Mice lacking Sμ tandem repeats maintain RNA polymerase patterns but exhibit histone modification pattern shifts linked to class switch site locations.

    Science.gov (United States)

    Balter, Barbara B; Ciccone, David N; Oettinger, Marjorie A; Selsing, Erik

    2012-08-01

    Antibody switching involves class switch recombination (CSR) events between switch (S) regions located upstream of heavy chain constant (C) genes. Mechanisms targeting CSR to S-regions are not clear. Deletion of Sμ tandem repeat (SμTR) sequences causes CSR to shift into downstream regions that do not undergo CSR in WT B-cells, including the Cμ-region. We now find that, in SμTR(-/-) B cells, Sμ chromatin histone modification patterns also shift downstream relative to WT and coincide with SμTR(-/-) CSR locations. Our results suggest that histone H3 acetylation and methylation are involved in accessibility of switch regions and that these modifications are not dependent on the underlying sequence, but may be controlled by the location of upstream promoter or regulatory elements. Our studies also show RNA polymerase II (RNAPII) loading increases in the Eμ/Iμ region in stimulated B cells; these increases are independent of SμTR sequences. Longer Sμ deletions have been reported to eliminate increases in RNAPII density, therefore we suggest that sequences between Iμ and Sμ (possibly the Iμ splicing region as well as G-tracts that are involved in stable RNA:DNA complex formation during transcription) might control the RNAPII density increases.

  5. Non-fragile hybrid guaranteed cost control for a class of uncertain switched linear systems

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    This paper focuses on the problem of non-fragile hybrid guaranteed cost control for a class of uncertain switched linear systems. The controller gain to be designed is assumed to have additive gain variations. Based on multiple-Lyapunov function technique, the design of non-fragile hybrid guaranteed cost controllers is derived to make the corresponding closed-loop system asymptotically stable for all admissible uncertainties. Furthermore, a convex optimization approach with LMIs constraints is introduced to select the optimal non-fragile guaranteed cost controllers. Finally, a simulation example illustrates the effectiveness of the proposed approach.

  6. Design of Filter for a Class of Switched Linear Neutral Systems

    Directory of Open Access Journals (Sweden)

    Caiyun Wu

    2013-01-01

    Full Text Available This paper is concerned with the filtering problem for a class of switched linear neutral systems with time-varying delays. The time-varying delays appear not only in the state but also in the state derivatives. Based on the average dwell time approach and the piecewise Lyapunov functional technique, sufficient conditions are proposed for the exponential stability of the filtering error dynamic system. Then, the corresponding solvability condition for a desired filter satisfying a weighted performance is established. All the conditions obtained are delay-dependent. Finally, two numerical examples are given to illustrate the effectiveness of the proposed theory.

  7. Insertional events as well as translocations may arise during aberrant immunoglobulin switch recombination in a patient with multiple myeloma.

    Science.gov (United States)

    Pratt, G; Fenton, J A; Davies, F E; Rawstron, A C; Richards, S J; Collins, J E; Owen, R G; Jack, A S; Smith, G M; Morgan, G J

    2001-02-01

    The majority of patients with multiple myeloma have translocations involving the immunoglobulin heavy chain switch regions on chromosome 14q32 and a promiscuous range of partner chromosomes. We describe a patient with an insertion of 132 bp of chromosome 22q12 sequence into the 5' region flanking S(mu) on chromosome 14q32. The 132 bp region from chromosome 22q12 contains the whole of exon 3 from a novel gene of unknown function in man. The significance of such insertional events remains unclear. The description of insertional events occurring as a result of abnormal switch recombination suggests that, in myeloma, dysregulation of oncogenes may occur by a mechanism other than chromosomal translocation.

  8. Disodium cromoglycate inhibits S mu-->S epsilon deletional switch recombination and IgE synthesis in human B cells

    OpenAIRE

    1994-01-01

    IgE synthesis requires interleukin 4 (IL-4) and a T-B cell interaction that involves the B cell antigen CD40 and its ligand expressed on activated T cells. IL-4 induces epsilon germline transcription whereas ligation of CD40 results in deletional S mu-->S epsilon switch recombination, expression of mature epsilon transcripts, and IgE synthesis and secretion. We demonstrate that disodium cromoglycate (DSCG), a drug commonly used for the prophylactic treatment of allergic disease, inhibits T ce...

  9. A Butter Aroma Recombinate Activates Human Class-I Odorant Receptors.

    Science.gov (United States)

    Geithe, Christiane; Andersen, Gaby; Malki, Agne; Krautwurst, Dietmar

    2015-11-01

    With ∼400 olfactory G protein-coupled receptors (GPCR), humans sensitively perceive ∼230 key aroma compounds as best natural agonists of ∼10000 food volatiles. An understanding of odorant coding, thus, critically depends on the knowledge about interactions of key food aroma chemicals and their mixtures with their cognate receptors. Genetically designed test cell systems enable the screening, deorphaning, and characterization of single odorant receptors (OR). This study shows for the food aroma-specific and quantitative butter aroma recombinate, and its single components, specific in vitro class-I OR activity patterns, as well as the activation of selected OR in a concentration-dependent manner. Recently, chemosensory receptors, especially class-I OR, were demonstrated to be expressed on blood leukocytes, which may encounter foodborne aroma compounds postprandially. This study shows that butter aroma recombinate induced chemotaxis of isolated human neutrophils in a defined gradient, and in a concentration-dependent and pertussis toxin-sensitive manner, suggesting at least a GPCR-mediated activation of blood leukocytes by key food odorants.

  10. Observer-Based Robust Tracking Control for a Class of Switched Nonlinear Cascade Systems

    Directory of Open Access Journals (Sweden)

    Ben Niu

    2013-01-01

    Full Text Available This paper is devoted to robust output feedback tracking control design for a class of switched nonlinear cascade systems. The main goal is to ensure the global input-to-state stable (ISS property of the tracking error nonlinear dynamics with respect to the unknown structural system uncertainties and external disturbances. First, a nonlinear observer is constructed through state transformation to reconstruct the unavailable states, where only one parameter should be determined. Then, by virtue of the nonlinear sliding mode control (SMC, a discontinuous nonlinear output feedback controller is designed using a backstepping like design procedure to ensure the ISS property. Finally, an example is provided to show the effectiveness of the proposed approach.

  11. Immunogenicity of recombinant class 1 protein from Neisseria meningitidis refolded into phospholipid vesicles and detergent.

    Science.gov (United States)

    Niebla, O; Alvarez, A; Martín, A; Rodríguez, A; Delgado, M; Falcón, V; Guillén, G

    2001-05-14

    The possibility of eliciting bactericidal antibodies against a recombinant class 1 protein (P1) from Neisseria meningitidis, joined to the first 45 amino acids of the neisserial LpdA protein (PM82), was examined. P1 was produced in Escherichia coli as intracellular inclusion bodies, from which it was purified and reconstituted by (a) inclusion into phospholipid vesicles and detergent and (b) refolding in 0.1% SDS. When Balb/c mice were immunised, high titres of subtype-specific bactericidal antibodies against P1 were obtained in both cases. These results suggest that in spite of being a denaturing agent, it is possible to use SDS to reconstitute the P1 protein in a conformation that exposes the immunodominat regions.

  12. Expression and characterization of recombinant single-chain salmon class I MHC fused with beta2-microglobulin with biological activity

    DEFF Research Database (Denmark)

    Zhao, Heng; Stet, René J M; Skjødt, Karsten;

    2008-01-01

    Heterodimeric class I major histocompatibility complex (MHC) molecules consist of a putative 45-kDa heavy chain and a 12-kDa beta2-microglobulin (beta2m) light chain. The knowledge about MHC genes in Atlantic salmon accumulated during the last decade has allowed us to generate soluble and stable...... antibodies were successfully produced against both the MHC class I heavy chain and beta(2)m, and showed binding to the recombinant molecule. The recombinant complex Sasabeta2mUBA*0301 was expressed and isolated; the production was scaled up by adjusting to its optimal conditions. Subsequently...

  13. Finite-time H∞ control for a class of discrete-time switched time-delay systems with quantized feedback

    Science.gov (United States)

    Song, Haiyu; Yu, Li; Zhang, Dan; Zhang, Wen-An

    2012-12-01

    This paper is concerned with the finite-time quantized H∞ control problem for a class of discrete-time switched time-delay systems with time-varying exogenous disturbances. By using the sector bound approach and the average dwell time method, sufficient conditions are derived for the switched system to be finite-time bounded and ensure a prescribed H∞ disturbance attenuation level, and a mode-dependent quantized state feedback controller is designed by solving an optimization problem. Two illustrative examples are provided to demonstrate the effectiveness of the proposed theoretical results.

  14. Diversity of metalloproteinases in Bothrops neuwiedi snake venom transcripts: evidences for recombination between different classes of SVMPs

    Directory of Open Access Journals (Sweden)

    Valente Richard H

    2011-11-01

    Full Text Available Abstract Background Snake venom metalloproteinases (SVMPs are widely distributed in snake venoms and are versatile toxins, targeting many important elements involved in hemostasis, such as basement membrane proteins, clotting proteins, platelets, endothelial and inflammatory cells. The functional diversity of SVMPs is in part due to the structural organization of different combinations of catalytic, disintegrin, disintegrin-like and cysteine-rich domains, which categorizes SVMPs in 3 classes of precursor molecules (PI, PII and PIII further divided in 11 subclasses, 6 of them belonging to PII group. This heterogeneity is currently correlated to genetic accelerated evolution and post-translational modifications. Results Thirty-one SVMP cDNAs were full length cloned from a single specimen of Bothrops neuwiedi snake, sequenced and grouped in eleven distinct sequences and further analyzed by cladistic analysis. Class P-I and class P-III sequences presented the expected tree topology for fibrinolytic and hemorrhagic SVMPs, respectively. In opposition, three distinct segregations were observed for class P-II sequences. P-IIb showed the typical segregation of class P-II SVMPs. However, P-IIa grouped with class P-I cDNAs presenting a 100% identity in the 365 bp at their 5' ends, suggesting post-transcription events for interclass recombination. In addition, catalytic domain of P-IIx sequences segregated with non-hemorrhagic class P-III SVMPs while their disintegrin domain grouped with other class P-II disintegrin domains suggesting independent evolution of catalytic and disintegrin domains. Complementary regions within cDNA sequences were noted and may participate in recombination either at DNA or RNA levels. Proteins predicted by these cDNAs show the main features of the correspondent classes of SVMP, but P-IIb and P-IIx included two additional cysteines cysteines at the C-termini of the disintegrin domains in positions not yet described. Conclusions In

  15. Stabilization of a class of discrete-time switched systems via observer-based output feedback

    Institute of Scientific and Technical Information of China (English)

    Jiao LI; Yuzhong LIU

    2007-01-01

    In this paper, observer-based static output feedback control problem for discrete-time uncertain switched systems is investigated under an arbitrary switching rule. The main method used in this note is combining switched. Lyapunov function (SLF) method with Finsler's Lemma. Based on linear matrix inequality (LMI) a less conservative stability condition is established and this condition allows extra degree of freedom for stability analysis. Finally, a simulation example is given to illustrate the efficiency of the result.

  16. Robust H∞ Control for a Class of Uncertain Switched Fuzzy Time-Delay Systems Based on T-S Models

    Directory of Open Access Journals (Sweden)

    Yang Cui

    2013-01-01

    Full Text Available The problem of robust H∞ control for a class of uncertain switched fuzzy time-delay systems is discussed for system described by T-S fuzzy model with Lyapunov stable theory and linear matrix inequality approach. A sufficient condition in terms of the LMI is derived such that the stability of the closed-loop systems is guaranteed. The continuous state feedback controller is built to ensure the asymptotically stable closed-loop system for all allowable uncertainties, with the switching law designed to implement the global asymptotic stability of uncertain switched fuzzy time-delay systems. In this model, each and every subsystem of the switched systems is an uncertain fuzzy one to which the parallel distributed compensation (PDC controller of each sub fuzzy system system is proposed with its main condition given in a more solvable form of convex combinations. Such a switched control system is highly robust to varying parameters. A simulation shows the feasibility and effectiveness of the design method.

  17. Novel conditions on exponential stability of a class of delayed neural networks with state-dependent switching.

    Science.gov (United States)

    Zhang, Guodong; Shen, Yi

    2015-11-01

    This paper is concerned with the global exponential stability on a class of delayed neural networks with state-dependent switching. Under the novel conditions, some sufficient criteria ensuring exponential stability of the proposed system are obtained. In particular, the obtained conditions complement and improve earlier publications on conventional neural networks with continuous or discontinuous right-hand side. Numerical simulations are also presented to illustrate the effectiveness of the obtained results.

  18. Delay-dependent stability and stabilization of a class of linear switched time-varying delay systems

    Institute of Scientific and Technical Information of China (English)

    Zhang Lixian; Wang Changhong; Goo Huijun

    2007-01-01

    The stability and stabilization of a class of linear switched time-varying delay systems are investigated.A piecewise quadratic Lyapunov function (PWQLF) is constructed and is used to obtain the stability conditions based on the linear matrix inequalities (LMIs).The stabilizing controller for this class of system is then designed and the solution of the desired controller can be obtained by a cone complementary linearization algorithm.Numerical examples are provided to illustrate the less conservativeness of the new stability and the validity of the controller design procedures.

  19. An approach to mapping haplotype-specific recombination sites in human MHC class III

    Energy Technology Data Exchange (ETDEWEB)

    Levo, A.; Westman, P.; Partanen, J. [Finnish Red Cross Blood Transfusion Service, Helsinki (Finland)

    1996-12-31

    Studies of the major histocompatibility complex (MHC) in mouse indicate that the recombination sites are not randomly distributed and their occurrence is haplotype-dependent. No data concerning haplotype-specific recombination sites in human are available due to the low number of informative families. To investigate haplotype-specific recombination sites in human MHC, we describe an approach based on identification of recombinant haplotypes derived from one conserved haplotype at the population level. The recombination sites were mapped by comparing polymorphic markers between the recombinant and assumed original haplotypes. We tested this approach on the extended haplotype HLA A3; B47; Bf{sup *}F; C4A{sup *}1; C4B{sup *}Q0; DR7, which is most suitable for this analysis. First, it carries a number of rare markers, and second, the haplotype, albeit rare in the general population, is frequent in patients with 21-hydroxylase (21OH) defect. We observed recombinants derived from this haplotype in patients with 21OH defect. All these haplotypes had the centromeric part (from Bf to DR) identical to the original haplotype, but they differed in HLA A and B. We therefore assumed that they underwent recombinations in the segment that separates the Bf and HLA B genes. Polymorphic markers indicated that all break points mapped to two segments near the TNF locus. This approach makes possible the mapping of preferential recombination sites in different haplotypes. 20 refs., 1 fig., 1 tab.

  20. Classes in Translating and Interpreting Produce Differential Gains in Switching and Updating

    Science.gov (United States)

    Dong, Yanping; Liu, Yuhua

    2016-01-01

    The present longitudinal study was intended to investigate whether the two bilingual experiences of written translation and consecutive interpreting (featured with similar language switching experience but different processing demands) would produce different cognitive control effects in young adults. Three groups of Chinese–English young adult bilinguals, who differed mainly in their half-year long bilingual experience: one for general L2 training, one for written translation and one for oral consecutive interpreting, were tested twice on the number Stroop, switching color-shape and N-back tasks. The results show that the interpreting experience produced significant cognitive advantages in switching (switch cost) and updating, while the translating experience produced marginally significant improvements in updating. The findings indicate that the experience of language switching under higher processing demands brings more domain-general advantages, suggesting that processing demand may be a decisive factor for the presence or absence of the hot-debated bilingual advantages. PMID:27625620

  1. H∞ Control Based on LMIs for a Class of Time-delay Switched Systems

    Institute of Scientific and Technical Information of China (English)

    Chun-ming LI; Xue-min TIAN

    2010-01-01

    The problem of H∞ stability analysis and control synthesis of switched systems with delayed states under arbitrary switching laws is considered. By means of Lyapunov function and linear matrix inequality tools, sufficient condition of H∞ stability is presented in terms of linear matrix inequalities. Furthermore, the robust H∞ control synthesis via state feedback and output feedback is studied. Finally, a numerical example is given to demonstrate the effectiveness of the proposed method.

  2. A High-Voltage class-D power amplifier with switching frequency regulation for improved high-efficiency output power range

    NARCIS (Netherlands)

    Ma, Haifeng; Zee, van der Ronan; Nauta, Bram

    2015-01-01

    This paper describes the power dissipation analysis and the design of an efficiency-improved high-voltage class-D power amplifier. The amplifier adaptively regulates its switching frequency for optimal power efficiency across the full output power range. This is based on detecting the switching outp

  3. High-level recombinant protein production in CHO cells using an adenoviral vector and the cumate gene-switch.

    Science.gov (United States)

    Gaillet, Bruno; Gilbert, Rénald; Amziani, Rachid; Guilbault, Claire; Gadoury, Christine; Caron, Antoine W; Mullick, Alaka; Garnier, Alain; Massie, Bernard

    2007-01-01

    To facilitate and accelerate the production of eukaryotic proteins with correct post-translational modifications, we have developed a protein production system based on the transduction of Chinese hamster ovary (CHO) cells using adenovirus vectors (AdVs). We have engineered a CHO cell line (CHO-cTA) that stably expresses the transactivator (cTA) of our newly developed cumate gene-switch transcription system. This cell line is adapted to suspension culture and can grow in serum-free and protein-free medium. To increase the transduction level of AdVs, we have also generated a cell line (CHO-cTA-CAR) that expresses additional amounts of the coxackievirus and adenovirus receptor (CAR) on its surface. Recombinant protein production was tested using an AdV carrying the secreted alkaline phosphatase (SEAP) under the control of the CR5 promoter, which is strongly and specifically activated by binding to cTA. The SEAP expression was linked to the expression of the green fluorescent protein (GFP) through an internal ribosome entry site (IRES) to facilitate titration of the AdV. We monitored SEAP expression on a daily basis for 9 days after transduction of CHO-cTA and CHO-cTA-CAR using different quantities of AdVs at 37 and 30 degrees C. Incubation at the latter temperature increased the production of SEAP at least 10-fold, and the presence of CAR increased the transduction level of the AdV. Maximum SEAP production (63 mg/L) was achieved at 6-7 days post-infection at 30 degrees C by transducing CHO-cTA-CAR with 500 infectious particles/cell. Because numerous AdVs can now be generated within a few weeks and large-scale production of AdVs is now a routine procedure, this system could be used to produce rapidly milligram quantities of a battery of recombinant proteins as well as for large-scale protein production.

  4. A Single Residue Switch for Mg2+-dependent Inhibition Characterizes Plant Class II Diterpene Cyclases from Primary and Secondary Metabolism*

    Science.gov (United States)

    Mann, Francis M.; Prisic, Sladjana; Davenport, Emily K.; Determan, Mara K.; Coates, Robert M.; Peters, Reuben J.

    2010-01-01

    Class II diterpene cyclases mediate the acid-initiated cycloisomerization reaction that serves as the committed step in biosynthesis of the large class of labdane-related diterpenoid natural products, which includes the important gibberellin plant hormones. Intriguingly, these enzymes are differentially susceptible to inhibition by their Mg2+ cofactor, with those involved in gibberellin biosynthesis being more sensitive to such inhibition than those devoted to secondary metabolism, which presumably limits flux toward the potent gibberellin phytohormones. Such inhibition has been suggested to arise from intrasteric Mg2+ binding to the DXDD motif that cooperatively acts as the catalytic acid, whose affinity must then be modulated in some fashion. While further investigating class II diterpene cyclase catalysis, we discovered a conserved basic residue that seems to act as a counter ion to the DXDD motif, enhancing the ability of aspartic acid to carry out the requisite energetically difficult protonation of a carbon-carbon double bond and also affecting inhibitory Mg2+ binding. Notably, this residue is conserved as a histidine in enzymes involved in gibberellin biosynthesis and as an arginine in those dedicated to secondary metabolism. Interchanging the identity of these residues is sufficient to switch the sensitivity of the parent enzyme to inhibition by Mg2+. These striking findings indicate that this is a single residue switch for Mg2+ inhibition, which not only supports the importance of this biochemical regulatory mechanism in limiting gibberellin biosynthesis, but the importance of its release, presumably to enable higher flux, into secondary metabolism. PMID:20430888

  5. Ig synthesis and class switching do not require the presence of the hs4 enhancer in the 3' IgH regulatory region.

    Science.gov (United States)

    Vincent-Fabert, Christelle; Truffinet, Véronique; Fiancette, Remi; Cogné, Nadine; Cogné, Michel; Denizot, Yves

    2009-06-01

    Several studies have reported that regulatory elements located 3' of the IgH locus (namely hs3a, hs1,2, hs3b, and hs4) might play a role during class switch recombination (CSR) and Ig synthesis. While individual deletion of hs3a or hs1,2 had no effect, pairwise deletion of hs3b (an inverted copy of hs3a) and hs4 markedly affected CSR and Ig expression. Among these two elements, hs4 was tentatively presented with the master role due to its unique status within the 3' regulatory region: distal position outside repeated regions, early activation in pre-B cells, strong activity throughout B cell ontogeny. To clarify its role, we generated mice with a clean deletion of the hs4 after replacement with a floxed neo(R) cassette. Surprisingly, and as for previous deletion of hs3a or hs1,2, deletion of hs4 did not affect either in vivo CSR or the secretion level of any Ig isotype. In vitro CSR and Ig secretion in response to LPS and cytokines was not affected either. The only noticeable effects of the hs4 deletion were a decrease in the number of B splenocytes and a decreased membrane IgM expression. In conclusion, while dispensable for CSR and Ig transcription in plasma cells, hs4 mostly appears to contribute to Ig transcription in resting B lymphocytes.

  6. A PTIP–PA1 subcomplex promotes transcription for IgH class switching independently from the associated MLL3/MLL4 methyltransferase complex

    Science.gov (United States)

    Starnes, Linda M.; Su, Dan; Pikkupeura, Laura M.; Weinert, Brian T.; Santos, Margarida A.; Mund, Andreas; Soria, Rebeca; Cho, Young-Wook; Pozdnyakova, Irina; Kubec Højfeldt, Martina; Vala, Andrea; Yang, Wenjing; López-Méndez, Blanca; Lee, Ji-Eun; Peng, Weiqun; Yuan, Joan; Ge, Kai; Montoya, Guillermo; Nussenzweig, André; Choudhary, Chunaram; Daniel, Jeremy A.

    2016-01-01

    Class switch recombination (CSR) diversifies antibodies for productive immune responses while maintaining stability of the B-cell genome. Transcription at the immunoglobulin heavy chain (Igh) locus targets CSR-associated DNA damage and is promoted by the BRCT domain-containing PTIP (Pax transactivation domain-interacting protein). Although PTIP is a unique component of the mixed-lineage leukemia 3 (MLL3)/MLL4 chromatin-modifying complex, the mechanisms for how PTIP promotes transcription remain unclear. Here we dissected the minimal structural requirements of PTIP and its different protein complexes using quantitative proteomics in primary lymphocytes. We found that PTIP functions in transcription and CSR separately from its association with the MLL3/MLL4 complex and from its localization to sites of DNA damage. We identified a tandem BRCT domain of PTIP that is sufficient for CSR and identified PA1 as its main functional protein partner. Collectively, we provide genetic and biochemical evidence that a PTIP–PA1 subcomplex functions independently from the MLL3/MLL4 complex to mediate transcription during CSR. These results further our understanding of how multifunctional chromatin-modifying complexes are organized by subcomplexes that harbor unique and distinct activities. PMID:26744420

  7. A PTIP-PA1 subcomplex promotes transcription for IgH class switching independently from the associated MLL3/MLL4 methyltransferase complex.

    Science.gov (United States)

    Starnes, Linda M; Su, Dan; Pikkupeura, Laura M; Weinert, Brian T; Santos, Margarida A; Mund, Andreas; Soria, Rebeca; Cho, Young-Wook; Pozdnyakova, Irina; Kubec Højfeldt, Martina; Vala, Andrea; Yang, Wenjing; López-Méndez, Blanca; Lee, Ji-Eun; Peng, Weiqun; Yuan, Joan; Ge, Kai; Montoya, Guillermo; Nussenzweig, André; Choudhary, Chunaram; Daniel, Jeremy A

    2016-01-15

    Class switch recombination (CSR) diversifies antibodies for productive immune responses while maintaining stability of the B-cell genome. Transcription at the immunoglobulin heavy chain (Igh) locus targets CSR-associated DNA damage and is promoted by the BRCT domain-containing PTIP (Pax transactivation domain-interacting protein). Although PTIP is a unique component of the mixed-lineage leukemia 3 (MLL3)/MLL4 chromatin-modifying complex, the mechanisms for how PTIP promotes transcription remain unclear. Here we dissected the minimal structural requirements of PTIP and its different protein complexes using quantitative proteomics in primary lymphocytes. We found that PTIP functions in transcription and CSR separately from its association with the MLL3/MLL4 complex and from its localization to sites of DNA damage. We identified a tandem BRCT domain of PTIP that is sufficient for CSR and identified PA1 as its main functional protein partner. Collectively, we provide genetic and biochemical evidence that a PTIP-PA1 subcomplex functions independently from the MLL3/MLL4 complex to mediate transcription during CSR. These results further our understanding of how multifunctional chromatin-modifying complexes are organized by subcomplexes that harbor unique and distinct activities. PMID:26744420

  8. Delay-dependent finite-time boundedness of a class of Markovian switching neural networks with time-varying delays.

    Science.gov (United States)

    Zhong, Qishui; Cheng, Jun; Zhao, Yuqing

    2015-07-01

    In this paper, a novel method is developed for delay-dependent finite-time boundedness of a class of Markovian switching neural networks with time-varying delays. New sufficient condition for stochastic boundness of Markovian jumping neural networks is presented and proved by an newly augmented stochastic Lyapunov-Krasovskii functional and novel activation function conditions, the state trajectory remains in a bounded region of the state space over a given finite-time interval. Finally, a numerical example is given to illustrate the efficiency and less conservative of the proposed method.

  9. Direct Adaptive Fuzzy Sliding Mode Control with Variable Universe Fuzzy Switching Term for a Class of MIMO Nonlinear Systems

    Directory of Open Access Journals (Sweden)

    Guo Haigang

    2012-01-01

    Full Text Available Combining adaptive fuzzy sliding mode control with fuzzy or variable universe fuzzy switching technique, this study develops two novel direct adaptive schemes for a class of MIMO nonlinear systems with uncertainties and external disturbances. The proposed control schemes consist of fuzzy equivalent control terms, fuzzy switching control terms (in scheme one or variable universe fuzzy switching control terms (in scheme two, and compensation control terms. The compensation control terms are used to relax the assumption on fuzzy approximation error. Based on Lyapunov stability theory, the parameters update laws are adaptively tuned online and the global asymptotic stability of the closed-loop system can be guaranteed. The major contribution of this study is to develop a novel framework for designing direct adaptive fuzzy sliding mode control scheme facing model uncertainties and external disturbances. The derived schemes can effectively solve the chattering problem and the equivalent control calculation in that environment. Simulation results performed on a two-link robotic manipulator demonstrate the feasibility of the proposed control schemes.

  10. Dectin-1 agonist selectively induces IgG1 class switching by LPS-activated mouse B cells.

    Science.gov (United States)

    Seo, Beom-Seok; Park, Ha-Yan; Yoon, Hee-Kyung; Yoo, Yung-Choon; Lee, Junglim; Park, Seok-Rae

    2016-10-01

    Heat-killed Saccharomyces cerevisiae (HKSC) is an agonist for Dectin-1, a major fungal cell wall β-glucan receptor. We previously reported that HKSC selectively enhances IgG1 production by LPS-activated mouse B cells. To determine if this IgG1 selectivity is caused by selective IgG1 class switching, we performed RT-PCRs for measuring germline transcripts (GLTs), flow cytometric analyses for detecting Ig-expressing cells, and ELISPOT assays for measuring the number of Ig-secreting cells in HKSC/LPS-stimulated mouse B cell cultures. HKSC selectively enhanced expression of GLTγ1, the number of IgG1-expressing cells, and the number of IgG1-secreting B cells in the presence of LPS stimulation. In addition, HKSC induced the expression of CD69, an activation marker for B lymphocytes, and the expression of surface Dectin-1. Two Dectin-1 antagonists, laminarin and a neutralizing Dectin-1 antibody, selectively diminished HKSC-reinforced IgG1 production by LPS-stimulated B cells. Furthermore, depleted zymosan (dzn), a Dectin-1 agonist with increased selectivity, also selectively enhanced GLTγ1 transcription. The Dectin-1 antagonists blocked dzn-induced IgG1 production by LPS-activated B cells. Collectively, these results suggest that Dectin-1 agonists selectively induce IgG1 class switching by direct stimulation of Dectin-1 on LPS-activated B cells resulting in selective production of IgG1.

  11. Uracil excision by endogenous SMUG1 glycosylase promotes efficient Ig class switching and impacts on A:T substitutions during somatic mutation.

    Science.gov (United States)

    Dingler, Felix A; Kemmerich, Kristin; Neuberger, Michael S; Rada, Cristina

    2014-07-01

    Excision of uracil introduced into the immunoglobulin loci by AID is central to antibody diversification. While predominantly carried out by the UNG uracil-DNA glycosylase as reflected by deficiency in immunoglobulin class switching in Ung(-/-) mice, the deficiency is incomplete, as evidenced by the emergence of switched IgG in the serum of Ung(-/-) mice. Lack of switching in mice deficient in both UNG and MSH2 suggested that mismatch repair initiated a backup pathway. We now show that most of the residual class switching in Ung(-/-) mice depends upon the endogenous SMUG1 uracil-DNA glycosylase, with in vitro switching to IgG1 as well as serum IgG3, IgG2b, and IgA greatly diminished in Ung(-/-) Smug1(-/-) mice, and that Smug1 partially compensates for Ung deficiency over time. Nonetheless, using a highly MSH2-dependent mechanism, Ung(-/-) Smug1(-/-) mice can still produce detectable levels of switched isotypes, especially IgG1. While not affecting the pattern of base substitutions, SMUG1 deficiency in an Ung(-/-) background further reduces somatic hypermutation at A:T base pairs. Our data reveal an essential requirement for uracil excision in class switching and in facilitating noncanonical mismatch repair for the A:T phase of hypermutation presumably by creating nicks near the U:G lesion recognized by MSH2.

  12. Regression of nifedipine-induced gingival hyperplasia following switch to a same class calcium channel blocker, isradipine.

    Science.gov (United States)

    Westbrook, P; Bednarczyk, E M; Carlson, M; Sheehan, H; Bissada, N F

    1997-07-01

    Patients with nifedipine-induced gingival hyperplasia (GH) often require continued calcium channel blocker therapy. Switches to diltiazem and verapamil have been described; however, these drugs are of a different chemical class and present therapeutic limitations in some patients. The purpose of this study was to evaluate the effect on nifedipine-induced GH of a switch to a dihydropyridine derivative with a low incidence of GH. Fourteen patients with nifedipine-induced GH were given a medical exam and a periodontal exam. The following parameters were assessed: probing depth (PD), gingival margin (GM), gingival thickness (GT), plaque index (PI), and gingival index (GI). Intraoral photographs, study models, and a gingival biopsy for histological examination were taken. Following baseline measures, patients were randomized to continued treatment with nifedipine or an equivalent dose of isradipine in a single-blind fashion. Biweekly periodontal parameters were taken for 8 weeks. At the end of 8 weeks, some patients elected to receive 4 weeks of open label isradipine therapy, with biweekly examination continuing through the open label phase. The isradipine treatment arm showed a mean decrease in PD of 0.59 mm at week 8 (P hyperplasia, while 66% of patients treated with nifedipine demonstrated an increase in hyperplasia, a significant difference (P < 0.05). When combined with open label data, patients switching therapy to isradipine exhibited an increase in GM (increase in recession) of 0.74 mm from baseline to week 12 (P < 0.05). No patients treated with isradipine exhibited an increase in gingival overgrowth. All patients exhibited adequate control of hypertension. We conclude that in hypertensive patients with nifedipine-induced GH, switching hypertensive therapy to isradipine may result in a regression of GH. When coupled with aggressive oral hygiene treatment, this drug may provide a reasonable option for patients requiring dihydropyridine treatment.

  13. Efficient assembly of recombinant major histocompatibility complex class I molecules with preformed disulfide bonds

    DEFF Research Database (Denmark)

    Ostergaard Pedersen, L; Nissen, Mogens Holst; Hansen, N J;

    2001-01-01

    The expression of major histocompatibility class I (MHC-I) crucially depends upon the binding of appropriate peptides. MHC-I from natural sources are therefore always preoccupied with peptides complicating their purification and analysis. Here, we present an efficient solution to this problem...... suggests that de novo folding of denatured MHC-I molecules proceed efficiently if directed by preformed disulfide bond(s). Importantly, these molecules express serological epitopes and stain specific T cells; and they bind peptides specifically. Several denatured MHC-I heavy chains were analyzed and shown...

  14. On Delay Independent Stabilization Analysis for a Class of Switched Large-Scale Time-Delay Systems

    Directory of Open Access Journals (Sweden)

    Chi-Jo Wang

    2013-01-01

    Full Text Available In view of the state-driven switching method, the sufficient stability conditions with delay independence will be derived for the switched large-scale time-delay systems. A new stability criterion of switched large-scale time-delay systems is deduced by Lyapunov stability theorem. The method can be applied to cases when all individual switched systems are unstable. Finally, one example is exploited to illustrate the proposed schemes.

  15. A Stability Condition with Delay-Dependence for a Class of Switched Large-Scale Time-Delay Systems

    Directory of Open Access Journals (Sweden)

    Chi-Jo Wang

    2013-01-01

    Full Text Available By using the time-switched method and the comparison theorem, we derived a criterion of delay-dependent stability for the switched large-scale time-delay systems. To guarantee the exponential stability for the switched large-scale time-delay systems with stability margin λ, the total activation time ratio of the switching law is determined. An example is used to illustrate the effectiveness of our result.

  16. Selective inhibition of class switching to IgG and IgE by recruitment of the HoxC4 and Oct-1 homeodomain proteins and Ku70/Ku86 to newly identified ATTT cis-elements.

    Science.gov (United States)

    Schaffer, András; Kim, Edmund C; Wu, Xiaoping; Zan, Hong; Testoni, Lucia; Salamon, Szilvia; Cerutti, Andrea; Casali, Paolo

    2003-06-20

    Immunoglobulin (Ig) class switching is central to the maturation of the antibody response as IgG, IgA, and IgE are endowed with more diverse biological effector functions than IgM. It is induced upon engagement of CD40 on B lymphocytes by CD40L expressed by activated CD4+ T cells and exposure of B cells to T cell-secreted cytokines including interleukin-4 and transforming growth factor-beta. It begins with germ line IH-CH transcription and unfolds through class switch DNA recombination (CSR). We show here that the HoxC4 and Oct-1 homeodomain proteins together with the Ku70/Ku86 heterodimer bind as a complex to newly identified switch (S) regulatory ATTT elements (SREs) in the Igamma and Iepsilon promoters and downstream regions to dampen basal germ line Igamma-Cgamma and Iepsilon-Cepsilon transcriptions and repress CSR to Cgamma and Cepsilon. This mechanism is inactive in the Calpha1/Calpha2 loci because of the lack of SREs in the Ialpha1/Ialpha2 promoters. Accordingly, in resting human IgM+IgD+ B cells, HoxC4, Oct-1, and Ku70/Ku86 can be readily identified as bound to the Igamma and Iepsilon promoters but not the Ialpha1/Ialpha2 promoters. CD40 signaling dissociates the HoxC4.Oct-1. Ku complex from the Igamma and Iepsilon promoter SREs, thereby relieving the IH-CH transcriptional repression and allowing CSR to unfold. Dissociation of HoxC4.Oct-1. Ku from DNA is hampered by CD153 engagement, a CD40-signaling inhibitor. Thus, these findings outline a HoxC4.Oct-1. Ku-dependent mechanism of selective regulation of class switching to IgG and IgE and further suggest distinct co-evolution and shared CSR activation pathways in the Cgamma and Cepsilon as opposed to the Calpha1/Calpha2 loci.

  17. The Molecular Switching Mechanism at the Conserved D(E)RY Motif in Class-A GPCRs.

    Science.gov (United States)

    Sandoval, Angelica; Eichler, Stefanie; Madathil, Sineej; Reeves, Philip J; Fahmy, Karim; Böckmann, Rainer A

    2016-07-12

    The disruption of ionic and H-bond interactions between the cytosolic ends of transmembrane helices TM3 and TM6 of class-A (rhodopsin-like) G protein-coupled receptors (GPCRs) is a hallmark for their activation by chemical or physical stimuli. In the bovine photoreceptor rhodopsin, this is accompanied by proton uptake at Glu(134) in the class-conserved D(E)RY motif. Studies on TM3 model peptides proposed a crucial role of the lipid bilayer in linking protonation to stabilization of an active state-like conformation. However, the molecular details of this linkage could not be resolved and have been addressed in this study by molecular dynamics (MD) simulations on TM3 model peptides in a bilayer of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). We show that protonation of the conserved glutamic acid alters the peptide insertion depth in the membrane, its side-chain rotamer preferences, and stabilizes the C-terminal helical structure. These factors contribute to the rise of the side-chain pKa (> 6) and to reduced polarity around the TM3 C terminus as confirmed by fluorescence spectroscopy. Helix stabilization requires the protonated carboxyl group; unexpectedly, this stabilization could not be evoked with an amide in MD simulations. Additionally, time-resolved Fourier transform infrared (FTIR) spectroscopy of TM3 model peptides revealed a different kinetics for lipid ester carbonyl hydration, suggesting that the carboxyl is linked to more extended H-bond clusters than an amide. Remarkably, this was seen as well in DOPC-reconstituted Glu(134)- and Gln(134)-containing bovine opsin mutants and demonstrates that the D(E)RY motif is a hydrated microdomain. The function of the D(E)RY motif as a proton switch is suggested to be based on the reorganization of the H-bond network at the membrane interface. PMID:27410736

  18. Global Uniform Asymptotic Stability of a Class of Switched Linear Systems with an Infinite Number of Subsystems

    Directory of Open Access Journals (Sweden)

    L. F. Araghi

    2014-01-01

    Full Text Available Stability of switching systems with an infinite number of subsystems is important in some structure of systems, like fuzzy systems, neural networks, and so forth. Because of the relationship between stability of a set of matrices and switching systems, this paper first studies the stability of a set of matrices, then and the results are applied for stability of switching systems. Some new conditions for globally uniformly asymptotically stability (GUAS of discrete-time switched linear systems with an infinite number of subsystems are proposed. The paper considers some examples and simulation results.

  19. Electrostatic switches that mediate the pH-dependent conformational change of “short” recombinant human pseudocathepsin D

    OpenAIRE

    Goldfarb, Nathan E.; Lam MT, Minh T.; Bose, Arjo K.; Patel, Ambar M.; Duckworth, Alexander J.; Ben M Dunn

    2005-01-01

    Human Cathepsin D (hCatD) is an aspartic peptidase with a low pH optimum. X-ray crystal structures have been solved for an active, low pH (pH 5.1) form (CatDlo) [Baldwin ET, Bhat, T.N., Gulnik, S., Hosur, M.V., Sowder, R.C., Cachau, R.E., Collins, J., Silva, A.M. and Erickson J.W. (1993) Proc. Natl. Acad. Sci. 90:6796–6800] and an inactive, high pH (pH 7.5) form (CatDhi) [Lee AY, Gulnik SV, Erickson JW. (1998) Nat Struct Biol 5:866–871]. It has been suggested that ionizable switches involving...

  20. Expression and characterization of recombinant single-chain salmon class I MHC fused with ß2-microglobulin with biological activity

    NARCIS (Netherlands)

    Zhao, H.; Stet, R.J.M.; Skjodt, K.; Savelkoul, H.F.J.

    2008-01-01

    Heterodimeric class I major histocompatibility complex (MHC) molecules consist of a putative 45-kDa heavy chain and a 12-kDa ß2-microglobulin (ß2m) light chain. The knowledge about MHC genes in Atlantic salmon accumulated during the last decade has allowed us to generate soluble and stable MHC class

  1. Variable-Voltage Class-E Power Amplifiers

    NARCIS (Netherlands)

    Acar, Mustafa; Annema, Anne Johan; Nauta, Bram

    2007-01-01

    The Class-E power amplifier is widely used due to its high efficiency, resulting from switching at zero voltage and zero slope of the switch voltage. In this paper, we extend general analytical solutions for the Class-E power amplifier to the ideal single-ended Variable-Voltage Class-E (Class-EVV) p

  2. Low risk of inhibitor formation in haemophilia A patients following en masse switch in treatment to a third generation full length plasma and albumin-free recombinant factor VIII product (ADVATE®).

