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Sample records for multiple circulating recombinant

  1. Novel HIV-1 recombinants spreading across multiple risk groups in the United Kingdom: the identification and phylogeography of Circulating Recombinant Form (CRF 50_A1D.

    Geraldine M Foster

    Full Text Available An increase in non-B HIV-1 infections among men who have sex with men (MSM in the United Kingdom (UK has created opportunities for novel recombinants to arise and become established. We used molecular mapping to characterize the importance of such recombinants to the UK HIV epidemic, in order to gain insights into transmission dynamics that can inform control strategies.A total of 55,556 pol (reverse transcriptase and protease sequences in the UK HIV Drug Resistance Database were analyzed using Subtype Classification Using Evolutionary Algorithms (SCUEAL. Overall 72 patients shared the same A1/D recombination breakpoint in pol, comprising predominantly MSM but also heterosexuals and injecting drug users (IDUs. In six MSM, full-length single genome amplification of plasma HIV-1 RNA was performed in order to characterize the A1/D recombinant. Subtypes and recombination breakpoints were identified using sliding window and jumping profile hidden markov model approaches. Global maximum likelihood trees of gag, pol and env genes were drawn using FastTree version 2.1. Five of the six strains showed the same novel A1/D recombinant (8 breakpoints, which has been classified as CRF50_A1D. The sixth strain showed a complex CRF50_A1D/B/U structure. Divergence dates and phylogeographic inferences were determined using Bayesian Evolutionary Analysis using Sampling Trees (BEAST. This estimated that CRF50_A1D emerged in the UK around 1992 in MSM, with subsequent transmissions to heterosexuals and IDUs. Analysis of CRF50_A1D/B/U demonstrated that around the year 2000 CRF50_A1D underwent recombination with a subtype B strain.We report the identification of CRF50_A1D, a novel circulating recombinant that emerged in UK MSM around 1992, with subsequent onward transmission to heterosexuals and IDUs, and more recent recombination with subtype B. These findings highlight the changing dynamics of HIV transmission in the UK and the converging of the two previously

  2. Molecular Diversity of HIV-1 among People Who Inject Drugs in Kuala Lumpur, Malaysia: Massive Expansion of Circulating Recombinant Form (CRF) 33_01B and Emergence of Multiple Unique Recombinant Clusters

    Chow, Wei Zhen; Ng, Kim Tien; Yong, Yean Kong; Azmel, Azureen; Takebe, Yutaka; Al-Darraji, Haider Abdulrazzaq Abed; Kamarulzaman, Adeeba; Tee, Kok Keng

    2013-01-01

    Since the discovery of HIV-1 circulating recombinant form (CRF) 33_01B in Malaysia in the early 2000 s, continuous genetic diversification and active recombination involving CRF33_01B and other circulating genotypes in the region including CRF01_AE and subtype B′ of Thai origin, have led to the emergence of novel CRFs and unique recombinant forms. The history and magnitude of CRF33_01B transmission among various risk groups including people who inject drugs (PWID) however have not been investigated despite the high epidemiological impact of CRF33_01B in the region. We update the most recent molecular epidemiology of HIV-1 among PWIDs recruited in Malaysia between 2010 and 2011 by population sequencing and phylogenetic analysis of 128 gag-pol sequences. HIV-1 CRF33_01B was circulating among 71% of PWIDs whilst a lower prevalence of other previously dominant HIV-1 genotypes [subtype B′ (11%) and CRF01_AE (5%)] and CRF01_AE/B′ unique recombinants (13%) were detected, indicating a significant shift in genotype replacement in this population. Three clusters of CRF01_AE/B′ recombinants displaying divergent yet phylogenetically-related mosaic genomes to CRF33_01B were identified and characterized, suggestive of an abrupt emergence of multiple novel CRF clades. Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC) sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers) and later on became endemic around the early 2000 s. Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population. The emergence of numerous previously unknown recombinant clades highlights the

  3. Molecular diversity of HIV-1 among people who inject drugs in Kuala Lumpur, Malaysia: massive expansion of circulating recombinant form (CRF) 33_01B and emergence of multiple unique recombinant clusters.

    Chow, Wei Zhen; Ong, Lai Yee; Razak, Siti Humaira; Lee, Yeat Mei; Ng, Kim Tien; Yong, Yean Kong; Azmel, Azureen; Takebe, Yutaka; Al-Darraji, Haider Abdulrazzaq Abed; Kamarulzaman, Adeeba; Tee, Kok Keng

    2013-01-01

    Since the discovery of HIV-1 circulating recombinant form (CRF) 33_01B in Malaysia in the early 2000 s, continuous genetic diversification and active recombination involving CRF33_01B and other circulating genotypes in the region including CRF01_AE and subtype B' of Thai origin, have led to the emergence of novel CRFs and unique recombinant forms. The history and magnitude of CRF33_01B transmission among various risk groups including people who inject drugs (PWID) however have not been investigated despite the high epidemiological impact of CRF33_01B in the region. We update the most recent molecular epidemiology of HIV-1 among PWIDs recruited in Malaysia between 2010 and 2011 by population sequencing and phylogenetic analysis of 128 gag-pol sequences. HIV-1 CRF33_01B was circulating among 71% of PWIDs whilst a lower prevalence of other previously dominant HIV-1 genotypes [subtype B' (11%) and CRF01_AE (5%)] and CRF01_AE/B' unique recombinants (13%) were detected, indicating a significant shift in genotype replacement in this population. Three clusters of CRF01_AE/B' recombinants displaying divergent yet phylogenetically-related mosaic genomes to CRF33_01B were identified and characterized, suggestive of an abrupt emergence of multiple novel CRF clades. Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC) sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers) and later on became endemic around the early 2000 s. Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population. The emergence of numerous previously unknown recombinant clades highlights the escalating

  4. Molecular diversity of HIV-1 among people who inject drugs in Kuala Lumpur, Malaysia: massive expansion of circulating recombinant form (CRF 33_01B and emergence of multiple unique recombinant clusters.

    Wei Zhen Chow

    Full Text Available Since the discovery of HIV-1 circulating recombinant form (CRF 33_01B in Malaysia in the early 2000 s, continuous genetic diversification and active recombination involving CRF33_01B and other circulating genotypes in the region including CRF01_AE and subtype B' of Thai origin, have led to the emergence of novel CRFs and unique recombinant forms. The history and magnitude of CRF33_01B transmission among various risk groups including people who inject drugs (PWID however have not been investigated despite the high epidemiological impact of CRF33_01B in the region. We update the most recent molecular epidemiology of HIV-1 among PWIDs recruited in Malaysia between 2010 and 2011 by population sequencing and phylogenetic analysis of 128 gag-pol sequences. HIV-1 CRF33_01B was circulating among 71% of PWIDs whilst a lower prevalence of other previously dominant HIV-1 genotypes [subtype B' (11% and CRF01_AE (5%] and CRF01_AE/B' unique recombinants (13% were detected, indicating a significant shift in genotype replacement in this population. Three clusters of CRF01_AE/B' recombinants displaying divergent yet phylogenetically-related mosaic genomes to CRF33_01B were identified and characterized, suggestive of an abrupt emergence of multiple novel CRF clades. Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers and later on became endemic around the early 2000 s. Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population. The emergence of numerous previously unknown recombinant clades highlights the

  5. Containment air circulation for optimal hydrogen recombination

    Spinks, N.; Krause, M.

    1997-01-01

    An accepted first-line defense for hydrogen mitigation is to design for the hydrogen to be rapidly mixed with the containment atmosphere and diluted to below flammability concentrations. Then, as hydrogen continues to be produced in the longer term, recombiners can be used to remove hydrogen: recombiners can be located in forced-air ducts or passive recombiners can be distributed within containment and the heat of recombination used to promote local air circulation. However, this principle does not eliminate the possibility of high hydrogen concentrations at locations removed from the recombiners. An improvement on this strategy is to arrange for a specific, buoyancy-driven, overall circulation of the containment atmosphere such that the recombiners can be located within the recirculation flow, immediately downstream of the hydrogen source. This would make the mixing process more predictable and solve the mass-transfer problem associated with distributed recombiners. Ideally, the recombiners would be located just above the hydrogen source so that the heat of recombination would assist the overall circulation. In this way, the hydrogen would be removed as close as possible to the source, thereby minimizing the amount of hydrogen immediately downstream of the source and reducing the hydrogen concentration to acceptable levels at other locations. Such a strategy requires the containment volume to be divided into an upflow path, past the hydrogen source and the recombiner, and a downflow path to complete the circuit. The flow could be generated actively using fans or passively using buoyancy forces arising from the difference in density of gases in the upfiow and downflow paths; the gases in the downflow path being cooled at an elevated heat sink. (author)

  6. Recombination pattern reanalysis of some HIV-1 circulating recombination forms suggest the necessity and difficulty of revision.

    Lei Jia

    Full Text Available Recombination is one of the major mechanisms underlying the generation of HIV-1 variability. Currently 61 circulating recombinant forms of HIV-1 have been identified. With the development of recombination detection techniques and accumulation of HIV-1 reference stains, more accurate mosaic structures of circulating recombinant forms (CRFs, like CRF04 and CRF06, have undergone repeated analysis and upgrades. Such revisions may also be necessary for other CRFs. Unlike previous studies, whose results are based primarily on a single recombination detection program, the current study was based on multiple recombination analysis, which may have produced more impartial results.Representative references of 3 categories of intersubtype recombinants were selected, including BC recombinants (CRF07 and CRF08, BG recombinants (CRF23 and CRF24, and BF recombinants (CRF38 and CRF44. They were reanalyzed in detail using both the jumping profile hidden Markov model and RDP3.The results indicate that revisions and upgrades are very necessary and the entire re-analysis suggested 2 types of revision: (i length of inserted fragments; and (ii number of inserted fragments. The reanalysis also indicated that determination of small regions of about 200 bases or fewer should be performed with more caution.Results indicated that the involvement of multiple recombination detection programs is very necessary. Additionally, results suggested two major challenges, one involving the difficulty of accurately determining the locations of breakpoints and the second involving identification of small regions of about 200 bases or fewer with greater caution. Both indicate the complexity of HIV-1 recombination. The resolution would depend critically on development of a recombination analysis algorithm, accumulation of HIV-1 stains, and a higher sequencing quality. With the changes in recombination pattern, phylogenetic relationships of some CRFs may also change. All these results may

  7. Frequent intra-subtype recombination among HIV-1 circulating in Tanzania.

    Ireen E Kiwelu

    Full Text Available The study estimated the prevalence of HIV-1 intra-subtype recombinant variants among female bar and hotel workers in Tanzania. While intra-subtype recombination occurs in HIV-1, it is generally underestimated. HIV-1 env gp120 V1-C5 quasispecies from 45 subjects were generated by single-genome amplification and sequencing (median (IQR of 38 (28-50 sequences per subject. Recombination analysis was performed using seven methods implemented within the recombination detection program version 3, RDP3. HIV-1 sequences were considered recombinant if recombination signals were detected by at least three methods with p-values of ≤0.05 after Bonferroni correction for multiple comparisons. HIV-1 in 38 (84% subjects showed evidence for intra-subtype recombination including 22 with HIV-1 subtype A1, 13 with HIV-1 subtype C, and 3 with HIV-1 subtype D. The distribution of intra-patient recombination breakpoints suggested ongoing recombination and showed selective enrichment of recombinant variants in 23 (60% subjects. The number of subjects with evidence of intra-subtype recombination increased from 29 (69% to 36 (82% over one year of follow-up, although the increase did not reach statistical significance. Adjustment for intra-subtype recombination is important for the analysis of multiplicity of HIV infection. This is the first report of high prevalence of intra-subtype recombination in the HIV/AIDS epidemic in Tanzania, a region where multiple HIV-1 subtypes co-circulate. HIV-1 intra-subtype recombination increases viral diversity and presents additional challenges for HIV-1 vaccine design.

  8. Recombinant Vaccinia Virus: Immunization against Multiple Pathogens

    Perkus, Marion E.; Piccini, Antonia; Lipinskas, Bernard R.; Paoletti, Enzo

    1985-09-01

    The coding sequences for the hepatitis B virus surface antigen, the herpes simplex virus glycoprotein D, and the influenza virus hemagglutinin were inserted into a single vaccinia virus genome. Rabbits inoculated intravenously or intradermally with this polyvalent vaccinia virus recombinant produced antibodies reactive to all three authentic foreign antigens. In addition, the feasibility of multiple rounds of vaccination with recombinant vaccinia virus was demonstrated.

  9. Recombination of Globally Circulating Varicella-Zoster Virus

    Depledge, Daniel P.; Kundu, Samit; Atkinson, Claire; Brown, Julianne; Haque, Tanzina; Hussaini, Yusuf; MacMahon, Eithne; Molyneaux, Pamela; Papaevangelou, Vassiliki; Sengupta, Nitu; Koay, Evelyn S. C.; Tang, Julian W.; Underhill, Gillian S.; Grahn, Anna; Studahl, Marie; Breuer, Judith; Bergström, Tomas

    2015-01-01

    ABSTRACT Varicella-zoster virus (VZV) is a human herpesvirus, which during primary infection typically causes varicella (chicken pox) and establishes lifelong latency in sensory and autonomic ganglia. Later in life, the virus may reactivate to cause herpes zoster (HZ; also known as shingles). To prevent these diseases, a live-attenuated heterogeneous vaccine preparation, vOka, is used routinely in many countries worldwide. Recent studies of another alphaherpesvirus, infectious laryngotracheitis virus, demonstrate that live-attenuated vaccine strains can recombine in vivo, creating virulent progeny. These findings raised concerns about using attenuated herpesvirus vaccines under conditions that favor recombination. To investigate whether VZV may undergo recombination, which is a prerequisite for VZV vaccination to create such conditions, we here analyzed 115 complete VZV genomes. Our results demonstrate that recombination occurs frequently for VZV. It thus seems that VZV is fully capable of recombination if given the opportunity, which may have important implications for continued VZV vaccination. Although no interclade vaccine-wild-type recombinant strains were found, intraclade recombinants were frequently detected in clade 2, which harbors the vaccine strains, suggesting that the vaccine strains have already been involved in recombination events, either in vivo or in vitro during passages in cell culture. Finally, previous partial and complete genomic studies have described strains that do not cluster phylogenetically to any of the five established clades. The additional VZV strains sequenced here, in combination with those previously published, have enabled us to formally define a novel sixth VZV clade. IMPORTANCE Although genetic recombination has been demonstrated to frequently occur for other human alphaherpesviruses, herpes simplex viruses 1 and 2, only a few ancient and isolated recent recombination events have hitherto been demonstrated for VZV. In the

  10. Recombination among multiple mitochondrial pseudogenes from a passerine genus

    Nielsen, Kirstine Klitgaard; Arctander, P.

    2001-01-01

    to the observed differences in substitution patterns 58% of the cloned sequences were identified as pseudogenes. Recombination could be traced in 19% of the inferred nuclear pseudogenes, but this figure probably represents a Significant underestimation of the factual recombination events. The nonrecombined...... pseudogenes consisted of multiple haplotypes found to diverge from 1 to 16% from the mitochondrial gene. The number of mitochondrial nuclear copies and their apparent frequent recombination suggest that pseudogenes constitute a serious potential risk in confounding phylogenetic studies and population genetic...

  11. Circulating autoantibodies to recombinant lipocortin-1 in asthma.

    Chung, K F; Podgorski, M R; Goulding, N J; Godolphin, J L; Sharland, P R; O'Connor, B; Flower, R J; Barnes, P J

    1991-03-01

    One of the postulated mechanisms of corticosteroid action is through the de novo synthesis and release of lipocortins. We assayed circulating antibodies to lipocortin-1 in sera obtained from normal (n = 67) and asthmatic (n = 57) subjects using an ELISA technique. Asthmatic subjects with a wide range of severity, with the mildest needing only occasional inhaled beta-agonist therapy to the most severe needing maintenance oral corticosteroid treatment, were recruited from our Asthma Clinic and classified into five categories according to the need of therapy. Median values of IgM and IgG lipocortin-1 antibody for normal subjects were 19.3 (interquartile range (r) = 11.0-30.4) and 16.9 (r = 10.54-29.4) ELISA units (EU) ml-1 respectively. These levels were significantly elevated in asthmatic subjects: IgM = 43.9 EU ml-1 (r = 31.7-64.5) and IgG = 29.0 EU ml-1 (r = 21.2-44.7) (P less than 0.001). There was no significant relationship between the levels of lipocortin antibody and the clinical severity of asthma. Asthmatics with significantly raised levels of antibody were found within all five categories of severity. We conclude that the level of this antibody is not related to severity of asthma, to previous or current corticosteroid therapy or to the development of corticosteroid resistance.

  12. Multiple barriers to recombination between divergent HIV-1 variants revealed by a dual-marker recombination assay

    Nikolaitchik, Olga A; Galli, Andrea; Moore, Michael D

    2011-01-01

    Recombination is a major force for generating human immunodeficiency virus type 1 (HIV-1) diversity and produces numerous recombinants circulating in the human population. We previously established a cell-based system using green fluorescent protein gene (gfp) as a reporter to study the mechanisms...... of HIV-1 recombination. We now report an improved system capable of detecting recombination using authentic viral sequences. Frameshift mutations were introduced into the gag gene so that parental viruses do not express full-length Gag; however, recombination can generate a progeny virus that expresses...

  13. Multiple states in the late Eocene ocean circulation

    Baatsen, M. L. J.; von der Heydt, A. S.; Kliphuis, M.; Viebahn, J.; Dijkstra, H. A.

    2018-04-01

    The Eocene-Oligocene Transition (EOT) marks a major step within the Cenozoic climate in going from a greenhouse into an icehouse state, with the formation of a continental-scale Antarctic ice sheet. The roles of steadily decreasing CO2 concentrations versus changes in ocean circulation at the EOT are still debated and the threshold for Antarctic glaciation is obscured by uncertainties in global geometry. Here, a detailed study of the late Eocene ocean circulation is carried out using an ocean general circulation model under two slightly different geography reconstructions of the middle-to-late Eocene (38 Ma). Using the same atmospheric forcing, both geographies give a profoundly different equilibrium ocean circulation state. The underlying reason for this sensitivity is the presence of multiple equilibria characterised by either North or South Pacific deep water formation. A possible shift from a southern towards a northern overturning circulation would result in significant changes in the global heat distribution and consequently make the Southern Hemisphere climate more susceptible for significant cooling and ice sheet formation on Antarctica.

  14. Emergence of recombinant forms in geographic regions with co-circulating HIV subtypes in the dynamic HIV-1 epidemic

    Zhang, Ming [Los Alamos National Laboratory; Letiner, Thomas K [Los Alamos National Laboratory; Korber, Bette T [Los Alamos National Laboratory; Foley, Brian [Los Alamos National Laboratory

    2009-01-01

    We have reexamined the subtype designations of {approx}10,000 subtype A, B, C, G, and AG, BC, BF recombinant sequences, and compared the results of the new analysis with their published designations. Intersubtype recombinants dominate HIV epidemics in three different geographical regions. The circulating recombinant from (CRF) CRF02-AG, common in West Central Africa, appears to result from a recombination event that occurred early in the divergence between subtypes A and G, although additional more recent recombination events may have contributed to the breakpoint pattern in this recombinant lineage as well. The Chinese recombinant epidemic strains CRF07 and CRF08, in contrast, result from recent recombinations between more contemporary strains. Nevertheless, CRF07 and CRF08 contributed to many subsequent recombination events. The BF recombinant epidemics in two HIV-1 epicenters in South America are not independent and BF epidemics in South America have an unusually high fraction of unique recombinant forms (URFs) that have each been found only once and carry distinctive breakpoints. Taken together, these analyses reveal a complex and dynamic picture of the current HIV-1 epidemic, and suggest a means of grouping and tracking relationships between viruses through preservation of shared breakpints.

  15. The Mutational Landscape of Circulating Tumor Cells in Multiple Myeloma

    Yuji Mishima

    2017-04-01

    Full Text Available The development of sensitive and non-invasive “liquid biopsies” presents new opportunities for longitudinal monitoring of tumor dissemination and clonal evolution. The number of circulating tumor cells (CTCs is prognostic in multiple myeloma (MM, but there is little information on their genetic features. Here, we have analyzed the genomic landscape of CTCs from 29 MM patients, including eight cases with matched/paired bone marrow (BM tumor cells. Our results show that 100% of clonal mutations in patient BM were detected in CTCs and that 99% of clonal mutations in CTCs were present in BM MM. These include typical driver mutations in MM such as in KRAS, NRAS, or BRAF. These data suggest that BM and CTC samples have similar clonal structures, as discordances between the two were restricted to subclonal mutations. Accordingly, our results pave the way for potentially less invasive mutation screening of MM patients through characterization of CTCs.

  16. Molecular Evolution of a Type 1 Wild-Vaccine Poliovirus Recombinant during Widespread Circulation in China

    Liu, Hong-Mei; Zheng, Du-Ping; Zhang, Li-Bi; Oberste, M. Steven; Pallansch, Mark A.; Kew, Olen M.

    2000-01-01

    Type 1 wild-vaccine recombinant polioviruses were isolated from poliomyelitis patients in China from 1991 to 1993. We compared the sequences of 34 recombinant isolates over the 1,353-nucleotide (nt) genomic interval (nt 2480 to 3832) encoding the major capsid protein, VP1, and the protease, 2A. All recombinants had a 367-nt block of sequence (nt 3271 to 3637) derived from the Sabin 1 oral poliovirus vaccine strain spanning the 3′-terminal sequences of VP1 (115 nt) and the 5′ half of 2A (252 nt). The remaining VP1 sequences were closely (up to 99.5%) related to those of a major genotype of wild type 1 poliovirus endemic to China up to 1994. In contrast, the non-vaccine-derived sequences at the 3′ half of 2A were more distantly related (polioviruses from China. The vaccine-derived sequences of the earliest (April 1991) isolates completely matched those of Sabin 1. Later isolates diverged from the early isolates primarily by accumulation of synonymous base substitutions (at a rate of ∼3.7 × 10−2 substitutions per synonymous site per year) over the entire VP1-2A interval. Distinct evolutionary lineages were found in different Chinese provinces. From the combined epidemiologic and evolutionary analyses, we propose that the recombinant virus arose during mixed infection of a single individual in northern China in early 1991 and that its progeny spread by multiple independent chains of transmission into some of the most populous areas of China within a year of the initiating infection. PMID:11070012

  17. Characterization and frequency of a newly identified HIV-1 BF1 intersubtype circulating recombinant form in São Paulo, Brazil

    Neto Walter

    2010-04-01

    Full Text Available Abstract Background HIV circulating recombinant forms (CRFs play an important role in the global and regional HIV epidemics, particularly in regions where multiple subtypes are circulating. To date, several (>40 CRFs are recognized worldwide with five currently circulating in Brazil. Here, we report the characterization of near full-length genome sequences (NFLG of six phylogenetically related HIV-1 BF1 intersubtype recombinants (five from this study and one from other published sequences representing CRF46_BF1. Methods Initially, we selected 36 samples from 888 adult patients residing in São Paulo who had previously been diagnosed as being infected with subclade F1 based on pol subgenomic fragment sequencing. Proviral DNA integrated in peripheral blood mononuclear cells (PBMC was amplified from the purified genomic DNA of all 36-blood samples by five overlapping PCR fragments followed by direct sequencing. Sequence data were obtained from the five fragments that showed identical genomic structure and phylogenetic trees were constructed and compared with previously published sequences. Genuine subclade F1 sequences and any other sequences that exhibited unique mosaic structures were omitted from further analysis Results Of the 36 samples analyzed, only six sequences, inferred from the pol region as subclade F1, displayed BF1 identical mosaic genomes with a single intersubtype breakpoint identified at the nef-U3 overlap (HXB2 position 9347-9365; LTR region. Five of these isolates formed a rigid cluster in phylogentic trees from different subclade F1 fragment regions, which we can now designate as CRF46_BF1. According to our estimate, the new CRF accounts for 0.56% of the HIV-1 circulating strains in São Paulo. Comparison with previously published sequences revealed an additional five isolates that share an identical mosaic structure with those reported in our study. Despite sharing a similar recombinant structure, only one sequence appeared to

  18. Detection and Characterization of Circulating Tumour Cells in Multiple Myeloma

    Liangxuan Zhang

    2016-06-01

    Full Text Available Multiple myeloma (MM remains an incurable disease despite recent therapeutic improvements. The ability to detect and characterize MM circulating tumour cells (CTCs in peripheral blood provides an alternative to replace or augment invasive bone marrow (BM biopsies with a simple blood draw, providing real-time, clinically relevant information leading to improved disease manage‐ ment and therapy selection. Here we have developed and qualified an enrichment-free, cell-based immunofluores‐ cence MM CTC assay that utilizes an automated digital pathology algorithm to distinguish MM CTCs from white blood cells (WBCs on the basis of CD138 and CD45 expression levels, as well as a number of morphological parameters. These MM CTCs were further characterized for expression of phospho-ribosomal protein S6 (pS6 as a readout for PI3K/AKT pathway activation. Clinical feasi‐ bility of the assay was established by testing blood samples from a small cohort of patients, where we detected popu‐ lations of both CD138pos and CD138neg MM CTCs. In this study, we developed an immunofluorescent cell-based assay to detect and characterize CTCs in MM.

  19. Detection and Characterization of Circulating Tumour Cells in Multiple Myeloma

    Liangxuan Zhang

    2016-01-01

    Full Text Available Multiple myeloma (MM remains an incurable disease despite recent therapeutic improvements. The ability to detect and characterize MM circulating tumour cells (CTCs in peripheral blood provides an alternative to replace or augment invasive bone marrow (BM biopsies with a simple blood draw, providing real-time, clinically relevant information leading to improved disease management and therapy selection. Here we have developed and qualified an enrichment-free, cell-based immunofluorescence MM CTC assay that utilizes an automated digital pathology algorithm to distinguish MM CTCs from white blood cells (WBCs on the basis of CD138 and CD45 expression levels, as well as a number of morphological parameters. These MM CTCs were further characterized for expression of phospho-ribosomal protein S6 (pS6 as a readout for PI3K/AKT pathway activation. Clinical feasibility of the assay was established by testing blood samples from a small cohort of patients, where we detected populations of both CD138 pos and CD138 neg MM CTCs. In this study, we developed an immunofluorescent cell-based assay to detect and characterize CTCs in MM.

  20. Molecular study of Porcine Circovirus type 2 in wild boars and domestic pigs in Uruguay from 2010 to 2014: Predominance of recombinant circulating strains.

    Ramos, Natalia; Porley, Dario; Mirazo, Santiago; Castro, Gustavo; Cabrera, Karina; Lozano, Alejandra; Arbiza, Juan

    2017-12-30

    Porcine Circovirus type 2 (PCV2) is a worldwide distributed pathogen and one of the most economically relevant swine infections. Four genotypes have been recognized and it is well known that PCV2a, PCV2b and PCV2d have a global distribution. However, the information about recombinant strains circulation and their influence in driving PCV2 evolution is a poorly studied area. In Uruguay, PCV2 associated symptoms began to be frequently observed in pigs from different farms since 2010. The main purpose of this study was to thoroughly investigate the molecular epidemiology of PCV2 in nationwide swine herds and free-living wild boars during the period 2010-2014, providing an extensive viral sequence dataset. Surprisingly, the findings revealed a predominance of recombinant strains circulation, evidencing for the first time in the field that PCV2 recombination can lead to the emergence of strains able to compete and potentially displace parental ones. In addition, the circulation of the genotypes PCV2d (29%), PCV2b (10.5%) and PCV2a (7.9%) were also observed. Since 2013, a high circulation of PCV2d was identified in the country and probably reflected the recent global scenario of the emergence of this genotype. In addition, fluctuations in the frequency of PCV2 infection in the period evaluated may suggest a limitation of biosecurity strategies implemented in Uruguay for the disease control, including the instability of vaccination practices. On the other hand, the sustained PCV2 infection observed in wild boar population and the similarity among circulating viral strains from these animals and domestic pigs, suggested that wild animals could serve as permanent reservoir of the disease. Altogether, this work put forward that many factors play a role in PCV2 heterogeneity including rapid viral spread and evolution, recombination, wide movement within national boundaries and multiples introduction events resulting of international trade. Continuous monitoring of viral

  1. Characterization of recombination features and the genetic basis in multiple cattle breeds.

    Shen, Botong; Jiang, Jicai; Seroussi, Eyal; Liu, George E; Ma, Li

    2018-04-27

    Crossover generated by meiotic recombination is a fundamental event that facilitates meiosis and sexual reproduction. Comparative studies have shown wide variation in recombination rate among species, but the characterization of recombination features between cattle breeds has not yet been performed. Cattle populations in North America count millions, and the dairy industry has genotyped millions of individuals with pedigree information that provide a unique opportunity to study breed-level variations in recombination. Based on large pedigrees of Jersey, Ayrshire and Brown Swiss cattle with genotype data, we identified over 3.4 million maternal and paternal crossover events from 161,309 three-generation families. We constructed six breed- and sex-specific genome-wide recombination maps using 58,982 autosomal SNPs for two sexes in the three dairy cattle breeds. A comparative analysis of the six recombination maps revealed similar global recombination patterns between cattle breeds but with significant differences between sexes. We confirmed that male recombination map is 10% longer than the female map in all three cattle breeds, consistent with previously reported results in Holstein cattle. When comparing recombination hotspot regions between cattle breeds, we found that 30% and 10% of the hotspots were shared between breeds in males and females, respectively, with each breed exhibiting some breed-specific hotspots. Finally, our multiple-breed GWAS found that SNPs in eight loci affected recombination rate and that the PRDM9 gene associated with hotspot usage in multiple cattle breeds, indicating a shared genetic basis for recombination across dairy cattle breeds. Collectively, our results generated breed- and sex-specific recombination maps for multiple cattle breeds, provided a comprehensive characterization and comparison of recombination patterns between breeds, and expanded our understanding of the breed-level variations in recombination features within an

  2. Recombiner

    Kikuchi, Nobuo.

    1983-01-01

    Purpose: To shorten the pre-heating time for a recombiner and obtain a uniform temperature distribution for the charged catalyst layer in a BWR type reactor. Constitution: A pre-heating heater is disposed to the outer periphery of a vessel for a recombiner packed with catalysts for recombining hydrogen and oxygen in gases flowing through a radioactive gaseous wastes processing system. Heat pipes for transmitting the heat applied to said container to the catalyst are disposed vertically and horizontally within the container. Different length of the heat pipes are combined. In this way, pre-heating time for the recombiner before the operation start and before the system switching can be shortened and the uniform pre-heating for the inside of the recombiner is also made possible. Further, heater control in the pre-heating can be carried out effectively and with ease. (Moriyama, K.)

  3. Recombiner

    Osumi, Morimichi.

    1979-01-01

    Purpose: To provide a recombiner which is capable of converting hydrogen gas into water by use of high-frequency heating at comparatively low temperatures and is safe and cheap in cost. Constitution: Hydrogen gas is introduced from an outer pipeline to the main structure of a recombiner, and when it passes through the vicinity of the central part of the recombiner, it is reacted with copper oxide (CuO 2 ) heated to a temperature more than 300 0 C by a high-frequency heater, and converted gently into water by reduction operation (2H 2 + CuO 2 → Cu + 2H 2 O). The thus prepared water is exhausted through the outer pipeline to a suppression pool. A part of hydrogen gas which has not been converted completely into water by the reaction and is remaining as hydrogen is recovered through exhaust nozzles and again introduced into the main structure of the recombiner. (Yoshino, Y.)

  4. Genetic Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF74_01B) Identified among Intravenous Drug Users in Malaysia: Recombination History and Phylogenetic Linkage with Previously Defined Recombinant Lineages.

    Cheong, Hui Ting; Chow, Wei Zhen; Takebe, Yutaka; Chook, Jack Bee; Chan, Kok Gan; Al-Darraji, Haider Abdulrazzaq Abed; Koh, Clayton; Kamarulzaman, Adeeba; Tee, Kok Keng

    2015-01-01

    In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs). Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs), especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B' that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the region.

  5. Genetic Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF74_01B Identified among Intravenous Drug Users in Malaysia: Recombination History and Phylogenetic Linkage with Previously Defined Recombinant Lineages.

    Hui Ting Cheong

    Full Text Available In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs. Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs, especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B' that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the region.

  6. Recombinant alpha-interferon as salvage therapy in multiple myeloma

    1989-08-05

    Aug 5, 1989 ... Ten patients with end-stage multiple myeloma refractory to conventional chemotherapy and ... malities and relief of pain using local radiotherapy. However, .... therapy programmes. However, the role of this agent remains.

  7. [Genetic recombination in vaccine poliovirus: comparative study in strains excreted in course of vaccination by oral poliovirus vaccine and circulating strains].

    Haddad-Boubaker, S; Ould-Mohamed-Abdallah, M V; Ben-Yahia, A; Triki, H

    2010-12-01

    Recombination is one of the major mechanisms of evolution in poliovirus. In this work, recombination was assessed in children during vaccination with OPV and among circulating vaccine strains isolated in Tunisia during the last 15 years in order to identify a possible role of recombination in the response to the vaccine or the acquisition of an increased transmissibility. This study included 250 poliovirus isolates: 137 vaccine isolates, excreted by children during primary vaccination with OPV and 113 isolates obtained from acute flaccid paralytic (AFP) cases and healthy contacts. Recombination was first assessed using a double PCR-RFLP, and sequencing. Nineteen per cent of recombinant strains were identified: 20% of strains excreted by vaccinees among 18% of circulating strains. The proportion of recombinant in isolates of serotype1 was very low in the two groups while the proportions of recombinants in serotypes 2 and 3 were different. In vaccinees, the frequency of recombinants in serotype3 decreased during the course of vaccination: 54% after the first dose, 32% after the second and 14% after the third dose. These results suggest that recombination enhances the ability of serotype3 vaccine strains to induce an immune response. Apart from recent vaccination, it may contribute to a more effective transmissibility of vaccine strains among human population. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

  8. Recombination in liquid filled ionisation chambers with multiple charge carrier species: Theoretical and numerical results

    Aguiar, P.; González-Castaño, D.M.; Gómez, F.; Pardo-Montero, J.

    2014-01-01

    Liquid-filled ionisation chambers (LICs) are used in radiotherapy for dosimetry and quality assurance. Volume recombination can be quite important in LICs for moderate dose rates, causing non-linearities in the dose rate response of these detectors, and needs to be corrected for. This effect is usually described with Greening and Boag models for continuous and pulsed radiation respectively. Such models assume that the charge is carried by two different species, positive and negative ions, each of those species with a given mobility. However, LICs operating in non-ultrapure mode can contain different types of electronegative impurities with different mobilities, thus increasing the number of different charge carriers. If this is the case, Greening and Boag models can be no longer valid and need to be reformulated. In this work we present a theoretical and numerical study of volume recombination in parallel-plate LICs with multiple charge carrier species, extending Boag and Greening models. Results from a recent publication that reported three different mobilities in an isooctane-filled LIC have been used to study the effect of extra carrier species on recombination. We have found that in pulsed beams the inclusion of extra mobilities does not affect volume recombination much, a behaviour that was expected because Boag formula for charge collection efficiency does not depend on the mobilities of the charge carriers if the Debye relationship between mobilities and recombination constant holds. This is not the case in continuous radiation, where the presence of extra charge carrier species significantly affects the amount of volume recombination. - Highlights: • Analytical extension of Greening and Boag theories to multiple charge carriers. • Detailed numerical study of process of volume recombination in LICs. • Recombination in pulsed beams is independent of number and mobilities of carriers. • Multiple charge carriers have a significant effect in continuous

  9. Recombiner

    Saalfrank, H.

    1985-01-01

    Air containing hydrogen can be oxidized by heating in a container called a recombiner, in order to avoid the collection of hydrogen. The container is long and a large number of straight heating bars are arranged in parallel in it and they are flanged to a lid. The heating bars are surrounded by tubes, in order to obtain good heat transfer by a narrow annular gap. (orig.) [de

  10. Phylogenetic and molecular epidemiological studies reveal evidence of multiple past recombination events between infectious laryngotracheitis viruses.

    Sang-Won Lee

    Full Text Available In contrast to the RNA viruses, the genome of large DNA viruses such as herpesviruses have been considered to be relatively stable. Intra-specific recombination has been proposed as an important, but underestimated, driving force in herpesvirus evolution. Recently, two distinct field strains of infectious laryngotracheitis virus (ILTV have been shown to have arisen from independent recombination events between different commercial ILTV vaccines. In this study we sequenced the genomes of additional ILTV strains and also utilized other recently updated complete genome sequences of ILTV to confirm the existence of a number of ILTV recombinants in nature. Multiple recombination events were detected in the unique long and repeat regions of the genome, but not in the unique short region. Most recombinants contained a pair of crossover points between two distinct lineages of ILTV, corresponding to the European origin and the Australian origin vaccine strains of ILTV. These results suggest that there are two distinct genotypic lineages of ILTV and that these commonly recombine in the field.

  11. Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia.

    Sabir, Jamal S M; Lam, Tommy T-Y; Ahmed, Mohamed M M; Li, Lifeng; Shen, Yongyi; Abo-Aba, Salah E M; Qureshi, Muhammd I; Abu-Zeid, Mohamed; Zhang, Yu; Khiyami, Mohammad A; Alharbi, Njud S; Hajrah, Nahid H; Sabir, Meshaal J; Mutwakil, Mohammed H Z; Kabli, Saleh A; Alsulaimany, Faten A S; Obaid, Abdullah Y; Zhou, Boping; Smith, David K; Holmes, Edward C; Zhu, Huachen; Guan, Yi

    2016-01-01

    Outbreaks of Middle East respiratory syndrome (MERS) raise questions about the prevalence and evolution of the MERS coronavirus (CoV) in its animal reservoir. Our surveillance in Saudi Arabia in 2014 and 2015 showed that viruses of the MERS-CoV species and a human CoV 229E-related lineage co-circulated at high prevalence, with frequent co-infections in the upper respiratory tract of dromedary camels. viruses of the betacoronavirus 1 species, we found that dromedary camels share three CoV species with humans. Several MERS-CoV lineages were present in camels, including a recombinant lineage that has been dominant since December 2014 and that subsequently led to the human outbreaks in 2015. Camels therefore serve as an important reservoir for the maintenance and diversification of the MERS-CoVs and are the source of human infections with this virus. Copyright © 2016, American Association for the Advancement of Science.

  12. Recombination events and variability among full-length genomes of co-circulating molluscum contagiosum virus subtypes 1 and 2.

    López-Bueno, Alberto; Parras-Moltó, Marcos; López-Barrantes, Olivia; Belda, Sylvia; Alejo, Alí

    2017-05-01

    Molluscum contagiosum virus (MCV) is the sole member of the Molluscipoxvirus genus and causes a highly prevalent human disease of the skin characterized by the formation of a variable number of lesions that can persist for prolonged periods of time. Two major genotypes, subtype 1 and subtype 2, are recognized, although currently only a single complete genomic sequence corresponding to MCV subtype 1 is available. Using next-generation sequencing techniques, we report the complete genomic sequence of four new MCV isolates, including the first one derived from a subtype 2. Comparisons suggest a relatively distant evolutionary split between both MCV subtypes. Further, our data illustrate concurrent circulation of distinct viruses within a population and reveal the existence of recombination events among them. These results help identify a set of MCV genes with potentially relevant roles in molluscum contagiosum epidemiology and pathogenesis.

  13. Multiple recombinants in two dengue virus, serotype-2 isolates from patients from Oaxaca, Mexico.

    Perez-Ramirez, Gerardo; Diaz-Badillo, Alvaro; Camacho-Nuez, Minerva; Cisneros, Alejandro; Munoz, Maria de Lourdes

    2009-12-15

    Dengue (DEN) is a serious cause of mortality and morbidity in the world including Mexico, where the infection is endemic. One of the states with the highest rate of dengue cases is Oaxaca. The cause of DEN is a positive-sense RNA virus, the dengue virus (DENV) that evolves rapidly increasing its variability due to the absence of a repair mechanism that leads to approximately one mutational event per genome replication; which results in enhancement of viral adaptation, including the escape from host immune responses. Additionally, recombination may play a role in driving the evolution of DENV, which may potentially affect virulence and cause host tropism changes. Recombination in DENV has not been described in Mexican strains, neither has been described the relevance in virus evolution in an endemic state such as Oaxaca where the four serotypes of DENV are circulating. To study whether there are isolates from Oaxaca having recombination, we obtained the sequence of 6 different isolates of DENV-2 Asian/American genotype from the outbreak 2005-6, one clone of the C(91)-prM-E-NS1(2400) structural genes, and 10 clones of the E gene from the isolate MEX_OAX_1656_05. Evidence of recombination was found by using different methods along with two softwares: RDP3 and GARD. The Oaxaca MEX_OAX_1656_05 and MEX_OAX_1038_05 isolates sequenced in this study were recombinant viruses that incorporate the genome sequence from the Cosmopolitan genotype. Furthermore, the clone of the E gene namely MEX_OAX_165607_05 from this study was also recombinant, incorporating genome sequence from the American genotype. This is the first report of recombination in DENV-2 in Mexico. Given such a recombinant activity new genomic combinations were produced, this could play a significant role in the DENV evolution and must be considered as a potentially important mechanism generating genetic variation in this virus with serious implications for the vaccines and drugs formulation as occurs for other

  14. Multiple recombinants in two dengue virus, serotype-2 isolates from patients from Oaxaca, Mexico

    Cisneros Alejandro

    2009-12-01

    Full Text Available Abstract Background Dengue (DEN is a serious cause of mortality and morbidity in the world including Mexico, where the infection is endemic. One of the states with the highest rate of dengue cases is Oaxaca. The cause of DEN is a positive-sense RNA virus, the dengue virus (DENV that evolves rapidly increasing its variability due to the absence of a repair mechanism that leads to approximately one mutational event per genome replication; which results in enhancement of viral adaptation, including the escape from host immune responses. Additionally, recombination may play a role in driving the evolution of DENV, which may potentially affect virulence and cause host tropism changes. Recombination in DENV has not been described in Mexican strains, neither has been described the relevance in virus evolution in an endemic state such as Oaxaca where the four serotypes of DENV are circulating. Results To study whether there are isolates from Oaxaca having recombination, we obtained the sequence of 6 different isolates of DENV-2 Asian/American genotype from the outbreak 2005-6, one clone of the C(91-prM-E-NS1(2400 structural genes, and 10 clones of the E gene from the isolate MEX_OAX_1656_05. Evidence of recombination was found by using different methods along with two softwares: RDP3 and GARD. The Oaxaca MEX_OAX_1656_05 and MEX_OAX_1038_05 isolates sequenced in this study were recombinant viruses that incorporate the genome sequence from the Cosmopolitan genotype. Furthermore, the clone of the E gene namely MEX_OAX_165607_05 from this study was also recombinant, incorporating genome sequence from the American genotype. Conclusions This is the first report of recombination in DENV-2 in Mexico. Given such a recombinant activity new genomic combinations were produced, this could play a significant role in the DENV evolution and must be considered as a potentially important mechanism generating genetic variation in this virus with serious implications for

  15. Importation and co-circulation of multiple serotypes of dengue virus in Sarawak, Malaysia.

    Holmes, Edward C; Tio, Phaik-Hooi; Perera, David; Muhi, Jamail; Cardosa, Jane

    2009-07-01

    Although dengue is a common disease in South-East Asia, there is a marked absence of virological data from the Malaysian state of Sarawak located on the island of Borneo. From 1997 to 2002 we noted the co-circulation of DENV-2, DENV-3 and DENV-4 in Sarawak. To determine the origins of these Sarawak viruses we obtained the complete E gene sequences of 21 isolates. A phylogenetic analysis revealed multiple entries of DENV-2 and DENV-4 into Sarawak, such that multiple lineages co-circulate, yet with little exportation from Sarawak. Notably, all viral isolates were most closely related to those circulating in different localities in South-East Asia. In sum, our analysis reveals a frequent traffic of DENV in South-East Asia, with Sarawak representing a local sink population.

  16. Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution

    Aachmann-Andersen, Niels Jacob; Just Christensen, Søren; Lisbjerg, Kristian

    2014-01-01

    The membrane-assisted isoform immunoassay (MAIIA) quantitates erythropoietin (EPO) isoforms as percentages of migrated isoforms (PMI). We evaluated the effect of recombinant human EPO (rhEPO) on the distribution of EPO isoforms in plasma in a randomized, placebo-controlled, double-blinded, cross......-over study. 16 healthy subjects received either low-dose Epoetin beta (5000 IU on days 1, 3, 5, 7, 9, 11 and 13); high-dose Epoetin beta (30.000 IU on days 1, 2 and 3 and placebo on days 5, 7, 9, 11 and 13); or placebo on all days. PMI on days 4, 11 and 25 was determined by interaction of N......-acetyl glucosamine with the glycosylation dependent desorption of EPO isoforms. At day 25, plasma-EPO in both rhEPO groups had returned to values not different from the placebo group. PMI with placebo, reflecting the endogenous EPO isoforms, averaged 82.5 (10.3) % (mean (SD)). High-dose Epoetin beta decreased PMI...

  17. Fourteen types of co-circulating recombinant enterovirus were associated with hand, foot, and mouth disease in children from Wenzhou, China.

    Guo, Wen-Ping; Lin, Xian-Dan; Chen, Yi-Ping; Liu, Qi; Wang, Wen; Wang, Cai-Qiao; Li, Ming-Hui; Sun, Xiao-Yu; Shi, Mang; Holmes, Edward C; Zhang, Yong-Zhen

    2015-09-01

    Although hand, foot, and mouth disease (HFMD) is a major public concern in China, the prevalence and clinical symptoms associated with the different agents of HFMD in this country remain poorly understood. We investigated the clinical and molecular characteristics of enteroviruses in patients with HFMD from Wenzhou, China. Patients with laboratory-confirmed HFMD admitted to the Yuying Children's Hospital in Wenzhou, China during 2013 were included in this study. Viral RNA sequences were amplified using RT-PCR, determined by sequencing, and compared by phylogenetic analysis. A total of 955 clinically diagnosed HFMD cases were determined using PCR, with whole viral genomes obtained for each enterovirus type. 14 types of enterovirus belonging to two viral species were identified. Notably, Coxsackievirus A6 (CV-A6) was the most common species detected (77.8%), followed by EV-A71 (8.2%) and CV-A10 (8.1%). Phylogenetic analysis revealed multiple independent introductions of these viruses into Wenzhou. In addition, the enterovirus observed in Wenzhou had a recombinant history, with two or three recombination breakpoints. Although the illness associated with CV-A6 was milder than that of EV-A71, CV-A6 infection caused more widespread rash, larger blisters, and subsequent skin peeling and/or nail shedding. Our study revealed the co-circulation of 14 types of enteroviruses in a single location - Wenzhou, China - with CV-A6 virus the predominant agent of HFMD. This work highlights the need to perform larger-scale surveillance to fully understand the epidemiology of enteroviruses in China and the wider Asia-Pacific region. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution.

    Niels Jacob Aachmann-Andersen

    Full Text Available The membrane-assisted isoform immunoassay (MAIIA quantitates erythropoietin (EPO isoforms as percentages of migrated isoforms (PMI. We evaluated the effect of recombinant human EPO (rhEPO on the distribution of EPO isoforms in plasma in a randomized, placebo-controlled, double-blinded, cross-over study. 16 healthy subjects received either low-dose Epoetin beta (5000 IU on days 1, 3, 5, 7, 9, 11 and 13; high-dose Epoetin beta (30.000 IU on days 1, 2 and 3 and placebo on days 5, 7, 9, 11 and 13; or placebo on all days. PMI on days 4, 11 and 25 was determined by interaction of N-acetyl glucosamine with the glycosylation dependent desorption of EPO isoforms. At day 25, plasma-EPO in both rhEPO groups had returned to values not different from the placebo group. PMI with placebo, reflecting the endogenous EPO isoforms, averaged 82.5 (10.3 % (mean (SD. High-dose Epoetin beta decreased PMI on days 4 and 11 to 31.0 (4.2% (p<0.00001 and 45.2 (7.3% (p<0.00001. Low-dose Epoetin beta decreased PMI on days 4 and 11 to 46.0 (12.8% (p<0.00001 and 46.1 (10.4% (p<0.00001. In both rhEPO groups, PMI on day 25 was still decreased (high-dose Epoetin beta: 72.9 (19.4% (p=0.029; low-dose Epoetin beta: 73.1 (17.8% (p=0.039. In conclusion, Epoetin beta leaves a footprint in the plasma-EPO isoform pattern. MAIIA can detect changes in EPO isoform distribution up til at least three weeks after administration of Epoetin beta even though the total EPO concentration has returned to normal.

  19. Recombinant Goose Circoviruses Circulating in Domesticated and Wild Geese in Poland

    Tomasz Stenzel

    2018-03-01

    Full Text Available Circoviruses are circular single-stranded DNA (ssDNA viruses that infect a variety of animals, both domestic and wild. Circovirus infection in birds is associated with immunosuppression and this in turn predisposes the infected animals to secondary infections that can lead to mortality. Farmed geese (Anser anser in many parts of the world are infected with circoviruses. The majority of the current genomic information for goose circoviruses (GoCVs (n = 40 are from birds sampled in China and Taiwan, and only two genome sequences are available from Europe (Germany and Poland. In this study, we sampled 23 wild and 19 domestic geese from the Gopło Lake area in Poland. We determined the genomes of GoCV from 21 geese; 14 domestic Greylag geese (Anser anser, three wild Greylag geese (A. anser, three bean geese (A. fabalis, and one white fronted goose (A. albifrons. These genomes share 83–95% nucleotide pairwise identities with previously identified GoCV genomes, most are recombinants with exchanged fragment sizes up to 50% of the genome. Higher diversity levels can be seen within the genomes from domestic geese compared with those from wild geese. In the GoCV capsid protein (cp and replication associated protein (rep gene sequences we found that episodic positive selection appears to largely mirror those of beak and feather disease virus and pigeon circovirus. Analysis of the secondary structure of the ssDNA genome revealed a conserved stem-loop structure with the G-C rich stem having a high degree of negative selection on these nucleotides.

  20. Production of Mucosally Transmissible SHIV Challenge Stocks from HIV-1 Circulating Recombinant Form 01_AE env Sequences.

    Lawrence J Tartaglia

    2016-02-01

    Full Text Available Simian-human immunodeficiency virus (SHIV challenge stocks are critical for preclinical testing of vaccines, antibodies, and other interventions aimed to prevent HIV-1. A major unmet need for the field has been the lack of a SHIV challenge stock expressing circulating recombinant form 01_AE (CRF01_AE env sequences. We therefore sought to develop mucosally transmissible SHIV challenge stocks containing HIV-1 CRF01_AE env derived from acutely HIV-1 infected individuals from Thailand. SHIV-AE6, SHIV-AE6RM, and SHIV-AE16 contained env sequences that were >99% identical to the original HIV-1 isolate and did not require in vivo passaging. These viruses exhibited CCR5 tropism and displayed a tier 2 neutralization phenotype. These challenge stocks efficiently infected rhesus monkeys by the intrarectal route, replicated to high levels during acute infection, and established chronic viremia in a subset of animals. SHIV-AE16 was titrated for use in single, high dose as well as repetitive, low dose intrarectal challenge studies. These SHIV challenge stocks should facilitate the preclinical evaluation of vaccines, monoclonal antibodies, and other interventions targeted at preventing HIV-1 CRF01_AE infection.

  1. A BAC-bacterial recombination method to generate physically linked multiple gene reporter DNA constructs

    Gong Shiaochin

    2009-03-01

    Full Text Available Abstract Background Reporter gene mice are valuable animal models for biological research providing a gene expression readout that can contribute to cellular characterization within the context of a developmental process. With the advancement of bacterial recombination techniques to engineer reporter gene constructs from BAC genomic clones and the generation of optically distinguishable fluorescent protein reporter genes, there is an unprecedented capability to engineer more informative transgenic reporter mouse models relative to what has been traditionally available. Results We demonstrate here our first effort on the development of a three stage bacterial recombination strategy to physically link multiple genes together with their respective fluorescent protein (FP reporters in one DNA fragment. This strategy uses bacterial recombination techniques to: (1 subclone genes of interest into BAC linking vectors, (2 insert desired reporter genes into respective genes and (3 link different gene-reporters together. As proof of concept, we have generated a single DNA fragment containing the genes Trap, Dmp1, and Ibsp driving the expression of ECFP, mCherry, and Topaz FP reporter genes, respectively. Using this DNA construct, we have successfully generated transgenic reporter mice that retain two to three gene readouts. Conclusion The three stage methodology to link multiple genes with their respective fluorescent protein reporter works with reasonable efficiency. Moreover, gene linkage allows for their common chromosomal integration into a single locus. However, the testing of this multi-reporter DNA construct by transgenesis does suggest that the linkage of two different genes together, despite their large size, can still create a positional effect. We believe that gene choice, genomic DNA fragment size and the presence of endogenous insulator elements are critical variables.

  2. A BAC-bacterial recombination method to generate physically linked multiple gene reporter DNA constructs.

    Maye, Peter; Stover, Mary Louise; Liu, Yaling; Rowe, David W; Gong, Shiaochin; Lichtler, Alexander C

    2009-03-13

    Reporter gene mice are valuable animal models for biological research providing a gene expression readout that can contribute to cellular characterization within the context of a developmental process. With the advancement of bacterial recombination techniques to engineer reporter gene constructs from BAC genomic clones and the generation of optically distinguishable fluorescent protein reporter genes, there is an unprecedented capability to engineer more informative transgenic reporter mouse models relative to what has been traditionally available. We demonstrate here our first effort on the development of a three stage bacterial recombination strategy to physically link multiple genes together with their respective fluorescent protein (FP) reporters in one DNA fragment. This strategy uses bacterial recombination techniques to: (1) subclone genes of interest into BAC linking vectors, (2) insert desired reporter genes into respective genes and (3) link different gene-reporters together. As proof of concept, we have generated a single DNA fragment containing the genes Trap, Dmp1, and Ibsp driving the expression of ECFP, mCherry, and Topaz FP reporter genes, respectively. Using this DNA construct, we have successfully generated transgenic reporter mice that retain two to three gene readouts. The three stage methodology to link multiple genes with their respective fluorescent protein reporter works with reasonable efficiency. Moreover, gene linkage allows for their common chromosomal integration into a single locus. However, the testing of this multi-reporter DNA construct by transgenesis does suggest that the linkage of two different genes together, despite their large size, can still create a positional effect. We believe that gene choice, genomic DNA fragment size and the presence of endogenous insulator elements are critical variables.

  3. Increasing airline travel may facilitate co-circulation of multiple dengue virus serotypes in Asia.

    Tian, Huaiyu; Sun, Zhe; Faria, Nuno Rodrigues; Yang, Jing; Cazelles, Bernard; Huang, Shanqian; Xu, Bo; Yang, Qiqi; Pybus, Oliver G; Xu, Bing

    2017-08-01

    The incidence of dengue has grown dramatically in recent decades worldwide, especially in Southeast Asia and the Americas with substantial transmission in 2014-2015. Yet the mechanisms underlying the spatio-temporal circulation of dengue virus (DENV) serotypes at large geographical scales remain elusive. Here we investigate the co-circulation in Asia of DENV serotypes 1-3 from 1956 to 2015, using a statistical framework that jointly estimates migration history and quantifies potential predictors of viral spatial diffusion, including socio-economic, air transportation and maritime mobility data. We find that the spread of DENV-1, -2 and -3 lineages in Asia is significantly associated with air traffic. Our analyses suggest the network centrality of air traffic hubs such as Thailand and India contribute to seeding dengue epidemics, whilst China, Cambodia, Indonesia, and Singapore may establish viral diffusion links with multiple countries in Asia. Phylogeographic reconstructions help to explain how growing air transportation networks could influence the dynamics of DENV circulation.

  4. Increasing airline travel may facilitate co-circulation of multiple dengue virus serotypes in Asia.

    Huaiyu Tian

    2017-08-01

    Full Text Available The incidence of dengue has grown dramatically in recent decades worldwide, especially in Southeast Asia and the Americas with substantial transmission in 2014-2015. Yet the mechanisms underlying the spatio-temporal circulation of dengue virus (DENV serotypes at large geographical scales remain elusive. Here we investigate the co-circulation in Asia of DENV serotypes 1-3 from 1956 to 2015, using a statistical framework that jointly estimates migration history and quantifies potential predictors of viral spatial diffusion, including socio-economic, air transportation and maritime mobility data. We find that the spread of DENV-1, -2 and -3 lineages in Asia is significantly associated with air traffic. Our analyses suggest the network centrality of air traffic hubs such as Thailand and India contribute to seeding dengue epidemics, whilst China, Cambodia, Indonesia, and Singapore may establish viral diffusion links with multiple countries in Asia. Phylogeographic reconstructions help to explain how growing air transportation networks could influence the dynamics of DENV circulation.