    LENUS (Irish Health Repository)

    Bacon, C L

    2011-05-01

    Previous studies have suggested that development of inhibitors in previously treated patients (PTPs) may be attributable to a switch in factor VIII (FVIII) therapeutic product. Consequently, it is widely recognized that inhibitor development must be assessed in PTPs following the introduction of any new FVIII product. Following a national tender process in 2006, all patients with haemophilia A in Ireland changed their FVIII treatment product en masse to a plasma and albumin-free recombinant full-length FVIII product (ADVATE(®)). In this study, we retrospectively reviewed the case records of Irish PTPs to evaluate risk of inhibitor formation following this treatment switch. One hundred and thirteen patients participated in the study. Most patients (89%) had severe haemophilia. Only one of 96 patients with no inhibitor history developed an inhibitor. Prior to the switch in his recombinant FVIII (rFVIII) treatment of choice, this child had only experienced three exposure days (EDs). Consequently, in total he had only received 6 EDs when his inhibitor was first diagnosed. In keeping with this lack of de novo inhibitor development, we observed no evidence of any recurrent inhibitor formation in any of 16 patients with previously documented inhibitors. Similarly, following a previous en masse switch, we have previously reported that changing from a Chinese hamster ovary cell-produced to a baby hamster kidney cell-produced rFVIII was also associated with a low risk of inhibitor formation in PTPs. Our cumulative findings from these two studies clearly emphasizes that the risk of inhibitor development for PTPs following changes in commercial rFVIII product is low, at least in the Irish population.

  3. An integrated 80V 45W class-D power amplifier with optimal-efficiency-tracking switching frequency regulation

    NARCIS (Netherlands)

    Ma, Haifeng; Zee, van der Ronan; Nauta, Bram

    2014-01-01

    Piezoelectric actuators are widely used in smart materials for vibration and noise control, precision actuators, etc. [1]. These actuators are largely capacitive and the reactive power applied on them can go to several tens of Watts. Highvoltage, high-power class-D amplifiers [2]-[5] are ideal drive

  4. A Magnetically-Switched, Rotating Black Hole Model For the Production of Extragalactic Radio Jets and the Fanaroff and Riley Class Division

    CERN Document Server

    Meier, D L

    1998-01-01

    A model is presented in which both Fanaroff and Riley class I and II extragalactic jets are produced by magnetized accretion disk coronae in the ergospheres of rotating black holes. While the jets are produced in the accretion disk itself, the output power still is an increasing function of the black hole angular momentum. For high enough spin, the black hole triggers the magnetic switch, producing highly-relativistic, kinetic-energy-dominated jets instead of Poynting-flux-dominated ones for lower spin. The coronal mass densities needed to trigger the switch at the observed FR break power are quite small ($\\sim 10^{-15} g cm^{-3}$), implying that the source of the jet material may be either a pair plasma or very tenuous electron-proton corona, not the main accretion disk itself. The model explains the differences in morphology and Mach number between FR I and II sources and the observed trend for massive galaxies to undergo the FR I/II transition at higher radio power. It also is consistent with the energy co...

  5. Adaptive neural network tracking control for a class of switched stochastic pure-feedback nonlinear systems with backlash-like hysteresis

    Science.gov (United States)

    Niu, Ben; Qin, Tian; Fan, Xiaodong

    2016-10-01

    In this paper, an adaptive neural network tracking control approach is proposed for a class of switched stochastic pure-feedback nonlinear systems with backlash-like hysteresis. In the design procedure, an affine variable is constructed, which avoids the use of the mean value theorem, and the additional first-order low-pass filter is employed to deal with the problem of explosion of complexity. Then, a common Lyapunov function and a state feedback controller are explicitly obtained for all subsystems. It is proved that the proposed controller that guarantees all signals in the closed-loop system are semi-globally uniformly ultimately bounded and the tracking error remains an adjustable neighbourhood of the origin. Finally, simulation results show the effectiveness of the presented control design approach.

  6. Characterization of MHC class I in a long-distance migrant shorebird suggests multiple transcribed genes and intergenic recombination

    NARCIS (Netherlands)

    Buehler, Deborah M.; Verkuil, Yvonne I.; Tavares, Erika S.; Baker, Allan J.

    2013-01-01

    The major histocompatibility complex (MHC) includes highly polymorphic gene families encoding proteins crucial to the vertebrate acquired immune system. Classical MHC class I (MHCI) genes code for molecules expressed on the surfaces of most nucleated cells and are associated with defense against int

  7. Treatment with Recombinant Trichinella spiralis Cathepsin B-like Protein Ameliorates Intestinal Ischemia/Reperfusion Injury in Mice by Promoting a Switch from M1 to M2 Macrophages.

    Science.gov (United States)

    Liu, Wei-Feng; Wen, Shi-Hong; Zhan, Jian-Hua; Li, Yun-Sheng; Shen, Jian-Tong; Yang, Wen-Jing; Zhou, Xing-Wang; Liu, Ke-Xuan

    2015-07-01

    Intestinal ischemia/reperfusion (I/R) injury, in which macrophages play a key role, can cause high morbidity and mortality. The switch from classically (M1) to alternatively (M2) activated macrophages, which is dependent on the activation of STAT6 signaling, has been shown to protect organs from I/R injuries. In the current study, the effects of recombinant Trichinella spiralis cathepsin B-like protein (rTsCPB) on intestinal I/R injury and the potential mechanism related to macrophage phenotypes switch were investigated. In a mouse I/R model undergoing 60-min intestinal ischemia followed by 2-h or 7-d reperfusion, we demonstrated that intestinal I/R caused significant intestinal injury and induced a switch from M2 to M1 macrophages, evidenced by a decrease in levels of M2 markers (arginase-1 and found in inflammatory zone protein), an increase in levels of M1 markers (inducible NO synthase and CCR7), and a decrease in the ratio of M2/M1 macrophages. RTsCPB reversed intestinal I/R-induced M2-M1 transition and promoted M1-M2 phenotype switch evidenced by a significant decrease in M1 markers, an increase in M2 markers, and the ratio of M2/M1 macrophages. Meanwhile, rTsCPB significantly ameliorated intestinal injury and improved intestinal function and survival rate of animals, accompanied by a decrease in neutrophil infiltration and an increase in cell proliferation in the intestine. However, a selective STAT6 inhibitor, AS1517499, reversed the protective effects of rTsCPB by inhibiting M1 to M2 transition. These findings suggest that intestinal I/R injury causes a switch from M2 to M1 macrophages and that rTsCPB ameliorates intestinal injury by promoting STAT6-dependent M1 to M2 transition. PMID:25987744

  8. A low-power low-error single-ended virtually-grounded-drain class AB switched-current memory cell

    Directory of Open Access Journals (Sweden)

    Banlue Srisuchinwong

    2007-01-01

    Full Text Available A low-power low-error single-ended virtually-grounded-drain class AB switched-current memory cell is presented. The proposed circuit is relatively simple, based on a basic class AB SI memory cell and a levelshiftedgrounded-gate amplifier. No large differential circuitry and complicated clocking schemes are required. All charge-injection, clock-feedthrough and conduction errors are reduced. As a design exampleusing 0.5-μm CMOS technology, the power consumption is 120 μW at the bias current of 25 μA and supply voltage of 2V. The optimal sampling frequency is at 45MHz. The SNR, SDR and SFDR are 59.7 dB, 61 dB and73 dB, respectively. The total harmonic distortion is less than 0.4%. The transmission gain error and the DC offset current error are less than 0.025 and 0.75 μA, respectively. Demonstrations of a forward differenceintegrator and comparisons to other approaches are also presented.

  9. On stability of switched linear systems with perturbed switching paths

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    This paper addresses the stability issue of switched linear systems with perturbed switching paths. First,by introducing thenotions of child-path and parent-path, we are able to define the distance between two switching paths by means of their switching matrices chains. Next, we present the nice properties of the defined distance. Then, a stability criterion is presented for a class of switched linear systems with perturbed switching paths. Finally, an illustrative example is presented to verify the effectiveness of the approach.

  10. Induction of antigen-presenting capacity in tumor cells upon infection with non-replicating recombinant vaccinia virus encoding murine MHC class II and costimulatory molecules.

    Science.gov (United States)

    Marti, W R; Oertli, D; Meko, J B; Norton, J A; Tsung, K

    1997-01-15

    The possibility of inducing antigen-presenting capacity in cells normally lacking such capacity, currently represents a major goal in vaccine research. To address this issue we attempted to generate 'artificial' APC able to stimulate CD4+ T cell responses when tumor cells were infected with a single, recombinant, vaccinia virus (rVV) containing the two genes encoding murine MHC class II I-Ak and a third gene encoding the murine B7-1 (mB7-1) costimulatory molecule. To minimize the cytopathic effect and to improve safety, in view of possible in vivo applications, we made this rVV replication incompetent by Psoralen and long wave UV treatment. Tumor cells infected with rVV encoding I-Ak alone, pulsed with hen egg white lysozyme peptide (HEL46-61), induced IL-2 secretion by an antigen-specific T hybridoma. Tumor cells infected with the rVV encoding mB7-1 provided costimulation for activating resting CD4+ T cells in the presence of ConA. Tumor cells infected with the rVV encoding I-Ak and mB7-1, and pulsed with chicken ovotransferrin peptide (conalbumin133-145), induced a significantly higher response in a specific Th2 cell clone (D10.G4.1) as compared to cells infected with rVV encoding I-Ak molecules only. Thus, this replication incompetent rVV represents a safe, multiple gene, vector system able to confer in one single infection step effective APC capacity to non-professional APCs.

  11. Plasmonic enhanced ultrafast switch.

    Energy Technology Data Exchange (ETDEWEB)

    Subramania,Ganapathi Subramanian; Reno, John Louis; Passmore, Brandon Scott; Harris, Tom.; Shaner, Eric Arthur; Barrick, Todd A.

    2009-09-01

    Ultrafast electronic switches fabricated from defective material have been used for several decades in order to produce picosecond electrical transients and TeraHertz radiation. Due to the ultrashort recombination time in the photoconductor materials used, these switches are inefficient and are ultimately limited by the amount of optical power that can be applied to the switch before self-destruction. The goal of this work is to create ultrafast (sub-picosecond response) photoconductive switches on GaAs that are enhanced through plasmonic coupling structures. Here, the plasmonic coupler primarily plays the role of being a radiation condenser which will cause carriers to be generated adjacent to metallic electrodes where they can more efficiently be collected.

  12. Generalized analytical design equations for variable slope class-e power amplifiers

    NARCIS (Netherlands)

    Acar, Mustafa; Annema, Anne Johan; Nauta, Bram

    2006-01-01

    The Class-E power amplifier is widely used because of its high efficiency, resulting from switching at zero voltage and zero slope of the switch voltage. In this paper, we extend our general analytical solutions for the Class-E power amplifier to the ideal single-ended Variable Slope Class-E (Class-

  13. Expression of Recombinant Antibodies

    OpenAIRE

    Frenzel, André; Hust, Michael; Schirrmann, Thomas

    2013-01-01

    Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transg...

  14. The Pragmatic Adaptability of Teachers’Code-switching in EFL Class-rooms of the Urban and Rural Junior Middle Schools

    Institute of Scientific and Technical Information of China (English)

    侯燕

    2014-01-01

    Based on Verschueren’s Linguistic Adaptation Theory(1999) and Yu Guodong’s Linguistic Adaptation Model(2001), the present paper analyzes teachers’code-switching in both urban and rural junior middle schools from the pragmatic perspec-tive of adaptation.

  15. Integrated network analysis identifies fight-club nodes as a class of hubs encompassing key putative switch genes that induce major transcriptome reprogramming during grapevine development.

    Science.gov (United States)

    Palumbo, Maria Concetta; Zenoni, Sara; Fasoli, Marianna; Massonnet, Mélanie; Farina, Lorenzo; Castiglione, Filippo; Pezzotti, Mario; Paci, Paola

    2014-12-01

    We developed an approach that integrates different network-based methods to analyze the correlation network arising from large-scale gene expression data. By studying grapevine (Vitis vinifera) and tomato (Solanum lycopersicum) gene expression atlases and a grapevine berry transcriptomic data set during the transition from immature to mature growth, we identified a category named "fight-club hubs" characterized by a marked negative correlation with the expression profiles of neighboring genes in the network. A special subset named "switch genes" was identified, with the additional property of many significant negative correlations outside their own group in the network. Switch genes are involved in multiple processes and include transcription factors that may be considered master regulators of the previously reported transcriptome remodeling that marks the developmental shift from immature to mature growth. All switch genes, expressed at low levels in vegetative/green tissues, showed a significant increase in mature/woody organs, suggesting a potential regulatory role during the developmental transition. Finally, our analysis of tomato gene expression data sets showed that wild-type switch genes are downregulated in ripening-deficient mutants. The identification of known master regulators of tomato fruit maturation suggests our method is suitable for the detection of key regulators of organ development in different fleshy fruit crops.

  16. The Smallest Molecular Switch

    OpenAIRE

    Emberly, Eldon G.; Kirczenow, George

    2003-01-01

    Ab-initio total energy calculations reveal benzene-dithiolate (BDT) molecules on a gold surface, contacted by a monoatomic gold STM tip to have two classes of low energy conformations with differing symmetries. Lateral motion of the tip or excitation of the molecule cause it to change from one conformation class to the other and to switch between a strongly and a weakly conducting state. Thus, surprisingly, despite their apparent simplicity these Au/BDT/Au nanowires are shown to be electrical...

  17. Bilingual Teachers’ In-class Code-switching Mechanism from the Perspective of Taxonomy of Educational Objectives%双语教师课堂语码转换机制设计研究

    Institute of Scientific and Technical Information of China (English)

    高昂之

    2016-01-01

    以美国教育心理学家本杰明·布卢姆的教育目标分类学为理论依据,选取理论中学习者的知识过程维度和认知过程维度为参照,以高校《国际贸易实务》双语课为例,对双语教师的课堂语码转换机制进行设计,旨在厘清双语教师课堂教学中汉英双语的使用比重、转换方式和转换情境。%This paper aims to design an in-class code-switching mechanism for bilingual teachers from the theoretical perspective of taxonomy of educational objectives of Benjamin Bloom, American educator and psychologist and in the dimensions of knowledge and cognition. It examines the case of the bilingual course of International Trade Practice to highlight bilingual teachers’ Chinese-English code-switching proportion, switching mode and situation respectively.

  18. The splicing regulator PTBP2 interacts with the cytidine deaminase AID and promotes binding of AID to switch-region DNA.

    Science.gov (United States)

    Nowak, Urszula; Matthews, Allysia J; Zheng, Simin; Chaudhuri, Jayanta

    2011-02-01

    During immunoglobulin class-switch recombination (CSR), the cytidine deaminase AID induces double-strand breaks into transcribed, repetitive DNA elements called switch sequences. The mechanism that promotes the binding of AID specifically to switch regions remains to be elucidated. Here we used a proteomic screen with in vivo biotinylation of AID to identify the splicing regulator PTBP2 as a protein that interacts with AID. Knockdown of PTBP2 mediated by short hairpin RNA in B cells led to a decrease in binding of AID to transcribed switch regions, which resulted in considerable impairment of CSR. PTBP2 is thus an effector of CSR that promotes the binding of AID to switch-region DNA.

  19. Software Switching for Data Acquisition

    CERN Document Server

    CERN. Geneva; , David

    2016-01-01

    In this talk we discuss the feasibility of replacing telecom-class routers with a topology of commodity servers acting as software switches in data acquisition. We extend the popular software switch, Open vSwitch, with a dedicated, throughput-oriented buffering mechanism. We compare the performance under heavy many-to-one congestion to typical Ethernet switches and evaluate the scalability when building larger topologies, exploiting the integration with software-defined networking technologies. Please note that David Malone will speak on behalf of Grzegorz Jereczek.

  20. Differences in meiotic recombination rates in childhood acute lymphoblastic leukemia at an MHC class II hotspot close to disease associated haplotypes.

    Directory of Open Access Journals (Sweden)

    Pamela Thompson

    Full Text Available Childhood Acute Lymphoblastic Leukemia (ALL is a malignant lymphoid disease of which B-cell precursor- (BCP and T-cell- (T ALL are subtypes. The role of alleles encoded by major histocompatibility loci (MHC have been examined in a number of previous studies and results indicating weak, multi-allele associations between the HLA-DPB1 locus and BCP-ALL suggested a role for immunosusceptibility and possibly infection. Two independent SNP association studies of ALL identified loci approximately 37 kb from one another and flanking a strong meiotic recombination hotspot (DNA3, adjacent to HLA-DOA and centromeric of HLA-DPB1. To determine the relationship between this observation and HLA-DPB1 associations, we constructed high density SNP haplotypes of the 316 kb region from HLA-DMB to COL11A2 in childhood ALL and controls using a UK GWAS data subset and the software PHASE. Of four haplotype blocks identified, predicted haplotypes in Block 1 (centromeric of DNA3 differed significantly between BCP-ALL and controls (P = 0.002 and in Block 4 (including HLA-DPB1 between T-ALL and controls (P = 0.049. Of specific common (>5% haplotypes in Block 1, two were less frequent in BCP-ALL, and in Block 4 a single haplotype was more frequent in T-ALL, compared to controls. Unexpectedly, we also observed apparent differences in ancestral meiotic recombination rates at DNA3, with BCP-ALL showing increased and T-ALL decreased levels compared to controls. In silico analysis using LDsplit sotware indicated that recombination rates at DNA3 are influenced by flanking loci, including SNPs identified in childhood ALL association studies. The observed differences in rates of meiotic recombination at this hotspot, and potentially others, may be a characteristic of childhood leukemia and contribute to disease susceptibility, alternatively they may reflect interactions between ALL-associated haplotypes in this region.

  1. Independent Roles of Switching and Hypermutation in the Development and Persistence of B Lymphocyte Memory.

    Science.gov (United States)

    Gitlin, Alexander D; von Boehmer, Lotta; Gazumyan, Anna; Shulman, Ziv; Oliveira, Thiago Y; Nussenzweig, Michel C

    2016-04-19

    Somatic hypermutation (SHM) and class-switch recombination (CSR) increase the affinity and diversify the effector functions of antibodies during immune responses. Although SHM and CSR are fundamentally different, their independent roles in regulating B cell fate have been difficult to uncouple because a single enzyme, activation-induced cytidine deaminase (encoded by Aicda), initiates both reactions. Here, we used a combination of Aicda and antibody mutant alleles that separate the effects of CSR and SHM on polyclonal immune responses. We found that class-switching to IgG1 biased the fate choice made by B cells, favoring the plasma cell over memory cell fate without significantly affecting clonal expansion in the germinal center (GC). In contrast, SHM reduced the longevity of memory B cells by creating polyreactive specificities that were selected against over time. Our data define the independent contributions of SHM and CSR to the generation and persistence of memory in the antibody system. PMID:26944202

  2. Pseudospark switches

    International Nuclear Information System (INIS)

    The pseudospark discharge is bound to a geometrical structure which is particularly well suited for switching high currents and voltages at high power levels. This type of discharge offers the potential for improvement in essentially all areas of switching operation: peak current and current density, current rise, stand-off voltage, reverse current capability, cathode life, and forward drop. The first pseudospark switch was built at CERN at 1981. Since then, the basic switching characteristics of pseudospark chambers have been studied in detail. The main feature of a pseudospark switch is the confinement of the discharge plasma to the device axis. The current transition to the hollow electrodes is spread over a rather large surface area. Another essential feature is the easy and precise triggering of the pseudospark switch from the interior of the hollow electrodes, relatively far from the main discharge gap. Nanosecond delay and jitter values can be achieved with trigger energies of less than 0.1 mJ, although cathode heating is not required. Pseudospark gaps may cover a wide range of high-voltage, high-current, and high-pulse-power switching at repetition rates of many kilohertz. This report reviews the basic researh on pseudospark switches which has been going on at CERN. So far, applications have been developed in the range of thyratron-like medium-power switches at typically 20 to 40 kV and 0.5 to 10 kA. High-current pseudospark switches have been built for a high-power 20 kJ pulse generator which is being used for long-term tests of plasma lenses developed for the future CERN Antiproton Collector (ACOL). The high-current switches have operated for several hundred thousand shots, with 20 to 50 ns jitter at 16 kV charging voltage and more than 100 kA peak current amplitude. (orig.)

  3. CIRCUIT SWITCHING VERSUS PACKET SWITCHING

    OpenAIRE

    Sneps-Sneppe, Manfred

    2015-01-01

    Communication specialists around the world are facing the same problem: shifting from circuit switching (CS) to packet switching (CS). Communication service providers are favoring “All-over-IP” technologies hoping to boost their profits by providing multimedia services. The main stakeholder in this field of the paradigm shift is the industry itself: packet switching hardware manufacturers are going to earn billions of dollars and thus pay engineers and journalists many millions for the promot...

  4. Optical switches and switching methods

    Energy Technology Data Exchange (ETDEWEB)

    Doty, Michael

    2008-03-04

    A device and method for collecting subject responses, particularly during magnetic imaging experiments and testing using a method such as functional MRI. The device comprises a non-metallic input device which is coupled via fiber optic cables to a computer or other data collection device. One or more optical switches transmit the subject's responses. The input device keeps the subject's fingers comfortably aligned with the switches by partially immobilizing the forearm, wrist, and/or hand of the subject. Also a robust nonmetallic switch, particularly for use with the input device and methods for optical switching.

  5. A PARALLEL SWITCH FABRIC BASED ON CROSSBAR

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    With the increase of link rate, the arbitrator of centralized switch fabric becomes too complicated to implement. A parallel switch fabric based on crossbar, named as PSFBC (Parallel Switch Fabric Based on Crossbar), has been proposed in this paper. PSFBC is composed of k switches whose rate is 1/k of link', these switches exchange cells in parallel; this increases the arbitrator's period and make it easy to implement. Load is evenly distributed to each switch with FCFS (First Come First Serve) rule, it can keep the order of cells in one stream. A multi-class queue scheduling policy is used in PSFBC to ensure the quality of realtime streams. Experiments show that the load on each switch in PSFBC is well balanced, its average delay of cells is little and its performance is very close to centralized switch; and with the increase of number of parallel switches, the loss of PSFBC's performance keeps very small, it becomes easier to implement.

  6. Regulation of epsilon germline transcription and switch region mutations by IgH locus 3' enhancers in transgenic mice.

    Science.gov (United States)

    Laurencikiene, Jurga; Tamosiunas, Vytas; Severinson, Eva

    2007-01-01

    Germline (GL) transcription is regulated by specific promoters and immunoglobulin heavy chain (IgH) 3' locus enhancers and is necessary for Ig class-switch recombination (CSR). We have generated different transgenic lines containing the GL epsilon promoter, switch (S) epsilon region, and constant (C) epsilon region with or without the DNase I-sensitive regions (HS) 3A-HS1,2 or HS3B-HS4 3' IgH enhancer pairs. The enhancerless construct was expressed in B cells activated by interleukin (IL)-4 and CD40, thus resembling regulation of the endogenous gene. Both enhancer-containing transgenes efficiently increased expression in B cells and were strongly up-regulated by stimuli. In addition, Sepsilon regions of the transgene containing HS3B-HS4 were mutated in activated, sorted B cells. Such mutations are known to precede CSR and are dependent on activation-induced cytidine deaminase (AID). Our findings show that all elements necessary for recruitment of the recombination machinery are present in the transgene containing HS3 and HS4. These enhancers probably provide something more specific than mere increased accessibility of switch regions. We propose that transcription factors binding the enhancers help to target the recombination machinery to the switch regions.

  7. Construction of MHC class Ⅱ transactivator recombinant adenovirus vector%MHC Ⅱ类转激活因子基因的重组腺病毒载体的构建

    Institute of Scientific and Technical Information of China (English)

    张敏敏; 杨骅; 金晶; 吴红玉; 李兆申

    2009-01-01

    Objective To construct a recombinant adenovirus vector containing the gene of major histocompatibility complex(MHC)class Ⅱ transactivator(C Ⅱ TA).Methods The restriction fragment of CIITA was inserted into pUC57 vector with EeoR Ⅰ and Xho Ⅰ.Then,recombinant plasmid pShutde-GFP-CMV CⅡTA was constructed with EcoR Ⅰ and Sal Ⅰ,and was confirmed by restriction enzyme digestion and sequeneing.After the treatment with Ⅰ-Ceu Ⅰ and Ⅰ-See Ⅰ,the fragment C Ⅱ TA from recombinant plasmid DShuttle-GFP-CMV.CⅡTA Was inserted into vector pAdxsi.And the pAdxsi-GFP-C Ⅱ TA wag packed into liposome,and was transfected to 293 cens.Results Recombinant plasmid pShuttle-GFP-CMV-C Ⅱ TA Was constructed successfully. After packed into vector pAdxsi, and transfected to 293 cells, significant virus Dlaques were observed,which showed the successful homologous recombination.The titer of the purified AdC Ⅱ TA was 2.0×10~(11) PFU/ml.Conclusions Recombinant adenovirus AdC Ⅱ TA containing gene of MHC class Ⅱ transactivator was established successfully.%目的 构建含有主要组织相容性复合物(major histocompatibility complex,MHC)Ⅱ类分子激活物(CⅡTA)基因的重组腺病毒载体.方法 回收CⅡTA的PCR产物插人pUC57中,用EcoR Ⅰ和Xho Ⅰ双酶切,U-Gene凝胶回收纯化3300bp目的基因片段.用EcoR Ⅰ和sal Ⅰ双酶切质粒载体pShuttle-GFP-CMV,用T4DNA连接酶将上述目的基因片段与pShuttle-GFP-CMV片段连接,得到穿梭质粒pShuttle-GFP-CMV-C Ⅱ TA,并经Kpn Ⅰ单酶切及测序鉴定.Ⅰ-Ceu Ⅰ/Ⅰ-See Ⅰ双酶切处理,回收目的片段,将pAdxsi载体片段和插入片段进行酶连接,得到腺病毒质粒pAdxsi-GFP-C Ⅱ TA,经Xho Ⅰ酶切鉴定后转染HEK293细胞并培养出毒.扩增、纯化重组腺病毒AdCⅡTA,并测定病毒滴度.结果 重组穿梭质粒pShuttle-GFP-CMV-C ⅡTA经Kpn Ⅰ单酶切及测序分析,证实与GeneBank中公布的小鼠CⅡTA(NM_007575)序列完全相

  8. 47 CFR 32.2210 - Central office-switching.

    Science.gov (United States)

    2010-10-01

    ... Central office—switching. This account shall be used by Class B companies to record the original cost of switching assets of the type and character required of Class A companies in Accounts 2211 through 2212. ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Central office-switching. 32.2210 Section...

  9. Recombination instability

    DEFF Research Database (Denmark)

    D'Angelo, N.

    1967-01-01

    A recombination instability is considered which may arise in a plasma if the temperature dependence of the volume recombination coefficient, alpha, is sufficiently strong. Two cases are analyzed: (a) a steady-state plasma produced in a neutral gas by X-rays or high energy electrons; and (b...

  10. Analysis of interchromosomal mitotic recombination.

    Science.gov (United States)

    McGill, C B; Shafer, B K; Higgins, D R; Strathern, J N

    1990-07-01

    A novel synthetic locus is described that provides a simple assay system for characterizing mitotic recombinants. The locus consists of the TRP1 and HIS3 genes inserted into chromosome III of S. cerevisiae between the CRY1 and MAT loci. Defined trp1 and his3 alleles have been generated that allow the selection of interchromosomal recombinants in this interval. Trp+ or His+ recombinants can be divided into several classes based on coupling of the other alleles in the interval. The tight linkage of the CRY1 and MAT loci, combined with the drug resistance and cell type phenotypes that they respectively control, facilitates the classification of the recombinants without resorting to tetrad dissection. We present the distribution of spontaneous recombinants among the classes defined by this analysis. The data suggest that the recombination intermediate can have regions of symmetric strand exchange and that co-conversion tracts can extend over 1-3 kb. Continuous conversion tracts are favored over discontinuous tracts. The distribution among the classes defined by this analysis is altered in recombinants induced by UV irradiation.

  11. Mechanisms and factors that influence high frequency retroviral recombination

    DEFF Research Database (Denmark)

    Delviks-Frankenberry, Krista; Galli, Andrea; Nikolaitchik, Olga;

    2011-01-01

    With constantly changing environmental selection pressures, retroviruses rely upon recombination to reassort polymorphisms in their genomes and increase genetic diversity, which improves the chances for the survival of their population. Recombination occurs during DNA synthesis, whereby reverse...... transcriptase undergoes template switching events between the two copackaged RNAs, resulting in a viral recombinant with portions of the genetic information from each parental RNA. This review summarizes our current understanding of the factors and mechanisms influencing retroviral recombination, fidelity......, and vaccine development....

  12. Non-fragile H∞ Control for a Class of Uncertain Time-Delay Switched Systems%一类不确定时滞切换系统的非脆弱H∞控制

    Institute of Scientific and Technical Information of China (English)

    李春吉; 陈霞

    2012-01-01

    讨论了一类不确定时滞切换系统在特定切换条件下的非脆弱状态反馈的H∞控制问题.主要利用凸组合技术、公共Lyapunov函数及线性矩阵不等式等方法,给出了在不确定时滞切换系统中存在非脆弱状态反馈控制器并且满足H∞性能指标γ的充分条件.最后给出了仿真算例,验证了其结果的有效性.定理的条件是以线性矩阵不等式形式给出的,因此便于工程实现.%The problem of non-fragile state feedback H∞ control for a class of uncertain time-delay switched systems was discussed on the particularly switched condition.Based on the common Lyapunov function,convex combination technique and linear matrix inequality,the sufficient condition for the existence of non-fragile state feedback controller was given,and this condition also met the H∞ performance index.In the end,the simulation example was given to verify the effectiveness of the proposed method.The condition of the theorem in the form of linear matrix inquality was put forward,which is easy to realize in practice.

  13. Nondisjunction of chromosome 15: Origin and recombination

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, W.P.; Bernasconi, F.; Schinzel, A.A.; Mutirangura, A.; Ledbetter, D.H. (Baylor College of Medicine, Houston, TX (United States)); Langlois, S. (Univ. of Britisch Columbia, Vancouver (Canada)); Morris, M.A.; Malcolm, S.

    1993-09-01

    Thirty-two cases of uniparental disomy (UPD), ascertained from Prader-Willi syndrome patients (N=27) and Angelman syndrome patients (N-5), are used to investigate the pattern of recombination associated with nondisjunction of chromosome 15. In addition, the meiotic stage of nondisjunction is inferred by using markers mapping near the centromere. Two basic approaches to the analysis of recombination in specific pairwise intervals along the chromosome. This method shows a significant reduction in recombination for two of five intervals examined. Second, the observed frequency of each recombinant class (i.e., zero, one, two, three, or more observable crossovers) is compared with expected values. This is useful for testing whether the reduction in recombination can be attributed solely to a proportion of cases with no recombination at all (because of asynapsis), with the remaining groups showing normal recombination (or even excess recombination), or whether recombination is uniformly reduced. Analysis of maternal UPD(15) data shows a slight reduction in the multiple-recombinant classes, with a corresponding increase in both the zero- and one-recombinant classes over expected values. The majority, more than 82%, of the extra chromosomes in maternal UPD(15) cases are due to meiotic I nondisjunction events. In contrast, more paternal UPD(15) cases so far examined appear to have a postzygotic origin of the extra paternal chromosome. 33 refs., 1 fig., 7 tabs.

  14. Switched steerable multiple beam antenna system

    Science.gov (United States)

    Iwasaki, Richard S.

    1988-09-01

    A steerable multibeam five element cross-feed cluster antenna system is described. The feed power is divided into five branches. Each branch includes a switching network comprised of a plurality of time delay elements each individually controlled by a respective electromagnetic latching switch. Frequency independent individual two-dimensional beam steering at intermediate (IF) scanning frequencies is thereby provided wherein discrete incremental time delays are introduced by the switching networks into each branch and the signals recombined thereafter to form each beam. The electromagnetic latched switching reduces power consumption and permits higher power switching and reciprocal coincident tranmsit and receive operation. Frequency independence due to incremental time delay switching permits coincident reciprocal operation and steering for transmit-receive signal paths carrying different transmit-receive frequencies. Diagonal quarter wave plates in the waveguides alter polarization from the circular to orthogonal linear to provide transmitter-receiver isolation.

  15. Learner Code-Switching versus English Only

    Science.gov (United States)

    Sampson, Andrew

    2012-01-01

    This article describes a study into the functions of code-switching in EFL classes at a Colombian language school. It was undertaken to decide whether the official "English-only" policy in place in this and other classrooms is pedagogically justified. The results suggest that code-switching may not necessarily be connected to ability level and…

  16. On formalism and stability of switched systems

    DEFF Research Database (Denmark)

    Leth, John-Josef; Wisniewski, Rafal

    2012-01-01

    In this paper, we formulate a uniform mathematical framework for studying switched systems with piecewise linear partitioned state space and state dependent switching. Based on known results from the theory of differential inclusions, we devise a Lyapunov stability theorem suitable for this class...

  17. State-dependent switching control of switched positive fractional-order systems.

    Science.gov (United States)

    Zhao, Xudong; Yin, Yunfei; Zheng, Xiaolong

    2016-05-01

    In this paper, the problem of switching stabilization for a class of continuous-time switched positive fractional-order systems is studied by using state-dependent switching. First, the asymptotic stability condition of switched positive fractional-order systems with state-dependent switching is given, which is based on the fractional co-positive Lyapunov method. Moreover, by the sliding sector method, the stability condition of switched positive fractional-order systems whose subsystems are possibly all unstable is obtained. A variable structure (VS) switching law with sliding sector is also proposed to guarantee the switched positive fractional-order system to be asymptotically stable. Finally, two numerical examples are given to demonstrate the advantages and effectiveness of our developed results.

  18. The strength of an Ig switch region is determined by its ability to drive R loop formation and its number of WGCW sites.

    Science.gov (United States)

    Zhang, Zheng Z; Pannunzio, Nicholas R; Han, Li; Hsieh, Chih-Lin; Yu, Kefei; Lieber, Michael R

    2014-07-24

    R loops exist at the murine IgH switch regions and possibly other locations, but their functional importance is unclear. In biochemical systems, R loop initiation requires DNA sequence regions containing clusters of G nucleotides, but cellular studies have not been done. Here, we vary the G-clustering, total switch region length, and the number of target sites (WGCW sites for the activation-induced deaminase) at synthetic switch regions in a murine B cell line to determine the effect on class switch recombination (CSR). G-clusters increase CSR regardless of their immediate proximity to the WGCW sites. This increase is accompanied by an increase in R loop formation. CSR efficiency correlates better with the absolute number of WGCW sites in the switch region rather than the total switch region length or density of WGCW sites. Thus, the overall strength of the switch region depends on G-clusters, which initiate R loop formation, and on the number of WGCW sites. PMID:25017067

  19. The Strength of an Ig Switch Region Is Determined by Its Ability to Drive R Loop Formation and Its Number of WGCW Sites

    Directory of Open Access Journals (Sweden)

    Zheng Z. Zhang

    2014-07-01

    Full Text Available R loops exist at the murine IgH switch regions and possibly other locations, but their functional importance is unclear. In biochemical systems, R loop initiation requires DNA sequence regions containing clusters of G nucleotides, but cellular studies have not been done. Here, we vary the G-clustering, total switch region length, and the number of target sites (WGCW sites for the activation-induced deaminase at synthetic switch regions in a murine B cell line to determine the effect on class switch recombination (CSR. G-clusters increase CSR regardless of their immediate proximity to the WGCW sites. This increase is accompanied by an increase in R loop formation. CSR efficiency correlates better with the absolute number of WGCW sites in the switch region rather than the total switch region length or density of WGCW sites. Thus, the overall strength of the switch region depends on G-clusters, which initiate R loop formation, and on the number of WGCW sites.

  20. Controlled release from recombinant polymers.

    Science.gov (United States)

    Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza

    2014-09-28

    Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed.

  1. Robust Stability Analysis of Nonlinear Switched Systems with Filippov Solutions

    DEFF Research Database (Denmark)

    Ahmadi, Mohamadreza; Mojallali, Hamed; Wisniewski, Rafal;

    2012-01-01

    This paper addresses the stability problem of a class of nonlinear switched systems with partitioned state-space and state-dependent switching. In lieu of the Caratheodory solutions, the general Filippov solutions are considered. This encapsulates solutions with infinite switching in finite time....... which provides sufficient means to construct the corresponding Lyapunov functions via available semi-definite programming techniques....

  2. Infection with an H2 recombinant herpes simplex virus vector results in expression of MHC class I antigens on the surfaces of human neuroblastoma cells in vitro and mouse sensory neurons in vivo.

    Science.gov (United States)

    Abendroth, A; Simmons, A; Efstathiou, S; Pereira, R A

    2000-10-01

    The majority of neurons in herpes simplex virus (HSV)-infected murine sensory ganglia are transiently induced to express MHC-I antigens at the cell surface, whereas only a minority are themselves productively infected. The aim of the current work was to determine whether MHC-I antigens can be expressed on the surfaces of infected neurons in addition to their uninfected neighbours. To address this aim a recombinant HSV type 1 strain, S-130, was used to deliver a mouse H2K(d) gene, under control of the HCMV IE-1 promoter/enhancer, into human neuroblastoma cells in vitro and mouse primary sensory neurons in vivo. S-130 expressed H2K(d) antigens on the surfaces of IMR-32 cells, a human neuroblastoma cell line that expresses very low levels of MHC-I constitutively. In K562 cells, which do not express MHC-I constitutively, H2K(d) and beta(2)-microglobulin (beta(2)m) were shown to be co-expressed at the cell surface following S-130 infection. This observation was taken as evidence that class I heavy chain (alphaC) molecules encoded by the expression cassette in the HSV genome were transported to the cell surface as stable complexes with beta(2)m. Significantly, after introduction of S-130 into flank skin, H2K(d) antigens were detected on the surfaces of primary sensory neurons in ganglia innervating the inoculation site. Our data show that HSV-infected murine primary sensory neurons and human neuroblastoma cells are capable of expressing cell-surface MHC-I molecules encoded by a transgene. From this, we infer that up-regulation of alphaC expression is, in principle, sufficient to overcome potential impediments to neuronal cell surface expression of MHC-I complexes.

  3. Wide Bandgap Extrinsic Photoconductive Switches

    Science.gov (United States)

    Sullivan, James Stephen

    Wide Bandgap Extrinsic Photoconductive Switches Semi-insulating Gallium Nitride, 4H and 6H Silicon Carbide are attractive materials for compact, high voltage, extrinsic, photoconductive switches due to their wide bandgap, high dark resistance, high critical electric field strength and high electron saturation velocity. These wide bandgap semiconductors are made semi-insulating by the addition of vanadium (4H and 6H-SiC) and iron (2H-GaN) impurities that form deep acceptors. These deep acceptors trap electrons donated from shallow donor impurities. The electrons can be optically excited from these deep acceptor levels into the conduction band to transition the wide bandgap semiconductor materials from a semi-insulating to a conducting state. Extrinsic photoconductive switches with opposing electrodes have been constructed using vanadium compensated 6H-SiC and iron compensated 2H-GaN. These extrinsic photoconductive switches were tested at high voltage and high power to determine if they could be successfully used as the closing switch in compact medical accelerators. The successful development of a vanadium compensated, 6H-SiC extrinsic photoconductive switch for use as a closing switch for compact accelerator applications was realized by improvements made to the vanadium, nitrogen and boron impurity densities. The changes made to the impurity densities were based on the physical intuition outlined and simple rate equation models. The final 6H-SiC impurity 'recipe' calls for vanadium, nitrogen and boron densities of 2.5 e17 cm-3, 1.25e17 cm-3 and ≤ 1e16 cm-3, respectively. This recipe was originally developed to maximize the quantum efficiency of the vanadium compensated 6H-SiC, while maintaining a thermally stable semi-insulating material. The rate equation models indicate that, besides increasing the quantum efficiency, the impurity recipe should be expected to also increase the carrier recombination time. Three generations of 6H-SiC materials were tested. The

  4. Switching-mode Audio Power Amplifiers with Direct Energy Conversion

    DEFF Research Database (Denmark)

    Ljusev, Petar; Andersen, Michael Andreas E.

    2005-01-01

    This paper presents a new class of switching-mode audio power amplifiers, which are capable of direct energy conversion from the AC mains to the audio output. They represent an ultimate integration of a switching-mode power supply and a Class D audio power amplifier, where the intermediate DC bus...

  5. Nanoelectromechanical contact switches

    Science.gov (United States)

    Loh, Owen Y.; Espinosa, Horacio D.

    2012-05-01

    Nanoelectromechanical (NEM) switches are similar to conventional semiconductor switches in that they can be used as relays, transistors, logic devices and sensors. However, the operating principles of NEM switches and semiconductor switches are fundamentally different. These differences give NEM switches an advantage over semiconductor switches in some applications -- for example, NEM switches perform much better in extreme environments -- but semiconductor switches benefit from a much superior manufacturing infrastructure. Here we review the potential of NEM-switch technologies to complement or selectively replace conventional complementary metal-oxide semiconductor technology, and identify the challenges involved in the large-scale manufacture of a representative set of NEM-based devices.

  6. An evaluation of Access Tier local area network switches.

    Energy Technology Data Exchange (ETDEWEB)

    Eldridge, John M.; Olsberg, Ronald R.

    2004-06-01

    This reports tabulates the Test and Evaluation results of the Access Class Switch tests conducted by members of Department 9336. About 15 switches were reviewed for use in the enterprise network as access tier switches as defined in a three tier architecture. The Access Switch Tier has several functions including: aggregate customer desktop ports, preserve and apply QoS tags, provide switched LAN access, provide VLAN assignment, as well as others. The typical switch size is 48 or less user ports. The evaluation team reviewed network switch evaluation reports from the Tolly Group as well as other sources. We then used these reports as a starting point to identify particular switches for evaluation. In general we reviewed the products of dominant equipment manufacturers. Also, based on architectural design requirements, the majority of the switches tested were of relatively small monolithic unit variety.

  7. CO2 laser pulse switching by optically excited semiconductors

    International Nuclear Information System (INIS)

    The construction and the study of a semi-conductor optical switch used for generating short infrared pulses and to analyse the semiconductor characteristics, are presented. The switch response time depends on semiconductor and control laser characteristics. The results obtained using a Ge switch controlled by N2, NdYag and Dye lasers are presented. The response time was 50 ns limited by Ge recombination time. The reflectivity increased from 7% to 59% using N2 laser to control the switch. A simple model for semiconductor optical properties that explain very well the experimental results, is also presented. (author)

  8. Switched on!

    CERN Multimedia

    2008-01-01

    Like a star arriving on stage, impatiently followed by each member of CERN personnel and by millions of eyes around the world, the first beam of protons has circulated in the LHC. After years in the making and months of increasing anticipation, today the work of hundreds of people has borne fruit. WELL DONE to all! Successfully steered around the 27 kilometres of the world’s most powerful particle accelerator at 10:28 this morning, this first beam of protons circulating in the ring marks a key moment in the transition from over two decades of preparation to a new era of scientific discovery. "It’s a fantastic moment," said the LHC project leader Lyn Evans, "we can now look forward to a new era of understanding about the origins and evolution of the universe". Starting up a major new particle accelerator takes much more than flipping a switch. Thousands of individual elements have to work in harmony, timings have to be synchronize...

  9. ADAPTIVE GENERALIZED PREDICTIVE CONTROL OF SWITCHED SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    WANG Yi-jing; WANG Long

    2005-01-01

    The problem of adaptive generalized predictive control which consists of output prediction errors for a class of switched systems is studied. The switching law is determined by the output predictive errors of a finite number of subsystems. For the single subsystem and multiple subsystems cases, it is proved that the given direct algorithm of generalized predictive control guarantees the global convergence of the system. This algorithm overcomes the inherent drawbacks of the slow convergence and large transient errors for the conventional adaptive control.

  10. New pulse modulator with low switching frequency

    OpenAIRE

    Golub V. S.

    2014-01-01

    The author presents an integrating pulse modulator (analog signal converter) with the pulse frequency and duration modulation similar to sigma-delta modulation (with low switching frequency), without quantization. The modulator is characterized by the absence of the quantization noise inherent in sigma-delta modulator, and a low switching frequency, unlike the pulse-frequency modulator. The modulator is recommended, in particular, to convert signals at the input of the class D power amplifier.

  11. New pulse modulator with low switching frequency

    Directory of Open Access Journals (Sweden)

    Golub V. S.

    2014-12-01

    Full Text Available The author presents an integrating pulse modulator (analog signal converter with the pulse frequency and duration modulation similar to sigma-delta modulation (with low switching frequency, without quantization. The modulator is characterized by the absence of the quantization noise inherent in sigma-delta modulator, and a low switching frequency, unlike the pulse-frequency modulator. The modulator is recommended, in particular, to convert signals at the input of the class D power amplifier.

  12. Understanding Markov-switching rational expectations models

    OpenAIRE

    Roger E.A. Farmer; Daniel F. Waggoner; Zha, Tao

    2009-01-01

    We develop a set of necessary and sufficient conditions for equilibria to be determinate in a class of forward-looking Markov-switching rational expectations models, and we develop an algorithm to check these conditions in practice. We use three examples, based on the new Keynesian model of monetary policy, to illustrate our technique. Our work connects applied econometric models of Markov switching with forward-looking rational expectations models and allows an applied researcher to construc...

  13. Robust Tracking Control for Switched Fuzzy Systems with Fast Switching Controller

    Directory of Open Access Journals (Sweden)

    Hong Yang

    2012-01-01

    Full Text Available This paper addresses the problem of designing robust tracking controls for a class of switched fuzzy (SF systems with time delay. A switched fuzzy system, which differs from existing ones, is firstly employed to describe a nonlinear system. Next, a fast switching controller consisting of a number of simple subcontrollers is proposed. The smooth transition is governed by using the fast switching controller. Tracking hybrid control schemes which are based upon a combination of the H∞ tracking theory, fast switching control algorithm, and switching law design are developed such that the H∞ model referent tracking performance is guaranteed. Since convex combination techniques are used to derive the delay independent criteria, some subsystems are allowed to be unstable. Finally, various comparisons of the elaborated examples are conducted to demonstrate the effectiveness of the proposed control design approach. All results illustrate good control performances as desired.

  14. Radiation hard vacuum switch

    Science.gov (United States)

    Boettcher, Gordon E.

    1990-01-01

    A vacuum switch with an isolated trigger probe which is not directly connected to the switching electrodes. The vacuum switch within the plasmatron is triggered by plasma expansion initiated by the trigger probe which travels through an opening to reach the vacuum switch elements. The plasma arc created is directed by the opening to the space between the anode and cathode of the vacuum switch to cause conduction.

  15. Recombinant Technology and Probiotics

    Directory of Open Access Journals (Sweden)

    Icy D’Silva

    2011-09-01

    Full Text Available Recombinant technology has led the way to monumental advances in the development of useful molecules, including the development of safe probiotics. The development of novel approaches using recombinant technology and probiotics that allow accurate targeting of therapeutics to the mucosa is an interesting area of research. The creation and use of recombinant probiotics expressing recombinantovalbumin, recombinant ovalbumin mutants and yet-to-be-designed recombinant hypo/non-allergenic molecules offer the opportunity to further investigate their effects for food, nutrition, environment andhealth. This review highlights advances in native probiotics and recombinant probiotics expressing native and recombinant molecules for food, nutrition, environment and health.

  16. Cost functions in optical burst-switched networks

    OpenAIRE

    Klusek, Bartlomiej

    2006-01-01

    Optical Burst Switching (OBS) is a new paradigm for an all-optical Internet. It combines the best features of Optical Circuit Switching (OCS) and Optical Packet Switching (OPS) while avoidmg the mam problems associated with those networks .Namely, it offers good granularity, but its hardware requirements are lower than those of OPS. In a backbone network, low loss ratio is of particular importance. Also, to meet varying user requirements, it should support multiple classes of service. In ...

  17. Robust feedback switching control: dynamic programming and viscosity solutions

    OpenAIRE

    Bayraktar, Erhan; Cosso, Andrea; Pham, Huyen

    2014-01-01

    We consider a robust switching control problem. The controller only observes the evolution of the state process, and thus uses feedback (closed-loop) switching strategies, a non standard class of switching controls introduced in this paper. The adverse player (nature) chooses open-loop controls that represent the so-called Knightian uncertainty, i.e., misspecifications of the model. The (half) game switcher versus nature is then formulated as a two-step (robust) optimization problem. We devel...

  18. Understanding household switching behavior in the retail electricity market

    International Nuclear Information System (INIS)

    Deregulation of the Danish retail electricity market nearly a decade ago has produced little consumer switching among suppliers or renegotiation of supplier service contracts. From an energy policy perspective, a certain amount of supplier switching is an important indicator of the success of market deregulation. This argues that poor relationship management and a lack of economic benefits are two critical barriers to consumer switching. Latent class analysis indicates that only 11.4% of consumers are non-switchers, whereas 41.1% can be considered potential switchers and approximately one-half (47.5%) can be considered apathetic consumers. We also discuss the managerial implications for both electricity suppliers and policy makers. - Highlights: • This paper investigates the barriers for electricity supplier switching in Denmark. • Four switching barriers were identified. • Relationship management and economic benefits are critical for consumer switching. • Three consumer segments for electricity supplier switching were identified

  19. Switching mode power supplies

    OpenAIRE

    Beard, David W.

    1980-01-01

    The subject of switching mode power supplies was examined. A comparison between linear regulators and switching mode power supplies was made to show the options available for the various types of convertors. Two switching mode power supplies were constructed and tested. The operating efficiency of both systems was found to be more than eighty percent over the specified input voltage and load current conditions. The switching mode power supply circuits required additional ...

  20. Heat Switches for ADRs

    Science.gov (United States)

    DiPirro, M. J.; Shirron, P. J.

    2014-01-01

    Heat switches are key elements in the cyclic operation of Adiabatic Demagnetization Refrigerators (ADRs). Several of the types of heat switches that have been used for ADRs are described in this paper. Key elements in selection and design of these switches include not only ON/OFF switching ratio, but also method of actuation, size, weight, and structural soundness. Some of the trade-off are detailed in this paper.

  1. Controller Architectures for Switching

    DEFF Research Database (Denmark)

    Niemann, Hans Henrik; Poulsen, Niels Kjølstad

    2009-01-01

    This paper investigate different controller architectures in connection with controller switching. The controller switching is derived by using the Youla-Jabr-Bongiorno-Kucera (YJBK) parameterization. A number of different architectures for the implementation of the YJBK parameterization are...... described and applied in connection with controller switching. An architecture that does not include inversion of the coprime factors is introduced. This architecture will make controller switching particular simple....

  2. MOSFET as a Switch

    OpenAIRE

    Dhaval Agrawal

    2014-01-01

    s as a switch. Also it shows the different problems and some remedy to solve those problems with equations and simulatis as a switch. Also it shows the different problems and some remedy to solve those problems with equations and simulatis as a switch. Also it shows the different problems and some remedy to solve those problems with equations and simulatis as a switch. Also it shows the different problems and some remedy to solve those problems with equations and simulatis as ...

  3. H-infinity control for cascade minimum-phase switched nonlinear systems

    Institute of Scientific and Technical Information of China (English)

    Shengzhi ZHAO; Jun ZHAO

    2005-01-01

    This paper is concerned with the H-infinity control problem for a class of cascade switched nonlinear systems.Each switched system in this class is composed of a zero-input asymptotically stable nonlinear part,which is also a switched system,and a linearizable part which is controllable.Conditions under which the H-infinity control problem is solvable under arbitrary switching law and under some designed switching law are derived respectively.The nonlinear state feedback and switching law are designed.We exploit the structural characteristics of the switched nonlinear systems to construct common Lyapunov functions for arbitrary switching and to find a single Lyapunov function for designed switching law.The proposed methods do not rely on the solutions of Hamilton-Jacobi inequalities.

  4. Robust stabilisation and L2 -gain analysis for switched systems with actuator saturation under asynchronous switching

    Science.gov (United States)

    Wang, Juan; Zhao, Jun

    2016-09-01

    Robust stabilisation and L2-gain analysis for a class of switched systems with actuator saturation are studied in this paper. The switching signal of the controllers lags behind that of the system modes, which leads to the asynchronous switching between the candidate controllers and the subsystems. By combining the piecewise Lyapunov function method with the convex hull technique, sufficient conditions in terms of LMIs for the solvability of the robust stabilisation and weighted L2-gain problems are presented respectively under the dwell time scheme. Finally, a numerical example is given to demonstrate the feasibility and effectiveness of the proposed results.

  5. Q-Switching in a Neodymium Laser

    Science.gov (United States)

    Holgado, Warein; Sola, Inigo J.; Jarque, Enrique Conejero; Jarabo, Sebastian; Roso, Luis

    2012-01-01

    We present a laboratory experiment for advanced undergraduate or graduate laser-related classes to study the performance of a neodymium laser. In the experiment, the student has to build the neodymium laser using an open cavity. After that, the cavity losses are modulated with an optical chopper located inside, so the Q-switching regime is…

  6. Analysis of a digital microstrip optical switch: a novel method

    Science.gov (United States)

    Al-Ruwaihi, Khalid M.; Hindy, Moataza A.

    1997-02-01

    A time domain analysis of an optically controlled digital microstrip switch for microwave integrated circuits on Si substrates is studied. A new model for high-frequency pulse propagation on a microstrip optical switch for different optical parameters is presented. A frequency-dependent macromodel for a microstrip line with a gap is implemented in Spice 3, taking into consideration high-frequency pulse dispersion, conductor and dielectric losses, metallization thickness, gap length, and different optical parameters such as optical energy, surface recombination velocities, and diffusion of generated carriers. In addition, the developed model has been used to optimize the switching frequency, gap length, level of optical power, and suitable substrate material parameters.

  7. Opc expression, LPS immunotype switch and pilin conversion contribute to serum resistance of unencapsulated meningococci.

    Directory of Open Access Journals (Sweden)

    Kerstin Hubert

    Full Text Available Neisseria meningitidis employs polysaccharides and outer membrane proteins to cope with human serum complement attack. To screen for factors influencing serum resistance, an assay was developed based on a colorimetric serum bactericidal assay. The screening used a genetically modified sequence type (ST-41/44 clonal complex (cc strain lacking LPS sialylation, polysaccharide capsule, the factor H binding protein (fHbp and MutS, a protein of the DNA repair mechanism. After killing of >99.9% of the bacterial cells by serum treatment, the colorimetric assay was used to screen 1000 colonies, of which 35 showed enhanced serum resistance. Three mutant classes were identified. In the first class of mutants, enhanced expression of Opc was identified. Opc expression was associated with vitronectin binding and reduced membrane attack complex deposition confirming recent observations. Lipopolysaccharide (LPS immunotype switch from immunotype L3 to L8/L1 by lgtA and lgtC phase variation represented the second class. Isogenic mutant analysis demonstrated that in ST-41/44 cc strains the L8/L1 immunotype was more serum resistant than the L3 immunotype. Consecutive analysis revealed that the immunotypes L8 and L1 were frequently observed in ST-41/44 cc isolates from both carriage and disease. Immunotype switch to L8/L1 is therefore suggested to contribute to the adaptive capacity of this meningococcal lineage. The third mutant class displayed a pilE allelic exchange associated with enhanced autoaggregation. The mutation of the C terminal hypervariable region D of PilE included a residue previously associated with increased pilus bundle formation. We suggest that autoaggregation reduced the surface area accessible to serum complement and protected from killing. The study highlights the ability of meningococci to adapt to environmental stress by phase variation and intrachromosomal recombination affecting subcapsular antigens.

  8. Clinical Evaluation of Recombinant Human Epidermal Growth Factor Dressing on Facial Skin after Q -switched Alexandrite Laser Therapy for Nevus Fusco -Caeruleus Zygomaticus%重组人表皮生长因子面膜护理颧部褐青色痣激光术后创面的临床评价

    Institute of Scientific and Technical Information of China (English)

    刘刚; 严蕾; 王芳

    2014-01-01

    目的:评估重组人表皮生长因子(EGF)面膜对颧部褐青色痣激光术后皮肤创面修复能力的临床疗效和安全性。方法:选择56例接受颧部褐青色痣激光治疗的患者,随机分为两组,实验组29例,激光术后即刻使用 EGF 面膜冷敷,并于治疗后隔1天敷1次,连续使用10天,每次20分钟;对照组27例,治疗后即刻用冰敷20分钟,并在术后10天内,常规使用红霉素软膏作为创面护理。分别于治疗后即刻,冷敷20分钟后、治疗后第1、3、5天及第9天,记录两组患者的症状、体征及创面愈合脱痂情况。结果:实验组29例患者经过 EGF 面膜冷敷后,术后的主观症状,如刺痛、灼热及紧绷感等得到明显缓解,结痂时间及痂壳脱落时间缩短,且脱落后创面光滑无红肿,整个过程无不良反应。结论:EGF 面膜用于颧部褐青色痣激光术后,可以改善术后的主观症状,减轻红斑、水肿等不良反应,促进皮肤创面快速修复。%Objective To evaluate the clinical curative ef ect and safety of recombinant human epidermal growth factor dressings applied after laser therapy for Nevus Fusco -Caeruleus Zy-gomaticus.Methods Altogether 56 patients with Nevus Fusco -Caeruleus Zygomaticus were enrol ed in this clinical trial.After the treatment with Q -switched Alexandrite Laser,the patients were randomly divided into two groups.The 29 patients in the experimental group were smeared with recombinant human epidermal growth factor dressings on the face for 20 minutes immediately after laser therapy,and then once every 2 days for 10 days,While 27 patients in the control group were treated by Erythromycin ointment.Symptoms,physical signs and wound healing of two groups were recorded immediately,20 minutes,1,3,5 and 9 days after treatment respectively.Results Compared with the control group,the experimental group showed a bet er improvement of acute inflammatory responses

  9. Recombinant DNA in Medicine

    OpenAIRE

    Cederbaum, Stephen D.; Fareed, George C.; Lovett, Michael A.; Shapiro, Larry J.

    1984-01-01

    Studies in bacteria and bacterial viruses have led to methods to manipulate and recombine DNA in unique and reproducible ways and to amplify these recombined molecules millions of times. Once properly identified, the recombinant DNA molecules can be used in various ways useful in medicine and human biology. There are many applications for recombinant DNA technology. Cloned complementary DNA has been used to produce various human proteins in microorganisms. Insulin and growth hormone have been...

  10. Improving baculovirus recombination

    OpenAIRE

    Zhao, Yuguang; Chapman, David A. G.; Jones, Ian M.

    2003-01-01

    Recombinant baculoviruses have established themselves as a favoured technology for the high-level expression of recombinant proteins. The construction of recombinant viruses, however, is a time consuming step that restricts consideration of the technology for high throughput developments. Here we use a targeted gene knockout technology to inactivate an essential viral gene that lies adjacent to the locus used for recombination. Viral DNA prepared from the knockout fails to initiate an infecti...

  11. Molecular mechanisms of DNA recombination: testing mitotic and meiotic models

    International Nuclear Information System (INIS)

    A hyperhaploid n + 1 strain of Saccharomyces cerevisiae (LBL1) disomic for chromosome VII was employed to isolate hyper-rec and hypo-rec mutations affecting spontaneous mitotic gene conversion and intergenic recombination. The genotype of LBL1 permits simultaneous and independent identification of rec mutations that enhance or diminish gene conversion and those that enhance or diminish intergenic recombination. Five phenotypic groups of rec mutants were isolated following ultraviolet light mutagenesis. Rec mutations that simultaneously abolish or enhance both classes of recombinational events were detected. These results demonstrate that gene conversion and intergenic recombination are under joint genetic control in mitotic cells. Conversion-specific and intergenic recombination-specific rec mutants were also recovered. Their properties indicate that conversion and intergenic recombination are separable pheonomena dependent upon discrete REC genes. The rec mutants isolated in LBL1 provide a method to test molecular models of mitotic and meiotic recombination

  12. Genetic Recombination as a Chemical Reaction Network

    OpenAIRE

    Müller, Stefan; Hofbauer, Josef

    2015-01-01

    The process of genetic recombination can be seen as a chemical reaction network with mass-action kinetics. We review the known results on existence, uniqueness, and global stability of an equilibrium in every compatibility class and for all rate constants, from both the population genetics and the reaction networks point of view.

  13. Variable time-period optical switching: a novel OBS implementation

    Institute of Scientific and Technical Information of China (English)

    Jinsong Zhang(张劲松); Mingcui Cao(曹明翠); Fengguang Luo(罗风光); Tao Chen(陈涛)

    2003-01-01

    In this paper, we proposed a novel optical switching method based on optical burst switching (OBS), we call it variable time-period optical switching (VTPOS). It can both support circuit services and other immerged packet services. It has better usability of bandwidth, shorter offset and latency time than others of unidirectional transport signaling mechanisms for OBS. It supports deflection switching for improve blocking performance without the need of schedule buffer. It introduces a time pointer and phase indicator that made synchronous more precisely and requires less guard time, it also classifies the different services classes with a relative QoS model.

  14. Geometry of the Limit Sets of Linear Switched Systems

    CERN Document Server

    Balde, Moussa

    2010-01-01

    The paper is concerned with asymptotic stability properties of linear switched systems. Under the hypothesis that all the subsystems share a non strict quadratic Lyapunov function, we provide a large class of switching signals for which a large class of switched systems are asymptotically stable. For this purpose we define what we call non chaotic inputs, which generalize the different notions of inputs with dwell time. Next we turn our attention to the behaviour for possibly chaotic inputs. To finish we give a sufficient condition for a system composed of a pair of Hurwitz matrices to be asymptotically stable for all inputs.

  15. Fission yeast mating-type switching: programmed damage and repair

    DEFF Research Database (Denmark)

    Egel, Richard

    2005-01-01

    Mating-type switching in fission yeast follows similar rules as in budding yeast, but the underlying mechanisms are entirely different. Whilst the initiating double-strand cut in Saccharomyces cerevisiae requires recombinational repair for survival, the initial damage in Schizosaccharomyces pombe...

  16. Hairpin-induced tRNA-mediated (HITME) recombination in HIV-1

    NARCIS (Netherlands)

    P. Konstantinova; P. de Haan; A.T. Das; B. Berkhout

    2006-01-01

    Recombination due to template switching during reverse transcription is a major source of genetic variability in retroviruses. In the present study we forced a recombination event in human immunodeficiency virus type 1 (HIV-1) by electroporation of T cells with DNA from a molecular HIV-1 clone that

  17. Photoionization and Recombination

    Science.gov (United States)

    Nahar, Sultana N.

    2000-01-01

    Theoretically self-consistent calculations for photoionization and (e + ion) recombination are described. The same eigenfunction expansion for the ion is employed in coupled channel calculations for both processes, thus ensuring consistency between cross sections and rates. The theoretical treatment of (e + ion) recombination subsumes both the non-resonant recombination ("radiative recombination"), and the resonant recombination ("di-electronic recombination") processes in a unified scheme. In addition to the total, unified recombination rates, level-specific recombination rates and photoionization cross sections are obtained for a large number of atomic levels. Both relativistic Breit-Pauli, and non-relativistic LS coupling, calculations are carried out in the close coupling approximation using the R-matrix method. Although the calculations are computationally intensive, they yield nearly all photoionization and recombination parameters needed for astrophysical photoionization models with higher precision than hitherto possible, estimated at about 10-20% from comparison with experimentally available data (including experimentally derived DR rates). Results are electronically available for over 40 atoms and ions. Photoionization and recombination of He-, and Li-like C and Fe are described for X-ray modeling. The unified method yields total and complete (e+ion) recombination rate coefficients, that can not otherwise be obtained theoretically or experimentally.

  18. Introduction to Optical Burst Switching

    OpenAIRE

    KERNÁCS János; SZILÁGYI Szabolcs

    2010-01-01

    Optical Burst Switching (OBS) isconsidered a popular switching paradigm for therealization of all-optical networks due to the balance itoffers between the coarse-grained Optical CircuitSwitching (OSC) and fine-grained Optical PacketSwitching (OPS). Given that the data are switched allopticallyat the burst level, Optical Burst Switchingcombines the transparency of Optical CircuitSwitching with the benefits of statistical multiplexingin Optical Packet Switching.

  19. Saturated Switching Systems

    CERN Document Server

    Benzaouia, Abdellah

    2012-01-01

    Saturated Switching Systems treats the problem of actuator saturation, inherent in all dynamical systems by using two approaches: positive invariance in which the controller is designed to work within a region of non-saturating linear behaviour; and saturation technique which allows saturation but guarantees asymptotic stability. The results obtained are extended from the linear systems in which they were first developed to switching systems with uncertainties, 2D switching systems, switching systems with Markovian jumping and switching systems of the Takagi-Sugeno type. The text represents a thoroughly referenced distillation of results obtained in this field during the last decade. The selected tool for analysis and design of stabilizing controllers is based on multiple Lyapunov functions and linear matrix inequalities. All the results are illustrated with numerical examples and figures many of them being modelled using MATLAB®. Saturated Switching Systems will be of interest to academic researchers in con...

  20. Recombineering Homologous Recombination Constructs in Drosophila

    OpenAIRE

    Carreira-Rosario, Arnaldo; Scoggin, Shane; Shalaby, Nevine A.; Williams, Nathan David; Hiesinger, P. Robin; Buszczak, Michael

    2013-01-01

    The continued development of techniques for fast, large-scale manipulation of endogenous gene loci will broaden the use of Drosophila melanogaster as a genetic model organism for human-disease related research. Recent years have seen technical advancements like homologous recombination and recombineering. However, generating unequivocal null mutations or tagging endogenous proteins remains a substantial effort for most genes. Here, we describe and demonstrate techniques for using recombineeri...

  1. Stochastic Switching Circuit Synthesis

    OpenAIRE

    Wilhelm, Daniel; Bruck, Jehoshua

    2009-01-01

    Shannon in his 1938 Masterpsilas Thesis demonstrated that any Boolean function can be realized by a switching relay circuit, leading to the development of deterministic digital logic. Here, we replace each classical switch with a probabilistic switch (pswitch). We present algorithms for synthesizing circuits closed with a desired probability, including an algorithm that generates optimal size circuits for any binary fraction. We also introduce a new duality property for series-parallel stocha...

  2. Atomic Scale Plasmonic Switch

    OpenAIRE

    Emboras, A.; Niegemann, J.; Ma, P; Haffner, C; Pedersen, A.; Luisier, M.; Hafner, C; Schimmel, T.; Leuthold, J.

    2016-01-01

    The atom sets an ultimate scaling limit to Moore’s law in the electronics industry. While electronics research already explores atomic scales devices, photonics research still deals with devices at the micrometer scale. Here we demonstrate that photonic scaling, similar to electronics, is only limited by the atom. More precisely, we introduce an electrically controlled plasmonic switch operating at the atomic scale. The switch allows for fast and reproducible switching by means of the relocat...

  3. FreeSWITCH Cookbook

    CERN Document Server

    Minessale, Anthony

    2012-01-01

    This is a problem-solution approach to take your FreeSWITCH skills to the next level, where everything is explained in a practical way. If you are a system administrator, hobbyist, or someone who uses FreeSWITCH on a regular basis, this book is for you. Whether you are a FreeSWITCH expert or just getting started, this book will take your skills to the next level.

  4. Guaranteed cost control with constructing switching law of uncertain discrete-time switched systems

    Institute of Scientific and Technical Information of China (English)

    Zhang Ying; Duan Guangren

    2007-01-01

    A guaranteed cost control problem for a class of linear discrete-time switched systems with normbounded uncertainties is considered in this article. The purpose is to construct a switching rule and design a state feedback control law, such that, the closed-loop system is asymptotically stable and the closed-loop cost function value is not more than a specified upper bound for all admissible uncertainties under the constructed switching rule.A sufficient condition for the existence of guaranteed cost controllers and switching rules is derived based on the Lyapunov theory together with the linear matrix inequality (LMI) approach. Furthermore, a convex optimization problem with LMI constraints is formulated to select the suboptimal guaranteed cost controller. A numerical example demonstrates the validity of the proposed design approach.

  5. Development of a rapid in vitro protein refolding assay which discriminates between peptide-bound and peptide-free forms of recombinant porcine major histocompatibility class I complex (SLA-I)

    DEFF Research Database (Denmark)

    Oleksiewicz, M.B.; Kristensen, B.; Ladekjaer-Mikkelsen, A.S.;

    2002-01-01

    The extracellular domains of swine leukocyte antigen class I (SLA-I, major histocompatibility complex protein class 1) were cloned and sequenced for two haplotypes (114 and H7) which do not share any alleles based on serological typing, and which are the most important in Danish farmed pigs....... The extracellular domain of SLA-I was connected to porcine beta2 microglobulin by glycine-rich linkers. The engineered sin.-le-chain proteins, consisting of fused SLA-I and beta2 microglobulin, were overexpressed as inclusion bodies in Escherichia coli. Also, variants were made of the single-chain proteins......, by linking them through glycine-rich linkers to peptides representing T-cell epitopes from classical swine fever virus (CSFV) and foot-and-mouth disease virus (FMDV). An in vitro refold assay was developed, using a monoclonal anti-SLA antibody (PT85A) to gauge refolding. The single best-defined, SLA...

  6. Asymmetrical Switch Costs in Children

    Science.gov (United States)

    Ellefson, Michelle R.; Shapiron, Laura R.; Chater, Nick

    2006-01-01

    Switching between tasks produces decreases in performance as compared to repeating the same task. Asymmetrical switch costs occur when switching between two tasks of unequal difficulty. This asymmetry occurs because the cost is greater when switching to the less difficult task than when switching to the more difficult task. Various theories about…

  7. Optical switching device

    NARCIS (Netherlands)

    Broeder, F.J.A. den; Hanzen, R.M.N.; Duine, P.A.; Jungblut, R.M.; Draijer, C.; Roozeboom, F.; Sluis, P. van der

    2000-01-01

    A description is given of an optical switching device (1) comprising a transparent substrate (3), a switching film (5) of a hydride compound of a trivalent transition or rare earth metal having a thickness of 300 nm, and a palladium capping layer (7) having a thickness of 30 nm. The capping layer is

  8. Multidimensional set switching.

    Science.gov (United States)

    Hahn, Sowon; Andersen, George J; Kramer, Arthur F

    2003-06-01

    The present study examined the organization of preparatory processes that underlie set switching and, more specifically, switch costs. On each trial, subjects performed one of two perceptual judgment tasks, color or shape discrimination. Subjects also responded with one of two different response sets. The task set and/or the response set switched from one to the other after 2-6 repeated trials. Response set, task set, and double set switches were performed in both blocked and randomized conditions. Subjects performed with short (100-msec) and long (800-msec) preparatory intervals. Task and response set switches had an additive effect on reaction times (RTs) in the blocked condition. Such a pattern of results suggests a serial organization of preparatory processes when the nature of switches is predictable. However, task and response set switches had an underadditive effect on RTs in the random condition when subjects performed with a brief cue-to-target interval. This pattern of results suggests overlapping task and response set preparation. These findings are discussed in terms of strategic control of preparatory processes in set switching. PMID:12921431

  9. Switch on, switch off: stiction in nanoelectromechanical switches

    KAUST Repository

    Wagner, Till J W

    2013-06-13

    We present a theoretical investigation of stiction in nanoscale electromechanical contact switches. We develop a mathematical model to describe the deflection of a cantilever beam in response to both electrostatic and van der Waals forces. Particular focus is given to the question of whether adhesive van der Waals forces cause the cantilever to remain in the \\'ON\\' state even when the electrostatic forces are removed. In contrast to previous studies, our theory accounts for deflections with large slopes (i.e. geometrically nonlinear). We solve the resulting equations numerically to study how a cantilever beam adheres to a rigid electrode: transitions between \\'free\\', \\'pinned\\' and \\'clamped\\' states are shown to be discontinuous and to exhibit significant hysteresis. Our findings are compared to previous results from linearized models and the implications for nanoelectromechanical cantilever switch design are discussed. © 2013 IOP Publishing Ltd.

  10. [Switching and combining strategies of antidepressant medications].

    Science.gov (United States)

    Charpeaud, Thomas; Moliere, Fanny; Bubrovszky, Maxime; Haesebaert, Frédéric; Allaïli, Najib; Bation, Rémy; Nieto, Isabel; Richieri, Raphaëlle; Saba, Ghassen; Bellivier, Frank; Bennabi, Djamila; Holtzmann, Jérôme; Camus, Vincent; Courtet, Philippe; Courvoisier, Pierre; d'Amato, Thierry; Doumy, Olivier; Garnier, Marion; Bougerol, Thierry; Lançon, Christophe; Haffen, Emmanuel; Leboyer, Marion; Llorca, Pierre-Michel; Vaiva, Guillaume; El-Hage, Wissam; Aouizerate, Bruno

    2016-03-01

    Switching antidepressant medication may be helpful in depressed patients having no benefit from the initial antidepressant treatment. Before considering switching strategy, the initial antidepressant treatment should produce no therapeutic effect after at least 4 weeks of administration at adequate dosage. Choosing an antidepressant of pharmacologically distinct profile fails to consistently demonstrate a significant superiority in terms of effectiveness over the switching to another antidepressant within the same pharmacological class. Augmenting SSRI/SNRIs with mirtazapine/mianserin has become the most recommended strategy of antidepressant combinations. Augmenting SSRI with tricyclic drugs is now a less recommended strategy of antidepressant combinations given the increased risk for the occurrence of pharmacokinetic drug-drug interactions and adverse effects.

  11. Balanced truncation for linear switched systems

    DEFF Research Database (Denmark)

    Petreczky, Mihaly; Wisniewski, Rafal; Leth, John-Josef

    2013-01-01

    in this paper, we provide a bound on the approximation error in the L2L2 norm for continuous-time and the l2l2 norm for discrete-time linear switched systems. We provide a system theoretic interpretation of grammians and their singular values. Furthermore, we show that the performance of balanced truncation......In this paper, we present a theoretical analysis of the model reduction algorithm for linear switched systems from Shaker and Wisniewski (2011, 2009) and . This algorithm is a reminiscence of the balanced truncation method for linear parameter varying systems (Wood et al., 1996) [3]. Specifically...... depends only on the input–output map and not on the choice of the state-space representation. For a class of stable discrete-time linear switched systems (so called strongly stable systems), we define nice controllability and nice observability grammians, which are genuinely related to reachability...

  12. Single Atom Plasmonic Switch

    CERN Document Server

    Emboras, Alexandros; Ma, Ping; Haffner, Christian; Luisier, Mathieu; Hafner, Christian; Schimmel, Thomas; Leuthold, Juerg

    2015-01-01

    The atom sets an ultimate scaling limit to Moores law in the electronics industry. And while electronics research already explores atomic scales devices, photonics research still deals with devices at the micrometer scale. Here we demonstrate that photonic scaling-similar to electronics-is only limited by the atom. More precisely, we introduce an electrically controlled single atom plasmonic switch. The switch allows for fast and reproducible switching by means of the relocation of an individual or at most - a few atoms in a plasmonic cavity. Depending on the location of the atom either of two distinct plasmonic cavity resonance states are supported. Experimental results show reversible digital optical switching with an extinction ration of 10 dB and operation at room temperature with femtojoule (fJ) power consumption for a single switch operation. This demonstration of a CMOS compatible, integrated quantum device allowing to control photons at the single-atom level opens intriguing perspectives for a fully i...

  13. Towards single molecule switches.

    Science.gov (United States)

    Zhang, Jia Lin; Zhong, Jian Qiang; Lin, Jia Dan; Hu, Wen Ping; Wu, Kai; Xu, Guo Qin; Wee, Andrew T S; Chen, Wei

    2015-05-21

    The concept of using single molecules as key building blocks for logic gates, diodes and transistors to perform basic functions of digital electronic devices at the molecular scale has been explored over the past decades. However, in addition to mimicking the basic functions of current silicon devices, molecules often possess unique properties that have no parallel in conventional materials and promise new hybrid devices with novel functions that cannot be achieved with equivalent solid-state devices. The most appealing example is the molecular switch. Over the past decade, molecular switches on surfaces have been intensely investigated. A variety of external stimuli such as light, electric field, temperature, tunneling electrons and even chemical stimulus have been used to activate these molecular switches between bistable or even multiple states by manipulating molecular conformations, dipole orientations, spin states, charge states and even chemical bond formation. The switching event can occur either on surfaces or in break junctions. The aim of this review is to highlight recent advances in molecular switches triggered by various external stimuli, as investigated by low-temperature scanning tunneling microscopy (LT-STM) and the break junction technique. We begin by presenting the molecular switches triggered by various external stimuli that do not provide single molecule selectivity, referred to as non-selective switching. Special focus is then given to selective single molecule switching realized using the LT-STM tip on surfaces. Single molecule switches operated by different mechanisms are reviewed and discussed. Finally, molecular switches embedded in self-assembled monolayers (SAMs) and single molecule junctions are addressed. PMID:25757483

  14. A Metabolic Switch

    DEFF Research Database (Denmark)

    Hjorth, Poul G.

    Our muscles are metabolically flexible, i.e., they are capable of `switching' between two types of oxidation: (1) when fasting, a predominantly lipid oxidation with high rates of fatty acid uptake, and (2) when fed, suppression of lipid oxidation in favour of increased glucose uptake, oxidation...... and storage, in response to insulin. One of the many manifestations of obesity and Type 2 diabetes is an insulin resistance of the skeletal muscles, which suppresses this metabolic switch. This talk describes recent development of a low-dimensional system of ODEs that model the metabolic switch, displaying...

  15. JUNOS Enterprise Switching

    CERN Document Server

    Reynolds, Harry

    2009-01-01

    JUNOS Enterprise Switching is the only detailed technical book on Juniper Networks' new Ethernet-switching EX product platform. With this book, you'll learn all about the hardware and ASIC design prowess of the EX platform, as well as the JUNOS Software that powers it. Not only is this extremely practical book a useful, hands-on manual to the EX platform, it also makes an excellent study guide for certification exams in the JNTCP enterprise tracks. The authors have based JUNOS Enterprise Switching on their own Juniper training practices and programs, as well as the configuration, maintenanc

  16. Switch mode power supply

    International Nuclear Information System (INIS)

    This book concentrates on switch mode power supply. It has four parts, which are introduction of switch mode power supply with DC-DC converter such as Buck converter boost converter, Buck-boost converter and PWM control circuit, explanation for SMPS with DC-DC converter modeling and power mode control, resonance converter like resonance switch, converter, multi resonance converter and series resonance and parallel resonance converters, basic test of SMPS with PWM control circuit, Buck converter, Boost converter, flyback converter, forward converter and IC for control circuit.

  17. SPARK GAP SWITCH

    Science.gov (United States)

    Neal, R.B.

    1957-12-17

    An improved triggered spark gap switch is described, capable of precisely controllable firing time while switching very large amounts of power. The invention in general comprises three electrodes adjustably spaced and adapted to have a large potential impressed between the outer electrodes. The central electrode includes two separate elements electrically connected togetaer and spaced apart to define a pair of spark gaps between the end electrodes. Means are provided to cause the gas flow in the switch to pass towards the central electrode, through a passage in each separate element, and out an exit disposed between the two separate central electrode elements in order to withdraw ions from the spark gap.

  18. Generalized Multi-Cell Switched-Inductor and Switched-Capacitor Z-source Inverters

    DEFF Research Database (Denmark)

    Li, Ding; Chiang Loh, Poh; Zhu, Miao;

    2013-01-01

    -type Z-source in- verters were earlier proposed. These new classes of inverters are generally more robust and less sensitive to electromagnetic noises. However, their boosting capabilities are somehow compromised by high component stresses and poorer spectral performances caused by low modulation ratios....... Their boosting gains are, therefore, limited in practice. To overcome these shortcomings, the generalized switched-inductor and switched-capacitor Z-source inverters are proposed, whose extra boosting abilities and other advantages have already been verified in simulation and experiment....

  19. Robust H∞ Control for Switched Nonlinear System with Multiple Delays

    Directory of Open Access Journals (Sweden)

    Juan Liu

    2015-01-01

    Full Text Available This paper focuses on the problem of robust H∞ control for a class of switched nonlinear systems with multiple time delays which are allowed to appear not only in state but also in input. We will design a controller and a switching law under which the system is “robust stable” and has performance L2-gain γ. Besides, multiple Lyapunov-Razumikhin functions which are relatively less conservative are introduced to investigate the stability of the candidate switched system. In detail, firstly, for uncertain nonlinear switched system with time-varying delays, sufficient condition is given by inequalities which are equivalent to LMIs, so it is easy to be solved; then, as a special case, nonlinear switched system with constant time delay is also considered. Finally, by providing numerical examples, the feasibility of the proposed approach is demonstrated.

  20. Switch Attention to Listen

    OpenAIRE

    Dhamani, Imran; Leung, Johahn; Carlile, Simon; Sharma, Mridula

    2013-01-01

    The aim of this research was to evaluate the ability to switch attention and selectively attend to relevant information in children (10–15 years) with persistent listening difficulties in noisy environments. A wide battery of clinical tests indicated that children with complaints of listening difficulties had otherwise normal hearing sensitivity and auditory processing skills. Here we show that these children are markedly slower to switch their attention compared to their age-matched peers. T...

  1. Switching to Photonics

    OpenAIRE

    Hinton, Harvard S.

    1992-01-01

    The use of hardware that exploits the interplay of photons and electrons to switch voice, data, and video is discussed. The two directions being taken by current research-guided-wave and free-space photonics-are examined. Photonic time-slot interchanges are described. Multidivisional fabrics, based on a combination of space-division and time-division multiplexing, are considered, as is the wavelength-division-based photonic packet switch, another kind of multidimensional fabric. The use of se...