  5. Microsurgical treatment of carotid-ophthalmic aneurysm associated with multiple anterior and posterior circulation aneurysms

    Wang, Jiantao; Kan, Zhisheng; Wang, Shuo

    2017-01-01

    Abstract Background: The clipping of multiple intracranial aneurysms in 1 stage is uncommon. In this case, we report clipping of an ophthalmic aneurysm associated with multiple anterior and posterior circulation aneurysms via the Dolenc approach. Methods: The main symptoms of the patient are headache, along with nausea and vomiting. The patient's arteriogram revealed a wide-necked aneurysm of the right ophthalmic artery, an irregular aneurysm of the anterior communicating artery, and a basilar artery aneurysm. The surgical intervention for these aneurysms is a challenge because of the complex anatomical relationship with the surrounding structures. The 3 aneurysms, which were not amenable to a single intervention, were successfully clipped in 1 incision. Results: After surgery, the patient reported feeling well. One year after surgery, the patient had no SAH recurrence. Conclusions: Occasionally, surgical treatment was used even for aneurysms of the carotid-ophthalmic artery with aneurysms of anterior communicating artery and basilar artery, which are contraindicated for interventional therapy. PMID:28422878

  6. Deleting multiple lytic genes enhances biomass yield and production of recombinant proteins by Bacillus subtilis.

    Wang, Yi; Chen, Zhenmin; Zhao, Ruili; Jin, Tingting; Zhang, Xiaoming; Chen, Xiangdong

    2014-08-31

    Bacillus subtilis is widely used in agriculture and industrial biotechnology; however, cell autolysis significantly decreases its yield in liquid cultures. Numerous factors mediate the lysis of B. subtilis, such as cannibalism factors, prophages, and peptidoglycan (PG) hydrolases. The aim of this work was to use molecular genetic techniques to develop a new strategy to prevent cell lysis and enhance biomass as well as the production of recombinant proteins. Five genes or genetic elements representing three different functional categories were studied as follows: lytC encoding PG hydrolases, the prophage genes xpf and yqxG-yqxH-cwlA (yGlA), and skfA and sdpC that encode cannibalism factors. Cell lysis was reduced and biomass was enhanced by deleting individually skfA, sdpC, xpf, and lytC. We constructed the multiple deletion mutant LM2531 (skfA sdpC lytC xpf) and found that after 4 h of culture, its biomass yield was significantly increased compared with that of prototypical B. subtilis 168 (wild-type) strain and that 15% and 92% of the cells were lysed in cultures of LM2531 and wild-type, respectively. Moreover, two expression vectors were constructed for producing recombinant proteins (β-galactosidase and nattokinase) under the control of the P43 promoter. Cultures of LM2531 and wild-type transformants produced 13741 U/ml and 7991 U/ml of intracellular β-galactosidase, respectively (1.72-fold increase). Further, the level of secreted nattokinase produced by strain LM2531 increased by 2.6-fold compared with wild-type (5226 IU/ml vs. 2028 IU/ml, respectively). Our novel, systematic multigene deletion approach designed to inhibit cell lysis significantly increased the biomass yield and the production of recombinant proteins by B. subtilis. These findings show promise for guiding efforts to manipulate the genomes of other B. subtilis strains that are used for industrial purposes.

  7. Monoclonal antibodies and recombinant immunoglobulins for the treatment of multiple sclerosis.

    Gensicke, Henrik; Leppert, David; Yaldizli, Özgür; Lindberg, Raija L P; Mehling, Matthias; Kappos, Ludwig; Kuhle, Jens

    2012-01-01

    Multiple sclerosis (MS) is an inflammatory and degenerative disease leading to demyelination and axonal damage in the CNS. Autoimmunity plays a central role in MS pathogenesis. Per definition, monoclonal antibodies are recombinant biological compounds with a well defined target, thus carrying the promise of targeting pathogenic cells or molecules with high specificity, avoiding undesired off-target effects. Natalizumab was the first monoclonal antibody to be approved for the treatment of MS. Several other monoclonal antibodies are in development and have demonstrated promising efficacy in phase II studies. They can be categorized according to their mode of action into compounds targeting (i) leukocyte migration into the CNS (natalizumab); (ii) cytolytic antibodies (rituximab, ocrelizumab, ofatumumab, alemtuzumab); or (iii) antibodies and recombinant proteins targeting cytokines and chemokines and their receptors (daclizumab, ustekinumab, atacicept, tabalumab [Ly-2127399], secukinumab [AIN457]). In this review, we discuss the specific molecular targets, clinical efficacy and safety of these compounds and discuss criteria to anticipate the position of monoclonal antibodies in the diversifying armamentarium of MS therapy in the coming years.

  8. Prognostic impact of circulating plasma cells in patients with multiple myeloma: implications for plasma cell leukemia definition.

    Granell, Miquel; Calvo, Xavier; Garcia-Guiñón, Antoni; Escoda, Lourdes; Abella, Eugènia; Martínez, Clara Mª; Teixidó, Montserrat; Gimenez, Mª Teresa; Senín, Alicia; Sanz, Patricia; Campoy, Desirée; Vicent, Ana; Arenillas, Leonor; Rosiñol, Laura; Sierra, Jorge; Bladé, Joan; de Larrea, Carlos Fernández

    2017-06-01

    The presence of circulating plasma cells in patients with multiple myeloma is considered a marker for highly proliferative disease. In the study herein, the impact of circulating plasma cells assessed by cytology on survival of patients with multiple myeloma was analyzed. Wright-Giemsa stained peripheral blood smears of 482 patients with newly diagnosed myeloma or plasma cell leukemia were reviewed and patients were classified into 4 categories according to the percentage of circulating plasma cells: 0%, 1-4%, 5-20%, and plasma cell leukemia with the following frequencies: 382 (79.2%), 83 (17.2%), 12 (2.5%) and 5 (1.0%), respectively. Median overall survival according to the circulating plasma cells group was 47, 50, 6 and 14 months, respectively. At multivariate analysis, the presence of 5 to 20% circulating plasma cells was associated with a worse overall survival (relative risk 4.9, 95% CI 2.6-9.3) independently of age, creatinine, the Durie-Salmon system stage and the International Staging System (ISS) stage. Patients with ≥5% circulating plasma cells had lower platelet counts (median 86×10 9 /L vs 214×10 9 /L, P <0.0001) and higher bone marrow plasma cells (median 53% vs 36%, P =0.004). The presence of ≥5% circulating plasma cells in patients with multiple myeloma has a similar adverse prognostic impact as plasma cell leukemia. Copyright© Ferrata Storti Foundation.

  9. Co-Circulation and Genomic Recombination of Coxsackievirus A16 and Enterovirus 71 during a Large Outbreak of Hand, Foot, and Mouth Disease in Central China

    Liu, Weiyong; Wu, Shimin; Xiong, Ying; Li, Tongya; Wen, Zhou; Yan, Mingzhe; Qin, Kai; Liu, Yingle; Wu, Jianguo

    2014-01-01

    A total of 1844 patients with hand, foot, and mouth disease (HFMD), most of them were children of age 1–3-year-old, in Central China were hospitalized from 2011 to 2012. Among them, 422 were infected with coxsackievirus A16 (CVA16), 334 were infected with enterovirus 71 (EV71), 38 were co-infected with EV71 and CVA16, and 35 were infected with other enteroviruses. Molecular epidemiology analysis revealed that EV71 and CVA16 were detected year-round, but EV71 circulated mainly in July and CVA16 circulated predominantly in November, and incidence of HFMD was reduced in January and February and increased in March. Clinical data showed that hyperglycemia and neurologic complications were significantly higher in EV71-infected patients, while upper respiratory tract infection and C-reactive protein were significantly higher in CVA16-associated patients. 124 EV71 and 80 CVA16 strains were isolated, among them 56 and 68 EV71 strains were C4a and C4b, while 25 and 55 CVA16 strains were B1a and B1b, respectively. Similarity plots and bootscan analyses based on entire genomic sequences revealed that the three C4a sub-genotype EV71 strains were recombinant with C4b sub-genotype EV71 in 2B–2C region, and the three CVA16 strains were recombinant with EV71 in 2A–2B region. Thus, CVA16 and EV71 were the major causative agents in a large HFMD outbreak in Central China. HFMD incidence was high for children among household contact and was detected year-round, but outbreak was seasonal dependent. CVA16 B1b and EV71 C4b reemerged and caused a large epidemic in China after a quiet period of many years. Moreover, EV71 and CVA16 were co-circulated during the outbreak, which may have contributed to the genomic recombination between the pathogens. It should gain more attention as there may be an upward trend in co-circulation of the two pathogens globally and the new role recombination plays in the emergence of new enterovirus variants. PMID:24776922

  10. Co-circulation and genomic recombination of coxsackievirus A16 and enterovirus 71 during a large outbreak of hand, foot, and mouth disease in Central China.

    Weiyong Liu

    Full Text Available A total of 1844 patients with hand, foot, and mouth disease (HFMD, most of them were children of age 1-3-year-old, in Central China were hospitalized from 2011 to 2012. Among them, 422 were infected with coxsackievirus A16 (CVA16, 334 were infected with enterovirus 71 (EV71, 38 were co-infected with EV71 and CVA16, and 35 were infected with other enteroviruses. Molecular epidemiology analysis revealed that EV71 and CVA16 were detected year-round, but EV71 circulated mainly in July and CVA16 circulated predominantly in November, and incidence of HFMD was reduced in January and February and increased in March. Clinical data showed that hyperglycemia and neurologic complications were significantly higher in EV71-infected patients, while upper respiratory tract infection and C-reactive protein were significantly higher in CVA16-associated patients. 124 EV71 and 80 CVA16 strains were isolated, among them 56 and 68 EV71 strains were C4a and C4b, while 25 and 55 CVA16 strains were B1a and B1b, respectively. Similarity plots and bootscan analyses based on entire genomic sequences revealed that the three C4a sub-genotype EV71 strains were recombinant with C4b sub-genotype EV71 in 2B-2C region, and the three CVA16 strains were recombinant with EV71 in 2A-2B region. Thus, CVA16 and EV71 were the major causative agents in a large HFMD outbreak in Central China. HFMD incidence was high for children among household contact and was detected year-round, but outbreak was seasonal dependent. CVA16 B1b and EV71 C4b reemerged and caused a large epidemic in China after a quiet period of many years. Moreover, EV71 and CVA16 were co-circulated during the outbreak, which may have contributed to the genomic recombination between the pathogens. It should gain more attention as there may be an upward trend in co-circulation of the two pathogens globally and the new role recombination plays in the emergence of new enterovirus variants.

  11. Interactions of Multiple Atmospheric Circulation Drive the Drought in Tarim River Basin

    Wu, Yong-Ping; Feng, Guo-Lin; Li, Bai-Lian

    2016-05-01

    Global warming is likely to cause overall drying of land surfaces and aridity increasing leading to expansion of dry climate zones. There is an increased risk of extremely arid environment and large deserts developed progressively in the central Asia. However, the key factors causing the drying in mid-Asia remain inconclusive. Here, we analyzed the relationship among precipitation, water vapor transportation in Tarim River Basin (TRB) and Multiple Atmospheric Circulation (MAC) to explore the mechanism of MAC driving the drying in TRB, through comparing MAC between abundant and scarce precipitation years. We found that Westerly Circulation (WC) and Asian Summer Monsoon (ASM) are likely to promote the precipitation respectively. Whereas, they not only have their own influence but also restrict each other and facilitate the forming of peculiar water vapor transport channel for TRB, which is probably to restrain the precipitation and its distribution pattern and accelerate the drying in this region. Our results enrich the findings on mechanisms of wet places becoming wetter while dry areas getting drier under the global warming.

  12. Application of Multiple-Population Genetic Algorithm in Optimizing the Train-Set Circulation Plan Problem

    Yu Zhou

    2017-01-01

    Full Text Available The train-set circulation plan problem (TCPP belongs to the rolling stock scheduling (RSS problem and is similar to the aircraft routing problem (ARP in airline operations and the vehicle routing problem (VRP in the logistics field. However, TCPP involves additional complexity due to the maintenance constraint of train-sets: train-sets must conduct maintenance tasks after running for a certain time and distance. The TCPP is nondeterministic polynomial hard (NP-hard. There is no available algorithm that can obtain the optimal global solution, and many factors such as the utilization mode and the maintenance mode impact the solution of the TCPP. This paper proposes a train-set circulation optimization model to minimize the total connection time and maintenance costs and describes the design of an efficient multiple-population genetic algorithm (MPGA to solve this model. A realistic high-speed railway (HSR case is selected to verify our model and algorithm, and, then, a comparison of different algorithms is carried out. Furthermore, a new maintenance mode is proposed, and related implementation requirements are discussed.

  13. BF integrase genes of HIV-1 circulating in São Paulo, Brazil, with a recurrent recombination region.

    Atila Iamarino

    Full Text Available Although some studies have shown diversity in HIV integrase (IN genes, none has focused particularly on the gene evolving in epidemics in the context of recombination. The IN gene in 157 HIV-1 integrase inhibitor-naïve patients from the São Paulo State, Brazil, were sequenced tallying 128 of subtype B (23 of which were found in non-B genomes, 17 of subtype F (8 of which were found in recombinant genomes, 11 integrases were BF recombinants, and 1 from subtype C. Crucially, we found that 4 BF recombinant viruses shared a recurrent recombination breakpoint region between positions 4900 and 4924 (relative to the HXB2 that includes 2 gRNA loops, where the RT may stutter. Since these recombinants had independent phylogenetic origin, we argue that these results suggest a possible recombination hotspot not observed so far in BF CRF in particular, or in any other HIV-1 CRF in general. Additionally, 40% of the drug-naïve and 45% of the drug-treated patients had at least 1 raltegravir (RAL or elvitegravir (EVG resistance-associated amino acid change, but no major resistance mutations were found, in line with other studies. Importantly, V151I was the most common minor resistance mutation among B, F, and BF IN genes. Most codon sites of the IN genes had higher rates of synonymous substitutions (dS indicative of a strong negative selection. Nevertheless, several codon sites mainly in the subtype B were found under positive selection. Consequently, we observed a higher genetic diversity in the B portions of the mosaics, possibly due to the more recent introduction of subtype F on top of an ongoing subtype B epidemics and a fast spread of subtype F alleles among the B population.

  14. Three novel, multiple recombinant types of species of human mastadenovirus D (HAdV-D 73, 74 & 75) isolated from diarrhoeal faeces of immunocompromised patients.

    Hage, Elias; Dhingra, Akshay; Liebert, Uwe G; Bergs, Sandra; Ganzenmueller, Tina; Heim, Albert

    2017-11-02

    Species D is the largest of the seven species of human mastadenoviruses (HAdV), but few of its multiple types are associated with asevere disease, e.g. epidemic keratoconjunctivitis. Many other types are hardly ever associated with significant diseases in immunocompetent patients, but have been isolated from the diarrhoeal faeces of terminal AIDS patients suggesting their role as opportunistic pathogens. Three novel HAdV-D strains were isolated from the faeces of three immunocompromised adult patients (clinical diagnoses: lymphoma, myelodysplastic syndrome and AIDS CDC3B, respectively). These strains were not typeable by imputed serology of the hexon and fibre gene and therefore complete genomic sequences were generated by next-generation sequencing (NGS). All three strains were multiple recombinants and fulfilled the criteria for designation as types 73, 74 and 75 with the penton/hexon/fibre genotype codes P67H45F27, P70H74F51 and P75H26F29, respectively. A novel genomic backbone and also a novel hexon neutralization epitope sequence were discovered in type 74, and a novel penton sequence in type 75. At the complete genome level, types 73, 74 and 75 were closely related neither to each other nor to type 70, which was previously isolated in the same region. However, these four HAdV-D types were closely related to each other in single genes and gene regions, e.g. penton, E1 and E4 due to recombination events in their phylogeny. In conclusion, regional co-circulation of opportunistic HAdV-D types facilitated co- and super-infections, which are essential for homologous recombination, and thus resulted in the evolution of novel genotypes by lateral gene transfer.

  15. Whole genome characterization of a novel porcine reproductive and respiratory syndrome virus 1 isolate: Genetic evidence for recombination between Amervac vaccine and circulating strains in mainland China.

    Chen, Nanhua; Liu, Qiaorong; Qiao, Mingming; Deng, Xiaoyu; Chen, Xizhao; Sun, Ming

    2017-10-01

    Genotype 1 porcine reproductive and respiratory syndrome virus (PRRSV 1) have been continuously isolated in China in recent years. Complete genome sequences of these isolates are important to investigate the prevalence and evolution of Chinese PRRSV 1. Herein, we describe the isolation of a novel PRRSV 1 isolate, denominated HLJB1, in the Heilongjiang province of China. Complete genome sequencing of HLJB1 showed that it shares 90.66% and 58.21% nucleotide identities with PRRSV 1 and 2 prototypic strains Lelystad virus and ATCC VR-2332, respectively. HLJB1 has a unique 5-amino-acid insertion in nsp2, which has never been described in other PRRSV 1 isolates. Whole genome-based phylogenetic analysis revealed that all Chinese PRRSV 1 isolates are clustered in pan-European subtype 1 and can be divided into four subgroups. HLJB1 resides in the subgroup of BJEU06-1-like isolates but is also closely related to the Amervac-like isolates. Additionally, recombination analyses suggested that HLJB1 is a recombinant from the Amervac vaccine and the BJEU06-1 isolate. To our best knowledge, our results provide the first genetic evidence for recombination between Amervac vaccine and circulating strains. These findings are also beneficial for studying the origin and evolution of PRRSV 1 in China. Copyright © 2017. Published by Elsevier B.V.

  16. Isolation and characterization of a replication-competent molecular clone of an HIV-1 circulating recombinant form (CRF33_01B.

    Kok Keng Tee

    Full Text Available A growing number of emerging HIV-1 recombinants classified as circulating recombinant forms (CRFs have been identified in Southeast Asia in recent years, establishing a molecular diversity of increasing complexity in the region. Here, we constructed a replication-competent HIV-1 clone for CRF33_01B (designated p05MYKL045.1, a newly identified recombinant comprised of CRF01_AE and subtype B. p05MYKL045.1 was reconstituted by cloning of the near full-length HIV-1 sequence from a newly-diagnosed individual presumably infected heterosexually in Kuala Lumpur, Malaysia. The chimeric clone, which contains the 5' LTR (long terminal repeat region of p93JP-NH1 (a previously isolated CRF01_AE infectious clone, showed robust viral replication in the human peripheral blood mononuclear cells. This clone demonstrated robust viral propagation and profound syncytium formation in CD4+, CXCR4-expressing human glioma NP-2 cells, indicating that p05MYKL045.1 is a CXCR4-using virus. Viral propagation, however, was not detected in various human T cell lines including MT-2, M8166, Sup-T1, H9, Jurkat, Molt-4 and PM1. p05MYKL045.1 appears to proliferate only in restricted host range, suggesting that unknown viral and/or cellular host factors may play a role in viral infectivity and replication in human T cell lines. Availability of a CRF33_01B molecular clone will be useful in facilitating the development of vaccine candidates that match the HIV-1 strains circulating in Southeast Asia.

  17. Dissection of Recombination Attributes for Multiple Maize Populations Using a Common SNP Assay

    Haiying Guan

    2017-11-01

    Full Text Available Recombination is a vital characteristic for quantitative trait loci mapping and breeding to enhance the yield potential of maize. However, recombination characteristics in globally used segregating populations have never been evaluated at similar genetic marker densities. This study aimed to divulge the characteristics of recombination events, recombinant chromosomal segments, and recombination frequency for four dissimilar populations. These populations were doubled haploid (DH, recombination inbred line (RIL, intermated B73xMo17 (IBM, and multi-parent advanced generation inter-cross (MAGIC, using the Illumina MaizeSNP50 BeadChip to provide markers. Our results revealed that the average number of recombination events was 16, 41, 72, and 86 per line in DH, RIL, IBM, and MAGIC populations, respectively. Accordingly, the average length of recombinant chromosomal segments was 84.8, 47.3, 29.2, and 20.4 Mb in DH, RIL, IBM, and MAGIC populations, respectively. Furtherly, the recombination frequency varied in different genomic regions and population types [DH (0–12.7 cM/Mb, RIL (0–15.5 cM/Mb, IBM (0–24.1 cM/Mb, MAGIC (0–42.3 cM/Mb]. Utilizing different sub-sets of lines, the recombination bin number and size were analyzed in each population. Additionally, different sub-sets of markers and lines were employed to estimate the recombination bin number and size via formulas for relationship in these populations. The relationship between recombination events and recombination bin length was also examined. Our results contribute to determining the most suitable number of genetic markers, lines in each population, and population type for successful mapping and breeding.

  18. Scavenging Circulating Mitochondrial DNA as a Potential Therapeutic Option for Multiple Organ Dysfunction in Trauma Hemorrhage.

    Aswani, Andrew; Manson, Joanna; Itagaki, Kiyoshi; Chiazza, Fausto; Collino, Massimo; Wupeng, Winston Liao; Chan, Tze Khee; Wong, W S Fred; Hauser, Carl J; Thiemermann, Chris; Brohi, Karim

    2018-01-01

    Trauma is a leading cause of death worldwide with 5.8 million deaths occurring yearly. Almost 40% of trauma deaths are due to bleeding and occur in the first few hours after injury. Of the remaining severely injured patients up to 25% develop a dysregulated immune response leading to multiple organ dysfunction syndrome (MODS). Despite improvements in trauma care, the morbidity and mortality of this condition remains very high. Massive traumatic injury can overwhelm endogenous homeostatic mechanisms even with prompt treatment. The underlying mechanisms driving MODS are also not fully elucidated. As a result, successful therapies for trauma-related MODS are lacking. Trauma causes tissue damage that releases a large number of endogenous damage-associated molecular patterns (DAMPs). Mitochondrial DAMPs released in trauma, such as mitochondrial DNA (mtDNA), could help to explain part of the immune response in trauma given the structural similarities between mitochondria and bacteria. MtDNA, like bacterial DNA, contains an abundance of highly stimulatory unmethylated CpG DNA motifs that signal through toll-like receptor-9 to produce inflammation. MtDNA has been shown to be highly damaging when injected into healthy animals causing acute organ injury to develop. Elevated circulating levels of mtDNA have been reported in trauma patients but an association with clinically meaningful outcomes has not been established in a large cohort. We aimed to determine whether mtDNA released after clinical trauma hemorrhage is sufficient for the development of MODS. Secondly, we aimed to determine the extent of mtDNA release with varying degrees of tissue injury and hemorrhagic shock in a clinically relevant rodent model. Our final aim was to determine whether neutralizing mtDNA with the nucleic acid scavenging polymer, hexadimethrine bromide (HDMBr), at a clinically relevant time point in vivo would reduce the severity of organ injury in this model. We have shown that the release of mt

  19. Scavenging Circulating Mitochondrial DNA as a Potential Therapeutic Option for Multiple Organ Dysfunction in Trauma Hemorrhage

    Andrew Aswani

    2018-05-01

    Full Text Available Trauma is a leading cause of death worldwide with 5.8 million deaths occurring yearly. Almost 40% of trauma deaths are due to bleeding and occur in the first few hours after injury. Of the remaining severely injured patients up to 25% develop a dysregulated immune response leading to multiple organ dysfunction syndrome (MODS. Despite improvements in trauma care, the morbidity and mortality of this condition remains very high. Massive traumatic injury can overwhelm endogenous homeostatic mechanisms even with prompt treatment. The underlying mechanisms driving MODS are also not fully elucidated. As a result, successful therapies for trauma-related MODS are lacking. Trauma causes tissue damage that releases a large number of endogenous damage-associated molecular patterns (DAMPs. Mitochondrial DAMPs released in trauma, such as mitochondrial DNA (mtDNA, could help to explain part of the immune response in trauma given the structural similarities between mitochondria and bacteria. MtDNA, like bacterial DNA, contains an abundance of highly stimulatory unmethylated CpG DNA motifs that signal through toll-like receptor-9 to produce inflammation. MtDNA has been shown to be highly damaging when injected into healthy animals causing acute organ injury to develop. Elevated circulating levels of mtDNA have been reported in trauma patients but an association with clinically meaningful outcomes has not been established in a large cohort. We aimed to determine whether mtDNA released after clinical trauma hemorrhage is sufficient for the development of MODS. Secondly, we aimed to determine the extent of mtDNA release with varying degrees of tissue injury and hemorrhagic shock in a clinically relevant rodent model. Our final aim was to determine whether neutralizing mtDNA with the nucleic acid scavenging polymer, hexadimethrine bromide (HDMBr, at a clinically relevant time point in vivo would reduce the severity of organ injury in this model. Conclusions: We have

  20. Circulating vitamin D binding protein levels are not associated with relapses or with vitamin D status in multiple sclerosis

    Smolders, J; Peelen, Evelyn; Thewissen, Mariëlle; Menheere, Paul; Damoiseaux, Jan; Hupperts, Raymond

    BACKGROUND: A low vitamin D status has been associated with multiple sclerosis (MS). Most circulating vitamin D metabolites are bound to vitamin D binding protein (DBP). OBJECTIVES: The purpose of this study was to explore whether there is an association between MS and DBP. METHODS: We compared DBP

  1. Development of a Recombination System for the Generation of Occlusion Positive Genetically Modified Anticarsia Gemmatalis Multiple Nucleopolyhedrovirus

    Santiago Haase

    2015-03-01

    Full Text Available Anticarsia gemmatalis is an important pest in legume crops in South America and it has been successfully controlled using Anticarsia gemmatalis Multiple Nucleopolyhedrovirus (AgMNPV in subtropical climate zones. Nevertheless, in temperate climates its speed of kill is too slow. Taking this into account, genetic modification of AgMNPV could lead to improvements of its biopesticidal properties. Here we report the generation of a two-component system that allows the production of recombinant AgMNPV. This system is based on a parental AgMNPV in which the polyhedrin gene (polh was replaced by a bacterial β-galactosidase (lacZ gene flanked by two target sites for the homing endonuclease I-PpoI. Co-transfection of insect cells with linearized (I-PpoI-digested parental genome and a transfer vector allowed the restitution of polh and the expression of a heterologous gene upon homologous recombination, with a low background of non-recombinant AgMNPV. The system was validated by constructing a recombinant occlusion-positive (polh+ AgMNPV expressing the green fluorescent protein gene (gfp. This recombinant virus infected larvae normally per os and led to the expression of GFP in cell culture as well as in A. gemmatalis larvae. These results demonstrate that the system is an efficient method for the generation of recombinant AgMNPV expressing heterologous genes, which can be used for manifold purposes, including biotechnological and pharmaceutical applications and the production of orally infectious recombinants with improved biopesticidal properties.

  2. Steady state flow analysis of two-phase natural circulation in multiple parallel channel loop

    Bhusare, V.H.; Bagul, R.K.; Joshi, J.B.; Nayak, A.K.; Kannan, Umasankari; Pilkhwal, D.S.; Vijayan, P.K.

    2016-01-01

    Highlights: • Liquid circulation velocity increases with increasing superficial gas velocity. • Total two-phase pressure drop decreases with increasing superficial gas velocity. • Channels with larger driving force have maximum circulation velocities. • Good agreement between experimental and model predictions. - Abstract: In this work, steady state flow analysis has been carried out experimentally in order to estimate the liquid circulation velocities and two-phase pressure drop in air–water multichannel circulating loop. Experiments were performed in 15 channel circulating loop. Single phase and two-phase pressure drops in the channels have been measured experimentally and have been compared with theoretical model of Joshi et al. (1990). Experimental measurements show good agreement with model.

  3. Smoking reduces circulating CD26hi CD161hi MAIT cells in healthy individuals and patients with multiple sclerosis

    Ammitzbøll, Cecilie; Börnsen, Lars; Romme Christensen, Jeppe

    2017-01-01

    Upon chronic cigarette smoke exposure, inhaled antigens and irritants cause altered lung immune homeostasis. Circulating immune cells are affected, and smoking is associated with an increased risk of developing various disorders, including multiple sclerosis (MS). This study was conducted......-induced proliferation and cytokine secretion in smokers and nonsmokers in a cohort of 100 healthy individuals (HI). In addition, we analyzed immune cell subsets associated with smoking in 2 independent cohorts of patients with MS. In HI smokers compared with nonsmokers, we found increased blood cell counts...... to determine the impact of smoking on circulating immune cell subsets. Furthermore, we determined whether any smoking-associated changes were related to MS. With the use of flow cytometry, CFSE assays, and ELISpot assays, we analyzed circulating immune cell phenotypes and quantified antigen...

  4. GroEL-GroES assisted folding of multiple recombinant proteins simultaneously over-expressed in Escherichia coli.

    Goyal, Megha; Chaudhuri, Tapan K

    2015-07-01

    Folding of aggregation prone recombinant proteins through co-expression of chaperonin GroEL and GroES has been a popular practice in the effort to optimize preparation of functional protein in Escherichia coli. Considering the demand for functional recombinant protein products, it is desirable to apply the chaperone assisted protein folding strategy for enhancing the yield of properly folded protein. Toward the same direction, it is also worth attempting folding of multiple recombinant proteins simultaneously over-expressed in E. coli through the assistance of co-expressed GroEL-ES. The genesis of this thinking was originated from the fact that cellular GroEL and GroES assist in the folding of several endogenous proteins expressed in the bacterial cell. Here we present the experimental findings from our study on co-expressed GroEL-GroES assisted folding of simultaneously over-expressed proteins maltodextrin glucosidase (MalZ) and yeast mitochondrial aconitase (mAco). Both proteins mentioned here are relatively larger and aggregation prone, mostly form inclusion bodies, and undergo GroEL-ES assisted folding in E. coli cells during over-expression. It has been reported that the relative yield of properly folded functional forms of MalZ and mAco with the exogenous GroEL-ES assistance were comparable with the results when these proteins were overexpressed alone. This observation is quite promising and highlights the fact that GroEL and GroES can assist in the folding of multiple substrate proteins simultaneously when over-expressed in E. coli. This method might be a potential tool for enhanced production of multiple functional recombinant proteins simultaneously in E. coli. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Strategies to obtain multiple recombinant modified vaccinia Ankara vectors. Applications to influenza vaccines.

    Barbieri, Andrea; Panigada, Maddalena; Soprana, Elisa; Di Mario, Giuseppina; Gubinelli, Francesco; Bernasconi, Valentina; Recagni, Marta; Donatelli, Isabella; Castrucci, Maria R; Siccardi, Antonio G

    2018-01-01

    As a vaccination vector, MVA has been widely investigated both in animal models and humans. The construction of recombinant MVA (rMVA) relies on homologous recombination between an acceptor virus and a donor plasmid in infected/transfected permissive cells. Our construction strategy "Red-to-Green gene swapping" - based on the exchange of two fluorescent markers within the flanking regions of MVA deletion ΔIII, coupled to fluorescence activated cell sorting - is here extended to a second insertion site, within the flanking regions of MVA deletion ΔVI. Exploiting this strategy, both double and triple rMVA were constructed, expressing as transgenes the influenza A proteins HA, NP, M1, and PB1. Upon validation of the harbored transgenes co-expression, double and triple recombinants rMVA(ΔIII)-NP-P2A-M1 and rMVA(ΔIII)-NP-P2A-M1-(ΔVI)-PB1 were assayed for in vivo immunogenicity and protection against lethal challenge. In vivo responses were identical to those obtained with the reported combinations of single recombinants, supporting the feasibility and reliability of the present improvement and the extension of Red-to-Green gene swapping to insertion sites other than ΔIII. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Risk group characteristics and viral transmission clusters in South-East Asian patients infected with HIV-1 circulating recombinant form (CRF)01_AE and subtype B

    Oyomopito, Rebecca A; Chen, Yen-Ju; Sungkanuparph, Somnuek; Kantor, Rami; Merati, Tuti; Yam, Wing-Cheong; Sirisanthana, Thira; Li, Patrick CK; Kantipong, Pacharee; Phanuphak, Praphan; Lee, Chris KC; Kamarulzaman, Adeeba; Ditangco, Rossana; Huang, Szu-Wei; Sohn, Annette H; Law, Matthew; Chen, Yi Ming A

    2016-01-01

    HIV-1 epidemics in Asian countries are driven by varying exposures. The epidemiology of the regional pandemic has been changing with the spread of HIV-1 to lower-risk populations through sexual transmission. Common HIV-1 genotypes include subtype B and circulating recombinant form (CRF)01_AE. Our objective was to use HIV-1 genotypic data to better quantify local epidemics. TASER-M is a multi-centre prospective cohort of HIV-infected patients. Associations between HIV-exposure, patient gender, country of sample origin and HIV-1 genotype were evaluated by multivariate logistic regression. Phylogenetic methods were used on genotypic data to investigate transmission relationships. A total of 1086 patients from Thailand, Hong Kong, Malaysia and the Philippines were included in analyses. Proportions of males within countries varied (Thailand: 55.6%, Hong Kong: 86.1%, Malaysia: 81.4%, Philippines: 93.8%; p Malaysia: 47.8%, Philippines: 25.0%; p <0.001). After adjustment, we found increased subtype B infection among men-who-have-sex with-men, relative to heterosexual-reported exposures (OR = 2.4, p <0.001). We further describe four transmission clusters of 8–15 treatment naive, predominantly symptomatic patients (two each for subtype B and CRF01_AE). Risk-group sub-populations differed with respect to the infecting HIV-1 genotype. Homosexual exposure patients had a higher odds of being infected with subtype B. Where HIV-1 genotypes circulate within countries or patient risk-groups, local monitoring of genotype-specific transmissions may play a role in focussing public health prevention strategies. Phylogenetic evaluations provide complementary information for surveillance and monitoring of viruses with high mutation rates such as HIV-1 and Ebola. PMID:26362956

  7. CIRCULATING ANTIBODIES TO ERYTHROPOIETIN ARE ASSOCIATED WITH LOWER EFFICACY OF RECOMBINANT EPOETIN TREATMENT IN PATIENTS UNDERGOING HAEMODIALYSIS

    V. D. Nazarov

    2018-01-01

    Full Text Available Biological preparations (BP obtained by gene engineering possess a special characteristic called immunogenicity, i.e. propensity of biological drugs to induce an undesired immune response associated with arising anti-drug antibodies. These antibodies can change BP pharmacokinetics and pharmacodynamics, and therapeutical efficacy. A significant proportion of hemodialysis patients with end-stage renal disease treated by recombinant erythropoietin (rEPO have clinical features of resistance to such therapy. The aim of the study was to investigate whether anti-rEPO antibodies are associated with hemoglobin concentrations (Hb and red blood cells counts (RBC in hemodialysis patients, receiving long-term rEPO therapy. This research was performed at the Research Institute of Nephrology at the First St. Petersburg I.Pavlov State Medical University. Thirty-seven hemodialysis patients (pts with end-stage renal disease and anemia treated with different rEPO formulations were included into the study. The patients were further divided into two groups: those with diminished and normal clinical response to rEPO therapy (DCR, n = 21 vs NCR group, n = 16, respectively. To determine threshold levels of antibodies to rEPO-beta (Roche, Switzerland we tested blood serum samples of 35 healthy blood donors who never received rEPO in the past. Concentration of antibodies was measured by means of dot-blot method. The threshold antibody concentrations were defined by measurement of anti-rEPO concentrations in 2-fold stepwise dilutions (1:10 to 1:200 of blood sera from 35 healthy donors .The threshold value for rEPO-binding antibodies was 20.27 µg/ml (95 CI%±0.43. Antibodies to rEPO were found in 54 % of serum samples in the patients. Anti-rEPO antibodies concentrations correlated with mean values of hemoglobin and erythrocyte counts over a period of 12-months for the entire group of hemodialysis patients (r = -0.368, p = 0.025 and r = -0.336, p = 0.042 respectively

  8. HIV-1 transmission between MSM and heterosexuals, and increasing proportions of circulating recombinant forms in the Nordic Countries

    Esbjörnsson, Joakim; Mild, Mattias; Audelin, Anne; Fonager, Jannik; Skar, Helena; Bruun Jørgensen, Louise; Liitsola, Kirsi; Björkman, Per; Bratt, Göran; Gisslén, Magnus; Sönnerborg, Anders; Nielsen, Claus; Medstrand, Patrik; Albert, Jan

    2016-01-01

    Increased knowledge about HIV-1 transmission dynamics in different transmission groups and geographical regions is fundamental for assessing and designing prevention efforts against HIV-1 spread. Since the first reported cases of HIV infection during the early 1980s, the HIV-1 epidemic in the Nordic countries has been dominated by HIV-1 subtype B and MSM transmission. HIV-1 pol sequences and clinical data of 51 per cent of all newly diagnosed HIV-1 infections in Sweden, Denmark, and Finland in the period 2000–2012 (N = 3,802) were analysed together with a large reference sequence dataset (N = 4,537) by trend analysis and phylogenetics. Analysis of the eight dominating subtypes and CRFs in the Nordic countries (A, B, C, D, G, CRF01_AE, CRF02_AG, and CRF06_cpx) showed that the subtype B proportion decreased while the CRF proportion increased over the study period. A majority (57 per cent) of the Nordic sequences formed transmission clusters, with evidence of mixing both geographically and between transmission groups. Detailed analyses showed multiple occasions of transmissions from MSM to heterosexuals and that active transmission clusters more often involved single than multiple Nordic countries. The strongest geographical link was between Denmark and Sweden. Finally, Denmark had a larger proportion of heterosexual domestic spread of HIV-1 subtype B (75 per cent) compared with Sweden (49 per cent) and Finland (57 per cent). We describe different HIV-1 transmission patterns between countries and transmission groups in a large geographical region. Our results may have implications for public health interventions in targeting HIV-1 transmission networks and identifying where to introduce such interventions. PMID:27774303

  9. Standardization and validation of a cytometric bead assay to assess antibodies to multiple Plasmodium falciparum recombinant antigens

    Ondigo Bartholomew N

    2012-12-01

    Full Text Available Abstract Background Multiplex cytometric bead assay (CBA have a number of advantages over ELISA for antibody testing, but little information is available on standardization and validation of antibody CBA to multiple Plasmodium falciparum antigens. The present study was set to determine optimal parameters for multiplex testing of antibodies to P. falciparum antigens, and to compare results of multiplex CBA to ELISA. Methods Antibodies to ten recombinant P. falciparum antigens were measured by CBA and ELISA in samples from 30 individuals from a malaria endemic area of Kenya and compared to known positive and negative control plasma samples. Optimal antigen amounts, monoplex vs multiplex testing, plasma dilution, optimal buffer, number of beads required were assessed for CBA testing, and results from CBA vs. ELISA testing were compared. Results Optimal amounts for CBA antibody testing differed according to antigen. Results for monoplex CBA testing correlated strongly with multiplex testing for all antigens (r = 0.88-0.99, P values from Conclusion With optimization, CBA may be the preferred method of testing for antibodies to P. falciparum antigens, as CBA can test for antibodies to multiple recombinant antigens from a single plasma sample and produces a greater range of values in positive samples and lower background readings for blank samples than ELISA.

  10. Circulating antibody to myelin basic protein in relapsing-remitting multiple sclerosis

    Biggins, J.A.; Taylor, A.; Caspary, E.A.

    1978-01-01

    Sera from multiple sclerosis patients with relapsing-remitting disease and normal subjects were tested for antibody to myelin basic protein by a sensitive radioimmunoassay. The results showed a marginally decreased titre in multiple sclerosis superimposed on a seasonal variation. There was no correlation with the clinical state of the patients. Results are discussed briefly in relation to humoral antibody function in multiple sclerosis and experimental autoimmune encephalitis. (author)

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

    Watanabe, Daisuke; Brockman, Mark A.; Ndung'u, Thumbi; Mathews, Lydia; Lucas, William T.; Murphy, Cynthia G.; Felber, Barbara K.; Pavlakis, George N.; Deluca, Neal A.; Knipe, David M.

    2007-01-01

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

  12. Effect of Natalizumab on Circulating CD4(+) T-Cells in Multiple Sclerosis

    Börnsen, Lars; Christensen, Jeppe Romme; Ratzer, Rikke

    2012-01-01

    in general or myelin-reactive T-cells in particular showed signs of increased immune activation. Furthermore we examined the effects of natalizumab on CD4(+) T-cell responses to myelin in vitro. Natalizumab-treated MS patients had significantly increased numbers of effector-memory T-cells in the blood. In T-cells......(HIGH) T-cells, in blood, and natalizumab decreased the expression of CD134 on MBP-reactive CD26(HIGH)CD4(+) T-cells in vitro. Otherwise CD4(+) T-cells from natalizumab-treated and untreated MS patients showed similar responses to MBP. In conclusion natalizumab treatment selectively increased...... transmigration of circulating immune-cells across the vascular endothelium into the CNS. Recent studies suggested that natalizumab treated MS patients have an increased T-cell pool in the blood compartment which may be selectively enriched in activated T-cells. Proposed causes are sequestration of activated T-cells...

  13. Multiple antigens of Yersinia pestis delivered by live recombinant attenuated Salmonella vaccine strains elicit protective immunity against plague.

    Sanapala, Shilpa; Rahav, Hannah; Patel, Hetal; Sun, Wei; Curtiss, Roy

    2016-05-05

    Based on our improved novel Salmonella vaccine delivery platform, we optimized the recombinant attenuated Salmonella typhimurium vaccine (RASV) χ12094 to deliver multiple Yersinia pestis antigens. These included LcrV196 (amino acids, 131-326), Psn encoded on pYA5383 and F1 encoded in the chromosome, their synthesis did not cause adverse effects on bacterial growth. Oral immunization with χ12094(pYA5383) simultaneously stimulated high antibody titers to LcrV, Psn and F1 in mice and presented complete protection against both subcutaneous (s.c.) and intranasal (i.n.) challenges with high lethal doses of Y. pestis CO92. Moreover, no deaths or other disease symptoms were observed in SCID mice orally immunized with χ12094(pYA5383) over a 60-day period. Therefore, the trivalent S. typhimurium-based live vaccine shows promise for a next-generation plague vaccine. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. A paclitaxel-loaded recombinant polypeptide nanoparticle outperforms Abraxane in multiple murine cancer models

    Bhattacharyya, Jayanta; Bellucci, Joseph J.; Weitzhandler, Isaac; McDaniel, Jonathan R.; Spasojevic, Ivan; Li, Xinghai; Lin, Chao-Chieh; Chi, Jen-Tsan Ashley; Chilkoti, Ashutosh

    2015-08-01

    Packaging clinically relevant hydrophobic drugs into a self-assembled nanoparticle can improve their aqueous solubility, plasma half-life, tumour-specific uptake and therapeutic potential. To this end, here we conjugated paclitaxel (PTX) to recombinant chimeric polypeptides (CPs) that spontaneously self-assemble into ~60 nm near-monodisperse nanoparticles that increased the systemic exposure of PTX by sevenfold compared with free drug and twofold compared with the Food and Drug Administration-approved taxane nanoformulation (Abraxane). The tumour uptake of the CP-PTX nanoparticle was fivefold greater than free drug and twofold greater than Abraxane. In a murine cancer model of human triple-negative breast cancer and prostate cancer, CP-PTX induced near-complete tumour regression after a single dose in both tumour models, whereas at the same dose, no mice treated with Abraxane survived for >80 days (breast) and 60 days (prostate), respectively. These results show that a molecularly engineered nanoparticle with precisely engineered design features outperforms Abraxane, the current gold standard for PTX delivery.

  15. Multiple disease resistance to fungal and oomycete pathogens using a recombinant inbred line population in pepper

    Incorporating disease resistance into cultivars is a primary focus of modern breeding programs. Resistance to pathogens is often introgressed from landrace or wild individuals with poor fruit quality into commercial-quality cultivars. Sites of multiple disease resistance (MDR) are regions or “hotspo...

  16. Circulating Extracellular Histones Are Clinically Relevant Mediators of Multiple Organ Injury.

    Kawai, Chihiro; Kotani, Hirokazu; Miyao, Masashi; Ishida, Tokiko; Jemail, Leila; Abiru, Hitoshi; Tamaki, Keiji

    2016-04-01

    Extracellular histones are a damage-associated molecular pattern (DAMP) involved in the pathogenesis of various diseases. The mechanisms of histone-mediated injury in certain organs have been extensively studied, but an understanding of the pathophysiological role of histone-mediated injury in multiple organ injury remains elusive. To elucidate this role, we systemically subjected C57BL/6 mice to various doses of histones and performed a chronological evaluation of the morphological and functional changes in the lungs, liver, and kidneys. Notably, histone administration ultimately led to death after a dose-dependent aggravation of multiple organ injury. In chronological studies, pulmonary and hepatic injuries occurred within 15 minutes, whereas renal injuries presented at a later phase, suggesting that susceptibility to extracellular histones varies among organs. Histones bound to pulmonary and hepatic endothelial cells immediately after administration, leading to endothelial damage, which could be ameliorated by pretreatment with heparin. Furthermore, release of another DAMP, high-mobility group protein box 1, followed the histone-induced tissue damage, and an antibody against the molecule ameliorated hepatic and renal failure in a late phase. These findings indicate that extracellular histones induce multiple organ injury in two progressive stages-direct injury to endothelial cells and the subsequent release of other DAMPs-and that combination therapies against extracellular histones and high-mobility group protein box 1 may be a promising strategy for treating multiple organ injury. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. Circulating Regulatory T-Cells in Monoclonal Gammopathies of Uncertain Significance and Multiple Myeloma: In Search of a Role

    Giovanni D’Arena

    2016-01-01

    Full Text Available The frequency and function of regulatory T-cells (Tregs in multiple myeloma (MM are still matter of debate. The percentage and absolute number of circulating Tregs (CD4+CD25+high  densityCD127-/low  density from 39 patients with untreated MM and 44 patients with monoclonal gammopathies of uncertain significance (MGUS were tested and compared with 20 healthy subjects as controls. The mean percentage number of circulating Tregs was 2.1%  ± 1.0 (range 0.75–6.1% in MM patients; 2.1%  ± 0.9 (range 0.3–4.4% in MGUS; and 1.5%  ± 0.4 (range 0.9–2.1% in controls (p ns. Mean absolute number of Tregs was 36.3/μL ± 23.7 (range 6.7–149/μL in MM; 38.8/μL ± 19.1 (range 4.3–87/μL in MGUS; and 39.4/μL ± 12.5 (range 18–63/μL in controls (p ns. After a median follow-up of 38 months, 5 MGUS and 2 smoldering MM (SMM transformed into overt MM; however Tregs number did not predict this evolution. With respect to MM patients and after a median follow-up of 33 months, Tregs did not show any significant correlation with main clinical and laboratory characteristics. Finally, from a functional point of view, Tregs displayed an effective suppressor function, irrespective of disease status. This study indicates that the number of circulating Tregs does not differ in different monoclonal gammopathies and normal subjects and do not correlate with clinical features of MM.

  18. Circulating CD4+CXCR5+ T cells contribute to proinflammatory responses in multiple ways in coronary artery disease.

    Ding, Ru; Gao, Wenwu; He, Zhiqing; Wu, Feng; Chu, Yang; Wu, Jie; Ma, Lan; Liang, Chun

    2017-11-01

    Coronary artery disease (CAD) is a common subtype of cardiovascular disease. The major contributing event is atherosclerosis, which is a progressive inflammatory condition resulting in the thickening of the arterial wall and the formation of atheromatous plaques. Recent evidence suggests that circulating CD4 + CXCR5 + T cells can contribute to inflammatory reactions. In this study, the frequency, phenotype, and function of circulating CD4 + CXCR5 + T cells in CAD patients were examined. Data showed that circulating CD4 + CXCR5 + T cells in CAD patients were enriched with a PD-1 + CCR7 - subset, which was previously identified as the most potent in B cell help. The CD4 + CXCR5 + T cells in CAD patients also secreted significantly higher levels of IFN-γ, IL-17A, and IL-21 than those from healthy controls. Depleting the PD-1 + population significantly reduced the cytokine secretion. Interestingly, the CD4 + CXCR5 + PD-1 - T cells significantly upregulated PD-1 following anti-CD3/CD28 or SEB stimulation. CD4 + CXCR5 + T cells from CAD patients also demonstrated more potent capacity to stimulate B cell inflammation than those from healthy individuals. The phosphorylation of STAT1 and STAT3 were significantly higher in B cells incubated with CD4 + CXCR5 + T cells from CAD than controls. The IL-6 and IFN-γ expression were also significantly higher in B cells incubated with CD4 + CXCR5 + T cells from CAD. Together, this study demonstrated that CAD patients presented a highly activated CD4 + CXCR5 + T cell subset that could contribute to proinflammatory responses in multiple ways. The possibility of using CD4 + CXCR5 + T cells as a therapeutic target should therefore be examined in CAD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Steam drum level dynamics in a multiple loop natural circulation system of a pressure-tube type boiling water reactor

    Jain, Vikas; Kulkarni, P.P.; Nayak, A.K.; Vijayan, P.K.; Saha, D.; Sinha, R.K.

    2011-01-01

    Highlights: → We have highlighted the problem of drum level dynamics in a multiple loop type NC system using RELAP5 code. → The need of interconnections in steam and liquid spaces close to drum is established. → The steam space interconnections equalize pressure and liquid space interconnections equalize level. → With this scheme, the system can withstand anomalous conditions. → However, the controller is found to be inevitable for inventory balance. - Abstract: Advanced Heavy Water Reactor (AHWR) is a pressure tube type boiling water reactor employing natural circulation as the mode of heat removal under all the operating conditions. Main heat transport system (MHTS) of AHWR is essentially a multi-loop natural circulation system with all the loops connected to each other. Each loop of MHTS has a steam drum that provides for gravity based steam-water separation. Steam drum level is a very critical parameter especially in multi-loop natural circulation systems as large departures from the set point may lead to ineffective separation of steam-water or may affect the driving head. However, such a system is susceptible to steam drum level anomalies under postulated asymmetrical operating conditions among the different quadrants of the core like feedwater flow distribution anomaly among the steam drums or power anomaly among the core quadrants. Analyses were carried out to probe such scenarios and unravel the underlying dynamics of steam drum level using system code RELAP5/Mod3.2. In addition, a scheme to obviate such problem in a passive manner without dependence on level controller was examined. It was concluded that steam drums need to be connected in the liquid as well as steam space to make the system tolerant to asymmetrical operating conditions.

  20. Multiple protein biomarker assessment for recombinant bovine somatotropin (rbST abuse in cattle.

    Susann K J Ludwig

    Full Text Available Biomarker profiling, as a rapid screening approach for detection of hormone abuse, requires well selected candidate biomarkers and a thorough in vivo biomarker evaluation as previously done for detection of growth hormone doping in athletes. The bovine equivalent of growth hormone, called recombinant bovine somatotropin (rbST is (illegally administered to enhance milk production in dairy cows. In this study, first a generic sample pre-treatment and 4-plex flow cytometric immunoassay (FCIA were developed for simultaneous measurement of four candidate biomarkers selected from literature: insulin-like growth factor 1 (IGF-1, its binding protein 2 (IGFBP2, osteocalcin and endogenously produced antibodies against rbST. Next, bovine serum samples from two extensive controlled rbST animal treatment studies were used for in vivo validation and biomarker evaluation. Finally, advanced statistic tools were tested for the assessment of biomarker combination quality aiming to correctly identify rbST-treated animals. The statistical prediction tool k-nearest neighbours using a combination of the biomarkers osteocalcin and endogenously produced antibodies against rbST proved to be very reliable and correctly predicted 95% of the treated samples starting from the second rbST injection until the end of the treatment period and even thereafter. With the same biomarker combination, only 12% of untreated animals appeared false-positive. This reliability meets the requirements of Commission Decision 2002/657/EC for screening methods in veterinary control. From the results of this multidisciplinary study, it is concluded that the osteocalcin - anti-rbST-antibodies combination represent fit-for-purpose biomarkers for screening of rbST abuse in dairy cattle and can be reliably measured in both the developed 4-plex FCIA as well as in a cost-effective 2-plex microsphere-based binding assay. This screening method can be incorporated in routine veterinary monitoring

  1. Mobilization of Neural Precursors in the Circulating Blood of Patients with Multiple Sclerosis

    2013-09-01

    Bongarzone ER. Expression of sonic hedgehog targeted genes in peripheral blood mononuclear cells of patients with multiple sclerosis. Society for...recovery in a rat spinal cord injury model. Spine (Phila Pa 1976) 34:249-254. Schwartz PH, Bryant PJ, Fuja TJ, Su H, O’Dowd DK, Klassen H (2003...Print Program#/Poster#: 322.13 Presentation Title: Expression of sonic  hedgehog  targeted genes in peripheral blood mononuclear cells of patients with

  2. Endogenous and recombinant type I interferons and disease activity in multiple sclerosis

    Sellebjerg, Finn; Krakauer, Martin; Limborg, Signe

    2012-01-01

    the percentage of CD4+ T cells expressing CD71 and HLA-DR (activated T cells), and this was associated with an increased risk of clinical disease activity. In contrast, induction of CD71 and HLA-DR was not observed in untreated MS patients with evidence of endogenous type IFN I activity. In conclusion......Although treatment of multiple sclerosis (MS) with the type I interferon (IFN) IFN-ß lowers disease activity, the role of endogenous type I IFN in MS remains controversial. We studied CD4+ T cells and CD4+ T cell subsets, monocytes and dendritic cells by flow cytometry and analysed the relationship...... with endogenous type I IFN-like activity, the effect of IFN-ß therapy, and clinical and magnetic resonance imaging (MRI) disease activity in MS patients. Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4) on CD4+CD26(high) T cells (Th1 helper cells...

  3. Standardization and validation of a cytometric bead assay to assess antibodies to multiple Plasmodium falciparum recombinant antigens.

    Ondigo, Bartholomew N; Park, Gregory S; Gose, Severin O; Ho, Benjamin M; Ochola, Lyticia A; Ayodo, George O; Ofulla, Ayub V; John, Chandy C

    2012-12-21

    Multiplex cytometric bead assay (CBA) have a number of advantages over ELISA for antibody testing, but little information is available on standardization and validation of antibody CBA to multiple Plasmodium falciparum antigens. The present study was set to determine optimal parameters for multiplex testing of antibodies to P. falciparum antigens, and to compare results of multiplex CBA to ELISA. Antibodies to ten recombinant P. falciparum antigens were measured by CBA and ELISA in samples from 30 individuals from a malaria endemic area of Kenya and compared to known positive and negative control plasma samples. Optimal antigen amounts, monoplex vs multiplex testing, plasma dilution, optimal buffer, number of beads required were assessed for CBA testing, and results from CBA vs. ELISA testing were compared. Optimal amounts for CBA antibody testing differed according to antigen. Results for monoplex CBA testing correlated strongly with multiplex testing for all antigens (r = 0.88-0.99, P values from <0.0001 - 0.004), and antibodies to variants of the same antigen were accurately distinguished within a multiplex reaction. Plasma dilutions of 1:100 or 1:200 were optimal for all antigens for CBA testing. Plasma diluted in a buffer containing 0.05% sodium azide, 0.5% polyvinylalcohol, and 0.8% polyvinylpyrrolidone had the lowest background activity. CBA median fluorescence intensity (MFI) values with 1,000 antigen-conjugated beads/well did not differ significantly from MFI with 5,000 beads/well. CBA and ELISA results correlated well for all antigens except apical membrane antigen-1 (AMA-1). CBA testing produced a greater range of values in samples from malaria endemic areas and less background reactivity for blank samples than ELISA. With optimization, CBA may be the preferred method of testing for antibodies to P. falciparum antigens, as CBA can test for antibodies to multiple recombinant antigens from a single plasma sample and produces a greater range of values in

  4. Multiple Targets for Novel Therapy of FSGS Associated with Circulating Permeability Factor

    Virginia J. Savin

    2017-01-01

    Full Text Available A plasma component is responsible for altered glomerular permeability in patients with focal segmental glomerulosclerosis. Evidence includes recurrence after renal transplantation, remission after plasmapheresis, proteinuria in infants of affected mothers, transfer of proteinuria to experimental animals, and impaired glomerular permeability after exposure to patient plasma. Therapy may include decreasing synthesis of the injurious agent, removing or blocking its interaction with cells, or blocking signaling or enhancing cell defenses to restore the permeability barrier and prevent progression. Agents that may prevent the synthesis of the permeability factor include cytotoxic agents or aggressive chemotherapy. Extracorporeal therapies include plasmapheresis, immunoadsorption with protein A or anti-immunoglobulin, or lipopheresis. Oral or intravenous galactose also decreases Palb activity. Studies of glomeruli have shown that several strategies prevent the action of FSGS sera. These include blocking receptor-ligand interactions, modulating cell reactions using indomethacin or eicosanoids 20-HETE or 8,9-EET, and enhancing cytoskeleton and protein interactions using calcineurin inhibitors, glucocorticoids, or rituximab. We have identified cardiotrophin-like cytokine factor 1 (CLCF-1 as a candidate for the permeability factor. Therapies specific to CLCF-1 include potential use of cytokine receptor-like factor (CRLF-1 and inhibition of Janus kinase 2. Combined therapy using multiple modalities offers therapy to reverse proteinuria and prevent scarring.

  5. Increase in Middle East Respiratory Syndrome-Coronavirus Cases in Saudi Arabia Linked to Hospital Outbreak With Continued Circulation of Recombinant Virus, July 1–August 31, 2015

    Assiri, Abdullah M.; Biggs, Holly M.; Abedi, Glen R.; Lu, Xiaoyan; Bin Saeed, Abdulaziz; Abdalla, Osman; Mohammed, Mutaz; Al-Abdely, Hail M.; Algarni, Homoud S.; Alhakeem, Raafat F.; Almasri, Malak M.; Alsharef, Ali A.; Nooh, Randa; Erdman, Dean D.; Gerber, Susan I.; Watson, John T.

    2016-01-01

    During July–August 2015, the number of cases of Middle East respiratory syndrome (MERS) reported from Saudi Arabia increased dramatically. We reviewed the 143 confirmed cases from this period and classified each based upon likely transmission source. We found that the surge in cases resulted predominantly (90%) from secondary transmission largely attributable to an outbreak at a single healthcare facility in Riyadh. Genome sequencing of MERS coronavirus from 6 cases demonstrated continued circulation of the recently described recombinant virus. A single unique frameshift deletion in open reading frame 5 was detected in the viral sequence from 1 case. PMID:27704019

  6. Lipid peroxidation and total cholesterol in HAART-naïve patients infected with circulating recombinant forms of human immunodeficiency virus type-1 in Cameroon.

    Georges Teto

    different subtypes obtained after sequencing were CRF02_AG (43.3%, CRF01_AE (20%, A1 (23.3%, H (6.7%, and G (6.7%. None of the HIV-1 subtypes significantly influenced the levels of the biochemical parameters, but by grouping them as pure subtypes and circulating recombinant forms (CRFs, the CRF significantly influenced TC levels. TC was significantly lower in patients infected with CRF (0.87±0.27 g/l compared to patients infected with pure HIV-1 subtypes (1.32±0.68 g/l (p<0.017. MDA levels were also significantly higher in patients infected with HIV-1CRF01_AE (0.50±0.10 µM, compared to patients infected with CRF02_AG (0. 38±0. 08 µM (p<0.018.These results show that HIV infection in Cameroon is associated with significant decrease in TAA, LDLC, HDLC and TC, and increased MDA concentration and LPI indices which seem to be linked to the severity of HIV infection as assessed by CD4 cell count. The data suggests increased oxidative stress and lipid peroxidation in HIV-infected patients in Cameroon, and an influence of CRFs on TC and MDA levels.

  7. Effect of natalizumab treatment on circulating plasmacytoid dendritic cells: a cross-sectional observational study in patients with multiple sclerosis.

    Pia Kivisäkk

    Full Text Available Dendritic cells (DCs serve a critical role both in promoting and inhibiting adaptive immunity. The goal of this study was to investigate the effect of natalizumab (NTZ treatment on DC numbers, phenotype, and function in patients with multiple sclerosis (MS.Frequency and phenotype of myeloid and plasmacytoid DCs (MDCs and PDCs, respectively were analyzed in blood from two separate cohorts of untreated, interferon-treated, or NTZ-treated MS patients. In addition, PDCs were stimulated with CpG-containing oligonucleotides or co-cultured with homologous T cells in the presence or absence of NTZ in vitro to determine functional effects of NTZ treatment.We observed that NTZ treatment was associated with a 25-50% reduction in PDC frequency in peripheral blood as compared to untreated MS patients, while the frequency of MDCs was unchanged. PDCs in NTZ-treated patients displayed a mature, activated phenotype with increased expression of HLA-DR, TLR9, CCR7, IL-6 and IL-12. In contrast, in vitro treatment with NTZ did not increase markers of PDC activation or their ability to induce T cell differentiation.Our study shows that NTZ treatment is associated with a reduced frequency of PDCs in the peripheral circulation, but that PDCs in NTZ-treated individuals display an activated phenotype. Taken together the data suggests that transmigration of activated PDCs is preferentially affected by blockade of integrin α4 leading to an increased frequency of activated PDCs in blood.

  8. Flow cytometric analysis reveals the high levels of platelet activation parameters in circulation of multiple sclerosis patients.

    Morel, Agnieszka; Rywaniak, Joanna; Bijak, Michał; Miller, Elżbieta; Niwald, Marta; Saluk, Joanna

    2017-06-01

    The epidemiological studies confirm an increased risk of cardiovascular disease in multiple sclerosis, especially prothrombotic events directly associated with abnormal platelet activity. The aim of our study was to investigate the level of blood platelet activation in the circulation of patients with chronic phase of multiple sclerosis (SP MS) and their reactivity in response to typical platelets' physiological agonists. We examined 85 SP MS patients diagnosed according to the revised McDonald's criteria and 50 healthy volunteers as a control group. The platelet activation and reactivity were assessed using flow cytometry analysis of the following: P-selectin expression (CD62P), activation of GP IIb/IIIa complex (PAC-1 binding), and formation of platelet microparticles (PMPs) and platelet aggregates (PA) in agonist-stimulated (ADP, collagen) and unstimulated whole blood samples. Furthermore, we measured the level of soluble P-selectin (sP-selectin) in plasma using ELISA method, to evaluate the in vivo level of platelet activation, both in healthy and SP MS subjects. We found a statistically significant increase in P-selectin expression, GP IIb/IIIa activation, and formation of PMPs and PA, as well as in unstimulated and agonist-stimulated (ADP, collagen) platelets in whole blood samples from patients with SP MS in comparison to the control group. We also determined the higher sP-selectin level in plasma of SP MS subjects than in the control group. Based on the obtained results, we might conclude that during the course of SP MS platelets are chronically activated and display hyperreactivity to physiological agonists, such as ADP or collagen.

  9. Endemic dengue associated with the co-circulation of multiple viral lineages and localized density-dependent transmission.

    Jayna Raghwani

    2011-06-01

    Full Text Available Dengue is one of the most important infectious diseases of humans and has spread throughout much of the tropical and subtropical world. Despite this widespread dispersal, the determinants of dengue transmission in endemic populations are not well understood, although essential for virus control. To address this issue we performed a phylogeographic analysis of 751 complete genome sequences of dengue 1 virus (DENV-1 sampled from both rural (Dong Thap and urban (Ho Chi Minh City populations in southern Viet Nam during the period 2003-2008. We show that DENV-1 in Viet Nam exhibits strong spatial clustering, with likely importation from Cambodia on multiple occasions. Notably, multiple lineages of DENV-1 co-circulated in Ho Chi Minh City. That these lineages emerged at approximately the same time and dispersed over similar spatial regions suggests that they are of broadly equivalent fitness. We also observed an important relationship between the density of the human host population and the dispersion rate of dengue, such that DENV-1 tends to move from urban to rural populations, and that densely populated regions within Ho Chi Minh City act as major transmission foci. Despite these fluid dynamics, the dispersion rates of DENV-1 are relatively low, particularly in Ho Chi Minh City where the virus moves less than an average of 20 km/year. These low rates suggest a major role for mosquito-mediated dispersal, such that DENV-1 does not need to move great distances to infect a new host when there are abundant susceptibles, and imply that control measures should be directed toward the most densely populated urban environments.

  10. Genomic Analysis of 15 Human Coronaviruses OC43 (HCoV-OC43s Circulating in France from 2001 to 2013 Reveals a High Intra-Specific Diversity with New Recombinant Genotypes

    Nathalie Kin

    2015-05-01

    Full Text Available Human coronavirus OC43 (HCoV-OC43 is one of five currently circulating human coronaviruses responsible for respiratory infections. Like all coronaviruses, it is characterized by its genome’s high plasticity. The objectives of the current study were to detect genetically distinct genotypes and eventually recombinant genotypes in samples collected in Lower Normandy between 2001 and 2013. To this end, we sequenced complete nsp12, S, and N genes of 15 molecular isolates of HCoV-OC43 from clinical samples and compared them to available data from the USA, Belgium, and Hong-Kong. A new cluster E was invariably detected from nsp12, S, and N data while the analysis of nsp12 and N genes revealed the existence of new F and G clusters respectively. The association of these different clusters of genes in our specimens led to the description of thirteen genetically distinct genotypes, among which eight recombinant viruses were discovered. Identification of these recombinant viruses, together with temporal analysis and tMRCA estimation, provides important information for understanding the dynamics of the evolution of these epidemic coronaviruses.

  11. Nonhomologous recombination between defective poliovirus and coxsackievirus genomes suggests a new model of genetic plasticity for picornaviruses.

    Holmblat, Barbara; Jégouic, Sophie; Muslin, Claire; Blondel, Bruno; Joffret, Marie-Line; Delpeyroux, Francis

    2014-08-05

    Most of the circulating vaccine-derived polioviruses (cVDPVs) implicated in poliomyelitis outbreaks in Madagascar have been shown to be recombinants between the type 2 poliovirus (PV) strain of the oral polio vaccine (Sabin 2) and another species C human enterovirus (HEV-C), such as type 17 coxsackie A virus (CA17) in particular. We studied intertypic genetic exchanges between PV and non-PV HEV-C by developing a recombination model, making it possible to rescue defective type 2 PV RNA genomes with a short deletion at the 3' end by the cotransfection of cells with defective or infectious CA17 RNAs. We isolated over 200 different PV/CA17 recombinants, using murine cells expressing the human PV receptor (PVR) and selecting viruses with PV capsids. We found some homologous (H) recombinants and, mostly, nonhomologous (NH) recombinants presenting duplications of parental sequences preferentially located in the regions encoding proteins 2A, 2B, and 3A. Short duplications appeared to be stable, whereas longer duplications were excised during passaging in cultured cells or after multiplication in PVR-transgenic mice, generating H recombinants with diverse sites of recombination. This suggests that NH recombination events may be a transient, intermediate step in the generation and selection of the fittest H recombinants. In addition to the classical copy-choice mechanism of recombination thought to generate mostly H recombinants, there may also be a modular mechanism of recombination, involving NH recombinant precursors, shaping the genomes of recombinant enteroviruses and other picornaviruses. Importance: The multiplication of circulating vaccine-derived polioviruses (cVDPVs) in poorly immunized human populations can render these viruses pathogenic, causing poliomyelitis outbreaks. Most cVDPVs are intertypic recombinants between a poliovirus (PV) strain and another human enterovirus, such as type 17 coxsackie A viruses (CA17). For further studies of the genetic exchanges

  12. Complete genome sequences of two avian infectious bronchitis viruses isolated in Egypt: Evidence for genetic drift and genetic recombination in the circulating viruses.

    Abozeid, Hassanein H; Paldurai, Anandan; Khattar, Sunil K; Afifi, Manal A; El-Kady, Magdy F; El-Deeb, Ayman H; Samal, Siba K

    2017-09-01

    Avian infectious bronchitis virus (IBV) is highly prevalent in chicken populations and is responsible for severe economic losses to poultry industry worldwide. In this study, we report the complete genome sequences of two IBV field strains, CU/1/2014 and CU/4/2014, isolated from vaccinated chickens in Egypt in 2014. The genome lengths of the strains CU/1/2014 and CU/4/2014 were 27,615 and 27,637 nucleotides, respectively. Both strains have a common genome organization in the order of 5'-UTR-1a-1b-S-3a-3b-E-M-4b-4c-5a-5b-N-6b-UTR-poly(A) tail-3'. Interestingly, strain CU/1/2014 showed a novel 15-nt deletion in the 4b-4c gene junction region. Phylogenetic analysis of the full S1 genes showed that the strains CU/1/2014 and CU/4/2014 belonged to IBV genotypes GI-1 lineage and GI-23 lineage, respectively. The genome of strain CU/1/2014 is closely related to vaccine strain H120 but showed genome-wide point mutations that lead to 27, 14, 11, 1, 1, 2, 2, and 2 amino acid differences between the two strains in 1a, 1b, S, 3a, M, 4b, 4c, and N proteins, respectively, suggesting that strain CU/1/2014 is probably a revertant of the vaccine strain H120 and evolved by accumulation of point mutations. Recombination analysis of strain CU/4/2014 showed evidence for recombination from at least three different IBV strains, namely, the Italian strain 90254/2005 (QX-like strain), 4/91, and H120. These results indicate the continuing evolution of IBV field strains by genetic drift and by genetic recombination leading to outbreaks in the vaccinated chicken populations in Egypt. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Unique properties of multiple tandem copies of the M26 recombination hotspot in mitosis and meiosis in Schizosaccharomyces pombe.

    Steiner, Walter W; Recor, Chelsea L; Zakrzewski, Bethany M

    2016-11-15

    The M26 hotspot of the fission yeast Schizosaccharomyces pombe is one of the best-characterized eukaryotic hotspots of recombination. The hotspot requires a seven bp sequence, ATGACGT, that serves as a binding site for the Atf1-Pcr1 transcription factor, which is also required for activity. The M26 hotspot is active in meiosis but not mitosis and is active in some but not all chromosomal contexts and not on a plasmid. A longer palindromic version of M26, ATGACGTCAT, shows significantly greater activity than the seven bp sequence. Here, we tested whether the properties of the seven bp sequence were also true of the longer sequence by placing one, two, or three copies of the sequence into the ade6 gene, where M26 was originally discovered. These constructs were tested for activity when located on a plasmid or on a chromosome in mitosis and meiosis. We found that two copies of the 10bp M26 motif on a chromosome were significantly more active for meiotic recombination than one, but no further increase was observed with three copies. However, three copies of M26 on a chromosome created an Atf1-dependent mitotic recombination hotspot. When located on a plasmid, M26 also appears to behave as a mitotic recombination hotspot; however, this behavior most likely results from Atf1-dependent inter-allelic complementation between the plasmid and chromosomal ade6 alleles. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Evidence for possible biological advantages of the newly emerging HIV-1 circulating recombinant form from Malaysia - CRF33_01B in comparison to its progenitors - CRF01_AE and subtype B.

    Lau, Katherine A; Wang, Bin; Miranda-Saksena, Monica; Boadle, Ross; Kamarulzaman, Adeeba; Ng, Kee-Peng; Saksena, Nitin K

    2010-04-01

    In Malaysia, co-circulation of CRF01_AE and subtype B has resulted in the emergence of the second generation derivative; CRF33_01B in approximately 20% of its HIV-1 infected individuals. Our objective was to identify possible biological advantages that CRF33_01B possesses over its progenitors. Biological and molecular comparisons of CRF33_01B against its parental subtypes clearly show that CRF33_01B replicated better in activated whole peripheral blood mononuclear cells (PBMCs) and CD4+ T-lymphocytes, but not monocyte-derived macrophages (MDMs). Also, its acquired fitness was greater than CRF01_AE but not subtype B. Moreover, CRF33_01B has higher rate of apoptotic cell death and syncytia induction compared to subtype B. These adaptive and survival abilities could have been acquired by CRF33_01B due to the incorporation of subtype B fragments into the gag-RT region of its full-length genome. Our studies confirm the previously held belief that HIV-1 strains may harbor enhanced biological fitness upon recombination. We therefore estimate a possible gradual replacement of the current predominance of CRF01_AE, as well as wider dissemination of CRF33_01B, together with the identification of other new CRF01_AE/B inter-subtype recombinants in Malaysia.

  15. Unique Safety Issues Associated with Virus Vectored Vaccines: Potential for and Theoretical Consequences of Recombination with Wild Type Virus Strains

    Condit, Richard C.; Williamson, Anna-Lise; Sheets, Rebecca; Seligman, Stephen J.; Monath, Thomas P.; Excler, Jean-Louis; Gurwith, Marc; Bok, Karin; Robertson, James S.; Kim, Denny; Hendry, Michael; Singh, Vidisha; Mac, Lisa M.; Chen, Robert T.

    2016-01-01

    In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration. To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains. PMID:27346303

  16. Multiple cell upset cross-section modeling: A possible interpretation for the role of the ion energy-loss straggling and Auger recombination

    Zebrev, G.I.; Zemtsov, K.S.

    2016-01-01

    We found that the energy deposition fluctuations in the sensitive volumes may cause the multiple cell upset (MCU) multiplicity scatter in the nanoscale (with feature sizes less than 100 nm) memories. A microdosimetric model of the MCU cross-section dependence on LET is proposed. It was shown that ideally a staircase-shaped cross-section vs LET curve spreads due to the energy-loss straggling impact into a quasi-linear dependence with a slope depending on the memory cell area, the cell critical energy and efficiency of charge collection. This paper also presents a new model of the Auger recombination as a limiting process of the electron–hole charge yield, especially at the high-LET ion impact. A modified form of the MCU cross-section vs LET data interpolation is proposed, discussed and validated.

  17. Multiple cell upset cross-section modeling: A possible interpretation for the role of the ion energy-loss straggling and Auger recombination

    Zebrev, G.I., E-mail: gizebrev@mephi.ru; Zemtsov, K.S.

    2016-08-11

    We found that the energy deposition fluctuations in the sensitive volumes may cause the multiple cell upset (MCU) multiplicity scatter in the nanoscale (with feature sizes less than 100 nm) memories. A microdosimetric model of the MCU cross-section dependence on LET is proposed. It was shown that ideally a staircase-shaped cross-section vs LET curve spreads due to the energy-loss straggling impact into a quasi-linear dependence with a slope depending on the memory cell area, the cell critical energy and efficiency of charge collection. This paper also presents a new model of the Auger recombination as a limiting process of the electron–hole charge yield, especially at the high-LET ion impact. A modified form of the MCU cross-section vs LET data interpolation is proposed, discussed and validated.

  18. Circulating dendritic cells of multiple sclerosis patients are proinflammatory and their frequency is correlated with MS-associated genetic risk factors.

    Thewissen, Kristof; Nuyts, Amber H; Deckx, Nathalie; Van Wijmeersch, Bart; Nagels, Guy; D'hooghe, Marie; Willekens, Barbara; Cras, Patrick; Eijnde, Bert O; Goossens, Herman; Van Tendeloo, Viggo F I; Stinissen, Piet; Berneman, Zwi N; Hellings, Niels; Cools, Nathalie

    2014-04-01

    The role of the adaptive immune system and more specifically T cells in the pathogenesis of multiple sclerosis (MS) has been studied extensively. Emerging evidence suggests that dendritic cells (DCs), which are innate immune cells, also contribute to MS. This study aimed to characterize circulating DC populations in MS and to investigate the contribution of MS-associated genetic risk factors to DCs. Ex vivo analysis of conventional (cDCs) and plasmacytoid DCs (pDCs) was carried out on peripheral blood of MS patients (n = 110) and age- and gender-matched healthy controls (n = 112). Circulating pDCs were significantly decreased in patients with chronic progressive MS compared to relapsing-remitting MS and healthy controls. While no differences in cDCs frequency were found between the different study groups, HLA-DRB1*1501(+) MS patients and patients not carrying the protective IL-7Rα haplotype 2 have reduced frequencies of circulating cDCs and pDCs, respectively. MS-derived DCs showed enhanced IL-12p70 production upon TLR ligation and had an increased expression of the migratory molecules CCR5 and CCR7 as well as an enhanced in vitro chemotaxis. DCs in MS are in a pro-inflammatory state, have a migratory phenotype and are affected by genetic risk factors, thereby contributing to pathogenic responses.

  19. Recombinant Programming

    Pawlak , Renaud; Cuesta , Carlos; Younessi , Houman

    2004-01-01

    This research report presents a promising new approach to computation called Recombinant Programming. The novelty of our approach is that it separates the program into two layers of computation: the recombination and the interpretation layer. The recombination layer takes sequences as inputs and allows the programmer to recombine these sequences through the definition of cohesive code units called extensions. The output of such recombination is a mesh that can be used by the interpretation la...

  20. Taking multiple infections of cells and recombination into account leads to small within-host effective-population-size estimates of HIV-1.

    Rajesh Balagam

    2011-01-01

    Full Text Available Whether HIV-1 evolution in infected individuals is dominated by deterministic or stochastic effects remains unclear because current estimates of the effective population size of HIV-1 in vivo, N(e, are widely varying. Models assuming HIV-1 evolution to be neutral estimate N(e~10²-10⁴, smaller than the inverse mutation rate of HIV-1 (~10⁵, implying the predominance of stochastic forces. In contrast, a model that includes selection estimates N(e>10⁵, suggesting that deterministic forces would hold sway. The consequent uncertainty in the nature of HIV-1 evolution compromises our ability to describe disease progression and outcomes of therapy. We perform detailed bit-string simulations of viral evolution that consider large genome lengths and incorporate the key evolutionary processes underlying the genomic diversification of HIV-1 in infected individuals, namely, mutation, multiple infections of cells, recombination, selection, and epistatic interactions between multiple loci. Our simulations describe quantitatively the evolution of HIV-1 diversity and divergence in patients. From comparisons of our simulations with patient data, we estimate N(e~10³-10⁴, implying predominantly stochastic evolution. Interestingly, we find that N(e and the viral generation time are correlated with the disease progression time, presenting a route to a priori prediction of disease progression in patients. Further, we show that the previous estimate of N(e>10⁵ reduces as the frequencies of multiple infections of cells and recombination assumed increase. Our simulations with N(e~10³-10⁴ may be employed to estimate markers of disease progression and outcomes of therapy that depend on the evolution of viral diversity and divergence.

  1. Distinct pattern of lesion distribution in multiple sclerosis is associated with different circulating T-helper and helper-like innate lymphoid cell subsets.

    Gross, Catharina C; Schulte-Mecklenbeck, Andreas; Hanning, Uta; Posevitz-Fejfár, Anita; Korsukewitz, Catharina; Schwab, Nicholas; Meuth, Sven G; Wiendl, Heinz; Klotz, Luisa

    2017-06-01

    Distinct lesion topography in relapsing-remitting multiple sclerosis (RRMS) might be due to different antigen presentation and/or trafficking routes of immune cells into the central nervous system (CNS). To investigate whether distinct lesion patterns in multiple sclerosis (MS) might be associated with a predominance of distinct circulating T-helper cell subset as well as their innate counterparts. Flow cytometric analysis of lymphocytes derived from the peripheral blood of patients with exclusively cerebral (n = 20) or predominantly spinal (n = 12) disease manifestation. Patients with exclusively cerebral or preferential spinal lesion manifestation were associated with increased proportions of circulating granulocyte-macrophage colony-stimulating factor (GM-CSF) producing T H 1 cells or interleukin (IL)-17-producing T H 17 cells, respectively. In contrast, proportions of peripheral IL-17/IL-22-producing lymphoid tissue inducer (LTi), the innate counterpart of T H 17 cells, were enhanced in RRMS patients with exclusively cerebral lesion topography. Distinct T-helper and T-helper-like innate lymphoid cell (ILC) subsets are associated with different lesion topography in RRMS.

  2. Effects of L-arabinose efflux on λ Red recombination-mediated gene knockout in multiple-antimicrobial-resistant Salmonella enterica serovar Choleraesuis.

    Liao, Shi-Wei; Lee, Jen-Jie; Ptak, Christopher P; Wu, Ying-Chen; Hsuan, Shih-Ling; Kuo, Chih-Jung; Chen, Ter-Hsin

    2018-03-01

    In this study, six swine-derived multiple-antimicrobial-resistant (MAR) strains of Salmonella Choleraesuis (S. Choleraesuis) were demonstrated to possess higher efflux pump activity than the wild-type (WT). L-Arabinose, a common inducer for gene expression, modulated S. Choleraesuis efflux pump activity in a dose-dependent manner. At low L-arabinose concentrations, increasing L-arabinose led to a corresponding increase in fluorophore efflux, while at higher L-arabinose concentrations, increasing L-arabinose decreased fluorophore efflux activity. The WT S. Choleraesuis that lacks TolC (ΔtolC), an efflux protein associated with bacterial antibiotic resistance and virulence, was demonstrated to possess a significantly reduced ability to extrude L-arabinose. Further, due to the rapid export of L-arabinose, an efficient method for recombination-mediated gene knockout, the L-arabinose-inducible bacteriophage λ Red recombinase system, has a reduced recombination frequency (~ 12.5%) in clinically isolated MAR Salmonella strains. An increased recombination frequency (up to 60%) can be achieved using a higher concentration of L-arabinose (fivefold) for genetic manipulation and functional analysis for MAR Salmonella using the λ Red system. The study suggests that L-arabinose serves not only as an inducer of the TolC-dependent efflux system but also acts as a competitive substrate of the efflux system. In addition, understanding the TolC-dependent efflux of L-arabinose should facilitate the optimization of L-arabinose induction in strains with high efflux activity.

  3. Recombination dynamics of excitons with low non-radiative component in semi-polar (10-11)-oriented GaN/AlGaN multiple quantum wells

    Rosales, D.; Gil, B.; Bretagnon, T.; Guizal, B.; Izyumskaya, N.; Monavarian, M.; Zhang, F.; Okur, S.; Avrutin, V.; Özgür, Ü.; Morkoç, H.

    2014-01-01

    Optical properties of GaN/Al 0.2 Ga 0.8 N multiple quantum wells grown with semi-polar (10-11) orientation on patterned 7°-off Si (001) substrates have been investigated. Studies performed at 8 K reveal the in-plane anisotropic behavior of the QW photoluminescence (PL) intensity for this semi-polar orientation. The time resolved PL measurements were carried out in the temperature range from 8 to 295 K to deduce the effective recombination decay times, with respective radiative and non-radiative contributions. The non-radiative component remains relatively weak with increasing temperature, indicative of high crystalline quality. The radiative decay time is a consequence of contribution from both localized and free excitons. We report an effective density of interfacial defects of 2.3 × 10 12 cm −2 and a radiative recombination time of τ loc  = 355 ps for the localized excitons. This latter value is significantly larger than those reported for the non-polar structures, which we attribute to the presence of a weak residual electric field in the semi-polar QW layers

  4. Recombination dynamics of excitons with low non-radiative component in semi-polar (10-11)-oriented GaN/AlGaN multiple quantum wells

    Rosales, D.; Gil, B.; Bretagnon, T.; Guizal, B.; Izyumskaya, N.; Monavarian, M.; Zhang, F.; Okur, S.; Avrutin, V.; Özgür, Ü.; Morkoç, H.

    2014-09-01

    Optical properties of GaN/Al0.2Ga0.8N multiple quantum wells grown with semi-polar (10-11) orientation on patterned 7°-off Si (001) substrates have been investigated. Studies performed at 8 K reveal the in-plane anisotropic behavior of the QW photoluminescence (PL) intensity for this semi-polar orientation. The time resolved PL measurements were carried out in the temperature range from 8 to 295 K to deduce the effective recombination decay times, with respective radiative and non-radiative contributions. The non-radiative component remains relatively weak with increasing temperature, indicative of high crystalline quality. The radiative decay time is a consequence of contribution from both localized and free excitons. We report an effective density of interfacial defects of 2.3 × 1012 cm-2 and a radiative recombination time of τloc = 355 ps for the localized excitons. This latter value is significantly larger than those reported for the non-polar structures, which we attribute to the presence of a weak residual electric field in the semi-polar QW layers.

  5. Recombination dynamics of excitons with low non-radiative component in semi-polar (10-11)-oriented GaN/AlGaN multiple quantum wells

    Rosales, D.; Gil, B.; Bretagnon, T.; Guizal, B. [CNRS, Laboratoire Charles Coulomb, UMR 5221, F-34095 Montpellier (France); Université Montpellier 2, Laboratoire Charles Coulomb, UMR 5221, F-34095 Montpellier (France); Izyumskaya, N.; Monavarian, M.; Zhang, F.; Okur, S.; Avrutin, V.; Özgür, Ü.; Morkoç, H. [Department of Electrical and Computer Engineering, Virginia Commonwealth University, Richmond, Virginia 23238 (United States)

    2014-09-07

    Optical properties of GaN/Al{sub 0.2}Ga{sub 0.8}N multiple quantum wells grown with semi-polar (10-11) orientation on patterned 7°-off Si (001) substrates have been investigated. Studies performed at 8 K reveal the in-plane anisotropic behavior of the QW photoluminescence (PL) intensity for this semi-polar orientation. The time resolved PL measurements were carried out in the temperature range from 8 to 295 K to deduce the effective recombination decay times, with respective radiative and non-radiative contributions. The non-radiative component remains relatively weak with increasing temperature, indicative of high crystalline quality. The radiative decay time is a consequence of contribution from both localized and free excitons. We report an effective density of interfacial defects of 2.3 × 10{sup 12} cm{sup −2} and a radiative recombination time of τ{sub loc} = 355 ps for the localized excitons. This latter value is significantly larger than those reported for the non-polar structures, which we attribute to the presence of a weak residual electric field in the semi-polar QW layers.

  6. FEASIBILITY ANALYSIS FOR INSTALLING A CIRCULATING FLUIDIZED BED BOILER FOR COFIRING MULTIPLE BIOFUELS AND OTHER WASTES WITH COAL AT PENN STATE UNIVERSITY

    Bruce G. Miller; Sharon Falcone Miller; Robert Cooper; John Gaudlip; Matthew Lapinsky; Rhett McLaren; William Serencsits; Neil Raskin; Tom Steitz; Joseph J. Battista

    2003-03-26

    The Pennsylvania State University, utilizing funds furnished by the U.S. Department of Energy's Biomass Power Program, investigated the installation of a state-of-the-art circulating fluidized bed boiler at Penn State's University Park campus for cofiring multiple biofuels and other wastes with coal, and developing a test program to evaluate cofiring biofuels and coal-based feedstocks. The study was performed using a team that included personnel from Penn State's Energy Institute, Office of Physical Plant, and College of Agricultural Sciences; Foster Wheeler Energy Services, Inc.; Foster Wheeler Energy Corporation; Parsons Energy and Chemicals Group, Inc.; and Cofiring Alternatives. The activities included assessing potential feedstocks at the University Park campus and surrounding region with an emphasis on biomass materials, collecting and analyzing potential feedstocks, assessing agglomeration, deposition, and corrosion tendencies, identifying the optimum location for the boiler system through an internal site selection process, performing a three circulating fluidized bed (CFB) boiler design and a 15-year boiler plant transition plan, determining the costs associated with installing the boiler system, developing a preliminary test program, determining the associated costs for the test program, and exploring potential emissions credits when using the biomass CFB boiler.

  7. Circulating IGF-1, IGFB-3, GH and TSH levels in multiple sclerosis and their relationship with treatment.

    Akcali, Aylin; Bal, Berrin; Erbagci, Binnur

    2017-07-01

    Improving the proficiency of oligodendrocytes in their ability to repair myelin damage is one of the major goals of multiple sclerosis treatment. Insulin-like growth factor-1 (IGF-1) is one of several polypeptides that are considered to have potential benefits in that sense. In the present study, we aimed to determine serum levels of IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3), thyroid stimulating hormone (TSH) and growth hormone (GH) among treated and non-treated patients with Relapsing-Remitting Multiple Sclerosis (RRMS) and a healthy control group. The study enrolled 100 RRMS patients and 100 age- and sex-matched control subjects diagnosed with definite multiple sclerosis (MS). Serum GH, IGF-1, IGFBP-3, and TSH levels were studied. The number of relapses and Expanded Disability Status Scale were negatively correlated and IGFBP-3 and GH were positively correlated with IGF-1. A statistically significant difference was not observed when patients were divided into two subgroups as patients treated with a MS-specific therapy (n = 54) and non-treated patients (n = 46). TSH and IGFBP-3 values were significantly lower in patient group vs. While no difference was determined with in IGF-1 levels, low levels of IGF-1 was in correlation with the least levels of IGFBP-3. To understand the relation between IGF-1 and IGFBP-3, the role of low levels of IGFBP-3 and TSH may be studied with clinic isolated syndrome patients and the evolution of these patients to definite MS.

  8. Systematic comparison of co-expression of multiple recombinant thermophilic enzymes in Escherichia coli BL21(DE3).

    Chen, Hui; Huang, Rui; Zhang, Y-H Percival

    2017-06-01

    The precise control of multiple heterologous enzyme expression levels in one Escherichia coli strain is important for cascade biocatalysis, metabolic engineering, synthetic biology, natural product synthesis, and studies of complexed proteins. We systematically investigated the co-expression of up to four thermophilic enzymes (i.e., α-glucan phosphorylase (αGP), phosphoglucomutase (PGM), glucose 6-phosphate dehydrogenase (G6PDH), and 6-phosphogluconate dehydrogenase (6PGDH)) in E. coli BL21(DE3) by adding T7 promoter or T7 terminator of each gene for multiple genes in tandem, changing gene alignment, and comparing one or two plasmid systems. It was found that the addition of T7 terminator after each gene was useful to decrease the influence of the upstream gene. The co-expression of the four enzymes in E. coli BL21(DE3) was demonstrated to generate two NADPH molecules from one glucose unit of maltodextrin, where NADPH was oxidized to convert xylose to xylitol. The best four-gene co-expression system was based on two plasmids (pET and pACYC) which harbored two genes. As a result, apparent enzymatic activities of the four enzymes were regulated to be at similar levels and the overall four-enzyme activity was the highest based on the formation of xylitol. This study provides useful information for the precise control of multi-enzyme-coordinated expression in E. coli BL21(DE3).

  9. Frequency and genetic characterization of V(DD)J recombinants in the human peripheral blood antibody repertoire.

    Briney, Bryan S; Willis, Jordan R; Hicar, Mark D; Thomas, James W; Crowe, James E

    2012-09-01

    Antibody heavy-chain recombination that results in the incorporation of multiple diversity (D) genes, although uncommon, contributes substantially to the diversity of the human antibody repertoire. Such recombination allows the generation of heavy chain complementarity determining region 3 (HCDR3) regions of extreme length and enables junctional regions that, because of the nucleotide bias of N-addition regions, are difficult to produce through normal V(D)J recombination. Although this non-classical recombination process has been observed infrequently, comprehensive analysis of the frequency and genetic characteristics of such events in the human peripheral blood antibody repertoire has not been possible because of the rarity of such recombinants and the limitations of traditional sequencing technologies. Here, through the use of high-throughput sequencing of the normal human peripheral blood antibody repertoire, we analysed the frequency and genetic characteristics of V(DD)J recombinants. We found that these recombinations were present in approximately 1 in 800 circulating B cells, and that the frequency was severely reduced in memory cell subsets. We also found that V(DD)J recombination can occur across the spectrum of diversity genes, indicating that virtually all recombination signal sequences that flank diversity genes are amenable to V(DD)J recombination. Finally, we observed a repertoire bias in the diversity gene repertoire at the upstream (5') position, and discovered that this bias was primarily attributable to the order of diversity genes in the genomic locus. © 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.

  10. Co-circulation of multiple subtypes of enterovirus A71 (EV- A71) genotype C, including novel recombinants characterised by use of whole genome sequencing (WGS), Denmark 2016

    Midgley, Sofie E; Nielsen, Astrid G; Trebbien, Ramona

    2017-01-01

    In Europe, enterovirus A71 (EV-A71) has primarily been associated with sporadic cases of neurological disease. The recent emergence of new genotypes and larger outbreaks with severely ill patients demonstrates a potential for the spread of new, highly pathogenic EV-A71 strains. Detection and char......In Europe, enterovirus A71 (EV-A71) has primarily been associated with sporadic cases of neurological disease. The recent emergence of new genotypes and larger outbreaks with severely ill patients demonstrates a potential for the spread of new, highly pathogenic EV-A71 strains. Detection...

  11. Evaluation of a multiple-cycle, recombinant virus, growth competition assay that uses flow cytometry to measure replication efficiency of human immunodeficiency virus type 1 in cell culture.

    Dykes, Carrie; Wang, Jiong; Jin, Xia; Planelles, Vicente; An, Dong Sung; Tallo, Amanda; Huang, Yangxin; Wu, Hulin; Demeter, Lisa M

    2006-06-01

    Human immunodeficiency virus type 1 (HIV-1) replication efficiency or fitness, as measured in cell culture, has been postulated to correlate with clinical outcome of HIV infection, although this is still controversial. One limitation is the lack of high-throughput assays that can measure replication efficiency over multiple rounds of replication. We have developed a multiple-cycle growth competition assay to measure HIV-1 replication efficiency that uses flow cytometry to determine the relative proportions of test and reference viruses, each of which expresses a different reporter gene in place of nef. The reporter genes are expressed on the surface of infected cells and are detected by commercially available fluorescence-labeled antibodies. This method is less labor-intensive than those that require isolation and amplification of nucleic acids. The two reporter gene products are detected with similar specificity and sensitivity, and the proportion of infected cells in culture correlates with the amount of viral p24 antigen produced in the culture supernatant. HIV replication efficiencies of six different drug-resistant site-directed mutants were reproducibly quantified and were similar to those obtained with a growth competition assay in which the relative proportion of each variant was measured by sequence analysis, indicating that recombination between the pol and reporter genes was negligible. This assay also reproducibly quantified the relative fitness conferred by protease and reverse transcriptase sequences containing multiple drug resistance mutations, amplified from patient plasma. This flow cytometry-based growth competition assay offers advantages over current assays for HIV replication efficiency and should prove useful for the evaluation of patient samples in clinical trials.

  12. The Asd+-DadB+ Dual-Plasmid System Offers a Novel Means To Deliver Multiple Protective Antigens by a Recombinant Attenuated Salmonella Vaccine

    Xin, Wei; Wanda, Soo-Young; Zhang, Xiangmin; Santander, Javier; Scarpellini, Giorgio; Ellis, Karen; Alamuri, Praveen

    2012-01-01

    We developed means to deliver multiple heterologous antigens on dual plasmids with non-antibiotic-resistance markers in a single recombinant attenuated vaccine strain of Salmonella enterica serotype Typhimurium. The first component of this delivery system is a strain of S. Typhimurium carrying genomic deletions in alr, dadB, and asd, resulting in obligate requirements for diaminopimelic acid (DAP) and d-alanine for growth. The second component is the Asd+-DadB+ plasmid pair carrying wild-type copies of asdA and dadB, respectively, to complement the mutations. To evaluate the protection efficacy of the dual-plasmid vaccine, S. Typhimurium strain χ9760 (a strain with multiple attenuating mutations: Δasd Δalr ΔdadB ΔrecF) was transformed with Asd+ and DadB+ plasmids specifying pneumococcal antigens PspA and PspC, respectively. Both plasmids were stable in χ9760 for 50 generations when grown in nonselective medium. This was significantly (P < 0.05) greater than the stability seen in its recF+ counterpart χ9590 and could be attributed to reduced interplasmid recombination in χ9760. Oral immunization of BALB/c mice with 1 × 109 CFU of χ9760 (carrying Asd+-PspA and DadB+-PspC plasmids) elicited a dominant Th1-type serum IgG response against both antigens and protected mice against intraperitoneal challenge with 200 50% lethal doses (LD50s) of virulent Streptococcus pneumoniae strain WU2 or intravenous challenge with 100 LD50s of virulent S. pneumoniae strain L81905 or intranasal challenge with a lethal dose of S. pneumoniae A66.1 in a pneumonia model. Protection offered by χ9760 was superior to that offered by the mixture of two strains, χ9828 (Asd+-PspA) and χ11026 (DadB+-PspC). This novel dual-plasmid system marks a remarkable improvement in the development of live bacterial vaccines. PMID:22868499

  13. The Asd(+)-DadB(+) dual-plasmid system offers a novel means to deliver multiple protective antigens by a recombinant attenuated Salmonella vaccine.

    Xin, Wei; Wanda, Soo-Young; Zhang, Xiangmin; Santander, Javier; Scarpellini, Giorgio; Ellis, Karen; Alamuri, Praveen; Curtiss, Roy

    2012-10-01

    We developed means to deliver multiple heterologous antigens on dual plasmids with non-antibiotic-resistance markers in a single recombinant attenuated vaccine strain of Salmonella enterica serotype Typhimurium. The first component of this delivery system is a strain of S. Typhimurium carrying genomic deletions in alr, dadB, and asd, resulting in obligate requirements for diaminopimelic acid (DAP) and d-alanine for growth. The second component is the Asd(+)-DadB(+) plasmid pair carrying wild-type copies of asdA and dadB, respectively, to complement the mutations. To evaluate the protection efficacy of the dual-plasmid vaccine, S. Typhimurium strain χ9760 (a strain with multiple attenuating mutations: Δasd Δalr ΔdadB ΔrecF) was transformed with Asd(+) and DadB(+) plasmids specifying pneumococcal antigens PspA and PspC, respectively. Both plasmids were stable in χ9760 for 50 generations when grown in nonselective medium. This was significantly (P < 0.05) greater than the stability seen in its recF(+) counterpart χ9590 and could be attributed to reduced interplasmid recombination in χ9760. Oral immunization of BALB/c mice with 1 × 10(9) CFU of χ9760 (carrying Asd(+)-PspA and DadB(+)-PspC plasmids) elicited a dominant Th1-type serum IgG response against both antigens and protected mice against intraperitoneal challenge with 200 50% lethal doses (LD(50)s) of virulent Streptococcus pneumoniae strain WU2 or intravenous challenge with 100 LD(50)s of virulent S. pneumoniae strain L81905 or intranasal challenge with a lethal dose of S. pneumoniae A66.1 in a pneumonia model. Protection offered by χ9760 was superior to that offered by the mixture of two strains, χ9828 (Asd(+)-PspA) and χ11026 (DadB(+)-PspC). This novel dual-plasmid system marks a remarkable improvement in the development of live bacterial vaccines.

  14. FEASIBILITY ANALYSIS FOR INSTALLING A CIRCULATING FLUIDIZED BED BOILER FOR COFIRING MULTIPLE BIOFUELS AND OTHER WASTES WITH COAL AT PENN STATE UNIVERSITY

    Bruce G. Miller; Sharon Falcone Miller; Robert Cooper; Douglas Donovan; John Gaudlip; Matthew Lapinsky; William Serencsits; Neil Raskin; Dale Lamke; Joseph J. Battista

    2001-01-01

    The Pennsylvania State University, under contract to the U.S. Department of Energy (DOE), National Energy Technology Laboratory (NETL) is performing a feasibility analysis on installing a state-of-the-art circulating fluidized bed (CFB) boiler and ceramic filter emission control device at Penn State's University Park campus for cofiring multiple biofuels and other wastes with coal, and developing a test program to evaluate cofiring multiple biofuels and coal-based feedstocks. Penn State currently operates an aging stoker-fired steam plant at its University Park campus and has spent considerable resources over the last ten to fifteen years investigating boiler replacements and performing life extension studies. This effort, in combination with a variety of agricultural and other wastes generated at the agricultural-based university and the surrounding rural community, has led Penn State to assemble a team of fluidized bed and cofiring experts to assess the feasibility of installing a CFB boiler for cofiring biomass and other wastes along with coal-based fuels. The objective of the project is being accomplished using a team that includes personnel from Penn State's Energy Institute and the Office of Physical Plant, Foster Wheeler Energy Services, Inc., and Cofiring Alternatives

  15. Nonhomologous Recombination between Defective Poliovirus and Coxsackievirus Genomes Suggests a New Model of Genetic Plasticity for Picornaviruses

    Holmblat, Barbara; Jégouic, Sophie; Muslin, Claire; Blondel, Bruno; Joffret, Marie-Line

    2014-01-01

    ABSTRACT Most of the circulating vaccine-derived polioviruses (cVDPVs) implicated in poliomyelitis outbreaks in Madagascar have been shown to be recombinants between the type 2 poliovirus (PV) strain of the oral polio vaccine (Sabin 2) and another species C human enterovirus (HEV-C), such as type 17 coxsackie A virus (CA17) in particular. We studied intertypic genetic exchanges between PV and non-PV HEV-C by developing a recombination model, making it possible to rescue defective type 2 PV RNA genomes with a short deletion at the 3′ end by the cotransfection of cells with defective or infectious CA17 RNAs. We isolated over 200 different PV/CA17 recombinants, using murine cells expressing the human PV receptor (PVR) and selecting viruses with PV capsids. We found some homologous (H) recombinants and, mostly, nonhomologous (NH) recombinants presenting duplications of parental sequences preferentially located in the regions encoding proteins 2A, 2B, and 3A. Short duplications appeared to be stable, whereas longer duplications were excised during passaging in cultured cells or after multiplication in PVR-transgenic mice, generating H recombinants with diverse sites of recombination. This suggests that NH recombination events may be a transient, intermediate step in the generation and selection of the fittest H recombinants. In addition to the classical copy-choice mechanism of recombination thought to generate mostly H recombinants, there may also be a modular mechanism of recombination, involving NH recombinant precursors, shaping the genomes of recombinant enteroviruses and other picornaviruses. PMID:25096874

  16. Recombinant innovation and endogenous technological transitions

    Frenken, K.; Izquierdo, L.R.; Zeppini, P.

    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

  17. Recombinant Innovation and Endogenous Transitions

    Koen Frenken; Luis R. Izquierdo; Paolo 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 switching costs allowing agents to escape a technological lock-in. As a result, recombinant innovations speed up technological progress allowing transitions that are impossible with only branching ...

  18. Optimization of a multi-gene HIV-1 recombinant subtype CRF02AG DNA vaccine for expression of multiple immunogenic forms

    Ellenberger, Dennis; Li Bin; Smith, James; Yi Hong; Folks, Thomas; Robinson, Harriet; Butera, Salvatore

    2004-01-01

    We developed an AIDS vaccine for Western and West-Central Africa based on a DNA plasmid vector expressing HIV-1 recombinant subtype CRF02 A G gag, pol, and env genes. To optimize the production of noninfectious HIV-like particles (VLPs) and potentially improve the effectiveness of the vaccine, we generated four potential vaccine constructs: the parental (IC2) and three modifications (IC25, IC48, and IC90) containing mutations within the HIV protease. While the parental construct IC2 expressed aggregates of Gag proteins, the IC25 construct resulted in the production of immature VLPs (the core comprises unprocessed Pr 55Gag ). The remaining two constructs (IC48 and IC90) produced mature VLPs (the core comprises processed capsid p24) in addition to immature VLPs and aggregates of Gag proteins. VLPs incorporated significant levels of mature gp120 envelope glycoprotein. Importantly, the mature VLPs were fusion competent and entered coreceptor-specific target cells. The production of multiple antigenic forms, including fusion-competent VLPs, by candidate DNA vaccine constructs may provide immunologic advantages for induction of protective cellular and humoral responses against HIV-1 proteins

  19. Genetic Recombination

    Whitehouse, H. L. K.

    1973-01-01

    Discusses the mechanisms of genetic recombination with particular emphasis on the study of the fungus Sordaria brevicollis. The study of recombination is facilitated by the use of mutants of this fungus in which the color of the ascospores is affected. (JR)

  20. Radiative recombination mechanism of carriers in InGaN/AlInGaN multiple quantum wells with varying aluminum content

    Liu, Tong [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China); Jiao, Shujie, E-mail: shujiejiao@gmail.com [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China); Key Laboratory for Photonic and Electric Bandgap Materials, Ministry of Education, Harbin Normal University, Harbin 150001 (China); Key Laboratory of Nanodevices and Applications, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123 (China); Wang, Dongbo [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China); Gao, Shiyong, E-mail: gaoshiyong@hit.edu.cn [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China); Yang, Tianpeng [EpiTop Optoelectronic Co., Ltd., Pingxiang 337000 (China); Liang, Hongwei [School of Physics and Optoelectronic Engineering, Dalian University of Technology, Dalian 116024 (China); Zhao, Liancheng [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China)

    2015-02-05

    Highlights: • Structural and optical properties of In GaN/Al{sub x}In{sub y}Ga{sub 1−x−y}N MQWs were investigated. • The existence of In-rich clusters has been verified by Raman spectra. • The degree of localization effect increase with increasing Al content in barriers. • The origin of the deep localized states could be assigned to the larger QCSE. • Recombination mechanism of carriers with increasing temperature has been proposed. - Abstract: The structural and optical properties of In{sub 0.20}Ga{sub 0.80}N/Al{sub x}In{sub y}Ga{sub 1−x−y}N multiple quantum wells samples with varying Al content in barrier layers grown on sapphire substrates by metalorganic chemical vapor deposition have been investigated by means of high-resolution X-ray diffraction, Raman scattering measurements and temperature-dependent photoluminescence. Raman measurements verified the existence of In-rich clusters in ternary and quaternary layers. At 10 K and 300 K, the PL spectrum of each sample is dominated by a sharp emission peak arising from In{sub 0.20}Ga{sub 0.80}N well layers. The anomalous temperature-dependent S-shaped behaviors of emission energies have been observed, indicating the presence of localized states induced by the potential fluctuations in the quantum wells due to the inhomogeneous distribution of In-rich clusters. The degree of the localization effect and the transition temperatures between different temperature regions can be enhanced by increasing Al content in barrier layers. The improvement of the localized states emission has been observed at the lower energy side of band gap emission of quantum wells with increasing Al content. The origin of the deep localized states could be attributed to the larger quantum-confined Stark effect in the quantum wells with higher Al content. The recombination mechanism of carriers between band edge and localized states was proposed for interpreting of the emission characteristics.

  1. Nitrogen-doped multiple graphene aerogel/gold nanostar as the electrochemical sensing platform for ultrasensitive detection of circulating free DNA in human serum.

    Ruiyi, Li; Ling, Liu; Hongxia, Bei; Zaijun, Li

    2016-05-15

    Graphene aerogel has attracted increasing attention due to its large specific surface area, high-conductivity and electronic interaction. The paper reported a facile synthesis of nitrogen-doped multiple graphene aerogel/gold nanostar (termed as N-doped MGA/GNS) and its use as the electrochemical sensing platform for detection of double stranded (dsDNA). On the one hand, the N-doped MGA offers a much better electrochemical performance compared with classical graphene aerogel. Interestingly, the performance can be enhanced by only increasing the cycle number of graphene oxide gelation. On the other hand, the hybridization with GNS further enhances the electrocatalytic activity towards Fe(CN)6(3-/4-). In addition, the N-doped MGA/GNS provides a well-defined three-dimensional architecture. The unique structure make it is easy to combine with dsDNA to form the electroactive bioconjugate. The integration not only triggers an ultrafast DNA electron and charge transfer, but also realizes a significant synergy between N-doped MGA, GNS and dsDNA. As a result, the electrochemical sensor based on the hybrid exhibits highly sensitive differential pulse voltammetric response (DPV) towards dsDNA. The DPV signal linearly increases with the increase of dsDNA concentration in the range from 1.0×10(-)(21) g ml(-)(1) to 1.0×10(-16) g ml(-1) with the detection limit of 3.9×10(-22) g ml(-1) (S/N=3). The sensitivity is much more than that of all reported DNA sensors. The analytical method was successfully applied in the electrochemical detection of circulating free DNA in human serum. The study also opens a window on the electrical properties of multiple graphene aerogel and DNA as well their hybrids to meet the needs of further applications as special nanoelectronics in molecule diagnosis, bioanalysis and catalysis. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Impact of cladribine therapy on changes in circulating dendritic cell subsets, T cells and B cells in patients with multiple sclerosis.

    Mitosek-Szewczyk, Krystyna; Tabarkiewicz, Jacek; Wilczynska, Barbara; Lobejko, Katarzyna; Berbecki, Jerzy; Nastaj, Marcin; Dworzanska, Ewa; Kolodziejczyk, Beata; Stelmasiak, Zbigniew; Rolinski, Jacek

    2013-09-15

    Cladribine causes sustained reduction in peripheral T and B cell populations while sparing other immune cells. We determined two populations of dendritic cells (DCs): namely CD1c(+)/CD19(-) (myeloid DCs) and CD303(+)/CD123(+) (plasmacytoid DCs), CD19(+) B lymphocytes, CD3(+) T lymphocytes and CD4(+) or CD8(+) subpopulations in patients with multiple sclerosis after cladribine therapy. We examined 50 patients with secondary progressive multiple sclerosis (SP MS) according to McDonalds et al.'s criteria, 2001 [15]. Blood samples were collected before the initiation of cladribine therapy and after 1st, 2nd, 3th, 4th and 5th courses of treatment. DC subsets, T and B cells were analyzed by flow cytometry. During cladribine treatment the myeloid DCs CD1c(+)/CD19(-) did not change (p=0.73175), and the plasmacytoid DCs CD303(+)/CD123(+) significantly increased (p=0.00034) which resulted in significant changes in the ratio of myeloid DCs to plasmacytoid DCs (p=0.00273). During therapy, B lymphocyte CD19(+) significantly decreased (p=0.00005) and significant changes in CD4(+) cells (p=0.00191), changes in CD8(+) cells (p=0.05760) and significant changes in CD3(+) (p=0.01822) were found. We noticed significant trend to increase the CD303(+) circulating the dendritic cells. This population produces large amounts of IFN-alfa. We found significant and rapid decrease in B cells and CD4(+) Th cells. Our results suggest two possible ways of beneficial cladribine influence on immune system in MS. Induction of IFN-alfa producing cells and their predominance over BDCA-1(+) DCs, which are associated with cytotoxic response. Additionally, cladribine could influence two populations of lymphocytes: B cells and Th lymphocytes responsible for induction of immune response against myelin antigens. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Comparative genomic analysis reveals multiple long terminal repeats, lineage-specific amplification, and frequent interelement recombination for Cassandra retrotransposon in pear (Pyrus bretschneideri Rehd.).

    Yin, Hao; Du, Jianchang; Li, Leiting; Jin, Cong; Fan, Lian; Li, Meng; Wu, Jun; Zhang, Shaoling

    2014-06-04

    Cassandra transposable elements belong to a specific group of terminal-repeat retrotransposons in miniature (TRIM). Although Cassandra TRIM elements have been found in almost all vascular plants, detailed investigations on the nature, abundance, amplification timeframe, and evolution have not been performed in an individual genome. We therefore conducted a comprehensive analysis of Cassandra retrotransposons using the newly sequenced pear genome along with four other Rosaceae species, including apple, peach, mei, and woodland strawberry. Our data reveal several interesting findings for this particular retrotransposon family: 1) A large number of the intact copies contain three, four, or five long terminal repeats (LTRs) (∼20% in pear); 2) intact copies and solo LTRs with or without target site duplications are both common (∼80% vs. 20%) in each genome; 3) the elements exhibit an overall unbiased distribution among the chromosomes; 4) the elements are most successfully amplified in pear (5,032 copies); and 5) the evolutionary relationships of these elements vary among different lineages, species, and evolutionary time. These results indicate that Cassandra retrotransposons contain more complex structures (elements with multiple LTRs) than what we have known previously, and that frequent interelement unequal recombination followed by transposition may play a critical role in shaping and reshaping host genomes. Thus this study provides insights into the property, propensity, and molecular mechanisms governing the formation and amplification of Cassandra retrotransposons, and enhances our understanding of the structural variation, evolutionary history, and transposition process of LTR retrotransposons in plants. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  4. Instruments for oral disease-intervention strategies : recombinant Lactobacillus casei expressing tetanus toxin fragment C for vaccination or myelin proteins for oral tolerance induction in multiple sclerosis

    Maassen, C.B.M.; Laman, J.D.; Heijne den Bak-Glashouwer, M.J.; Tielen, F.J.; Holten-Neelen, J.C.P.A. van; Hoogteijling, L.; Antonissen, C.; Leer, R.J.; Pouwels, P.H.; Boersma, W.J.A.; Shaw, D.M.

    1999-01-01

    Lactobacillus strains possess properties that make them attractive candidates as vehicles for oral administration of therapeutics. In this report we describe the construction and analysis of recombinant Lactobacillus casei applicable in oral vaccination against an infectious disease (tetanus) and in

  5. Spectrum Recombination.

    Greenslade, Thomas B., Jr.

    1984-01-01

    Describes several methods of executing lecture demonstrations involving the recombination of the spectrum. Groups the techniques into two general classes: bringing selected portions of the spectrum together using lenses or mirrors and blurring the colors by rapid movement or foreshortening. (JM)

  6. A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.

    Andrea D Coviello

    Full Text Available Sex hormone-binding globulin (SHBG is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8 × 10(-106, PRMT6 (rs17496332, 1p13.3, p = 1.4 × 10(-11, GCKR (rs780093, 2p23.3, p = 2.2 × 10(-16, ZBTB10 (rs440837, 8q21.13, p = 3.4 × 10(-09, JMJD1C (rs7910927, 10q21.3, p = 6.1 × 10(-35, SLCO1B1 (rs4149056, 12p12.1, p = 1.9 × 10(-08, NR2F2 (rs8023580, 15q26.2, p = 8.3 × 10(-12, ZNF652 (rs2411984, 17q21.32, p = 3.5 × 10(-14, TDGF3 (rs1573036, Xq22.3, p = 4.1 × 10(-14, LHCGR (rs10454142, 2p16.3, p = 1.3 × 10(-07, BAIAP2L1 (rs3779195, 7q21.3, p = 2.7 × 10(-08, and UGT2B15 (rs293428, 4q13.2, p = 5.5 × 10(-06. These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5 × 10(-08, women p = 0.66, heterogeneity p = 0.003. Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion

  7. Characterization of a recombinant humanized anti-cocaine monoclonal antibody produced from multiple clones for the selection of a master cell bank candidate.