  2. High Power Switching Transistor

    Science.gov (United States)

    Hower, P. L.; Kao, Y. C.; Carnahan, D. C.

    1983-01-01

    Improved switching transistors handle 400-A peak currents and up to 1,200 V. Using large diameter silicon wafers with twice effective area as D60T, form basis for D7 family of power switching transistors. Package includes npn wafer, emitter preform, and base-contact insert. Applications are: 25to 50-kilowatt high-frequency dc/dc inverters, VSCF converters, and motor controllers for electrical vehicles.

  3. Photonics in switching

    CERN Document Server

    Midwinter, John E; Kelley, Paul

    1993-01-01

    Photonics in Switching provides a broad, balanced overview of the use of optics or photonics in switching, from materials and devices to system architecture. The chapters, each written by an expert in the field, survey the key technologies, setting them in context and highlighting their benefits and possible applications. This book is a valuable resource for those working in the communications industry, either at the professional or student level, who do not have extensive background knowledge or the underlying physics of the technology.

  4. Ferroelectric switching of elastin

    OpenAIRE

    Liu, Yuanming; Cai, Hong-Ling; Zelisko, Matthew; WANG, YUNJIE; Sun, Jinglan; Yan, Fei; Ma, Feiyue; Wang, Peiqi; Chen, Qian Nataly; Zheng, Hairong; Meng, Xiangjian; SHARMA, PRADEEP; Zhang, Yanhang; Li, Jiangyu

    2014-01-01

    Ferroelectricity has long been speculated to have important biological functions, although its very existence in biology has never been firmly established. Here, we present, to our knowledge, the first macroscopic observation of ferroelectric switching in a biological system, and we elucidate the origin and mechanism underpinning ferroelectric switching of elastin. It is discovered that the polarization in elastin is intrinsic at the monomer level, analogous to the unit cell level polarizatio...

  5. Recombinant methods and materials

    Energy Technology Data Exchange (ETDEWEB)

    Roizman, B.; Post, L.E.

    1988-09-06

    This patent describes a method for stably effecting the insertion or deletion of a selected DNA sequence at a specific site in a viral genome. The method consists of: (1) isolating from the genome a linear DNA fragment comprising both (a) the specific site determined for insertion or deletion of selected DNA sequence and (b) flanking DNA sequences normally preceding and following the site; (2) preparing first and second altered genome fragments from the fragment isolated in step (1). (a) the first altered fragment comprising the fragment comprising a thymidine kinase gene in a position intermediate the ends of the fragment, and (b) the second altered fragment comprising the fragment having the selected DNA sequence inserted therein or deleted therefrom; (3) contacting the genome with the first altered fragment under conditions permitting recombination at sites of DNA sequence homology, selecting for a recombinant genome comprising the thymidine kinase gene, and isolating the recombinant genome; and (4) contacting the recombinant genome isolated in step (3) with the second altered fragment under conditions permitting recombination at sites of DNA sequence homology, selecting for a recombinant genome lacking the thymidine kinase gene, and isolating the recombinant genome product.

  6. Finding a stabilising switching law for switching nonlinear models

    Science.gov (United States)

    Lendek, Zs.; Raica, P.; Lauber, J.; Guerra, T. M.

    2016-09-01

    This paper considers the stabilisation of switching nonlinear models by switching between the subsystems. We assume that arbitrary switching between two subsystems is possible once a subsystem has been active for a predefined number of samples. We use a Takagi-Sugeno representation of the models and a switching Lyapunov function is employed to develop sufficient stability conditions. If the conditions are satisfied, we construct a switching law that stabilises the system. The application of the conditions is illustrated in several examples.

  7. Analysis and Synthesis of pHEMT Class-E Amplifiers with Shunt Inductor including ON-State Active-Device Resistance Effects

    OpenAIRE

    Thian, Mury; Fusco, Vincent

    2006-01-01

    In this theoretical paper, the analysis of the effect that ON-state active-device resistance has on the performance of a Class-E tuned power amplifier using a shunt inductor topology is presented. The work is focused on the relatively unexplored area of design facilitation of Class-E tuned amplifiers where intrinsically low-output-capacitance monolithic microwave integrated circuit switching devices such as pseudomorphic high electron mobility transistors are used. In the paper, the switching...

  8. Optical switching systems using nanostructures

    DEFF Research Database (Denmark)

    Stubkjær, Kristian

    2004-01-01

    High capacity multiservice optical networks require compact and efficient switches. The potential benefits of optical switch elements based on nanostructured material are reviewed considering various material systems.......High capacity multiservice optical networks require compact and efficient switches. The potential benefits of optical switch elements based on nanostructured material are reviewed considering various material systems....

  9. Understanding and Supporting Window Switching

    NARCIS (Netherlands)

    Tak, S.

    2011-01-01

    Switching between windows on a computer is a frequent activity, but finding and switching to the target window can be inefficient. This thesis aims to better un-derstand and support window switching. It explores two issues: (1) the lack of knowledge of how people currently interact with and switch b

  10. A Transformer Class E Amplifier

    Directory of Open Access Journals (Sweden)

    Mikolajewski Miroslaw

    2014-12-01

    Full Text Available In a high-efficiency Class E ZVS resonant amplifier a matching and isolation transformer can replace some or even all inductive components of the amplifier thus simplifying the circuit and reducing its cost. In the paper a theoretical analysis, a design example and its experimental verification for a transformer Class E amplifier are presented. In the experimental amplifier with a transformer as the only inductive component in the circuit high efficiency ηMAX = 0.95 was achieved for supply voltage VI = 36 V, maximum output power POMAX = 100 W and the switching frequency f = 300 kHz. Measured parameters and waveforms showed a good agreement with theoretical predictions. Moreover, the relative bandwidth of the switching frequency was only 19% to obtain output power control from 4.8 W to POMAX with efficiency not less than 0.9 in the regulation range.

  11. Response switching and self-efficacy in Peer Instruction classrooms

    Science.gov (United States)

    Miller, Kelly; Schell, Julie; Ho, Andrew; Lukoff, Brian; Mazur, Eric

    2015-06-01

    Peer Instruction, a well-known student-centered teaching method, engages students during class through structured, frequent questioning and is often facilitated by classroom response systems. The central feature of any Peer Instruction class is a conceptual question designed to help resolve student misconceptions about subject matter. We provide students two opportunities to answer each question—once after a round of individual reflection and then again after a discussion round with a peer. The second round provides students the choice to "switch" their original response to a different answer. The percentage of right answers typically increases after peer discussion: most students who answer incorrectly in the individual round switch to the correct answer after the peer discussion. However, for any given question there are also students who switch their initially right answer to a wrong answer and students who switch their initially wrong answer to a different wrong answer. In this study, we analyze response switching over one semester of an introductory electricity and magnetism course taught using Peer Instruction at Harvard University. Two key features emerge from our analysis: First, response switching correlates with academic self-efficacy. Students with low self-efficacy switch their responses more than students with high self-efficacy. Second, switching also correlates with the difficulty of the question; students switch to incorrect responses more often when the question is difficult. These findings indicate that instructors may need to provide greater support for difficult questions, such as supplying cues during lectures, increasing times for discussions, or ensuring effective pairing (such as having a student with one right answer in the pair). Additionally, the connection between response switching and self-efficacy motivates interventions to increase student self-efficacy at the beginning of the semester by helping students develop early mastery or

  12. Stability and Stabilization of Block-cascading Switched Linear Systems

    Institute of Scientific and Technical Information of China (English)

    Ya-Hong Zhu; Dai-Zhan Cheng

    2006-01-01

    The main purpose of this paper is to investigate the problem of quadratic stability and stabilization in switched linear systems using reducible Lie algebra. First, we investigate the structure of all real invariant subspaces for a given linear system. The result is then used to provide a comparable cascading form for switching models. Using the commoncascading form, a common quadratic Lyapunov function is (QLFs) is explored by finding common QLFs of diagonal blocks.In addition, a cascading Quaker Lemma is proved. Combining it with stability results, the problem of feedback stabilization for a class of switched linear systems is solved.

  13. A Novel Single-Switch Single-Stage Electronic Ballast

    Institute of Scientific and Technical Information of China (English)

    Lu-Hua Zhu; Xing-Bi Chen; Hong-Sheng Zhong

    2009-01-01

    A single-stage single-switch high- frequency electronic ballast topology is presented. The circuit topology is the integration of a buck power- factor-correction (PFC) converter and a class E resonant inverter with only one active power switch. The buck converter is operated in discontinuous conduction mode and at a fixed switching frequency, and constant duty cycle to achieve high power factor and it can be controlled easily. Detailed analysis of the operation and characteristics of the circuit is provided. Simulation results satisfy present standard require- ments.

  14. Low inductance gas switching.

    Energy Technology Data Exchange (ETDEWEB)

    Chavez, Ray; Harjes, Henry Charles III; Wallace, Zachariah; Elizondo, Juan E.

    2007-10-01

    The laser trigger switch (LTS) is a key component in ZR-type pulsed power systems. In ZR, the pulse rise time through the LTS is > 200 ns and additional stages of pulse compression are required to achieve the desired <100 ns rise time. The inductance of the LTS ({approx}500nH) in large part determines the energy transfer time through the switch and there is much to be gained in improving system performance and reducing system costs by reducing this inductance. The current path through the cascade section of the ZR LTS is at a diameter of {approx} 6-inches which is certainly not optimal from an inductance point of view. The LTS connects components of much greater diameter (typically 4-5 feet). In this LDRD the viability of switch concepts in which the diameter of cascade section is greatly increased have been investigated. The key technical question to be answered was, will the desired multi-channel behavior be maintained in a cascade section of larger diameter. This LDRD proceeded in 2 distinct phases. The original plan for the LDRD was to develop a promising switch concept and then design, build, and test a moderate scale switch which would demonstrate the key features of the concept. In phase I, a switch concept which meet all electrical design criteria and had a calculated inductance of 150 nH was developed. A 1.5 MV test switch was designed and fabrication was initiated. The LDRD was then redirected due to budgetary concerns. The fabrication of the switch was halted and the focus of the LDRD was shifted to small scale experiments designed to answer the key technical question concerning multi-channel behavior. In phase II, the Multi-channel switch test bed (MCST) was designed and constructed. The purpose of MCST was to provide a versatile, fast turn around facility for the study the multi-channel electrical breakdown behavior of a ZR type cascade switch gap in a parameter space near that of a ZR LTS. Parameter scans on source impedance, gap tilt, gap spacing and

  15. Colony mutants of compatible nocardiae displaying variations in recombining capacity.

    Science.gov (United States)

    Brownell, G H; Walsh, R S

    1972-03-01

    Colonial morphology mutants of Nocardia erythropolis were isolated following ultraviolet (UV) irradiation. The alleles rou-1/smo-1 were located by recombinant analysis and found to be linked to previously mapped characters. On the basis of recombinant class type patterns obtained from various selective characters it was postulated that the rou-1 allele may span a region of unique nucleotides in the Mat-Ce genome. Recombination frequencies of rou-1 and smo-2 bearing mutants of the Mat-Ce mating type were found to differ by over 1000 fold. Attempts to demonstrate that low recombination frequencies produced by the Smo mutants were due to Rec(-) genes were unsuccessful. No increased sensitivity to either UV or X irradiation was observed by the Smo mutants. Acriflavine treatment of either Rou or Smo colony mutants failed to accelerate reversion or to alter the recombining potentials of the mutants.

  16. Comparison of Memory Assignment Schemes for Switch Architectures with Shareable Parallel Memory Modules

    Directory of Open Access Journals (Sweden)

    Sanjeev Kumar

    2010-01-01

    Full Text Available Switching Architectures deploying shareable parallel memory modules are quite versatile in their ability to scale to higher capacity while retaining the advantage of sharing its entire memory resource among all input and output ports. The two main classes of such architectures, namely, the Shared Multibuffer-(SMB- based switch and the Sliding-Window-(SW- based packet switch, both deploy parallel memory modules that are physically separate but logically connected. Inspite of their similarity in regards to using shareable parallel memory modules, they differ in switching control and scheduling of packets to parallel memory modules. SMB switch uses centralized control whereas the SW switch uses a decentralized control for switching operations. In this paper, we present a new memory assignment scheme for the Sliding-Window (SW switch for assigning packets to parallel memory modules that maximizes the parallel storage of packets to multiple memory modules. We compare the performance of a sliding-window switch deploying this new memory assignment scheme with that of an SMB switch architecture under conditions of identical traffic type and memory resources deployed. The simulation results show that the new memory assignment scheme for the sliding window switch maximizes parallel storage of packets input in a given switch cycle, and it does not require speed-up of memory modules. Furthermore, it provides a superior performance compared to that of the SMB switch under the constraints of fixed memory-bandwidth and memory resources.

  17. Energy reversible switching from amorphous metal based nanoelectromechanical switch

    KAUST Repository

    Mayet, Abdulilah M.

    2013-08-01

    We report observation of energy reversible switching from amorphous metal based nanoelectromechanical (NEM) switch. For ultra-low power electronics, NEM switches can be used as a complementary switching element in many nanoelectronic system applications. Its inherent zero power consumption because of mechanical detachment is an attractive feature. However, its operating voltage needs to be in the realm of 1 volt or lower. Appropriate design and lower Young\\'s modulus can contribute achieving lower operating voltage. Therefore, we have developed amorphous metal with low Young\\'s modulus and in this paper reporting the energy reversible switching from a laterally actuated double electrode NEM switch. © 2013 IEEE.

  18. Influence of an English Lecturer's Code-Switching Practice on Student?s Confidence in the Subject

    OpenAIRE

    Lee Yi Ling; Ng Yu Jin; Chong Seng Tong; Mohd. Ariff Tarmizi; Nurhanis Sahiddan

    2014-01-01

    Malaysian classrooms are culturally-diverse and used to the practice of switching from one language to another. This practice is known as code-switching. Code-switching takes place not only among students? communication but also among educators in order to facilitate students? learning process. The factors of educators code-switching in class has been an area of study frequently explored by scholars. Nonetheless, not many have looked at it from the students? perspectives in response to what t...

  19. Laboratory Switching Power Supply

    OpenAIRE

    Slezák, Jakub

    2009-01-01

    This bachelor’s thesis is concerned with design switching power supply based on forward converter with output voltage regulated in the range of 3 to 30V and load current to 1 A. First of all, it discusses the theoretical solution of basic types of converters and switching power supply problems. Followed by a proposal of various parts source, which was first established in the test version on the test board. Then was proposed printed circuit board and complete mechanical solutions. Source is a...

  20. Photonics in Switching

    OpenAIRE

    Hinton, Harvard S.

    1992-01-01

    One of the keys to the future of telecommunications companies will be their ability to provide new broadband services to both the business community and residential customers. With the new services will come the need for the equivalent of a broadband switching office. Such a system could require the capability of supporting in excess of 10000 users with broadband channel bit rates exceeding 100 Mb/s. This implies a switching fabric the aggregate bit rate of which could be greater than 1 Tb/s....

  1. Regulation of Meiotic Recombination

    Energy Technology Data Exchange (ETDEWEB)

    Gregory p. Copenhaver

    2011-11-09

    Meiotic recombination results in the heritable rearrangement of DNA, primarily through reciprocal exchange between homologous chromosome or gene conversion. In plants these events are critical for ensuring proper chromosome segregation, facilitating DNA repair and providing a basis for genetic diversity. Understanding this fundamental biological mechanism will directly facilitate trait mapping, conventional plant breeding, and development of genetic engineering techniques that will help support the responsible production and conversion of renewable resources for fuels, chemicals, and the conservation of energy (1-3). Substantial progress has been made in understanding the basal recombination machinery, much of which is conserved in organisms as diverse as yeast, plants and mammals (4, 5). Significantly less is known about the factors that regulate how often and where that basal machinery acts on higher eukaryotic chromosomes. One important mechanism for regulating the frequency and distribution of meiotic recombination is crossover interference - or the ability of one recombination event to influence nearby events. The MUS81 gene is thought to play an important role in regulating the influence of interference on crossing over. The immediate goals of this project are to use reverse genetics to identify mutants in two putative MUS81 homologs in the model plant Arabidopsis thaliana, characterize those mutants and initiate a novel forward genetic screen for additional regulators of meiotic recombination. The long-term goal of the project is to understand how meiotic recombination is regulated in higher eukaryotes with an emphasis on the molecular basis of crossover interference. The ability to monitor recombination in all four meiotic products (tetrad analysis) has been a powerful tool in the arsenal of yeast geneticists. Previously, the qrt mutant of Arabidopsis, which causes the four pollen products of male meiosis to remain attached, was developed as a facile system

  2. Genetic recombination in plant-infecting messenger-sense RNA viruses: overview and research perspectives

    Directory of Open Access Journals (Sweden)

    Jozef Julian Bujarski

    2013-03-01

    Full Text Available RNA recombination is one of the driving forces of genetic variability in (+-strand RNA viruses. Various types of RNA-RNA crossovers were described including crosses between the same or different viral RNAs or between viral and cellular RNAs. Likewise, a variety of molecular mechanisms are known to support RNA recombination, such as replicative events (based on internal or end-to-end replicase switchings along with nonreplicative joining among RNA fragments of viral and/or cellular origin. Such mechanisms as RNA decay or RNA interference are responsible for RNA fragmentation and trans-esterification reactions which are likely accountable for ligation of RNA fragments. Numerous host factors were found to affect the profiles of viral RNA recombinants and significant differences in recombination frequency were observed among various RNA viruses. Comparative analyses of viral sequences allowed for the development of evolutionary models in order to explain adaptive phenotypic changes and co-evolving sites. Many questions remain to be answered by forthcoming RNA recombination research. (i How various factors modulate the ability of viral replicase to switch templates, (ii What is the intracellular location of RNA-RNA template switchings, (iii Mechanisms and factors responsible for non-replicative RNA recombination, (iv Mechanisms of integration of RNA viral sequences with cellular genomic DNA, and (v What is the role of RNA splicing and ribozyme activity. From an evolutionary stand point, it is not known how RNA viruses parasitize new host species via recombination, nor is it obvious what the contribution of RNA recombination is among other RNA modification pathways. We do not understand why the frequency of RNA recombination varies so much among RNA viruses and the status of RNA recombination as a form of sex is not well documented.

  3. Dynamics of all-optically switched micropillar resonances

    CERN Document Server

    Thyrrestrup, Henri; Ctistis, Georgios; Claudon, Julien; Vos, Willem L

    2014-01-01

    Here we do frequency and time resolved switching of a single GaAs/AlGa micropillar cavity with a pillar diameter of 6 mu using a ultrafast pump-probe setup. The switching is achieved by two-photon excitation of free carriers by an femtosecond pump pulse. We observe a simultaneously frequency shift of the first two transverse micropillar modes and obtain high resolution frequency traces of the two resonances in time. A difference in the the maximum switching magnitude of 12% point is caused by spatial inhomogeneous excitation of carriers in the pillar. The relaxation dynamic of the two resonances show a strongly non-exponential decay. We interpret the non-exponential dynamics in term of a second order decay model for the spontaneous recombination of electron and hole for the free carriers and a slow free carrier trapping time of ~300 ps.

  4. Phosphorylation: The Molecular Switch of Double-Strand Break Repair

    Directory of Open Access Journals (Sweden)

    K. C. Summers

    2011-01-01

    Full Text Available Repair of double-stranded breaks (DSBs is vital to maintaining genomic stability. In mammalian cells, DSBs are resolved in one of the following complex repair pathways: nonhomologous end-joining (NHEJ, homologous recombination (HR, or the inclusive DNA damage response (DDR. These repair pathways rely on factors that utilize reversible phosphorylation of proteins as molecular switches to regulate DNA repair. Many of these molecular switches overlap and play key roles in multiple pathways. For example, the NHEJ pathway and the DDR both utilize DNA-PK phosphorylation, whereas the HR pathway mediates repair with phosphorylation of RPA2, BRCA1, and BRCA2. Also, the DDR pathway utilizes the kinases ATM and ATR, as well as the phosphorylation of H2AX and MDC1. Together, these molecular switches regulate repair of DSBs by aiding in DSB recognition, pathway initiation, recruitment of repair factors, and the maintenance of repair mechanisms.

  5. High-speed switching characteristics of integrated optoelectronic crossbar switch

    Science.gov (United States)

    Gouin, Francois L.; Almeida, Carlos; Callender, Claire L.; Robitaille, Lucie; Noad, Julian P.

    1999-04-01

    Optoelectronic (OE) switching is a promising approach for routing signals in fiber optic networks. Recently, the integration of a 4 X 4 MSM array with optical surface waveguides has been reported. This technique greatly simplifies the packaging of an OE switch. The on-chip polyimide optical waveguides perform the optical signal distribution to a matrix of MSMs which are responsible for the switching operation itself. Photoresponse bandwidths exceeding 4 GHz have been demonstrated. Another important characteristic of a switch is the switching speed since it determines the reconfiguration time. Mechanical and thermal optical waveguide switches offer switching speeds of the order of milliseconds which is sufficient for network traffic management but too slow for packet switching. We report measurements on the switching characteristics of a 4 X 4 optoelectronic switch performed in both the frequency and time domain. In the time domain, the individual crosspoints exhibit a rise time of 3 ns. However, a sizeable overshoot and ringing settles only after 35 ns. This constitutes the reconfiguration time at present. This is confirmed by measurements in the frequency domain of the electrical transmission from control line to output line. The 3-dB switching bandwidth is a few hundred megahertz. The 35 ns reconfiguration time indicates that it is already suitable for packet switching in a 10 Mb/s network. Switching speed measurements on individual MSMs suggests that modifications to the switch circuit could improve the switching time. The switch could also find application as a component in the wavelength conversion circuit of a WDM fiber optic network.

  6. Impulsive control for synchronizing delayed discrete complex networks with switching topology

    OpenAIRE

    Li, Chaojie; Gao, David Y; Liu, Chao; Chen, Guo

    2013-01-01

    In this paper, global exponential synchronization of a class of discrete delayed complex networks with switching topology has been investigated by using Lyapunov-Ruzimiki method. The impulsive scheme is designed to work at the time instant of switching occurrence. A time-varying delay-dependent criterion for impulsive synchronization is given to ensure the delayed discrete complex networks switching topology tending to a synchronous state. Furthermore, a numerical simulation is given to illus...

  7. Optimal control of uncertain stochastic systems with Markovian switching and its applications to portfolio decisions

    OpenAIRE

    Weiyin Fei

    2014-01-01

    This paper first describes a class of uncertain stochastic control systems with Markovian switching, and derives an It\\^o-Liu formula for Markov-modulated processes. And we characterize an optimal control law, which satisfies the generalized Hamilton-Jacobi-Bellman (HJB) equation with Markovian switching. Then, by using the generalized HJB equation, we deduce the optimal consumption and portfolio policies under uncertain stochastic financial markets with Markovian switching. Finally, for cons...

  8. Ligand-responsive RNA switches: viral translation regulators, therapeutic targets, and tunable building blocks for nanotechnology

    OpenAIRE

    Boerneke, Mark A.

    2016-01-01

    Ligand-responsive RNA mechanical switches represent a new class of simple and small switching modules which regulate viral translation initiation by adopting well-defined ligand-free and bound conformational states without undergoing large secondary structure rearrangements, distinguishing them from metabolite-sensing riboswitches. Initially discovered in the internal ribosome entry site (IRES) of hepatitis C virus (HCV), RNA switch motifs have now been discovered in the genomes of diverse o...

  9. Two portable recombination enhancers direct donor choice in fission yeast heterochromatin

    DEFF Research Database (Denmark)

    Jakociunas, Tadas; Holm, Lærke Rebekka; Hansen, Janne Verhein;

    2013-01-01

    Mating-type switching in fission yeast results from gene conversions of the active mat1 locus by heterochromatic donors. mat1 is preferentially converted by mat2-P in M cells and by mat3-M in P cells. Here, we report that donor choice is governed by two portable recombination enhancers capable...... of promoting use of their adjacent cassette even when they are transposed to an ectopic location within the mat2-mat3 heterochromatic domain. Cells whose silent cassettes are swapped to mat2-M mat3-P switch mating-type poorly due to a defect in directionality but cells whose recombination enhancers were...

  10. A Switched Capacitor Harmonic Compensation Part for Switching Supplies

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    A new approach based on switched capacitor network to harmonic compensation for switching supplies is presented in the paper,The basic principle is discussed.SPICE simulation is applied to analyze the behaviour of the switched capacitor harmonic compensation part.

  11. Optical packet switched networks

    DEFF Research Database (Denmark)

    Hansen, Peter Bukhave

    1999-01-01

    in interferometric wavelength converters is investigated showing that a 10 Gbit/s 19 4x4 swich blocks can be cascaded at a BER of 10-14. An analytical traffic model enables the calculation of the traffice performance of a WDM packet network. Hereby the importance of WDM and wavelegth conversion in the switch blocks...... is investigated showing more constant gain characteristics and an increased saturation input power from -17 to -4 dBm. Dynamically, the GC-SOA is demonstrated to perform better at bit rates over 10 Gbit/s for RZ than NRZ signals. Additionally, a 4x4 passive InP mach-Zehnder interferometric space switch has been...... power dynamic range (IPDR). Moreover, the IPDR of the IWC alone is only -3.5 dB at 10 Gbit/s, however, control schemes are introduced yielding an IPDR of both -28 dB and -40 dB. Finally, the feasibility of an all-optical WDM packet switch block is demonstrated at 20 Gbit/s for a 4x4 switch block with 4...

  12. Optical Packet Switching Demostrator

    DEFF Research Database (Denmark)

    Mortensen, Brian Bach; Berger, Michael Stübert

    2002-01-01

    In the IST project DAVID (data and voice integration over DWDM) work is carried out defining possible architectures of future optical packet switched networks. The feasibility of the architecture is to be verified in a demonstration set-up. This article describes the demonstrator set-up and the...

  13. Switched Multistage Vector Quantizer

    Directory of Open Access Journals (Sweden)

    M Satya Sai Ram

    2010-01-01

    Full Text Available This paper investigates the use of a new hybrid vector quantizer called Switched Multi stage vector quantization (SWMSVQ technique using hard and soft decision schemes, for coding of narrow band speech signals. This technique is a hybrid of Switch vector quantization technique and Multi stage vector quantization technique. SWMSVQ quantizes the linear predictive coefficients (LPC in terms of the line spectral frequencies (LSF. The spectral distortion performance, computational complexity and memory requirements of SWMSVQ using hard and soft decision schemes are compared with Split vector quantization (SVQ technique, Multi stage vector quantization (MSVQ technique, Switched Split vector quantization (SSVQ technique using hard decision scheme, and Multi Switched Split Vector quantization (MSSVQ technique using hard decision scheme. From results it is proved that SWMSVQ using soft decision scheme is having less spectral distortion, computational complexity and memory requirements when compared to SVQ, MSVQ, SSVQ and SWMSVQ using hard decision scheme, but high when compared to MSSVQ using hard decision scheme. So from results it is proved that SWMSVQ using soft decision scheme is better when compared to SVQ, MSVQ, SSVQ and SWMSVQ using hard decision schemes in terms of spectral distortion, computational complexity and memory requirements but is having greater spectral distortion, computational complexity and memory requirements when compared to MSSVQ using hard decision.

  14. Photonic MEMS switch applications

    Science.gov (United States)

    Husain, Anis

    2001-07-01

    As carriers and service providers continue their quest for profitable network solutions, they have shifted their focus from raw bandwidth to rapid provisioning, delivery and management of revenue generating services. Inherently transparent to data rate the transmission wavelength and data format, MEMS add scalability, reliability, low power and compact size providing flexible solutions to the management and/or fiber channels in long haul, metro, and access networks. MEMS based photonic switches have gone from the lab to commercial availability and are now currently in carrier trials and volume production. 2D MEMS switches offer low up-front deployment costs while remaining scalable to large arrays. They allow for transparent, native protocol transmission. 2D switches enable rapid service turn-up and management for many existing and emerging revenue rich services such as storage connectivity, optical Ethernet, wavelength leasing and optical VPN. As the network services evolve, the larger 3D MEMS switches, which provide greater scalability and flexibility, will become economically viable to serve the ever-increasing needs.

  15. DIGITAL TELEPHONE SWITCH: SOFTWARE

    Directory of Open Access Journals (Sweden)

    J. G. Viveros Talavera

    2003-07-01

    Full Text Available This paper describes the design of the program of control for a Digital Phone Switch (PBAX with a maximumcapacity of one hundred and twenty-eight lines (extensions and trunks. The control program was designedusing object-oriented programming and concurrent programming techniques.

  16. The Octopus switch

    NARCIS (Netherlands)

    Havinga, Paul Johannes Mattheus

    2000-01-01

    This chapter1 discusses the interconnection architecture of the Mobile Digital Companion. The approach to build a low-power handheld multimedia computer presented here is to have autonomous, reconfigurable modules such as network, video and audio devices, interconnected by a switch rather than by a

  17. Ultrafast gas switching experiments

    International Nuclear Information System (INIS)

    We describe recent experiments which studied the physics of ultrafast gas breakdown under the extreme overvoltages which occur when a high pressure gas switch is pulse charged to hundreds of kV in 1 ns or less. The highly overvolted peaking gaps produce powerful electromagnetic pulses with risetimes Khz at > 100 kV/m E field

  18. Kiowa Creek Switching Station

    Energy Technology Data Exchange (ETDEWEB)

    1990-03-01

    The Western Area Power Administration (Western) proposes to construct, operate, and maintain a new Kiowa Creek Switching Station near Orchard in Morgan County, Colorado. Kiowa Creek Switching Station would consist of a fenced area of approximately 300 by 300 feet and contain various electrical equipment typical for a switching station. As part of this new construction, approximately one mile of an existing 115-kilovolt (kV) transmission line will be removed and replaced with a double circuit overhead line. The project will also include a short (one-third mile) realignment of an existing line to permit connection with the new switching station. In accordance with the Council on Environmental Quality (CEQ) regulations for implementing the procedural provisions of the National Environmental Policy Act of 1969 (NEPA), 40 CFR Parts 1500--1508, the Department of Energy (DOE) has determined that an environmental impact statement (EIS) is not required for the proposed project. This determination is based on the information contained in this environmental assessment (EA) prepared by Western. The EA identifies and evaluates the environmental and socioeconomic effects of the proposed action, and concludes that the advance impacts on the human environment resulting from the proposed project would not be significant. 8 refs., 3 figs., 1 tab.

  19. Recombinant Helicobacter pylori catalase

    Institute of Scientific and Technical Information of China (English)

    Yang Bai; Ya-Li Zhang; Jian-Feng Jin; Ji-De Wang; Zhao-Shan Zhang

    2003-01-01

    AIM: To construct a recombinant strain which highly expresses catalase of Helicobacter pylori(H.pylori) and assay the activity of H. pylori catalase.METHODS: The catalase DNA was amplified from H. pylori chromosomal DNA with PCR techniques and inserted into the prokaryotie expression vector pET-22b (+), and then was transformed into the BL21 (DE3) E. coli strain which expressed catalase recombinant protein. The activity of H.pylori catalase was assayed by the Beers & Sizers.RESULTS: DNA sequence analysis showed that the sequence of catalase DNA was the same as GenBank's research. The catalase recombinant protein amounted to 24.4 % of the total bacterial protein after induced with IPTG for 3 hours at 37 ℃ and the activity of H. pylori catalase was high in the BL21 (DE3) E. coli strain.CONCLUSION: A clone expressing high activity H. pylori catalase is obtained, laying a good foundation for further studies.

  20. Closing photoconductive semiconductor switches

    Energy Technology Data Exchange (ETDEWEB)

    Loubriel, G.M.; Zutavern, F.J.; Hjalmarson, H.P.; O' Malley, M.W.

    1989-01-01

    One of the most important limitations of Photoconductive Semiconductor Switches (PCSS) for pulsed power applications is the high laser powers required to activate the switches. In this paper, we discuss recent developments on two different aspects of GaAs PCSS that result in reductions in laser power by a factor of nearly 1000. The advantages of using GaAs over Si are many. First of all, the resistivity of GaAs can be orders of magnitude higher than that of the highest resistivity Si material, thus allowing GaAs switches to withstand dc voltages without thermal runaway. Secondly, GaAs has a higher carrier mobility than Si and, thus, is more efficient (per carrier). Finally, GaAs switches can have naturally fast (ns) opening times at room temperature and low fields, microsecond opening times at liquid nitrogen temperature of 77 K, or, on demand, closing and opening at high fields and room temperature by a mechanism called lock-on (see Ref. 1). By contrast, Si switches typically opening times of milliseconds. The amount of laser light required to trigger GaAs for lock-on, or at 77 K, is about three orders of magnitude lower than at room temperature. In this paper we describe the study of lock-on in GaAs and InP, as well as switching of GaAs at 77 K. We shall show that when GaAs is switched at 77 K, the carrier lifetime is about three orders of magnitude longer than it is at room temperature. We shall explain the change in lifetime in terms of the change in electron capture cross section of the deep levels in GaAs (these are defect or impurity levels in the band gap). In the second section, we describe the lock-on effect, now seen in GaAs and InP, and at fields as high as 70 kV/cm. We show how lock-on can be tailored by changing the GaAs temperature or by neutron bombardment. In the third section, we discuss possible lock-on mechanisms. 5 refs., 5 figs.

  1. Molecular Rotors as Switches

    Directory of Open Access Journals (Sweden)

    Kang L. Wang

    2012-08-01

    Full Text Available The use of a functional molecular unit acting as a state variable provides an attractive alternative for the next generations of nanoscale electronics. It may help overcome the limits of conventional MOSFETd due to their potential scalability, low-cost, low variability, and highly integratable characteristics as well as the capability to exploit bottom-up self-assembly processes. This bottom-up construction and the operation of nanoscale machines/devices, in which the molecular motion can be controlled to perform functions, have been studied for their functionalities. Being triggered by external stimuli such as light, electricity or chemical reagents, these devices have shown various functions including those of diodes, rectifiers, memories, resonant tunnel junctions and single settable molecular switches that can be electronically configured for logic gates. Molecule-specific electronic switching has also been reported for several of these device structures, including nanopores containing oligo(phenylene ethynylene monolayers, and planar junctions incorporating rotaxane and catenane monolayers for the construction and operation of complex molecular machines. A specific electrically driven surface mounted molecular rotor is described in detail in this review. The rotor is comprised of a monolayer of redox-active ligated copper compounds sandwiched between a gold electrode and a highly-doped P+ Si. This electrically driven sandwich-type monolayer molecular rotor device showed an on/off ratio of approximately 104, a read window of about 2.5 V, and a retention time of greater than 104 s. The rotation speed of this type of molecular rotor has been reported to be in the picosecond timescale, which provides a potential of high switching speed applications. Current-voltage spectroscopy (I-V revealed a temperature-dependent negative differential resistance (NDR associated with the device. The analysis of the device

  2. Electrodeposited polymer encapsulated nickel sulphide thin films: frequency switching material

    Energy Technology Data Exchange (ETDEWEB)

    Jana, Sumanta, E-mail: sumantajana85@gmail.com [Department of Chemistry, Bengal Engineering and Science University, Botanic Garden, Howrah 711103, WB (India); Mukherjee, Nillohit [Centre of Excellence for Green Energy and Sensor Systems, Bengal Engineering and Science University, Howrah 711103, WB (India); Chakraborty, Biswajit [Department of Chemistry, Vivekananda Mahavidyalay, Burdwan 713103, WB (India); Mitra, Bibhas Chandra [Department of Physics, Bengal Engineering and Science University, Botanic Garden, Howrah 711103, WB (India); Mondal, Anup, E-mail: anupmondal2000@yahoo.co.in [Department of Chemistry, Bengal Engineering and Science University, Botanic Garden, Howrah 711103, WB (India)

    2014-05-01

    Graphical abstract: Polyvinylpyrrolidone encapsulated NiS thin films were synthesized electrochemically. The light induced frequency switching study of the synthesized material was carried out and it was observed that the films performed well as a switching device under 1 Sun illumination. This pulse generation within an insulating polymer encapsulated semicondctor matrix (PVP NiS) might be due to surface covering which leads to reduction of recombination process. Highlights: • PVP-NiS thin films were electrochemically synthesized. • Encapsulation of PVP causes surface modification of NiS by reducing surface states. • The synthesized thin films were used as frequency switching material which generates ~ 50 Hz frequency under 1 Sun irradiation. Abstract: Polyvinylpyrrolidone (PVP) encapsulated nickel sulfide (NiS) thin films have been synthesized electrochemically from aqueous solution of hydrated nickel chloride (NiCl₂, 6H₂O), thioacetamide (CH₃C(S) NH₂) (TAA) and polyvinylpyrrolidone (PVP). Surface modification of nickel sulfide (NiS) thin films was achieved by this polymer encapsulation. X-ray diffraction (XRD), high resolution transmission electron microscope (HRTEM), field emission scanning electron microscopy (FESEM) and Energy dispersive X-radiation (EDAX) techniques were used for the characterization of thin films. Infrared spectroscopy (IR) confirmed the formation of polymer encapsulated semiconductor. Frequency switching generation study shows that the encapsulated material could be used as a frequency switching device that generates a frequency ~ 50 Hz under 1 Sun illumination. Encapsulation with PVP causes surface modification that reduces the surface states and barrier height. As a result, the width of the depletion region decreases. So the number of electron-hole pairs increases. Consequently, the number of excitons and exciton related emission increases and this leads to reduction of recombination process and shows photo induced

  3. A high performance switching audio amplifier using sliding mode control

    OpenAIRE

    Pillonnet, Gael; Cellier, Rémy; Abouchi, Nacer; Chiollaz, Monique

    2008-01-01

    International audience The switching audio amplifiers are widely used in various portable and consumer electronics due to their high efficiency, but suffers from low audio performances due to inherent nonlinearity. This paper presents an integrated class D audio amplifier with low consumption and high audio performances. It includes a power stage and an efficient control based on sliding mode technique. This monolithic class D amplifier is capable of delivering up to 1W into 8Ω load at les...

  4. Recombination in ionized gases

    International Nuclear Information System (INIS)

    In this paper it is shown how capture-stabilized methodology (both macroscopic and microscopic) can provide a generic basis for a unified treatment of all of the above recombination mechanisms. A new semiclassical theory of dissociative recombination is also presented in an effort to gain further insight into the physics not included in the first-order treatment and difficult to extract from numerical quantal treatments based on configuration mixing and on multichannel quantum defect theory. A simple analytical expression more accurate than the standard first-order result is obtained for the cross section σ and rate coefficient α. (author)

  5. True ferroelectric switching in thin films of trialkylbenzene-1,3,5-tricarboxamide (BTA).

    Science.gov (United States)

    Gorbunov, A V; Putzeys, T; Urbanavičiūtė, I; Janssen, R A J; Wübbenhorst, M; Sijbesma, R P; Kemerink, M

    2016-08-24

    We have investigated the ferroelectric polarization switching properties of trialkylbenzene-1,3,5-tricarboxamide (BTA), which is a model system for a large class of novel organic ferroelectric materials. In the solid state BTAs form a liquid crystalline columnar hexagonal phase that provides long range order that was previously shown to give rise to hysteretic dipolar switching. In this work the nature of the polar switching process is investigated by a combination of dielectric relaxation spectroscopy, depth-resolved pyroelectric response measurements, and classical frequency- and time-dependent electrical switching. We show that BTAs, when brought in a homeotropically aligned hexagonal liquid crystalline phase, are truly ferroelectric. Analysis of the transient switching behavior suggests that the ferroelectric switching is limited by a highly dispersive nucleation process, giving rise to a wide distribution of switching times. PMID:27510767

  6. Recombination analysis and structure prediction show correlation between breakpoint clusters and RNA hairpins in the pol gene of human immunodeficiency virus type 1 unique recombinant forms

    DEFF Research Database (Denmark)

    Galli, Andrea; Lai, Alessia; Corvasce, Stefano;

    2008-01-01

    Recombination is recognized as a primary force in human immunodeficiency virus type 1 (HIV-1) evolution, increasing viral diversity through reshuffling of genomic portions. The strand-switching activity of reverse transcriptase is required to complete HIV-1 replication and can occur randomly...

  7. Universality class in conformal inflation

    Energy Technology Data Exchange (ETDEWEB)

    Kallosh, Renata; Linde, Andrei, E-mail: kallosh@stanford.edu, E-mail: alinde@stanford.edu [Department of Physics and SITP, Stanford University, Stanford, California 94305 (United States)

    2013-07-01

    We develop a new class of chaotic inflation models with spontaneously broken conformal invariance. Observational consequences of a broad class of such models are stable with respect to strong deformations of the scalar potential. This universality is a critical phenomenon near the point of enhanced symmetry, SO(1,1), in case of conformal inflation. It appears because of the exponential stretching of the moduli space and the resulting exponential flattening of scalar potentials upon switching from the Jordan frame to the Einstein frame in this class of models. This result resembles stretching and flattening of inhomogeneities during inflationary expansion. It has a simple interpretation in terms of velocity versus rapidity near the Kähler cone in the moduli space, similar to the light cone of special theory of relativity. This effect makes inflation possible even in the models with very steep potentials. We describe conformal and superconformal versions of this cosmological attractor mechanism.