    Wetzel, Hanna N; Webster, Rose P; Saeed, Fatima O; Kirley, Terence L; Ball, William J; Norman, Andrew B

    2017-06-03

    We have generated a humanized anti-cocaine monoclonal antibody (mAb), which is at an advanced stage of pre-clinical development. We report here in vitro binding affinity studies, and in vivo pharmacokinetic and efficacy studies of the recombinant mAb. The overall aim was to characterize the recombinant antibody from each of the three highest producing transfected clones and to select one to establish a master cell bank. In mAb pharmacokinetic studies, after injection with h2E2 (120 mg/kg iv) blood was collected from the tail tip of mice over 28 days. Antibody concentrations were quantified using ELISA. The h2E2 concentration as a function of time was fit using a two-compartment pharmacokinetic model. To test in vivo efficacy, mice were injected with h2E2 (120 mg/kg iv), then one hour later injected with an equimolar dose of cocaine. Blood and brain were collected 5 min after cocaine administration. Cocaine concentrations were quantified using LC/MS. The affinity of the antibody for cocaine was determined using a [ 3 H] cocaine binding assay. All three antibodies had long elimination half-lives, 2-5 nM Kd for cocaine, and prevented cocaine's entry into the brain by sequestering it in the plasma. Pharmacokinetic and radioligand binding assays supported designation of the highest producing clone 85 as the master cell bank candidate. Overall, the recombinant h2E2 showed favorable binding properties, pharmacokinetics, and in vivo efficacy. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Branching innovation, recombinant innovation, and endogenous technological transitions

    Frenken, K.; Izquierdo, L.; Zeppini, P.

    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

  9. Semi-passive pad (post-accident dilution) system combined with recombiners or igniters for e.g., multiple-unit VVER

    Eckardt, B.A.

    1997-01-01

    In order to reduce the risk associated with hypothetical severe nuclear accidents, it has been necessary to develop means for hydrogen control which are capable of handling high H 2 production rates of several m 3 /s. These systems and components should be of simple and, as far as possible, passive design. Moreover, their efficiency must not be affected by the H 2 production scenario. To meet these requirements, Siemens has supplemented its dual process for hydrogen reduction using recombiners and igniters by developing a new process: the semi-passive Post-Accident Dilution (PAD) System. The objective of the work presented in this paper was to design an alternative approach for hydrogen control comprising post-accident CO 2 dilution combined with recombiners or igniters for postulated severe accidents that result in significant hydrogen releases. The combined technique was to keep the dynamic loads arising inside the containment to within a range of only a few millibars, even in the event of transient hydrogen release and distribution processes accompanied by combustion, and was thus to prevent any hazard for safety-related equipment. (author)

  10. Protection against multiple influenza A virus strains induced by candidate recombinant vaccine based on heterologous M2e peptides linked to flagellin.

    Liudmila A Stepanova

    Full Text Available Matrix 2 protein ectodomain (M2e is considered a promising candidate for a broadly protective influenza vaccine. M2e-based vaccines against human influenza A provide only partial protection against avian influenza viruses because of differences in the M2e sequences. In this work, we evaluated the possibility of obtaining equal protection and immune response by using recombinant protein on the basis of flagellin as a carrier of the M2e peptides of human and avian influenza A viruses. Recombinant protein was generated by the fusion of two tandem copies of consensus M2e sequence from human influenza A and two copies of M2e from avian A/H5N1 viruses to flagellin (Flg-2M2eh2M2ek. Intranasal immunisation of Balb/c mice with recombinant protein significantly elicited anti-M2e IgG in serum, IgG and sIgA in BAL. Antibodies induced by the fusion protein Flg-2M2eh2M2ek bound efficiently to synthetic peptides corresponding to the human consensus M2e sequence as well as to the M2e sequence of A/Chicken/Kurgan/05/05 RG (H5N1 and recognised native M2e epitopes exposed on the surface of the MDCK cells infected with A/PR/8/34 (H1N1 and A/Chicken/Kurgan/05/05 RG (H5N1 to an equal degree. Immunisation led to both anti-M2e IgG1 and IgG2a response with IgG1 prevalence. We observed a significant intracellular production of IL-4, but not IFN-γ, by CD4+ T-cells in spleen of mice following immunisation with Flg-2M2eh2M2ek. Immunisation with the Flg-2M2eh2M2ek fusion protein provided similar protection from lethal challenge with human influenza A viruses (H1N1, H3N2 and avian influenza virus (H5N1. Immunised mice experienced significantly less weight loss and decreased lung viral titres compared to control mice. The data obtained show the potential for the development of an M2e-flagellin candidate influenza vaccine with broad spectrum protection against influenza A viruses of various origins.

  11. Characterisation of Population Pharmacokinetics and Endogenous Follicle Stimulating Hormone (FSH) Levels after Multiple Dosing of a Recombinant Human FSH, FE 999049, in Healthy Women

    Rose, Trine Høyer; Röshammer, Daniel; Erichsen, Lars

    2016-01-01

    : Longitudinal measurements of FSH, luteinising hormone, progesterone, estradiol, and inhibin B levels were collected after repeated subcutaneous dosing with 225 IU of FE 999049 in 24 gonadotropin downregulated healthy women. The FSH data were described using nonlinear mixed-effects modelling. Results...... increased with body weight in accordance with an allometrically scaled power exponent of 0.75 and 1, respectively. Endogenous FSH levels were lower in individuals with higher progesterone levels at baseline and were further suppressed over time with increasing inhibin B levels. Conclusions......: This characterisation of FE 999049 population pharmacokinetics after repeated dosing is in line with previous findings after single-dose administration. The results provide a basis for study design and data evaluation in the future development of recombinant FSH products, and show it can be of importance to account...

  12. Characterization of foot-and-mouth disease viruses from Ugandan cattle outbreaks during 2012-2013: Evidence for circulation of multiple serotypes

    Namatovu, Alice; Tjørnehøj, Kirsten; Belsham, Graham

    2015-01-01

    To investigate the foot-and-mouth disease virus (FMDV) serotypes circulating in Uganda’s cattle population, both serological and virological analyses of samples from outbreaks that occurred during 2012-2013 were performed. Altogether, 79 sera and 60 oropharyngeal fluid (OP)/tissue/oral swab samples...... were collected from herds with reported FMD outbreaks in seven different Ugandan districts. Overall, 61/79 (77%) of the cattle sera were positive for antibodies against FMDV by PrioCHECK® FMDV NS ELISA and solid phase blocking ELISA detected titres ≥ 80 for serotypes O, SAT 1, SAT 2 and SAT 3 in 41, 45...... Kiruhura, Isingiro and Ntungamo districts. Consistent with the detection of high levels of neutralising antibodies against SAT 2, was the isolation of a SAT 2 FMDV from Isingiro; sequencing (for the VP1 coding region) indicated that this virus belonged to lineage I within this serotype, like the currently...

  13. Circulation of multiple subtypes of bovine viral diarrhoea virus type 1 with no evidence for HoBi-like pestivirus in cattle herds of southern Italy.

    Lanave, G; Decaro, N; Lucente, M S; Guercio, A; Cavaliere, N; Purpari, G; Padalino, I; Larocca, V; Antoci, F; Marino, P A; Buonavoglia, C; Elia, G

    2017-06-01

    Pestiviruses of cattle include bovine viral diarrhoea 1 (BVDV-1) and 2 (BVDV-2) plus an emerging group, named HoBi-like pestivirus. In the present paper, the results of an epidemiological survey for pestiviruses circulating in cattle in southern Italy are presented. Molecular assays carried out on a total of 924 bovine samples detected 74 BVDV strains, including 73 BVDV-1 and 1 BVDV-2 viruses. Phylogenetic analysis carried out on partial 5'UTR and N pro sequences revealed the presence of 6 different subtypes of BVDV-1 and a single BVDV-2c strain. BVDV-1 displayed a high level of genetic heterogeneity, which can have both prophylactic and diagnostic implications. In addition, the detection of BVDV-2c highlights the need for a continuous surveillance for the emergence of new pestivirus strains in cattle farms in southern Italy. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Recombinant Collagenlike Proteins

    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.

  15. Endovascular treatment of chronic cerebro spinal venous insufficiency in patients with multiple sclerosis modifies circulating markers of endothelial dysfunction and coagulation activation: a prospective study.

    Napolitano, Mariasanta; Bruno, Aldo; Mastrangelo, Diego; De Vizia, Marcella; Bernardo, Benedetto; Rosa, Buonagura; De Lucia, Domenico

    2014-10-01

    We performed a monocentric observational prospective study to evaluate coagulation activation and endothelial dysfunction parameters in patients with multiple sclerosis undergoing endovascular treatment for cerebro-spinal-venous insufficiency. Between February 2011 and July 2012, 144 endovascular procedures in 110 patients with multiple sclerosis and chronical cerebro-spinal venous insufficiency were performed and they were prospectively analyzed. Each patient was included in the study according to previously published criteria, assessed by the investigators before enrollment. Endothelial dysfunction and coagulation activation parameters were determined before the procedure and during follow-up at 1, 3, 6, 9, 12, 15 and 18 months after treatment, respectively. After the endovascular procedure, patients were treated with standard therapies, with the addition of mesoglycan. Fifty-five percent of patients experienced a favorable outcome of multiple sclerosis within 1 month after treatment, 25% regressed in the following 3 months, 24.9% did not experience any benefit. In only 0.1% patients, acute recurrence was observed and it was treated with high-dose immunosuppressive therapy. No major complications were observed. Coagulation activation and endothelial dysfunction parameters were shown to be reduced at 1 month and stable up to 12-month follow-up, and they were furthermore associated with a good clinical outcome. Endovascular procedures performed by a qualified staff are well tolerated; they can be associated with other currently adopted treatments. Correlations between inflammation, coagulation activation and neurodegenerative disorders are here supported by the observed variations in plasma levels of markers of coagulation activation and endothelial dysfunction.

  16. Characterization of Foot-And-Mouth Disease Viruses (FMDVs) from Ugandan Cattle Outbreaks during 2012-2013: Evidence for Circulation of Multiple Serotypes

    Namatovu, Alice; Tjørnehøj, Kirsten; Belsham, Graham J.; Dhikusooka, Moses T.; Wekesa, Sabenzia N.; Muwanika, Vincent B.; Siegismund, Hans R.; Ayebazibwe, Chrisostom

    2015-01-01

    To investigate the foot-and-mouth disease virus (FMDV) serotypes circulating in Uganda’s cattle population, both serological and virological analyses of samples from outbreaks that occurred during 2012–2013 were performed. Altogether, 79 sera and 60 oropharyngeal fluid (OP)/tissue/oral swab samples were collected from herds with reported FMD outbreaks in seven different Ugandan districts. Overall, 61/79 (77%) of the cattle sera were positive for antibodies against FMDV by PrioCHECK FMDV NS ELISA and solid phase blocking ELISA detected titres ≥ 80 for serotypes O, SAT 1, SAT 2 and SAT 3 in 41, 45, 30 and 45 of these 61 seropositive samples, respectively. Virus neutralisation tests detected the highest levels of neutralising antibodies (titres ≥ 45) against serotype O in the herds from Kween and Rakai districts, against SAT 1 in the herd from Nwoya district and against SAT 2 in the herds from Kiruhura, Isingiro and Ntungamo districts. The isolation of a SAT 2 FMDV from Isingiro was consistent with the detection of high levels of neutralising antibodies against SAT 2; sequencing (for the VP1 coding region) indicated that this virus belonged to lineage I within this serotype, like the currently used vaccine strain. From the Wakiso district 11 tissue/swab samples were collected; serotype A FMDV, genotype Africa (G-I), was isolated from the epithelial samples. This study shows that within a period of less than one year, FMD outbreaks in Uganda were caused by four different serotypes namely O, A, SAT 1 and SAT 2. Therefore, to enhance the control of FMD in Uganda, there is need for efficient and timely determination of outbreak virus strains/serotypes and vaccine matching. The value of incorporating serotype A antigen into the imported vaccines along with the current serotype O, SAT 1 and SAT 2 strains should be considered. PMID:25664876

  17. Recombining without Hotspots: A Comprehensive Evolutionary Portrait of Recombination in Two Closely Related Species of Drosophila

    Smukowski Heil, Caiti S.; Ellison, Chris; Dubin, Matthew; Noor, Mohamed A.F.

    2015-01-01

    Meiotic recombination rate varies across the genome within and between individuals, populations, and species in virtually all taxa studied. In almost every species, this variation takes the form of discrete recombination hotspots, determined in some mammals by a protein called PRDM9. Hotspots and their determinants have a profound effect on the genomic landscape, and share certain features that extend across the tree of life. Drosophila, in contrast, are anomalous in their absence of hotspots, PRDM9, and other species-specific differences in the determination of recombination. To better understand the evolution of meiosis and general patterns of recombination across diverse taxa, we present a truly comprehensive portrait of recombination across time, combining recently published cross-based contemporary recombination estimates from each of two sister species with newly obtained linkage-disequilibrium-based historic estimates of recombination from both of these species. Using Drosophila pseudoobscura and Drosophila miranda as a model system, we compare recombination rate between species at multiple scales, and we suggest that Drosophila replicate the pattern seen in human–chimpanzee in which recombination rate is conserved at broad scales. We also find evidence of a species-wide recombination modifier(s), resulting in both a present and historic genome-wide elevation of recombination rates in D. miranda, and identify broad scale effects on recombination from the presence of an inversion. Finally, we reveal an unprecedented view of the distribution of recombination in D. pseudoobscura, illustrating patterns of linked selection and where recombination is taking place. Overall, by combining these estimation approaches, we highlight key similarities and differences in recombination between Drosophila and other organisms. PMID:26430062

  18. Recombining without Hotspots: A Comprehensive Evolutionary Portrait of Recombination in Two Closely Related Species of Drosophila.

    Smukowski Heil, Caiti S; Ellison, Chris; Dubin, Matthew; Noor, Mohamed A F

    2015-10-01

    Meiotic recombination rate varies across the genome within and between individuals, populations, and species in virtually all taxa studied. In almost every species, this variation takes the form of discrete recombination hotspots, determined in some mammals by a protein called PRDM9. Hotspots and their determinants have a profound effect on the genomic landscape, and share certain features that extend across the tree of life. Drosophila, in contrast, are anomalous in their absence of hotspots, PRDM9, and other species-specific differences in the determination of recombination. To better understand the evolution of meiosis and general patterns of recombination across diverse taxa, we present a truly comprehensive portrait of recombination across time, combining recently published cross-based contemporary recombination estimates from each of two sister species with newly obtained linkage-disequilibrium-based historic estimates of recombination from both of these species. Using Drosophila pseudoobscura and Drosophila miranda as a model system, we compare recombination rate between species at multiple scales, and we suggest that Drosophila replicate the pattern seen in human-chimpanzee in which recombination rate is conserved at broad scales. We also find evidence of a species-wide recombination modifier(s), resulting in both a present and historic genome-wide elevation of recombination rates in D. miranda, and identify broad scale effects on recombination from the presence of an inversion. Finally, we reveal an unprecedented view of the distribution of recombination in D. pseudoobscura, illustrating patterns of linked selection and where recombination is taking place. Overall, by combining these estimation approaches, we highlight key similarities and differences in recombination between Drosophila and other organisms. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  19. Effects of quantum well growth temperature on the recombination efficiency of InGaN/GaN multiple quantum wells that emit in the green and blue spectral regions

    Hammersley, S.; Dawson, P. [School of Physics and Astronomy, Photon Science Institute, University of Manchester, Manchester M13 9PL (United Kingdom); Kappers, M. J.; Massabuau, F. C.-P.; Sahonta, S.-L.; Oliver, R. A.; Humphreys, C. J. [Department of Materials Science and Metallurgy, University of Cambridge, 27 Charles Babbage Road, Cambridge CB3 0FS (United Kingdom)

    2015-09-28

    InGaN-based light emitting diodes and multiple quantum wells designed to emit in the green spectral region exhibit, in general, lower internal quantum efficiencies than their blue-emitting counter parts, a phenomenon referred to as the “green gap.” One of the main differences between green-emitting and blue-emitting samples is that the quantum well growth temperature is lower for structures designed to emit at longer wavelengths, in order to reduce the effects of In desorption. In this paper, we report on the impact of the quantum well growth temperature on the optical properties of InGaN/GaN multiple quantum wells designed to emit at 460 nm and 530 nm. It was found that for both sets of samples increasing the temperature at which the InGaN quantum well was grown, while maintaining the same indium composition, led to an increase in the internal quantum efficiency measured at 300 K. These increases in internal quantum efficiency are shown to be due reductions in the non-radiative recombination rate which we attribute to reductions in point defect incorporation.

  20. Effects of quantum well growth temperature on the recombination efficiency of InGaN/GaN multiple quantum wells that emit in the green and blue spectral regions

    Hammersley, S.; Dawson, P.; Kappers, M. J.; Massabuau, F. C.-P.; Sahonta, S.-L.; Oliver, R. A.; Humphreys, C. J.

    2015-01-01

    InGaN-based light emitting diodes and multiple quantum wells designed to emit in the green spectral region exhibit, in general, lower internal quantum efficiencies than their blue-emitting counter parts, a phenomenon referred to as the “green gap.” One of the main differences between green-emitting and blue-emitting samples is that the quantum well growth temperature is lower for structures designed to emit at longer wavelengths, in order to reduce the effects of In desorption. In this paper, we report on the impact of the quantum well growth temperature on the optical properties of InGaN/GaN multiple quantum wells designed to emit at 460 nm and 530 nm. It was found that for both sets of samples increasing the temperature at which the InGaN quantum well was grown, while maintaining the same indium composition, led to an increase in the internal quantum efficiency measured at 300 K. These increases in internal quantum efficiency are shown to be due reductions in the non-radiative recombination rate which we attribute to reductions in point defect incorporation

  1. Therapeutic Recombinant Monoclonal Antibodies

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  2. Molecular requirements for radiation-activated recombination

    Stevens, Craig W.; Zeng Ming; Stamato, Thomas; Cerniglia, George

    1997-01-01

    Purpose/Objective: The major stumbling block to successful gene therapy today is poor gene transfer. We hypothesized that ionizing radiation might activate cellular recombination, and so improve stable gene transfer. We further hypothesized that known DNA-damage-repair proteins might also be important in radiation-activated recombination. Materials and Methods: The effect of irradiation on stable gene transfer efficiency was determined in human (A549 and 39F) and rodent (NIH/3T3) cell lines. Continuous low dose rate and multiple radiation fractions were also tested. Nuclear extracts were made and the effect of irradiation on inter-plasmid recombination/ligation determined. Multiple DNA damage-repair deficient cell lines were tested for radiation-activated recombination. Results: A significant radiation dose-dependent improvement in stable plasmid transfection (by as much as 1300 fold) is demonstrated in neoplastic and primary cells. An improvement in transient plasmid transfection is also seen, with as much as 85% of cells transiently expressing b-galactosidase (20-50 fold improvement). Stable transfection is only improved for linearized or nicked plasmids. Cells have improved gene transfer for at least 96 hours after irradiation. Both fractionated and continuous low dose rate irradiation are effective at improving stable gene transfer in mammalian cells, thus making relatively high radiation dose delivery clinically feasible. Inter-plasmid recombination is radiation dose dependent in nuclear extract assays, and the type of overhang (3', 5' or blunt end) significantly affects recombination efficiency and the type of product. The most common end-joining activity involves filling-in of the overhang followed by blunt end ligation. Adenovirus is a linear, double stranded DNA virus. We demonstrate that adenoviral infection efficiency is increased by irradiation. The duration of transgene expression is lengthened because the virus integrates with high efficiency (∼10

  3. Recombination Modulates How Selection Affects Linked Sites in Drosophila

    McGaugh, Suzanne E.; Heil, Caiti S. S.; Manzano-Winkler, Brenda; Loewe, Laurence; Goldstein, Steve; Himmel, Tiffany L.; Noor, Mohamed A. F.

    2012-01-01

    One of the most influential observations in molecular evolution has been a strong association between local recombination rate and nucleotide polymorphisms across the genome. This is interpreted as evidence for ubiquitous natural selection. The alternative explanation, that recombination is mutagenic, has been rejected by the absence of a similar association between local recombination rate and nucleotide divergence between species. However, many recent studies show that recombination rates are often very different even in closely related species, questioning whether an association between recombination rate and divergence between species has been tested satisfactorily. To circumvent this problem, we directly surveyed recombination across approximately 43% of the D. pseudoobscura physical genome in two separate recombination maps and 31% of the D. miranda physical genome, and we identified both global and local differences in recombination rate between these two closely related species. Using only regions with conserved recombination rates between and within species and accounting for multiple covariates, our data support the conclusion that recombination is positively related to diversity because recombination modulates Hill–Robertson effects in the genome and not because recombination is predominately mutagenic. Finally, we find evidence for dips in diversity around nonsynonymous substitutions. We infer that at least some of this reduction in diversity resulted from selective sweeps and examine these dips in the context of recombination rate. PMID:23152720

  4. Photoionization and Recombination

    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.

  5. Novel canine circovirus strains from Thailand: Evidence for genetic recombination.

    Piewbang, Chutchai; Jo, Wendy K; Puff, Christina; van der Vries, Erhard; Kesdangsakonwut, Sawang; Rungsipipat, Anudep; Kruppa, Jochen; Jung, Klaus; Baumgärtner, Wolfgang; Techangamsuwan, Somporn; Ludlow, Martin; Osterhaus, Albert D M E

    2018-05-14

    Canine circoviruses (CanineCV's), belonging to the genus Circovirus of the Circoviridae family, were detected by next generation sequencing in samples from Thai dogs with respiratory symptoms. Genetic characterization and phylogenetic analysis of nearly complete CanineCV genomes suggested that natural recombination had occurred among different lineages of CanineCV's. Similarity plot and bootscaning analyses indicated that American and Chinese viruses had served as major and minor parental viruses, respectively. Positions of recombination breakpoints were estimated using maximum-likelihood frameworks with statistical significant testing. The putative recombination event was located in the Replicase gene, intersecting with open reading frame-3. Analysis of nucleotide changes confirmed the origin of the recombination event. This is the first description of naturally occurring recombinant CanineCV's that have resulted in the circulation of newly emerging CanineCV lineages.

  6. Recombination of cluster ions

    Johnsen, Rainer

    1993-01-01

    Some of our recent work on molecular band emissions from recombination of molecular dimer ions (N4(+) and CO(+) CO) is discussed. Much of the experimental work was done by Y. S. Cao; the results on N4(+) recombination have been published. A brief progress report is given on our ongoing measurements of neutral products of recombination using the flowing-afterglow Langmuir-probe technique in conjunction with laser-induced fluorescence.

  7. Poliovirus Polymerase Leu420 Facilitates RNA Recombination and Ribavirin Resistance

    Kempf, Brian J.; Peersen, Olve B.

    2016-01-01

    ABSTRACT RNA recombination is important in the formation of picornavirus species groups and the ongoing evolution of viruses within species groups. In this study, we examined the structure and function of poliovirus polymerase, 3Dpol, as it relates to RNA recombination. Recombination occurs when nascent RNA products exchange one viral RNA template for another during RNA replication. Because recombination is a natural aspect of picornavirus replication, we hypothesized that some features of 3Dpol may exist, in part, to facilitate RNA recombination. Furthermore, we reasoned that alanine substitution mutations that disrupt 3Dpol-RNA interactions within the polymerase elongation complex might increase and/or decrease the magnitudes of recombination. We found that an L420A mutation in 3Dpol decreased the frequency of RNA recombination, whereas alanine substitutions at other sites in 3Dpol increased the frequency of recombination. The 3Dpol Leu420 side chain interacts with a ribose in the nascent RNA product 3 nucleotides from the active site of the polymerase. Notably, the L420A mutation that reduced recombination also rendered the virus more susceptible to inhibition by ribavirin, coincident with the accumulation of ribavirin-induced G→A and C→U mutations in viral RNA. We conclude that 3Dpol Leu420 is critically important for RNA recombination and that RNA recombination contributes to ribavirin resistance. IMPORTANCE Recombination contributes to the formation of picornavirus species groups and the emergence of circulating vaccine-derived polioviruses (cVDPVs). The recombinant viruses that arise in nature are occasionally more fit than either parental strain, especially when the two partners in recombination are closely related, i.e., members of characteristic species groups, such as enterovirus species groups A to H or rhinovirus species groups A to C. Our study shows that RNA recombination requires conserved features of the viral polymerase. Furthermore, a

  8. CRMAGE: CRISPR Optimized MAGE Recombineering

    Ronda, Carlotta; Pedersen, Lasse Ebdrup; Sommer, Morten Otto Alexander

    2016-01-01

    A bottleneck in metabolic engineering and systems biology approaches is the lack of efficient genome engineering technologies. Here, we combine CRISPR/Cas9 and λ Red recombineering based MAGE technology (CRMAGE) to create a highly efficient and fast method for genome engineering of Escherichia coli...... that are assembled by a USER-cloning approach enabling quick and cost efficient gRNA replacement. CRMAGE furthermore utilizes CRISPR/Cas9 for efficient plasmid curing, thereby enabling multiple engineering rounds per day. To facilitate the design process, a web-based tool was developed to predict both the λ Red...

  9. Microwave circulator design

    Linkhart, Douglas K

    2014-01-01

    Circulator design has advanced significantly since the first edition of this book was published 25 years ago. The objective of this second edition is to present theory, information, and design procedures that will enable microwave engineers and technicians to design and build circulators successfully. This resource contains a discussion of the various units used in the circulator design computations, as well as covers the theory of operation. This book presents numerous applications, giving microwave engineers new ideas about how to solve problems using circulators. Design examples are provided, which demonstrate how to apply the information to real-world design tasks.

  10. Circulation pump mounting

    Skalicky, A.

    1976-01-01

    The suspension is described of nuclear reactor circulating pumps enabling their dilatation with a minimum reverse force consisting of spacing rods supported with one end in the anchor joints and provided with springs and screw joints engaging the circulating pump shoes. The spacing rods are equipped with side vibration dampers anchored in the shaft side wall and on the body of the circulating pump drive body. The negative reverse force F of the spacing rods is given by the relation F=Q/l.y, where Q is the weight of the circulating pump, l is the spatial distance between the shoe joints and anchor joints, and y is the deflection of the circulating pump vertical axis from the mean equilibrium position. The described suspension is advantageous in that that the reverse force for the deflection from the mean equilibrium position is minimal, dynamic behaviour is better, and construction costs are lower compared to suspension design used so far. (J.B.)

  11. Activated recombinant adenovirus proteinases

    Anderson, Carl W.; Mangel, Walter F.

    1999-08-10

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying said peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described.

  12. Hadron correlations from recombination

    Fries, Rainer J [School of Physics and Astronomy, University of Minnesota, Minneapolis, MN 55455 (United States)

    2005-01-01

    Quark recombination is a successful model to describe the hadronization of a deconfined quark gluon plasma. Jet-like dihadron correlations measured at RHIC provide a challenge for this picture. We discuss how correlations between hadrons can arise from correlations between partons before hadronization. An enhancement of correlations through the recombination process, similar to the enhancement of elliptic flow is found. Hot spots from completely or partially quenched jets are a likely source of such parton correlations.

  13. Seasonal overturning circulation in the Red Sea: 2. Winter circulation

    Yao, Fengchao; Hoteit, Ibrahim; Pratt, Lawrence J.; Bower, Amy S.; Kö hl, Armin; Gopalakrishnan, Ganesh; Rivas, David

    2014-01-01

    The shallow winter overturning circulation in the Red Sea is studied using a 50 year high-resolution MITgcm (MIT general circulation model) simulation with realistic atmospheric forcing. The overturning circulation for a typical year, represented

  14. Evidence for Within-Host Genetic Recombination among the Human Pegiviral Strains in HIV Infected Subjects.

    Wu, Haoming; Padhi, Abinash; Xu, Junqiang; Gong, Xiaoyan; Tien, Po

    2016-01-01

    The non-pathogenic Human Pegivirus (HPgV, formerly GBV-C/HGV), the most prevalent RNA virus worldwide, is known to be associated with reduced morbidity and mortality in HIV-infected individuals. Although previous studies documented its ubiquity and important role in HIV-infected individuals, little is known about the underlying genetic mechanisms that maintain high genetic diversity of HPgV within the HIV-infected individuals. To assess the within-host genetic diversity of HPgV and forces that maintain such diversity within the co-infected hosts, we performed phylogenetic analyses taking into account 229 HPgV partial E1-E2 clonal sequences representing 15 male and 8 female co-infected HIV patients from Hubei province of central China. Our results revealed the presence of eleven strongly supported clades. While nine clades belonged to genotype 3, two clades belonged to genotype 2. Additionally, four clades that belonged to genotype 3 exhibited inter-clade recombination events. The presence of clonal sequences representing multiple clades within the HIV-infected individual provided the evidence of co-circulation of HPgV strains across the region. Of the 23 patients, six patients (i.e., five males and one female) were detected to have HPgV recombinant sequences. Our results also revealed that while male patients shared the viral strains with other patients, viral strains from the female patients had restricted dispersal. Taken together, the present study revealed that multiple infections with divergent HPgV viral strains may have caused within-host genetic recombination, predominantly in male patients, and therefore, could be the major driver in shaping genetic diversity of HPgV.

  15. Regulation of Meiotic Recombination

    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

  16. Two novel porcine epidemic diarrhea virus (PEDV) recombinants from a natural recombinant and distinct subtypes of PEDV variants.

    Chen, Nanhua; Li, Shuangjie; Zhou, Rongyun; Zhu, Meiqin; He, Shan; Ye, Mengxue; Huang, Yucheng; Li, Shuai; Zhu, Cong; Xia, Pengpeng; Zhu, Jianzhong

    2017-10-15

    Porcine epidemic diarrhea virus (PEDV) causes devastating impact on global pig-breeding industry and current vaccines have become not effective against the circulating PEDV variants since 2011. During the up-to-date investigation of PEDV prevalence in Fujian China 2016, PEDV was identified in vaccinated pig farms suffering severe diarrhea while other common diarrhea-associated pathogens were not detected. Complete genomes of two PEDV representatives (XM1-2 and XM2-4) were determined. Genomic comparison showed that these two viruses share the highest nucleotide identities (99.10% and 98.79%) with the 2011 ZMDZY strain, but only 96.65% and 96.50% nucleotide identities with the attenuated CV777 strain. Amino acid alignment of spike (S) proteins indicated that they have the similar mutation, insertion and deletion pattern as other Chinese PEDV variants but also contain several unique substitutions. Phylogenetic analysis showed that 2016 PEDV variants belong to the cluster of recombination strains but form a new branch. Recombination detection suggested that both XM1-2 and XM2-4 are inter-subgroup recombinants with breakpoints within ORF1b. Remarkably, the natural recombinant HNQX-3 isolate serves as a parental virus for both natural recombinants identified in this study. This up-to-date investigation provides the direct evidence that natural recombinants may serve as parental viruses to generate recombined PEDV progenies that are probably associated with the vaccination failure. Copyright © 2017. Published by Elsevier B.V.

  17. Polyploidization increases meiotic recombination frequency in Arabidopsis

    Rehmsmeier Marc

    2011-04-01

    Full Text Available Abstract Background Polyploidization is the multiplication of the whole chromosome complement and has occurred frequently in vascular plants. Maintenance of stable polyploid state over generations requires special mechanisms to control pairing and distribution of more than two homologous chromosomes during meiosis. Since a minimal number of crossover events is essential for correct chromosome segregation, we investigated whether polyploidy has an influence on the frequency of meiotic recombination. Results Using two genetically linked transgenes providing seed-specific fluorescence, we compared a high number of progeny from diploid and tetraploid Arabidopsis plants. We show that rates of meiotic recombination in reciprocal crosses of genetically identical diploid and autotetraploid Arabidopsis plants were significantly higher in tetraploids compared to diploids. Although male and female gametogenesis differ substantially in meiotic recombination frequency, both rates were equally increased in tetraploids. To investigate whether multivalent formation in autotetraploids was responsible for the increased recombination rates, we also performed corresponding experiments with allotetraploid plants showing strict bivalent pairing. We found similarly increased rates in auto- and allotetraploids, suggesting that the ploidy effect is independent of chromosome pairing configurations. Conclusions The evolutionary success of polyploid plants in nature and under domestication has been attributed to buffering of mutations and sub- and neo-functionalization of duplicated genes. Should the data described here be representative for polyploid plants, enhanced meiotic recombination, and the resulting rapid creation of genetic diversity, could have also contributed to their prevalence.

  18. Recombinational repair: workshop summary

    Howard-Flanders, P.

    1983-01-01

    Recombinational repair may or may not be synonymous with postreplication repair. Considerable progress has been made in the study of the relevant enzymes, particularly those from bacteria. In this workshop we focus on the recombination enzyme RecA protein. What structural changes take place in the protein and in DNA during repair. How does homologous pairing take place. How is ATP hydrolysis coupled to the stand exchange reaction and the formation of heteroduplx DNA. Turning to another enzyme needed for certain kinds of bacterial recombination, we will ask whether the purified recB protein and recC protein complement each other and are sufficient for exonuclease V activity. In higher cells, we would like to know whether sister exchanges, which occur in bacteria after uv irradiation, are also seen in animal cells

  19. Comparative analysis of the molecular mechanisms of recombination in hepatitis C virus

    Galli, Andrea; Bukh, Jens

    2014-01-01

    Genetic recombination is an important evolutionary mechanism for RNA viruses. The significance of this phenomenon for hepatitis C virus (HCV) has recently become evident, with the identification of circulating recombinant forms in HCV-infected individuals and by novel data from studies permitted...... by advances in HCV cell culture systems and genotyping protocols. HCV is readily able to produce viable recombinants, using replicative and non-replicative molecular mechanisms. However, our knowledge of the required molecular mechanisms remains limited. Understanding how HCV recombines might be instrumental...... for a better monitoring of global epidemiology, to clarify the virus evolution, and evaluate the impact of recombinant forms on the efficacy of oncoming combination drug therapies. For the latter, frequency and location of recombination events could affect the efficacy of multidrug regimens. This review...

  20. Parton recombination model

    Hwa, R.C.

    1978-08-01

    Low P/sub T/ meson production in hadronic collisions is described in the framework of the parton model. The recombination of quark and antiquark is suggested as the dominant mechanism in the large x region. Phenomenological evidences for the mechanism are given. The application to meson initiated reactions yields the quark distribution in mesons. 21 references

  1. The role of recombination in the emergence of a complex and dynamic HIV epidemic

    Morgenstern Burkhard

    2010-03-01

    Full Text Available Abstract Background Inter-subtype recombinants dominate the HIV epidemics in three geographical regions. To better understand the role of HIV recombinants in shaping the current HIV epidemic, we here present the results of a large-scale subtyping analysis of 9435 HIV-1 sequences that involve subtypes A, B, C, G, F and the epidemiologically important recombinants derived from three continents. Results The circulating recombinant form CRF02_AG, common in West Central Africa, appears to result from recombination events that occurred early in the divergence between subtypes A and G, followed by additional recent recombination events that contribute to the breakpoint pattern defining the current recombinant lineage. This finding also corrects a recent claim that G is a recombinant and a descendant of CRF02, which was suggested to be a pure subtype. The BC and BF recombinants in China and South America, respectively, are derived from recent recombination between contemporary parental lineages. Shared breakpoints in South America BF recombinants indicate that the HIV-1 epidemics in Argentina and Brazil are not independent. Therefore, the contemporary HIV-1 epidemic has recombinant lineages of both ancient and more recent origins. Conclusions Taken together, we show that these recombinant lineages, which are highly prevalent in the current HIV epidemic, are a mixture of ancient and recent recombination. The HIV pandemic is moving towards having increasing complexity and higher prevalence of recombinant forms, sometimes existing as "families" of related forms. We find that the classification of some CRF designations need to be revised as a consequence of (1 an estimated > 5% error in the original subtype assignments deposited in the Los Alamos sequence database; (2 an increasing number of CRFs are defined while they do not readily fit into groupings for molecular epidemiology and vaccine design; and (3 a dynamic HIV epidemic context.

  2. In vivo production of recombinant proteins using occluded recombinant AcMNPV-derived baculovirus vectors.

    Guijarro-Pardo, Eva; Gómez-Sebastián, Silvia; Escribano, José M

    2017-12-01

    Trichoplusia ni insect larvae infected with vectors derived from the Autographa californica multiple nucleopolyhedrovirus (AcMNPV), are an excellent alternative to insect cells cultured in conventional bioreactors to produce recombinant proteins because productivity and cost-efficiency reasons. However, there is still a lot of work to do to reduce the manual procedures commonly required in this production platform that limit its scalability. To increase the scalability of this platform technology, a current bottleneck to be circumvented in the future is the need of injection for the inoculation of larvae with polyhedrin negative baculovirus vectors (Polh-) because of the lack of oral infectivity of these viruses, which are commonly used for production in insect cell cultures. In this work we have developed a straightforward alternative to obtain orally infective vectors derived from AcMNPV and expressing recombinant proteins that can be administered to the insect larvae (Trichoplusia ni) by feeding, formulated in the insect diet. The approach developed was based on the use of a recombinant polyhedrin protein expressed by a recombinant vector (Polh+), able to co-occlude any recombinant Polh- baculovirus vector expressing a recombinant protein. A second alternative was developed by the generation of a dual vector co-expressing the recombinant polyhedrin protein and the foreign gene of interest to obtain the occluded viruses. Additionally, by the incorporation of a reporter gene into the helper Polh+ vector, it was possible the follow-up visualization of the co-occluded viruses infection in insect larvae and will help to homogenize infection conditions. By using these methodologies, the production of recombinant proteins in per os infected larvae, without manual infection procedures, was very similar in yield to that obtained by manual injection of recombinant Polh- AcMNPV-based vectors expressing the same proteins. However, further analyses will be required for a

  3. Recombination Promoted by DNA Viruses: Phage λ to Herpes Simplex Virus

    Weller, Sandra K.; Sawitzke, James A.

    2015-01-01

    The purpose of this review is to explore recombination strategies in DNA viruses. Homologous recombination is a universal genetic process that plays multiple roles in the biology of all organisms, including viruses. Recombination and DNA replication are interconnected, with recombination being essential for repairing DNA damage and supporting replication of the viral genome. Recombination also creates genetic diversity, and viral recombination mechanisms have important implications for understanding viral origins as well as the dynamic nature of viral-host interactions. Both bacteriophage λ and herpes simplex virus (HSV) display high rates of recombination, both utilizing their own proteins and commandeering cellular proteins to promote recombination reactions. We focus primarily on λ and HSV, as they have proven amenable to both genetic and biochemical analysis and have recently been shown to exhibit some surprising similarities that will guide future studies. PMID:25002096

  4. Prdm9 Controls Activation of Mammalian Recombination Hotspots

    Parvanov, Emil D.; Petkov, Petko M.; Paigen, Kenneth

    2009-01-01

    Mammalian meiotic recombination, which preferentially occurs at specialized sites called hotspots, assures the orderly segregation of meiotic chromosomes and creates genetic variation among offspring. A locus on mouse Chr 17, that controls activation of recombination at multiple distant hotspots, has been mapped within a 181 Kb interval, three of whose genes can be eliminated as candidates. The remaining gene, Prdm9, codes for a zinc finger containing histone H3K4 trimethylase that is uniquel...

  5. Arctic circulation regimes.

    Proshutinsky, Andrey; Dukhovskoy, Dmitry; Timmermans, Mary-Louise; Krishfield, Richard; Bamber, Jonathan L

    2015-10-13

    Between 1948 and 1996, mean annual environmental parameters in the Arctic experienced a well-pronounced decadal variability with two basic circulation patterns: cyclonic and anticyclonic alternating at 5 to 7 year intervals. During cyclonic regimes, low sea-level atmospheric pressure (SLP) dominated over the Arctic Ocean driving sea ice and the upper ocean counterclockwise; the Arctic atmosphere was relatively warm and humid, and freshwater flux from the Arctic Ocean towards the subarctic seas was intensified. By contrast, during anticylonic circulation regimes, high SLP dominated driving sea ice and the upper ocean clockwise. Meanwhile, the atmosphere was cold and dry and the freshwater flux from the Arctic to the subarctic seas was reduced. Since 1997, however, the Arctic system has been under the influence of an anticyclonic circulation regime (17 years) with a set of environmental parameters that are atypical for this regime. We discuss a hypothesis explaining the causes and mechanisms regulating the intensity and duration of Arctic circulation regimes, and speculate how changes in freshwater fluxes from the Arctic Ocean and Greenland impact environmental conditions and interrupt their decadal variability. © 2015 The Authors.

  6. Site directed recombination

    Jurka, Jerzy W.

    1997-01-01

    Enhanced homologous recombination is obtained by employing a consensus sequence which has been found to be associated with integration of repeat sequences, such as Alu and ID. The consensus sequence or sequence having a single transition mutation determines one site of a double break which allows for high efficiency of integration at the site. By introducing single or double stranded DNA having the consensus sequence flanking region joined to a sequence of interest, one can reproducibly direct integration of the sequence of interest at one or a limited number of sites. In this way, specific sites can be identified and homologous recombination achieved at the site by employing a second flanking sequence associated with a sequence proximal to the 3'-nick.

  7. Identifying recombinants in human and primate immunodeficiency virus sequence alignments using quartet scanning

    Martin Darren P

    2009-04-01

    Full Text Available Abstract Background Recombination has a profound impact on the evolution of viruses, but characterizing recombination patterns in molecular sequences remains a challenging endeavor. Despite its importance in molecular evolutionary studies, identifying the sequences that exhibit such patterns has received comparatively less attention in the recombination detection framework. Here, we extend a quartet-mapping based recombination detection method to enable identification of recombinant sequences without prior specifications of either query and reference sequences. Through simulations we evaluate different recombinant identification statistics and significance tests. We compare the quartet approach with triplet-based methods that employ additional heuristic tests to identify parental and recombinant sequences. Results Analysis of phylogenetic simulations reveal that identifying the descendents of relatively old recombination events is a challenging task for all methods available, and that quartet scanning performs relatively well compared to the triplet based methods. The use of quartet scanning is further demonstrated by analyzing both well-established and putative HIV-1 recombinant strains. In agreement with recent findings, we provide evidence that the presumed circulating recombinant CRF02_AG is a 'pure' lineage, whereas the presumed parental lineage subtype G has a recombinant origin. We also demonstrate HIV-1 intrasubtype recombination, confirm the hybrid origin of SIV in chimpanzees and further disentangle the recombinant history of SIV lineages in a primate immunodeficiency virus data set. Conclusion Quartet scanning makes a valuable addition to triplet-based methods for identifying recombinant sequences without prior specifications of either query and reference sequences. The new method is available in the VisRD v.3.0 package http://www.cmp.uea.ac.uk/~vlm/visrd.

  8. Nonradiative recombination in semiconductors

    Abakumov, VN; Yassievich, IN

    1991-01-01

    In recent years, great progress has been made in the understandingof recombination processes controlling the number of excessfree carriers in semiconductors under nonequilibrium conditions. As a result, it is now possible to give a comprehensivetheoretical description of these processes. The authors haveselected a number of experimental results which elucidate theunderlying physical problems and enable a test of theoreticalmodels. The following topics are dealt with: phenomenological theory ofrecombination, theoretical models of shallow and deep localizedstates, cascade model of carrier captu

  9. Recombination epoch revisited

    Krolik, J.H.

    1989-01-01

    Previous studies of cosmological recombination have shown that this process produces as a by-product a highly superthermal population of Ly-alpha photons which retard completion of recombination. Cosmological redshifting was thought to determine the frequency distribution of the photons, while two-photon decay of hydrogen's 2s state was thought to control their numbers. It is shown here that frequency diffusion due to photon scattering dominate the cosmological redshift in the frequency range near line center which fixes the ratio of ground state to excited state population, while incoherent scattering into the far-red damping wing effectively destroys Ly-alpha photons as a rate which is competitive with two-photon decay. The former effect tends to hold back recombination, while the latter tends to accelerate it; the net results depends on cosmological parameters, particularly the combination Omega(b) h/sq rt (2q0), where Omega(b) is the fraction of the critical density provided by baryons. 18 references

  10. Dielectronic recombination theory

    LaGattuta, K.J.

    1991-01-01

    A theory now in wide use for the calculation of dielectronic recombination cross sections (σ DR ) and rate coefficients (α DR ) was one introduced originally by Feshbach for nuclear physics applications, and then later adapted for atomic scattering problems by Hahn. In the following, we briefly review this theory in a very general form, which allows one to account for the effects of overlapping and interacting resonances, as well as continuum-continuum coupling. An extension of our notation will then also allow for the inclusion of the effects of direct radiative recombination, along with a treatment of the interference between radiative and dielectronic recombination. Other approaches to the calculation of σ DR have been described by Fano and by Seaton. We will not consider those theories here. Calculations of α DR have progressed considerably over the last 25 years, since the early work of Burgess. Advances in the reliability of theoretical predictions have also been promoted recently b a variety of direct laboratory measurements of σ DR . While the measurements of σ DR for δn ≠ 0 excitations have tended to agree very well with calculations, the case of δn = 0 has been much problematic. However, by invoking a mechanism originally proposed by Jacobs, which takes into account the effect of stray electric fields on high Rydberg states (HRS) participating in the DR process, new calculations have improved the agreement between theory and experiment for these cases. Nevertheless, certain discrepancies still remain

  11. Four Closely Related HIV-1 CRF01_AE/CRF07_BC Recombinant Forms Identified in East China.

    Li, Fan; Li, Yuxueyun; Feng, Yi; Hu, Jing; Ruan, Yuhua; Xing, Hui; Shao, Yiming

    2017-07-01

    Five near full-length genomes of novel second-generation HIV-1 recombinant virus (JS150021, JS150029, JS150129, JS150132, and AH150183) were identified from five HIV-positive people in Jiangsu and Anhui province, east China. Phylogenic analyses showed that these five sequences are all composed of two well-established circulating recombinant forms (CRFs) CRF07_BC and CRF01_AE, grouped into four new discovered recombinant forms, which show several very similar but not identical recombinant breakpoints. The four recombinant forms are also identified to be a sort of family or related viruses, seems to be the results of different recombination events. The emergence of a serious new closely related CRF07_BC/CRF01_AE recombinant strain indicates the increasing complexity of sexual transmission of the HIV-1 epidemic in China.

  12. Correlates of Circulating 25-Hydroxyvitamin D

    McCullough, Marjorie L.; Weinstein, Stephanie J.; Freedman, D. Michal; Helzlsouer, Kathy; Flanders, W. Dana; Koenig, Karen; Kolonel, Laurence; Laden, Francine; Le Marchand, Loic; Purdue, Mark; Snyder, Kirk; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael; Virtamo, Jarmo; Yang, Gong

    2010-01-01

    Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geogra...

  13. Variation in Recombination Rate and Its Genetic Determinism in Sheep Populations.

    Petit, Morgane; Astruc, Jean-Michel; Sarry, Julien; Drouilhet, Laurence; Fabre, Stéphane; Moreno, Carole R; Servin, Bertrand

    2017-10-01

    Recombination is a complex biological process that results from a cascade of multiple events during meiosis. Understanding the genetic determinism of recombination can help to understand if and how these events are interacting. To tackle this question, we studied the patterns of recombination in sheep, using multiple approaches and data sets. We constructed male recombination maps in a dairy breed from the south of France (the Lacaune breed) at a fine scale by combining meiotic recombination rates from a large pedigree genotyped with a 50K SNP array and historical recombination rates from a sample of unrelated individuals genotyped with a 600K SNP array. This analysis revealed recombination patterns in sheep similar to other mammals but also genome regions that have likely been affected by directional and diversifying selection. We estimated the average recombination rate of Lacaune sheep at 1.5 cM/Mb, identified ∼50,000 crossover hotspots on the genome, and found a high correlation between historical and meiotic recombination rate estimates. A genome-wide association study revealed two major loci affecting interindividual variation in recombination rate in Lacaune, including the RNF212 and HEI10 genes and possibly two other loci of smaller effects including the KCNJ15 and FSHR genes. The comparison of these new results to those obtained previously in a distantly related population of domestic sheep (the Soay) revealed that Soay and Lacaune males have a very similar distribution of recombination along the genome. The two data sets were thus combined to create more precise male meiotic recombination maps in Sheep. However, despite their similar recombination maps, Soay and Lacaune males were found to exhibit different heritabilities and QTL effects for interindividual variation in genome-wide recombination rates. This highlights the robustness of recombination patterns to underlying variation in their genetic determinism. Copyright © 2017 by the Genetics Society

  14. Robust Protection against Highly Virulent Foot-and-Mouth Disease Virus in Swine by Combination Treatment with Recombinant Adenoviruses Expressing Porcine Alpha and Gamma Interferons and Multiple Small Interfering RNAs

    Park, Jong-Hyeon; Lee, Kwang-Nyeong; Kim, Se-Kyung; You, Su-Hwa; Kim, Taeseong; Tark, Dongseob; Lee, Hyang-Sim; Seo, Min-Goo; Kim, Byounghan

    2015-01-01

    ABSTRACT Because the currently available vaccines against foot-and-mouth disease (FMD) provide no protection until 4 to 7 days postvaccination, the only alternative method to halt the spread of the FMD virus (FMDV) during outbreaks is the application of antiviral agents. Combination treatment strategies have been used to enhance the efficacy of antiviral agents, and such strategies may be advantageous in overcoming viral mechanisms of resistance to antiviral treatments. We have developed recombinant adenoviruses (Ads) for the simultaneous expression of porcine alpha and gamma interferons (Ad-porcine IFN-αγ) as well as 3 small interfering RNAs (Ad-3siRNA) targeting FMDV mRNAs encoding nonstructural proteins. The antiviral effects of Ad-porcine IFN-αγ and Ad-3siRNA expression were tested in combination in porcine cells, suckling mice, and swine. We observed enhanced antiviral effects in porcine cells and mice as well as robust protection against the highly pathogenic strain O/Andong/SKR/2010 and increased expression of cytokines in swine following combination treatment. In addition, we showed that combination treatment was effective against all serotypes of FMDV. Therefore, we suggest that the combined treatment with Ad-porcine IFN-αγ and Ad-3siRNA may offer fast-acting antiviral protection and be used with a vaccine during the period that the vaccine does not provide protection against FMD. IMPORTANCE The use of current foot-and-mouth disease (FMD) vaccines to induce rapid protection provides limited effectiveness because the protection does not become effective until a minimum of 4 days after vaccination. Therefore, during outbreaks antiviral agents remain the only available treatment to confer rapid protection and reduce the spread of foot-and-mouth disease virus (FMDV) in livestock until vaccine-induced protective immunity can become effective. Interferons (IFNs) and small interfering RNAs (siRNAs) have been reported to be effective antiviral agents against

  15. Controlled humidity gas circulators

    Gruner, S.M.

    1981-01-01

    A programmable circulator capable of regulating the humidity of a gas stream over a wide range of humidity is described. An optical dew-point hygrometer is used as a feedback element to control the addition or removal of water vapor. Typical regulation of the gas is to a dew-point temperature of +- 0.2 0 C and to an accuracy limited by the dew-point hygrometer

  16. Fluid circulation control device

    Benard, Henri; Henocque, Jean.

    1982-01-01

    Horizontal fluid circulation control device, of the type having a pivoting flap. This device is intended for being fitted in the pipes of hydraulic installation, particularly in a bleed and venting system of a nuclear power station shifting radioactive or contaminated liquids. The characteristic of this device is the cut-out at the top of the flap to allow the air contained in the pipes to flow freely [fr

  17. A molecular recombination map of Antirrhinum majus

    Hudson Andrew

    2010-12-01

    Full Text Available Abstract Background Genetic recombination maps provide important frameworks for comparative genomics, identifying gene functions, assembling genome sequences and for breeding. The molecular recombination map currently available for the model eudicot Antirrhinum majus is the result of a cross with Antirrhinum molle, limiting its usefulness within A. majus. Results We created a molecular linkage map of A. majus based on segregation of markers in the F2 population of two inbred lab strains of A. majus. The resulting map consisted of over 300 markers in eight linkage groups, which could be aligned with a classical recombination map and the A. majus karyotype. The distribution of recombination frequencies and distorted transmission of parental alleles differed from those of a previous inter-species hybrid. The differences varied in magnitude and direction between chromosomes, suggesting that they had multiple causes. The map, which covered an estimated of 95% of the genome with an average interval of 2 cM, was used to analyze the distribution of a newly discovered family of MITE transposons and tested for its utility in positioning seven mutations that affect aspects of plant size. Conclusions The current map has an estimated interval of 1.28 Mb between markers. It shows a lower level of transmission ratio distortion and a longer length than the previous inter-species map, making it potentially more useful. The molecular recombination map further indicates that the IDLE MITE transposons are distributed throughout the genome and are relatively stable. The map proved effective in mapping classical morphological mutations of A. majus.

  18. Detection and characterization of hepatitis A virus circulating in Egypt.

    Hamza, Hazem; Abd-Elshafy, Dina Nadeem; Fayed, Sayed A; Bahgat, Mahmoud Mohamed; El-Esnawy, Nagwa Abass; Abdel-Mobdy, Emam

    2017-07-01

    Hepatitis A virus (HAV) still poses a considerable problem worldwide. In the current study, hepatitis A virus was recovered from wastewater samples collected from three wastewater treatment plants over one year. Using RT-PCR, HAV was detected in 43 out of 68 samples (63.2%) representing both inlet and outlet. Eleven positive samples were subjected to sequencing targeting the VP1-2A junction region. Phylogenetic analysis revealed that all samples belonged to subgenotype IB with few substitutions at the amino acid level. The complete sequence of one isolate (HAV/Egy/BI-11/2015) showed that the similarity at the amino acid level was not reflected at the nucleotide level. However, the deduced amino acid sequence derived from the complete nucleotide sequence showed distinct substitutions in the 2B, 2C, and 3A regions. Recombination analysis revealed a recombination event between X75215 (subgenotype IA) and AF268396 (subgenotype IB) involving a portion of the 2B nonstructural protein coding region (nucleotides 3757-3868) assuming the herein characterized sequence an actual recombinant. Despite the role of recombination in picornaviruses evolution, its involvement in HAV evolution has rarely been reported, and this may be due to the limited available complete HAV sequences. To our knowledge, this represents the first characterized complete sequence of an Egyptian isolate and the described recombination event provides an important update on the circulating HAV strains in Egypt.

  19. Triplet formation in the ion recombination in irradiated liquids

    Bartczak, W.M.; Tachiya, M.; Hummel, A.

    1990-01-01

    The formation of singlet and triplet excited stages in the ion recombination in groups of oppositely charged ions (or positive ions and electrons) in nonpolar liquids, as occurs in the tracks of high energy electrons, is considered. Theoretical studies on triplet formation in groups of ion pairs have thus far concentrated on the case where recombination of the negative ions with any of the positive ions in the group is equally probable (random recombination). In this paper the probability for geminate recombination (electron and parent positive ion) vs cross-recombination (an electron with a positive ion other than its parent ion) in multiple ion pair groups is calculated by computer simulation and the effect of the initial spatial configuration of the charged species is investigated. It is also shown explicitly that the probability for singlet formation as a result of cross recombination is equal to 1/4, when spin relaxation by magnetic interaction with the medium and by exchange interaction can be neglected. The effect of the preferential recombination on the singlet formation probability is illustrated and recent experimental results on singlet to triplet ratios are discussed. (author)

  20. RPA homologs and ssDNA processing during meiotic recombination.

    Ribeiro, Jonathan; Abby, Emilie; Livera, Gabriel; Martini, Emmanuelle

    2016-06-01

    Meiotic homologous recombination is a specialized process that involves homologous chromosome pairing and strand exchange to guarantee proper chromosome segregation and genetic diversity. The formation and repair of DNA double-strand breaks (DSBs) during meiotic recombination differs from those during mitotic recombination in that the homologous chromosome rather than the sister chromatid is the preferred repair template. The processing of single-stranded DNA (ssDNA) formed on intermediate recombination structures is central to driving the specific outcomes of DSB repair during meiosis. Replication protein A (RPA) is the main ssDNA-binding protein complex involved in DNA metabolism. However, the existence of RPA orthologs in plants and the recent discovery of meiosis specific with OB domains (MEIOB), a widely conserved meiosis-specific RPA1 paralog, strongly suggest that multiple RPA complexes evolved and specialized to subdivide their roles during DNA metabolism. Here we review ssDNA formation and maturation during mitotic and meiotic recombination underlying the meiotic specific features. We describe and discuss the existence and properties of MEIOB and multiple RPA subunits in plants and highlight how they can provide meiosis-specific fates to ssDNA processing during homologous recombination. Understanding the functions of these RPA homologs and how they interact with the canonical RPA subunits is of major interest in the fields of meiosis and DNA repair.

  1. A Nestin-cre transgenic mouse is insufficient for recombination in early embryonic neural progenitors

    Huixuan Liang

    2012-09-01

    Nestin-cre transgenic mice have been widely used to direct recombination to neural stem cells (NSCs and intermediate neural progenitor cells (NPCs. Here we report that a readily utilized, and the only commercially available, Nestin-cre line is insufficient for directing recombination in early embryonic NSCs and NPCs. Analysis of recombination efficiency in multiple cre-dependent reporters and a genetic mosaic line revealed consistent temporal and spatial patterns of recombination in NSCs and NPCs. For comparison we utilized a knock-in Emx1cre line and found robust recombination in NSCs and NPCs in ventricular and subventricular zones of the cerebral cortices as early as embryonic day 12.5. In addition we found that the rate of Nestin-cre driven recombination only reaches sufficiently high levels in NSCs and NPCs during late embryonic and early postnatal periods. These findings are important when commercially available cre lines are considered for directing recombination to embryonic NSCs and NPCs.

  2. Expression of recombinant Antibodies

    André eFrenzel

    2013-07-01

    Full Text Available 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 transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines and transgenic plants are promising to obtain antibodies with human-like post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications.

  3. On the relict recombination lines

    Bershtejn, I.N.; Bernshtejn, D.N.; Dubrovich, V.K.

    1977-01-01

    Accurate numerical calculation of intensities and profiles of hydrogen recombination lines of cosmological origin is made. Relie radiation distortions stipulated by recombination quantum release at the irrevocable recombination are investigated. Mean number calculation is given for guantums educing for one irrevocably-lost electron. The account is taken of the educed quantums interraction with matter. The main quantum-matter interrraction mechanisms are considered: electronic blow broadening; free-free, free-bound, bound-bound absorptions Recombination dynamics is investigated depending on hydrogen density and total density of all the matter kinds in the Universe

  4. Recombinational Cloning Using Gateway and In-Fusion Cloning Schemes

    Throop, Andrea L.; LaBaer, Joshua

    2015-01-01

    The comprehensive study of protein structure and function, or proteomics, depends on the obtainability of full-length cDNAs in species-specific expression vectors and subsequent functional analysis of the expressed protein. Recombinational cloning is a universal cloning technique based on site-specific recombination that is independent of the insert DNA sequence of interest, which differentiates this method from the classical restriction enzyme-based cloning methods. Recombinational cloning enables rapid and efficient parallel transfer of DNA inserts into multiple expression systems. This unit summarizes strategies for generating expression-ready clones using the most popular recombinational cloning technologies, including the commercially available Gateway® (Life Technologies) and In-Fusion® (Clontech) cloning technologies. PMID:25827088

  5. 3D Visualization of Global Ocean Circulation

    Nelson, V. G.; Sharma, R.; Zhang, E.; Schmittner, A.; Jenny, B.

    2015-12-01

    Advanced 3D visualization techniques are seldom used to explore the dynamic behavior of ocean circulation. Streamlines are an effective method for visualization of flow, and they can be designed to clearly show the dynamic behavior of a fluidic system. We employ vector field editing and extraction software to examine the topology of velocity vector fields generated by a 3D global circulation model coupled to a one-layer atmosphere model simulating preindustrial and last glacial maximum (LGM) conditions. This results in a streamline-based visualization along multiple density isosurfaces on which we visualize points of vertical exchange and the distribution of properties such as temperature and biogeochemical tracers. Previous work involving this model examined the change in the energetics driving overturning circulation and mixing between simulations of LGM and preindustrial conditions. This visualization elucidates the relationship between locations of vertical exchange and mixing, as well as demonstrates the effects of circulation and mixing on the distribution of tracers such as carbon isotopes.

  6. The Time Scale of Recombination Rate Evolution in Great Apes

    Stevison, Laurie S.; Woerner, August E.; Kidd, Jeffrey M.; Kelley, Joanna L.; Veeramah, Krishna R.; McManus, Kimberly F.; Bustamante, Carlos D.; Hammer, Michael F.; Wall, Jeffrey D.

    2016-01-01

    Abstract We present three linkage-disequilibrium (LD)-based recombination maps generated using whole-genome sequence data from 10 Nigerian chimpanzees, 13 bonobos, and 15 western gorillas, collected as part of the Great Ape Genome Project (Prado-Martinez J, et al. 2013. Great ape genetic diversity and population history. Nature 499:471–475). We also identified species-specific recombination hotspots in each group using a modified LDhot framework, which greatly improves statistical power to detect hotspots at varying strengths. We show that fewer hotspots are shared among chimpanzee subspecies than within human populations, further narrowing the time scale of complete hotspot turnover. Further, using species-specific PRDM9 sequences to predict potential binding sites (PBS), we show higher predicted PRDM9 binding in recombination hotspots as compared to matched cold spot regions in multiple great ape species, including at least one chimpanzee subspecies. We found that correlations between broad-scale recombination rates decline more rapidly than nucleotide divergence between species. We also compared the skew of recombination rates at centromeres and telomeres between species and show a skew from chromosome means extending as far as 10–15 Mb from chromosome ends. Further, we examined broad-scale recombination rate changes near a translocation in gorillas and found minimal differences as compared to other great ape species perhaps because the coordinates relative to the chromosome ends were unaffected. Finally, on the basis of multiple linear regression analysis, we found that various correlates of recombination rate persist throughout the African great apes including repeats, diversity, and divergence. Our study is the first to analyze within- and between-species genome-wide recombination rate variation in several close relatives. PMID:26671457

  7. Dissociative recombination of dications

    Seiersen, K.; Heber, O.; Jensen, M.J.; Safvan, C.P.; Andersen, L. H.

    2003-01-01

    Dissociative recombination (DR) of doubly-charged positive ions has been studied at the heavy ion storage ring ASTRID. Low-energy electrons were scattered on the dication of the N 2 molecule, and the absolute cross section was measured in the energy range of 10 -4 -50 eV. From the measured cross section, a thermal rate coefficient of 5.8x10 -7 cm 3 s -1 at 300 K was extracted. Furthermore, we present new results on the CO 2+ DR rate, and a summary and comparison of measured DR rate coefficients for both the singly and doubly-charged ions of CO, CO 2 , and N 2 is presented

  8. Radiology of liver circulation

    Hermine, C.L.

    1985-01-01

    This book proposes that careful evaluation of the arterioportogram is the cornerstone in assessing portal flow obstruction, being the most consistent of all observations including liver histology, portal venous pressure, size and number of portosystemic collaterals, and wedged hepatic venous pressure. Very brief chapters cover normal hepatic circulation and angiographic methods. Contrast volumes and flow rates for celiac, hepatic, and superior mesenteric injection are given, with the timing for venous phase radiographs. In the main body of the text, portal obstruction is divided very simply into presinusoidal (all proximal causes) and postsinusoidal (all distal causes, including Budd-Chiari). Changes are discussed regarding the splenic artery and spleen; hepatic artery and its branches; portal flow rate and direction; and arterioportal shunting and portosystemic collateral circulation in minimal, moderate, severe, and very severe portal obstruction and in recognizable entities such as prehepatic portal and hepatic venous obstructions. The major emphasis in this section is the recognition and understanding of flow changes by which level and severity of obstruction are assessed (not simply the anatomy of portosystemic collateral venous flow). Excellent final chapters discuss the question of portal hypertension without obstruction, and the contribution of arterioportography to the treatment of portal hypertension, again with an emphasis on hemodynamics before and after shunt surgery. There is a fascinating final chapter on segmental intrahepatic obstruction without portal hypertension that explains much of the unusual contrast enhancement sometimes seen in CT scanning of hepatic mass lesions

  9. Circulation of Stars

    Boitani, P.

    2016-01-01

    Since the dawn of man, contemplation of the stars has been a primary impulse in human beings, who proliferated their knowledge of the stars all over the world. Aristotle sees this as the product of primeval and perennial “wonder” which gives rise to what we call science, philosophy, and poetry. Astronomy, astrology, and star art (painting, architecture, literature, and music) go hand in hand through millennia in all cultures of the planet (and all use catasterisms to explain certain phenomena). Some of these developments are independent of each other, i.e., they take place in one culture independently of others. Some, on the other hand, are the product of the “circulation of stars.” There are two ways of looking at this. One seeks out forms, the other concentrates on the passing of specific lore from one area to another through time. The former relies on archetypes (for instance, with catasterism), the latter constitutes a historical process. In this paper I present some of the surprising ways in which the circulation of stars has occurred—from East to West, from East to the Far East, and from West to East, at times simultaneously.

  10. Expression of active recombinant human alpha 1-antitrypsin in transgenic rabbits

    Massoud, M.; Bischoff, Rainer; Dalemans, W.; Pointu, H.; Attal, J.; Schultz, H.; Clesse, D.; Stinnakre, M.G.; Pavirani, A.; Houdebine, L.M.

    1991-01-01

    A DNA construct containing the human alpha 1-antitrypsin gene including 1.5 and 4 kb of 5' and 3' flanking sequences, was microinjected into the pronucleus of rabbit embryos. The recombinant human protein was (a) expressed in the blood circulation of F0 and F1 transgenic rabbits at an average

  11. Cell biology of mitotic recombination

    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...

  12. Hadron Correlations and Parton Recombination

    Fries, R.J. [School of Physics and Astronomy, University of Minnesota, Minneapolis, MN 55455 (United States)]. E-mail: rjfries@comp.tamu.edu

    2007-02-15

    Parton recombination has been found to be an extremely useful model to understand hadron production at the Relativistic Heavy Ion Collider. It is particularly important to explore its connections with hard processes. This article reviews some of the aspects of the quark recombination model and places particular emphasis on hadron correlations.

  13. Prdm9 controls activation of mammalian recombination hotspots.

    Parvanov, Emil D; Petkov, Petko M; Paigen, Kenneth

    2010-02-12

    Mammalian meiotic recombination, which preferentially occurs at specialized sites called hotspots, ensures the orderly segregation of meiotic chromosomes and creates genetic variation among offspring. A locus on mouse chromosome 17, which controls activation of recombination at multiple distant hotspots, has been mapped within a 181-kilobase interval, three of whose genes can be eliminated as candidates. The remaining gene, Prdm9, codes for a zinc finger containing histone H3K4 trimethylase that is expressed in early meiosis and whose deficiency results in sterility in both sexes. Mus musculus exhibits five alleles of Prdm9; human populations exhibit two predominant alleles and multiple minor alleles. The identification of Prdm9 as a protein regulating mammalian recombination hotspots initiates molecular studies of this important biological control system.

  14. Auger recombination in sodium iodide

    McAllister, Andrew; Kioupakis, Emmanouil; Åberg, Daniel; Schleife, André

    2014-03-01

    Scintillators are an important tool used to detect high energy radiation - both in the interest of national security and in medicine. However, scintillator detectors currently suffer from lower energy resolutions than expected from basic counting statistics. This has been attributed to non-proportional light yield compared to incoming radiation, but the specific mechanism for this non-proportionality has not been identified. Auger recombination is a non-radiative process that could be contributing to the non-proportionality of scintillating materials. Auger recombination comes in two types - direct and phonon-assisted. We have used first-principles calculations to study Auger recombination in sodium iodide, a well characterized scintillating material. Our findings indicate that phonon-assisted Auger recombination is stronger in sodium iodide than direct Auger recombination. Computational resources provided by LLNL and NERSC. Funding provided by NA-22.

  15. Circulation Systems Past and Present

    Maurice J. Freedman

    1981-01-01

    Full Text Available A review of the development of circulation systems shows two areas of change. The librarian's perception of circulation control has shifted from a broad service orientation to a narrow record-keeping approach and recently back again. The technological development of circulation sys-tems has evolved from manual systems to the online systems of today. The trade-offs and deficiencies of earlier systems in relation to the comprehensive services made possible by the online computer are detailed.

  16. The ocean circulation inverse problem

    Wunsch, C

    1996-01-01

    .... This book addresses the problem of inferring the state of the ocean circulation, understanding it dynamically, and even forecasting it through a quantitative combination of theory and observation...

  17. Natural Circulation Phenomena and Modelling for Advanced Water Cooled Reactors

    2012-03-01

    The role of natural circulation in advanced water cooled reactor design has been extended with the adoption of passive safety systems. Some designs utilize natural circulation to remove core heat during normal operation. Most passive safety systems used in evolutionary and innovative water cooled reactor designs are driven by natural circulation. The use of passive systems based on natural circulation can eliminate the costs associated with the installation, maintenance and operation of active systems that require multiple pumps with independent and redundant electric power supplies. However, considering the weak driving forces of passive systems based on natural circulation, careful design and analysis methods must be employed to ensure that the systems perform their intended functions. Several IAEA Member States with advanced reactor development programmes are actively conducting investigations of natural circulation to support the development of advanced water cooled reactor designs with passive safety systems. To foster international collaboration on the enabling technology of passive systems that utilize natural circulation, in 2004 the IAEA initiated a coordinated research project (CRP) on Natural Circulation Phenomena, Modelling and Reliability of Passive Systems that Utilize Natural Circulation. Three reports were published within the framework of this CRP. The first report (IAEA-TECDOC-1474) contains the material developed for the first IAEA training course on natural circulation in water cooled nuclear power plants. The second report (IAEA-TECDOC-1624) describes passive safety systems in a wide range of advanced water cooled nuclear power plant designs, with the goal of gaining insights into system design, operation and reliability. This third, and last, report summarizes the research studies completed by participating institutes during the CRP period.

  18. Genetic and evolutionary correlates of fine-scale recombination rate variation in Drosophila persimilis.

    Stevison, Laurie S; Noor, Mohamed A F

    2010-12-01

    Recombination is fundamental to meiosis in many species and generates variation on which natural selection can act, yet fine-scale linkage maps are cumbersome to construct. We generated a fine-scale map of recombination rates across two major chromosomes in Drosophila persimilis using 181 SNP markers spanning two of five major chromosome arms. Using this map, we report significant fine-scale heterogeneity of local recombination rates. However, we also observed "recombinational neighborhoods," where adjacent intervals had similar recombination rates after excluding regions near the centromere and telomere. We further found significant positive associations of fine-scale recombination rate with repetitive element abundance and a 13-bp sequence motif known to associate with human recombination rates. We noted strong crossover interference extending 5-7 Mb from the initial crossover event. Further, we observed that fine-scale recombination rates in D. persimilis are strongly correlated with those obtained from a comparable study of its sister species, D. pseudoobscura. We documented a significant relationship between recombination rates and intron nucleotide sequence diversity within species, but no relationship between recombination rate and intron divergence between species. These results are consistent with selection models (hitchhiking and background selection) rather than mutagenic recombination models for explaining the relationship of recombination with nucleotide diversity within species. Finally, we found significant correlations between recombination rate and GC content, supporting both GC-biased gene conversion (BGC) models and selection-driven codon bias models. Overall, this genome-enabled map of fine-scale recombination rates allowed us to confirm findings of broader-scale studies and identify multiple novel features that merit further investigation.

  19. Predicting ongoing pregnancy following ovulation induction with recombinant FSH in women with polycystic ovary syndrome

    van Wely, Madelon; Bayram, Neriman; van der Veen, Fulco; Bossuyt, Patrick M. M.

    2005-01-01

    BACKGROUND: Ovulation induction with recombinant FSH (rFSH) is common in women with polycystic ovary syndrome (PCOS) not responding to clomiphene citrate treatment, despite the associated risk of multiple pregnancies. We analysed clinical, ultrasonographic and endocrine parameters during initial

  20. Oxygen-hydrogen recombination system

    Sato, Shuichiro; Takejima, Masaki.

    1981-01-01

    Purpose: To avoid reduction in the performance of catalyst used for an oxygen-hydrogen recombiner in the off gas processing system of a nuclear reactor. Constitution: A thermometer is provided for the detection of temperature in an oxygen-hydrogen recombiner. A cooling pipe is provided in the recombiner and cooling medium is introduced externally. The cooling medium may be water or air. In accordance with the detection value from the thermometer, ON-OFF control is carried out for a valve to control the flow rate of the cooling medium thereby rendering the temperature in the recombiner to a predetermined value. This can prevent the catalyst from being exposed to high temperature and avoid the reduction in the performance of the catalyst. (Ikeda, J.)

  1. Controlled Release from Recombinant Polymers

    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 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. PMID:24956486

  2. Sino-Danish Brain Circulation

    Bertelsen, Rasmus Gjedssø; Du, Xiangyun; Søndergaard, Morten Karnøe

    2014-01-01

    China is faced with urgent needs to develop an economically and environmentally sustainable economy based on innovation and knowledge. Brain circulation and research and business investments from the outside are central for this development. Sino-American brain circulation and research...... and investment by overseas researchers and entrepreneurs are well described. In that case, the US is the center of global R&D and S&T. However, the brain circulation and research and investments between a small open Scandinavian economy, such as Denmark, and the huge developing economy of China are not well...... understood. In this case, Denmark is very highly developed, but a satellite in the global R&D and S&T system. With time and the growth of China as a R&D and S&T power house, both Denmark and China will benefit from brain circulation between them. Such brain circulation is likely to play a key role in flows...

  3. Hydrogen recombiner development at AECL

    Dewit, W.A.; Koroll, G.W.; Loesel Sitar, J.; Graham, W.R.C.

    1997-01-01

    Catalytic recombiners have been developed at AECL for the purpose of hydrogen removal in post-accident nuclear containment buildings. The recombiners are based on a particular catalyst designed by AECL which has extraordinary resistance to fouling from water and water vapour and a large thermodynamic range of operation. The catalysts were developed, originally, for the purpose of heavy water manufacturing by way of a catalytic exchange process. Application of these catalyst materials in recombiners for containment applications began in the late 1980's. The first application was a passive recombiner, qualified for use in control of radiolytic hydrogen in the headspace of a pool-type experimental reactor of AECL design in 1988. The passive, or natural convection recombiner concept has continued development to commercial stage for application in power reactor containments. This paper reviews the AECL recombiner development, describes the current model and shows results from tests of full-scale recombiners in the Large Scale Vented Combustion Test Facility at AECL-WL. The AECL recombiner is designed for compactness and ease of engineering into containment. The design is a simple, open-ended rectangular enclosure with catalyst elements arranged inside to promote optimum convective flow driven by heat of recombination at the catalyst surface. Self start, as evidenced by catalyst heating and initiation of flow, is achieved in less than 1% hydrogen, with available oxygen, at room temperature and 100% relative humidity. This low temperature start-up in condensing atmospheres is viewed as the most challenging condition for wet-proofing effectiveness. Cold start-up is a vital performance requirement in containments, such as CANDU, where engineered air-cooling systems are operating and where long-term hydrogen control is required, after containment atmospheres have cooled. Once started, the removal capacity scales linearly with the inlet cross-section area and the partial

  4. [Genomic characteristics and recombination of enterovirus 71 strains isolated in Henan Province between 2008 and 2010].

    Wei, Hai-Yan; Xu, Yu-Ling; Huang, Xue-Yong; Ma, Hong; Chen, Hao-Min; Xu, Bian-Li

    2011-09-01

    To reveal the genetic features and recombination of enterovirus 71 isolates between 2008 and 2010. A total of 5 enterovirus 71 isolates were sequenced completely and phylogenetic analysis and recombination were performed. Phylogenetic analysis based on VP1 regions revealed that the Henan enterovirus 71 between 2008 and 2010 belonged to C4a in subgenotype C4. Bootscan analyses and phylogenetic analysis based on the 5'UTR, P1, P2, P3 genomic regions revealed the recombinations between EV71 genotypes B and C at the 2A-2B junction, and between EV71 genotype B and CA16 strain G-10 at the 3B-3C junction. Henan enterovirus 71 isolates between 2008 and 2010 belonged to C4a in subgenotype C4 which was the predominant virus genotype circulating in mainland China since 2004, a combination of intratypic and intertypic recombination were found in EV71 subgenotype C4.

  5. Review of Parton Recombination Models

    Bass, Steffen A

    2006-01-01

    Parton recombination models have been very successful in explaining data taken at RHIC on hadron spectra and emission patterns in Au+Au collisions at transverse momenta above 2 GeV/c, which have exhibited features which could not be understood in the framework of basic perturbative QCD. In this article I will review the current status on recombination models and outline which future challenges need to be addressed by this class of models

  6. Recombinant snake venom prothrombin activators

    L?vgren, 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 ...

  7. Natural Circulation with Boiling

    Mathisen, R P

    1967-09-15

    A number of parameters with dominant influence on the power level at hydrodynamic instability in natural circulation, two-phase flow, have been studied experimentally. The geometrical dependent quantities were: the system driving head, the boiling channel and riser dimensions, the single-phase as well as the two phase flow restrictions. The parameters influencing the liquid properties were the system pressure and the test section inlet subcooling. The threshold of instability was determined by plotting the noise characteristics in the mass flow records against power. The flow responses to artificially obtained power disturbances at instability conditions were also measured in order to study the nature of hydrodynamic instability. The results presented give a review over relatively wide ranges of the main parameters, mainly concerning the coolant performance in both single and parallel boiling channel flow. With regard to the power limits the experimental results verified that the single boiling channel performance was intimately related to that of the parallel channels. In the latter case the additional inter-channel factors with attenuating effects were studied. Some optimum values of the parameters were observed.

  8. Circulation in a Short Cylindrical Couette System

    Akira Kageyama; Hantao Ji; Jeremy Goodman

    2003-07-08

    In preparation for an experimental study of magnetorotational instability (MRI) in liquid metal, we explore Couette flows having height comparable to the gap between cylinders, centrifugally stable rotation, and high Reynolds number. Experiments in water are compared with numerical simulations. The flow is very different from that of an ideal, infinitely long Couette system. Simulations show that endcaps co-rotating with the outer cylinder drive a strong poloidal circulation that redistributes angular momentum. Predicted toroidal flow profiles agree well with experimental measurements. Spin-down times scale with Reynolds number as expected for laminar Ekman circulation; extrapolation from two-dimensional simulations at Re less than or equal to 3200 agrees remarkably well with experiment at Re approximately equal to 106. This suggests that turbulence does not dominate the effective viscosity. Further detailed numerical studies reveal a strong radially inward flow near both endcaps. After turning vertically along the inner cylinder, these flows converge at the midplane and depart the boundary in a radial jet. To minimize this circulation in the MRI experiment, endcaps consisting of multiple, differentially rotating rings are proposed. Simulations predict that an adequate approximation to the ideal Couette profile can be obtained with a few rings.

  9. Circulation in a Short Cylindrical Couette System

    Akira Kageyama; Hantao Ji; Jeremy Goodman

    2003-01-01

    In preparation for an experimental study of magnetorotational instability (MRI) in liquid metal, we explore Couette flows having height comparable to the gap between cylinders, centrifugally stable rotation, and high Reynolds number. Experiments in water are compared with numerical simulations. The flow is very different from that of an ideal, infinitely long Couette system. Simulations show that endcaps co-rotating with the outer cylinder drive a strong poloidal circulation that redistributes angular momentum. Predicted toroidal flow profiles agree well with experimental measurements. Spin-down times scale with Reynolds number as expected for laminar Ekman circulation; extrapolation from two-dimensional simulations at Re less than or equal to 3200 agrees remarkably well with experiment at Re approximately equal to 106. This suggests that turbulence does not dominate the effective viscosity. Further detailed numerical studies reveal a strong radially inward flow near both endcaps. After turning vertically along the inner cylinder, these flows converge at the midplane and depart the boundary in a radial jet. To minimize this circulation in the MRI experiment, endcaps consisting of multiple, differentially rotating rings are proposed. Simulations predict that an adequate approximation to the ideal Couette profile can be obtained with a few rings

  10. Delayed recombination and cosmic parameters

    Galli, Silvia; Melchiorri, Alessandro; Bean, Rachel; Silk, Joseph

    2008-01-01

    Current cosmological constraints from cosmic microwave background anisotropies are typically derived assuming a standard recombination scheme, however additional resonance and ionizing radiation sources can delay recombination, altering the cosmic ionization history and the cosmological inferences drawn from the cosmic microwave background data. We show that for recent observations of the cosmic microwave background anisotropy, from the Wilkinson microwave anisotropy probe satellite mission (WMAP) 5-year survey and from the arcminute cosmology bolometer array receiver experiment, additional resonance radiation is nearly degenerate with variations in the spectral index, n s , and has a marked effect on uncertainties in constraints on the Hubble constant, age of the universe, curvature and the upper bound on the neutrino mass. When a modified recombination scheme is considered, the redshift of recombination is constrained to z * =1078±11, with uncertainties in the measurement weaker by 1 order of magnitude than those obtained under the assumption of standard recombination while constraints on the shift parameter are shifted by 1σ to R=1.734±0.028. From the WMAP5 data we obtain the following constraints on the resonance and ionization sources parameters: ε α i <0.058 at 95% c.l.. Although delayed recombination limits the precision of parameter estimation from the WMAP satellite, we demonstrate that this should not be the case for future, smaller angular scales measurements, such as those by the Planck satellite mission.

  11. Whole Genome Analysis of Two Novel Type 2 Porcine Reproductive and Respiratory Syndrome Viruses with Complex Genome Recombination between Lineage 8, 3, and 1 Strains Identified in Southwestern China

    Long Zhou

    2018-06-01

    Full Text Available Recombination among porcine reproductive and respiratory syndrome viruses (PRRSVs is thought to contribute to the emergence of new PRRSV variants. In this study, two newly emerged PRRSV strains, designated SCcd16 and SCya17, are isolated from lung tissues of piglets in Southwestern China. Genome comparative analysis reveals that SCcd16/SCya17 exhibit 93.1%/93.2%, 86.9%/87.0%, 85.3%/85.7%, and 83.6%/82.0% nucleotide similarity to PRRSVs JXA1, VR-2332, QYYZ and NADC30, respectively. They only exhibit 44.8%/45.1% sequence identity with LV (PRRSV-1, indicating that both emergent strains belong to the PRRSV-2 genotype. Genomic sequence alignment shows that SCcd16 and SCya17 have the same discontinuous 30-amino acid (aa deletion in Nsp2 of the highly pathogenic Chinese PRRSV strain JXA1, when compared to strain VR-2332. Notably, SCya17 shows a unique 5-nt deletion in its 3’-UTR. Phylogenetic analysis shows that both of the isolates are classified in the QYYZ-like lineage based on ORF5 genotyping, whereas they appear to constitute an inter-lineage between JXA1-like and QYYZ-like lineages based on their genomic sequences. Furthermore, recombination analyses reveal that the two newly emerged PRRSV isolates share the same novel recombination pattern. They have both likely originated from multiple recombination events between lineage 8 (JXA1-like, lineage 1 (NADC30-like, and lineage 3 (QYYZ-like strains that have circulated in China recently. The genomic data from SCcd16 and SCya17 indicate that there is on going evolution of PRRSV field strains through genetic recombination, leading to outbreaks in the pig populations in Southwestern China.

  12. Seasonal overturning circulation in the Red Sea: 2. Winter circulation

    Yao, Fengchao; Hoteit, Ibrahim; Pratt, Larry J.; Bower, Amy S.; Köhl, Armin; Gopalakrishnan, Ganesh; Rivas, David

    2014-04-01

    The shallow winter overturning circulation in the Red Sea is studied using a 50 year high-resolution MITgcm (MIT general circulation model) simulation with realistic atmospheric forcing. The overturning circulation for a typical year, represented by 1980, and the climatological mean are analyzed using model output to delineate the three-dimensional structure and to investigate the underlying dynamical mechanisms. The horizontal model circulation in the winter of 1980 is dominated by energetic eddies. The climatological model mean results suggest that the surface inflow intensifies in a western boundary current in the southern Red Sea that switches to an eastern boundary current north of 24°N. The overturning is accomplished through a cyclonic recirculation and a cross-basin overturning circulation in the northern Red Sea, with major sinking occurring along a narrow band of width about 20 km along the eastern boundary and weaker upwelling along the western boundary. The northward pressure gradient force, strong vertical mixing, and horizontal mixing near the boundary are the essential dynamical components in the model's winter overturning circulation. The simulated water exchange is not hydraulically controlled in the Strait of Bab el Mandeb; instead, the exchange is limited by bottom and lateral boundary friction and, to a lesser extent, by interfacial friction due to the vertical viscosity at the interface between the inflow and the outflow.

  13. Seawater bicarbonate removal during hydrothermal circulation

    Proskurowski, G. K.; Seewald, J.; Sylva, S. P.; Reeves, E.; Lilley, M. D.

    2013-12-01

    High temperature fluids sampled at hydrothermal vents represent a complex alteration product of water-rock reactions on a multi-component mixture of source fluids. Sources to high-temperature hydrothermal samples include the 'original' seawater present in the recharge limb of circulation, magmatically influenced fluids added at depth as well as any seawater entrained during sampling. High-temperature hydrothermal fluids are typically enriched in magmatic volatiles, with CO2 the dominant species, characterized by concentrations of 10's-100's of mmol/kg (1, 2). Typically, the high concentration of CO2 relative to background seawater bicarbonate concentrations (~2.3 mmol/kg) obscures a full analysis of the fate of seawater bicarbonate during high-temperature hydrothermal circulation. Here we present data from a suite of samples collected over the past 15 years from high-temperature hydrothermal vents at 9N, Endeavour, Lau Basin, and the MAR that have endmember CO2 concentrations less than 10 mmol/kg. Using stable and radiocarbon isotope measurements these samples provide a unique opportunity to examine the balance between 'original' seawater bicarbonate and CO2 added from magmatic sources. Multiple lines of evidence from multiple hydrothermal settings consistently points to the removal of ~80% of the 'original' 2.3 mmol/kg seawater bicarbonate. Assuming that this removal occurs in the low-temperature, 'recharge' limb of hydrothermal circulation, this removal process is widely occurring and has important contributions to the global carbon cycle over geologic time. 1. Lilley MD, Butterfield DA, Lupton JE, & Olson EJ (2003) Magmatic events can produce rapid changes in hydrothermal vent chemistry. Nature 422(6934):878-881. 2. Seewald J, Cruse A, & Saccocia P (2003) Aqueous volatiles in hydrothermal fluids from the Main Endeavour Field, northern Juan de Fuca Ridge: temporal variability following earthquake activity. Earth and Planetary Science Letters 216(4):575-590.

  14. Recombining overlapping BACs into a single larger BAC

    Huxley Clare

    2004-01-01

    Full Text Available Abstract Background BAC clones containing entire mammalian genes including all the transcribed region and long range controlling elements are very useful for functional analysis. Sequenced BACs are available for most of the human and mouse genomes and in many cases these contain intact genes. However, large genes often span more than one BAC, and single BACs covering the entire region of interest are not available. Here we describe a system for linking two or more overlapping BACs into a single clone by homologous recombination. Results The method was used to link a 61-kb insert carrying the final 5 exons of the human CFTR gene onto a 160-kb BAC carrying the first 22 exons. Two rounds of homologous recombination were carried out in the EL350 strain of bacteria which can be induced for the Red genes. In the first round, the inserts of the two overlapping BACs were subcloned into modified BAC vectors using homologous recombination. In the second round, the BAC to be added was linearised with the very rare-cutting enzyme I-PpoI and electroporated into recombination efficient EL350 bacteria carrying the other BAC. Recombined BACs were identified by antibiotic selection and PCR screening and 10% of clones contained the correctly recombined 220-kb BAC. Conclusion The system can be used to link the inserts from any overlapping BAC or PAC clones. The original orientation of the inserts is not important and desired regions of the inserts can be selected. The size limit for the fragments recombined may be larger than the 61 kb used here and multiple BACs in a contig could be combined by alternating use of the two pBACLink vectors. This system should be of use to many investigators wishing to carry out functional analysis on large mammalian genes which are not available in single BAC clones.

  15. Experimental studies in a single-phase parallel channel natural circulation system. Preliminary results

    Bodkha, Kapil; Pilkhwal, D.S.; Jana, S.S.; Vijayan, P.K.

    2016-01-01

    Natural circulation systems find extensive applications in industrial engineering systems. One of the applications is in nuclear reactor where the decay heat is removed by natural circulation of the fluid under off-normal conditions. The upcoming reactor designs make use of natural circulation in order to remove the heat from core under normal operating conditions also. These reactors employ multiple vertical fuel channels with provision of on-power refueling/defueling. Natural circulation systems are relatively simple, safe and reliable when compared to forced circulation systems. However, natural circulation systems are prone to encounter flow instabilities which are highly undesirable for various reasons. Presence of parallel channels under natural circulation makes the system more complicated. To examine the behavior of parallel channel system, studies were carried out for single-phase natural circulation flow in a multiple vertical channel system. The objective of the present work is to study the flow behavior of the parallel heated channel system under natural circulation for different operating conditions. Steady state and transient studies have been carried out in a parallel channel natural circulation system with three heated channels. The paper brings out the details of the system considered, different cases analyzed and preliminary results of studies carried out on a single-phase parallel channel system.

  16. PROGENITORS OF RECOMBINING SUPERNOVA REMNANTS

    Moriya, Takashi J., E-mail: takashi.moriya@ipmu.jp [Kavli Institute for the Physics and Mathematics of the Universe, Todai Institutes for Advanced Study, University of Tokyo, Kashiwanoha 5-1-5, Kashiwa, Chiba 277-8583 (Japan)

    2012-05-01

    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 ionization temperature higher than the electron temperature, has been 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 supernova explosion. If the circumstellar medium is dense enough, collisional ionization equilibrium can be established in the early stage of the evolution of the supernova remnant and subsequent adiabatic cooling, which occurs after the shock wave gets out of the dense circumstellar medium, makes the electron temperature lower than the ionization temperature. We study the circumstellar medium around several supernova progenitors and show which supernova progenitors can have a circumstellar medium dense enough to establish collisional ionization equilibrium soon after the explosion. We find that the circumstellar medium around red supergiants (especially massive ones) and the circumstellar medium dense enough to make Type IIn supernovae can establish collisional ionization equilibrium soon after the explosion and can evolve to become recombining supernova remnants. Wolf-Rayet stars and white dwarfs have the possibility to be recombining supernova remnants but the fraction is expected to be very small. As the occurrence rate of the explosions of red supergiants is much higher than that of Type IIn supernovae, the major progenitors of recombining supernova remnants are likely to be red supergiants.

  17. Meiotic recombination in human oocytes.

    Edith Y Cheng

    2009-09-01

    Full Text Available Studies of human trisomies indicate a remarkable relationship between abnormal meiotic recombination and subsequent nondisjunction at maternal meiosis I or II. Specifically, failure to recombine or recombination events located either too near to or too far from the centromere have been linked to the origin of human trisomies. It should be possible to identify these abnormal crossover configurations by using immunofluorescence methodology to directly examine the meiotic recombination process in the human female. Accordingly, we initiated studies of crossover-associated proteins (e.g., MLH1 in human fetal oocytes to analyze their number and distribution on nondisjunction-prone human chromosomes and, more generally, to characterize genome-wide levels of recombination in the human female. Our analyses indicate that the number of MLH1 foci is lower than predicted from genetic linkage analysis, but its localization pattern conforms to that expected for a crossover-associated protein. In studies of individual chromosomes, our observations provide evidence for the presence of "vulnerable" crossover configurations in the fetal oocyte, consistent with the idea that these are subsequently translated into nondisjunctional events in the adult oocyte.

  18. Recombination between Poliovirus and Coxsackie A Viruses of Species C: A Model of Viral Genetic Plasticity and Emergence

    Francis Delpeyroux

    2011-08-01

    Full Text Available Genetic recombination in RNA viruses was discovered many years ago for poliovirus (PV, an enterovirus of the Picornaviridae family, and studied using PV or other picornaviruses as models. Recently, recombination was shown to be a general phenomenon between different types of enteroviruses of the same species. In particular, the interest for this mechanism of genetic plasticity was renewed with the emergence of pathogenic recombinant circulating vaccine-derived polioviruses (cVDPVs, which were implicated in poliomyelitis outbreaks in several regions of the world with insufficient vaccination coverage. Most of these cVDPVs had mosaic genomes constituted of mutated poliovaccine capsid sequences and part or all of the non-structural sequences from other human enteroviruses of species C (HEV-C, in particular coxsackie A viruses. A study in Madagascar showed that recombinant cVDPVs had been co-circulating in a small population of children with many different HEV-C types. This viral ecosystem showed a surprising and extensive biodiversity associated to several types and recombinant genotypes, indicating that intertypic genetic recombination was not only a mechanism of evolution for HEV-C, but an usual mode of genetic plasticity shaping viral diversity. Results suggested that recombination may be, in conjunction with mutations, implicated in the phenotypic diversity of enterovirus strains and in the emergence of new pathogenic strains. Nevertheless, little is known about the rules and mechanisms which govern genetic exchanges between HEV-C types, as well as about the importance of intertypic recombination in generating phenotypic variation. This review summarizes our current knowledge of the mechanisms of evolution of PV, in particular recombination events leading to the emergence of recombinant cVDPVs.

  19. Recombination between poliovirus and coxsackie A viruses of species C: a model of viral genetic plasticity and emergence.

    Combelas, Nicolas; Holmblat, Barbara; Joffret, Marie-Line; Colbère-Garapin, Florence; Delpeyroux, Francis

    2011-08-01

    Genetic recombination in RNA viruses was discovered many years ago for poliovirus (PV), an enterovirus of the Picornaviridae family, and studied using PV or other picornaviruses as models. Recently, recombination was shown to be a general phenomenon between different types of enteroviruses of the same species. In particular, the interest for this mechanism of genetic plasticity was renewed with the emergence of pathogenic recombinant circulating vaccine-derived polioviruses (cVDPVs), which were implicated in poliomyelitis outbreaks in several regions of the world with insufficient vaccination coverage. Most of these cVDPVs had mosaic genomes constituted of mutated poliovaccine capsid sequences and part or all of the non-structural sequences from other human enteroviruses of species C (HEV-C), in particular coxsackie A viruses. A study in Madagascar showed that recombinant cVDPVs had been co-circulating in a small population of children with many different HEV-C types. This viral ecosystem showed a surprising and extensive biodiversity associated to several types and recombinant genotypes, indicating that intertypic genetic recombination was not only a mechanism of evolution for HEV-C, but an usual mode of genetic plasticity shaping viral diversity. Results suggested that recombination may be, in conjunction with mutations, implicated in the phenotypic diversity of enterovirus strains and in the emergence of new pathogenic strains. Nevertheless, little is known about the rules and mechanisms which govern genetic exchanges between HEV-C types, as well as about the importance of intertypic recombination in generating phenotypic variation. This review summarizes our current knowledge of the mechanisms of evolution of PV, in particular recombination events leading to the emergence of recombinant cVDPVs.

  20. Electric hydrogen recombiner special tests

    Wilson, J.F.

    1975-12-01

    Westinghouse has produced an electric hydrogen recombiner to control hydrogen levels in reactor containments following a postulated loss-of-coolant accident. The recombiner underwent extensive testing for NRC qualification (see WCAP 7709-L and Supplements 1, 2, 3, 4). As a result, WCAP 7709-L and Supplements 1, 2, 3, and 4 have been accepted by the NRC for reference in applications not committed to IEEE-323-1974. Supplement 5 and the next supplement will demonstrate conformance to IEEE-323-1974. This supplement describes additional tests, beyond those necessary to qualify the system, which will be referenced in supplement 6. Each test has demonstrated a considerable margin of safety over required performance. Concurrently, the test results increased the fund of technical information on the electric hydrogen recombiner

  1. Homologous Recombination as a Replication Fork Escort: Fork-Protection and Recovery

    Audrey Costes

    2012-12-01

    Full Text Available Homologous recombination is a universal mechanism that allows DNA repair and ensures the efficiency of DNA replication. The substrate initiating the process of homologous recombination is a single-stranded DNA that promotes a strand exchange reaction resulting in a genetic exchange that promotes genetic diversity and DNA repair. The molecular mechanisms by which homologous recombination repairs a double-strand break have been extensively studied and are now well characterized. However, the mechanisms by which homologous recombination contribute to DNA replication in eukaryotes remains poorly understood. Studies in bacteria have identified multiple roles for the machinery of homologous recombination at replication forks. Here, we review our understanding of the molecular pathways involving the homologous recombination machinery to support the robustness of DNA replication. In addition to its role in fork-recovery and in rebuilding a functional replication fork apparatus, homologous recombination may also act as a fork-protection mechanism. We discuss that some of the fork-escort functions of homologous recombination might be achieved by loading of the recombination machinery at inactivated forks without a need for a strand exchange step; as well as the consequence of such a model for the stability of eukaryotic genomes.

  2. Development and characterization of recombinant ovine coagulation factor VIII.

    Philip M Zakas

    Full Text Available Animal models of the bleeding disorder, hemophilia A, have been an integral component of the biopharmaceutical development process and have facilitated the development of recombinant coagulation factor VIII (fVIII products capable of restoring median survival of persons with hemophilia A to that of the general population. However, there remain several limitations to recombinant fVIII as a biotherapeutic, including invasiveness of intravenous infusion, short half-life, immunogenicity, and lack of availability to the majority of the world's population. The recently described ovine model of hemophilia A is the largest and most accurate phenocopy. Affected sheep die prematurely due to bleeding-related pathogenesis and display robust adaptive humoral immunity to non-ovine fVIII. Herein, we describe the development and characterization of recombinant ovine fVIII (ofVIII to support further the utility of the ovine hemophilia A model. Full-length and B-domain deleted (BDD ofVIII cDNAs were generated and demonstrated to facilitate greater biosynthetic rates than their human fVIII counterparts while both BDD constructs showed greater expression rates than the same-species full-length versions. A top recombinant BDD ofVIII producing baby hamster kidney clone was identified and used to biosynthesize raw material for purification and biochemical characterization. Highly purified recombinant BDD ofVIII preparations possess a specific activity nearly 2-fold higher than recombinant BDD human fVIII and display a differential glycosylation pattern. However, binding to the carrier protein, von Willebrand factor, which is critical for stability of fVIII in circulation, is indistinguishable. Decay of thrombin-activated ofVIIIa is 2-fold slower than human fVIII indicating greater intrinsic stability. Furthermore, intravenous administration of ofVIII effectively reverses the bleeding phenotype in the murine model of hemophilia A. Recombinant ofVIII should facilitate

  3. Effects of collisions on level populations and dielectronic recombination rates of multiply charged ions

    Jacobs, V.L.; Davis, J.

    1978-01-01

    A generalization of previously reported statistical theories is developed for determining the excited-level populations and the ionization-recombination balance of multiply charged atomic ions in an optically thin high-temperature plasma. Account is taken of the most important collisional and radiative processes involving bound and autoionizing levels in three consecutive ionization stages. We obtain a set of rate equations for the population densities of the low-lying levels which contains effective excitation, ionization, and recombination rates describing indirect transitions through the more highly excited bound and autoionizing levels. The familiar corona-model equations for the ground-state populations are recovered by making the assumption that all excited states decay by only spontaneous radiative or autoionization processes. When collisional processes become efficient in depopulating the highly excited levels important in dielectronic recombination, the effective rate of recombination must be described by a collisional-dielectronic recombination coefficient. Results of calculations are presented for the collisional-dielectronic recombination rate coefficients for recombination of Fe +8 --Fe +13 ions. At an electron density of 10 16 cm -3 , dielectronic recombination is still the dominant recombination process. However, the collisional-dielectronic recombination rate coefficients are found to be reduced by about an order of magnitude from their corona-model values due to the effects of multiple-collisional excitations on the populations of the highly excited bound levels of the recombined ion. The dielectronic recombination rates into these highly excited levels are found to be enhanced by the effects of collisionally induced angular momentum redistribution on the populations of the autoionizing levels

  4. Cattle Sex-Specific Recombination and Genetic Control from a Large Pedigree Analysis.

    Ma, Li; O'Connell, Jeffrey R; VanRaden, Paul M; Shen, Botong; Padhi, Abinash; Sun, Chuanyu; Bickhart, Derek M; Cole, John B; Null, Daniel J; Liu, George E; Da, Yang; Wiggans, George R

    2015-11-01

    Meiotic recombination is an essential biological process that generates genetic diversity and ensures proper segregation of chromosomes during meiosis. From a large USDA dairy cattle pedigree with over half a million genotyped animals, we extracted 186,927 three-generation families, identified over 8.5 million maternal and paternal recombination events, and constructed sex-specific recombination maps for 59,309 autosomal SNPs. The recombination map spans for 25.5 Morgans in males and 23.2 Morgans in females, for a total studied region of 2,516 Mb (986 kb/cM in males and 1,085 kb/cM in females). The male map is 10% longer than the female map and the sex difference is most pronounced in the subtelomeric regions. We identified 1,792 male and 1,885 female putative recombination hotspots, with 720 hotspots shared between sexes. These hotspots encompass 3% of the genome but account for 25% of the genome-wide recombination events in both sexes. During the past forty years, males showed a decreasing trend in recombination rate that coincided with the artificial selection for milk production. Sex-specific GWAS analyses identified PRDM9 and CPLX1 to have significant effects on genome-wide recombination rate in both sexes. Two novel loci, NEK9 and REC114, were associated with recombination rate in both sexes, whereas three loci, MSH4, SMC3 and CEP55, affected recombination rate in females only. Among the multiple PRDM9 paralogues on the bovine genome, our GWAS of recombination hotspot usage together with linkage analysis identified the PRDM9 paralogue on chromosome 1 to be associated in the U.S. Holstein data. Given the largest sample size ever reported for such studies, our results reveal new insights into the understanding of cattle and mammalian recombination.

  5. Acoustic monitoring of the BOR-60 reactor circulating pump state

    Efimov, V.N.; Myntsov, A.A.

    1988-01-01

    Diagnostics methods for circulation pumps of the experimental BOR-60 fast reactor are described. The results of signal processing during a microcompain, as well as detected anomalies in pump operation in the earth stage are presented. Analysis carried out for an acoustic signal envelope has shown high efficiency of the method. When oscillations of a mechanical shaft are present, the envelope level increases 1.5 times. More detailed investigation is carried out by the analysis of the spectrum of the pump acoustic signal envelope. During abnormal operation there are peaks, corresponding to the circulation frequency, and harmonics multiple of it, in the spectrum. 6 figs

  6. Effects of Dissociation/Recombination on the Day–Night Temperature Contrasts of Ultra-hot Jupiters

    Komacek, Thaddeus D.; Tan, Xianyu

    2018-05-01

    Secondary eclipse observations of ultra-hot Jupiters have found evidence that hydrogen is dissociated on their daysides. Additionally, full-phase light curve observations of ultra-hot Jupiters show a smaller day-night emitted flux contrast than that expected from previous theory. Recently, it was proposed by Bell & Cowan (2018) that the heat intake to dissociate hydrogen and heat release due to recombination of dissociated hydrogen can affect the atmospheric circulation of ultra-hot Jupiters. In this work, we add cooling/heating due to dissociation/recombination into the analytic theory of Komacek & Showman (2016) and Zhang & Showman (2017) for the dayside-nightside temperature contrasts of hot Jupiters. We find that at high values of incident stellar flux, the day-night temperature contrast of ultra-hot Jupiters may decrease with increasing incident stellar flux due to dissociation/recombination, the opposite of that expected without including the effects of dissociation/recombination. We propose that a combination of a greater number of full-phase light curve observations of ultra-hot Jupiters and future General Circulation Models that include the effects of dissociation/recombination could determine in detail how the atmospheric circulation of ultra-hot Jupiters differs from that of cooler planets.

  7. Seasonal overturning circulation in the Red Sea: 2. Winter circulation

    Yao, Fengchao

    2014-04-01

    The shallow winter overturning circulation in the Red Sea is studied using a 50 year high-resolution MITgcm (MIT general circulation model) simulation with realistic atmospheric forcing. The overturning circulation for a typical year, represented by 1980, and the climatological mean are analyzed using model output to delineate the three-dimensional structure and to investigate the underlying dynamical mechanisms. The horizontal model circulation in the winter of 1980 is dominated by energetic eddies. The climatological model mean results suggest that the surface inflow intensifies in a western boundary current in the southern Red Sea that switches to an eastern boundary current north of 24N. The overturning is accomplished through a cyclonic recirculation and a cross-basin overturning circulation in the northern Red Sea, with major sinking occurring along a narrow band of width about 20 km along the eastern boundary and weaker upwelling along the western boundary. The northward pressure gradient force, strong vertical mixing, and horizontal mixing near the boundary are the essential dynamical components in the model\\'s winter overturning circulation. The simulated water exchange is not hydraulically controlled in the Strait of Bab el Mandeb; instead, the exchange is limited by bottom and lateral boundary friction and, to a lesser extent, by interfacial friction due to the vertical viscosity at the interface between the inflow and the outflow. Key Points Sinking occurs in a narrow boundary layer along the eastern boundary Surface western boundary current switches into an eastern boundary current Water exchange in the Strait of Bab el Mandeb is not hydraulically controlled © 2014. American Geophysical Union. All Rights Reserved.

  8. The Contribution of Genetic Recombination to CRISPR Array Evolution.

    Kupczok, Anne; Landan, Giddy; Dagan, Tal

    2015-06-16

    CRISPR (clustered regularly interspaced short palindromic repeats) is a microbial immune system against foreign DNA. Recognition sequences (spacers) encoded within the CRISPR array mediate the immune reaction in a sequence-specific manner. The known mechanisms for the evolution of CRISPR arrays include spacer acquisition from foreign DNA elements at the time of invasion and array erosion through spacer deletion. Here, we consider the contribution of genetic recombination between homologous CRISPR arrays to the evolution of spacer repertoire. Acquisition of spacers from exogenic arrays via recombination may confer the recipient with immunity against unencountered antagonists. For this purpose, we develop a novel method for the detection of recombination in CRISPR arrays by modeling the spacer order in arrays from multiple strains from the same species. Because the evolutionary signal of spacer recombination may be similar to that of pervasive spacer deletions or independent spacer acquisition, our method entails a robustness analysis of the recombination inference by a statistical comparison to resampled and perturbed data sets. We analyze CRISPR data sets from four bacterial species: two Gammaproteobacteria species harboring CRISPR type I and two Streptococcus species harboring CRISPR type II loci. We find that CRISPR array evolution in Escherichia coli and Streptococcus agalactiae can be explained solely by vertical inheritance and differential spacer deletion. In Pseudomonas aeruginosa, we find an excess of single spacers potentially incorporated into the CRISPR locus during independent acquisition events. In Streptococcus thermophilus, evidence for spacer acquisition by recombination is present in 5 out of 70 strains. Genetic recombination has been proposed to accelerate adaptation by combining beneficial mutations that arose in independent lineages. However, for most species under study, we find that CRISPR evolution is shaped mainly by spacer acquisition and

  9. Production and recombination of gluons

    Temiraliev, A.T.

    2006-01-01

    Full text: Nonlinear Markov process of parton production has been considered. The Kolmogorov equation is applied for the evolution equation based on the approximation of independent gluons production in every decay act. We introduced a 'crossing' parameter and used the combination relations to obtain nonlinear recombination equation for the evolution of gluon structure function. (author)

  10. Recombinator of hydrogen and oxygen

    Stejskal, J.; Klein, O.; Scholtz, G.; Schmidt, P.; Olaussson, A.

    1976-01-01

    Improvements are proposed for the well known reactors for the catalytic recombination of hydrogen and oxygen, which should permit this being used in contiuous operation in nuclear reactors (BWRs). The improvements concern the geometric arrangement of gas-inlet and -outlet pipes, the inclination of the axis of the catalyst container and the introduction of remote operation. (UWI) [de

  11. Improving recombinant protein purification yield

    Production of adequate amounts of recombinant proteins is essential for antibody production, biochemical activity study, and structural determination during the post-genomic era. It’s technologically challenging and a limiting factor for tung oil research because analytical reagents such as high qua...

  12. Recombination in hepatitis C virus.

    González-Candelas, Fernando; López-Labrador, F Xavier; Bracho, María Alma

    2011-10-01

    Hepatitis C virus (HCV) is a Flavivirus with a positive-sense, single-stranded RNA genome of about 9,600 nucleotides. It is a major cause of liver disease, infecting almost 200 million people all over the world. Similarly to most RNA viruses, HCV displays very high levels of genetic diversity which have been used to differentiate six major genotypes and about 80 subtypes. Although the different genotypes and subtypes share basic biological and pathogenic features they differ in clinical outcomes, response to treatment and epidemiology. The first HCV recombinant strain, in which different genome segments derived from parentals of different genotypes, was described in St. Petersburg (Russia) in 2002. Since then, there have been only a few more than a dozen reports including descriptions of HCV recombinants at all levels: between genotypes, between subtypes of the same genotype and even between strains of the same subtype. Here, we review the literature considering the reasons underlying the difficulties for unequivocally establishing recombination in this virus along with the analytical methods necessary to do it. Finally, we analyze the potential consequences, especially in clinical practice, of HCV recombination in light of the coming new therapeutic approaches against this virus.

  13. The Invertibility, Explicit Determinants, and Inverses of Circulant and Left Circulant and g-Circulant Matrices Involving Any Continuous Fibonacci and Lucas Numbers

    Zhaolin Jiang

    2014-01-01

    Full Text Available Circulant matrices play an important role in solving delay differential equations. In this paper, circulant type matrices including the circulant and left circulant and g-circulant matrices with any continuous Fibonacci and Lucas numbers are considered. Firstly, the invertibility of the circulant matrix is discussed and the explicit determinant and the inverse matrices by constructing the transformation matrices are presented. Furthermore, the invertibility of the left circulant and g-circulant matrices is also studied. We obtain the explicit determinants and the inverse matrices of the left circulant and g-circulant matrices by utilizing the relationship between left circulant, g-circulant matrices and circulant matrix, respectively.

  14. Live recombinant BHV/BRSV vaccine

    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

  15. Hadron production at RHIC: recombination of quarks

    Fries, Rainer J [School of Physics and Astronomy, University of Minnesota, Minneapolis, MN 55455 (United States)

    2005-01-01

    We discuss quark recombination applied to the hadronization of a quark gluon plasma. It has been shown that the quark recombination model can explain essential features of hadron production measured in high energy heavy ion collisions.

  16. Affinity purification of recombinant human plasminogen activator ...

    Affinity purification of recombinant human plasminogen activator from ... Screening antibody was performed using rhPA milk in an ELISA-elution assay. ... useful for purifying other tPA mutants or other novel recombinant milkderived proteins.

  17. Graded Recombination Layers for Multijunction Photovoltaics

    Koleilat, Ghada I.; Wang, Xihua; Sargent, Edward H.

    2012-01-01

    it to achieve multicolor and spectrally tunable behavior. In series-connected current-matched multijunction devices, the recombination layers must allow the hole current from one cell to recombine, with high efficiency and low voltage loss, with the electron

  18. Evidence of recombination in Hepatitis C Virus populations infecting a hemophiliac patient

    Cristina Juan

    2009-11-01

    Full Text Available Abstract Background/Aim Hepatitis C virus (HCV infection is an important cause of morbidity and mortality in patients affected by hereditary bleeding disorders. HCV, as others RNA virus, exploit all possible mechanisms of genetic variation to ensure their survival, such as recombination and mutation. In order to gain insight into the genetic variability of HCV virus strains circulating in hemophiliac patients, we have performed a phylogenetic analysis of HCV strains isolated from 10 patients with this kind of pathology. Methods Putative recombinant sequence was identified with the use of GARD program. Statistical support for the presence of a recombination event was done by the use of LARD program. Results A new intragenotypic recombinant strain (1b/1a was detected in 1 out of the 10 hemophiliac patient studied. The recombination event was located at position 387 of the HCV genome (relative to strain AF009606, sub-type 1a corresponding to the core gene region. Conclusion Although recombination may not appear to be common among natural populations of HCV it should be considered as a possible mechanism for generating genetic diversity in hemophiliacs patients.