  8. Job Switching and Wage Growth

    OpenAIRE

    Faberman, R. Jason; Justiniano, Alejandro

    2015-01-01

    This article shows a remarkably strong relationship between job switching and nominal wage growth. We also find a fairly strong relationship between job switching and the cyclical component of inflation. Furthermore, job switching seems to be predictive of both wage growth and inflation.

  9. Language Switching and Language Competition

    Science.gov (United States)

    Macizo, Pedro; Bajo, Teresa; Paolieri, Daniela

    2012-01-01

    This study examined the asymmetrical language switching cost in a word reading task (Experiment 1) and in a categorization task (Experiment 2 and 3). In Experiment 1, Spanish-English bilinguals named words in first language (L1) and second language (L2) in a switching paradigm. They were slower to switch from their weaker L2 to their more dominant…

  10. Exponential stability of switched systems with impulsive effect

    Institute of Scientific and Technical Information of China (English)

    Guangdeng ZONG; Yuqiang WU

    2005-01-01

    The exponential stability of a class of switched systems containing stable and unstable subsystems with impulsive effect is analyzed by using the matrix measure concept and the average dwell-time approach.It is shown that if appropriately a large amount of the average dwell-time and the ratio of the total activation time of the subsystems with negative matrix measure to the total activation time of the subsystems with nonnegative matrix measure is chosen,the exponential stability of a desired degree is guaranteed.Using the proposed switching scheme,we studied the robust exponential stability for a class of switched systems with impulsive effect and structure perturbations.Simulations validate the main results.

  11. Abacus switch: a new scalable multicast ATM switch

    Science.gov (United States)

    Chao, H. Jonathan; Park, Jin-Soo; Choe, Byeong-Seog

    1995-10-01

    This paper describes a new architecture for a scalable multicast ATM switch from a few tens to thousands of input ports. The switch, called Abacus switch, has a nonblocking memoryless switch fabric followed by small switch modules at the output ports; the switch has input and output buffers. Cell replication, cell routing, output contention resolution, and cell addressing are all performed distributedly in the Abacus switch so that it can be scaled up to thousnads input and output ports. A novel algorithm has been proposed to resolve output port contention while achieving input and output ports. A novel algorithm has been proposed to reolve output port contention while achieving input buffers sharing, fairness among the input ports, and multicast call splitting. The channel grouping concept is also adopted in the switch to reduce the hardware complexity and improve the switch's throughput. The Abacus switch has a regular structure and thus has the advantages of: 1) easy expansion, 2) relaxed synchronization for data and clock signals, and 3) building the switch fabric using existing CMOS technology.

  12. Biochemical switching device: how to turn on (off) the switch.

    Science.gov (United States)

    Okamoto, M; Sakai, T; Hayashi, K

    1989-01-01

    We previously showed with computer simulations that cyclic enzyme systems have the reliability of ON-OFF types of operation (McCulloch-Pitts' neuronic equation) and the applicability for a switching circuit in a biocomputer. The switching time was inevitably determined in accordance with the difference in amount between two inputs of the system. This characteristic is, however, a disadvantage for practical use of a switching device; we need to improve the system in order for the switching time to optionally be changed. We shall present here how to turn on (off) the switch independently of the modes of two inputs. By introducing pulse perturbation, we could optionally set up the switching time of a cyclic enzyme system (biochemical switching device). PMID:2720139

  13. Synchronization Between Two Different Switched Chaotic Systems By Switching Control

    Directory of Open Access Journals (Sweden)

    Du Li Ming

    2016-01-01

    Full Text Available This paper is concerned with the synchronization problem of two different switched chaotic systems, considering the general case that the master-slave switched chaotic systems have uncertainties. Two basic problems are considered: one is projective synchronization of switched chaotic systems under arbitrary switching; the other is projective synchronization of switched chaotic systems by design of switching when synchronization cannot achieved by using any subsystems alone. For the two problems, common Lyapunov function method and multiple Lyapunov function method are used respectively, an adaptive control scheme has been presented, some sufficient synchronization conditions are attainted, and the switching signal is designed. Finally, the numerical simulation is provide to show the effectiveness of our method.

  14. Assessment of Recombination in the S-segment Genome of Crimean-Congo Hemorrhagic Fever Virus in Iran

    Directory of Open Access Journals (Sweden)

    Sadegh Chinikar

    2015-10-01

    Full Text Available  Background: Crimean-Congo Hemorrhagic Fever Virus (CCHFV belongs to genus Nairovirus and family Bunyaviridae. The main aim of this study was to investigate the extent of recombination in S-segment genome of CCHFV in Iran.Methods: Samples were isolated from Iranian patients and those available in GenBank, and analyzed by phyloge­netic and bootscan methods.Results: Through comparison of the phylogenetic trees based on full length sequences and partial fragments in the S-segment genome of CCHFV, genetic switch was evident, due to recombination event. Moreover, evidence of multi­ple recombination events was detected in query isolates when bootscan analysis was used by SimPlot software.Conclusion: Switch of different genomic regions between different strains by recombination could contribute to CCHFV diversification and evolution. The occurrence of recombination in CCHFV has a critical impact on epidemi­ological investigations and vaccine design. 

  15. My Class

    Institute of Scientific and Technical Information of China (English)

    赵传怡

    2006-01-01

    My name is Zhao Chuanyi.I am in Class Ten Grade seven.There are 61 students in our class.And 26 are girls and 35 are boys.One is from America.Boys like football and basketball.Girls like singing and dancing.We are all

  16. Word classes

    DEFF Research Database (Denmark)

    Rijkhoff, Jan

    2007-01-01

    a parts-of-speech system that includes the categories Verb, Noun, Adjective and Adverb, other languages may use only a subset of these four lexical categories. Furthermore, quite a few languages have a major word class whose members cannot be classified in terms of the categories Verb – Noun – Adjective...

  17. Recombinant DNA for Teachers.

    Science.gov (United States)

    Duvall, James G., III

    1992-01-01

    A science teacher describes his experience at a workshop to learn to teach the Cold Spring Harbor DNA Science Laboratory Protocols. These protocols lead students through processes for taking E. coli cells and transforming them into a new antibiotic resistant strain. The workshop featured discussions of the role of DNA recombinant technology in…

  18. Recombineering Pseudomonas syringae

    Science.gov (United States)

    Here we report the identification of functions that promote genomic recombination of linear DNA introduced into Pseudomonas cells by electroporation. The genes encoding these functions were identified in Pseudomonas syringae pv. syringae B728a based on similarity to the lambda Red Exo/Beta and RecE...

  19. Class size versus class composition

    DEFF Research Database (Denmark)

    Jones, Sam

    Raising schooling quality in low-income countries is a pressing challenge. Substantial research has considered the impact of cutting class sizes on skills acquisition. Considerably less attention has been given to the extent to which peer effects, which refer to class composition, also may affect...... outcomes. This study uses new microdata from East Africa, incorporating test score data for over 250,000 children, to compare the likely efficacy of these two types of interventions. Endogeneity bias is addressed via fixed effects and instrumental variables techniques. Although these may not fully mitigate...

  20. Practical switching power supply design

    CERN Document Server

    Brown, Martin C

    1990-01-01

    Take the ""black magic"" out of switching power supplies with Practical Switching Power Supply Design! This is a comprehensive ""hands-on"" guide to the theory behind, and design of, PWM and resonant switching supplies. You'll find information on switching supply operation and selecting an appropriate topology for your application. There's extensive coverage of buck, boost, flyback, push-pull, half bridge, and full bridge regulator circuits. Special attention is given to semiconductors used in switching supplies. RFI/EMI reduction, grounding, testing, and safety standards are also deta

  1. Switched Matrix Accelerator

    International Nuclear Information System (INIS)

    We describe a new concept for a microwave circuit functioning as a charged-particle accelerator at mm-wavelengths, permitting an accelerating gradient higher than conventional passive circuits can withstand consistent with cyclic fatigue. The device provides acceleration for multiple bunches in parallel channels, and permits a short exposure time for the conducting surface of the accelerating cavities. Our analysis includes scalings based on a smooth transmission line model and a complementary treatment with a coupled-cavity simulation. We provide also an electromagnetic design for the accelerating structure, arriving at rough dimensions for a seven-cell accelerator matched to standard waveguide and suitable for bench tests at low power in air at 91.392. GHz. A critical element in the concept is a fast mm-wave switch suitable for operation at high-power, and we present the considerations for implementation in an H-plane tee. We discuss the use of diamond as the photoconductor switch medium

  2. Monopole Charge Domain in High-Gain Gallium Arsenide Photoconductive Switches

    Institute of Scientific and Technical Information of China (English)

    施卫; 陈二柱; 张显斌; 李琦

    2002-01-01

    Considering that semi-insulating gallium arsenide photoconductive switches can be triggered into the high gain mode and no reliable theories can account for the observed transient characteristics, we propose the monopole charge domain model to explain the peculiar switching phenomena occurring in the high gain mode and we discuss the requirements for the lock-on switching. During operation on this mode, the applied field across the switch and the lock-on field are all larger than the Gunn threshold field. Our developed monopole charge domain is based on the transferred-electron effect, but the domain is only composed of large numbers of electrons piled up due to the negative differential mobility. Using the model and taking the physical mechanism of the avalanche impact ionization and recombination radiation into consideration, we interpret the typical phenomena of the lock-on effect, such as the time delay between the beginning of optical illumination and turning-on of the switch, and the conduction mechanism of the sustaining phase. Under different conditions of bias field intensity and incident light energy, the time delay of the switching is calculated. The results show that the physical mechanisms of impact ionization and recombination radiation occurring in the monopole charge domain are responsible for the lock-on switching.

  3. Python Switch Statement

    Directory of Open Access Journals (Sweden)

    2008-06-01

    Full Text Available The Python programming language does not have a built in switch/case control structure as found in many other high level programming languages. It is thought by some that this is a deficiency in the language, and the control structure should be added. This paper demonstrates that not only is the control structure not needed, but that the methods available in Python are more expressive than built in case statements in other high level languages.

  4. Magnetic Cellular Switches

    OpenAIRE

    Overby, Darryl R.; Alenghat, Francis J.; Montoya-Zavala, Martín; Bei, HuCheng; Oh, Philmo; Karavitis, John; Ingber, Donald E.

    2004-01-01

    This paper focuses on the development of magnetic cellular switches to enable magnetic control of intracellular functions in living mammalian cells, including receptor signal transduction and gene transcription. Our approach takes advantage of the mechanosensitivity of adenosine 3′,5′-monophosphate (cAMP) induction and downstream transcription controlled by the cAMP regulatory element (CRE) to engineer gene constructs that optically report gene expression in living cells. We activate transcri...

  5. Beyond the switch

    DEFF Research Database (Denmark)

    Aliakseyeu, Dzmitry; Meerbeek, Bernt; Mason, Jon;

    2014-01-01

    and established lighting network, and with the advent of the LED, new types of lighting output are now possible. However, the current approach for controlling such systems is to simply replace the light switch with a somewhat more sophisticated smartphone-based remote control. The focus of this workshop......, to your car and to your office, will also be explored during this workshop as a part of a connected lifestyle between different contexts....

  6. MCT/MOSFET Switch

    Science.gov (United States)

    Rippel, Wally E.

    1990-01-01

    Metal-oxide/semiconductor-controlled thyristor (MCT) and metal-oxide/semiconductor field-effect transistor (MOSFET) connected in switching circuit to obtain better performance. Offers high utilization of silicon, low forward voltage drop during "on" period of operating cycle, fast turnon and turnoff, and large turnoff safe operating area. Includes ability to operate at high temperatures, high static blocking voltage, and ease of drive.

  7. Cygnus Diverter Switch Analysis

    Energy Technology Data Exchange (ETDEWEB)

    G. Corrow, M. Hansen, D. Henderson, C. Mitton et al.

    2008-02-01

    The Cygnus Dual Beam Radiographic Facility consists of two 2.25-MV, 60-kA, 50-ns x-ray sources fielded in an underground laboratory at the Nevada Test Site. The tests performed in this laboratory involve study of the dynamic properties of plutonium and are called subcritical experiments. From end-to-end, the Cygnus machines utilize the following components: Marx generator, water-filled pulse-forming line (PFL), waterfilled coaxial transmission line (WTL), 3-cell inductive voltage adder (IVA), and rod-pinch diode. The upstream WTL interface to the PFL is via a radial insulator with coaxial geometry. The downstream WTL terminates in a manifold where the center conductor splits into three lines which individually connect to each of the IVA cell inputs. There is an impedance mismatch at this juncture. It is a concern that a reflected pulse due to anomalous behavior in the IVA or diode might initiate breakdown upon arrival at the upstream PFL/WTL insulator. Therefore near the beginning of the WTL a radial diverter switch is installed to protect the insulator from over voltage and breakdown. The diverter has adjustable gap spacing, and an in-line aqueous-solution (sodium thiosulfate) resistor array for energy dissipation. There are capacitive voltage probes at both ends of the WTL and on the diverter switch. These voltage signals will be analyzed to determine diverter performance. Using this analysis the usefulness of the diverter switch will be evaluated.

  8. Purification of a Recombinant Glutathione Transferase from the Causative Agent of Hydatidosis, "Echinococcus granulosus"

    Science.gov (United States)

    Fleitas, Andrea L.; Randall, Lía M.; Möller, Matías N.; Denicola, Ana

    2016-01-01

    This practical class activity was designed to introduce students to recombinant protein expression and purification. The principal goal is to shed light on basic aspects concerning recombinant protein production, in particular protein expression, chromatography methods for protein purification, and enzyme activity as a tool to evaluate purity and…

  9. A Collaborative, Investigative Recombinant DNA Technology Course with Laboratory

    Science.gov (United States)

    Pezzementi, Leo; Johnson, Joy F.

    2002-01-01

    A recombinant DNA technology course was designed to promote contextual, collaborative, inquiry-based learning of science where students learn from one another and have a sense of ownership of their education. The class stressed group presentations and critical reading and discussion of scientific articles. The laboratory consisted of two research…

  10. Robust exponential stability of uncertain discrete time impulsive switching systems with state delay

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A new class of hybrid impulsive and switching models are introduced and their robust exponential stability and control synthesis are addressed.The proposed switched system is composed of stable subsystems and unstable subsystems,which not only involves state delay and norm-bounded time-varying parameter uncertainties,but also contains the impulsive switching effects between the subsystems.Based on the extension of the system dimension and the concept of average dwell time,a kind of practically useful switching rule is presented which guarantees the desired robust exponential stability.A swished state feedback controller is also given.

  11. Active Learning with Monty Hall in a Game Theory Class

    Science.gov (United States)

    Brokaw, Alan J.; Merz, Thomas E.

    2004-01-01

    The authors describe a game that students can play on the first day of a game theory class. The game introduces the 4 essential elements of any game and is designed so that its sequel, also played on the first day of class, has students playing the well-known Monty Hall game, which raises the question: Should you switch doors? By implementing a…

  12. AECL passive autocatalytic recombiners

    Energy Technology Data Exchange (ETDEWEB)

    Gardner, L.B.; Marcinkowska, K. [Atomic Energy of Canada Limited, Chalk River, Ontario (Canada)

    2012-03-15

    Atomic Energy of Canada Limited's (AECL) Passive Autocatalytic Recombiner (PAR) is a passive device used for hydrogen mitigation under post-accident conditions in nuclear reactor containment. The PAR employs a proprietary AECL catalyst which promotes the exothermal reaction between hydrogen and oxygen to form water vapour. The heat of reaction combined with the PAR geometry establishes a convective flow through the recombiner, where ambient hydrogen-rich gas enters the PAR inlet and hot, humid, hydrogen-depleted gas exits the outlet. AECL's PAR has been extensively qualified for CANDU and light water reactors (LWRs), and has been supplied to France, Finland, Ukraine, South Korea and is currently being deployed in Canadian nuclear power plants. (author)

  13. AECL passive autocatalytic recombiners

    Energy Technology Data Exchange (ETDEWEB)

    Gardner, L.B.; Marcinkowska, K. [Atomic Energy of Canada Limited, Chalk River, Ontario (Canada)

    2011-07-01

    Atomic Energy of Canada Limited's (AECL) Passive Autocatalytic Recombiner (PAR) is a passive device used for hydrogen mitigation under post-accident conditions in nuclear reactor containment. The PAR employs a proprietary AECL catalyst which promotes the exothermal reaction between hydrogen and oxygen to form water vapour. The heat of reaction combined with the PAR geometry establishes a convective flow through the recombiner, where ambient hydrogen-rich gas enters the PAR inlet and hot, humid, hydrogen-depleted gas exits the outlet. AECL's PAR has been extensively qualified for CANDU and light water reactors (LWRs), and has been supplied to France, Finland, Ukraine, South Korea and is currently being deployed in Canadian nuclear power plants. (author)

  14. Observer-Based Robust Control of Uncertain Switched Fuzzy Systems with Combined Switching Controller

    Directory of Open Access Journals (Sweden)

    Hong Yang

    2013-01-01

    Full Text Available The observer-based robust control for a class of switched fuzzy (SF time-delay systems involving uncertainties and external disturbances is investigated in this paper. A switched fuzzy system, which differs from existing ones, is firstly employed to describe a nonlinear system. Next, a combined switching controller is proposed. The designed controller based on the observer instead of the state information integrates the advantages of both the switching controllers and the supplementary controllers but eliminates their disadvantages. The proposed controller provides good performance during the transient period, and the chattering effect is removed when the system state approaches the origin. Sufficient condition for the solvability of the robust control problem is given for the case that the state of system is not available. Since convex combination techniques are used to derive the delay-independent criteria, some subsystems are allowed to be unstable. Finally, various comparisons of the elaborated examples are conducted to demonstrate the effectiveness of the proposed control design approach.

  15. RECOMBINANT INFLUENZA VACCINES

    OpenAIRE

    Sedova, E.; Shcherbinin, D.; Migunov, A.; Smirnov, Iu; Logunov, D.; Shmarov, M.; Tsybalova, L.; Naroditskiĭ, B.; O. Kiselev; Gintsburg, A.

    2012-01-01

    This review covers the problems encountered in the construction and production of new recombinant influenza vaccines. New approaches to the development of influenza vaccines are investigated; they include reverse genetics methods, production of virus-like particles, and DNA- and viral vector-based vaccines. Such approaches as the delivery of foreign genes by DNA- and viral vector-based vaccines can preserve the native structure of antigens. Adenoviral vectors are a promising gene-delivery pla...

  16. Soluble recombinant influenza vaccines.

    OpenAIRE

    Fiers, W; Neirynck, S; Deroo, T; Saelens, X; Jou, W M

    2001-01-01

    Soluble, recombinant forms of influenza A virus haemagglutinin and neuraminidase have been produced in cells of lower eukaryotes, and shown in a mouse model to induce complete protective immunity against a lethal virus challenge. Soluble neuraminidase, produced in a baculovirus system, consisted of tetramers, dimers and monomers. Only the tetramers were enzymatically active. The immunogenicity decreased very considerably in the order tetra > di > mono. Therefore, we fused the head part of the...

  17. Genetic recombination in Escherichia coli : II. Calculation of incorporation frequency and relative map distance by recombinant analysis

    NARCIS (Netherlands)

    Haan, P.G. de; Verhoef, C.

    1966-01-01

    In this paper a mathematical analysis based on the physical exchange of genetic material is presented for a four-factor cross. The incorporation frequency of donor markers and the relative map distances may be accurately estimated from the frequencies of the eight recombinant classes. The results ob

  18. Switching the polarity of a bacteriophage integration system.

    Science.gov (United States)

    Smith, Matthew C A; Till, Rob; Smith, Margaret C M

    2004-03-01

    During lysogenic growth many temperate bacteriophage genomes are integrated into the host's chromosome and efficient integration and excision are therefore an essential part of the phage life cycle. The Streptomyces phage phiC31 encodes an integrase related to the resolvase/invertases and is evolutionarily and mechanistically distinct from the integrase of phage lambda. We show that during phiC31 integration the polarity of the recombination sites, attB and attP, is dependent on the sequences of the two base pairs (bp) where crossover occurs. A loss or switch in polarity of the recombination sites can occur by mutation of this dinucleotide, leading to incorrectly joined products. The properties of the mutant sites implies that phiC31 integrase interacts symmetrically with the substrates, which during synapsis can align apparently freely in either of two alternative forms that lead to correct or incorrect joining of products. Analysis of the topologies of the reaction products provided evidence that integrase can synapse and activate strand exchange even when recombinant products cannot form due to mismatches at the crossover site. The topologies of the recombination products are complex and indicative of multiple pathways to product formation. The efficiency of integration of a phiC31 derivative, KC859, into an attB site with switched polarity was assayed in vivo and shown to be no different from integration into a wild-type attB. Thus neither the host nor KC859 express a factor that influences the alignment of the recombination sites at synapsis.

  19. Class distinction

    Science.gov (United States)

    White, M. Catherine

    Typical 101 courses discourage many students from pursuing higher level science and math courses. Introductory classes in science and math serve largely as a filter, screening out all but the most promising students, and leaving the majority of college graduates—including most prospective teachers—with little understanding of how science works, according to a study conducted for the National Science Foundation. Because few teachers, particularly at the elementary level, experience any collegiate science teaching that stresses skills of inquiry and investigation, they simply never learn to use those methods in their teaching, the report states.

  20. Research Progress on Multimode Interference Switches

    Institute of Scientific and Technical Information of China (English)

    GAO Qing; SHENG Zhi-rui; JIANG Xiao-qing; WANG Ming-hua

    2005-01-01

    Optical switches are key components for constructing optical communication networks, so it is necessary to design optical switches and optical switch arrays with high performance and low cost. As one type of optical switches, the multimode interference(MMI) switches have received considerable attention due to their unique merits. The structures and operation principles of various types of MMI switches are introduced,and the recent progresses of MMI switches are also discussed.

  1. Circuit model of Rimfire switch

    International Nuclear Information System (INIS)

    A cascade gaps circuit model for Rimfire switch has been developed. The circuit model includes all stray capacitances and spark channel on-state conduction characteristics. It can not only describe the behavior of Rimfire switch, but also allow analysis of the time varying voltage and current at each part of the switch, describing the internal characters of the switch. PSpice was used to implement the cascade gaps circuit model and simulate a 700 kV Rimfire switch. The simulation shows that, the voltage of the whole switch will be higher than 700 kV when the laser triggered section has broken down but all cascade gaps keep dielectric, and the voltage of all gaps attenuates with high frequency oscillation. (authors)

  2. The economics of lamp switching

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-01

    The effect of switching off fluorescent lamps, in terms of electricity cost, was discussed. Fluorescent lamps are designed to burn for thousands of hours. Initially, it was believed that turning them off was not economical. However, with new fluorescent lamps available today, this no longer holds true. It was shown that as energy costs increase, it is advantageous to switch lamps off in office buildings during lunch, coffee breaks and other non-essential periods. Also, as labour and lamp costs increase it becomes even more economical to turn lamps on only when needed in some areas such as washrooms, stockrooms, etc. Inexpensive photo-electric and time-switch controls are readily available for automatic switching to eliminate the `human error` of forgetting to turn light off when they are not required. Over time, the energy saved would offset the cost of the switch controllers and the reduction in lamp life caused by repeated switching. 4 tabs., 2 figs.

  3. Ad 2.0: a novel recombineering platform for high-throughput generation of tailored adenoviruses.

    Science.gov (United States)

    Mück-Häusl, Martin; Solanki, Manish; Zhang, Wenli; Ruzsics, Zsolt; Ehrhardt, Anja

    2015-04-30

    Recombinant adenoviruses containing a double-stranded DNA genome of 26-45 kb were broadly explored in basic virology, for vaccination purposes, for treatment of tumors based on oncolytic virotherapy, or simply as a tool for efficient gene transfer. However, the majority of recombinant adenoviral vectors (AdVs) is based on a small fraction of adenovirus types and their genetic modification. Recombineering techniques provide powerful tools for arbitrary engineering of recombinant DNA. Here, we adopted a seamless recombineering technology for high-throughput and arbitrary genetic engineering of recombinant adenoviral DNA molecules. Our cloning platform which also includes a novel recombination pipeline is based on bacterial artificial chromosomes (BACs). It enables generation of novel recombinant adenoviruses from different sources and switching between commonly used early generation AdVs and the last generation high-capacity AdVs lacking all viral coding sequences making them attractive candidates for clinical use. In combination with a novel recombination pipeline allowing cloning of AdVs containing large and complex transgenes and the possibility to generate arbitrary chimeric capsid-modified adenoviruses, these techniques allow generation of tailored AdVs with distinct features. Our technologies will pave the way toward broader applications of AdVs in molecular medicine including gene therapy and vaccination studies. PMID:25609697

  4. Switching Fuzzy Guaranteed Cost Control for Nonlinear Networked Control Systems

    Directory of Open Access Journals (Sweden)

    Linqin Cai

    2014-01-01

    Full Text Available This paper deals with the problem of guaranteed cost control for a class of nonlinear networked control systems (NCSs with time-varying delay. A guaranteed cost controller design method is proposed to achieve the desired control performance based on the switched T-S fuzzy model. The switching mechanism is introduced to handle the uncertainties of NCSs. Based on Lyapunov functional approach, some sufficient conditions for the existence of state feedback robust guaranteed cost controller are presented. Simulation results show that the proposed method is effective to guarantee system’s global asymptotic stability and quality of service (QoS.

  5. STOCHASTIC ADAPTIVE SWITCHING CONTROL BASED ON MULTIPLE MODELS

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yanxia; GUO Lei

    2002-01-01

    It is well known that the transient behaviors of the traditional adaptive control may be very poor in general, and that the adaptive control designed based on switching between multiple models is an intuitively appealing and practically feasible approach to improve the transient performances. In this paper, we shall prove that for a typical class of linear systems disturbed by random noises, the multiple model based least-squares (LS)adaptive switching control is stable and convergent, and has the same convergence rate as that established for the standard least-squares-based self-tunning regulators. Moreover,the mixed case combining adaptive models with fixed models is also considered.

  6. High Efficient CMOS Class-E Power Amplifier with a New Output Power Control Scheme

    Directory of Open Access Journals (Sweden)

    MESHKIN Reza

    2013-05-01

    Full Text Available This paper presents the design of a novel RF power amplifier (PA with a new output power control scheme suitable for RF-ICs and portable systems. Employing a class-E amplifier as a drivertogether with soft-switching property of the main power stage switching mode class-E PA helps to achieve better efficiency and increases the capability of circuit integration. A new circuit scheme for efficient output power control is introduced in the proposed PAbased on the array of switches and compensated shunt capacitors with different sizes. This technique improves the Power-Added-Efficiency (PAE and its drop specially at lower output power levels in comparison with conventional power control methods. The layoutof the designed PA is made in 0.18um 1P6M CMOS process, and the chip area is 1.7mm2. simulation results show that the designed PA delivers 21.09dBm output power to a 50 standard load from a 1.8V supply voltage at 2.4GHz operating frequency with 57% PAE. Additionally, the output power of the PA is controlled with steps of 1-dBm by using the proposed array of switches and capacitors.

  7. Noise-induced coherent switch

    Institute of Scientific and Technical Information of China (English)

    YUAN ZhanJiang; ZHANG Jiadun; ZHOU TianShou

    2008-01-01

    Taking the famous genetic toggle switch as an example, we numerically investigated the effect of noise on bistability. We found that extrinsic noise resulting from stochastic fluctuations in synthesis and degradation rates and from the environmental fluctuation in gene regulatory processes can induce coherent switch, and that there is an optimal noise intensity such that the noise not only can induce this switch, but also can amplify a weak input signal. In addition, we found that the intrinsic noise introduced through the Poisson τ-leap algorithm cannot induce such a switch.

  8. Noise-induced coherent switch

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Taking the famous genetic toggle switch as an example,we numerically investigated the effect of noise on bistability.We found that extrinsic noise resulting from stochastic fluctuations in synthesis and degradation rates and from the environmental fluctuation in gene regulatory processes can induce coherent switch,and that there is an optimal noise intensity such that the noise not only can induce this switch,but also can amplify a weak input signal.In addition,we found that the intrinsic noise introduced through the Poisson τ-leap algorithm cannot induce such a switch.

  9. Recent developments in switching theory

    CERN Document Server

    Mukhopadhyay, Amar

    2013-01-01

    Electrical Science Series: Recent Developments in Switching Theory covers the progress in the study of the switching theory. The book discusses the simplified proof of Post's theorem on completeness of logic primitives; the role of feedback in combinational switching circuits; and the systematic procedure for the design of Lupanov decoding networks. The text also describes the classical results on counting theorems and their application to the classification of switching functions under different notions of equivalence, including linear and affine equivalences. The development of abstract har

  10. Neuromorphic atomic switch networks.

    Directory of Open Access Journals (Sweden)

    Audrius V Avizienis

    Full Text Available Efforts to emulate the formidable information processing capabilities of the brain through neuromorphic engineering have been bolstered by recent progress in the fabrication of nonlinear, nanoscale circuit elements that exhibit synapse-like operational characteristics. However, conventional fabrication techniques are unable to efficiently generate structures with the highly complex interconnectivity found in biological neuronal networks. Here we demonstrate the physical realization of a self-assembled neuromorphic device which implements basic concepts of systems neuroscience through a hardware-based platform comprised of over a billion interconnected atomic-switch inorganic synapses embedded in a complex network of silver nanowires. Observations of network activation and passive harmonic generation demonstrate a collective response to input stimulus in agreement with recent theoretical predictions. Further, emergent behaviors unique to the complex network of atomic switches and akin to brain function are observed, namely spatially distributed memory, recurrent dynamics and the activation of feedforward subnetworks. These devices display the functional characteristics required for implementing unconventional, biologically and neurally inspired computational methodologies in a synthetic experimental system.

  11. Recombinant Collagenlike Proteins

    Science.gov (United States)

    Fertala, Andzej

    2007-01-01

    A group of collagenlike recombinant proteins containing high densities of biologically active sites has been invented. The method used to express these proteins is similar to a method of expressing recombinant procollagens and collagens described in U. S. Patent 5,593,859, "Synthesis of human procollagens and collagens in recombinant DNA systems." Customized collagenous proteins are needed for biomedical applications. In particular, fibrillar collagens are attractive for production of matrices needed for tissue engineering and drug delivery. Prior to this invention, there was no way of producing customized collagenous proteins for these and other applications. Heretofore, collagenous proteins have been produced by use of such biological systems as yeasts, bacteria, and transgenic animals and plants. These products are normal collagens that can also be extracted from such sources as tendons, bones, and hides. These products cannot be made to consist only of biologically active, specific amino acid sequences that may be needed for specific applications. Prior to this invention, it had been established that fibrillar collagens consist of domains that are responsible for such processes as interaction with cells, binding of growth factors, and interaction with a number of structural proteins present in the extracellular matrix. A normal collagen consists of a sequence of domains that can be represented by a corresponding sequence of labels, e.g., D1D2D3D4. A collagenlike protein of the present invention contains regions of collagen II that contain multiples of a single domain (e.g., D1D1D1D1 or D4D4D4D4) chosen for its specific biological activity. By virtue of the multiplicity of the chosen domain, the density of sites having that specific biological activity is greater than it is in a normal collagen. A collagenlike protein according to this invention can thus be made to have properties that are necessary for tissue engineering.

  12. Primordial magnetogenesis before recombination

    CERN Document Server

    Fabre, Ophélia

    2015-01-01

    The origin of large magnetic fields in the Universe remains currently unknown. We investigate here a mechanism before recombination based on known physics. The source of the vorticity is due to the changes in the photon distribution function caused by the fluctuations in the background photons. We show that the magnetic field generated in the MHD limit, due to the Coulomb scattering, is of the order $10^{-49}$ G. We explicitly show that the magnetic fields generated from this process are sustainable and are not erased by resistive diffusion. We compare the results with current observations and discuss the implications.

  13. LCT protective dump-switch tests

    International Nuclear Information System (INIS)

    Each of the six coils in the Large Coil Task (LCT) has a separate power supply, dump resistor, and switching circuit. Each switching circuit contains five switches, two of which are redundant. The three remaining switches perform separate duties in an emergency dump situation. These three switches were tested to determine their ability to meet the LCT conditions

  14. Hybrid switch for resonant power converters

    Science.gov (United States)

    Lai, Jih-Sheng; Yu, Wensong

    2014-09-09

    A hybrid switch comprising two semiconductor switches connected in parallel but having different voltage drop characteristics as a function of current facilitates attainment of zero voltage switching and reduces conduction losses to complement reduction of switching losses achieved through zero voltage switching in power converters such as high-current inverters.

  15. Convertible resistive switching characteristics between memory switching and threshold switching in a single ferritin-based memristor.

    Science.gov (United States)

    Zhang, Chaochao; Shang, Jie; Xue, Wuhong; Tan, Hongwei; Pan, Liang; Yang, Xi; Guo, Shanshan; Hao, Jian; Liu, Gang; Li, Run-Wei

    2016-04-01

    A bio-memristor fabricated with ferritin exhibits novel resistive switching characteristics wherein memory switching and threshold switching are made steadily coexistent and inter-convertible through controlling the magnitude of compliance current presets. PMID:26967024

  16. EDITORIAL: Molecular switches at surfaces Molecular switches at surfaces

    Science.gov (United States)

    Weinelt, Martin; von Oppen, Felix

    2012-10-01

    In nature, molecules exploit interaction with their environment to realize complex functionalities on the nanometer length scale. Physical, chemical and/or biological specificity is frequently achieved by the switching of molecules between microscopically different states. Paradigmatic examples are the energy production in proton pumps of bacteria or the signal conversion in human vision, which rely on switching molecules between different configurations or conformations by external stimuli. The remarkable reproducibility and unparalleled fatigue resistance of these natural processes makes it highly desirable to emulate nature and develop artificial systems with molecular functionalities. A promising avenue towards this goal is to anchor the molecular switches at surfaces, offering new pathways to control their functional properties, to apply electrical contacts, or to integrate switches into larger systems. Anchoring at surfaces allows one to access the full range from individual molecular switches to self-assembled monolayers of well-defined geometry and to customize the coupling between molecules and substrate or between adsorbed molecules. Progress in this field requires both synthesis and preparation of appropriate molecular systems and control over suitable external stimuli, such as light, heat, or electrical currents. To optimize switching and generate function, it is essential to unravel the geometric structure, the electronic properties and the dynamic interactions of the molecular switches on surfaces. This special section, Molecular Switches at Surfaces, collects 17 contributions describing different aspects of this research field. They analyze elementary processes, both in single molecules and in ensembles of molecules, which involve molecular switching and concomitant changes of optical, electronic, or magnetic properties. Two topical reviews summarize the current status, including both challenges and achievements in the field of molecular switches on

  17. Battery switch for downhole tools

    Science.gov (United States)

    Boling, Brian E.

    2010-02-23

    An electrical circuit for a downhole tool may include a battery, a load electrically connected to the battery, and at least one switch electrically connected in series with the battery and to the load. The at least one switch may be configured to close when a tool temperature exceeds a selected temperature.

  18. Molecule-Based Rheology Switching

    NARCIS (Netherlands)

    Paulusse, Jos M.J.; Sijbesma, Rint P.

    2006-01-01

    Sound-activated switching: The rheological behavior of fluids can be affected by external stimuli, as demonstrated by electrochemically and photochemically induced changes in viscosity and sol–gel transitions. Recently, ultrasound has emerged as a novel rheology switch for supramolecular polymers an

  19. Switching Costs in Accounting Services

    OpenAIRE

    Fatih Koç; Nisa Kıymet Şahin

    2015-01-01

    Switching cost is defined as possible costs that customers may encounter when they want to change the firm they buy service, and an important subject in terms of accounting services. Particularly, small business entrepreneurs’ not having knowledge about accounting procedures, and sharing private information with accounting firms make switching costs more important for accounting services. Thus, the aim of this study is...

  20. Estimating treatment effects with treatment switching via semicompeting risks models: an application to a colorectal cancer study

    OpenAIRE

    Zeng, Donglin; Chen, Qingxia; Chen, Ming-Hui; Ibrahim, Joseph G.

    2011-01-01

    Treatment switching is a frequent occurrence in clinical trials, where, during the course of the trial, patients who fail on the control treatment may change to the experimental treatment. Analysing the data without accounting for switching yields highly biased and inefficient estimates of the treatment effect. In this paper, we propose a novel class of semiparametric semicompeting risks transition survival models to accommodate treatment switches. Theoretical properties of the proposed model...

  1. Experiments in magnetic switching

    International Nuclear Information System (INIS)

    Magnetic switching offers an alternative to overcoming the rep-rate and life limitations of the spark gaps in the ETA/ATA induction accelerators. The principle has been applied for many years to radar modulators but at much lower power levels and longer pulse lengths. Comparatively recent developments in magnetic materials together with some optimal circuits have made it possible to go well beyond the state of the art. A magnetic modulator has been built which steps up and compresses a 25 kV, 5 μs pulse into a 250 kV, 50 ns pulse. A second magnetic modulator has been built and installed to replace four Blumleins and spark gaps in order to provide triggers for the complete ETA injector and accelerator. The paper outlines some practical and theoretical considerations affecting the design of the magnetic pulse generator

  2. Optimized scalable network switch

    Energy Technology Data Exchange (ETDEWEB)

    Blumrich, Matthias A. (Ridgefield, CT); Chen, Dong (Croton on Hudson, NY); Coteus, Paul W. (Yorktown Heights, NY)

    2010-02-23

    In a massively parallel computing system having a plurality of nodes configured in m multi-dimensions, each node including a computing device, a method for routing packets towards their destination nodes is provided which includes generating at least one of a 2m plurality of compact bit vectors containing information derived from downstream nodes. A multilevel arbitration process in which downstream information stored in the compact vectors, such as link status information and fullness of downstream buffers, is used to determine a preferred direction and virtual channel for packet transmission. Preferred direction ranges are encoded and virtual channels are selected by examining the plurality of compact bit vectors. This dynamic routing method eliminates the necessity of routing tables, thus enhancing scalability of the switch.

  3. Switching Tracking Control for Planar Systems with Transient Performance Constraints

    Institute of Scientific and Technical Information of China (English)

    SU Qing-Yu; SUN Xi-Ming; ZHAO Jun

    2013-01-01

    This paper studies the output tracking problem for a class of planar systems with some given transient performance constraints which are determined by the overshoot and the settling time.The problem of switched static output feedback tracking with output constraints (SSOFTOC) is proposed and solved for the first time.The static output feedback controllers and a so-called conic switching law are designed under which the output of the closed-loop switched system can track the step signal asymptotically without violating the transient performance constraints.Furthermore,an optimal weighted transient performance is obtained by.solving a nonlinear programming problem.Finally,a numerical example and an application to aircraft turbofan engine are given to illustrate the effectiveness and the applicability of the proposed method.

  4. Development and fabrication of improved power transistor switches

    Science.gov (United States)

    Hower, P. L.; Chu, C. K.

    1979-01-01

    A new class of high-voltage power transistors was achieved by adapting present interdigitated thyristor processing techniques to the fabrication of npn Si transistors. Present devices are 2.3 cm in diameter and have V sub CEO (sus) in the range of 400 to 600V. V sub CEO (sus) = 450V devices were made with an (h sub FE)(I sub C) product of 900A at V sub CE = 2.5V. The electrical performance obtained was consistent with the predictions of an optimum design theory specifically developed for power switching transistors. The device design, wafer processing, and assembly techniques are described. Experimental measurements of the dc characteristics, forward SOA, and switching times are included. A new method of characterizing the switching performance of power transistors is proposed.

  5. Amorphous metal based nanoelectromechanical switch

    KAUST Repository

    Mayet, Abdulilah M.

    2013-04-01

    Nanoelectromechanical (NEM) switch is an interesting ultra-low power option which can operate in the harsh environment and can be a complementary element in complex digital circuitry. Although significant advancement is happening in this field, report on ultra-low voltage (pull-in) switch which offers high switching speed and area efficiency is yet to be made. One key challenge to achieve such characteristics is to fabricate nano-scale switches with amorphous metal so the shape and dimensional integrity are maintained to achieve the desired performance. Therefore, we report a tungsten alloy based amorphous metal with fabrication process development of laterally actuated dual gated NEM switches with 100 nm width and 200 nm air-gap to result in <5 volts of actuation voltage (Vpull-in). © 2013 IEEE.