  19. Connecting the Production Multiple

    Lichen, Alex Yu; Mouritsen, Jan

    &OP process itself is a fluid object, but there is still possibility to organise the messy Production. There are connections between the Production multiple and the managerial technology fluid. The fluid enacted the multiplicity of Production thus making it more difficult to be organised because there were...... in opposite directions. They are all part of the fluid object. There is no single chain of circulating references that makes the object a matter of fact. Accounting fluidity means that references drift back and forth and enact new realities also connected to the chain. In this setting future research may......This paper is about objects. It follows post ANT trajectories and finds that objects are multiple and fluid. Extant classic ANT inspired accounting research largely sees accounting inscriptions as immutable mobiles. Although multiplicity of objects upon which accounting acts has been explored...

  20. Population inversion in recombining hydrogen plasma

    Furukane, Utaro; Yokota, Toshiaki; Oda, Toshiatsu.

    1978-11-01

    The collisional-radiative model is applied to a recombining hydrogen plasma in order to investigate the plasma condition in which the population inversion between the energy levels of hydrogen can be generated. The population inversion is expected in a plasma where the three body recombination has a large contribution to the recombining processes and the effective recombination rate is beyond a certain value for a given electron density and temperature. Calculated results are presented in figures and tables. (author)

  1. Regulation of homologous recombination in eukaryotes

    Heyer, Wolf-Dietrich; Ehmsen, Kirk T.; Liu, Jie

    2010-01-01

    Homologous recombination is required for accurate chromosome segregation during the first meiotic division and constitutes a key repair and tolerance pathway for complex DNA damage including DNA double-stranded breaks, interstrand crosslinks, and DNA gaps. In addition, recombination and replication are inextricably linked, as recombination recovers stalled and broken replication forks enabling the evolution of larger genomes/replicons. Defects in recombination lead to genomic instability and ...

  2. Proper Sizing of Circulation Pumps

    Tommerup, Henrik M.; Nørgaard, Jørgen

    2007-01-01

    The paper describes the preliminary results from field tests of replacing various types of old pumps used for circulating water in heating systems in single- and double-family houses with new types of pumps. The tests were carried out in Denmark for the Danish Electricity Savings Trust, but the r......The paper describes the preliminary results from field tests of replacing various types of old pumps used for circulating water in heating systems in single- and double-family houses with new types of pumps. The tests were carried out in Denmark for the Danish Electricity Savings Trust...

  3. Correlates of Circulating 25-Hydroxyvitamin D

    McCullough, Marjorie L.; Weinstein, Stephanie J.; Freedman, D. Michal; Helzlsouer, Kathy; Flanders, W. Dana; Koenig, Karen; Kolonel, Laurence; Laden, Francine; Le Marchand, Loic; Purdue, Mark; Snyder, Kirk; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael; Virtamo, Jarmo; Yang, Gong; Yu, Kai; Zheng, Wei; Albanes, Demetrius; Ashby, Jason; Bertrand, Kimberly; Cai, Hui; Chen, Yu; Gallicchio, Lisa; Giovannucci, Edward; Jacobs, Eric J.; Hankinson, Susan E.; Hartge, Patricia; Hartmuller, Virginia; Harvey, Chinonye; Hayes, Richard B.; Horst, Ronald L.; Shu, Xiao-Ou

    2010-01-01

    Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes. PMID:20562191

  4. The effect of a single recombination event

    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...

  5. A trans-Complementing Recombination Trap Demonstrates a Low Propensity of Flaviviruses for Intermolecular Recombination▿

    Taucher, Christian; Berger, Angelika; Mandl, Christian W.

    2010-01-01

    Intermolecular recombination between the genomes of closely related RNA viruses can result in the emergence of novel strains with altered pathogenic potential and antigenicity. Although recombination between flavivirus genomes has never been demonstrated experimentally, the potential risk of generating undesirable recombinants has nevertheless been a matter of concern and controversy with respect to the development of live flavivirus vaccines. As an experimental system for investigating the ability of flavivirus genomes to recombine, we developed a “recombination trap,” which was designed to allow the products of rare recombination events to be selected and amplified. To do this, we established reciprocal packaging systems consisting of pairs of self-replicating subgenomic RNAs (replicons) derived from tick-borne encephalitis virus (TBEV), West Nile virus (WNV), and Japanese encephalitis virus (JEV) that could complement each other in trans and thus be propagated together in cell culture over multiple passages. Any infectious viruses with intact, full-length genomes that were generated by recombination of the two replicons would be selected and enriched by end point dilution passage, as was demonstrated in a spiking experiment in which a small amount of wild-type virus was mixed with the packaged replicons. Using the recombination trap and the JEV system, we detected two aberrant recombination events, both of which yielded unnatural genomes containing duplications. Infectious clones of both of these genomes yielded viruses with impaired growth properties. Despite the fact that the replicon pairs shared approximately 600 nucleotides of identical sequence where a precise homologous crossover event would have yielded a wild-type genome, this was not observed in any of these systems, and the TBEV and WNV systems did not yield any viable recombinant genomes at all. Our results show that intergenomic recombination can occur in the structural region of flaviviruses

  6. Genetic dependence of recombination in recD mutants of Escherichia coli

    Lovett, S.T.; Luisi-DeLuca, C.; Kolodner, R.D.

    1988-01-01

    RecBCD enzyme has multiple activities including helicase, exonuclease and endonuclease activities. Mutations in the genes recB or recC, encoding two subunits of the enzyme, reduce the frequency of many types of recombinational events. Mutations in recD, encoding the third subunit, do not reduce recombination even though most of the activities of the RecBCD enzyme are severely reduced. In this study, the genetic dependence of different types of recombination in recD mutants has been investigated. The effects of mutations in genes in the RecBCD pathway (recA and recC) as well as the genes specific for the RecF pathway (recF, recJ, recN, recO, recQ, ruv and lexA) were tested on conjugational, transductional and plasmid recombination, and on UV survival. recD mutants were hyper-recombinogenic for all the monitored recombination events, especially those involving plasmids, and all recombination events in recD strains required recA and recC. In addition, unlike recD+ strains, chromosomal recombination events and the repair of UV damage to DNA in recD strains were dependent on one RecF pathway gene, recJ. Only a subset of the tested recombination events were affected by ruv, recN, recQ, recO and lexA mutations

  7. Enrichment of intersubtype HIV-1 recombinants in a dual infection system using HIV-1 strain-specific siRNAs

    2011-01-01

    Background Intersubtype HIV-1 recombinants in the form of unique or stable circulating recombinants forms (CRFs) are responsible for over 20% of infections in the worldwide epidemic. Mechanisms controlling the generation, selection, and transmission of these intersubtype HIV-1 recombinants still require further investigation. All intersubtype HIV-1 recombinants are generated and evolve from initial dual infections, but are difficult to identify in the human population. In vitro studies provide the most practical system to study mechanisms, but the recombination rates are usually very low in dual infections with primary HIV-1 isolates. This study describes the use of HIV-1 isolate-specific siRNAs to enrich intersubtype HIV-1 recombinants and inhibit the parental HIV-1 isolates from a dual infection. Results Following a dual infection with subtype A and D primary HIV-1 isolates and two rounds of siRNA treatment, nearly 100% of replicative virus was resistant to a siRNA specific for an upstream target sequence in the subtype A envelope (env) gene as well as a siRNA specific for a downstream target sequence in the subtype D env gene. Only 20% (10/50) of the replicating virus had nucleotide substitutions in the siRNA-target sequence whereas the remaining 78% (39/50) harbored a recombination breakpoint that removed both siRNA target sequences, and rendered the intersubtype D/A recombinant virus resistant to the dual siRNA treatment. Since siRNAs target the newly transcribed HIV-1 mRNA, the siRNAs only enrich intersubtype env recombinants and do not influence the recombination process during reverse transcription. Using this system, a strong bias is selected for recombination breakpoints in the C2 region, whereas other HIV-1 env regions, most notably the hypervariable regions, were nearly devoid of intersubtype recombination breakpoints. Sequence conservation plays an important role in selecting for recombination breakpoints, but the lack of breakpoints in many conserved

  8. Multi-stage circulating fluidized bed syngas cooling

    Liu, Guohai; Vimalchand, Pannalal; Guan, Xiaofeng; Peng, WanWang

    2016-10-11

    A method and apparatus for cooling hot gas streams in the temperature range 800.degree. C. to 1600.degree. C. using multi-stage circulating fluid bed (CFB) coolers is disclosed. The invention relates to cooling the hot syngas from coal gasifiers in which the hot syngas entrains substances that foul, erode and corrode heat transfer surfaces upon contact in conventional coolers. The hot syngas is cooled by extracting and indirectly transferring heat to heat transfer surfaces with circulating inert solid particles in CFB syngas coolers. The CFB syngas coolers are staged to facilitate generation of steam at multiple conditions and hot boiler feed water that are necessary for power generation in an IGCC process. The multi-stage syngas cooler can include internally circulating fluid bed coolers, externally circulating fluid bed coolers and hybrid coolers that incorporate features of both internally and externally circulating fluid bed coolers. Higher process efficiencies can be realized as the invention can handle hot syngas from various types of gasifiers without the need for a less efficient precooling step.

  9. VanderLaan Circulant Type Matrices

    Hongyan Pan

    2015-01-01

    Full Text Available Circulant matrices have become a satisfactory tools in control methods for modern complex systems. In the paper, VanderLaan circulant type matrices are presented, which include VanderLaan circulant, left circulant, and g-circulant matrices. The nonsingularity of these special matrices is discussed by the surprising properties of VanderLaan numbers. The exact determinants of VanderLaan circulant type matrices are given by structuring transformation matrices, determinants of well-known tridiagonal matrices, and tridiagonal-like matrices. The explicit inverse matrices of these special matrices are obtained by structuring transformation matrices, inverses of known tridiagonal matrices, and quasi-tridiagonal matrices. Three kinds of norms and lower bound for the spread of VanderLaan circulant and left circulant matrix are given separately. And we gain the spectral norm of VanderLaan g-circulant matrix.

  10. Recombination Catalysts for Hypersonic Fuels

    Chinitz, W.

    1998-01-01

    The goal of commercially-viable access to space will require technologies that reduce propulsion system weight and complexity, while extracting maximum energy from the products of combustion. This work is directed toward developing effective nozzle recombination catalysts for the supersonic and hypersonic aeropropulsion engines used to provide such access to space. Effective nozzle recombination will significantly reduce rk=le length (hence, propulsion system weight) and reduce fuel requirements, further decreasing the vehicle's gross lift-off weight. Two such catalysts have been identified in this work, barium and antimony compounds, by developing chemical kinetic reaction mechanisms for these materials and determining the engine performance enhancement for a typical flight trajectory. Significant performance improvements are indicated, using only 2% (mole or mass) of these compounds in the combustor product gas.

  11. Mechanisms of sister chromatid recombination

    Nakai, Sayaka; Machida, Isamu; Tsuji, Satsuki

    1985-01-01

    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-G 2 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.)

  12. Interface recombination influence on carrier transport

    Konin, A

    2013-01-01

    A theory of interface recombination in the semiconductor–semiconductor junction is developed. The interface recombination rate dependence on the nonequilibrium carrier densities is derived on the basis of a model in which the interface recombination occurs through the mechanism of trapping. The general relation between the interface recombination parameters at small carrier density deviation from the equilibrium ones is obtained. The validity of this relation is proved considering the generation of the Hall electric field in the extrinsic semiconductor sample. The anomalous Hall electromotive force in a weak magnetic field was investigated and interpreted by means of a new interface recombination model. The experimental data corroborate the developed theory. (paper)

  13. Using an electrocautery strategy or recombinant follicle stimulating hormone to induce ovulation in polycystic ovary syndrome: randomised controlled trial

    Bayram, Neriman; van Wely, Madelon; Kaaijk, Eugenie M; Bossuyt, Patrick M M; van der Veen, Fulco

    2004-01-01

    Objective To compare the effectiveness of an electrocautery strategy with ovulation induction using recombinant follicle stimulating hormone in patients with polycystic ovary syndrome. Design Randomised controlled trial. Setting Secondary and tertiary hospitals in the Netherlands. Participants 168 patients with clomiphene citrate resistant polycystic ovary syndrome: 83 were allocated electrocautery and 85 were allocated recombinant follicle stimulating hormone. Intervention Laparoscopic electrocautery of the ovaries followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted, or induction of ovulation with recombinant follicle stimulating hormone. Main outcome measure Ongoing pregnancy within 12 months. Results. The cumulative rate of ongoing pregnancy after recombinant follicle stimulating hormone was 67%. With only electrocautery it was 34%, which increased to 49% after clomiphene citrate was given. Subsequent recombinant follicle stimulating hormone increased the rate to 67% at 12 months (rate ratio 1.01, 95% confidence interval 0.81 to 1.24). No complications occurred from electrocautery with or without clomiphene citrate. Patients allocated to electrocautery had a significantly lower risk of multiple pregnancy (0.11, 0.01 to 0.86). Conclusion The ongoing pregnancy rate from ovulation induction with laparoscopic electrocautery followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted, or recombinant follicle stimulating hormone, seems equivalent to ovulation induction with recombinant follicle stimulating hormone, but the former procedure carries a lower risk of multiple pregnancy. PMID:14739186

  14. Recombinant Cyclophilins Lack Nuclease Activity

    Manteca, Angel; Sanchez, Jesus

    2004-01-01

    Several single-domain prokaryotic and eukaryotic cyclophilins have been identified as also being unspecific nucleases with a role in DNA degradation during the lytic processes that accompany bacterial cell death and eukaryotic apoptosis. Evidence is provided here that the supposed nuclease activity of human and bacterial recombinant cyclophilins is due to contamination of the proteins by the host Escherichia coli endonuclease and is not an intrinsic property of these proteins.

  15. Workshop on Radio Recombination Lines

    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...

  16. Consequences of recombination on traditional phylogenetic analysis

    Schierup, M H; Hein, J

    2000-01-01

    We investigate the shape of a phylogenetic tree reconstructed from sequences evolving under the coalescent with recombination. The motivation is that evolutionary inferences are often made from phylogenetic trees reconstructed from population data even though recombination may well occur (mt......DNA or viral sequences) or does occur (nuclear sequences). We investigate the size and direction of biases when a single tree is reconstructed ignoring recombination. Standard software (PHYLIP) was used to construct the best phylogenetic tree from sequences simulated under the coalescent with recombination....... With recombination present, the length of terminal branches and the total branch length are larger, and the time to the most recent common ancestor smaller, than for a tree reconstructed from sequences evolving with no recombination. The effects are pronounced even for small levels of recombination that may...

  17. Fine-Scale Recombination Maps of Fungal Plant Pathogens Reveal Dynamic Recombination Landscapes and Intragenic Hotspots.

    Stukenbrock, Eva H; Dutheil, Julien Y

    2018-03-01

    Meiotic recombination is an important driver of evolution. Variability in the intensity of recombination across chromosomes can affect sequence composition, nucleotide variation, and rates of adaptation. In many organisms, recombination events are concentrated within short segments termed recombination hotspots. The variation in recombination rate and positions of recombination hotspot can be studied using population genomics data and statistical methods. In this study, we conducted population genomics analyses to address the evolution of recombination in two closely related fungal plant pathogens: the prominent wheat pathogen Zymoseptoria tritici and a sister species infecting wild grasses Z. ardabiliae We specifically addressed whether recombination landscapes, including hotspot positions, are conserved in the two recently diverged species and if recombination contributes to rapid evolution of pathogenicity traits. We conducted a detailed simulation analysis to assess the performance of methods of recombination rate estimation based on patterns of linkage disequilibrium, in particular in the context of high nucleotide diversity. Our analyses reveal overall high recombination rates, a lack of suppressed recombination in centromeres, and significantly lower recombination rates on chromosomes that are known to be accessory. The comparison of the recombination landscapes of the two species reveals a strong correlation of recombination rate at the megabase scale, but little correlation at smaller scales. The recombination landscapes in both pathogen species are dominated by frequent recombination hotspots across the genome including coding regions, suggesting a strong impact of recombination on gene evolution. A significant but small fraction of these hotspots colocalize between the two species, suggesting that hotspot dynamics contribute to the overall pattern of fast evolving recombination in these species. Copyright © 2018 Stukenbrock and Dutheil.

  18. Distinct Circulating Recombinant HIV-1 Strains Among Injecting Drug Users and Sex Workers in Afghanistan

    2010-05-01

    assessed sociodemographics, travel history, sex- work history, and activity for SWs and sexual -activity history for IDUs, past and current drug-use...behaviors, past and current STI symptoms, condom (men and women) and contraceptive (women only) use, and knowledge about HIV. SW participants received a...32.7 years. Most were married (72.7%) and had >6 years of formal education (72.7%). The mean reported duration of injecting was 2.45 years (SD¼ 1.63

  19. Purification and Autoactivation Method for Recombinant Coagulation Factor VII.

    Granovski, Vladimir; Freitas, Marcela C C; Abreu-Neto, Mario Soares; Covas, Dimas T

    2018-01-01

    Recombinant coagulation factor VII is a very important and complex protein employed for treatment of hemophiliac patients (hemophilia A/B) who develop inhibitors antibodies to conventional treatments (FVIII and FIX). The rFVII is a glycosylated molecule and circulates in plasma as zymogen of 50 kDa. When activated the molecule is cleaved to 20-30 kDa and has a half-life of about 3 h, needing to be processed fast and efficiently until freeze-drying. Here, we describe a very simple and fast purification sequence for rFVII using affinity FVII Select resin and a dialysis system that can be easily scaled up.

  20. Recombinant Protein Production of Earthworm Lumbrokinase for Potential Antithrombotic Application

    Kevin Yueju Wang

    2013-01-01

    Full Text Available Earthworms have been used as a traditional medicine in China, Japan, and other Far East countries for thousands of years. Oral administration of dry earthworm powder is considered as a potent and effective supplement for supporting healthy blood circulation. Lumbrokinases are a group of enzymes that were isolated and purified from different species of earthworms. These enzymes are recognized as fibrinolytic agents that can be used to treat various conditions associated with thrombosis. Many lumbrokinase (LK genes have been cloned and characterized. Advances in genetic technology have provided the ability to produce recombinant LK and have made it feasible to purify a single lumbrokinase enzyme for potential antithrombotic application. In this review, we focus on expression systems that can be used for lumbrokinase production. In particular, the advantages of using a transgenic plant system to produce edible lumbrokinase are described.

  1. Journalism as Cultures of Circulation

    Bødker, Henrik

    2013-01-01

    The universe of journalism has always consisted of interspersed texts, meanings and practices. Yet, much journalism research has often isolated either texts and/or contexts and as such assumed relations between professional practices, informed (rational) readers and (conceived) core texts...... of journalism. It is, however, more important than ever to shift attention away from texts to the processes through which they are circulated. This is partly because the many cultural forms of journalism (textual, institutional, technological, material, behavioural and imagined) are undergoing significant......, likes, comments, searches, journalist roles, writing and reading positions and identities etc. Such forms will be traced within the mediation of a specific event with the overall aim of beginning a theorization of the landscape of journalism as highly interrelated cultures of circulation....

  2. Radioisotopic evaluation of portal circulation

    Maliska, C.; Rosenthal, D.

    1986-01-01

    The use of a radio-tracer of portal circulation through the intestine, should prevent cruel punctures in the portal-vein or spleen as it is usually the case with traditional methods in the study of portal-system. The absorption of I-131 and Tc-99m, previously cheked in rabbits presented similar results in dogs. The time of circulation between terminal large-intestine and the liver (t-RF) was determined by external counting at hepatic level by recording radioactivity variation-time. In healthy animals the t-RF was from 20to 60 seconds, with average time of 42 seconds. In 2 animals with partial binding of portal-vein the t-RF went up to 110 and 120 seconds. (Author) [pt

  3. Ocean circulation generated magnetic signals

    Manoj, C.; Kuvshinov, A.; Maus, S.

    2006-01-01

    Conducting ocean water, as it flows through the Earth's magnetic field, generates secondary electric and magnetic fields. An assessment of the ocean-generated magnetic fields and their detectability may be of importance for geomagnetism and oceanography. Motivated by the clear identification...... of ocean tidal signatures in the CHAMP magnetic field data we estimate the ocean magnetic signals of steady flow using a global 3-D EM numerical solution. The required velocity data are from the ECCO ocean circulation experiment and alternatively from the OCCAM model for higher resolution. We assume...... of the magnetic field, as compared to the ECCO simulation. Besides the expected signatures of the global circulation patterns, we find significant seasonal variability of ocean magnetic signals in the Indian and Western Pacific Oceans. Compared to seasonal variation, interannual variations produce weaker signals....

  4. Specific modifications of histone tails, but not DNA methylation, mirror the temporal variation of mammalian recombination hotspots.

    Zeng, Jia; Yi, Soojin V

    2014-10-16

    Recombination clusters nonuniformly across mammalian genomes at discrete genomic loci referred to as recombination hotspots. Despite their ubiquitous presence, individual hotspots rapidly lose their activities, and the molecular and evolutionary mechanisms underlying such frequent hotspot turnovers (the so-called "recombination hotspot paradox") remain unresolved. Even though some sequence motifs are significantly associated with hotspots, multiple lines of evidence indicate that factors other than underlying sequences, such as epigenetic modifications, may affect the evolution of recombination hotspots. Thus, identifying epigenetic factors that covary with recombination at fine-scale is a promising step for this important research area. It was previously reported that recombination rates correlate with indirect measures of DNA methylation in the human genome. Here, we analyze experimentally determined DNA methylation and histone modification of human sperms, and show that the correlation between DNA methylation and recombination in long-range windows does not hold with respect to the spatial and temporal variation of recombination at hotspots. On the other hand, two histone modifications (H3K4me3 and H3K27me3) overlap extensively with recombination hotspots. Similar trends were observed in mice. These results indicate that specific histone modifications rather than DNA methylation are associated with the rapid evolution of recombination hotspots. Furthermore, many human recombination hotspots occupy "bivalent" chromatin regions that harbor both active (H3K4me3) and repressive (H3K27me3) marks. This may explain why human recombination hotspots tend to occur in nongenic regions, in contrast to yeast and Arabidopsis hotspots that are characterized by generally active chromatins. Our results highlight the dynamic epigenetic underpinnings of recombination hotspot evolution. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for

  5. Observations of Local Seychelles Circulation

    2015-09-30

    1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Observations of Local Seychelles Circulation Geno...goal for the proposed work is to develop predictive capabilities for physical oceanography for the Seychelles region in support of locally relevant...observations in the Seychelles region that will lead to long-term data collection efforts. In collaboration with local partnerships, we will carry out

  6. Circulating nucleic acids and evolution.

    Anker, Philippe; Stroun, Maurice

    2012-06-01

    J.B. Lamarck in 1809 was the first to present a theory of evolution. He proposed it was due to the adaptation of species to environmental changes, this adaptation being acquired by the offspring. In 1868, Darwin suggested that cells excrete gemmules, which circulate through the body and reach the gonads where they are transmitted to the next generation. His main argument came from graft hybrids. In the fifties and sixties, Russian geneticists, rejecting neo-Darwinism, said that acquired characteristics were the basis of evolution. The main experiments on which they based their theory were the transmission of hereditary characteristics by a special technique of grafting between two varieties of plants. We repeated this kind of experiment and also succeeded in obtaining hereditary modifications of the pupil plants that acquired some characteristics of the mentor variety. Rather than adopting the views of the Russian scientists, we suggested that DNA was circulating between the mentor and pupil plants. Hirata's group have shown recently, by using molecular techniques such as cloning, RFLP PCR and sequencing some genes of their graft hybrids of pepper plants, that transfer of informative molecules from the mentor to the pupil plant does exist. Nucleic acids are actively released by cells; they circulate in the body. They can transform oncogenically or trigger antibody response but the only genetic transformation showing that DNA can go from the soma to the germen comes from graft hybrids. This suggests that circulating nucleic acids, in this case DNA, like Darwin's gemmules, play a role in the mechanism of evolution.

  7. Improvement of Classification of Enterprise Circulating Funds

    Rohanova Hanna O.

    2014-01-01

    The goal of the article lies in revelation of possibilities of increase of efficiency of managing enterprise circulating funds by means of improvement of their classification features. Having analysed approaches of many economists to classification of enterprise circulating funds, systemised and supplementing them, the article offers grouping classification features of enterprise circulating funds. In the result of the study the article offers an expanded classification of circulating funds, ...

  8. Hall Effect Gyrators and Circulators

    Viola, Giovanni; DiVincenzo, David P.

    2014-04-01

    The electronic circulator and its close relative the gyrator are invaluable tools for noise management and signal routing in the current generation of low-temperature microwave systems for the implementation of new quantum technologies. The current implementation of these devices using the Faraday effect is satisfactory but requires a bulky structure whose physical dimension is close to the microwave wavelength employed. The Hall effect is an alternative nonreciprocal effect that can also be used to produce desired device functionality. We review earlier efforts to use an Ohmically contacted four-terminal Hall bar, explaining why this approach leads to unacceptably high device loss. We find that capacitive coupling to such a Hall conductor has much greater promise for achieving good circulator and gyrator functionality. We formulate a classical Ohm-Hall analysis for calculating the properties of such a device, and show how this classical theory simplifies remarkably in the limiting case of the Hall angle approaching 90°. In this limit, we find that either a four-terminal or a three-terminal capacitive device can give excellent circulator behavior, with device dimensions far smaller than the ac wavelength. An experiment is proposed to achieve GHz-band gyration in millimeter (and smaller) scale structures employing either semiconductor heterostructure or graphene Hall conductors. An inductively coupled scheme for realizing a Hall gyrator is also analyzed.

  9. Effects of nuclear mutations for recombination and repair functions and of caffeine on mitochondrial recombination

    Fraenkel, A.H.M.

    1974-01-01

    Studies of both prokaryotic and eukaryotic organisms indicate that pathways governing repair of damage to nuclear DNA caused by x-ray or ultraviolet irradiation overlap with those controlling recombination. Fourteen nuclear mutants of Saccharomyces cerevisiae were tested in order to determine whether these mutant genes affected mitochondrial recombination. None of the mutations studied significantly affected mitochondrial recombination. The nuclear recombination and repair pathways studied do not overlap with the nuclear pathway which controls recombination of mitochondrial DNA. A second set of experiments was designed to test the effect of caffeine on both nuclear and mitochondrial recombination in Saccharomyces cerevisiae. (U.S.)

  10. Designer genes. Recombinant antibody fragments for biological imaging

    Wu, A.M.; Yazaki, P.J. [Beckman Research Institute of the City of Hope, Duarte, CA (United States). Dept. of Molecular Biology

    2000-09-01

    Monoclonal antibodies (MAbs), with high specificity and high affinity for their target antigens, can be utilized for delivery of agents such as radionuclides, enzymes, drugs or toxins in vivo. However, the implementation of radiolabeled antibodies as magic bullets for detection and treatment of diseases such as cancer has required addressing several shortcomings of murine MAbs. These include their immunogenicity, sub-optimal targeting and pharmacokinetic properties, and practical issues of production and radiolabeling. Genetic engineering provides a powerful approach for redesigning antibodies for use in oncologic applications in vivo. Recombinant fragments have been produced that retain high affinity for target antigens, and display a combination of rapid, high-level tumor targeting with concomitant clearance from normal tissues and the circulation in animal models. An important first step was cloning and engineering of antibody heavy and light chain variable domains into single-chain Fvs (molecular weight, 25-17 kDa), in which the variable regions are joined via a synthetic linker peptide sequence. Although scFvs themselves showed limited tumor uptake in preclinical and clinical studies, they provide a useful building block for intermediate sized recombinant fragments. Covalently linked dimers or non-covalent dimers of scFvs (also known as diabodies) show improved targeting and clearance properties due to their higher molecular weight (55kDa) and increased avidity. Further gains can be made by generation of larger recombinant fragments, such as the minibody, an scFv-C{sub H}3 fusion protein that self-assembles into a bivalent dimer of 80 kDa. A systematic evaluation of scFv, diabody, minibody, and intact antibody (based on comparison of tumor uptakes, tumor: blood activity ratios, and calculation of an Imaging Figure of Merit) can form the basis for selection of combinations of recombinant fragments and radionuclides for imaging applications. Ease of engineering

  11. Designer genes. Recombinant antibody fragments for biological imaging

    Wu, A.M.; Yazaki, P.J.

    2000-01-01

    Monoclonal antibodies (MAbs), with high specificy and high affinity for their target antigens, can be utilized for delivery of agents such as radionuclides, enzymes, drugs or toxins in vivo. However, the implementation of radiolabeled antibodies as magic bullets for detection and treatment of diseases such as cancer has required addressing several shortcomings of murine MAbs. These include their immunogenicity, sub-optimal targeting and pharmacokinetic properties, and practical issues of production and radiolabeling. Genetic engineering provides a powerful approach for redesigning antibodies for use in oncologic applications in vivo. Recombinant fragments have been produced that retain high affinity for target antigens, and display a combination of rapid, high-level tumor targeting with concomitant clearance from normal tissues and the circulation in animal models. An important first step was cloning and engineering of antibody heavy and light chain variable domains into single-chain Fvs (molecular weight, 25-17 kDa), in which the variable regions are joined via a synthetic linker peptide sequence. Although scFvs themselves showed limited tumor uptake in preclinical and clinical studies, they provide a useful building block for intermediate sized recombinant fragments. Covalently linked dimers or non-covalent dimers of scFvs (also known as diabodies) show improved targeting and clearance properties due to their higher molecular weight (55kDa) and increased avidity. Further gains can be made by generation of larger recombinant fragments, such as the minibody, an scFv-C H 3 fusion protein that self-assembles into a bivalent dimer of 80 kDa. A systematic evaluation of scFv, diabody, minibody, and intact antibody (based on comparison of tumor uptakes, tumor: blood activity ratios, and calculation of an Imaging Figure of Merit) can form the basis for selection of combinations of recombinant fragments and radionuclides for imaging applications. Ease of engineering and

  12. Vaccine platform recombinant measles virus.

    Mühlebach, Michael D

    2017-10-01

    The classic development of vaccines is lengthy, tedious, and may not necessarily be successful as demonstrated by the case of HIV. This is especially a problem for emerging pathogens that are newly introduced into the human population and carry the inherent risk of pandemic spread in a naïve population. For such situations, a considerable number of different platform technologies are under development. These are also under development for pathogens, where directly derived vaccines are regarded as too complicated or even dangerous due to the induction of inefficient or unwanted immune responses causing considerable side-effects as for dengue virus. Among platform technologies are plasmid-based DNA vaccines, RNA replicons, single-round infectious vector particles, or replicating vaccine-based vectors encoding (a) critical antigen(s) of the target pathogens. Among the latter, recombinant measles viruses derived from vaccine strains have been tested. Measles vaccines are among the most effective and safest life-attenuated vaccines known. Therefore, the development of Schwarz-, Moraten-, or AIK-C-strain derived recombinant vaccines against a wide range of mostly viral, but also bacterial pathogens was quite straightforward. These vaccines generally induce powerful humoral and cellular immune responses in appropriate animal models, i.e., transgenic mice or non-human primates. Also in the recent first clinical phase I trial, the results have been quite encouraging. The trial indicated the expected safety and efficacy also in human patients, interestingly independent from the level of prevalent anti-measles immunity before the trial. Thereby, recombinant measles vaccines expressing additional antigens are a promising platform for future vaccines.

  13. Encoders for block-circulant LDPC codes

    Divsalar, Dariush (Inventor); Abbasfar, Aliazam (Inventor); Jones, Christopher R. (Inventor); Dolinar, Samuel J. (Inventor); Thorpe, Jeremy C. (Inventor); Andrews, Kenneth S. (Inventor); Yao, Kung (Inventor)

    2009-01-01

    Methods and apparatus to encode message input symbols in accordance with an accumulate-repeat-accumulate code with repetition three or four are disclosed. Block circulant matrices are used. A first method and apparatus make use of the block-circulant structure of the parity check matrix. A second method and apparatus use block-circulant generator matrices.

  14. Atomic excitation and recombination in external fields

    Nayfeh, M.H.; Clark, C.W.

    1985-01-01

    This volume offers a timely look at Rydberg states of atoms in external fields and dielectronic recombination. Each topic provides authoritative coverage, presents a fresh account of a flourishing field of current atomic physics and introduces new opportunities for discovery and development. Topics considered include electron-atom scattering in external fields; observations of regular and irregular motion as exemplified by the quadratic zeeman effect and other systems; Rydberg atoms in external fields and the Coulomb geometry; crossed-field effects in the absorption spectrum of lithium in a magnetic field; precise studies of static electric field ionization; widths and shapes of stark resonances in sodium above the saddle point; studies of electric field effects and barium autoionizing resonances; autoionization and dielectronic recombination in plasma electric microfields; dielectronic recombination measurements on multicharged ions; merged beam studies of dielectronic recombination; Rydberg atoms and dielectronic recombination in astrophysics; and observations on dielectronic recombination

  15. Recombination in Streptococcus pneumoniae Lineages Increase with Carriage Duration and Size of the Polysaccharide Capsule

    Andam, Cheryl P.; Harris, Simon R.; Cornick, Jennifer E.; Yang, Marie; Bricio-Moreno, Laura; Kamng’ona, Arox W.; French, Neil; Heyderman, Robert S.; Kadioglu, Aras; Everett, Dean B.; Bentley, Stephen D.

    2016-01-01

    ABSTRACT Streptococcus pneumoniae causes a high burden of invasive pneumococcal disease (IPD) globally, especially in children from resource-poor settings. Like many bacteria, the pneumococcus can import DNA from other strains or even species by transformation and homologous recombination, which has allowed the pneumococcus to evade clinical interventions such as antibiotics and pneumococcal conjugate vaccines (PCVs). Pneumococci are enclosed in a complex polysaccharide capsule that determines the serotype; the capsule varies in size and is associated with properties including carriage prevalence and virulence. We determined and quantified the association between capsule and recombination events using genomic data from a diverse collection of serotypes sampled in Malawi. We determined both the amount of variation introduced by recombination relative to mutation (the relative rate) and how many individual recombination events occur per isolate (the frequency). Using univariate analyses, we found an association between both recombination measures and multiple factors associated with the capsule, including duration and prevalence of carriage. Because many capsular factors are correlated, we used multivariate analysis to correct for collinearity. Capsule size and carriage duration remained positively associated with recombination, although with a reduced P value, and this effect may be mediated through some unassayed additional property associated with larger capsules. This work describes an important impact of serotype on recombination that has been previously overlooked. While the details of how this effect is achieved remain to be determined, it may have important consequences for the serotype-specific response to vaccines and other interventions. PMID:27677790

  16. Recombination in Streptococcus pneumoniae Lineages Increase with Carriage Duration and Size of the Polysaccharide Capsule

    Chrispin Chaguza

    2016-09-01

    Full Text Available Streptococcus pneumoniae causes a high burden of invasive pneumococcal disease (IPD globally, especially in children from resource-poor settings. Like many bacteria, the pneumococcus can import DNA from other strains or even species by transformation and homologous recombination, which has allowed the pneumococcus to evade clinical interventions such as antibiotics and pneumococcal conjugate vaccines (PCVs. Pneumococci are enclosed in a complex polysaccharide capsule that determines the serotype; the capsule varies in size and is associated with properties including carriage prevalence and virulence. We determined and quantified the association between capsule and recombination events using genomic data from a diverse collection of serotypes sampled in Malawi. We determined both the amount of variation introduced by recombination relative to mutation (the relative rate and how many individual recombination events occur per isolate (the frequency. Using univariate analyses, we found an association between both recombination measures and multiple factors associated with the capsule, including duration and prevalence of carriage. Because many capsular factors are correlated, we used multivariate analysis to correct for collinearity. Capsule size and carriage duration remained positively associated with recombination, although with a reduced P value, and this effect may be mediated through some unassayed additional property associated with larger capsules. This work describes an important impact of serotype on recombination that has been previously overlooked. While the details of how this effect is achieved remain to be determined, it may have important consequences for the serotype-specific response to vaccines and other interventions.

  17. Density dependence of dielectronic recombination in selenium

    Hagelstein, P.L.; Rosen, M.D.; Jacobs, V.L.

    1986-01-01

    Dielectronic recombination has been found to be the dominant recombination process in the determination of the ionization balance of selenium near the Ne-like sequence under conditions relevant to the exploding-foil EUV laser plasmas. The dielectronic recombination process tends to populate excited levels, and these levels in turn are more susceptible to subsequent excitation and ionization than are the ground-state ions. If one defines an effective recombination rate which includes, in addition to the primary recombination, the subsequent excitation and ionization of the additional excited-state population due to the primary recombination, then this effective recombination rate can be density-sensitive at relatively low electron density. We present results for this effective dielectronic recombination rate at an electron density of 3 x 10/sup 20/ electrons/cm 3 for recombination from Ne-like to Na-like selenium and from F-like to Ne-like selenium. In the former case, the effective recombination rate coefficient is found to be 1.8 x 10/sup -11/ cm 3 /sec at 1.0 keV, which is to be compared with the zero-density value of 2.8 x 10/sup -11/ cm 3 /sec. In the latter case (F-like to Ne-like), the effective recombination rate coefficient is found to be 1.3 x 10/sup -11/ cm 3 /sec, which is substantially reduced from the zero-density result of 3.3 x 10/sup -11/ cm 3 /sec. We have examined the effects of dielectronic recombination on the laser gain of the dominant Ne-like 3p-3s transitions and have compared our results with those presented by Whitten et al. [Phys. Rev. A 33, 2171 (1986)

  18. Responses of the Tropical Atmospheric Circulation to Climate Change and Connection to the Hydrological Cycle

    Ma, Jian; Chadwick, Robin; Seo, Kyong-Hwan; Dong, Changming; Huang, Gang; Foltz, Gregory R.; Jiang, Jonathan H.

    2018-05-01

    This review describes the climate change–induced responses of the tropical atmospheric circulation and their impacts on the hydrological cycle. We depict the theoretically predicted changes and diagnose physical mechanisms for observational and model-projected trends in large-scale and regional climate. The tropical circulation slows down with moisture and stratification changes, connecting to a poleward expansion of the Hadley cells and a shift of the intertropical convergence zone. Redistributions of regional precipitation consist of thermodynamic and dynamical components, including a strong offset between moisture increase and circulation weakening throughout the tropics. This allows other dynamical processes to dominate local circulation changes, such as a surface warming pattern effect over oceans and multiple mechanisms over land. To improve reliability in climate projections, more fundamental understandings of pattern formation, circulation change, and the balance of various processes redistributing land rainfall are suggested to be important.

  19. Rapid purification of recombinant histones.

    Klinker, Henrike; Haas, Caroline; Harrer, Nadine; Becker, Peter B; Mueller-Planitz, Felix

    2014-01-01

    The development of methods to assemble nucleosomes from recombinant histones decades ago has transformed chromatin research. Nevertheless, nucleosome reconstitution remains time consuming to this day, not least because the four individual histones must be purified first. Here, we present a streamlined purification protocol of recombinant histones from bacteria. We termed this method "rapid histone purification" (RHP) as it circumvents isolation of inclusion bodies and thereby cuts out the most time-consuming step of traditional purification protocols. Instead of inclusion body isolation, whole cell extracts are prepared under strongly denaturing conditions that directly solubilize inclusion bodies. By ion exchange chromatography, the histones are purified from the extracts. The protocol has been successfully applied to all four canonical Drosophila and human histones. RHP histones and histones that were purified from isolated inclusion bodies had similar purities. The different purification strategies also did not impact the quality of octamers reconstituted from these histones. We expect that the RHP protocol can be readily applied to the purification of canonical histones from other species as well as the numerous histone variants.

  20. The extent and importance of intragenic recombination

    de Silva Eric

    2004-11-01

    Full Text Available Abstract We have studied the recombination rate behaviour of a set of 140 genes which were investigated for their potential importance in inflammatory disease. Each gene was extensively sequenced in 24 individuals of African descent and 23 individuals of European descent, and the recombination process was studied separately in the two population samples. The results obtained from the two populations were highly correlated, suggesting that demographic bias does not affect our population genetic estimation procedure. We found evidence that levels of recombination correlate with levels of nucleotide diversity. High marker density allowed us to study recombination rate variation on a very fine spatial scale. We found that about 40 per cent of genes showed evidence of uniform recombination, while approximately 12 per cent of genes carried distinct signatures of recombination hotspots. On studying the locations of these hotspots, we found that they are not always confined to introns but can also stretch across exons. An investigation of the protein products of these genes suggested that recombination hotspots can sometimes separate exons belonging to different protein domains; however, this occurs much less frequently than might be expected based on evolutionary studies into the origins of recombination. This suggests that evolutionary analysis of the recombination process is greatly aided by considering nucleotide sequences and protein products jointly.

  1. Competition between replicative and translesion polymerases during homologous recombination repair in Drosophila.

    Daniel P Kane

    Full Text Available In metazoans, the mechanism by which DNA is synthesized during homologous recombination repair of double-strand breaks is poorly understood. Specifically, the identities of the polymerase(s that carry out repair synthesis and how they are recruited to repair sites are unclear. Here, we have investigated the roles of several different polymerases during homologous recombination repair in Drosophila melanogaster. Using a gap repair assay, we found that homologous recombination is impaired in Drosophila lacking DNA polymerase zeta and, to a lesser extent, polymerase eta. In addition, the Pol32 protein, part of the polymerase delta complex, is needed for repair requiring extensive synthesis. Loss of Rev1, which interacts with multiple translesion polymerases, results in increased synthesis during gap repair. Together, our findings support a model in which translesion polymerases and the polymerase delta complex compete during homologous recombination repair. In addition, they establish Rev1 as a crucial factor that regulates the extent of repair synthesis.

  2. [Molecular epidemiological analysis of HIV-1 variants circulating in Russia in 1987-2015].

    Lapovok, I A; Lopatukhin, A E; Kireev, D E; Kazennova, E V; Lebedev, A V; Bobkova, M R; Kolomeets, A N; Turbina, G I; Shipulin, G A; Ladnaya, N N; Pokrovsky, V V

    To simultaneously analyze HIV-1 samples from all Russian regions to characterize the epidemiology of HIV infection in the country as a whole. The most extensive study was conducted to examine nucleotide sequences of the pol gene of HIV-1 samples isolated from HIV-positive persons in different regions of Russia, with the diagnosis date being fixed during 1987-2015. The nucleotide sequences of the HIV-1 genome were analyzed using computer programs and on-line applications to identify a virus subtype and new recombinant forms. The nucleotide sequences of the pol gene were analyzed in 1697 HIV-1 samples and the findings were that the genetic variant subtype A1 (IDU-A) was dominant throughout the entire territory of Russia (in more than 80% of all infection cases). Other virus variants circulating in Russia were analyzed; the phenomenon of the higher distribution of the recombinant form CRF63/02A in Siberia, which had been previously described in the literature, was also confirmed. Four new recombinant forms generated by the virus subtype A1 (IDU-A) and B and two AG recombinant forms were found. There was a larger genetic distance between the viruses of IDU-A variant circulating among the injecting drug users and those infected through heterosexual contact, as well as a change in the viruses of subtype G that caused the outbreak in the south of the country over time in 1988-1989. The findings demonstrate continuous HIV-1 genetic variability and recombination over time in Russia, as well as increased genetic diversity with higher HIV infection rates in the population.

  3. Polyclonal antibodies for the detection of Trypanosoma cruzi circulating antigens.

    Edith S Málaga-Machaca

    2017-11-01

    Full Text Available Detection of Trypanosoma cruzi antigens in clinical samples is considered an important diagnostic tool for Chagas disease. The production and use of polyclonal antibodies may contribute to an increase in the sensitivity of immunodiagnosis of Chagas disease.Polyclonal antibodies were raised in alpacas, rabbits, and hens immunized with trypomastigote excreted-secreted antigen, membrane proteins, trypomastigote lysate antigen and recombinant 1F8 to produce polyclonal antibodies. Western blot analysis was performed to determine specificity of the developed antibodies. An antigen capture ELISA of circulating antigens in serum, plasma and urine samples was developed using IgY polyclonal antibodies against T. cruzi membrane antigens (capture antibody and IgG from alpaca raised against TESA. A total of 33 serum, 23 plasma and 9 urine samples were analyzed using the developed test. Among serum samples, compared to serology, the antigen capture ELISA tested positive in 55% of samples. All plasma samples from serology positive subjects were positive in the antigen capture ELISA. All urine positive samples had corresponding plasma samples that were also positive when tested by the antigen capture ELISA.Polyclonal antibodies are useful for detection of circulating antigens in both the plasma and urine of infected individuals. Detection of antigens is direct evidence of the presence of the parasite, and could be a better surrogate of current infection status.

  4. New recombinant vaccines for the prevention of meningococcal B disease

    Taha MK

    2012-06-01

    Full Text Available Muhamed-Kheir Taha, Ala-Eddine DeghmaneInstitut Pasteur, Unit of Invasive Bacterial Infections and National Reference Center for Meningococci, Paris, FranceAbstract: Meningococcal disease is a life-threatening invasive infection (mainly septicemia and meningitis that occurs as epidemic or sporadic cases. The causative agent, Neisseria meningitidis or meningococcus, is a capsulated Gram-negative bacterium. Current vaccines are prepared from the capsular polysaccharides (that also determine serogroups and are available against strains of serogroups A, C, Y, and W-135 that show variable distribution worldwide. Plain polysaccharide vaccines were first used and subsequently conjugate vaccines with enhanced immunogenicity were introduced. The capsular polysaccharide of meningococcal serogroup B is poorly immunogenic due to similarity to the human neural cells adhesion molecule. Tailor-made, strain-specific vaccines have been developed to control localized and clonal outbreaks due to meningococci of serogroup B but no “universal” vaccine is yet available. This unmet medical need was recently overcome using several subcapsular proteins to allow broad range coverage of strains and to reduce the risk of escape variants due to genetic diversity of the meningococcus. Several vaccines are under development that target major or minor surface proteins. One vaccine (Bexsero®; Novartis, under registration, is a multicomponent recombinant vaccine that showed an acceptable safety profile and covers around 80% of the currently circulating serogroup B isolates. However, its reactogenicity in infants seems to be high and the long term persistence of the immune response needs to be determined. Its activity on carriage, and therefore transmission, is under evaluation. Indirect protection is expected through restricting strain circulation and acquisition. This vaccine covers the circulating strains according to the presence of the targeted antigens in the

  5. The Dynamics of Hadley Circulation Variability and Change

    Davis, Nicholas Alexander

    The Hadley circulation exerts a dominant control on the surface climate of earth's tropical belt. Its converging surface winds fuel the tropical rains, while subsidence in the subtropics dries and stabilizes the atmosphere, creating deserts on land and stratocumulus decks over the oceans. Because of the strong meridional gradients in temperature and precipitation in the subtropics, any shift in the Hadley circulation edge could project as major changes in surface climate. While climate model simulations predict an expansion of the Hadley cells in response to greenhouse gas forcings, the mechanisms remain elusive. An analysis of the climatology, variability, and response of the Hadley circulation to radiative forcings in climate models and reanalyses illuminates the broader landscape in which Hadley cell expansion is realized. The expansion is a fundamental response of the atmosphere to increasing greenhouse gas concentrations as it scales with other key climate system changes, including polar amplification, increasing static stability, stratospheric cooling, and increasing global-mean surface temperatures. Multiple measures of the Hadley circulation edge latitudes co-vary with the latitudes of the eddy-driven jets on all timescales, and both exhibit a robust poleward shift in response to forcings. Further, across models there is a robust coupling between the eddy-driving on the Hadley cells and their width. On the other hand, the subtropical jet and tropopause break latitudes, two common observational proxies for the tropical belt edges, lack a strong statistical relationship with the Hadley cell edges and have no coherent response to forcings. This undermines theories for the Hadley cell width predicated on angular momentum conservation and calls for a new framework for understanding Hadley cell expansion. A numerical framework is developed within an idealized general circulation model to isolate the mean flow and eddy responses of the global atmosphere to

  6. Functional evaluation of circulating hematopoietic progenitors in Noonan syndrome

    TIMEUS, FABIO; CRESCENZIO, NICOLETTA; BALDASSARRE, GIUSEPPINA; DORIA, ALESSANDRA; VALLERO, STEFANO; FOGLIA, LUISELDA; PAGLIANO, SARA; ROSSI, CESARE; SILENGO, MARGHERITA CIRILLO; RAMENGHI, UGO; FAGIOLI, FRANCA; DI MONTEZEMOLO, LUCA CORDERO; FERRERO, GIOVANNI BATTISTA

    2013-01-01

    Noonan syndrome (NS) is an autosomal dominant disorder, characterized by short stature, multiple dysmorphisms and congenital heart defects. A myeloproliferative disorder (NS/MPD), resembling juvenile myelomonocytic leukemia (JMML), is occasionally diagnosed in infants with NS. In the present study, we performed a functional evaluation of the circulating hematopoietic progenitors in a series of NS, NS/MPD and JMML patients. The different functional patterns were compared with the aim to identify a possible NS subgroup worthy of stringent hematological follow-up for an increased risk of MPD development. We studied 27 NS and 5 JMML patients fulfilling EWOG-MDS criteria. The more frequent molecular defects observed in NS were mutations in the PTPN11 and SOS genes. The absolute count of monocytes, circulating CD34+ hematopoietic progenitors, their apoptotic rate and the number of circulating CFU-GMs cultured in the presence of decreasing concentrations or in the absence of granulocyte-macrophage colony-stimulating factor (GM-CSF) were evaluated. All JMML patients showed monocytosis >1,000/μl. Ten out of the 27 NS patients showed monocytosis >1,000/μl, which included the 3 NS/MPD patients. In JMML patients, circulating CD34+ cells were significantly increased (median, 109.8/μl; range, 44–232) with a low rate of apoptosis (median, 2.1%; range, 0.4–12.1%), and circulating CFU-GMs were hyper-responsive to GM-CSF. NS/MPD patients showed the same flow cytometric pattern as the JMML patients (median, CD34+ cells/μl, 205.7; range, 58–1374; median apoptotic rate, 1.4%; range, 0.2–2.4%) and their circulating CFU-GMs were hyper-responsive to GM-CSF. These functional alterations appeared 10 months before the typical clinical manifestations in 1 NS/MPD patient. In NS, the CD34+ absolute cell count and circulating CFU-GMs showed a normal pattern (median CD34+ cells/μl, 4.9; range, 1.3–17.5), whereas the CD34+ cell apoptotic rate was significantly decreased in

  7. The Effect of Recombinant Granulocyte Colony-Stimulating Factor on Oral and Periodontal Manifestations in a Patient with Cyclic Neutropenia: A Case Report

    Sergio Matarasso

    2009-01-01

    Full Text Available Cyclic Neutropenia (CN is characterized by recurrent infections, fever, oral ulcerations, and severe periodontitis as result of the reduced host defences. The previous studies have established the effectiveness of recombinant granulocyte colony-stimulating factor (GCSF to increase the number and the function of neutrophils in the peripheral blood in this disease. In a 20-year-old Caucasian female with a diagnosis of cyclic neutropenia, oral clinical examination revealed multiple painful ulcerations of the oral mucosa, poor oral hygiene conditions, marginal gingivitis, and moderate periodontitis. The patient received a treatment with G-CSF (Pegfilgrastim, 6 mg/month in order to improve her immunological status. Once a month nonsurgical periodontal treatment was carefully performed when absolute neutrophil count (ANC was ≥500/L. The treatment with G-CSF resulted in a rapid increase of circulating neutrophils that, despite its short duration, leaded to a reduction in infection related events and the resolution of the multiple oral ulcerations. The disappearance of oral pain allowed an efficacy nonsurgical treatment and a normal tooth brushing that determined a reduction of probing depth (PD≤4 mm and an improvement of the oral hygiene conditions recorded at 6-month follow-up.

  8. Diarrhea caused by circulating agents.

    Fabian, Elisabeth; Kump, Patrizia; Krejs, Guenter J

    2012-09-01

    Circulating agents cause intestinal secretion or changes in motility with decreased intestinal transit time, resulting in secretory-type diarrhea. Secretory diarrhea as opposed to osmotic diarrhea is characterized by large-volume, watery stools, often more than 1 L per day; by persistence of diarrhea when patients fast; and by the fact that on analysis of stool-water, measured osmolarity is identical to that calculated from the electrolytes present. Although sodium plays the main role in water and electrolyte absorption, chloride is the major ion involved in secretion. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Vasculitis of the mesenteric circulation.

    Koster, Matthew J; Warrington, Kenneth J

    2017-02-01

    Vasculitis of the mesenteric circulation is an uncommon but life-threatening manifestation of systemic vasculitis. Initial symptoms are frequently non-specific and therefore patients often present to primary care physicians and gastroenterologists with abdominal pain or gastrointestinal bleeding. Given the severity of the conditions associated with mesenteric vasculitis, it is imperative to appropriately diagnose and initiate treatment of suspected cases. This review will focus on diseases commonly associated with vasculitis of the mesenteric vessels. Imaging characteristics and clinical features assisting in diagnosis as well as initial approaches to treatment are emphasized. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Autonomic Regulation of Splanchnic Circulation

    Kathleen A Fraser

    1991-01-01

    Full Text Available The role of the autonomic nervous system in circulatory regulation of the splanchnic organs (stomach, small intestine, colon, liver, pancreas and spleen is reviewed. In general, the sympathetic nervous system is primarily involved in vasoconstriction, while the parasympathetic contributes to vasodilation. Vasoconstriction in the splanchnic circulation appears to be mediated by alpha-2 receptors and vasodilation by activation of primary afferent nerves with subsequent release of vasodilatory peptides, or by stimulation of beta-adrenergic receptors. As well, an important function of the autonomic nervous system is to provide a mechanism by which splanchnic vascular reserve can be mobilized during stress to maintain overall cardiovascular homeostasis.

  11. Multiple Perspectives / Multiple Readings

    Simon Biggs

    2005-01-01

    Full Text Available People experience things from their own physical point of view. What they see is usually a function of where they are and what physical attitude they adopt relative to the subject. With augmented vision (periscopes, mirrors, remote cameras, etc we are able to see things from places where we are not present. With time-shifting technologies, such as the video recorder, we can also see things from the past; a time and a place we may never have visited.In recent artistic work I have been exploring the implications of digital technology, interactivity and internet connectivity that allow people to not so much space/time-shift their visual experience of things but rather see what happens when everybody is simultaneously able to see what everybody else can see. This is extrapolated through the remote networking of sites that are actual installation spaces; where the physical movements of viewers in the space generate multiple perspectives, linked to other similar sites at remote locations or to other viewers entering the shared data-space through a web based version of the work.This text explores the processes involved in such a practice and reflects on related questions regarding the non-singularity of being and the sense of self as linked to time and place.

  12. Circulating microRNAs as Potential Biomarkers of Infectious Disease

    Correia, Carolina N.; Nalpas, Nicolas C.; McLoughlin, Kirsten E.; Browne, John A.; Gordon, Stephen V.; MacHugh, David E.; Shaughnessy, Ronan G.

    2017-01-01

    microRNAs (miRNAs) are a class of small non-coding endogenous RNA molecules that regulate a wide range of biological processes by post-transcriptionally regulating gene expression. Thousands of these molecules have been discovered to date, and multiple miRNAs have been shown to coordinately fine-tune cellular processes key to organismal development, homeostasis, neurobiology, immunobiology, and control of infection. The fundamental regulatory role of miRNAs in a variety of biological processes suggests that differential expression of these transcripts may be exploited as a novel source of molecular biomarkers for many different disease pathologies or abnormalities. This has been emphasized by the recent discovery of remarkably stable miRNAs in mammalian biofluids, which may originate from intracellular processes elsewhere in the body. The potential of circulating miRNAs as biomarkers of disease has mainly been demonstrated for various types of cancer. More recently, however, attention has focused on the use of circulating miRNAs as diagnostic/prognostic biomarkers of infectious disease; for example, human tuberculosis caused by infection with Mycobacterium tuberculosis, sepsis caused by multiple infectious agents, and viral hepatitis. Here, we review these developments and discuss prospects and challenges for translating circulating miRNA into novel diagnostics for infectious disease. PMID:28261201

  13. Intestinal circulation during inhalation anesthesia

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-01-01

    This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of 86 Rb and 9-microns spheres labeled with 141 Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO 2 ) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines

  14. Roadmap for cardiovascular circulation model

    Bradley, Christopher P.; Suresh, Vinod; Mithraratne, Kumar; Muller, Alexandre; Ho, Harvey; Ladd, David; Hellevik, Leif R.; Omholt, Stig W.; Chase, J. Geoffrey; Müller, Lucas O.; Watanabe, Sansuke M.; Blanco, Pablo J.; de Bono, Bernard; Hunter, Peter J.

    2016-01-01

    Abstract Computational models of many aspects of the mammalian cardiovascular circulation have been developed. Indeed, along with orthopaedics, this area of physiology is one that has attracted much interest from engineers, presumably because the equations governing blood flow in the vascular system are well understood and can be solved with well‐established numerical techniques. Unfortunately, there have been only a few attempts to create a comprehensive public domain resource for cardiovascular researchers. In this paper we propose a roadmap for developing an open source cardiovascular circulation model. The model should be registered to the musculo‐skeletal system. The computational infrastructure for the cardiovascular model should provide for near real‐time computation of blood flow and pressure in all parts of the body. The model should deal with vascular beds in all tissues, and the computational infrastructure for the model should provide links into CellML models of cell function and tissue function. In this work we review the literature associated with 1D blood flow modelling in the cardiovascular system, discuss model encoding standards, software and a model repository. We then describe the coordinate systems used to define the vascular geometry, derive the equations and discuss the implementation of these coupled equations in the open source computational software OpenCMISS. Finally, some preliminary results are presented and plans outlined for the next steps in the development of the model, the computational software and the graphical user interface for accessing the model. PMID:27506597

  15. Fundamental Studies of Recombinant Hydrogenases

    Adams, Michael W. [Univ. of Georgia, Athens, GA (United States)

    2014-01-25

    This research addressed the long term goals of understanding the assembly and organization of hydrogenase enzymes, of reducing them in size and complexity, of determining structure/function relationships, including energy conservation via charge separation across membranes, and in screening for novel H2 catalysts. A key overall goal of the proposed research was to define and characterize minimal hydrogenases that are produced in high yields and are oxygen-resistant. Remarkably, in spite of decades of research carried out on hydrogenases, it is not possible to readily manipulate or design the enzyme using molecular biology approaches since a recombinant form produced in a suitable host is not available. Such resources are essential if we are to understand what constitutes a “minimal” hydrogenase and design such catalysts with certain properties, such as resistance to oxygen, extreme stability and specificity for a given electron donor. The model system for our studies is Pyrococcus furiosus, a hyperthermophile that grows optimally at 100°C, which contains three different nickel-iron [NiFe-] containing hydrogenases. Hydrogenases I and II are cytoplasmic while the other, MBH, is an integral membrane protein that functions to both evolve H2 and pump protons. Three important breakthroughs were made during the funding period with P. furiosus soluble hydrogenase I (SHI). First, we produced an active recombinant form of SHI in E. coli by the co-expression of sixteen genes using anaerobically-induced promoters. Second, we genetically-engineered P. furiosus to overexpress SHI by an order of magnitude compared to the wild type strain. Third, we generated the first ‘minimal’ form of SHI, one that contained two rather than four subunits. This dimeric form was stable and active, and directly interacted with a pyruvate-oxidizing enzyme with any intermediate electron carrier. The research resulted in five peer-reviewed publications.

  16. Electron-ion recombination at low energy

    Andersen, L.H.

    1993-01-01

    The work is based on results obtained with a merged-beams experiment. A beam of electronics with a well characterized density and energy distribution was merged with a fast, monoenergetic ion beam. Results have been obtained for radiative recombination and dielectronic recombination at low relative energies (0 to ∼70eV). The obtained energy resolution was improved by about a factor of 30. High vacuum technology was used to suppress interactions with electrons from the environments. The velocity distribution of the electron beam was determined. State-selective dielectronic-recombination measurements were performable. Recombination processes were studied. The theoretical background for radiative recombination and Kramers' theory are reviewed. The quantum mechanical result and its relation to the semiclassical theory is discussed. Radiative recombination was also measured with several different non-bare ions, and the applicability of the semiclassical theory to non-bare ions was investigated. The use of an effective charge is discussed. For dielectronic recombination, the standard theoretical approach in the isolated resonance and independent-processes approximation is debated. The applicability of this method was tested. The theory was able to reproduce most of the experimental data except when the recombination process was sensitive to couplings between different electronic configurations. The influence of external perturbing electrostatic fields is discussed. (AB) (31 refs.)

  17. Recombination rate plasticity: revealing mechanisms by design

    Sefick, Stephen; Rushton, Chase

    2017-01-01

    For over a century, scientists have known that meiotic recombination rates can vary considerably among individuals, and that environmental conditions can modify recombination rates relative to the background. A variety of external and intrinsic factors such as temperature, age, sex and starvation can elicit ‘plastic’ responses in recombination rate. The influence of recombination rate plasticity on genetic diversity of the next generation has interesting and important implications for how populations evolve. Further, many questions remain regarding the mechanisms and molecular processes that contribute to recombination rate plasticity. Here, we review 100 years of experimental work on recombination rate plasticity conducted in Drosophila melanogaster. We categorize this work into four major classes of experimental designs, which we describe via classic studies in D. melanogaster. Based on these studies, we highlight molecular mechanisms that are supported by experimental results and relate these findings to studies in other systems. We synthesize lessons learned from this model system into experimental guidelines for using recent advances in genotyping technologies, to study recombination rate plasticity in non-model organisms. Specifically, we recommend (1) using fine-scale genome-wide markers, (2) collecting time-course data, (3) including crossover distribution measurements, and (4) using mixed effects models to analyse results. To illustrate this approach, we present an application adhering to these guidelines from empirical work we conducted in Drosophila pseudoobscura. This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’. PMID:29109222

  18. Electron-ion recombination in merged beams

    Wolf, A.; Habs, D.; Lampert, A.; Neumann, R.; Schramm, U.; Schuessler, T.; Schwalm, D.

    1993-01-01

    Detailed studies of recombination processes between electrons and highly charged ions have become possible by recent improvements of merged-beams experiments. We discuss in particular measurements with stored cooled ion beams at the Test Storage Ring (TSR) in Heidelberg. The cross section of dielectronic recombination was measured with high energy resolution for few-electron systems up to the nuclear charge of Cu at a relative energy up to 2.6 keV. At low energy (∼0.1 eV) total recombination rates of several ions were measured and compared with calculated radiative recombination rates. Laser-stimulated recombination of protons and of C 6+ ions was investigated as a function of the photon energy using visible radiation. Both the total recombination rates and the stimulated recombination spectra indicate that in spite of the short interaction time in merged beams, also collisional capture of electrons into weakly bound levels (related to three-body recombination) could be important

  19. Electronic recombination in some physics problems

    Guzman, O.

    1988-01-01

    This work is related to calculations of electronic recombination rates, as a function of electronic density, electronic temperature, and ion nuclear charge. Recombination times can be calculated and compared to cooling time, in cooling processes of ion beans by electrons from storage rings. (A.C.A.S.) [pt

  20. Generation of Modified Pestiviruses by Targeted Recombination

    Rasmussen, Thomas Bruun; Friis, Martin Barfred; Risager, Peter Christian

    involves targeted modification of viral cDNA genomes, cloned within BACs, by Red/ET recombination-mediated mutagenesis in E.coli DH10B cells. Using recombination-mediated mutagenesis for the targeted design, the work can be expedited and focused in principal on any sequence within the viral genome...

  1. Cell biology of homologous recombination in yeast

    Eckert-Boulet, Nadine Valerie; Rothstein, Rodney; Lisby, Michael

    2011-01-01

    Homologous recombination is an important pathway for error-free repair of DNA lesions, such as single- and double-strand breaks, and for rescue of collapsed replication forks. Here, we describe protocols for live cell imaging of single-lesion recombination events in the yeast Saccharomyces...

  2. Recombinant organisms for production of industrial products

    Adrio, Jose-Luis; Demain, Arnold L

    2009-01-01

    A revolution in industrial microbiology was sparked by the discoveries of ther double-stranded structure of DNA and the development of recombinant DNA technology. Traditional industrial microbiology was merged with molecular biology to yield improved recombinant processes for the industrial production of primary and secondary metabolites, protein biopharmaceuticals and industrial enzymes. Novel genetic techniques such as metabolic engineering, combinatorial biosynthesis and molecular breeding...

  3. Implementation of Moderator Circulation Test Temperature Measurement System

    Lim, Yeong Muk; Hong, Seok Boong; Kim, Min Seok; Choi, Hwa Rim [KAERI, Daejeon (Korea, Republic of); Kim, Hyung Shin [Chungnam University, Daejeon (Korea, Republic of)

    2016-05-15

    Moderator Circulation Test(MCT) facility is 1/4 scale facility designed to reproduce the important characteristics of moderator circulation in a CANDU6 calandria under a range of operating conditions. MCT is an equipment with 380 acrylic pipes instead of the heater rods and a preliminary measurement of velocity field using PIV(Particle Image Velocimetry) is performed under the iso-thermal test conditions. The Korea Atomic Energy Research Institute (KAERI) started implementation of MCT Temperature Measurement System (TMS) using multiple infrared sensors. To control multiple infrared sensors, MCT TMS is implemented using National Instruments (NI) LabVIEW programming language. The MCT TMS is implemented to measure sensor data of multiple infrared sensors using the LabVIEW. The 35 sensor pipes of MCT TMS are divided into 2 ports to meet the minimum measurement time of 0.2 seconds. The software of MCT TMS is designed using collection function and processing function. The MCT TMS has the function of monitoring the states of multiple infrared sensors. The GUI screen of MCT TMS is composed of sensor pipe categories for user.

  4. Implementation of Moderator Circulation Test Temperature Measurement System

    Lim, Yeong Muk; Hong, Seok Boong; Kim, Min Seok; Choi, Hwa Rim; Kim, Hyung Shin

    2016-01-01

    Moderator Circulation Test(MCT) facility is 1/4 scale facility designed to reproduce the important characteristics of moderator circulation in a CANDU6 calandria under a range of operating conditions. MCT is an equipment with 380 acrylic pipes instead of the heater rods and a preliminary measurement of velocity field using PIV(Particle Image Velocimetry) is performed under the iso-thermal test conditions. The Korea Atomic Energy Research Institute (KAERI) started implementation of MCT Temperature Measurement System (TMS) using multiple infrared sensors. To control multiple infrared sensors, MCT TMS is implemented using National Instruments (NI) LabVIEW programming language. The MCT TMS is implemented to measure sensor data of multiple infrared sensors using the LabVIEW. The 35 sensor pipes of MCT TMS are divided into 2 ports to meet the minimum measurement time of 0.2 seconds. The software of MCT TMS is designed using collection function and processing function. The MCT TMS has the function of monitoring the states of multiple infrared sensors. The GUI screen of MCT TMS is composed of sensor pipe categories for user

  5. RNAi and heterochromatin repress centromeric meiotic recombination

    Ellermeier, Chad; Higuchi, Emily C; Phadnis, Naina

    2010-01-01

    During meiosis, the formation of viable haploid gametes from diploid precursors requires that each homologous chromosome pair be properly segregated to produce an exact haploid set of chromosomes. Genetic recombination, which provides a physical connection between homologous chromosomes, is essen......During meiosis, the formation of viable haploid gametes from diploid precursors requires that each homologous chromosome pair be properly segregated to produce an exact haploid set of chromosomes. Genetic recombination, which provides a physical connection between homologous chromosomes....... Surprisingly, one mutant derepressed for recombination in the heterochromatic mating-type region during meiosis and several mutants derepressed for centromeric gene expression during mitotic growth are not derepressed for centromeric recombination during meiosis. These results reveal a complex relation between...... types of repression by heterochromatin. Our results also reveal a previously undemonstrated role for RNAi and heterochromatin in the repression of meiotic centromeric recombination and, potentially, in the prevention of birth defects by maintenance of proper chromosome segregation during meiosis....

  6. BIOTECHNOLOGY OF RECOMBINANT HORMONES IN DOPING

    Biljana Vitošević

    2011-09-01

    Full Text Available Recombinant DNA technology has allowed rapid progress in creating biosynthetic gene products for the treatment of many diseases. In this way it can produce large amounts of hormone, which is intended for the treatment of many pathological conditions. Recombinant hormones that are commonly used are insulin, growth hormone and erythropoietin. Precisely because of the availability of these recombinant hormones, it started their abuse by athletes. Experiments in animal models confirmed the potential effects of some of these hormones in increasing physical abilities, which attracted the attention of athletes who push the limits of their competitive capability by such manipulation. The risks of the use of recombinant hormones in doping include serious consequences for the health of athletes. Methods of detection of endogenous hormones from recombined based on the use of a monoclonal antibodies, capillary zone electrophoresis and protein biomarkers

  7. Effects of UV radiation on genetic recombination

    Vlahovic, K.; Zahradka, D.; Petranovic, M.; Petranovic, D.

    1996-01-01

    We have used the model consisting of Escherichia coli cells and l phage to study the effects of UV radiation on genetic recombination. We found two radiation induced processes that reduce or inhibit genetic recombination. One such process leads to the inability of prophage to excise itself from the irradiated bacterial chromosome by the site-specific recombination. The other process was shown to inhibit a type of general recombination by which the prophage transfers one of its genetic markers to the infecting homologous phage. Loss of the prophage ability to take part in both site-specific and general recombination was shown to develop in recB + but not in recB cells. From this we infer that the loss of prophage recombinogenicity in irradiated cells is a consequence of one process in which RecBCD enzyme (the product of recB, recC and recD genes) plays an essential role. (author)

  8. The role of recombinant IL-12 in enhancing immune responses induced by hepatitis B vaccine in mice

    Lu Qun; Zhou Lixia; Zhao Yanrong; Miao Xiaoguang; Jin Jie; Ke Jinshan; Qin Xuliang; He Zheng

    2007-01-01

    Objective: To study the role played by recombinant IL-12 in enhancing the intensity and quality of the immune response to hepatitis B vaccine in mice, and investigate the possibility of adding recombinant IL-12 as adjuvants to hepatitis B therapeutic vaccine. Methods: Recombinant IL-12 was injected together with hepatitis B vaccine into mice and special anti-HBsAb in the mice and the cellular immune responses were examined. Results: Recombinant IL-12 can obviously enhance T lymphocyte multiplication activity, accelerate excretion of cytokines IFN-γ and IL-2, and increase the IgG2a antibody in mice. Conclusion: Recombinant IL-12 can remarkably strengthen the cellular immune responses induced by the hepatitis B vaccine, and modulate the immune responses toward Thl. (authors)

  9. Apparatus and method for determining solids circulation rate

    Ludlow, J Christopher [Morgantown, WV; Spenik, James L [Morgantown, WV

    2012-02-14

    The invention relates to a method of determining bed velocity and solids circulation rate in a standpipe experiencing a moving packed bed flow, such as the in the standpipe section of a circulating bed fluidized reactor The method utilizes in-situ measurement of differential pressure over known axial lengths of the standpipe in conjunction with in-situ gas velocity measurement for a novel application of Ergun equations allowing determination of standpipe void fraction and moving packed bed velocity. The method takes advantage of the moving packed bed property of constant void fraction in order to integrate measured parameters into simultaneous solution of Ergun-based equations and conservation of mass equations across multiple sections of the standpipe.

  10. The Southern Ocean's role in ocean circulation and climate transients

    Thompson, A. F.; Stewart, A.; Hines, S.; Adkins, J. F.

    2017-12-01

    The ventilation of deep and intermediate density classes at the surface of the Southern Ocean impacts water mass modification and the air-sea exchange of heat and trace gases, which in turn influences the global overturning circulation and Earth's climate. Zonal variability occurs along the Antarctic Circumpolar Current and the Antarctic margins related to flow-topography interactions, variations in surface boundary conditions, and exchange with northern basins. Information about these zonal variations, and their impact on mass and tracer transport, are suppressed when the overturning is depicted as a two-dimensional (depth-latitude) streamfunction. Here we present an idealized, multi-basin, time-dependent circulation model that applies residual circulation theory in the Southern Ocean and allows for zonal water mass transfer between different ocean basins. This model efficiently determines the temporal evolution of the ocean's stratification, ventilation and overturning strength in response to perturbations in the external forcing. With this model we explore the dynamics that lead to transitions in the circulation structure between multiple, isolated cells and a three-dimensional, "figure-of-eight," circulation in which traditional upper and lower cells are interleaved. The transient model is also used to support a mechanistic explanation of the hemispheric asymmetry and phase lag associated with Dansgaard-Oeschger (DO) events during the last glacial period. In particular, the 200 year lag in southern hemisphere temperatures, following a perturbation in North Atlantic deep water formation, depends critically on the migration of Southern Ocean isopycnal outcropping in response to low-latitude stratification changes. Our results provide a self-consistent dynamical framework to explain various ocean overturning transitions that have occurred over the Earth's last 100,000 years, and motivate an exploration of these mechanisms in more sophisticated climate models.

  11. The unconventional xer recombination machinery of Streptococci/Lactococci

    Le Bourgeois, Pascal; Bugarel, Marie; Campo, Nathalie; Daveran-Mingot, Marie-Line; Labonte, Jessica; Lanfranchi, Daniel; Lautier, Thomas; Pages, Carine; Ritzenthaler, Paul

    Homologous recombination between circular sister chromosomes during DNA replication in bacteria can generate chromosome dimers that must be resolved into monomers prior to cell division. In Escherichia coli, dimer resolution is achieved by site-specific recombination, Xer recombination, involving

  12. Immunological and biological properties of recombinant Lol p 1.

    Boutin, Y; Lamontagne, P; Boulanger, J; Brunet, C; Hébert, J

    1997-03-01

    Current forms of allergy diagnosis and therapies are based on the use of natural allergenic extracts. Despite strong evidence that higher therapeutic efficacy may be achieved with purified allergens, the purification of multiple allergic components from extracts is a fastidious and sometimes an impossible task. However, the use of recombinant allergens may be an alternative to overcome this problem. In this study, we compared the immunological properties of recombinant (r) Lol p 1 with those of the natural protein. We cloned directly the gene encoding Lol p 1 from genomic DNA of ryegrass pollen. This gene was subcloned into the expression vector pMAL-c and expressed as fusion protein. Subsequently, rLol p 1 was cleaved from maltose-binding protein using factor Xa. Using binding inhibition and proliferative assays, we assessed the immunological properties of the recombinant allergens. The capacity of rLol p 1 to trigger basophil histamine release and to elicit a skin reaction was also assessed and compared to those of its natural counterpart. We found that the Lol p 1 gene has no introns since we amplified this gene directly from genomic DNA. We demonstrated that the binding sites of anti-Lol p 1 monoclonal antibody, specific human IgG and IgE antibody are well conserved on rLol p 1 as no difference in the binding inhibition profile was observed when using either natural or recombinant protein. At the T-cell level, rLol p 1 elicited a T-cell response in mice comparable to that observed with the natural protein. In addition, we demonstrated that the biological characteristics of rLol p 1 were comparable to those of the natural counterpart, in that rLol p 1 elicited a skin wheal reaction and induced basophil histamine release in grass-allergic patients only. The data indicate that natural Lol p 1 and rLol p 1 shared identical immunological and biological properties.

  13. Comparative evaluation of the diagnostic potential of recombinant envelope proteins and native cell culture purified viral antigens of Chikungunya virus.

    Khan, Mohsin; Dhanwani, Rekha; Kumar, Jyoti S; Rao, P V Lakshmana; Parida, Manmohan

    2014-07-01

    Despite the fact that Chikungunya resurgence is associated with epidemic of unprecedented magnitude, there are challenges in the field of its clinical diagnosis. However, serological tests in an ELISA format provide a rapid tool for the diagnosis of Chikungunya infection. Indeed, ELISAs based on recombinant proteins hold a great promise as these methods are cost effective and are free from the risk of handling biohazardous material. In this study, the performance of recombinant CHIKV antigens was compared in various ELISA formats for the diagnosis of Chikungunya. Two recombinant antigens derived from the envelope proteins of Chikungunya virus were prepared and evaluated by comparing their competence for detecting circulating antibodies in serum samples of patients infected with CHIKV using MAC-ELISA and indirect IgM-ELISA. The efficacy of the recombinant antigens was also compared with the native antigen. The indirect antibody capture IgM microplate ELISA revealed ≥90% concordance with the native antigen in detecting the CHIKV specific IgM antibodies whereas the recombinant antigen based MAC-ELISA showed 100% specificity. The recombinant antigens used in this study were effective and reliable targets for the diagnosis of CHIKV infection and also provide an alternative for native antigen use which is potentially biohazardous. © 2013 Wiley Periodicals, Inc.

  14. Uranus atmospheric dynamics and circulation

    Allison, Michael; Beebe, Reta F.; Conrath, Barney J.; Hinson, David P.; Ingersoll, Andrew P.

    1991-01-01

    The observations, models, and theories relevant to the atmospheric dynamics and meteorology of Uranus are discussed. The available models for the large-scale heat transport and atmospheric dynamics as well as diagnostic interpretations of the Voyager data are reviewed. Some pertinent ideas and questions regarding the global circulation balance are considered, partly in comparison with other planetary atmospheres. The available data indicate atmospheric rotation at midlatitudes nearly 200 m/s faster than that of the planetary magnetic field. Analysis of the dynamical deformation of the shape and size of isobaric surfaces measured by the Voyager radio-occultation experiment suggests a subrotating equator at comparable altitudes. Infrared temperature retrievals above the cloud deck indicate a smaller equator-to-pole contrast than expected for purely radiative-convective equilibrium, but show local variations implying a latitudinally correlated decrease with altitude in the cloud-tracked wind.

  15. Improvement of Classification of Enterprise Circulating Funds

    Rohanova Hanna O.

    2014-02-01

    Full Text Available The goal of the article lies in revelation of possibilities of increase of efficiency of managing enterprise circulating funds by means of improvement of their classification features. Having analysed approaches of many economists to classification of enterprise circulating funds, systemised and supplementing them, the article offers grouping classification features of enterprise circulating funds. In the result of the study the article offers an expanded classification of circulating funds, which clearly shows the role of circulating funds in managing enterprise finance and economy in general. The article supplements and groups classification features of enterprise circulating funds by: the organisation level, functioning character, sources of formation and their cost, and level of management efficiency. The article shows that the provided grouping of classification features of circulating funds allows exerting all-sided and purposeful influence upon indicators of efficiency of circulating funds functioning and facilitates their rational management in general. The prospect of further studies in this direction is identification of the level of attraction of loan resources by production enterprises for financing circulating funds.

  16. NPP Krsko natural circulation performance evaluation

    Segon, Velimir; Bajs, Tomislav; Frogheri, Monica

    1999-01-01

    The present document deals with an evaluation of the natural circulation performance of the Krsko nuclear power plant. Two calculation have been performed using the NPP Krsko nodalization (both similar to the LOBI A2-77 natural circulation experiment) - the first with the present steam generators at NPP Krsko (Westinghouse, 18% plugged), the second with the future steam generators (Siemens, 0% plugged). The results were evaluated using the natural circulation flow map derived in /1/, and were compared to evaluate the influence of the new steam generators on the natural circulation performance. (author)

  17. A blood circulation model for reference man

    Leggett, R.W.; Eckerman, K.F. [Oak Ridge National Lab., TN (United States); Williams, L.R. [Indiana Univ., South Bend, IN (United States). Div. of Liberal Arts and Sciences

    1996-12-31

    A dynamic blood circulation model that predicts the movement and gradual dispersion of a bolus of material in the circulation after its intravenous injection into an adult human. The main purpose of the model is improve the dosimetry of internally deposited radionuclides that decay in the circulation to a significant extent. The model partitions the blood volume into 24 separate organs or tissues, right heart chamber, left heart chamber, pulmonary circulation, arterial outflow to the aorta and large arteries, and venous return via the large veins. Model results were compared to data obtained from injection of carbon 11 labeled carbon monoxide or rubidium 86.

  18. A blood circulation model for reference man

    Leggett, R.W.; Eckerman, K.F.; Williams, L.R.

    1996-01-01

    A dynamic blood circulation model that predicts the movement and gradual dispersion of a bolus of material in the circulation after its intravenous injection into an adult human. The main purpose of the model is improve the dosimetry of internally deposited radionuclides that decay in the circulation to a significant extent. The model partitions the blood volume into 24 separate organs or tissues, right heart chamber, left heart chamber, pulmonary circulation, arterial outflow to the aorta and large arteries, and venous return via the large veins. Model results were compared to data obtained from injection of carbon 11 labeled carbon monoxide or rubidium 86

  19. Basic natural circulation characteristics of SBWR

    Kuran, S.; Soekmen, C. N.

    2001-01-01

    Natural circulation is an important passive heat removal mechanism for both existing and next generation light water reactors. Simplified Boiling Water Reactor (SBWR) is one of the advanced light water reactors that rely on natural circulation for normal as well as emergency core cooling. In this study, basic natural circulation characteristics of this reactor are examined on a flow loop that simulates the operation of SBWR. On this model, effect of system operating parameters on the steady state natural circulation characteristics inside the loop is studied via solving the transcendental equation for loop flow rate

  20. Vaccine escape recombinants emerge after pneumococcal vaccination in the United States.

    Brueggemann, Angela B; Pai, Rekha; Crook, Derrick W; Beall, Bernard

    2007-11-01

    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.

  1. Multiple sclerosis

    ... indwelling catheter Osteoporosis or thinning of the bones Pressure sores Side effects of medicines used to treat the ... Daily bowel care program Multiple sclerosis - discharge Preventing pressure ulcers Swallowing problems Images Multiple sclerosis MRI of the ...

  2. Sordaria, a model system to uncover links between meiotic pairing and recombination.

    Zickler, Denise; Espagne, Eric

    2016-06-01

    The mycelial fungus Sordaria macrospora was first used as experimental system for meiotic recombination. This review shows that it provides also a powerful cytological system for dissecting chromosome dynamics in wild-type and mutant meioses. Fundamental cytogenetic findings include: (1) the identification of presynaptic alignment as a key step in pairing of homologous chromosomes. (2) The discovery that biochemical complexes that mediate recombination at the DNA level concomitantly mediate pairing of homologs. (3) This pairing process involves not only resolution but also avoidance of chromosomal entanglements and the resolution system includes dissolution of constraining DNA recombination interactions, achieved by a unique role of Mlh1. (4) Discovery that the central components of the synaptonemal complex directly mediate the re-localization of the recombination proteins from on-axis to in-between homologue axis positions. (5) Identification of putative STUbL protein Hei10 as a structure-based signal transduction molecule that coordinates progression and differentiation of recombinational interactions at multiple stages. (6) Discovery that a single interference process mediates both nucleation of the SC and designation of crossover sites, thereby ensuring even spacing of both features. (7) Discovery of local modulation of sister-chromatid cohesion at sites of crossover recombination. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Electron-ion recombination rates for merged-beams experiments

    Pajek, M.

    1994-01-01

    Energy dependence of the electron-ion recombination rates are studied for different recombination processes (radiative recombination, three-body recombination, dissociative recombination) for Maxwellian relative velocity distribution of arbitrary asymmetry. The results are discussed in context of the electron-ion merged beams experiments in cooling ion storage rings. The question of indication of a possible contribution of the three-body recombination to the measured recombination rates versus relative energy is particularly addressed. Its influence on the electron beam temperature derived from the energy dependence of recombination rate is discussed

  4. First-principles study of Frenkel pair recombination in tungsten

    Qin, Shi-Yao; Jin, Shuo; Li, Yu-Hao; Zhou, Hong-Bo; Zhang, Ying; Lu, Guang-Hong

    2017-01-01

    The recombination of one Frenkel pair in tungsten has been investigated through first-principles simulation. Two different recombination types have been identified: instantaneous and thermally activated. The small recombination barriers for thermally activated recombination cases indicate that recombination can occur easily with a slightly increased temperature. For both of the two recombination types, recombination occurs through the self-interstitial atom moving towards the vacancy. The recombination process can be direct or through replacement sequences, depending on the vertical distance between the vacancy and the 〈1 1 1〉 line of self-interstitial atom pair.

  5. Induction of homologous recombination in Saccharomyces cerevisiae.

    Simon, J R; Moore, P D

    1988-09-01

    We have investigated the effects of UV irradiation of Saccharomyces cerevisiae in order to distinguish whether UV-induced recombination results from the induction of enzymes required for homologous recombination, or the production of substrate sites for recombination containing regions of DNA damage. We utilized split-dose experiments to investigate the induction of proteins required for survival, gene conversion, and mutation in a diploid strain of S. cerevisiae. We demonstrate that inducing doses of UV irradiation followed by a 6 h period of incubation render the cells resistant to challenge doses of UV irradiation. The effects of inducing and challenge doses of UV irradiation upon interchromosomal gene conversion and mutation are strictly additive. Using the yeast URA3 gene cloned in non-replicating single- and double-stranded plasmid vectors that integrate into chromosomal genes upon transformation, we show that UV irradiation of haploid yeast cells and homologous plasmid DNA sequences each stimulate homologous recombination approximately two-fold, and that these effects are additive. Non-specific DNA damage has little effect on the stimulation of homologous recombination, as shown by studies in which UV-irradiated heterologous DNA was included in transformation/recombination experiments. We further demonstrate that the effect of competing single- and double-stranded heterologous DNA sequences differs in UV-irradiated and unirradiated cells, suggesting an induction of recombinational machinery in UV-irradiated S. cerevisiae cells.

  6. Towards personalised therapy for von Willebrand disease: a future role for recombinant products.

    Favaloro, Emmanuel J

    2016-05-01

    von Willebrand disease (VWD) is reportedly the most common bleeding disorder and is caused by deficiencies and/or defects in the adhesive plasma protein von Willebrand factor (VWF). Functionally, normal VWF prevents bleeding by promoting both primary and secondary haemostasis. In respect to primary haemostasis, VWF binds to both platelets and sub-endothelial matrix components, especially collagen, to anchor platelets to damaged vascular tissue and promote thrombus formation. VWF also stabilises and protects factor VIII in the circulation, delivering FVIII to the site of injury, which then facilitates secondary haemostasis and fibrin formation/thrombus stabilisation. As a result of this, patients with VWD suffer a bleeding diathesis reflective of a primary defect caused by defective/deficient VWF, which in some patients is compounded by a reduction in FVIII. Management of VWD, therefore, chiefly entails replacement of VWF, and sometimes also FVIII, to protect against bleeding. The current report principally focuses on the future potential for "personalised" management of VWD, given the emerging options in recombinant therapies. Recombinant VWF has been developed and is undergoing clinical trials, and this promising therapy may soon change the way in which VWD is managed. In particular, we can envisage a personalised treatment approach using recombinant VWF, with or without recombinant FVIII, depending on the type of VWD, the extent of deficiencies, and the period and duration of treatment.

  7. Main circulator design features for HTR 100, HTR 500 and space heating plants

    Engel, J.; Glass, D.

    1988-01-01

    All design alternatives for modern high-temperature reactors have a common circulator concept: It is based on a vertical shaft design with a flying impeller. The circulators are equipped with active magnetic bearings and are driven by induction motors connected to variable-speed static converters. Due to their multiple functions during normal reactor operation and under accident conditions, extremely high requirements are made to safety-relevant circulators, since with the reactor pressurized as well as under depressurized conditions specified delivery heads and flow rates have to be ensured. The use of active magnetic bearings permits to obtain maintenance-free operation and functional safety to an extent which had not been achieved before. Magnetic bearings are therefore provided for the total range including primary gas circulators of a drive power of several MW as well as circulators for helium loops of reactor auxiliary systems. The essential feature for using active magnetic bearings is the retainer bearing technology, preventing contact between rotor and static circulator parts upon unintended deenergisation of the magnets. Results of current experiments are reported. Another aspect to be considered for reliable long-term operation for several decades is the effect of rotor dynamics. The various natural frequencies resulting from torsion and bending modes in view of a drive by a frequency-controlled induction motor have to be considered as well as the specific characteristics of the active magnetic bearings. Special attention has to be directed to the internal cooling loop so as to ensure that reactor temperature excursions in the event of deviation from normal operation can be overcome without damage. For circulator components exposed to temperature fields the design characteristics are determined by combining experimental and analytical methods. The coordination of all component parts is currently being optimized on a prototype circulator whose detailed

  8. Recombination every day: abundant recombination in a virus during a single multi-cellular host infection.

    Remy Froissart

    2005-03-01

    Full Text Available Viral recombination can dramatically impact evolution and epidemiology. In viruses, the recombination rate depends on the frequency of genetic exchange between different viral genomes within an infected host cell and on the frequency at which such co-infections occur. While the recombination rate has been recently evaluated in experimentally co-infected cell cultures for several viruses, direct quantification at the most biologically significant level, that of a host infection, is still lacking. This study fills this gap using the cauliflower mosaic virus as a model. We distributed four neutral markers along the viral genome, and co-inoculated host plants with marker-containing and wild-type viruses. The frequency of recombinant genomes was evaluated 21 d post-inoculation. On average, over 50% of viral genomes recovered after a single host infection were recombinants, clearly indicating that recombination is very frequent in this virus. Estimates of the recombination rate show that all regions of the genome are equally affected by this process. Assuming that ten viral replication cycles occurred during our experiment-based on data on the timing of coat protein detection-the per base and replication cycle recombination rate was on the order of 2 x 10(-5 to 4 x 10(-5. This first determination of a virus recombination rate during a single multi-cellular host infection indicates that recombination is very frequent in the everyday life of this virus.

  9. Application of passive auto catalytic recombiner (PAR) for BWR plants in Japan

    Kobayashi, K.; Murano, K.; Yamanari, S.; Yamamoto, Y.

    2001-01-01

    The passive auto-catalytic recombiner (PAR), which can recombine flammable gases such as hydrogen and oxygen with each other to avoid an explosion in case of a loss-of-coolant accident (LOCA), installed in the primary containment vessel does not require a power supply or dynamic equipment, while the existing flammability gas control system (FCS) of most BWRs as an outer loop of the primary containment vessel needs them to make flammable gases circulate through blowers and heaters in the system. PAR offers a number of advantages over existing FCS, such as high reliability, low cost due to much smaller amount of materials needed, good maintainability, good operability in case of a LOCA, and smaller space for installation. An experimental study has been carried out for the purpose of solving the problems of applying PAR to Japanese BWR plants instead of existing FCS, in which we grasped the basic characteristics of PAR. (author)

  10. Recombinant DNA production of spider silk proteins.

    Tokareva, Olena; Michalczechen-Lacerda, Valquíria A; Rech, Elíbio L; Kaplan, David L

    2013-11-01

    Spider dragline silk is considered to be the toughest biopolymer on Earth due to an extraordinary combination of strength and elasticity. Moreover, silks are biocompatible and biodegradable protein-based materials. Recent advances in genetic engineering make it possible to produce recombinant silks in heterologous hosts, opening up opportunities for large-scale production of recombinant silks for various biomedical and material science applications. We review the current strategies to produce recombinant spider silks. © 2013 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  11. Advances in recombinant antibody manufacturing.

    Kunert, Renate; Reinhart, David

    2016-04-01

    Since the first use of Chinese hamster ovary (CHO) cells for recombinant protein expression, production processes have steadily improved through numerous advances. In this review, we have highlighted several key milestones that have contributed to the success of CHO cells from the beginning of their use for monoclonal antibody (mAb) expression until today. The main factors influencing the yield of a production process are the time to accumulate a desired amount of biomass, the process duration, and the specific productivity. By comparing maximum cell densities and specific growth rates of various expression systems, we have emphasized the limiting parameters of different cellular systems and comprehensively described scientific approaches and techniques to improve host cell lines. Besides the quantitative evaluation of current systems, the quality-determining properties of a host cell line, namely post-translational modifications, were analyzed and compared to naturally occurring polyclonal immunoglobulin fractions from human plasma. In summary, numerous different expression systems for mAbs are available and also under scientific investigation. However, CHO cells are the most frequently investigated cell lines and remain the workhorse for mAb production until today.

  12. Structure and variances of equatorial zonal circulation in a multimodel ensemble

    Yu, B. [Environment Canada, Climate Data and Analysis Section, Climate Research Division, Toronto, ON (Canada); Zwiers, F.W. [University of Victoria, Pacific Climate Impacts Consortium, Victoria, BC (Canada); Boer, G.J. [Environment Canada, Canadian Centre for Climate Modeling and Analysis, Climate Research Division, Victoria, BC (Canada); Ting, M.F. [Columbia University, Lamont-Doherty Earth Observatory, Palisades, NY (United States)

    2012-11-15

    The structure and variance of the equatorial zonal circulation, as characterized by the atmospheric mass flux in the equatorial zonal plane, is examined and inter-compared in simulations from 9 CMIP3 coupled climate models with multiple ensemble members and the NCEP-NCAR and ERA-40 reanalyses. The climate model simulations analyzed here include twentieth century (20C3M) and twenty-first century (SRES A1B) simulations. We evaluate the 20C3M modeled zonal circulations by comparing them with those in the reanalyses. We then examine the variability of the circulation, its changes with global warming, and the associated thermodynamic maintenance. The tropical zonal circulation involves three major components situated over the Pacific, Indian, and Atlantic oceans. The three cells are supported by the corresponding diabatic heating extending deeply throughout the troposphere, with heating centers apparent in the mid-troposphere. Seasonal features appear in the zonal circulation, including variations in its intensity and longitudinal migration. Most models, and hence the multi-model mean, represent the annual and seasonal features of the circulation and the associated heating reasonably well. The multi-model mean reproduces the observed climatology better than any individual model, as indicated by the spatial pattern correlation and mean square difference of the mass flux and the diabatic heating compared to the reanalysis based values. Projected changes in the zonal circulation under A1B forcing are dominated by mass flux changes over the Pacific and Indian oceans. An eastward shift of the Pacific Walker circulation is clearly evident with global warming, with anomalous rising motion apparent over the equatorial central Pacific and anomalous sinking motions in the west and east, which favors an overall strengthening of the Walker circulation. The zonal circulation weakens and shifts westwards over the Indian Ocean under external forcing, whereas it strengthens and shifts

  13. MULTIPLE OBJECTS

    A. A. Bosov

    2015-04-01

    Full Text Available Purpose. The development of complicated techniques of production and management processes, information systems, computer science, applied objects of systems theory and others requires improvement of mathematical methods, new approaches for researches of application systems. And the variety and diversity of subject systems makes necessary the development of a model that generalizes the classical sets and their development – sets of sets. Multiple objects unlike sets are constructed by multiple structures and represented by the structure and content. The aim of the work is the analysis of multiple structures, generating multiple objects, the further development of operations on these objects in application systems. Methodology. To achieve the objectives of the researches, the structure of multiple objects represents as constructive trio, consisting of media, signatures and axiomatic. Multiple object is determined by the structure and content, as well as represented by hybrid superposition, composed of sets, multi-sets, ordered sets (lists and heterogeneous sets (sequences, corteges. Findings. In this paper we study the properties and characteristics of the components of hybrid multiple objects of complex systems, proposed assessments of their complexity, shown the rules of internal and external operations on objects of implementation. We introduce the relation of arbitrary order over multiple objects, we define the description of functions and display on objects of multiple structures. Originality.In this paper we consider the development of multiple structures, generating multiple objects.Practical value. The transition from the abstract to the subject of multiple structures requires the transformation of the system and multiple objects. Transformation involves three successive stages: specification (binding to the domain, interpretation (multiple sites and particularization (goals. The proposed describe systems approach based on hybrid sets

  14. Topical application of recombinant activated factor VII during cesarean delivery for placenta previa.

    Schjoldager, Birgit T B G; Mikkelsen, Emmeli; Lykke, Malene R; Præst, Jørgen; Hvas, Anne-Mette; Heslet, Lars; Secher, Niels J; Salvig, Jannie D; Uldbjerg, Niels

    2017-06-01

    During cesarean delivery in patients with placenta previa, hemorrhaging after removal of the placenta is often challenging. In this condition, the extraordinarily high concentration of tissue factor at the placenta site may constitute a principle of treatment as it activates coagulation very effectively. The presumption, however, is that tissue factor is bound to activated factor VII. We hypothesized that topical application of recombinant activated factor VII at the placenta site reduces bleeding without affecting intravascular coagulation. We included 5 cases with planned cesarean delivery for placenta previa. After removal of the placenta, the surgeon applied a swab soaked in recombinant activated factor VII containing saline (1 mg in 246 mL) to the placenta site for 2 minutes; this treatment was repeated once if the bleeding did not decrease sufficiently. We documented the treatment on video recordings and measured blood loss. Furthermore, we determined hemoglobin concentration, platelet count, international normalized ratio, activated partial thrombin time, fibrinogen (functional), factor VII:clot, and thrombin generation in peripheral blood prior to and 15 minutes after removal of the placenta. We also tested these blood coagulation variables in 5 women with cesarean delivery planned for other reasons. Mann-Whitney test was used for unpaired data. In all 5 cases, the uterotomy was closed under practically dry conditions and the median blood loss was 490 (range 300-800) mL. There were no adverse effects of recombinant activated factor VII and we did not measure factor VII to enter the circulation. Neither did we observe changes in thrombin generation, fibrinogen, activated partial thrombin time, international normalized ratio, and platelet count in the peripheral circulation (all P values >.20). This study indicates that in patients with placenta previa, topical recombinant activated factor VII may diminish bleeding from the placenta site without initiation

  15. Natural circulation in reactor coolant system

    Han, J.T.

    1987-01-01

    Reactor coolant system (RCS) natural circulation in a PWR is the buoyancy-driven coolant circulation between the core and the upper-plenum region (in-vessel circulation) with or without a countercurrent flow in the hot leg piping between the vessel and steam generators (ex-vessel circulation). This kind of multidimensional bouyancy-driven flow circulation serves as a means of transferring the heat from the core to the structures in the upper plenum, hot legs, and possibly steam generators. As a result, the RCS piping and other pressure boundaries may be heated to high temperatures at which the structural integrity is challenged. RCS natural circulation is likely to occur during the core uncovery period of the TMLB' accident in a PWR when the vessel upper plenum and hot leg are already drained and filled with steam and possibly other gaseous species. RCS natural circulation is being studied for the Surry plant during the TMLB' accident in which station blackout coincides with the loss of auxiliary feedwater and no operator actions. The effects of the multidimensional RCS natural circulation during the TMLB' accident are discussed

  16. Circulating follistatin in relation to energy metabolism

    Hansen, Jakob Schiøler; Plomgaard, Peter

    2016-01-01

    a relation to energy metabolism. In this narrative review, we attempt to reconcile the existing findings on circulating follistatin with the novel concept that circulating follistatin is a liver-derived molecule regulated by the glucagon-to-insulin ratio. The picture emerging is that conditions associated...

  17. Circulating Zinc-α2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome

    Lai, Yerui; Chen, Jinhua; Li, Ling; Yin, Jingxia; He, Junying; Yang, Mengliu; Jia, Yanjun; Liu, Dongfang; Liu, Hua; Liao, Yong; Yang, Gangyi

    2016-01-01

    The aim of study was to assess the relationship between zinc-α2-glycoprotein (ZAG) and androgen excess with insulin resistance in polycystic ovary syndrome (PCOS) women. 99 PCOS women and 100 healthy controls were recruited. Euglycemic-hyperinsulinemic clamp (EHC) was preformed to assess their insulin sensitivity. Circulating ZAG was determined with an ELISA kit. In healthy subjects, circulating ZAG levels exhibited a characteristic diurnal rhythm in humans, with a major nocturnal rise occurring between midnight and early morning. Circulating ZAG and M-value were much lower in PCOS women than in the controls. In all population, overweight/obese subjects had significantly lower circulating ZAG levels than lean individuals. Multiple linear regression analysis revealed that only M-value and the area under the curve for glucose were independently related factors to circulating ZAG in PCOS women. Multivariate logistic regression analysis showed that circulating ZAG was significantly associated with PCOS even after controlling for anthropometric variables, blood pressure, lipid profile and hormone levels. The PCOS women with high ZAG had fewer MetS, IGT and polycystic ovaries as compared with the low ZAG PCOS women. Taken together, circulating ZAG levels are reduced in women with PCOS and ZAG may be a cytokine associated with insulin resistance in PCOS women. PMID:27180914

  18. Laser-induced electron--ion recombination used to study enhanced spontaneous recombination during electron cooling

    Schramm, U.; Wolf, A.; Schuess ler, T.; Habs, D.; Schwalm, D.; Uwira, O.; Linkemann, J.; Mueller, A.

    1997-01-01

    Spontaneous recombination of highly charged ions with free electrons in merged velocity matched electron and ion beams has been observed in earlier experiments to occur at rates significantly higher than predicted by theoretical estimates. To study this enhanced spontaneous recombination, laser induced recombination spectra were measured both in velocity matched beams and in beams with well defined relative velocities, corresponding to relative electron-ion detuning energies ranging from 1 meV up to 6.5 meV where the spontaneous recombination enhancement was found to be strongly reduced. Based on a comparison with simplified calculations, the development of the recombination spectra for decreasing detuning energies indicates additional contributions at matched velocities which could be related to the energy distribution of electrons causing the spontaneous recombination rate enhancement

  19. Recombinant Human Papillomavirus (HPV) Bivalent Vaccine

    This page contains brief information about recombinant human papillomavirus (HPV) bivalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.

  20. Recombinant Human Papillomavirus (HPV) Nonavalent Vaccine

    This page contains brief information about recombinant human papillomavirus (HPV) nonavalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.

  1. Recombinant Human Papillomavirus (HPV) Quadrivalent Vaccine

    This page contains brief information about recombinant human papillomavirus (HPV) quadrivalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.

  2. Ultramicroscopic observation of recombinant adenoassociated virus ...

    Ultramicroscopic observation of recombinant adenoassociated virus type 2 on the surface of formvarcarbon coated copper grids under different relative humidity and incubation time using negative stain transmission electron microscopy.

  3. Recombinant vaccines: experimental and applied aspects

    Lorenzen, Niels

    1999-01-01

    Development of vaccines for aquaculture fish represent an important applied functional aspect of fish immunology research. Particularly in the case of recombinant vaccines, where a single antigen is usually expected to induce immunity to a specific pathogen, knowledge of mechanisms involved...... in induction of a protective immune response may become vital. The few recombinant vaccines licensd so far, despite much research during the last decade, illustrate that this is not a straightforward matter. However, as vaccine technology as well as our knowledge of the fish immune system is steadily improved......, these fields will open up a number of interesting research objectives of mutual benefit. Recent aspects of recombinant protein vaccines, live recombinant vaccines and DNA vaccines are discussed....

  4. New perspectives on recombinant human antibodies

    J. de Kruif (John); A.-R. van der Vuurst de Vries (Anne); L. Cilenti (L.); E. Boel (E.); W. van Ewijk (Willem); T. Logtenberg (Ton)

    1996-01-01

    textabstractThe limited potential of murine monoclonal antibodies for human immunotherapy has driven recent progress in recombinant antibody technology. Here, de Kruif and colleagues report on advances in the development and use of phage-antibody-display libraries.

  5. Construction of retroviral recombinant containing human tissue ...

    USER

    2010-03-29

    Mar 29, 2010 ... Recombinant retroviral vector containing human tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) gene was ..... heavy metal ions, the protein could be express in an .... involves adhesion, degradation and movement. To.

  6. Live recombinant BHV/BRSV vaccine

    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 protection of cattle against both Bovine herpesvirus infection and against Bovine Respiratory Syncytium virus infection. Also the invention relates to methods for the preparation of such live attenuated r...

  7. Co-factor activated recombinant adenovirus proteinases

    Anderson, Carl W.; Mangel, Walter F.

    1996-08-06

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying said peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described.

  8. Hadron correlations from recombination and fragmentation

    Fries, Rainer J [School of Physics and Astronomy, University of Minnesota, Minneapolis, MN 55455 (United States)

    2005-04-01

    We review the formalism of quark recombination applied to the hadronization of a quark-gluon plasma. Evidence in favour of the quark recombination model is outlined. Recent work on parton correlations, leading to detectable correlations between hadrons, is discussed. Hot spots from completely quenched jets are a likely source of such correlations which appear to be jet like. It will be discussed how such a picture compares with measurement of associated hadron yields at RHIC.

  9. Recombination of a fast expanding plasma

    Salvat, M.

    1979-05-01

    The goal of the following calculations is to determine numerically the recombination of dense plasmas (for instance of laser-produced plasmas). The recombination is computed for plasmas with initial densities of 10 24 27 [m -3 ] and with initial temperatures >= 50 eV. The ionization of the plasma remains essentially constant during the early phase of expansion. The time for which the ionization is 'frozen-in' grows with decreasing initial density and with increasing initial temperature. (orig.) [de

  10. Moderator circulation in CANDU reactors

    Fath, H.E.S.; Hussein, M.A.

    1989-01-01

    A two-dimensional computer code that is capable of predicting the moderator flow and temperature distribution inside CANDU calandria is presented. The code uses a new approach to simulate the calandria tube matrix by blocking the cells containing the tubes in the finite difference mesh. A jet momentum-dominant flow pattern is predicted in the nonisothermal case, and the effect of the buoyancy force, resulting from nuclear heating, is found to enhance the speed of circulation. Hot spots are located in low-velocity areas at the top of the calandria and below the inlet jet level between the fuel channels. A parametric study is carried out to investigate the effect of moderator inlet velocity,moderator inlet nozzle location, and geometric scaling. The results indicate that decreasing the moderator inlet velocity has no significant influence on the general features of the flow pattern (i.e., momentum dominant); however, too many high-temperature hot spots appear within the fuel channels

  11. Numerical Modeling of Ocean Circulation

    Miller, Robert N.

    2007-01-01

    The modelling of ocean circulation is important not only for its own sake, but also in terms of the prediction of weather patterns and the effects of climate change. This book introduces the basic computational techniques necessary for all models of the ocean and atmosphere, and the conditions they must satisfy. It describes the workings of ocean models, the problems that must be solved in their construction, and how to evaluate computational results. Major emphasis is placed on examining ocean models critically, and determining what they do well and what they do poorly. Numerical analysis is introduced as needed, and exercises are included to illustrate major points. Developed from notes for a course taught in physical oceanography at the College of Oceanic and Atmospheric Sciences at Oregon State University, this book is ideal for graduate students of oceanography, geophysics, climatology and atmospheric science, and researchers in oceanography and atmospheric science. Features examples and critical examination of ocean modelling and results Demonstrates the strengths and weaknesses of different approaches Includes exercises to illustrate major points and supplement mathematical and physical details

  12. Circulating microparticles: square the circle

    2013-01-01

    Background The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes. PMID:23607880

  13. Vertical mixing by Langmuir circulations

    McWilliams, James C.; Sullivan, Peter P.

    2001-01-01

    Wind and surface wave frequently induce Langmuir circulations (LC) in the upper ocean, and the LC contribute to mixing materials down from the surface. In this paper we analyze large-eddy simulation (LES) cases based on surface-wave-averaged, dynamical equations and show that the effect of the LC is a great increase in the vertical mixing efficiency for both material properties and momentum. We provide new confirmation that the previously proposed K-profile parameterization (KPP) model accurately characterizes the turbulent transport in a weakly convective, wind-driven boundary layer with stable interior stratification. We also propose a modest generalization of KPP for the regime of weakly convective Langmuir turbulence. This makes the KPP turbulent flux profiles match those in the LES case with LC present fairly well, especially so for material properties being transported downwards from the ocean surface. However, some open issues remain about how well the present LES and KPP formulations represent Langmuir turbulence, in part because wave-breaking effects are not yet included. (Author)

  14. Dissociation of recombinant prion autocatalysis from infectivity.

    Noble, Geoffrey P; Supattapone, Surachai

    2015-01-01

    Within the mammalian prion field, the existence of recombinant prion protein (PrP) conformers with self-replicating (ie. autocatalytic) activity in vitro but little to no infectious activity in vivo challenges a key prediction of the protein-only hypothesis of prion replication--that autocatalytic PrP conformers should be infectious. To understand this dissociation of autocatalysis from infectivity, we recently performed a structural and functional comparison between a highly infectious and non-infectious pair of autocatalytic recombinant PrP conformers derived from the same initial prion strain. (1) We identified restricted, C-terminal structural differences between these 2 conformers and provided evidence that these relatively subtle differences prevent the non-infectious conformer from templating the conversion of native PrP(C) substrates containing a glycosylphosphatidylinositol (GPI) anchor. (1) In this article we discuss a model, consistent with these findings, in which recombinant PrP, lacking post-translational modifications and associated folding constraints, is capable of adopting a wide variety of autocatalytic conformations. Only a subset of these recombinant conformers can be adopted by post-translationally modified native PrP(C), and this subset represents the recombinant conformers with high specific infectivity. We examine this model's implications for the generation of highly infectious recombinant prions and the protein-only hypothesis of prion replication.

  15. Mitigating Mitochondrial Genome Erosion Without Recombination.

    Radzvilavicius, Arunas L; Kokko, Hanna; Christie, Joshua R

    2017-11-01

    Mitochondria are ATP-producing organelles of bacterial ancestry that played a key role in the origin and early evolution of complex eukaryotic cells. Most modern eukaryotes transmit mitochondrial genes uniparentally, often without recombination among genetically divergent organelles. While this asymmetric inheritance maintains the efficacy of purifying selection at the level of the cell, the absence of recombination could also make the genome susceptible to Muller's ratchet. How mitochondria escape this irreversible defect accumulation is a fundamental unsolved question. Occasional paternal leakage could in principle promote recombination, but it would also compromise the purifying selection benefits of uniparental inheritance. We assess this tradeoff using a stochastic population-genetic model. In the absence of recombination, uniparental inheritance of freely-segregating genomes mitigates mutational erosion, while paternal leakage exacerbates the ratchet effect. Mitochondrial fusion-fission cycles ensure independent genome segregation, improving purifying selection. Paternal leakage provides opportunity for recombination to slow down the mutation accumulation, but always at a cost of increased steady-state mutation load. Our findings indicate that random segregation of mitochondrial genomes under uniparental inheritance can effectively combat the mutational meltdown, and that homologous recombination under paternal leakage might not be needed. Copyright © 2017 by the Genetics Society of America.

  16. 46 CFR 56.50-45 - Circulating pumps.

    2010-10-01

    ... APPURTENANCES Design Requirements Pertaining to Specific Systems § 56.50-45 Circulating pumps. (a) A main circulating pump and emergency means for circulating water through the main condenser shall be provided. The... circulating pump and the condenser. (b) Independent sea suctions shall be provided for the main circulating...

  17. Electron - ion recombination processes - an overview

    Hahn, Yukap

    1997-01-01

    Extensive theoretical and experimental studies have been carried out for the past 20 years on electron - ion recombination processes, as they are applied to the analysis of astrophysical and laboratory plasmas. We review the basic understanding gained through these efforts, with emphasis on some of the more recent progress made in recombination theory as the recombining system is affected by time-dependent electric fields and plasma particles at low temperature. Together with collisional ionization and excitation processes, recombination is important in determining ionization balance and excited-state population in non-equilibrium plasmas. The radiation emitted by plasmas is usually the principal medium with which to study the plasma condition, as it is produced mainly during the recombination and decay of excited states of ions inside the plasma. This is especially true when the plasma under study is not readily accessible by direct probes, as in astrophysical plasmas. Moreover, external probes may sometimes cause undesirable disturbances of the plasma. Electron-ion recombination proceeds in several different modes. The direct modes include three-body recombination (TBR) and one-step radiative recombination (RR), all to the ground- and singly-excited states of the target ions. By contrast, the indirect resonant mode is a two-step dielectronic recombination (DR), which proceeds first with the formation of doubly-excited states by radiationless excitation/capture. The resonant states thus formed may relax by autoionization and/or radiative cascades. For more exotic modes of recombination, we consider off-shell dielectronic recombination (radiative DR = RDR), in which an electron capture is accompanied by simultaneous radiative emission and excitation of the target ion. Some discussion on attachment of electrons to neutral atoms, resulting in the formation of negative ions, is also given. When resonance states involve one or more electrons in high Rydberg states

  18. Oligonucleotide recombination enabled site-specific mutagenesis in bacteria

    Recombineering refers to a strategy for engineering DNA sequences using a specialized mode of homologous recombination. This technology can be used for rapidly constructing precise changes in bacterial genome sequences in vivo. Oligo recombination is one type of recombineering that uses ssDNA olig...

  19. A newly emerging HIV-1 recombinant lineage (CRF58_01B) disseminating among people who inject drugs in Malaysia.

    Chow, Wei Zhen; Takebe, Yutaka; Syafina, Nur Ezreen; Prakasa, Malarvelli Soorya; Chan, Kok Gan; Al-Darraji, Haider Abdulrazzaq Abed; Koh, Clayton; Kamarulzaman, Adeeba; Tee, Kok Keng

    2014-01-01

    The HIV epidemic is primarily characterised by the circulation of HIV-1 group M (main) comprising of 11 subtypes and sub-subtypes (A1, A2, B-D, F1, F2, G, H, J, and K) and to date 55 circulating recombinant forms (CRFs). In Southeast Asia, active inter-subtype recombination involving three main circulating genotypes--subtype B (including subtype B', the Thai variant of subtype B), CRF01_AE, and CRF33_01B--have contributed to the emergence of novel unique recombinant forms. In the present study, we conducted the molecular epidemiological surveillance of HIV-1 gag-RT genes among 258 people who inject drugs (PWIDs) in Kuala Lumpur, Malaysia, between 2009 and 2011 whereby a novel CRF candidate was recently identified. The near full-length genome sequences obtained from six epidemiologically unlinked individuals showed identical mosaic structures consisting of subtype B' and CRF01_AE, with six unique recombination breakpoints in the gag-RT, pol, and env regions. Among the high-risk population of PWIDs in Malaysia, which was predominantly infected by CRF33_01B (>70%), CRF58_01B circulated at a low but significant prevalence (2.3%, 6/258). Interestingly, the CRF58_01B shared two unique recombination breakpoints with other established CRFs in the region: CRF33_01B, CRF48_01B, and CRF53_01B in the gag gene, and CRF15_01B (from Thailand) in the env gene. Extended Bayesian Markov chain Monte Carlo sampling analysis showed that CRF58_01B and other recently discovered CRFs were most likely to have originated in Malaysia, and that the recent spread of recombinant lineages in the country had little influence from neighbouring countries. The isolation, genetic characterization, and evolutionary features of CRF58_01B among PWIDs in Malaysia signify the increasingly complex HIV-1 diversity in Southeast Asia that may hold an implication on disease treatment, control, and prevention.