  6. Ferrite bead effect on Class-D amplifier audio quality

    OpenAIRE

    Haddad, Kevin El; Mrad, Roberto; Morel, Florent; Pillonnet, Gael; Vollaire, Christian; Nagari, Angelo

    2014-01-01

    International audience This paper studies the effect of ferrite beads on the audio quality of Class-D audio amplifiers. This latter is a switch-ing circuit which creates high frequency harmonics. Generally, a filter is used at the amplifier output for the sake of electro-magnetic compatibility (EMC). So often, in integrated solutions, this filter contains ferrite beads which are magnetic components and present nonlinear behavior. Time domain measurements and their equivalence in frequency ...

  7. Simulation method of ATM switch architecture and proposal for the delay priority control in ATM crosspoint switch; ATM kokanki no simulation shuho to crosspoint switch ni okeru chien yusen seigyo no teian

    Energy Technology Data Exchange (ETDEWEB)

    Doi, H. [Central Research Institute of Electric Power Industry, Tokyo (Japan)

    1996-03-01

    A simulation method for switch analysis of ATM (asynchronous transfer mode) switch architecture has been developed. When various electric power information is integrated in the ATM switch architecture, delay priority control method has been proposed, by which the delay time and delay time fluctuation can be guaranteed for important information, such as system protection control information. The simulation method has been developed for analyzing the output buffer type crosspoint switch. The analysis solutions of waiting time of cells at the switch were determined and compared with the simulation results. The both agreed well mutually, and the validity of this method was confirmed. Priority was added to the cells of crosspoint switch, and different buffer was given for each priority, to exchange the important information, selectively. Thus, a switch was proposed, by which the delay time and delay time fluctuation can be restricted. The mean waiting time of the high class cells was suppressed less than 1 cts even at the switch load factor of 0.98, and the fluctuation range of 4 cts was guaranteed. 11 refs., 19 figs.

  8. Channelized coplanar waveguide pin-diode switches

    Science.gov (United States)

    Ponchak, G. E.; Simons, R. N.

    1989-01-01

    Three different types of p-i-n diode, reflective CPW switches are presented. The first two switches are the series and the shunt mounted diode switches. Each has achieved greater than 15 dB of isolation over a broad bandwidth. The third switch is a narrow band, high isolation switched filter which has achieved 19 dB of isolation. Equivalent circuits and measured performance for each switch is presented.

  9. Primordial magnetogenesis before recombination

    Science.gov (United States)

    Fabre, Ophélia; Shankaranarayanan, S.

    2016-04-01

    The origin of large magnetic fields in the Universe remains currently unknown. We investigate here a mechanism before recombination based on known physics. The source of the vorticity is due to the changes in the photon distribution function caused by the fluctuations in the background photons. We show that the magnetic field generated in the MHD limit, due to the Coulomb scattering, is of the order 10-49 G on a coherence scale of 10 kpc. We explicitly show that the magnetic fields generated from this process are sustainable and are not erased by resistive diffusion. We compare the results with current observations and discuss the implications. Our seed magnetic fields are generated on small scales whereas the main mechanisms studied in the literature are on scale bigger than 1 Mpc. However, compared to more exotic theories generating seed magnetic fields on similar scales, the strength of our fields are generally smaller.

  10. Cell biology of mitotic recombination

    DEFF Research Database (Denmark)

    Lisby, Michael; Rothstein, Rodney

    2015-01-01

    Homologous recombination provides high-fidelity DNA repair throughout all domains of life. Live cell fluorescence microscopy offers the opportunity to image individual recombination events in real time providing insight into the in vivo biochemistry of the involved proteins and DNA molecules as w...

  11. Analysis of chickens for recombination within the MHC (B-complex)

    DEFF Research Database (Denmark)

    Skjødt, K; Koch, C; Crone, M

    1985-01-01

    In an attempt to further map the chicken MHC (the B complex), a systematic search for genetic recombinants within the B complex was performed by serotyping the progeny from F2 crosses of chickens by means of specific anti-class I, anti-class II, and anti-class IV alloantisera. Two recombinant B......-haplotypes (B21r and B15r) were found by analysing 2,656 F2 chickens representing 5,312 informative typings. In either case, the B-G (class IV) allele was recombined with both the B-F and B-L alleles of the opposite haplotype. MLC typings, tests for direct compatibility by GVH reactions, and absorption analyses...

  12. Bimolecular recombination in organic photovoltaics.

    Science.gov (United States)

    Lakhwani, Girish; Rao, Akshay; Friend, Richard H

    2014-01-01

    The recombination of electrons and holes is a major loss mechanism in photovoltaic devices that controls their performance. We review scientific literature on bimolecular recombination (BR) in bulk heterojunction organic photovoltaic devices to bring forward existing ideas on the origin and nature of BR and highlight both experimental and theoretical work done to quantify its extent. For these systems, Langevin theory fails to explain BR, and recombination dynamics turns out to be dependent on mobility, temperature, electric field, charge carrier concentration, and trapped charges. Relationships among the photocurrent, open-circuit voltage, fill factor, and morphology are discussed. Finally, we highlight the recent emergence of a molecular-level picture of recombination, taking into account the spin and delocalization of charges. Together with the macroscopic picture of recombination, these new insights allow for a comprehensive understanding of BR and provide design principles for future materials and devices.

  13. Computational capacity and energy consumption of complex resistive switch networks

    Directory of Open Access Journals (Sweden)

    Jens Bürger

    2015-12-01

    Full Text Available Resistive switches are a class of emerging nanoelectronics devices that exhibit a wide variety of switching characteristics closely resembling behaviors of biological synapses. Assembled into random networks, such resistive switches produce emerging behaviors far more complex than that of individual devices. This was previously demonstrated in simulations that exploit information processing within these random networks to solve tasks that require nonlinear computation as well as memory. Physical assemblies of such networks manifest complex spatial structures and basic processing capabilities often related to biologically-inspired computing. We model and simulate random resistive switch networks and analyze their computational capacities. We provide a detailed discussion of the relevant design parameters and establish the link to the physical assemblies by relating the modeling parameters to physical parameters. More globally connected networks and an increased network switching activity are means to increase the computational capacity linearly at the expense of exponentially growing energy consumption. We discuss a new modular approach that exhibits higher computational capacities, and energy consumption growing linearly with the number of networks used. The results show how to optimize the trade-o between computational capacity and energy e ciency and are relevant for the design and fabrication of novel computing architectures that harness random assemblies of emerging nanodevices.

  14. Multistable decision switches for flexible control of epigenetic differentiation.

    Directory of Open Access Journals (Sweden)

    Raúl Guantes

    2008-11-01

    Full Text Available It is now recognized that molecular circuits with positive feedback can induce two different gene expression states (bistability under the very same cellular conditions. Whether, and how, cells make use of the coexistence of a larger number of stable states (multistability is however largely unknown. Here, we first examine how autoregulation, a common attribute of genetic master regulators, facilitates multistability in two-component circuits. A systematic exploration of these modules' parameter space reveals two classes of molecular switches, involving transitions in bistable (progression switches or multistable (decision switches regimes. We demonstrate the potential of decision switches for multifaceted stimulus processing, including strength, duration, and flexible discrimination. These tasks enhance response specificity, help to store short-term memories of recent signaling events, stabilize transient gene expression, and enable stochastic fate commitment. The relevance of these circuits is further supported by biological data, because we find them in numerous developmental scenarios. Indeed, many of the presented information-processing features of decision switches could ultimately demonstrate a more flexible control of epigenetic differentiation.

  15. EXPONENTIAL ESTIMATES FOR STOCHASTIC DELAY HYBRID SYSTEMS WITH MARKOVIAN SWITCHING

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This paper deals with the problem of norm bounds for the solutions of stochastic hybrid systems with Markovian switching and time delay. Based on Lyapunov-Krasovskii theory for functional differential equations and the linear matrix inequality (LMI) approach, mean square exponential estimates for the solutions of this class of linear stochastic hybrid systems are derived. Finally, An example is illustrated to show the applicability and effectiveness of our method.

  16. Practical stability and instability of regime-switching diffusions

    Institute of Scientific and Technical Information of China (English)

    G.George YIN; Bo ZHANG; Chao ZHU

    2008-01-01

    This work is devoted to practical stability of a class of regime-switching diffusions.First,the notion of practical stability is introduced.Then,sufficient conditions for practical stability and practical instability in probability and in pth mean are provided using a Lyapunov function argument.In addition,easily verifiable conditions on drift and diffusion coefficients are also given.Moreover,examples are supplied for demonstration purposes.

  17. Very High Frequency Switch-Mode Power Supplies

    DEFF Research Database (Denmark)

    Madsen, Mickey Pierre

    of technologies for very high frequency switch mode power supplies. At these highly elevated frequencies normal bulky magnetics with heavy cores consisting of rare earth materials, can be replaced by air core inductors embedded in the printed circuit board. This is investigated thoroughly and both spirals...... of 70%, weight reduction of 81%, cost reduction of 56% and efficiency gain of 4.5%-points can be achieved with a very high frequency class DE converter, compared to a commercial product....

  18. Biomimetic production of silk-like recombinant squid sucker ring teeth proteins.

    Science.gov (United States)

    Ding, Dawei; Guerette, Paul A; Hoon, Shawn; Kong, Kiat Whye; Cornvik, Tobias; Nilsson, Martina; Kumar, Akshita; Lescar, Julien; Miserez, Ali

    2014-09-01

    The sucker ring teeth (SRT) of Humboldt squid exhibit mechanical properties that rival those of robust engineered synthetic polymers. Remarkably, these properties are achieved without a mineral phase or covalent cross-links. Instead, SRT are exclusively made of silk-like proteins called "suckerins", which assemble into nanoconfined β-sheet reinforced supramolecular networks. In this study, three streamlined strategies for full-length recombinant suckerin protein production and purification were developed. Recombinant suckerin exhibited high solubility and colloidal stability in aqueous-based solvents. In addition, the colloidal suspensions exhibited a concentration-dependent conformational switch, from random coil to β-sheet enriched structures. Our results demonstrate that recombinant suckerin can be produced in a facile manner in E. coli and processed from mild aqueous solutions into materials enriched in β-sheets. We suggest that recombinant suckerin-based materials offer potential for a range of biomedical and engineering applications. PMID:25068184

  19. Peptide Binding to HLA Class I Molecules: Homogenous, High-Throughput Screening, and Affinity Assays

    DEFF Research Database (Denmark)

    Harndahl, Mikkel; Justesen, Sune Frederik Lamdahl; Lamberth, Kasper;

    2009-01-01

    present a homogenous, proximity-based assay for detection of peptide binding to HLA class I molecules. It uses a conformation-dependent anti-HLA class I antibody, W6/32, as one tag and a biotinylated recombinant HLA class I molecule as the other tag, and a proximity-based signal is generated through...

  20. The magnetoelectrochemical switch.

    Science.gov (United States)

    Popa, Petru Lunca; Kemp, Neil T; Majjad, Hicham; Dalmas, Guillaume; Faramarzi, Vina; Andreas, Christian; Hertel, Riccardo; Doudin, Bernard

    2014-07-22

    In the field of spintronics, the archetype solid-state two-terminal device is the spin valve, where the resistance is controlled by the magnetization configuration. We show here how this concept of spin-dependent switch can be extended to magnetic electrodes in solution, by magnetic control of their chemical environment. Appropriate nanoscale design allows a huge enhancement of the magnetic force field experienced by paramagnetic molecular species in solutions, which changes between repulsive and attractive on changing the electrodes' magnetic orientations. Specifically, the field gradient force created within a sub-100-nm-sized nanogap separating two magnetic electrodes can be reversed by changing the orientation of the electrodes' magnetization relative to the current flowing between the electrodes. This can result in a breaking or making of an electric nanocontact, with a change of resistance by a factor of up to 10(3). The results reveal how an external field can impact chemical equilibrium in the vicinity of nanoscale magnetic circuits. PMID:25009179

  1. Electrically switched ion exchange

    Energy Technology Data Exchange (ETDEWEB)

    Lilga, M.A. [Pacific Northwest National Lab., Richland, WA (United States); Schwartz, D.T.; Genders, D.

    1997-10-01

    A variety of waste types containing radioactive {sup 137}Cs are found throughout the DOE complex. These waste types include water in reactor cooling basins, radioactive high-level waste (HLW) in underground storage tanks, and groundwater. Safety and regulatory requirements and economics require the removal of radiocesium before these wastes can be permanently disposed of. Electrically Switched Ion Exchange (ESIX) is an approach for radioactive cesium separation that combines IX and electrochemistry to provide a selective, reversible, and economic separation method that also produces little or no secondary waste. In the ESIX process, an electroactive IX film is deposited electrochemically onto a high-surface area electrode, and ion uptake and elution are controlled directly by modulating the potential of the film. For cesium, the electroactive films under investigation are ferrocyanides, which are well known to have high selectivities for cesium in concentrated sodium solutions. When a cathode potential is applied to the film, Fe{sup +3} is reduced to the Fe{sup +2} state, and a cation must be intercalated into the film to maintain charge neutrality (i.e., Cs{sup +} is loaded). Conversely, if an anodic potential is applied, a cation must be released from the film (i.e., Cs{sup +} is unloaded). Therefore, to load the film with cesium, the film is simply reduced; to unload cesium, the film is oxidized.

  2. Ergodic directional switching in mobile insect groups

    KAUST Repository

    Escudero, Carlos

    2010-07-29

    We obtain a Fokker-Planck equation describing experimental data on the collective motion of locusts. The noise is of internal origin and due to the discrete character and finite number of constituents of the swarm. The stationary probability distribution shows a rich phenomenology including nonmonotonic behavior of several order and disorder transition indicators in noise intensity. This complex behavior arises naturally as a result of the randomness in the system. Its counterintuitive character challenges standard interpretations of noise induced transitions and calls for an extension of this theory in order to capture the behavior of certain classes of biologically motivated models. Our results suggest that the collective switches of the group\\'s direction of motion might be due to a random ergodic effect and, as such, they are inherent to group formation. © 2010 The American Physical Society.

  3. Radio recombination lines from H II regions

    International Nuclear Information System (INIS)

    Radio recombination lines have been observed from forty-six H II regions. The Arecibo 1000-foot radio telescope was used to provide high sensitivity and high angular resolution at 1400 MHz (gain approx. 7.70K/Jy, HPBW = 3:2) and 2372 MHZ (gain approx. 6.30K/Jy, HPBW = 2'). Observations were made at 1400 MHz in the frequency switching mode, and at 2372 MHz in the total power mode. Gaussians were fit to be observed lines to derive velocities, line widths, and line temperatures. From the velocities kinematic distances were derived. For eleven sources H I absorption measurements were also made. The absorption spectra enabled the kinematic distance ambiguity to be resolved for some sources. The absorption spectra themselves were found to have extremely sharp, non-gaussian edges. One explanation for these is a model where the interstellar medium contains many H I cloudlets with T/sub s/less than or equal to 1000K and turbulent velocities less than or equal to 3 km/s. The H I absorption spectrum is then a superposition of many narrow gaussian profiles. It was also found from a comparison of H I absorption velocities with radio recombination line velocities that peculiar motions exist in the interstellar medium with velocities of up to 10 km/s. Using the measured line temperatures and continuum temperatures, estimates were desired of emission measures, electron temperatures, and electron densities, using a non-LTE analysis. Non-LTE effects were important only for the hottest and densest H II regions. The non-LTE calculations were checked through a comparison derivation of electron temperatures using hydrogen beta lines

  4. Wide Bandgap Extrinsic Photoconductive Switches

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, James S. [State Univ. of New York (SUNY), Plattsburgh, NY (United States); Univ. of California, Davis, CA (United States)

    2012-01-20

    Photoconductive semiconductor switches (PCSS) have been investigated since the late 1970s. Some devices have been developed that withstand tens of kilovolts and others that switch hundreds of amperes. However, no single device has been developed that can reliably withstand both high voltage and switch high current. Yet, photoconductive switches still hold the promise of reliable high voltage and high current operation with subnanosecond risetimes. Particularly since good quality, bulk, single crystal, wide bandgap semiconductor materials have recently become available. In this chapter we will review the basic operation of PCSS devices, status of PCSS devices and properties of the wide bandgap semiconductors 4H-SiC, 6H-SiC and 2H-GaN.

  5. Polariton condensates: Electrical spin switching

    Science.gov (United States)

    Liew, T. C. H.

    2016-10-01

    Ultra-low-power electronic switching of stable exciton-polariton spin states has now been achieved in a semiconductor microcavity. This opens a new route to the integration of spin-based photonics and electronics.

  6. Electromagnetic actuation in MEMS switches

    DEFF Research Database (Denmark)

    Oliveira Hansen, Roana Melina de; Mátéfi-Tempfli, Mária; Chemnitz, Steffen;

    Power electronics takes use of switches in order to convert and manage energy. The ideal switch with low power loss consists of electromechanic relays, but since they are bulky and expensive, semiconductors switches are more widely used for power electronic applications, resulting in power losses...... during energy conversion. Micro-Electro-Mechanical Systems (MEMS) consist of miniaturized mechanical and/or electro-mechanical elements fabricated using microfabrication techniques, and are good candidates for achieving a miniaturized electromechanic switch at the micro-scale with very little power loss...... constrains its integration through standard deposition methods. Electroplating is a deposition technique which allows the deposition of thick films, and the integration of this technique to standard cleanroom fabrication is one of the focuses of this project, leading to large-scale fabrication of a new...

  7. Multiuser Switched Diversity Scheduling Schemes

    CERN Document Server

    Shaqfeh, Mohammad; Alouini, Mohamed-Slim

    2012-01-01

    Multiuser switched-diversity scheduling schemes were recently proposed in order to overcome the heavy feedback requirements of conventional opportunistic scheduling schemes by applying a threshold-based, distributed, and ordered scheduling mechanism. The main idea behind these schemes is that slight reduction in the prospected multiuser diversity gains is an acceptable trade-off for great savings in terms of required channel-state-information feedback messages. In this work, we characterize the achievable rate region of multiuser switched diversity systems and compare it with the rate region of full feedback multiuser diversity systems. We propose also a novel proportional fair multiuser switched-based scheduling scheme and we demonstrate that it can be optimized using a practical and distributed method to obtain the feedback thresholds. We finally demonstrate by numerical examples that switched-diversity scheduling schemes operate within 0.3 bits/sec/Hz from the ultimate network capacity of full feedback sys...

  8. Observer-Based Robust Control for Switched Stochastic Systems with Time-Varying Delay

    Directory of Open Access Journals (Sweden)

    Guoxin Chen

    2013-01-01

    Full Text Available This paper investigates the problem of observer-based robust control for a class of switched stochastic systems with time-varying delay. Based on the average dwell time method, an exponential stability criterion for switched stochastic delay systems is proposed. Then, performance analysis and observer-based robust controller design for the underlying systems are developed. Finally, a numerical example is presented to illustrate the effectiveness of the proposed approach.

  9. Adaptive switching control of discrete time nonlinear systems based on multiple models

    Institute of Scientific and Technical Information of China (English)

    Rui KAN

    2004-01-01

    We use the approach of "optimal" switching to design the adaptive control because the design among multiple models is intuitively more practically feasible than the traditional adaptive control in improving the performances. We prove that for a typical class of nonlinear systems disturbed by random noise, the multiple model adaptive switching control based on WLS(Weighted Least Squares) or projected-LS (Least Squares) is stable and convergent.

  10. Direct-conversion switching-mode audio power amplifier with active capacitive voltage clamp

    DEFF Research Database (Denmark)

    Ljusev, Petar; Andersen, Michael Andreas E.

    2005-01-01

    This paper discusses the advantages and problems when implementing direct energy conversion switching-mode audio power amplifiers. It is shown that the total integration of the power supply and Class D audio power amplifier into one compact direct converter can simplify the design, increase...... efficiency, reduce the product volume and lower its cost. As an example, the principle of operation and the measurements made on a direct-conversion switching-mode audio power amplifier with active capacitive voltage clamp are presented....

  11. A power-efficient audio amplifier combining switching and linear techniques

    OpenAIRE

    Zee, van der, KG Kristoffer; Tuijl, van, B.A.J.

    1999-01-01

    Integrated Class D audio amplifiers are very power efficient, but require an external filter which prevents further integration. Also due to this filter, large feedback factors are hard to realise, so that the load influences the distortion- and transfer characteristics. The amplifier presented in this paper consists of a switching part that contains a much simpler filter, and a linear part that ensures a low distortion and flat frequency response. A 30W version was realised. The switching pa...

  12. Direct-conversion switching-mode audio power amplifier with active capacitive voltage clamp

    OpenAIRE

    Ljusev, Petar; Andersen, Michael Andreas E.

    2005-01-01

    This paper discusses the advantages and problems when implementing direct energy conversion switching-mode audio power amplifiers. It is shown that the total integration of the power supply and Class D audio power amplifier into one compact direct converter can simplify the design, increase efficiency, reduce the product volume and lower its cost. As an example, the principle of operation and the measurements made on a direct-conversion switching-mode audio power amplifier with active capacit...

  13. Stabilization Control for Linear Switching Stochastic Systems Against Time-Delay in Communication Channel

    Institute of Scientific and Technical Information of China (English)

    Dongfang Lv; Shen Cong

    2015-01-01

    The paper is concerned with stabilization problem for a class of stochastic switching systems with time⁃delay in the detection of switching signal. By using binomial model, Poisson process, and Wiener process to describe time⁃delay, switching signal, and exogenous disturbance, respectively, the system under investigation is entirely set in a stochastic framework. The influence of the random time⁃delay is combined into reconstructing the switching signal of overall closed⁃loop system and changes the distribution property of switching points. Therefore, based on the asymptotical behaviors of Poisson processes and Wiener processes, the almost surely exponential stability conditions are established. Furthermore, a design methodology is posed for solving the stabilization control.

  14. Exponential Stability of Time-Switched Two-Subsystem Nonlinear Systems with Application to Intermittent Control

    Directory of Open Access Journals (Sweden)

    Huang Tingwen

    2009-01-01

    Full Text Available This paper studies the exponential stability of a class of periodically time-switched nonlinear systems. Three cases of such systems which are composed, respectively, of a pair of unstable subsystems, of both stable and unstable subsystems, and of a pair of stable systems, are considered. For the first case, the proposed result shows that there exists periodically switching rule guaranteeing the exponential stability of the whole system with (sufficient small switching period if there is a Hurwitz linear convex combination of two uncertain linear systems derived from two subsystems by certain linearization. For the second case, we present two general switching criteria by means of multiple and single Lyapunov function, respectively. We also investigate the stability issue of the third case, and the switching criteria of exponential stability are proposed. The present results for the second case are further applied to the periodically intermittent control. Several numerical examples are also given to show the effectiveness of theoretical results.

  15. High PRF high current switch

    Science.gov (United States)

    Moran, Stuart L.; Hutcherson, R. Kenneth

    1990-03-27

    A triggerable, high voltage, high current, spark gap switch for use in pu power systems. The device comprises a pair of electrodes in a high pressure hydrogen environment that is triggered by introducing an arc between one electrode and a trigger pin. Unusually high repetition rates may be obtained by undervolting the switch, i.e., operating the trigger at voltages much below the self-breakdown voltage of the device.

  16. Product choice and product switching

    OpenAIRE

    Andrew B. Bernard; Redding, Stephen; Peter K. Schott

    2003-01-01

    This paper develops a model of endogenous product selection by firms. The theory is motivated by new evidence we present on the importance of product switching by U.S. manufacturers. Two-thirds of continuing firms change their product mix every five years, and product switches involve more than 40% of firm output and almost half of existing products. The theoretical model incorporates heterogeneous firms, heterogeneous products, and ongoing entry and exit. In equilibrium, firm productivity is...

  17. Statistical switching kinetics in ferroelectrics

    OpenAIRE

    Lou, X. J.

    2008-01-01

    By assuming a more realistic nucleation and polarization reversal scenario we build a new statistical switching model for ferroelectrics, which is different from either the Kolmogorov-Avrami-Ishibashi (KAI) model or the Nucleation-Limited-Switching (NLS) model. After incorporating a time-dependent depolarization field this model gives a good description about the retardation behavior in polycrystalline thin films at medium or low fields, which can not be described by the traditional KAI model...

  18. Superannuation: Switching and Roulette Wheels

    OpenAIRE

    Michael E. Drew

    2007-01-01

    The introduction of choice has resulted in Australia’s superannuation system providing unprecedented flexibility (through increased investment options and the timing choices) for members to optimise their expected benefits. This paper examines the impact of switching between investment options using a normalised ranked return or “roulette wheel” approach developed by Bauer and Dahlquist (2001) for the Australian setting. The paper tests various switching strategies for both single-sector and ...

  19. Ways to suppress click and pop for class D amplifiers

    Science.gov (United States)

    Haishi, Wang; Bo, Zhang; Jiang, Sun

    2012-08-01

    Undesirable audio click and pop may be generated in a speaker or headphone. Compared to linear (class A/B/AB) amplifiers, class D amplifiers that comprise of an input stage and a modulation stage are more prone to producing click and pop. This article analyzes sources that generate click and pop in class D amplifiers, and corresponding ways to suppress them. For a class D amplifier with a single-ended input, click and pop is likely to be due to two factors. One is from a voltage difference (VDIF) between the voltage of an input capacitance (VCIN) and a reference voltage (VREF) of the input stage, and the other one is from the non-linear switching during the setting up of the bias and feedback voltages/currents (BFVC) of the modulation stage. In this article, a fast charging loop is introduced into the input stage to charge VCIN to roughly near VREF. Then a correction loop further charges or discharges VCIN, substantially equalizing it with VREF. Dummy switches are introduced into the modulation stage to provide switching signals for setting up BFVC, and the power switches are disabled until the BFVC are set up successfully. A two channel single-ended class D amplifier with the above features is fabricated with 0.5 μm Bi-CMOS process. Road test and fast Fourier transform analysis indicate that there is no noticeable click and pop.

  20. Aspergillus: sex and recombination.

    Science.gov (United States)

    Varga, János; Szigeti, Gyöngyi; Baranyi, Nikolett; Kocsubé, Sándor; O'Gorman, Céline M; Dyer, Paul S

    2014-12-01

    The genus Aspergillus is one of the most widespread groups of fungi on Earth, comprised of about 300-350 species with very diverse lifestyles. Most species produce asexual propagula (conidia) on conidial heads. Despite their ubiquity, a sexual cycle has not yet been identified for most of the aspergilli. Where sexual reproduction is present, species exhibit either homothallic (self fertile) or heterothallic (obligate outcrossing) breeding systems. A parasexual cycle has also been described in some Aspergillus species. As in other fungi, sexual reproduction is governed by mating-type (MAT) genes, which determine sexual identity and are involved in regulating later stages of sexual development. Previous population genetic studies have indicated that some supposedly asexual aspergilli exhibit evidence of a recombining population structure, suggesting the presence of a cryptic sexual cycle. In addition, genome analyses have revealed networks of genes necessary for sexual reproduction in several Aspergillus species, again consistent with latent sexuality in these fungi. Knowledge of MAT gene presence has then successfully been applied to induce sexual reproduction between MAT1-1 and MAT1-2 isolates of certain supposedly asexual aspergilli. Recent progress in understanding the extent and significance of sexual reproduction is described here, with special emphasis on findings that are relevant to clinically important aspergilli. PMID:25118872

  1. Working Memory Costs of Task Switching

    Science.gov (United States)

    Liefooghe, Baptist; Barrouillet, Pierre; Vandierendonck, Andre; Camos, Valerie

    2008-01-01

    Although many accounts of task switching emphasize the importance of working memory as a substantial source of the switch cost, there is a lack of evidence demonstrating that task switching actually places additional demands on working memory. The present study addressed this issue by implementing task switching in continuous complex span tasks…

  2. Class Transitions in Black Holes

    CERN Document Server

    Chakrabarti, S K

    2005-01-01

    A black hole spectrum is known to change from the hard state to the soft state when the energy spectral index $\\alpha$ ($F_E \\propto E^{-\\alpha}$) in, say, 2-20 keV range changes from $\\alpha \\sim 0.5$ to $\\sim 1.5$. However, this `classical' definition which characterizes black holes like Cyg X-1, becomes less useful for many objects such as GRS 1915+105 in which the spectral slope is seen to vary from one to the other in a matter of seconds and depending on whether or not winds form, the spectral slope also changes. The light curves and the colour-colour diagrams may look completely different on different days depending on the frequency and mode of switching from one spectral state to the other. Though RXTE observations have yielded wealth of information on such `variability classes' in GRS 1915+105, very rarely one has been able to observe how the object goes from one class to the other. In the present review, we discuss possible origins of the class transition and present several examples of such transiti...

  3. Robust Finite-Time H∞ Control for Impulsive Switched Nonlinear Systems with State Delay

    Directory of Open Access Journals (Sweden)

    Jian Guo

    2012-01-01

    Full Text Available This paper investigates robust finite-time H∞ control for a class of impulsive switched nonlinear systems with time-delay. Firstly, using piecewise Lyapunov function, sufficient conditions ensuring finite-time boundedness of the impulsive switched system are derived. Then, finite-time H∞ performance analysis for impulsive switched systems is developed, and a robust finite-time H∞ state feedback controller is proposed to guarantee that the resulting closed-loop system is finite-time bounded with H∞ disturbance attenuation. All the results are given in terms of linear matrix inequalities (LMIs. Finally, two numerical examples are provided to show the effectiveness of the proposed method.

  4. Robust Stability Analysis and Synthesis for Switched Discrete-Time Systems with Time Delay

    Directory of Open Access Journals (Sweden)

    Liguo Zhang

    2010-01-01

    Full Text Available The problems of robust stability analysis and synthesis for a class of uncertain switched time-delay systems with polytopic type uncertainties are addressed. Based on the constructive use of an appropriate switched Lyapunov function, sufficient linear matrix inequalities (LMIs conditions are investigated to make such systems a uniform quadratic stability with an L2-gain smaller than a given constant level. System synthesis is to design switched feedback schemes, whether based on state, output measurements, or by using dynamic output feedback, to guarantee that the corresponding closed-loop system satisfies the LMIs conditions. Two numerical examples are provided that demonstrate the efficiency of this approach.

  5. Guaranteed Cost H∞ Controller Synthesis for Switched Systems Defined on Semi-algebraic Sets

    DEFF Research Database (Denmark)

    Ahmadi, Mohamadreza; Mojallali, Hamed; Wisniewski, Rafael

    2014-01-01

    A methodology to design guaranteed cost H∞ controllers for a class of switched systems with polynomial vector fields is proposed. To this end, we use sum of squares programming techniques. In addition, instead of the customary Carathéodory solutions, the analysis is performed in the framework...... feasibility tests leading to a stabilizing switching controller. Finally, we propose a scheme to synthesize stabilizing switching controllers with a guaranteed cost H∞ disturbance attenuation performance. The applicability of the proposed methods is elucidated thorough simulation analysis....

  6. Generation of Recombinant Monoclonal Antibodies from Immunised Mice and Rabbits via Flow Cytometry and Sorting of Antigen-Specific IgG+ Memory B Cells.

    Directory of Open Access Journals (Sweden)

    Dale O Starkie

    Full Text Available Single B cell screening strategies, which avoid both hybridoma fusion and combinatorial display, have emerged as important technologies for efficiently sampling the natural antibody repertoire of immunized animals and humans. Having access to a range of methods to interrogate different B cell subsets provides an attractive option to ensure large and diverse panels of high quality antibody are produced. The generation of multiple antibodies and having the ability to find rare B cell clones producing IgG with unique and desirable characteristics facilitates the identification of fit-for-purpose molecules that can be developed into therapeutic agents or research reagents. Here, we describe a multi-parameter flow cytometry single-cell sorting technique for the generation of antigen-specific recombinant monoclonal antibodies from single IgG+ memory B cells. Both mouse splenocytes and rabbit PBMC from immunised animals were used as a source of B cells. Reagents staining both B cells and other unwanted cell types enabled efficient identification of class-switched IgG+ memory B cells. Concurrent staining with antigen labelled separately with two spectrally-distinct fluorophores enabled antigen-specific B cells to be identified, i.e. those which bind to both antigen conjugates (double-positive. These cells were then typically sorted at one cell per well using FACS directly into a 96-well plate containing reverse transcriptase reaction mix. Following production of cDNA, PCR was performed to amplify cognate heavy and light chain variable region genes and generate transcriptionally-active PCR (TAP fragments. These linear expression cassettes were then used directly in a mammalian cell transfection to generate recombinant antibody for further testing. We were able to successfully generate antigen-specific recombinant antibodies from both the rabbit and mouse IgG+ memory B cell subset within one week. This included the generation of an anti-TNFR2 blocking

  7. Class Vectors: Embedding representation of Document Classes

    OpenAIRE

    Sachan, Devendra Singh; Kumar, Shailesh

    2015-01-01

    Distributed representations of words and paragraphs as semantic embeddings in high dimensional data are used across a number of Natural Language Understanding tasks such as retrieval, translation, and classification. In this work, we propose "Class Vectors" - a framework for learning a vector per class in the same embedding space as the word and paragraph embeddings. Similarity between these class vectors and word vectors are used as features to classify a document to a class. In experiment o...

  8. Effect of high-energy electrons component on recombination plasma with pulse plasma flow

    International Nuclear Information System (INIS)

    Experiments on a recombination plasma with pulse plasma flow have been performed in the linear divertor simulator TPD-SheetIV. The pulse plasma flow was generated using a switching circuit controlled by the electric potential of the adjacent floating electrode in the plasma source. The duration of the pulse was 0.3 ms at a frequency of 50 Hz. The time dependence of the electron density ne, temperature Te, and energy distribution function fe(E) were measured using a Langmuir probe. The ionization and recombination events are analyzed using the Collisional-Radiative model, taking into account high-energy electrons. (author)

  9. Principles of broadband switching and networking

    CERN Document Server

    Liew, Soung C

    2010-01-01

    An authoritative introduction to the roles of switching and transmission in broadband integrated services networks Principles of Broadband Switching and Networking explains the design and analysis of switch architectures suitable for broadband integrated services networks, emphasizing packet-switched interconnection networks with distributed routing algorithms. The text examines the mathematical properties of these networks, rather than specific implementation technologies. Although the pedagogical explanations in this book are in the context of switches, many of the fundamenta

  10. Experimental investigation of ion-ion recombination at atmospheric conditions

    Directory of Open Access Journals (Sweden)

    A. Franchin

    2015-02-01

    Full Text Available We present the results of laboratory measurements of the ion-ion recombination coefficient at different temperatures, relative humidities and concentrations of ozone and sulfur dioxide. The experiments were carried out using the Cosmics Leaving OUtdoor Droplets (CLOUD chamber at CERN, the walls of which are made of conductive material, making it possible to measure small ions. We produced ions in the chamber using a 3.5 GeV c−1 beam of positively-charged pions (π+ from the CERN Proton Synchrotron (PS and with galactic cosmic rays, when the PS was switched off. The range of the ion production rate varied from 2 to 100 cm−3s−1, covering the typical range of ionization throughout the troposphere. The temperature ranged from −55 to 20 °C, the relative humidity from 0 to 70%, the SO2 concentration from 0 to 40 ppb, and the ozone concentration from 200 to 700 ppb. At 20 °C and 40% RH, the retrieved ion-ion recombination coefficient was (2.3 ± 0.7 × 10−6cm3s−1. We observed no dependency of the ion-ion recombination coefficient on ozone concentration and a weak variation with sulfur dioxide concentration. However, we found a strong dependency of the ion-ion recombination coefficient on temperature. We compared our results with three different models and found an overall agreement for temperatures above 0 °C, but a disagreement at lower temperatures. We observed a strong dependency of the recombination coefficient on relative humidity, which has not been reported previously.

  11. Cell encoding recombinant human erythropoietin

    Energy Technology Data Exchange (ETDEWEB)

    Beck, A.K.; Withy, R.M.; Zabrecky, J.R.; Masiello, N.C.

    1990-09-04

    This patent describes a C127 cell transformed with a recombinant DNA vector. It comprises: a DNA sequence encoding human erythropoietin, the transformed cell being capable of producing N-linked and O-linked glycosylated human erythropoietin.

  12. Progenitors of Recombining Supernova Remnants

    OpenAIRE

    Moriya, Takashi J.

    2012-01-01

    Usual supernova remnants have either ionizing plasma or plasma in collisional ionization equilibrium, i.e., the ionization temperature is lower than or equal to the electron temperature. However, the existence of recombining supernova remnants, i.e., supernova remnants with the ionization temperature higher than the electron temperature, is recently confirmed. One suggested way to have recombining plasma in a supernova remnant is to have a dense circumstellar medium at the time of the superno...

  13. Recombinant snake venom prothrombin activators

    OpenAIRE

    Lövgren, Ann

    2012-01-01

    Three prothrombin activators; ecarin, which was originally isolated from the venom of the saw-scaled viper Echis carinatus, trocarin from the rough-scaled snake Tropidechis carinatus, and oscutarin from the Taipan snake Oxyuranus scutellatus, were expressed in mammalian cells with the purpose to obtain recombinant prothrombin activators that could be used to convert prothrombin to thrombin. We have previously reported that recombinant ecarin can efficiently generate thrombin without the need ...

  14. Plasmid recombination in Haemophilus influenzae

    Energy Technology Data Exchange (ETDEWEB)

    McCarthy, D.

    1982-01-01

    DNA recombination in exponential phase and competent Haemophilus influenzae was measured by an electron microscopic assay that relies on the conversion of plasmid RSF0885 monomers into multimeric forms. Dimer circles were present at a frequency of 2% in plasmid preparations from competent Rd (wild-type) cells; multimers were present at a frequency of 0.2% in preparations from exponential phase cells. Thus, plasmid recombination was stimulated in competent cells. Multimer formation occurred efficiently in cells of the transformation defective mutant rec2, implying that the rec2 gene product is not required for plasmid recombination. However, the absence of multimer plasmids in preparations from competent cells of the transformation defective mutant rec1 suggests that the rec1 gene product is required. Digestion of purified plasmids with restriction endonuclease PvuII, which makes a single cut in the monomer, revealed the presence of recombination intermediates composed of two linear plasmids joined to form two pairs of arms resembling the Greek letter chi. Length measurements of these arms taken from a population of recombination intermediates gave evidence that the plasmids were joined at sites of homology. The distributions of individual DNA strands, at the intersections of the four arms, could be resolved in some recombination intermediates and were of two types. The first type of junction appeared as a single-stranded arm appended to each corner. The second type of junction consisted of a single strand of DNA linking the two linear plasmids at a site of homology. The single-stranded linker was frequently situated at the edge of a short gap on one of the plasmids in the pair. The fine structures of the recombinational joints have been interpreted in terms of previously proposed models of recombination.

  15. Does Class Size Matter?

    Science.gov (United States)

    Ehrenberg, Ronald G.; Brewer, Dominic J.; Gamoran, Adam; Willms, J. Douglas

    2001-01-01

    Reports on the significance of class size to student learning. Includes an overview of class size in various countries, the importance of teacher adaptability, and the Asian paradox of large classes allied to high test scores. (MM)

  16. RxClass

    Data.gov (United States)

    U.S. Department of Health & Human Services — The RxClass Browser is a web application for exploring and navigating through the class hierarchies to find the RxNorm drug members associated with each class....

  17. A Virtual Class Calculus

    DEFF Research Database (Denmark)

    Ernst, Erik; Ostermann, Klaus; Cook, William Randall

    2006-01-01

    , not as static components of a class. When used as types, virtual classes depend upon object identity - each object instance introduces a new family of virtual class types. Virtual classes support large scale program composition techniques, including higher-order hierarchies and family polymorphism. The original......Virtual classes are class-valued attributes of objects. Like virtual methods, virtual classes are defined in an object's class and may be redefined within subclasses. They resemble inner classes, which are also defined within a class, but virtual classes are accessed through object instances...... definition of virtual classes in BETA left open the question of static type safety, since some type errors were not caught until runtime. Later the languages Caesar and gbeta have used a more strict static analysis in order to ensure static type safety. However, the existence of a sound, statically typed...

  18. SERUM ANTIBODIES TO WHOLE-CELL AND RECOMBINANT ANTIGENS OF BORRELIA BURGDORFERI IN COTTONTAIL RABBITS

    OpenAIRE

    Magnarelli, Louis A.; Norris, Steven J; Fikrig, Erol

    2012-01-01

    Archived serum samples, from 95 eastern cottontail rabbits (Sylvilagus floridanus) captured in New York, New York, USA and Millbrook, New York, USA, during 1985–86, were analyzed in solid-phase enzyme-linked immunosorbent assays (ELISA) for total and class-specific immunoglobulin (Ig) M antibodies to whole-cell or recombinant antigens of Borrelia burgdorferi sensu stricto. Using a polyvalent conjugate, rabbit sera contained antibodies to whole-cell and recombinant antigens (protein [p]35, p37...

  19. Optical and near-infrared recombination lines of oxygen ions from Cassiopeia A knots

    CERN Document Server

    Docenko, D

    2008-01-01

    Context. Fast-moving knots (FMK) in the Galactic supernova remnant Cassiopeia A consist mainly of metals and allow to study element production in supernovae and shock physics in great detail. Aims. We work out theoretically and suggest to observe previously unexplored class of spectral lines -- metal recombination lines in optical and near-infrared bands -- emitted by the cold ionized and cooling plasma in the fast-moving knots. Methods. By tracing ion radiative and dielectronic recombination, collisional $l$-redistribution and radiative cascade processes, we compute resulting oxygen, silicon and sulphur recombination line emissivities. It allows us to determine the oxygen recombination line fluxes, based on the fast-moving knot model of Sutherland and Dopita (1995b), that predicts existence of highly-ionized ions from moderate to very low plasma temperatures. Results. The calculations predict oxygen ion recombination line fluxes detectable on modern optical telescopes in the wavelength range from 0.5 to 3 mi...

  20. Replacement of Imu-Cmu intron by NeoR gene alters Imu germ-line expression but has no effect on V(D)J recombination.

    Science.gov (United States)

    Haddad, Dania; Dougier, Hei-Lanne; Laviolette, Nathalie; Puget, Nadine; Khamlichi, Ahmed Amine

    2010-02-01

    The NeoR gene has often been used to unravel the mechanisms underlying long-range interactions between promoters and enhancers during V(D)J assembly and class switch recombination (CSR) in the immunoglobulin heavy chain (IgH) locus. This approach led to the notion that CSR is regulated through competition of germ-line (GL) promoters for activities displayed by the 3' regulatory region (3'RR). This polarized long-range effect of the 3'RR is disturbed upon insertion of NeoR gene in the IgH constant (C(H)) region, where only GL transcription derived from upstream GL promoters is impaired. In the context of V(D)J recombination, replacement of Emu enhancer or Emu core enhancer (cEmu) by NeoR gene fully blocked V(D)J recombination and mu0 GL transcription which originates 5' of DQ52 and severely diminished Imu GL transcription derived from Emu/Imu promoter, suggesting a critical role for cEmu in the regulation of V(D)J recombination and of mu0 and Imu expression. Here we focus on the effect of NeoR gene on mu0 and Imu GL transcription in a mouse line in which the Imu-Cmu intron was replaced by a NeoR gene in the sense-orientation. B cell development was characterized by a marked but incomplete block at the pro-B cell stage. However, V(D)J recombination was unaffected in sorted pro-B and pre-B cells excluding an interference with the accessibility control function of Emu. mu0 GL transcription initiation was relatively normal but the maturation step seemed to be affected most likely through premature termination at NeoR polyadenylation sites. In contrast, Imu transcription initiation was impaired suggesting an interference of NeoR gene with the IgH enhancers that control Imu expression. Surprisingly, in stark contrast with the NeoR effect in the C(H) region, LPS-induced NeoR expression restored Imu transcript levels to normal. The data suggest that Emu enhancer may be the master control element that counteracts the down-regulatory "Neo effect" on Imu expression upon LPS

  1. IGBT: a solid state switch

    International Nuclear Information System (INIS)

    A Copper Vapour Laser Power Supply has been designed using a solid state switch consisting in eighteen Isolated Gate Bipolar Transistors (IGBT), -1200 volts, 400 Amps, each-in parallel. This paper presents the Isolated Gate Bipolar Transistor (IGBTs) replaced in the Power Electronic components evolution, and describes the IGBT conduction mechanism, presents the parallel association of IGBTs, and studies the application of these components to a Copper Vapour Laser Power Supply. The storage capacitor voltage is 820 volts, the peak current of the solid state switch is 17.000 Amps. The switch is connected on the primary of a step-up transformer, followed by a magnetic modulator. The reset of the magnetic modulator is provided by part of the laser reflected energy with a patented circuit. The charging circuit is a resonant circuit with a charge controlled by an IGBT switch. When the switch is open, the inductance energy is free-wheeled by an additional winding and does not extend the charging phase of the storage capacitor. The design allows the storage capacitor voltage to be very well regulated. This circuit is also patented. The electric pulse in the laser has 30.000 Volt peak voltage, 2000 Amp peak current, and is 200 nanoseconds long, for a 200 Watt optical power Copper Vapour Laser

  2. Improvement on Switching Characteristics and Switching Losses of IGBT by ZVS—PWM①

    Institute of Scientific and Technical Information of China (English)

    ZHANGChunjiang; GUHerong; 等

    1997-01-01

    The principle of ZVS-PWM inverting circuit is first described by means of inverting welder supply.The contrastive study is made on switching characteristics and switching losses of IGBT between ZVS-PWM and hard-switching.

  3. Contrasting roles of interallelic recombination at the HLA-A and HLA-B loci

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, A.L.; Hughes, M.K. (Pennsylvania State Univ., University Park (United States)); Watkins, D.I. (Univ. of Wisconsin, Madison (United States))

    1993-03-01

    A statistical study of DNA sequences of alleles at the highly polymorphic class I MHC loci of humans, HLA-A and HLA-B, showed evidence of both large-scale recombination events(involving recombination of exons 1-2 of one allele with exons 3-8 of another) and small scale recombination events (involving apparent exchange of short DNA segments). The latter events occurred disproportionately in the region of the gene encoding the antigen recognition site (ARS) of the class I molecule. Furthermore, they involved the ARS codons which are under the strongest selection favoring allelic diversity at the amino acid level. Thus, the frequency of recombinant alleles appears to have been increased by some form of balancing selection (such as overdominant selection) favoring heterozygosity in the ARS. These analyses also revealed a striking difference between the A and B loci. Recombination events appear to have occurred about twice as frequently at the B locus, and recombinants at the B locus were significantly more likely to affect polymorphic sites in the ARS. At the A locus, there are well-defined allelic lineages that have persisted since prior to the human-chimpanzee divergence; but at the B locus, there is no evidence for such long-lasting allelic lineages. Thus, relatively frequent interallelic recombination has apparently been a feature of the long-term evolution of the B locus but not of the A locus. 45 refs., 4 figs., 5 tabs.

  4. Analysis of the class E amplifier used as electronic ballast with dimming capability for photovoltaic applications

    Energy Technology Data Exchange (ETDEWEB)

    Ponce, M.; Arau, J. [CENIDET-Electro' , Cuernavaca (Mexico); Alonso, J.M.; Rico-Secades, M. [ATE, Universidad de Oviedo, Campus de Viesques s/n Gijon (Spain)

    2001-07-01

    The analysis and design of a dimmable electronic ballast based on the class E amplifier and fed from solar cells with 12V backup batteries is described. The class E amplifier uses a capacitive impedance inverter as resonant tank and one diode antiparallel with the switch; these elements allow implementation of a dimming feature for the ballast and ignition of the lamp while maintaining zero voltage commutations in the switch. The designed electronic ballast drives a 21W lamp and operates at a switching frequency of 370kHz. Dimming is implemented using an SG3524 in a voltage-controlled oscillator fashion. (Author)

  5. Critical dwell time of switched linear systems

    Institute of Scientific and Technical Information of China (English)

    Lijun ZHANG; Chunwen LI

    2006-01-01

    In this paper, we consider the relation between the switching dwell time and the stabilization of switched linear control systems. First of all, a concept of critical dwell time is given for switched linear systems without control inputs, and the critical dwell time is taken as an arbitrary given positive constant for a switched linear control systems with controllable switching models. Secondly, when a switched linear system has many stabilizable switching models, the problem of stabilization of the overall system is considered. An on-line feedback control is designed such that the overall system is asymptotically stabilizable under switching laws which depend only on those of uncontrollable subsystems of the switching models. Finally, when a switched system is partially controllable (While some switching models are probably unstabilizable), an on-line feedback control and a cyclic switching strategy are designed such that the overall system is asymptotically stabilizable if all switching models of this uncontrollable subsystems are asymptotically stable. In addition,algorithms for designing switching laws and controls are presented.

  6. PROMOTION, SWITCHING BARRIERS, AND LOYALTY

    Directory of Open Access Journals (Sweden)

    Gu-Shin Tung

    2011-06-01

    Full Text Available This paper investigates the causal relationships among promotion effects, switching barriers, and loyalty in the department stores. The relationship between switching barriers and loyalty reveals partially the same results as the switching barriers theory of Jones et al. (2000. The reasons arise from “too often” and “too similar” sales promotion programs of competitive department stores in Taiwan, leading the promotion effects to not contribute to the attractiveness of competitors. The promotion effects have a positive and significant influence on loyalty, which is consistent with the prior literature. Promotion effects are also the most important weight to loyalty in our tested model but it reveals a seeming loyalty, because the loyalty depends on the reward of promotion. The negative relationship between promotion effects and attractiveness of alternative supports the promotion effects, which can lower the attractiveness of competitors, but these similar promotion plans are not attributed to interpersonal relationships.

  7. Transcutaneous RF-Powered Implantable Minipump Driven by a Class-E Transmitter

    OpenAIRE

    Moore, William H.; Holschneider, Daniel P.; Givrad, Tina K.; Maarek, Jean-Michel I.

    2006-01-01

    We describe the design and testing of an inductive coupling system used to power an implantable minipump for applications in ambulating rats. A 2 MHz class-E oscillator driver powered a coil transmitter wound around a 33-cm-diameter rat cage. A receiver coil, a filtered rectifier, and a voltage-sensitive switch powered the implant. The implant DC current at the center of the primary coil (5.1 V) exceeded the level required to activate the solenoid valve in the pump. The variations of the impl...

  8. An integrated circuit/packet switched video conferencing system

    International Nuclear Information System (INIS)

    The HEP Network Resource Center (HEPNRC) at Fermilab and the Collider Detector Facility (CDF) collaboration have evolved a flexible, cost-effective, widely accessible video conferencing system for use by high energy physics collaborations and others wishing to use video conferencing. No current systems seemed to fully meet the needs of high energy physics collaborations. However, two classes of video conferencing technology: circuit-switched and packet-switched, if integrated, might encompass most of HEPS's needs. It was also realized that, even with this integration, some additional functions were needed and some of the existing functions were not always wanted. HEPNRC with the help of members of the CDF collaboration set out to develop such an integrated system using as many existing subsystems and components as possible. This system is called VUPAC (Video conferencing Using Packets and Circuits). This paper begins with brief descriptions of the circuit-switched and packet-switched video conferencing systems. Following this, issues and limitations of these systems are considered. Next the VUPAC system is described. Integration is accomplished primarily by a circuit/packet video conferencing interface. Augmentation is centered in another subsystem called MSB (Multiport MultiSession Bridge). Finally, there is a discussion of the future work needed in the evolution of this system. (author)

  9. Efficient performance simulation of class D amplifier output stages

    DEFF Research Database (Denmark)

    Nyboe, Flemming; Risbo, Lars; Andreani, Pietro

    2005-01-01

    Straightforward simulation of amplifier distortion involves transient simulation of operation on a sine wave input signal, and a subsequent FFT of the output voltage. This approach is very slow on class D amplifiers, since the switching behavior forces simulation time steps that are many orders...

  10. Finite-time quantised feedback asynchronously switched control of sampled-data switched linear systems

    Science.gov (United States)

    Wang, Ronghao; Xing, Jianchun; Li, Juelong; Xiang, Zhengrong

    2016-10-01

    This paper studies the problem of stabilising a sampled-data switched linear system by quantised feedback asynchronously switched controllers. The idea of a quantised feedback asynchronously switched control strategy originates in earlier work reflecting actual system characteristic of switching and quantising, respectively. A quantised scheme is designed depending on switching time using dynamic quantiser. When sampling time, system switching time and controller switching time are all not uniform, the proposed switching controllers guarantee the system to be finite-time stable by a piecewise Lyapunov function and the average dwell-time method. Simulation examples are provided to show the effectiveness of the developed results.

  11. Industry Switching in Developing Countries

    DEFF Research Database (Denmark)

    Newman, Carol; Rand, John; Tarp, Finn

    Firm turnover (i.e. firm entry and exit) is a well-recognized source of sectorlevel productivity growth across developing and developed countries. In contrast, the role and importance of firms switching activities from one sector to another is little understood. Firm switchers are likely to be un......Firm turnover (i.e. firm entry and exit) is a well-recognized source of sectorlevel productivity growth across developing and developed countries. In contrast, the role and importance of firms switching activities from one sector to another is little understood. Firm switchers are likely...

  12. CMOS integrated switching power converters

    CERN Document Server

    Villar-Pique, Gerard

    2011-01-01

    This book describes the structured design and optimization of efficient, energy processing integrated circuits. The approach is multidisciplinary, covering the monolithic integration of IC design techniques, power electronics and control theory. In particular, this book enables readers to conceive, synthesize, design and implement integrated circuits with high-density high-efficiency on-chip switching power regulators. Topics covered encompass the structured design of the on-chip power supply, efficiency optimization, IC-compatible power inductors and capacitors, power MOSFET switches and effi

  13. STABILITY OF SWITCHED POLYNOMIAL SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    Zhiqiang LI; Yupeng QIAO; Hongsheng QI; Daizhan CHENG

    2008-01-01

    This paper investigates the stability of (switched) polynomial systems. Using semi-tensor product of matrices, the paper develops two tools for testing the stability of a (switched) polynomial system. One is to convert a product of multi-variable polynomials into a canonical form, and the other is an easily verifiable sufficient condition to justify whether a multi-variable polynomial is positive definite. Using these two tools, the authors construct a polynomial function as a candidate Lyapunov function and via testing its derivative the authors provide some sufficient conditions for the global stability of polynomial systems.

  14. Statistical switching kinetics in ferroelectrics

    CERN Document Server

    Lou, X J

    2008-01-01

    By assuming a more realistic nucleation and polarization reversal scenario we build a new statistical switching model for ferroelectrics, which is different from either the Kolmogorov-Avrami-Ishibashi (KAI) model or the Nucleation-Limited-Switching (NLS) model. After incorporating a time-dependent depolarization field this model gives a good description about the retardation behavior in polycrystalline thin films at medium or low fields, which can not be described by the traditional KAI model. This model predicts correctly n=1 for polycrystalline thin films at high Eappl or ceramic bulks in the ideal case.

  15. Bumpless switching control for switched systems with partial actuator failures

    Science.gov (United States)

    Qi, Yiwen; Bao, Wen; Zhang, Qingxin; Chang, Juntao

    2016-11-01

    This study is concerned with the bumpless transfer problem for switched systems with partial actuator failures, in order to obtain smooth system performance output transition. Taking into account that the system requires a controller switching from current sub-controller to a fault-tolerant sub-controller after actuator fault. And bumpless transfer for control input cannot be traditionally designed when the actuator fault occurs, while performance smoothing can be considered and it is actually the ultimate goal of bumpless transfer. Specifically, the actuator fault model is firstly established and partial actuator fault is considered. Then, the system performance output signal is deemed as the main design variable of bumpless transfer, and closed-loop control systems both previous and after controller switching are constructed. Moreover, by using model matching thought and the adaptive sliding mode control technique, a bumpless transfer compensator design strategy is given to drive the performance output variable (after controller switching) to track the one of reference model. At last, simulation results of numeric and application examples demonstrate the effectiveness of the proposed bumpless transfer strategy.

  16. Switching in electrical transmission and distribution systems

    CERN Document Server

    Smeets, René; Kapetanovic, Mirsad; Peelo, David F; Janssen, Anton

    2014-01-01

    Switching in Electrical Transmission and Distribution Systems presents the issues and technological solutions associated with switching in power systems, from medium to ultra-high voltage. The book systematically discusses the electrical aspects of switching, details the way load and fault currents are interrupted, the impact of fault currents, and compares switching equipment in particular circuit-breakers. The authors also explain all examples of practical switching phenomena by examining real measurements from switching tests. Other highlights include: up to date commentary on new develo

  17. Inhibition of tumor angiogenesis by angiostatin: from recombinant protein to gene therapy.

    Science.gov (United States)

    Dell'Eva, Raffaella; Pfeffer, Ulrich; Indraccolo, S; Albini, Adriana; Noonan, Douglas

    2002-01-01

    Tumor growth, local invasion, and metastatic dissemination are dependent on the formation of new microvessels. The process of angiogenesis is regulated by a balance between pro-angiogenic and anti-angiogenic factors, and the shift to an angiogenic phenotype (the "angiogenic switch") is a key event in tumor progression. The use of anti-angiogenic agents to restore this balance represents a promising approach to cancer treatment. Known physiological inhibitors include trombospondin, several interleukins, and the proteolytic break-down products of several proteins. Angiostatin, an internal fragment of plasminogen, is one of the more potent of this latter class of angiogenesis inhibitors. Like endostatin, another anti-angiogenic peptide derived from collagen XVIII, angiostatin can induce tumor vasculature regression, leading to a complete cessation of tumor growth. Inhibitors of angiogenesis target normal endothelial cells, therefore the development of resistance to these drugs is unlikely. The efficacy of angiostatin has been demonstrated in animal models for many different types of solid tumors. Anti-angiogenic cancer therapy with angiostatin requires prolonged administration of the peptide. The production of the functional polypeptides is expensive and technical problems related to physical properties and purity are frequently encountered. Gene transfer represents an alternative method to deliver angiostatin. Gene therapy has the potential to produce the therapeutic agent in high concentrations in a local area for a sustained period, thereby avoiding the problems encountered with long-term administration of recombinant proteins, monoclonal antibodies, or anti-angiogenic drugs. In this review we compare the different gene therapy strategies that have been applied to angiostatin, with special regard to their ability to provide sufficient angiostatin at the target site. PMID:12901356

  18. Multiserver switch scheduling for high speed optical switches

    Science.gov (United States)

    Golla, Prasad; Blanton, John; Damm, Gerard

    2003-10-01

    A switch matrix implemented as an optical crossbar using semiconductor optical amplifiers is able to accommodate extreme concentrations of data traffic. Due to the need to reduce optical guard band overhead it is beneficial to switch fixed size bursts of data cells on a time slot basis. The high capacity of the optical matrix supports multiple optical ports per burst card, and the implementation of multiple queue servers per burst card helps make better use of the multiplicity of ports. Problems associated with arbitrating multiple ports and multiple servers per burst card have been resolved by extending the operation of existing iterative, single server scheduling algorithms. The multiserver arbitration time will be in proportion to the number of servers -- corresponding to the channels of DWDM link -- unless a reconciliation stage is used after each iteration when an arbiter per server is used. The reconciliation stage sets the problem of broken data dependencies between server arbitrations in this case. Further, to address the time limitations for computing the scheduling solution, parallel arbiter implementations have been developed and tested against single arbiter designs. Again, the broken dependencies between iterations of an arbitration are addressed through the use of a grant reconciliation stage. The use of multiple queue servers per burst card also resolves some of the data loss problems related to polarized traffic. Simulations of the multiple server and parallel arbiter implementations have demonstrated their efficiency compared to previous implementations. Compounded to this problem is maintaining high throughput of the switch matrix while observing data transit time limits. This involves balancing two contradictory requirements; switch or line card efficiency and data transit times. To improve efficiency it is desirable to transmit only full packets. However, to prevent loss of data due to timeout it will be necessary to transmit some incomplete

  19. Recombinant snake venom prothrombin activators.

    Science.gov (United States)

    Lövgren, Ann

    2013-01-01

    Three prothrombin activators; ecarin, which was originally isolated from the venom of the saw-scaled viper Echis carinatus, trocarin from the rough-scaled snake Tropidechis carinatus, and oscutarin from the Taipan snake Oxyuranus scutellatus, were expressed in mammalian cells with the purpose to obtain recombinant prothrombin activators that could be used to convert prothrombin to thrombin. We have previously reported that recombinant ecarin can efficiently generate thrombin without the need for additional cofactors, but does not discriminate non-carboxylated prothrombin from biologically active γ-carboxylated prothrombin. Here we report that recombinant trocarin and oscutarin could not efficiently generate thrombin without additional protein co-factors. We confirm that both trocarin and oscutarin are similar to human coagulation Factor X (FX), explaining the need for additional cofactors. Sequencing of a genomic fragment containing 7 out of the 8 exons coding for oscutarin further confirmed the similarity to human FX. PMID:23111318

  20. Heterogeneity in recombinant protein production

    DEFF Research Database (Denmark)

    Schalén, Martin; Johanson, Ted; Lundin, Luisa;

    2012-01-01

    . the cell physiology is affected. Cells are stressed, and this may severely affect growth, by-product accumulation, biomass yield and recombinant product yield. The stress caused by exposure to divergent microenvironments, genetic differences of individual cells, differing cell cycle stage and cell age, all...... contribute to make a population in a fermenter heterogeneous, resulting in cell-to-cell variation in physiological parameters of the microbial culture. Our study aims at investigating how population heterogeneity and recombinant protein production is affected by environmental gradients in bioreactors...... are simulated in small bioreactors and the population heterogeneity can be visualised by analysing single cells with flow cytometry. This can give new insights to cell physiology and recombinant protein production at the industrial scale....

  1. Meiotic recombination at the Lmp2 hotspot tolerates minor sequence divergence between homologous chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Yoshino, Masayasu; Sagai, Tomoko; Shiroishi, Toshihiko [National Institute of Genetics, Mishima (Japan)] [and others

    1996-06-01

    Recombination is widely considered to linearly depend on the length of the homologous sequences. An 11% mismatch decreases the rate of phage-plasmid recombination 240-fold. Two single nucleotide mismatches, which reduce the longest uninterrupted stretch of similarity from 232 base pairs (bp) to 134 bp, reduce gene conversion in mouse L cells 20-fold. The efficiency of gene targeting through homologous recombination in mouse embryonic stem cells can be increased by using an isogenic, rather than a non-isogenic, DNA construct. In this study we asked whether a high degree of sequence identity between homologous mouse chromosomes enhances meiotic recombination at a hotspot. Sites of meiotic recombination in the mouse major histocompatibility complex (MHC) class II region are not randomly distributed but are almost all clustered within short segments known as recombinational hotspots. The wm7 MHC haplotype, derived from Japanese wild mice Mus musculus molossinus, enhances meiotic recombination at a hotspot near the Lmp2 gene. Heterozygotes between the wm7 haplotype and the b or k haplotypes have yielded a high frequency of recombination (2.1%) in 1.3 kilobase kb segment of this hotspot. 20 refs., 2 figs.

  2. Transmission distortion affecting human noncrossover but not crossover recombination: a hidden source of meiotic drive.

    Directory of Open Access Journals (Sweden)

    Linda Odenthal-Hesse

    2014-02-01

    Full Text Available Meiotic recombination ensures the correct segregation of homologous chromosomes during gamete formation and contributes to DNA diversity through both large-scale reciprocal crossovers and very localised gene conversion events, also known as noncrossovers. Considerable progress has been made in understanding factors such as PRDM9 and SNP variants that influence the initiation of recombination at human hotspots but very little is known about factors acting downstream. To address this, we simultaneously analysed both types of recombinant molecule in sperm DNA at six highly active hotspots, and looked for disparity in the transmission of allelic variants indicative of any cis-acting influences. At two of the hotspots we identified a novel form of biased transmission that was exclusive to the noncrossover class of recombinant, and which presumably arises through differences between crossovers and noncrossovers in heteroduplex formation and biased mismatch repair. This form of biased gene conversion is not predicted to influence hotspot activity as previously noted for SNPs that affect recombination initiation, but does constitute a powerful and previously undetected source of recombination-driven meiotic drive that by extrapolation may affect thousands of recombination hotspots throughout the human genome. Intriguingly, at both of the hotspots described here, this drive favours strong (G/C over weak (A/T base pairs as might be predicted from the well-established correlations between high GC content and recombination activity in mammalian genomes.

  3. Transmission distortion affecting human noncrossover but not crossover recombination: a hidden source of meiotic drive.

    Science.gov (United States)

    Odenthal-Hesse, Linda; Berg, Ingrid L; Veselis, Amelia; Jeffreys, Alec J; May, Celia A

    2014-02-01

    Meiotic recombination ensures the correct segregation of homologous chromosomes during gamete formation and contributes to DNA diversity through both large-scale reciprocal crossovers and very localised gene conversion events, also known as noncrossovers. Considerable progress has been made in understanding factors such as PRDM9 and SNP variants that influence the initiation of recombination at human hotspots but very little is known about factors acting downstream. To address this, we simultaneously analysed both types of recombinant molecule in sperm DNA at six highly active hotspots, and looked for disparity in the transmission of allelic variants indicative of any cis-acting influences. At two of the hotspots we identified a novel form of biased transmission that was exclusive to the noncrossover class of recombinant, and which presumably arises through differences between crossovers and noncrossovers in heteroduplex formation and biased mismatch repair. This form of biased gene conversion is not predicted to influence hotspot activity as previously noted for SNPs that affect recombination initiation, but does constitute a powerful and previously undetected source of recombination-driven meiotic drive that by extrapolation may affect thousands of recombination hotspots throughout the human genome. Intriguingly, at both of the hotspots described here, this drive favours strong (G/C) over weak (A/T) base pairs as might be predicted from the well-established correlations between high GC content and recombination activity in mammalian genomes. PMID:24516398

  4. On-Chip Network Design Automation with Source Routing Switches

    Institute of Scientific and Technical Information of China (English)

    MA Liwei; SUN Yihe

    2007-01-01

    Network-on-chip (NoC) is a new design paradigm for system-on-chip intraconnections in the billion-transistor era. Application specific on-chip network design is essential for NoC success in this new era.This paper presents a class of source routing switch that can be used to efficiently form arbitrary network topologies and that can be optimized for various applications. Hardware description language versions of the networks can be generated automatically for simulations and for syntheses. A series of switches and networks has been configured with their performances including latency, delay, area, and power, and analyzed theoretically and experimentally. The results show that this NoC architecture provides a large design space for application specific on-chip network designs.

  5. Switching Equalization Algorithm Based on a New SNR Estimation Method

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    It is well-known that turbo equalization with the max-log-map (MLM) rather than the log-map (LM) algorithm is insensitive to signal to noise ratio (SNR) mismatch. As our first contribution, an improved MLM algorithm called scaled max-log-map (SMLM) algorithm is presented. Simulation results show that the SMLM scheme can dramatically outperform the MLM without sacrificing the robustness against SNR mismatch. Unfortunately, its performance is still inferior to that of the LM algorithm with exact SNR knowledge over the class of high-loss channels. As our second contribution, a switching turbo equalization scheme, which switches between the SMLM and LM schemes, is proposed to practically close the performance gap. It is based on a novel way to estimate the SNR from the reliability values of the extrinsic information of the SMLM algorithm.

  6. STOCHASTIC ADAPTIVE SWITCHING CONTROL BASED ON MULTIPLE MODELS

    Institute of Scientific and Technical Information of China (English)

    ZHANGYanxia; GUOLei

    2002-01-01

    It is well known that the transient behaviors of the traditional adaptive control may be very poor in general,and that the adaptive control designed based in switching between multiple models is an intuitively appealing and practically feasible approach to improve the transient performances.In this paper,we shall prove that for a typical class of linear systems disturbed by random noises,the multiple model based least-equares(LS)adaptive switching control is statble and convergent and has the same convergence rate as that established for the standard least-squares-based self-tunning regulators.Moreover,the mixed case combining adative models with fixed models is also considered.

  7. Industry switching in developing countries

    DEFF Research Database (Denmark)

    Newman, Carol; Rand, John; Tarp, Finn

    2013-01-01

    Firm turnover (i.e., firm entry and exit) is a well-recognized source of sector-level productivity growth. In contrast, the role and importance of firms that switch activities from one sector to another is not well understood. Firm switchers are likely to be unique, differing from both newly...

  8. Multiuser switched diversity scheduling schemes

    KAUST Repository

    Shaqfeh, Mohammad

    2012-09-01

    Multiuser switched-diversity scheduling schemes were recently proposed in order to overcome the heavy feedback requirements of conventional opportunistic scheduling schemes by applying a threshold-based, distributed, and ordered scheduling mechanism. The main idea behind these schemes is that slight reduction in the prospected multiuser diversity gains is an acceptable trade-off for great savings in terms of required channel-state-information feedback messages. In this work, we characterize the achievable rate region of multiuser switched diversity systems and compare it with the rate region of full feedback multiuser diversity systems. We propose also a novel proportional fair multiuser switched-based scheduling scheme and we demonstrate that it can be optimized using a practical and distributed method to obtain the feedback thresholds. We finally demonstrate by numerical examples that switched-diversity scheduling schemes operate within 0.3 bits/sec/Hz from the ultimate network capacity of full feedback systems in Rayleigh fading conditions. © 2012 IEEE.

  9. The Atlas load protection switch

    CERN Document Server

    Davis, H A; Dorr, G; Martínez, M; Gribble, R F; Nielsen, K E; Pierce, D; Parsons, W M

    1999-01-01

    Atlas is a high-energy pulsed-power facility under development to study materials properties and hydrodynamics experiments under extreme conditions. Atlas will implode heavy liner loads (m~45 gm) with a peak current of 27-32 MA delivered in 4 mu s, and is energized by 96, 240 kV Marx generators storing a total of 23 MJ. A key design requirement for Atlas is obtaining useful data for 95601130f all loads installed on the machine. Materials response calculations show current from a prefire can damage the load requiring expensive and time consuming replacement. Therefore, we have incorporated a set of fast-acting mechanical switches in the Atlas design to reduce the probability of a prefire damaging the load. These switches, referred to as the load protection switches, short the load through a very low inductance path during system charge. Once the capacitors have reached full charge, the switches open on a time scale short compared to the bank charge time, allowing current to flow to the load when the trigger pu...

  10. Switching Costs in Accounting Services

    Directory of Open Access Journals (Sweden)

    Fatih Koç

    2015-06-01

    Full Text Available Switching cost is defined as possible costs that customers may encounter when they want to change the firm they buy service, and an important subject in terms of accounting services. Particularly, small business entrepreneurs’ not having knowledge about accounting procedures, and sharing private information with accounting firms make switching costs more important for accounting services. Thus, the aim of this study is to investigate the concept of switching costs (relational cost, procedural cost and financial cost, its determinants (perceived service quality, service importance, and service failures, and consequences (re-purchasing, and recommen ding to others. Theresearch was conducted on small business entrepreneurs in down-town of Balıkesir in Turkey. Total 405 small business entrepreneur owners were interviewed. According to results of the study, perceived service quality positively affects all dimensions of switching costs, significance of service positively affects procedural and relational costs, and service failures negatively affect procedural and relational costs. The results showed that while procedural and relational costs positively affect re-purchasing and recommending to others variables, financial cost did not have any effect on these variables.

  11. Wide Bandgap Extrinsic Photoconductive Switches

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, James S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2013-07-03

    Semi-insulating Gallium Nitride, 4H and 6H Silicon Carbide are attractive materials for compact, high voltage, extrinsic, photoconductive switches due to their wide bandgap, high dark resistance, high critical electric field strength and high electron saturation velocity. These wide bandgap semiconductors are made semi-insulating by the addition of vanadium (4H and 6HSiC) and iron (2H-GaN) impurities that form deep acceptors. These deep acceptors trap electrons donated from shallow donor impurities. The electrons can be optically excited from these deep acceptor levels into the conduction band to transition the wide bandgap semiconductor materials from a semi-insulating to a conducting state. Extrinsic photoconductive switches with opposing electrodes have been constructed using vanadium compensated 6H-SiC and iron compensated 2H-GaN. These extrinsic photoconductive switches were tested at high voltage and high power to determine if they could be successfully used as the closing switch in compact medical accelerators.

  12. Intrinsic nanofilamentation in resistive switching

    KAUST Repository

    Wu, Xing

    2013-03-15

    Resistive switching materials are promising candidates for nonvolatile data storage and reconfiguration of electronic applications. Intensive studies have been carried out on sandwiched metal-insulator-metal structures to achieve high density on-chip circuitry and non-volatile memory storage. Here, we provide insight into the mechanisms that govern highly reproducible controlled resistive switching via a nanofilament by using an asymmetric metal-insulator-semiconductor structure. In-situ transmission electron microscopy is used to study in real-time the physical structure and analyze the chemical composition of the nanofilament dynamically during resistive switching. Electrical stressing using an external voltage was applied by a tungsten tip to the nanosized devices having hafnium oxide (HfO2) as the insulator layer. The formation and rupture of the nanofilaments result in up to three orders of magnitude change in the current flowing through the dielectric during the switching event. Oxygen vacancies and metal atoms from the anode constitute the chemistry of the nanofilament.

  13. The effect of a single recombination event

    DEFF Research Database (Denmark)

    Schierup, Mikkel Heide; Jensen, Thomas Mailund; Wiuf, Carsten

    We investigate the variance in how visible a single recombination event is in a SNP data set as a function of the type of recombination event and its age. Data is simulated under the coalescent with recombination and inference is by the popular composite likelihood methods. The major determinant...... of the effect of a recombination event is the genealogical type of the event and whether SNP variation is present that can reveal the genealogical consequences of the recombination event. Recombination events that only change some branch lengths in the genealogy have a very small, but detectable, effect....... The more lineages left when the recombination event occurs, the larger effect it has, implying that it is mainly young recombination events that we detect when estimating the rate. If the population is growing, though, more lineages are present back in time and relatively more ancient recombination events...

  14. Cas9-assisted recombineering in C. elegans: genome editing using in vivo assembly of linear DNAs

    Science.gov (United States)

    Paix, Alexandre; Schmidt, Helen; Seydoux, Geraldine

    2016-01-01

    Recombineering, the use of endogenous homologous recombination systems to recombine DNA in vivo, is a commonly used technique for genome editing in microbes. Recombineering has not yet been developed for animals, where non-homology-based mechanisms have been thought to dominate DNA repair. Here, we demonstrate, using Caenorhabditis elegans, that linear DNAs with short homologies (∼35 bases) engage in a highly efficient gene conversion mechanism. Linear DNA repair templates with homology to only one side of a double-strand break (DSB) initiate repair efficiently, and short overlaps between templates support template switching. We demonstrate the use of single-stranded, bridging oligonucleotides (ssODNs) to target PCR fragments for repair of DSBs induced by CRISPR/Cas9 on chromosomes. Based on these findings, we develop recombineering strategies for precise genome editing that expand the utility of ssODNs and eliminate in vitro cloning steps for template construction. We apply these methods to the generation of GFP knock-in alleles and gene replacements without co-integrated markers. We conclude that, like microbes, metazoans possess robust homology-dependent repair mechanisms that can be harnessed for recombineering and genome editing. PMID:27257074

  15. Digital Switching in the Quantum Domain

    CERN Document Server

    Tsai, I M

    2002-01-01

    In this paper, we present an architecture and implementation algorithm such that digital data can be switched in the quantum domain. First we define the connection digraph which can be used to describe the behavior of a switch at a given time, then we show how a connection digraph can be implemented using elementary quantum gates. The proposed mechanism supports unicasting as well as multicasting, and is strict-sense non-blocking. It can be applied to perform either circuit switching or packet switching. Compared with a traditional space or time domain switch, the proposed switching mechanism is more scalable. Assuming an n-by-n quantum switch, the space consumption grows linearly, i.e. O(n), while the time complexity is O(1) for unicasting, and O(log n) for multicasting. Based on these advantages, a high throughput switching device can be built simply by increasing the number of I/O ports.

  16. A Demonstration of Automatically Switched Optical Network

    Institute of Scientific and Technical Information of China (English)

    Weisheng Hu; Qingji Zeng; Yaohui Jin; Chun Jiang; Yue Wang; Xiaodong Wang; Chunlei Zhang; Yang Lu; Buwei Xu; Peigang Hu

    2003-01-01

    We build an automatically switched optical network (ASON) testbed with four optical cross-connect nodes. Many fundamental ASON features are demonstrated, which is implemented by control protocols based on generalized multi-protocol label switching (GMPLS) framework.

  17. Ultrafast Beam Switching Using Coupled VCSELs

    Science.gov (United States)

    Ning, Cun-Zheng; Goorjian, Peter

    2001-01-01

    We propose a new approach to performing ultrafast beam switching using two coupled Vertical-Cavity Surface-Emitting Lasers (VCSELs). The strategy is demonstrated by numerical simulation, showing a beam switching of 10 deg at 42 GHz.

  18. Coherent switching of semiconductor resonator solitons

    OpenAIRE

    Taranenko, V. B.; Ahlers, F. -J.; Pierz, K.

    2002-01-01

    We demonstrate switching on and off of spatial solitons in a semiconductor microresonator by injection of light coherent with the background illumination. Evidence results that the formation of the solitons and their switching does not involve thermal processes.

  19. Recombinant expression and purification of the tomato defensin TPP3 and its preliminary X-ray crystallographic analysis

    OpenAIRE

    Lay, Fung T.; Veneer, Prem K.; Hulett, Mark D.; Kvansakul, Marc

    2012-01-01

    TPP3 is a class II plant defensin from tomato. Here, the expression, purification, crystallization and preliminary X-ray crystallographic analysis of recombinant TPP3 are reported in order to define its structure and function in relation to other class II plant defensins.

  20. Theoretical and experimental study of fundamental differences in the noise suppression of high-speed SOA-based all-optical switches

    DEFF Research Database (Denmark)

    Nielsen, Mads Lønstrup; Mørk, Jesper; Suzuki, R.;

    2005-01-01

    We identify a fundamental difference between the ASE noise filtering properties of different all-optical SOA-based switch configurations, and divide the switches into two classes. An in-band ASE suppression ratio quantifying the difference is derived theoretically and the impact of the ASE...

  1. Dual fluorescent reporter pig for Cre recombination: transgene placement at the ROSA26 locus.

    Directory of Open Access Journals (Sweden)

    Shun Li

    Full Text Available We are extending the Cre/loxP site-specific recombination system to pigs, focussing on conditional and tissue-specific expression of oncogenic mutations to model human cancers. Identifying the location, pattern and extent of Cre recombination in vivo is an important aspect of this technology. Here we report pigs with a dual fluorochrome cassette under the control of the strong CAG promoter that switches expression after Cre-recombination, from membrane-targeted tandem dimer Tomato to membrane-targeted green fluorescent protein. The reporter cassette was placed at the porcine ROSA26 locus by conventional gene targeting using primary mesenchymal stem cells, and animals generated by nuclear transfer. Gene targeting efficiency was high, and analysis of foetal organs and primary cells indicated that the reporter is highly expressed and functional. Cre reporter pigs will provide a multipurpose indicator of Cre recombinase activity, an important new tool for the rapidly expanding field of porcine genetic modification.

  2. Recombinant mitochondrial genome with standard transmission route from Mediterranean mussel Mytilus galloprovincialis.

    Science.gov (United States)

    Śmietanka, Beata; Filipowicz, Monika; Burzyński, Artur

    2016-01-01

    Several bivalve species, including marine mussels Mytilus are atypical in having two gender-specific and highly divergent mtDNA genomes. This peculiar genetic system allows not only the recombination to occur but also facilitates its detection. Previous reports associated the existence of mosaic recombinant haplotypes with the switch of their transmission route. Here we report nearly complete sequence of a mitochondrial genome isolated from a homoplasmic female individual of Mediterranean Mytilus galloprovincialis. The genome has clear phylogenetic affinity with and organization identical to the M. galloprovincialis female haplotypes, in the coding part. However, the genome is very large, approximately 20,600 bp long, exclusively due to a long and complex control region. It contains an array of repeats, some of which are degenerated. A large part of the control region is derived from the paternal genome. This finding shows that not all haplotypes with recombinant control regions must be paternally inherited in Mytilus.

  3. Efficient Tracking of Large Classes of Experts

    CERN Document Server

    Gyorgy, András; Lugosi, Gábor

    2011-01-01

    In the framework for prediction of individual sequences, sequential prediction methods are to be constructed that perform nearly as well as the best expert from a given class. We consider prediction strategies that compete with the class of switching strategies that can segment a given sequence into several blocks, and follow the advice of a different "base" expert in each block. As usual, the performance of the algorithm is measured by the regret defined as the excess loss relative to the best switching strategy selected in hindsight for the particular sequence to be predicted. In this paper we construct prediction strategies of low computational cost for the case where the set of base experts is large. In particular we derive a family of efficient tracking algorithms that, for any prediction algorithm $\\A$ designed for the base class, can be implemented with time and space complexity $O(n^{\\gamma} \\log n)$ times larger than that of $\\A$, where $n$ is the time horizon and $\\gamma \\ge 0$ is a parameter of the...

  4. Spark gap switch with spiral gas flow

    Science.gov (United States)

    Brucker, John P.

    1989-01-01

    A spark gap switch having a contaminate removal system using an injected gas. An annular plate concentric with an electrode of the switch defines flow paths for the injected gas which form a strong spiral flow of the gas in the housing which is effective to remove contaminates from the switch surfaces. The gas along with the contaminates is exhausted from the housing through one of the ends of the switch.

  5. Extended ℋ∞ Estimation for Two-Dimensional Markov Jump Systems under Asynchronous Switching

    Directory of Open Access Journals (Sweden)

    Rui Zhang

    2013-01-01

    Full Text Available This paper is concerned with the problem of designing ℋ∞ filters for a class of two-dimensional (2D Markov jump systems under asynchronous switching. The problem under consideration is primarily motivated by a realistic situation that the switching of candidate filters may have a lag to the switching of system modes. Different from conventional techniques, by a suitable augmentation, the jumping process of the error system is represented by a two-component Markov chain. Then, the extended transition probabilities are provided for the error system. A stochastic Lyapunov function approach is proposed for the design of desired filters that ensure a prescribed ℋ∞ performance for admissible asynchronous switching. Finally, a numerical example is given to illustrate the effectiveness of the developed method.

  6. The increased importance of sector switching

    DEFF Research Database (Denmark)

    Frederiksen, Anders; Hansen, Jesper Rosenberg

    2014-01-01

    Sector switching is an important phenomenon that casts light on public–private differences. Yet our knowledge about its prevalence and trends is limited. We study sector switching using unique Danish register-based employer–employee data covering more than 25 years. We find that sector switching...

  7. Bootstrapped Low-Voltage Analog Switches

    DEFF Research Database (Denmark)

    Steensgaard-Madsen, Jesper

    1999-01-01

    Novel low-voltage constant-impedance analog switch circuits are proposed. The switch element is a single MOSFET, and constant-impedance operation is obtained using simple circuits to adjust the gate and bulk voltages relative to the switched signal. Low-voltage (1-volt) operation is made feasible...

  8. A gain-coefficient switched Alexandrite laser

    NARCIS (Netherlands)

    Lee, C. J.; van der Slot, P. J. M.; Boller, K. J.

    2013-01-01

    We report on a gain-coefficient switched Alexandrite laser. An electro-optic modulator is used to switch between high and low gain states by making use of the polarization dependent gain of Alexandrite. In gain-coefficient switched mode, the laser produces 85 ns pulses with a pulse energy of 240 mJ

  9. Switch for serial or parallel communication networks

    Science.gov (United States)

    Crosette, D.B.

    1994-07-19

    A communication switch apparatus and a method for use in a geographically extensive serial, parallel or hybrid communication network linking a multi-processor or parallel processing system has a very low software processing overhead in order to accommodate random burst of high density data. Associated with each processor is a communication switch. A data source and a data destination, a sensor suite or robot for example, may also be associated with a switch. The configuration of the switches in the network are coordinated through a master processor node and depends on the operational phase of the multi-processor network: data acquisition, data processing, and data exchange. The master processor node passes information on the state to be assumed by each switch to the processor node associated with the switch. The processor node then operates a series of multi-state switches internal to each communication switch. The communication switch does not parse and interpret communication protocol and message routing information. During a data acquisition phase, the communication switch couples sensors producing data to the processor node associated with the switch, to a downlink destination on the communications network, or to both. It also may couple an uplink data source to its processor node. During the data exchange phase, the switch couples its processor node or an uplink data source to a downlink destination (which may include a processor node or a robot), or couples an uplink source to its processor node and its processor node to a downlink destination. 9 figs.

  10. Mechanism of single atom switch on silicon

    DEFF Research Database (Denmark)

    Quaade, Ulrich; Stokbro, Kurt; Thirstrup, C.;

    1998-01-01

    We demonstrate single atom switch on silicon which operates by displacement of a hydrogen atom on the silicon (100) surface at room temperature. We find two principal effects by which the switch is controlled: a pronounced maximum of the switching probability as function of sample bias...

  11. Degree of Conversational Code-Switching Enhances Verbal Task Switching in Cantonese-English Bilinguals

    Science.gov (United States)

    Yim, Odilia; Bialystok, Ellen

    2012-01-01

    The study examined individual differences in code-switching to determine the relationship between code-switching frequency and performance in verbal and non-verbal task switching. Seventy-eight Cantonese-English bilinguals completed a semi-structured conversation to quantify natural code-switching, a verbal fluency task requiring language…

  12. AN EFFECTIVE MODEL TO EVALUATE BLOCKING PROBABILITY OF TIME-SLOTTED OPTICAL BURST SWITCHED NETWORKS

    Institute of Scientific and Technical Information of China (English)

    Yang Zongkai; Ou Liang; Tan Xiansi

    2006-01-01

    Time-slotted optical burst switched network is a potential technique to support IP over Wavelength Division Multiplexing (WDM) by introduce Time Division Multiplexing (TDM) channel to Optical Burst Switching (OBS) technology. This paper presents a framework to evaluate blocking performance of time-slotted OBS networks with multi-fiber wavelength channels. The proposed model is efficient for not only single class traffic such as individual circuit switch traffics or best-effort traffics but also mixed multi-class traffics.The effectiveness of the proposed model is validated by simulation results. The study shows that blocking performance of multi-fiber TS-OBS network is acceptable for future Internet services.

  13. Vaccine escape recombinants emerge after pneumococcal vaccination in the United States.

    Directory of Open Access Journals (Sweden)

    Angela B Brueggemann

    2007-11-01

    Full Text Available The heptavalent pneumococcal conjugate vaccine (PCV7 was introduced in the United States (US in 2000 and has significantly reduced invasive pneumococcal disease; however, the incidence of nonvaccine serotype invasive disease, particularly due to serotype 19A, has increased. The serotype 19A increase can be explained in part by expansion of a genotype that has been circulating in the US prior to vaccine implementation (and other countries since at least 1990, but also by the emergence of a novel "vaccine escape recombinant" pneumococcal strain. This strain has a genotype that previously was only associated with vaccine serotype 4, but now expresses a nonvaccine serotype 19A capsule. Based on prior evidence for capsular switching by recombination at the capsular locus, the genetic event that resulted in this novel serotype/genotype combination might be identifiable from the DNA sequence of individual pneumococcal strains. Therefore, the aim of this study was to characterise the putative recombinational event(s at the capsular locus that resulted in the change from a vaccine to a nonvaccine capsular type. Sequencing the capsular locus flanking regions of 51 vaccine escape (progeny, recipient, and putative donor pneumococci revealed a 39 kb recombinational fragment, which included the capsular locus, flanking regions, and two adjacent penicillin-binding proteins, and thus resulted in a capsular switch and penicillin nonsusceptibility in a single genetic event. Since 2003, 37 such vaccine escape strains have been detected, some of which had evolved further. Furthermore, two new types of serotype 19A vaccine escape strains emerged in 2005. To our knowledge, this is the first time a single recombinational event has been documented in vivo that resulted in both a change of serotype and penicillin nonsusceptibility. Vaccine escape by genetic recombination at the capsular locus has the potential to reduce PCV7 effectiveness in the longer term.

  14. Approaches to building single-stage AC/AC conversion switch-mode audio power amplifiers

    DEFF Research Database (Denmark)

    Ljusev, Petar; Andersen, Michael Andreas E.

    2004-01-01

    This paper discusses the possible topologies and promising approaches towards direct single-phase AC-AC conversion of the mains voltage for audio applications. When compared to standard Class-D switching audio power amplifiers with a separate power supply, it is expected that direct conversion...

  15. The Use of Dwell-Time Switching to Maintain a Formation with Only Range Sensing

    NARCIS (Netherlands)

    Cao, Ming; Morse, A. Stephen

    2008-01-01

    Using concepts from switched adaptive control theory plus a special parameterization of the class of 2×2 nonsingular matrices, a tractable and provably correct solution is given to the three landmark station keeping problem in the plane in which range measurements are the only sensed signals upon wh

  16. Exponential Stability of Uncertain T-S Fuzzy Switched Systems with Time Delay

    Institute of Scientific and Technical Information of China (English)

    Fatima Ahmida; El Houssaine Tissir

    2013-01-01

    This paper discusses the delay-dependent exponential stability of a class of uncertain T-S fuzzy switched systems with time delay.The method is based on Lyapunov stability theorem and free weighting matrices approach.Two illustrative examples are given to demonstrate the effectiveness of the proposed method.

  17. Soft-switching Grid-connected PV Inverter With Interleaved Flyback Topology

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The flyback topology has advantages of robustness and low cost and is proposed for 200-300 W class grid-connected photovoltaic inverter. However, the flyback converter is known for its low efficiency and low resolution control. Therefore, digitalized soft switching technique and algorithm are to be developed.

  18. Design of High-Voltage Switch-Mode Power Amplifier Based on Digital-Controlled Hybrid Multilevel Converter

    Directory of Open Access Journals (Sweden)

    Yanbin Hou

    2016-01-01

    Full Text Available Compared with conventional Class-A, Class-B, and Class-AB amplifiers, Class-D amplifier, also known as switching amplifier, employs pulse width modulation (PWM technology and solid-state switching devices, capable of achieving much higher efficiency. However, PWM-based switching amplifier is usually designed for low-voltage application, offering a maximum output voltage of several hundred Volts. Therefore, a step-up transformer is indispensably adopted in PWM-based Class-D amplifier to produce high-voltage output. In this paper, a switching amplifier without step-up transformer is developed based on digital pulse step modulation (PSM and hybrid multilevel converter. Under the control of input signal, cascaded power converters with separate DC sources operate in PSM switch mode to directly generate high-voltage and high-power output. The relevant topological structure, operating principle, and design scheme are introduced. Finally, a prototype system is built, which can provide power up to 1400 Watts and peak voltage up to ±1700 Volts. And the performance, including efficiency, linearity, and distortion, is evaluated by experimental tests.

  19. Preparing Recombinant Gonad Organ Cultures

    OpenAIRE

    sprotocols

    2014-01-01

    Authors: Blanche Capel and Jordan Batchvarov Corresponding author ([]()) ### INTRODUCTION It can be useful to assay migration between any two adjacent tissues during development. This protocol assays cell migration between the gonad and mesonephros using tissue recombination between genetically marked and unmarked tissue, combined with an organ culture technique. First, agar blocks are prepared in a custom-built mold. The size and sh...

  20. Controlled Release from Recombinant Polymers

    OpenAIRE

    Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza

    2014-01-01

    Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and tempor...

  1. Recombination hotspots flank the Cryptococcus mating-type locus: implications for the evolution of a fungal sex chromosome.

    Directory of Open Access Journals (Sweden)

    Yen-Ping Hsueh

    2006-11-01

    Full Text Available Recombination increases dramatically during meiosis to promote genetic exchange and generate recombinant progeny. Interestingly, meiotic recombination is unevenly distributed throughout genomes, and, as a consequence, genetic and physical map distances do not have a simple linear relationship. Recombination hotspots and coldspots have been described in many organisms and often reflect global features of chromosome structure. In particular, recombination frequencies are often distorted within or outside sex-determining regions of the genome. Here, we report that recombination is elevated adjacent to the mating-type locus (MAT in the pathogenic basidiomycete Cryptococcus neoformans. Among fungi, C. neoformans has an unusually large MAT locus, and recombination is suppressed between the two >100-kilobase mating-type specific alleles. When genetic markers were introduced at defined physical distances from MAT, we found the meiotic recombination frequency to be approximately 20% between MAT and a flanking marker at 5, 10, 50, or 100 kilobases from the right border. As a result, the physical/genetic map ratio in the regions adjacent to MAT is distorted approximately 10- to 50-fold compared to the genome-wide average. Moreover, recombination frequently occurred on both sides of MAT and negative interference between crossovers was observed. MAT heterozygosity was not required for enhanced recombination, implying that this process is not due to a physical distortion from the two non-paired alleles and could also occur during same-sex mating. Sequence analysis revealed a correlation between high G + C content and these hotspot regions. We hypothesize that the presence of recombinational activators may have driven several key events during the assembly and reshaping of the MAT locus and may have played similar roles in the origins of both metabolic and biosynthetic gene clusters. Our findings suggest that during meiosis the MAT locus may be exchanged onto

  2. Intragenic recombination in the CSR1 locus of Arabidopsis.

    Science.gov (United States)

    Mourad, G; Haughn, G; King, J

    1994-04-01

    Four classes of herbicides are known to inhibit plant acetolactate synthase (ALS). In Arabidopsis, ALS is encoded by a single gene, CSR1. The dominant csr1-1 allele encodes an ALS resistant to chlorsulfuron and triazolopyrimidine sulfonamide while the dominant csr1-2 allele encodes an ALS resistant to imazapyr and pyrimidyl-oxy-benzoate. The molecular distance between the point mutations in csr1-1 and csr1-2 is 1369 bp. Here we used multiherbicide resistance as a stringent selection to measure the intragenic recombination frequency between these two point mutations. We found this frequency to be 0.008 +/- 0.0028. The recombinant multiherbicide-resistant allele, csr1-4, provides an ideal marker for plant genetic transformation. PMID:8177214

  3. Investigation of the genes involved in antigenic switching at the vlsE locus in Borrelia burgdorferi: an essential role for the RuvAB branch migrase.

    Directory of Open Access Journals (Sweden)

    Ashley R Dresser

    2009-12-01

    Full Text Available Persistent infection by pathogenic organisms requires effective strategies for the defense of these organisms against the host immune response. A common strategy employed by many pathogens to escape immune recognition and clearance is to continually vary surface epitopes through recombinational shuffling of genetic information. Borrelia burgdorferi, a causative agent of Lyme borreliosis, encodes a surface-bound lipoprotein, VlsE. This protein is encoded by the vlsE locus carried at the right end of the linear plasmid lp28-1. Adjacent to the expression locus are 15 silent cassettes carrying information that is moved into the vlsE locus through segmental gene conversion events. The protein players and molecular mechanism of recombinational switching at vlsE have not been characterized. In this study, we analyzed the effect of the independent disruption of 17 genes that encode factors involved in DNA recombination, repair or replication on recombinational switching at the vlsE locus during murine infection. In Neisseria gonorrhoeae, 10 such genes have been implicated in recombinational switching at the pilE locus. Eight of these genes, including recA, are either absent from B. burgdorferi, or do not show an obvious requirement for switching at vlsE. The only genes that are required in both organisms are ruvA and ruvB, which encode subunits of a Holliday junction branch migrase. Disruption of these genes results in a dramatic decrease in vlsE recombination with a phenotype similar to that observed for lp28-1 or vls-minus spirochetes: productive infection at week 1 with clearance by day 21. In SCID mice, the persistence defect observed with ruvA and ruvB mutants was fully rescued as previously observed for vlsE-deficient B. burgdorferi. We report the requirement of the RuvAB branch migrase in recombinational switching at vlsE, the first essential factor to be identified in this process. These findings are supported by the independent work of Lin et

  4. A dual-mode highly efficient class-E stimulator controlled by a low-Q class-E power amplifier through duty cycle.

    Science.gov (United States)

    Chiu, Hung-Wei; Lu, Chien-Chi; Chuang, Jia-min; Lin, Wei-Tso; Lin, Chii-Wann; Kao, Ming-Chien; Lin, Mu-Lien

    2013-06-01

    This paper presents the design flow of two high-efficiency class-E amplifiers for the implantable electrical stimulation system. The implantable stimulator is a high-Q class-E driver that delivers a sine-wave pulsed radiofrequency (PRF) stimulation, which was verified to have a superior efficacy in pain relief to a square wave. The proposed duty-cycle-controlled class-E PRF driver designed with a high-Q factor has two operational modes that are able to achieve 100% DC-AC conversion, and involves only one switched series inductor and an unchanged parallel capacitor. The measured output amplitude under low-voltage (LV) mode using a 22% duty cycle was 0.98 V with 91% efficiency, and under high-voltage (HV) mode using a 47% duty cycle was 2.95 V with 92% efficiency. These modes were inductively controlled by a duty-cycle detector, which can detect the duty-cycle modulated signal generated from the external complementary low-Q class-E power amplifier (PA). The design methodology of the low-Q inductive interface for a non-50% duty cycle is presented. The experimental results exhibits that the 1.5-V PA that consumes DC power of 14.21 mW was able to deliver a 2.9-V sine wave to a 500 Ω load. The optimal 60% drain efficiency of the system from the PA to the load was obtained at a 10-mm coupling distance.

  5. Stability and kinetic studies on recombinant pyroglutamyl peptidase I and two mutant forms

    OpenAIRE

    Mtawae, Karima

    2005-01-01

    This thesis investigates the kinetic and stability characteristics of recombinant human brain pyroglutamyl peptidase PAPI, an omega exopeptidase which cleaves pyroglutamic acid from the N-terminus of peptides and proteins. Three classes of pyroglutamyl peptidase have been found in a variety of bacteria, plant, animal, and human tissues; the first class includes the bacterial and animal type 1, pyroglutamyl peptidase I. The genes encoding bacterial PAPI have been cloned and characterized previ...

  6. On the stabilization of switched linear stochastic systems with unobservable switching laws

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    This paper is concerned with the stabilization problem of switched linear stochastic systems with unobservable switching laws. In this paper the system switches among a finite family of linear stochastic systems. Since there are noise perturbations, the switching laws can not be identified in any finite time horizon. We prove that if each individual subsystem is controllable and the switching duration uniformly has a strict positive lower bound, then the system can be stabilized by using a controller that uses online state estimation.

  7. Qualitative aspects on closed loop power switching systems control

    Directory of Open Access Journals (Sweden)

    Dan Olaru

    2009-10-01

    Full Text Available The switching circuit control problem contains various aspects concerning the closed loop operation, the harmonically perturbation generation, the transient regime duration, the dynamic or stationary regime stability, the filtering devices costs, etc. The presented paper presents a class of control methods, based on some mathematical concepts that revel certain important advantages. In this approach there are analyzed only the aspects concerning the theoretical principles that are used and the behavior of certain types of model implementations. The numerical simulations certify the validity of the methods and enable the analysis of the functional operation. These are very useful for the future developments having a concrete and practical character.

  8. STABILITY OF A SWITCHED LINEAR SYSTEM

    Directory of Open Access Journals (Sweden)

    At-Tasneem Mohd Amin

    2012-12-01

    Full Text Available Hybrid systems are dynamic systems that arise out of the interaction of continuous state dynamics and discrete state dynamics. Switched systems, which are a type of hybrid system, have been given much attention by control systems research over the past decade. Problems with the controllability, observability, converseability and stabilizability of switched systems have always been discussed. In this paper, the trend in research regarding the stability of switched systems will be investigated. Then the variety of methods that have been discovered by researchers for stabilizing switched linear systems with arbitrary switching will be discussed in detail.

  9. Ultrafast all-optical switching in bacteriorhodopsin

    Science.gov (United States)

    Roy, Sukhdev; Singh, C. P.; Reddy, K. P. J.

    2001-04-01

    All-optical switching has been demonstrated in bacteriorhodopsin based on excited-state nonlinear absorption. A probe laser beam at 640 nm corresponding to the O-state absorption maximum is switched due to a strong pulsed pump laser beam at 570 nm, that corresponds to the maximum ground state absorption. We have studied the effect of variation in pulse width and in small signal absorption coefficient on the switching characteristics. The switching time decreases as the pulse width of the pump beam decreases and the small signal absorption coefficient increases. The switching contrast depends mainly on the peak pumping intensity.

  10. Secure videoconferencing equipment switching system and method

    Science.gov (United States)

    Hansen, Michael E.

    2009-01-13

    A switching system and method are provided to facilitate use of videoconference facilities over a plurality of security levels. The system includes a switch coupled to a plurality of codecs and communication networks. Audio/Visual peripheral components are connected to the switch. The switch couples control and data signals between the Audio/Visual peripheral components and one but nor both of the plurality of codecs. The switch additionally couples communication networks of the appropriate security level to each of the codecs. In this manner, a videoconferencing facility is provided for use on both secure and non-secure networks.

  11. Live recombinant BHV/BRSV vaccine

    NARCIS (Netherlands)

    Keil, G.M.; Rijsewijk, F.A.M.

    1998-01-01

    The present invention refers to synthetic Bovine Respiratory Syncytium virus genes. Also the invention relates to live attenuated Bovine Herpesvirus recombinants carrying such synthetic genes. Furthermore, the invention relates to vaccines based on these live attenuated recombinants, for the protect

  12. Recombinant innovation and endogenous technological transitions

    NARCIS (Netherlands)

    K. Frenken; L.R. Izquierdo; P. Zeppini

    2012-01-01

    We propose a model of technological transitions based on two different types of innovations. Branching innovations refer to technological improvements along a particular path, while recombinant innovations represent fusions of multiple paths. Recombinant innovations create "short-cuts" which reduce

  13. Shape memory thermal conduction switch

    Science.gov (United States)

    Vaidyanathan, Rajan (Inventor); Krishnan, Vinu (Inventor); Notardonato, William U. (Inventor)

    2010-01-01

    A thermal conduction switch includes a thermally-conductive first member having a first thermal contacting structure for securing the first member as a stationary member to a thermally regulated body or a body requiring thermal regulation. A movable thermally-conductive second member has a second thermal contacting surface. A thermally conductive coupler is interposed between the first member and the second member for thermally coupling the first member to the second member. At least one control spring is coupled between the first member and the second member. The control spring includes a NiTiFe comprising shape memory (SM) material that provides a phase change temperature <273 K, a transformation range <40 K, and a hysteresis of <10 K. A bias spring is between the first member and the second member. At the phase change the switch provides a distance change (displacement) between first and second member by at least 1 mm, such as 2 to 4 mm.

  14. Ultrafast photonic crystal optical switching

    Institute of Scientific and Technical Information of China (English)

    GONG Qi-huang; HU Xiao-yong

    2006-01-01

    Photonic crystal,a novel and artificial photonic material with periodic dielectric distribution,possesses photonic bandgap and can control the propagation states of photons.Photonic crystal has been considered to be a promising candidate for the future integrated photonic devices.The properties and the fabrication method of photonic crystal are expounded.The progresses of the study of ultrafast photonic crystal optical switching are discussed in detail.

  15. Polychromatic polariton laser selector switch

    OpenAIRE

    Grosso, G; Trebaol, S.; Wouters, M.; Morier-Genoud, F; Portella-Oberli, M. T.; Deveaud, B.

    2013-01-01

    Integration of optical elements into scalable chips has been at the center of a large effort in recent years. Concurrently, the separation between the diverse functions, namely switches, detectors or emitters increases significantly the final number of components on chip. Such technical limitations may be overcome by introducing agile devices able, for example, to simultaneously detect, process and emit a coherent signal. Such a pathway has been explored with different approaches that bear ad...

  16. Robust Stability of Switched Systems

    DEFF Research Database (Denmark)

    Sloth, Christoffer; Wisniewski, Rafael

    2014-01-01

    This paper presents a linear programming-based method for finding Lyapunov functions of switched systems with polynomial vector fields and parametric uncertainties. We propose to utilize a certificate of positivity in the Bernstein basis to find a Lyapunov function. A certificate of positivity...... in the Bernstein basis always exists if a polynomial is positive, and the Bernstein basis is shown to be well conditioned....

  17. EMI Prediction of Switching Converters

    OpenAIRE

    Trinchero, Riccardo; Stievano, Igor Simone; Canavero, Flavio

    2015-01-01

    This paper addresses the simulation of the conducted electromagnetic interference produced by circuits with periodically switching elements. The proposed method allows for the computation of their steady-state responses by means of augmented linear time-invariant equivalents built from circuit inspection only, and standard tools for circuit analysis. The approach is demonstrated on a real dc-dc boost converter by comparing simulation results with real measurements

  18. Static Switching Dynamic Buffer Circuit

    OpenAIRE

    Pandey, A. K.; R. A. Mishra; R. K. Nagaria

    2013-01-01

    We proposed footless domino logic buffer circuit. It minimizes redundant switching at the dynamic and the output nodes. The proposed circuit avoids propagation of precharge pulse to the output node and allows the dynamic node which saves power consumption. Simulation is done using 0.18 µm CMOS technology. We have calculated the power consumption, delay, and power delay product of the proposed circuit and compared the results with the existing circuits for different logic function, loading co...

  19. Switch for Good Community Program

    Energy Technology Data Exchange (ETDEWEB)

    Crawford, Tabitha; Amran, Martha

    2013-11-19

    Switch4Good is an energy-savings program that helps residents reduce consumption from behavior changes; it was co-developed by Balfour Beatty Military Housing Management (BB) and WattzOn in Phase I of this grant. The program was offered at 11 Navy bases. Three customer engagement strategies were evaluated, and it was found that Digital Nudges (a combination of monthly consumption statements with frequent messaging via text or email) was most cost-effective.

  20. Switching strategies to optimize search

    Science.gov (United States)

    Shlesinger, Michael F.

    2016-03-01

    Search strategies are explored when the search time is fixed, success is probabilistic and the estimate for success can diminish with time if there is not a successful result. Under the time constraint the problem is to find the optimal time to switch a search strategy or search location. Several variables are taken into account, including cost, gain, rate of success if a target is present and the probability that a target is present.

  1. Analytical Performance Evaluation of Different Switch Solutions

    Directory of Open Access Journals (Sweden)

    Francisco Sans

    2013-01-01

    Full Text Available The virtualization of the network access layer has opened new doors in how we perceive networks. With this virtualization of the network, it is possible to transform a regular PC with several network interface cards into a switch. PC-based switches are becoming an alternative to off-the-shelf switches, since they are cheaper. For this reason, it is important to evaluate the performance of PC-based switches. In this paper, we present a performance evaluation of two PC-based switches, using Open vSwitch and LiSA, and compare their performance with an off-the-shelf Cisco switch. The RTT, throughput, and fairness for UDP are measured for both Ethernet and Fast Ethernet technologies. From this research, we can conclude that the Cisco switch presents the best performance, and both PC-based switches have similar performance. Between Open vSwitch and LiSA, Open vSwitch represents a better choice since it has more features and is currently actively developed.

  2. Energy storage, compression, and switching. Vol. 2

    International Nuclear Information System (INIS)

    This book is a compilation of papers presented at the Second International Conference on Energy Storage, Compression, and Switching, which was held in order to assemble active researchers with a major interest in plasma physics, electron beams, electric and magnetic energy storage systems, high voltage and high current switches, free-electron lasers, and pellet implosion plasma focus. Topics covered include: Slow systems: 50-60 Hz machinery, homopolar generators, slow capacitors, inductors, and solid state switches; Intermediate systems: fast capacitor banks; superconducting storage and switching; gas, vacuum, and dielectric switching; nonlinear (magnetic) switching; imploding liners capacitors; explosive generators; and fuses; and Fast systems: Marx, Blumlein, oil, water, and pressurized water dielectrics; switches; magnetic insulation; electron beams; and plasmas

  3. Pinning Synchronization of Switched Complex Dynamical Networks

    Directory of Open Access Journals (Sweden)

    Liming Du

    2015-01-01

    Full Text Available Network topology and node dynamics play a key role in forming synchronization of complex networks. Unfortunately there is no effective synchronization criterion for pinning synchronization of complex dynamical networks with switching topology. In this paper, pinning synchronization of complex dynamical networks with switching topology is studied. Two basic problems are considered: one is pinning synchronization of switched complex networks under arbitrary switching; the other is pinning synchronization of switched complex networks by design of switching when synchronization cannot achieved by using any individual connection topology alone. For the two problems, common Lyapunov function method and single Lyapunov function method are used respectively, some global synchronization criteria are proposed and the designed switching law is given. Finally, simulation results verify the validity of the results.

  4. Coating possibilities for magnetic switches

    International Nuclear Information System (INIS)

    High average power magnetic pulse compression systems are now being considered for use in several applications such as the High Power Radiation Source (HiPoRS) project. Such systems will require high reliability magnetic switches (saturable inductors) that are very efficient and have long lifetimes. One of the weakest components in magnetic switches is their interlaminar insulation. Considerations related to dielectric breakdown, thermal management of compact designs, and economical approaches for achieving these needs must be addressed. Various dielectric insulation and coating materials have been applied to Metglas foil in an attempt to solve the complex technical and practical problems associated with large magnetic switch structures. This work reports various needs, studies, results, and proposals in selecting and evaluating continuous coating approaches for magnetic foil. Techniques such as electrophoretic polymer deposition and surface chemical oxidation are discussed. We also propose continuous photofabrication processes for applying dielectric ribs or spacers to the foil which permit circulation of dielectric liquids for cooling during repetitive operation. 10 refs., 8 figs., 11 tabs

  5. Determination of recombination in Mycoplasma hominis

    DEFF Research Database (Denmark)

    Jacobsen, Iben Søgaard; Boesen, Thomas; Mygind, Tina;

    2002-01-01

    indicating the presence of recombination. In order to test for intergenic recombination, phylogenetic trees were reconstructed for each of the genes but no well-supported bifurcating phylogenetic trees could be obtained. The genes were tested for intragenic recombination using the correlation between linkage...

  6. The Cosmology Large Angular Scale Surveyor (CLASS)

    Science.gov (United States)

    Harrington, Kathleen; Marriange, Tobias; Aamir, Ali; Appel, John W.; Bennett, Charles L.; Boone, Fletcher; Brewer, Michael; Chan, Manwei; Chuss, David T.; Colazo, Felipe; Denis, Kevin; Moseley, Samuel H.; Rostem, Karwan; Wollack, Edward

    2016-01-01

    The Cosmology Large Angular Scale Surveyor (CLASS) is a four telescope array designed to characterize relic primordial gravitational waves from in ation and the optical depth to reionization through a measurement of the polarized cosmic microwave background (CMB) on the largest angular scales. The frequencies of the four CLASS telescopes, one at 38 GHz, two at 93 GHz, and one dichroic system at 145/217 GHz, are chosen to avoid spectral regions of high atmospheric emission and span the minimum of the polarized Galactic foregrounds: synchrotron emission at lower frequencies and dust emission at higher frequencies. Low-noise transition edge sensor detectors and a rapid front-end polarization modulator provide a unique combination of high sensitivity, stability, and control of systematics. The CLASS site, at 5200 m in the Chilean Atacama desert, allows for daily mapping of up to 70% of the sky and enables the characterization of CMB polarization at the largest angular scales. Using this combination of a broad frequency range, large sky coverage, control over systematics, and high sensitivity, CLASS will observe the reionization and recombination peaks of the CMB E- and B-mode power spectra. CLASS will make a cosmic variance limited measurement of the optical depth to reionization and will measure or place upper limits on the tensor-to-scalar ratio, r, down to a level of 0.01 (95% C.L.).

  7. AID induces double-strand breaks at immunoglobulin switch regions and c-MYC causing chromosomal translocations in yeast THO mutants.

    Directory of Open Access Journals (Sweden)

    José F Ruiz

    2011-02-01

    Full Text Available Transcription of the switch (S regions of immunoglobulin genes in B cells generates stable R-loops that are targeted by Activation Induced Cytidine Deaminase (AID, triggering class switch recombination (CSR, as well as translocations with c-MYC responsible for Burkitt's lymphomas. In Saccharomyces cerevisiae, stable R-loops are formed co-transcriptionally in mutants of THO, a conserved nuclear complex involved in mRNP biogenesis. Such R-loops trigger genome instability and facilitate deamination by human AID. To understand the mechanisms that generate genome instability mediated by mRNP biogenesis impairment and by AID, we devised a yeast chromosomal system based on different segments of mammalian S regions and c-MYC for the analysis of chromosomal rearrangements in both wild-type and THO mutants. We demonstrate that AID acts in yeast at heterologous S and c-MYC transcribed sequences leading to double-strand breaks (DSBs which in turn cause chromosomal translocations via Non-Homologous End Joining (NHEJ. AID-induced translocations were strongly enhanced in yeast THO null mutants, consistent with the idea that AID-mediated DSBs depend on R-loop formation. Our study not only provides new clues to understand the role of mRNP biogenesis in preventing genome rearrangements and the mechanism of AID-mediated genome instability, but also shows that, once uracil residues are produced by AID-mediated deamination, these are processed into DSBs and chromosomal rearrangements by the general and conserved DNA repair functions present from yeast to human cells.

  8. Semisimple Classes of Semirings

    Institute of Scientific and Technical Information of China (English)

    U. Hebisch; H.J. Weinert

    2002-01-01

    A famous result of Sands states that a class S of associative rings is semisimple if and only if S is regular, coinductive, and extensionally closed. Here,we investigate semisimple classes in a Kurosh-Amitsur radical theory for semirings. We show that such a class S is regular, K-coinductive, and K-extensionally closed. But a characterization of semisimple classes of semirings needs a fourth condition, namely that S is inverse semi-isomorphically closed. We also obtain other characterizations and results for semisimple classes and for subdirect products of semirings.

  9. Loosely coupled class families

    DEFF Research Database (Denmark)

    Ernst, Erik

    2001-01-01

    are expressed using virtual classes seem to be very tightly coupled internally. While clients have achieved the freedom to dynamically use one or the other family, it seems that any given family contains a xed set of classes and we will need to create an entire family of its own just in order to replace one...... of the members with another class. This paper shows how to express class families in such a manner that the classes in these families can be used in many dierent combinations, still enabling family polymorphism and ensuring type safety....

  10. Class, Culture and Politics

    DEFF Research Database (Denmark)

    Harrits, Gitte Sommer

    2013-01-01

    Even though contemporary discussions of class have moved forward towards recognizing a multidimensional concept of class, empirical analyses tend to focus on cultural practices in a rather narrow sense, that is, as practices of cultural consumption or practices of education. As a result......, discussions within political sociology have not yet utilized the merits of a multidimensional conception of class. In light of this, the article suggests a comprehensive Bourdieusian framework for class analysis, integrating culture as both a structural phenomenon co-constitutive of class and as symbolic...

  11. Competitive Buffer Management with Class Segregation

    CERN Document Server

    Al-Bawani, Kamal

    2011-01-01

    We introduce a new model for buffer management of network switches with Quality of Service (QoS) requirements and give a tight analysis. Specifically, each network packet is associated with a numerical value, called Class of Service (CoS), which represents its priority. We are furthermore given a network switch with $m$ queues that have individual capacities. Each queue stores packets of a certain CoS, only. A stream of packets arrives over time at the switch and an online algorithm has to decide on the admission and transmission of packets. The objective is to maximize the total CoS-value of the transmitted packets. Our main contribution is a natural online $\\GREEDY$ algorithm, which accepts any arriving packet, if the corresponding CoS-queue is not full. It always sends a buffered packet with highest value. We show that this algorithm is 2-competitive. This result is essentially best-possible since we also show a lower bound of $2 - v_m / (\\sum_{i=1}^m v_i)$ on the competitiveness of any deterministic onlin...

  12. Inclusive particle spectra in the quark recombination model

    International Nuclear Information System (INIS)

    The present status of the simple and valon versions of the quark recombination model is reviewed. The model has previously been applied primarily to hadron-hadron collisions in which the fragmenting and produced particles share a single common valence quark. The application of the model is extended to two additional classes of hadron-hadron collisions. (1) Collisions in which no valence quarks are common to the fragmenting and produced particles. (2) Collisions in which all valence quarks of the fragmenting particle are also valence quarks of the produced particle

  13. Selection of Recombinant Human Antibodies.

    Science.gov (United States)

    Tomszak, Florian; Weber, Susanne; Zantow, Jonas; Schirrmann, Thomas; Hust, Michael; Frenzel, André

    2016-01-01

    Since the development of therapeutic antibodies the demand of recombinant human antibodies is steadily increasing. Traditionally, therapeutic antibodies were generated by immunization of rat or mice, the generation of hybridoma clones, cloning of the antibody genes and subsequent humanization and engineering of the lead candidates. In the last few years, techniques were developed that use transgenic animals with a human antibody gene repertoire. Here, modern recombinant DNA technologies can be combined with well established immunization and hybridoma technologies to generate already affinity maturated human antibodies. An alternative are in vitro technologies which enabled the generation of fully human antibodies from antibody gene libraries that even exceed the human antibody repertoire. Specific antibodies can be isolated from these libraries in a very short time and therefore reduce the development time of an antibody drug at a very early stage.In this review, we describe different technologies that are currently used for the in vitro and in vivo generation of human antibodies. PMID:27236551

  14. Mechanisms of sister chromatid recombination

    International Nuclear Information System (INIS)

    Studies using T948 as a model system have been carried out aimed at elucidating the mechanism of sister chromatid recombination (SCR). Characterization of U.V. light- and x-ray-induced SCR, the relationiship between SCR induction and DNA repair using rad mutations, and the relationship between SCR induction and the time of cell division using cdc mutations are presented. It has been supposed that SCR is induced at the phase of S-G2 following DNA replication, that postreplication break of DNA strands is strongly involved in the induction of SCR, and that induction type of SCR, i.e., conversion type or recombination type, is dependent upon the type of molecular damage of DNA. (Namekawa, K.)

  15. Recombinant erythropoietin in clinical practice

    OpenAIRE

    Ng, T; Marx, G.; Littlewood, T; Macdougall, I

    2003-01-01

    The introduction of recombinant human erythropoietin (RHuEPO) has revolutionised the treatment of patients with anaemia of chronic renal disease. Clinical studies have demonstrated that RHuEPO is also useful in various non-uraemic conditions including haematological and oncological disorders, prematurity, HIV infection, and perioperative therapies. Besides highlighting both the historical and functional aspects of RHuEPO, this review discusses the applications of RHuEPO in clinical practice a...

  16. Recombinant antibodies and tumor targeting

    OpenAIRE

    Sheikholvaezin, Ali

    2006-01-01

    Different antibody derived constructs are rapidly advancing as putative tools for treatment of malignant diseases. Antibody engineering has added significant new technologies to modify size, affinities, solubility, stability and biodistribution properties for immunoconjugates. In the present thesis, the aim was to increase our knowledge on how new recombinant antibodies could be tailored to optimize localization to experimental tumors in mice. One hybridoma, producing the monoclonal antibody ...

  17. Insulating oil, electrical for transformers and switches : a national standard of Canada

    International Nuclear Information System (INIS)

    Standard specifications for insulating oil used in power transformers, instrument transformers, bushings, bulk oil circuit breakers, oil circuit reclosers, and switches were provided. The specifications are divided into Class A and Class B depending on the requirement for kinematic viscosity at -40 degrees C. A Class S oil is also introduced for oil circuit breakers. The standards were prepared by the Technical Committee on Transformer and Switch Oils under the jurisdiction of the Steering Committee on Electrical Engineering, and has been formally approved by these committees. It has been also approved as a National Standard of Canada by the Standards Council of Canada. The document provides a list of reference publications, describes the samples and test procedures, properties and delivery requirements. 1 tab

  18. Workshop on Radio Recombination Lines

    CERN Document Server

    1980-01-01

    Since their first detection 15 years ago, radio recombination lines from several elements have been observed in a wide variety of objects including HII regions, planetary nebulae, molecular clouds, the diffuse interstellar medium, and recently, other galaxies. The observations span almost the entire range from 0.1 to 100 GHz, and employ both single­ djsh and aperture synthesis techniques. The theory of radio recombination lines has also advanced strongly, to the point where it is perhaps one of the best-understood in astro­ physics. In a parallel development, it has become possible over the last decade to study these same highly-excited atoms in the laboratory; this work provides further confirmation of the theoretical framework. However there has been continuing controversy over the astrophysical interpre­ tation of radio recombination line observations, especially regarding the role of stimulated emission. A workshop was held in Ottawa on 24-25 August, 1979, bringing together many of the active scientist...

  19. Ways to suppress click and pop for class D amplifiers

    Institute of Scientific and Technical Information of China (English)

    Wang Haishi; Zhang Bo; Sun Jiang

    2012-01-01

    Undesirable audio click and pop may be generated in a speaker or headphone.Compared to linear (class A/B/AB) amplifiers,class D amplifiers that comprise of an input stage and a modulation stage are more prone to producing click and pop.This article analyzes sources that generate click and pop in class D amplifiers,and corresponding ways to suppress them.For a class D amplifier with a single-ended input,click and pop is likely to be due to two factors.One is from a voltage difference (VDIF) between the voltage of an input capacitance (VCIN)and a reference voltage (VREF) of the input stage,and the other one is from the non-linear switching during the setting up of the bias and feedback voltages/currents (BFVC) of the modulation stage.In this article,a fast charging loop is introduced into the input stage to charge VCIN to roughly near VREF.Then a correction loop further charges or discharges VCIN,substantially equalizing it with VREF.Dummy switches are introduced into the modulation stage to provide switching signals for setting up BFVC,and the power switches are disabled until the BFVC are set up successfully.A two channel single-ended class D amplifier with the above features is fabricated with 0.5 μm Bi-CMOS process.Road test and fast Fourier transform analysis indicate that there is no noticeable click and pop.

  20. Design and Simulation of Routing-switching Protocol Based on Optical Switch Array

    Institute of Scientific and Technical Information of China (English)

    HE Wei; MAO You-ju; LIU Jiang

    2004-01-01

    An optical routing- switching technology based on optical switch array is proposed. The characteristics of the blocking and nonblocking networks are analyzed and compared, odd- even sorting network is used to realize optical routing- switching, relative routing- switching protocol is designed.Simulation test under load shows that it can reduce a blocking effectively and enhance an efficiency of switching. Further, it can transfer the processing and switching within parallel computer from electric domain to optical domain. It can make parallel computer coordinating computing and processing at much more higher speed, storing and transmitting even more efficiently.