  20. A newly emerging HIV-1 recombinant lineage (CRF58_01B disseminating among people who inject drugs in Malaysia.

    Wei Zhen Chow

    Full Text Available The HIV epidemic is primarily characterised by the circulation of HIV-1 group M (main comprising of 11 subtypes and sub-subtypes (A1, A2, B-D, F1, F2, G, H, J, and K and to date 55 circulating recombinant forms (CRFs. In Southeast Asia, active inter-subtype recombination involving three main circulating genotypes--subtype B (including subtype B', the Thai variant of subtype B, CRF01_AE, and CRF33_01B--have contributed to the emergence of novel unique recombinant forms. In the present study, we conducted the molecular epidemiological surveillance of HIV-1 gag-RT genes among 258 people who inject drugs (PWIDs in Kuala Lumpur, Malaysia, between 2009 and 2011 whereby a novel CRF candidate was recently identified. The near full-length genome sequences obtained from six epidemiologically unlinked individuals showed identical mosaic structures consisting of subtype B' and CRF01_AE, with six unique recombination breakpoints in the gag-RT, pol, and env regions. Among the high-risk population of PWIDs in Malaysia, which was predominantly infected by CRF33_01B (>70%, CRF58_01B circulated at a low but significant prevalence (2.3%, 6/258. Interestingly, the CRF58_01B shared two unique recombination breakpoints with other established CRFs in the region: CRF33_01B, CRF48_01B, and CRF53_01B in the gag gene, and CRF15_01B (from Thailand in the env gene. Extended Bayesian Markov chain Monte Carlo sampling analysis showed that CRF58_01B and other recently discovered CRFs were most likely to have originated in Malaysia, and that the recent spread of recombinant lineages in the country had little influence from neighbouring countries. The isolation, genetic characterization, and evolutionary features of CRF58_01B among PWIDs in Malaysia signify the increasingly complex HIV-1 diversity in Southeast Asia that may hold an implication on disease treatment, control, and prevention.

  1. Recombination analysis based on the complete genome of bocavirus

    Chen Shengxia

    2011-04-01

    Full Text Available Abstract Bocavirus include bovine parvovirus, minute virus of canine, porcine bocavirus, gorilla bocavirus, and Human bocaviruses 1-4 (HBoVs. Although recent reports showed that recombination happened in bocavirus, no systematical study investigated the recombination of bocavirus. The present study performed the phylogenetic and recombination analysis of bocavirus over the complete genomes available in GenBank. Results confirmed that recombination existed among bocavirus, including the likely inter-genotype recombination between HBoV1 and HBoV4, and intra-genotype recombination among HBoV2 variants. Moreover, it is the first report revealing the recombination that occurred between minute viruses of canine.

  2. Circulating histones are mediators of trauma-associated lung injury.

    Abrams, Simon T; Zhang, Nan; Manson, Joanna; Liu, Tingting; Dart, Caroline; Baluwa, Florence; Wang, Susan Siyu; Brohi, Karim; Kipar, Anja; Yu, Weiping; Wang, Guozheng; Toh, Cheng-Hock

    2013-01-15

    Acute lung injury is a common complication after severe trauma, which predisposes patients to multiple organ failure. This syndrome largely accounts for the late mortality that arises and despite many theories, the pathological mechanism is not fully understood. Discovery of histone-induced toxicity in mice presents a new dimension for elucidating the underlying pathophysiology. To investigate the pathological roles of circulating histones in trauma-induced lung injury. Circulating histone levels in patients with severe trauma were determined and correlated with respiratory failure and Sequential Organ Failure Assessment (SOFA) scores. Their cause-effect relationship was studied using cells and mouse models. In a cohort of 52 patients with severe nonthoracic blunt trauma, circulating histones surged immediately after trauma to levels that were toxic to cultured endothelial cells. The high levels were significantly associated with the incidence of acute lung injury and SOFA scores, as well as markers of endothelial damage and coagulation activation. In in vitro systems, histones damaged endothelial cells, stimulated cytokine release, and induced neutrophil extracellular trap formation and myeloperoxidase release. Cellular toxicity resulted from their direct membrane interaction and resultant calcium influx. In mouse models, cytokines and markers for endothelial damage and coagulation activation significantly increased immediately after trauma or histone infusion. Pathological examinations showed that lungs were the predominantly affected organ with edema, hemorrhage, microvascular thrombosis, and neutrophil congestion. An anti-histone antibody could reduce these changes and protect mice from histone-induced lethality. This study elucidates a new mechanism for acute lung injury after severe trauma and proposes that circulating histones are viable therapeutic targets for improving survival outcomes in patients.

  3. Circulating Histones Are Mediators of Trauma-associated Lung Injury

    Abrams, Simon T.; Zhang, Nan; Manson, Joanna; Liu, Tingting; Dart, Caroline; Baluwa, Florence; Wang, Susan Siyu; Brohi, Karim; Kipar, Anja; Yu, Weiping

    2013-01-01

    Rationale: Acute lung injury is a common complication after severe trauma, which predisposes patients to multiple organ failure. This syndrome largely accounts for the late mortality that arises and despite many theories, the pathological mechanism is not fully understood. Discovery of histone-induced toxicity in mice presents a new dimension for elucidating the underlying pathophysiology. Objectives: To investigate the pathological roles of circulating histones in trauma-induced lung injury. Methods: Circulating histone levels in patients with severe trauma were determined and correlated with respiratory failure and Sequential Organ Failure Assessment (SOFA) scores. Their cause–effect relationship was studied using cells and mouse models. Measurements and Main Results: In a cohort of 52 patients with severe nonthoracic blunt trauma, circulating histones surged immediately after trauma to levels that were toxic to cultured endothelial cells. The high levels were significantly associated with the incidence of acute lung injury and SOFA scores, as well as markers of endothelial damage and coagulation activation. In in vitro systems, histones damaged endothelial cells, stimulated cytokine release, and induced neutrophil extracellular trap formation and myeloperoxidase release. Cellular toxicity resulted from their direct membrane interaction and resultant calcium influx. In mouse models, cytokines and markers for endothelial damage and coagulation activation significantly increased immediately after trauma or histone infusion. Pathological examinations showed that lungs were the predominantly affected organ with edema, hemorrhage, microvascular thrombosis, and neutrophil congestion. An anti-histone antibody could reduce these changes and protect mice from histone-induced lethality. Conclusions: This study elucidates a new mechanism for acute lung injury after severe trauma and proposes that circulating histones are viable therapeutic targets for improving survival

  4. Genetic recombination of the hepatitis C virus: clinical implications.

    Morel, V; Fournier, C; François, C; Brochot, E; Helle, F; Duverlie, G; Castelain, S

    2011-02-01

    Genetic recombination is a well-known feature of RNA viruses that plays a significant role in their evolution. Although recombination is well documented for Flaviviridae family viruses, the first natural recombinant strain of hepatitis C virus (HCV) was identified as recently as 2002. Since then, a few other natural inter-genotypic, intra-genotypic and intra-subtype recombinant HCV strains have been described. However, the frequency of recombination may have been underestimated because not all known HCV recombinants are screened for in routine practice. Furthermore, the choice of treatment regimen and its predictive outcome remain problematic as the therapeutic strategy for HCV infection is genotype dependent. HCV recombination also raises many questions concerning its mechanisms and effects on the epidemiological and physiopathological features of the virus. This review provides an update on recombinant HCV strains, the process that gives rise to recombinants and clinical implications of recombination. © 2010 Blackwell Publishing Ltd.

  5. Development of CO2 circulators

    Donaldson, J.

    1988-01-01

    The development of the basic machine types we have supplied has not been without problems. The Windscale AGR (the prototype AGR) was a small 1.2 MW vertically up circulator with an inlet temperature of 237 deg. C (459 deg. F). Oil leakage problems occurred and were cured in the works test facility and the machine went into service with no other problems. The Horizontal 5 MW machines for Hinkley/Hunterston were not so fortunate with vibration problems, interface corrosion problems (effecting the whole reactor) and material dimensional stability problems. Oil ingress problems did not show up in test work but were later reported from site. These reports were initially exagerated due to the measuring techniques which took the operators some time to resolve. In the vertical 5 MW machines for Hartlepool and Heysham 1 there are two interesting factors, firstly a spar failure and secondly shaft axial stability. Many of the problems were due to modifications at site or our inability to model all aspects of site installation from which lessons for the future can be learned. The latest stations Torness and Heysham II incorporate these lessons. The machines have been designed with so much margin that during the resolution of the reactor control rod gag problems the machines were run continuously at 20% overload (6.3 MW). From an initial accident case of 350 deg. C inlet temperature, this increased to 458 deg. C and now stands at 585 deg. C. No modifications to the impeller were required. The site experience to date is good with no operational problems reported. (author). 4 figs

  6. SpaceX Dragon Air Circulation System

    Hernandez, Brenda; Piatrovich, Siarhei; Prina, Mauro

    2011-01-01

    The Dragon capsule is a reusable vehicle being developed by Space Exploration Technologies (SpaceX) that will provide commercial cargo transportation to the International Space Station (ISS). Dragon is designed to be a habitable module while it is berthed to ISS. As such, the Dragon Environmental Control System (ECS) consists of pressure control and pressure equalization, air sampling, fire detection, illumination, and an air circulation system. The air circulation system prevents pockets of stagnant air in Dragon that can be hazardous to the ISS crew. In addition, through the inter-module duct, the air circulation system provides fresh air from ISS into Dragon. To utilize the maximum volume of Dragon for cargo packaging, the Dragon ECS air circulation system is designed around cargo rack optimization. At the same time, the air circulation system is designed to meet the National Aeronautics Space Administration (NASA) inter-module and intra-module ventilation requirements and acoustic requirements. A flight like configuration of the Dragon capsule including the air circulation system was recently assembled for testing to assess the design for inter-module and intra-module ventilation and acoustics. The testing included the Dragon capsule, and flight configuration in the pressure section with cargo racks, lockers, all of the air circulation components, and acoustic treatment. The air circulation test was also used to verify the Computational Fluid Dynamics (CFD) model of the Dragon capsule. The CFD model included the same Dragon internal geometry that was assembled for the test. This paper will describe the Dragon air circulation system design which has been verified by testing the system and with CFD analysis.

  7. Multiple sclerosis

    Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P.; Shariat, K.; Kostopoulos, P.

    2008-01-01

    Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.) [de

  8. Identification of Novel Recombinant Forms of Hepatitis B Virus Generated from Genotypes Ae and G in HIV-1-Positive Japanese Men Who Have Sex with Men.

    Kojima, Yoko; Kawahata, Takuya; Mori, Haruyo; Furubayashi, Keiichi; Taniguchi, Yasushi; Itoda, Ichiro; Komano, Jun

    2015-07-01

    The rare hepatitis B virus (HBV) genotype G (HBV/G) coinfects HIV-1-positive individuals along with HBV/A and generates recombinants. However, the circulation of HBV A/G recombinants remains poorly understood. This molecular epidemiologic study examined HBV A/G recombinants in Japanese HIV-1-positive men who have sex with men (MSM). Initially, blood specimens submitted for confirmatory tests of HIV infection in Osaka and Tokyo, Japan, from 2006 to 2013 were examined for HIV-1, and HIV-1-positive specimens were screened for HBV. Among 817 specimens from HIV-1-positive individuals, HBsAg was detected in 59 specimens; of these, HBV/Ae (alternatively A2), a subgenotype of HBV/A prevalent in Europe and North America, was identified in 70.2%, HBV/C in 17.5%, and HBV/G in 10.5%, and HBV/E in 1.8% according to the core gene sequence. The full-length genome analysis of HBV was performed on HBV/G-positive specimens because some HBV A/G recombinants were historically overlooked by genotyping based on a partial genome analysis. It revealed that five of the specimens contained novel Ae/G recombinants, the core gene of which had a high sequence similarity to HBV/G. Detailed analyses showed that novel recombinants were coinfected with HBV/Ae in a recombinant-dominant fashion. No major drug-resistant mutations were found in the newly identified HBV Ae/G recombinants. Some of the individuals asymptomatically coinfected with HIV/HBV suffered mild liver injury. This study demonstrated that novel Ae/G HBV recombinants were identified in Japanese HIV-1-positive MSM. The pathogenicity of novel HBV Ae/G recombinants should be examined in a future longitudinal study. Surveillance of such viruses in HIV-1-positive individuals should be emphasized.

  9. Circulating microRNAs in breast cancer

    Hamam, Rimi; Hamam, Dana; Alsaleh, Khalid A.

    2017-01-01

    Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence...... in the past several years has highlighted the potential use of peripheral blood circulating nucleic acids such as DNA, mRNA and micro (mi)RNA in breast cancer diagnosis, prognosis and for monitoring response to anticancer therapy. Among these, circulating miRNA is increasingly recognized as a promising...... circulating miRNAs as diagnostic, prognostic or predictive biomarkers in breast cancer management....

  10. Efficient design of multiplier-less digital channelizers using recombination non-uniform filter banks

    Shaeen Kalathil

    2018-01-01

    Full Text Available A novel approach for the efficient realization of digital channelizers in software defined radios using recombination filter banks is proposed in this paper. Digital channelizer is the core of software defined radio. Computationally efficient design supporting multiple channels with different bandwidths and low complexity are inevitable requirements for the digital channelizers. Recombination filter banks method is used to obtain non-uniform filter banks with rational sampling factors, using a two stage structure. It consists of a uniform filter bank and trans-multiplexer. In this work, the uniform filter bank and trans-multiplexer are designed using cosine modulated filter banks. The prototype filter design is made simple, efficient and fast, using window method. The multiplier-less realization of recombination filter banks in the canonic signed digit space using nature inspired optimization algorithms, results in reduced implementation complexity.

  11. The sensitivity of $R_{pA}$ to colour recombination effects

    Zapp, Korinna Christina; Wiedemann, Urs Achim

    2016-01-01

    In hadronization models with color recombination, partons are allowed to regroup into color singlet structures that are different from those determined by the perturbative parton shower. This aims at modeling the possibility that soft interactions of partons with the underlying event can change color connections. If such an effect is at play in proton-proton collisions, it may be expected to be enhanced in proton-nucleus collisions due to the higher color charge density in the underlying event. Here, we provide a qualitative argument that color recombination effects could lead to a multiplicity dependent hardening of single inclusive hadron spectra that dies out very weakly with increasing transverse momentum. We present results of a (conservative) model implementation in the cluster hadronization model of the SHERPA event generator. In this model, we find that color recombination effects harden indeed the single inclusive hadron spectra without affecting the jet spectra, but that this effect does not depend ...

  12. Heterogeneous recombination among Hepatitis B virus genotypes.

    Castelhano, Nadine; Araujo, Natalia M; Arenas, Miguel

    2017-10-01

    The rapid evolution of Hepatitis B virus (HBV) through both evolutionary forces, mutation and recombination, allows this virus to generate a large variety of adapted variants at both intra and inter-host levels. It can, for instance, generate drug resistance or the diverse viral genotypes that currently exist in the HBV epidemics. Concerning the latter, it is known that recombination played a major role in the emergence and genetic diversification of novel genotypes. In this regard, the quantification of viral recombination in each genotype can provide relevant information to devise expectations about the evolutionary trends of the epidemic. Here we measured the amount of this evolutionary force by estimating global and local recombination rates in >4700 HBV complete genome sequences corresponding to nine (A to I) HBV genotypes. Counterintuitively, we found that genotype E presents extremely high levels of recombination, followed by genotypes B and C. On the other hand, genotype G presents the lowest level, where recombination is almost negligible. We discuss these findings in the light of known characteristics of these genotypes. Additionally, we present a phylogenetic network to depict the evolutionary history of the studied HBV genotypes. This network clearly classified all genotypes into specific groups and indicated that diverse pairs of genotypes are derived from a common ancestor (i.e., C-I, D-E and, F-H) although still the origin of this virus presented large uncertainty. Altogether we conclude that the amount of observed recombination is heterogeneous among HBV genotypes and that this heterogeneity can influence on the future expansion of the epidemic. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Disciplining Change, Displacing Frictions. Two Structural Dimensions of Digital Circulation Across Land Registry Database Integration

    Pelizza, Annalisa

    2016-01-01

    Data acquire meaning through circulation. Yet most approaches to high-quality data aim to flatten this stratification of meanings. In government, data quality is achieved through integrated systems of authentic registers that reduce multiple trajectories to a single, official one. These systems can

  14. Comparative genomic and phylogenetic approaches to characterize the role of genetic recombination in mycobacterial evolution.

    Smith, Silvia E; Showers-Corneli, Patrice; Dardenne, Caitlin N; Harpending, Henry H; Martin, Darren P; Beiko, Robert G

    2012-01-01

    The genus Mycobacterium encompasses over one hundred named species of environmental and pathogenic organisms, including the causative agents of devastating human diseases such as tuberculosis and leprosy. The success of these human pathogens is due in part to their ability to rapidly adapt to their changing environment and host. Recombination is the fastest way for bacterial genomes to acquire genetic material, but conflicting results about the extent of recombination in the genus Mycobacterium have been reported. We examined a data set comprising 18 distinct strains from 13 named species for evidence of recombination. Genomic regions common to all strains (accounting for 10% to 22% of the full genomes of all examined species) were aligned and concatenated in the chromosomal order of one mycobacterial reference species. The concatenated sequence was screened for evidence of recombination using a variety of statistical methods, with each proposed event evaluated by comparing maximum-likelihood phylogenies of the recombinant section with the non-recombinant portion of the dataset. Incongruent phylogenies were identified by comparing the site-wise log-likelihoods of each tree using multiple tests. We also used a phylogenomic approach to identify genes that may have been acquired through horizontal transfer from non-mycobacterial sources. The most frequent associated lineages (and potential gene transfer partners) in the Mycobacterium lineage-restricted gene trees are other members of suborder Corynebacterinae, but more-distant partners were identified as well. In two examined cases of potentially frequent and habitat-directed transfer (M. abscessus to Segniliparus and M. smegmatis to Streptomyces), observed sequence distances were small and consistent with a hypothesis of transfer, while in a third case (M. vanbaalenii to Streptomyces) distances were larger. The analyses described here indicate that whereas evidence of recombination in core regions within the genus is

  15. Vaccination with recombinant RNA replicon particles protects chickens from H5N1 highly pathogenic avian influenza virus.

    Stefan J Halbherr

    Full Text Available Highly pathogenic avian influenza viruses (HPAIV of subtype H5N1 not only cause a devastating disease in domestic chickens and turkeys but also pose a continuous threat to public health. In some countries, H5N1 viruses continue to circulate and evolve into new clades and subclades. The rapid evolution of these viruses represents a problem for virus diagnosis and control. In this work, recombinant vesicular stomatitis virus (VSV vectors expressing HA of subtype H5 were generated. To comply with biosafety issues the G gene was deleted from the VSV genome. The resulting vaccine vector VSV*ΔG(HA was propagated on helper cells providing the VSV G protein in trans. Vaccination of chickens with a single intramuscular dose of 2×10⁸ infectious replicon particles without adjuvant conferred complete protection from lethal H5N1 infection. Subsequent application of the same vaccine strongly boosted the humoral immune response and completely prevented shedding of challenge virus and transmission to sentinel birds. The vaccine allowed serological differentiation of infected from vaccinated animals (DIVA by employing a commercially available ELISA. Immunized chickens produced antibodies with neutralizing activity against multiple H5 viruses representing clades 1, 2.2, 2.5, and low-pathogenic avian influenza viruses (classical clade. Studies using chimeric H1/H5 hemagglutinins showed that the neutralizing activity was predominantly directed against the globular head domain. In summary, these results suggest that VSV replicon particles are safe and potent DIVA vaccines that may help to control avian influenza viruses in domestic poultry.

  16. Seawater circulating system in an aquaculture laboratory

    Chatterji, A.; Ingole, B.S.; Parulekar, A.H.

    The note gives an account, for the first time in India, of an Aquaculture Laboratory with open type seawater circulating system developed at the National Institute of Oceanography, Goa, India. Besides describing the details of the system...

  17. EOP MIT General Circulation Model (MITgcm)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data contains a regional implementation of the Massachusetts Institute of Technology general circulation model (MITgcm) at a 1-km spatial resolution for the...

  18. Seasonal Overturning Circulation in the Red Sea

    Yao, F.; Hoteit, I.; Koehl, A.

    2010-12-01

    The Red Sea exhibits a distinct seasonal overturning circulation. In winter, a typical two-layer exchange structure, with a fresher inflow from the Gulf of Aden on top of an outflow from the Red Sea, is established. In summer months (June to September) this circulation pattern is changed to a three-layer structure: a surface outflow from the Red Sea on top of a subsurface intrusion of the Gulf of Aden Intermediate Water and a weakened deep outflow. This seasonal variability is studied using a general circulation model, MITgcm, with 6 hourly NCEP atmospheric forcing. The model is able to reproduce the observed seasonal variability very well. The forcing mechanisms of the seasonal variability related to seasonal surface wind stress and buoyancy flux, and water mass transformation processes associated with the seasonal overturning circulation are analyzed and presented.

  19. Blocking device especially for circulating pumps

    Susil, J.; Vychodil, V.; Lorenc, P.

    1976-01-01

    The claim of the invention is a blocking device which blocks reverse flow occurring after the shutdown of circulating pumps, namely in the operation of nuclear power plants or in pumps with a high delivery head. (F.M.)

  20. Graded Recombination Layers for Multijunction Photovoltaics

    Koleilat, Ghada I.

    2012-06-13

    Multijunction devices consist of a stack of semiconductor junctions having bandgaps tuned across a broad spectrum. In solar cells this concept is used to increase the efficiency of photovoltaic harvesting, while light emitters and detectors use it to achieve multicolor and spectrally tunable behavior. In series-connected current-matched multijunction devices, the recombination layers must allow the hole current from one cell to recombine, with high efficiency and low voltage loss, with the electron current from the next cell. We recently reported a tandem solar cell in which the recombination layer was implemented using a progression of n-type oxides whose doping densities and work functions serve to connect, with negligible resistive loss at solar current densities, the constituent cells. Here we present the generalized conditions for design of efficient graded recombination layer solar devices. We report the number of interlayers and the requirements on work function and doping of each interlayer, to bridge an work function difference as high as 1.6 eV. We also find solutions that minimize the doping required of the interlayers in order to minimize optical absorption due to free carriers in the graded recombination layer (GRL). We demonstrate a family of new GRL designs experimentally and highlight the benefits of the progression of dopings and work functions in the interlayers. © 2012 American Chemical Society.

  1. SequenceLDhot: detecting recombination hotspots.

    Fearnhead, Paul

    2006-12-15

    There is much local variation in recombination rates across the human genome--with the majority of recombination occurring in recombination hotspots--short regions of around approximately 2 kb in length that have much higher recombination rates than neighbouring regions. Knowledge of this local variation is important, e.g. in the design and analysis of association studies for disease genes. Population genetic data, such as that generated by the HapMap project, can be used to infer the location of these hotspots. We present a new, efficient and powerful method for detecting recombination hotspots from population data. We compare our method with four current methods for detecting hotspots. It is orders of magnitude quicker, and has greater power, than two related approaches. It appears to be more powerful than HotspotFisher, though less accurate at inferring the precise positions of the hotspot. It was also more powerful than LDhot in some situations: particularly for weaker hotspots (10-40 times the background rate) when SNP density is lower (maths.lancs.ac.uk/~fearnhea/Hotspot.

  2. Multiple homicides.

    Copeland, A R

    1989-09-01

    A study of multiple homicides or multiple deaths involving a solitary incident of violence by another individual was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, during 1983-1987. A total of 107 multiple homicides were studied: 88 double, 17 triple, one quadruple, and one quintuple. The 236 victims were analyzed regarding age, race, sex, cause of death, toxicologic data, perpetrator, locale of the incident, and reason for the incident. This article compares this type of slaying with other types of homicide including those perpetrated by serial killers. Suggestions for future research in this field are offered.

  3. A Bacillus megaterium System for the Production of Recombinant Proteins and Protein Complexes.

    Biedendieck, Rebekka

    2016-01-01

    For many years the Gram-positive bacterium Bacillus megaterium has been used for the production and secretion of recombinant proteins. For this purpose it was systematically optimized. Plasmids with different inducible promoter systems, with different compatible origins, with small tags for protein purification and with various specific signals for protein secretion were combined with genetically improved host strains. Finally, the development of appropriate cultivation conditions for the production strains established this organism as a bacterial cell factory even for large proteins. Along with the overproduction of individual proteins the organism is now also used for the simultaneous coproduction of up to 14 recombinant proteins, multiple subsequently interacting or forming protein complexes. Some of these recombinant strains are successfully used for bioconversion or the biosynthesis of valuable components including vitamins. The titers in the g per liter scale for the intra- and extracellular recombinant protein production prove the high potential of B. megaterium for industrial applications. It is currently further enhanced for the production of recombinant proteins and multi-subunit protein complexes using directed genetic engineering approaches based on transcriptome, proteome, metabolome and fluxome data.

  4. Development of a recombinant poxvirus expressing bovine herpesvirus-1 glycoprotein D

    Ruiz Saenz, Julian; Osorio, Jorge E; Vera, Victor J.

    2012-01-01

    Bovine herpesvirus-1 is a DNA virus belonging to the family herpesviridae, which affects cattle, causing a wide spectrum of clinical manifestations and economic losses. The main immunogenic component is its envelope glycoprotein d (GD), which has been characterized and used as immunogen in different expression systems. The aim of this work was to generate a recombinant poxvirus (raccoonpox [RCN]) expressing a truncated version of BHV-1 GD to be used as a vaccine. to do this, it was amplified the gene for a truncated version of GD which subsequently was cloned in transfer plasmid PTK/IRES/TPA which has homology to sites of poxvirus thymidine kinase, an internal site of ribosome entry (IRES) and a secretory signal (TPA), generating the construct PTK/GD/IRES/TPA. to generate the recombinant RCN, we took BSC-1 cells and we infected with a wild type RCN (CDC/v71-i-85a) at a multiplicity of infection of 0.05, then cells were transfected with the construct PTK/GD/IRES/TPA, generating different viral populations with and without the gene of interest. To select recombinant viruses expressing the gene of interest, we performed a selection of recombinant thymidine kinase negative and positive for GD by three rounds of plaque purification on rat-2 cells monolayers which are thymidine kinase null and using bromodeoxyuridine. Recombinant viruses were recovered and confirmed by PCR and nucleotide sequencing and so called RCN-GD.

  5. Genome-wide recombination rate variation in a recombination map of cotton.

    Shen, Chao; Li, Ximei; Zhang, Ruiting; Lin, Zhongxu

    2017-01-01

    Recombination is crucial for genetic evolution, which not only provides new allele combinations but also influences the biological evolution and efficacy of natural selection. However, recombination variation is not well understood outside of the complex species' genomes, and it is particularly unclear in Gossypium. Cotton is the most important natural fibre crop and the second largest oil-seed crop. Here, we found that the genetic and physical maps distances did not have a simple linear relationship. Recombination rates were unevenly distributed throughout the cotton genome, which showed marked changes along the chromosome lengths and recombination was completely suppressed in the centromeric regions. Recombination rates significantly varied between A-subgenome (At) (range = 1.60 to 3.26 centimorgan/megabase [cM/Mb]) and D-subgenome (Dt) (range = 2.17 to 4.97 cM/Mb), which explained why the genetic maps of At and Dt are similar but the physical map of Dt is only half that of At. The translocation regions between A02 and A03 and between A04 and A05, and the inversion regions on A10, D10, A07 and D07 indicated relatively high recombination rates in the distal regions of the chromosomes. Recombination rates were positively correlated with the densities of genes, markers and the distance from the centromere, and negatively correlated with transposable elements (TEs). The gene ontology (GO) categories showed that genes in high recombination regions may tend to response to environmental stimuli, and genes in low recombination regions are related to mitosis and meiosis, which suggested that they may provide the primary driving force in adaptive evolution and assure the stability of basic cell cycle in a rapidly changing environment. Global knowledge of recombination rates will facilitate genetics and breeding in cotton.

  6. Estuarine turbidity, flushing, salinity, and circulation

    Pritchard, D. W.

    1972-01-01

    The effects of estuarine turbidity, flushing, salinity, and circulation on the ecology of the Chesapeake Bay are discussed. The sources of fresh water, the variations in salinity, and the circulation patterns created by temperature and salinity changes are analyzed. The application of remote sensors for long term observation of water temperatures is described. The sources of sediment and the biological effects resulting from increased sediments and siltation are identified.

  7. [Circulating tumor cells: cornerstone of personalized medicine].

    Rafii, A; Vidal, F; Rathat, G; Alix-Panabières, C

    2014-11-01

    Cancer treatment has evolved toward personalized medicine. It is mandatory for clinicians to ascertain tumor biological features in order to optimize patients' treatment. Identification and characterization of circulating tumor cells demonstrated a prognostic value in many solid tumors. Here, we describe the main technologies for identification and characterization of circulating tumor cells and their clinical application in gynecologic and breast cancers. Copyright © 2014. Published by Elsevier Masson SAS.

  8. Themes on circulation in the third world.

    Chapman, M; Prothero, R M

    1983-01-01

    "This article focuses upon circulation, or reciprocal flows of people, with specific reference to Third World societies." Aspects considered include attempts to standardize terminology and to formulate typologies of population movement; the development of explanatory models of circulation and modernization, social networks, family welfare, and capitalism; and "the transfer of methods and concepts to societies and populations different from those from which they initially evolved and in which they were first tested." excerpt

  9. Diffusion-driven and excitation-dependent recombination rate in blue InGaN/GaN quantum well structures

    Aleksiejūnas, R.; Gelžinytė, K.; Nargelas, S.; Jarašiūnas, K.; Vengris, M.; Armour, E. A.; Byrnes, D. P.; Arif, R. A.; Lee, S. M.; Papasouliotis, G. D.

    2014-01-01

    We report on diffusion-driven and excitation-dependent carrier recombination rate in multiple InGaN/GaN quantum wells by using photoluminescence, light-induced absorption, and diffraction techniques. We demonstrate gradually increasing with excitation carrier diffusivity and its correlation with the recombination rate. At low carrier densities, an increase in radiative emission and carrier lifetime was observed due to partial saturation of non-radiative recombination centers. However, at carrier densities above ∼5 × 10 18  cm −3 , a typical value of photoluminescence efficiency droop, a further increase of diffusivity forces the delocalized carriers to face higher number of fast non-radiative recombination centers leading to an increase of non-radiative losses

  10. Diffusion-driven and excitation-dependent recombination rate in blue InGaN/GaN quantum well structures

    Aleksiejūnas, R.; Gelžinytė, K.; Nargelas, S., E-mail: saulius.nargelas@ff.vu.lt; Jarašiūnas, K. [Department of Semiconductor Optoelectronics, Institute of Applied Research, Vilnius University, Saulėtekio 9–III, 10222 Vilnius (Lithuania); Vengris, M. [Laser Research Center, Vilnius University, Saulėtekio 10, 10223 Vilnius (Lithuania); Armour, E. A.; Byrnes, D. P.; Arif, R. A.; Lee, S. M.; Papasouliotis, G. D. [Veeco Instruments, Turbodisc Operations, 394 Elizabeth Avenue, Somerset, New Jersey 08873 (United States)

    2014-01-13

    We report on diffusion-driven and excitation-dependent carrier recombination rate in multiple InGaN/GaN quantum wells by using photoluminescence, light-induced absorption, and diffraction techniques. We demonstrate gradually increasing with excitation carrier diffusivity and its correlation with the recombination rate. At low carrier densities, an increase in radiative emission and carrier lifetime was observed due to partial saturation of non-radiative recombination centers. However, at carrier densities above ∼5 × 10{sup 18} cm{sup −3}, a typical value of photoluminescence efficiency droop, a further increase of diffusivity forces the delocalized carriers to face higher number of fast non-radiative recombination centers leading to an increase of non-radiative losses.

  11. Surgical myocardial revascularization without extracorporeal circulation

    Salomón Soriano Ordinola Rojas

    2003-05-01

    Full Text Available OBJECTIVE: To assess the immediate postoperative period of patients undergoing myocardial revascularization without extracorporeal circulation with different types of grafts. METHODS: One hundred and twelve patients, 89 (79.5% of whom were males, were revascularized without extracorporeal circulation. Their ages ranged from 39 to 85 years. The criteria for indicating myocardial revascularization without extracorporeal circulation were as follows: revascularized coronary artery caliber > 1.5 mm, lack of intramyocardial trajectory on coronary angiography, noncalcified coronary arteries, and tolerance of the heart to the different rotation maneuvers. RESULTS: Myocardial revascularization without extracorporeal circulation was performed in 112 patients. Three were converted to extracorporeal circulation, which required a longer hospital stay but did not impact mortality. During the procedure, the following events were observed: atrial fibrillation in 10 patients, ventricular fibrillation in 4, total transient atrioventricular block in 2, ventricular extrasystoles in 58, use of a device to retrieve red blood cells in 53, blood transfusion in 8, and arterial hypotension in 89 patients. Coronary angiography was performed in 20 patients on the seventh postoperative day when the grafts were patent. CONCLUSION: Myocardial revascularization without extracorporeal circulation is a reproducible technique that is an alternative for treating ischemic heart disease.

  12. Multiple Sclerosis

    Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the myelin sheath, the material that surrounds and protects your nerve cells. This damage slows down ...

  13. Multiple myeloma.

    Collins, Conor D

    2012-02-01

    Advances in the imaging and treatment of multiple myeloma have occurred over the past decade. This article summarises the current status and highlights how an understanding of both is necessary for optimum management.

  14. Multiple mononeuropathy

    ... with multiple mononeuropathy are prone to new nerve injuries at pressure points such as the knees and elbows. They should avoid putting pressure on these areas, for example, by not leaning on the elbows, crossing the knees, ...

  15. Broad-scale recombination patterns underlying proper disjunction in humans.

    Adi Fledel-Alon

    2009-09-01

    Full Text Available Although recombination is essential to the successful completion of human meiosis, it remains unclear how tightly the process is regulated and over what scale. To assess the nature and stringency of constraints on human recombination, we examined crossover patterns in transmissions to viable, non-trisomic offspring, using dense genotyping data collected in a large set of pedigrees. Our analysis supports a requirement for one chiasma per chromosome rather than per arm to ensure proper disjunction, with additional chiasmata occurring in proportion to physical length. The requirement is not absolute, however, as chromosome 21 seems to be frequently transmitted properly in the absence of a chiasma in females, a finding that raises the possibility of a back-up mechanism aiding in its correct segregation. We also found a set of double crossovers in surprisingly close proximity, as expected from a second pathway that is not subject to crossover interference. These findings point to multiple mechanisms that shape the distribution of crossovers, influencing proper disjunction in humans.

  16. Recombinant human erythropoietin in sports: a review

    Rafael Maia de Almeida Bento

    2003-06-01

    Full Text Available Erythropoietin is an endogenous hormone of glicoproteic nature secreted by the kidneys and is the main regulator of the erythropoiesis. An alteration in its production generates a disturbance in the plasmatic concentration giving rise to several types of pathologies related to the hematopoietic system. The recombinant forms of erythropoietin have indiscriminately been used by athletes, mainly in endurance sports, by increasing the erythrocytes concentration, generating a better delivery of oxygen to the muscle tissue. The administration of recombinant erythropoietin was prohibited by the International Olympic Committee and its use considered as doping. This review has the intention to describe the physical, biological and pharmacokinetic properties of the endogenous erythropoietin, as well as its recombinant form, describing also its use in sports and the process of searching methodologies for its detection in doping control.

  17. Regulation of Homologous Recombination by SUMOylation

    Pinela da Silva, Sonia Cristina

    factors such as the homologous recombination (HR) machinery. HR constitutes the main DSB repair pathway in Saccharomyces cerevisiae and despite being largely considered an error-free process and essential for genome stability, uncontrolled recombination can lead to loss of heterozygosity, translocations......, deletions, and genome rearrangements that can lead to cell death or cancer in humans. The post-translational modification by SUMO (small ubiquitinlike modifier) has proven to be an important regulator of HR and genome integrity, but the molecular mechanisms responsible for these roles are still unclear....... In this study I present new insights for the role of SUMOylation in regulating HR by dissecting the role of SUMO in the interaction between the central HR-mediator protein Rad52 and its paralogue Rad59 and the outcome of recombination. This data provides evidence for the importance of SUMO in promoting protein...

  18. Determination of recombination in Mycoplasma hominis

    Jacobsen, Iben Søgaard; Boesen, Thomas; Mygind, Tina

    2002-01-01

    disequilibrium and distance between the segregating sites, by the homoplasy ratio (H ratio), and by compatibility matrices. The gap gene showed well-supported evidence for high levels of recombination, whereas recombination was less frequent and not significant within the other genes. The analysis revealed......B-hitL, excinuclease ABC subunit A (uvrA) and glyceraldehyde-3-phosphate dehydrogenase (gap) genes. The level of variability of these M. hominis genes was low compared with the housekeeping genes from Helicobacter pylori and Neisseria meningitidis, but only few M. hominis isolates had identical sequences in all genes...... intergenic and intragenic recombination in M. hominis and this may explain the high intraspecies variability. The results obtained in the present study may be of importance for future population studies of Mycoplasma species....

  19. Constraints from jet calculus on quark recombination

    Jones, L.M.; Lassila, K.E.; Willen, D.

    1979-01-01

    Within the QCD jet calculus formalism, we deduce an equation describing recombination of quarks and antiquarks into mesons within a quark or gluon jet. This equation relates the recombination function R(x 1 ,x 2 ,x) used in current literature to the fragmentation function for producing that same meson out of the parton initiating the jet. We submit currently used recombination functions to our consistency test, taking as input mainly the u-quark fragmentation data into π + mesons, but also s-quark fragmentation into K - mesons. The constraint is well satisfied at large Q 2 for large moments. Our results depend on one parameter, Q 0 2 , the constraint equation being satisfied for small values of this parameter

  20. Recombination Processes and Nonlinear Markov Chains.

    Pirogov, Sergey; Rybko, Alexander; Kalinina, Anastasia; Gelfand, Mikhail

    2016-09-01

    Bacteria are known to exchange genetic information by horizontal gene transfer. Since the frequency of homologous recombination depends on the similarity between the recombining segments, several studies examined whether this could lead to the emergence of subspecies. Most of them simulated fixed-size Wright-Fisher populations, in which the genetic drift should be taken into account. Here, we use nonlinear Markov processes to describe a bacterial population evolving under mutation and recombination. We consider a population structure as a probability measure on the space of genomes. This approach implies the infinite population size limit, and thus, the genetic drift is not assumed. We prove that under these conditions, the emergence of subspecies is impossible.

  1. Transcription and recombination: when RNA meets DNA.

    Aguilera, Andrés; Gaillard, Hélène

    2014-08-01

    A particularly relevant phenomenon in cell physiology and proliferation is the fact that spontaneous mitotic recombination is strongly enhanced by transcription. The most accepted view is that transcription increases the occurrence of double-strand breaks and/or single-stranded DNA gaps that are repaired by recombination. Most breaks would arise as a consequence of the impact that transcription has on replication fork progression, provoking its stalling and/or breakage. Here, we discuss the mechanisms responsible for the cross talk between transcription and recombination, with emphasis on (1) the transcription-replication conflicts as the main source of recombinogenic DNA breaks, and (2) the formation of cotranscriptional R-loops as a major cause of such breaks. The new emerging questions and perspectives are discussed on the basis of the interference between transcription and replication, as well as the way RNA influences genome dynamics. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

  2. Exceptionally high levels of recombination across the honey bee genome.

    Beye, Martin; Gattermeier, Irene; Hasselmann, Martin; Gempe, Tanja; Schioett, Morten; Baines, John F; Schlipalius, David; Mougel, Florence; Emore, Christine; Rueppell, Olav; Sirviö, Anu; Guzmán-Novoa, Ernesto; Hunt, Greg; Solignac, Michel; Page, Robert E

    2006-11-01

    The first draft of the honey bee genome sequence and improved genetic maps are utilized to analyze a genome displaying 10 times higher levels of recombination (19 cM/Mb) than previously analyzed genomes of higher eukaryotes. The exceptionally high recombination rate is distributed genome-wide, but varies by two orders of magnitude. Analysis of chromosome, sequence, and gene parameters with respect to recombination showed that local recombination rate is associated with distance to the telomere, GC content, and the number of simple repeats as described for low-recombining genomes. Recombination rate does not decrease with chromosome size. On average 5.7 recombination events per chromosome pair per meiosis are found in the honey bee genome. This contrasts with a wide range of taxa that have a uniform recombination frequency of about 1.6 per chromosome pair. The excess of recombination activity does not support a mechanistic role of recombination in stabilizing pairs of homologous chromosome during chromosome pairing. Recombination rate is associated with gene size, suggesting that introns are larger in regions of low recombination and may improve the efficacy of selection in these regions. Very few transposons and no retrotransposons are present in the high-recombining genome. We propose evolutionary explanations for the exceptionally high genome-wide recombination rate.

  3. Finding trans-regulatory genes and protein complexes modulating meiotic recombination hotspots of human, mouse and yeast.

    Wu, Min; Kwoh, Chee-Keong; Li, Xiaoli; Zheng, Jie

    2014-09-11

    The regulatory mechanism of recombination is one of the most fundamental problems in genomics, with wide applications in genome wide association studies (GWAS), birth-defect diseases, molecular evolution, cancer research, etc. Recombination events cluster into short genomic regions called "recombination hotspots". Recently, a zinc finger protein PRDM9 was reported to regulate recombination hotspots in human and mouse genomes. In addition, a 13-mer motif contained in the binding sites of PRDM9 is found to be enriched in human hotspots. However, this 13-mer motif only covers a fraction of hotspots, indicating that PRDM9 is not the only regulator of recombination hotspots. Therefore, the challenge of discovering other regulators of recombination hotspots becomes significant. Furthermore, recombination is a complex process. Hence, multiple proteins acting as machinery, rather than individual proteins, are more likely to carry out this process in a precise and stable manner. Therefore, the extension of the prediction of individual trans-regulators to protein complexes is also highly desired. In this paper, we introduce a pipeline to identify genes and protein complexes associated with recombination hotspots. First, we prioritize proteins associated with hotspots based on their preference of binding to hotspots and coldspots. Second, using the above identified genes as seeds, we apply the Random Walk with Restart algorithm (RWR) to propagate their influences to other proteins in protein-protein interaction (PPI) networks. Hence, many proteins without DNA-binding information will also be assigned a score to implicate their roles in recombination hotspots. Third, we construct sub-PPI networks induced by top genes ranked by RWR for various species (e.g., yeast, human and mouse) and detect protein complexes in those sub-PPI networks. The GO term analysis show that our prioritizing methods and the RWR algorithm are capable of identifying novel genes associated with

  4. Thermal recombination: Beyond the valence quark approximation

    Mueller, B. [Department of Physics, Duke University, Durham, NC 27708 (United States); Fries, R.J. [School of Physics and Astronomy, University of Minnesota, Minneapolis, MN 55455 (United States)]. E-mail: fries@physics.umn.edu; Bass, S.A. [Department of Physics, Duke University, Durham, NC 27708 (United States); RIKEN BNL Research Center, Brookhaven National Laboratory, Upton, NY 11973 (United States)

    2005-07-07

    Quark counting rules derived from recombination models agree well with data on hadron production at intermediate transverse momenta in relativistic heavy-ion collisions. They convey a simple picture of hadrons consisting only of valence quarks. We discuss the inclusion of higher Fock states that add sea quarks and gluons to the hadron structure. We show that, when recombination occurs from a thermal medium, hadron spectra remain unaffected by the inclusion of higher Fock states. However, the quark number scaling for elliptic flow is somewhat affected. We discuss the implications for our understanding of data from the Relativistic Heavy Ion Collider.

  5. The recombination of a helium plasma

    Hollenstein, C.; Sayasov, Y.; Schneider, H.

    1975-01-01

    A helium plasma (Tsub(e) 15 cm -3 ) in the afterglow without magnetic field was investigated. The measurements of the electron density and temperature are presented. Laser interferometry and radiowave diagnostics were used. The measured exponential decay of the electron density and temperature was explained with the collisional-radiative recombination and the thermal conduction of the electrons towards the wall of the discharge vessel. The measured recombination coefficients were compared with measurements and calculations of other authors. The best agreement was found with the calculations by Drawin. (Auth.)

  6. Theoretical models for recombination in expanding gas

    Avron, Y.; Kahane, S.

    1978-09-01

    In laser isotope separation of atomic uranium, one is confronted with the theoretical problem of estimating the concentration of thermally ionized uranium atoms. To investigate this problem theoretical models for recombination in an expanding gas and in the absence of local thermal equilibrium have been constructed. The expansion of the gas is described by soluble models of the hydrodynamic equation, and the recombination by rate equations. General results for the freezing effect for the suitable ranges of the gas parameters are obtained. The impossibility of thermal equilibrium in expanding two-component systems is proven

  7. Whole-genome patterns of linkage disequilibrium across flycatcher populations clarify the causes and consequences of fine-scale recombination rate variation in birds.

    Kawakami, Takeshi; Mugal, Carina F; Suh, Alexander; Nater, Alexander; Burri, Reto; Smeds, Linnéa; Ellegren, Hans

    2017-08-01

    Recombination rate is heterogeneous across the genome of various species and so are genetic diversity and differentiation as a consequence of linked selection. However, we still lack a clear picture of the underlying mechanisms for regulating recombination. Here we estimated fine-scale population recombination rate based on the patterns of linkage disequilibrium across the genomes of multiple populations of two closely related flycatcher species (Ficedula albicollis and F. hypoleuca). This revealed an overall conservation of the recombination landscape between these species at the scale of 200 kb, but we also identified differences in the local rate of recombination despite their recent divergence (recombination rate in a lineage-specific manner, indicating differences in the extent of linked selection between species. We detected 400-3,085 recombination hotspots per population. Location of hotspots was conserved between species, but the intensity of hotspot activity varied between species. Recombination hotspots were primarily associated with CpG islands (CGIs), regardless of whether CGIs were at promoter regions or away from genes. Recombination hotspots were also associated with specific transposable elements (TEs), but this association appears indirect due to shared preferences of the transposition machinery and the recombination machinery for accessible open chromatin regions. Our results suggest that CGIs are a major determinant of the localization of recombination hotspots, and we propose that both the distribution of TEs and fine-scale variation in recombination rate may be associated with the evolution of the epigenetic landscape. © 2017 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

  8. Recombination coefficients in extrinsic n-InSb

    Schneider, W.; Groh, H.; Huebner, K.

    1976-01-01

    The bulk recombination coefficients for linear recombination via recombination centers as well as for direct recombination have been determined measuring the conductivity decay after two-photon absorption with a CO 2 laser. The Suhl effect was applied to measure the surface recombination velocity. The corresponding literature is discussed and compared with our results. We conclude that two different kinds of recombination centers are possible in n-InSb, with energy levels (0.1-0.12)eV above the valence band, or (0.14-0.2)eV respectively. (orig.) [de

  9. Hypoxia, leukocytes, and the pulmonary circulation.

    Stenmark, Kurt R; Davie, Neil J; Reeves, John T; Frid, Maria G

    2005-02-01

    Data are rapidly accumulating in support of the idea that circulating monocytes and/or mononuclear fibrocytes are recruited to the pulmonary circulation of chronically hypoxic animals and that these cells play an important role in the pulmonary hypertensive process. Hypoxic induction of monocyte chemoattractant protein-1, stromal cell-derived factor-1, vascular endothelial growth factor-A, endothelin-1, and tumor growth factor-beta(1) in pulmonary vessel wall cells, either directly or indirectly via signals from hypoxic lung epithelial cells, may be a critical first step in the recruitment of circulating leukocytes to the pulmonary circulation. In addition, hypoxic stress appears to induce release of increased numbers of monocytic progenitor cells from the bone marrow, and these cells may have upregulated expression of receptors for the chemokines produced by the lung circulation, which thus facilitates their specific recruitment to the pulmonary site. Once present, macrophages/fibrocytes may exert paracrine effects on resident pulmonary vessel wall cells stimulating proliferation, phenotypic modulation, and migration of resident fibroblasts and smooth muscle cells. They may also contribute directly to the remodeling process through increased production of collagen and/or differentiation into myofibroblasts. In addition, they could play a critical role in initiating and/or supporting neovascularization of the pulmonary artery vasa vasorum. The expanded vasa network may then act as a conduit for further delivery of circulating mononuclear cells to the pulmonary arterial wall, creating a feedforward loop of pathological remodeling. Future studies will need to determine the mechanisms that selectively induce leukocyte/fibrocyte recruitment to the lung circulation under hypoxic conditions, their direct role in the remodeling process via production of extracellular matrix and/or differentiation into myofibroblasts, their impact on the phenotype of resident smooth muscle

  10. [Multiple meningiomas].

    Terrier, L-M; François, P

    2016-06-01

    Multiple meningiomas (MMs) or meningiomatosis are defined by the presence of at least 2 lesions that appear simultaneously or not, at different intracranial locations, without the association of neurofibromatosis. They present 1-9 % of meningiomas with a female predominance. The occurrence of multiple meningiomas is not clear. There are 2 main hypotheses for their development, one that supports the independent evolution of these tumors and the other, completely opposite, that suggests the propagation of tumor cells of a unique clone transformation, through cerebrospinal fluid. NF2 gene mutation is an important intrinsic risk factor in the etiology of multiple meningiomas and some exogenous risk factors have been suspected but only ionizing radiation exposure has been proven. These tumors can grow anywhere in the skull but they are more frequently observed in supratentorial locations. Their histologic types are similar to unique meningiomas of psammomatous, fibroblastic, meningothelial or transitional type and in most cases are benign tumors. The prognosis of these tumors is eventually good and does not differ from the unique tumors except for the cases of radiation-induced multiple meningiomas, in the context of NF2 or when diagnosed in children where the outcome is less favorable. Each meningioma lesion should be dealt with individually and their multiple character should not justify their resection at all costs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance.

    José María Moreno-Navarrete

    Full Text Available Zonulin is the only physiological mediator known to regulate intestinal permeability reversibly by modulating intercellular tight junctions. To investigate the relationship between intestinal permeability and obesity-associated metabolic disturbances in humans, we aimed to study circulating zonulin according to obesity and insulin resistance. Circulating zonulin (ELISA was measured in 123 caucasian men in association with inflammatory and metabolic parameters (including minimal model-measured insulin sensitivity. Circulating zonulin increased with body mass index (BMI, waist to hip ratio (WHR, fasting insulin, fasting triglycerides, uric acid and IL-6, and negatively correlated with HDL-cholesterol and insulin sensitivity. In multiple regression analysis, insulin sensitivity (p = 0.002 contributed independently to circulating zonulin variance, after controlling for the effects of BMI, fasting triglycerides and age. When circulating IL-6 was added to this model, only BMI (p = 0.01 contributed independently to circulating zonulin variance. In conclusion, the relationship between insulin sensitivity and circulating zonulin might be mediated through the obesity-related circulating IL-6 increase.

  12. Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance.

    Moreno-Navarrete, José María; Sabater, Mònica; Ortega, Francisco; Ricart, Wifredo; Fernández-Real, José Manuel

    2012-01-01

    Zonulin is the only physiological mediator known to regulate intestinal permeability reversibly by modulating intercellular tight junctions. To investigate the relationship between intestinal permeability and obesity-associated metabolic disturbances in humans, we aimed to study circulating zonulin according to obesity and insulin resistance. Circulating zonulin (ELISA) was measured in 123 caucasian men in association with inflammatory and metabolic parameters (including minimal model-measured insulin sensitivity). Circulating zonulin increased with body mass index (BMI), waist to hip ratio (WHR), fasting insulin, fasting triglycerides, uric acid and IL-6, and negatively correlated with HDL-cholesterol and insulin sensitivity. In multiple regression analysis, insulin sensitivity (p = 0.002) contributed independently to circulating zonulin variance, after controlling for the effects of BMI, fasting triglycerides and age. When circulating IL-6 was added to this model, only BMI (p = 0.01) contributed independently to circulating zonulin variance. In conclusion, the relationship between insulin sensitivity and circulating zonulin might be mediated through the obesity-related circulating IL-6 increase.

  13. Assessing drivers of the IgG4 antibody reactivity to recombinant antigen Bm14 in Wuchereria bancrofti endemic populations in East Africa

    Hansen, Johanne Damgaard; Meyrowitsch, Dan W.; Rwegoshora, Rwehumbiza T.

    2016-01-01

    to the recombinant filarial antigen Bm14 in Wuchereria bancrofti endemic populations in East Africa. Sera collected during previous studies from 395 well characterized individuals with regard to age, sex, mf, CFA, household vector biting and household exposure to infective filarial larvae were tested for IgG4......A high proportion of the human population in lymphatic filariasis (LF) endemic areas is positive for filarial specific IgG4 antibodies, including many individuals without microfilariae (mf; circulating larvae in the human blood) or circulating filarial antigens (CFA; marker of adult worm infection...

  14. Pacific Circulation and the Resilience of its Equatorial Reefs

    Cohen, A. L.; Drenkard, E.

    2012-12-01

    High rates of calcification by tropical reef-building corals are paramount to the maintenance of healthy reefs. Investigations of the impact of ocean acidification in both laboratory and field studies demonstrate unequivocally the dependence of coral and coral reef calcification on the carbonate ion concentration of seawater, a dependence predicted by fundamental laws of physical chemistry. Nevertheless, results from a new generation of experiments that exploit the biology of coral calcification, suggest that effects of ocean acidification can - in some instances - be mitigated with simultaneous manipulation of multiple factors. These laboratory results imply that coral reefs in regions projected to experience changes in, for example, nutrient delivery, light and flow, in addition to pH and carbonate ion concentration, may be more resilient (or vulnerable) to the effects of ocean acidification alone. If demonstrated to be true, these observations have profound implications for the conservation and management of coral reefs in the 21st century. We quantified spatial and temporal variability in rates of calcification of a dominant Indo-Pacific reef building coral across sites where changes in ocean circulation patterns drive variability in multiple physical, chemical and biological parameters. Such changes are occurring against a background of variability and trends in carbonate system chemistry. Our field data provide support for hypotheses based on laboratory observations, and show that impacts of ocean acidification on coral calcification can be partially and in some cases, fully, offset by simultaneous changes in multiple factors. Our results imply that projected changes in oceanic and atmospheric circulation patterns, driven by global warming, must be considered when predicting coral reef resilience, or vulnerability, to 21st century ocean acidification.

  15. Biological evaluation of recombinant human erythropoietin in pharmaceutical products

    Ramos A.S.

    2003-01-01

    Full Text Available The potencies of mammalian cell-derived recombinant human erythropoietin pharmaceutical preparations, from a total of five manufacturers, were assessed by in vivo bioassay using standardized protocols. Eight-week-old normocythemic mice received a single subcutaneous injection followed by blood sampling 96 h later or multiple daily injections with blood sampling 24 h after the last injection. Reticulocyte counting by microscopic examination was employed as the end-point using the brilliant cresyl blue or selective hemolysis methods, together with automated flow cytometry. Different injection schedules were investigated and dose-response curves for the European Pharmacopoeia Biological Reference Preparation of erythropoietin were compared. Manual and automated methods of reticulocyte counting were correlated with respect to assay validity and precision. Using 8 mice per treatment group, intra-assay precision determined for all of the assays in the study showed coefficients of variation of 12.1-28.4% for the brilliant cresyl blue method, 14.1-30.8% for the selective hemolysis method and 8.5-19.7% for the flow cytometry method. Applying the single injection protocol, a combination of at least two independent assays was required to achieve the precision potency and confidence limits indicated by the manufacturers, while the multiple daily injection protocol yielded the same acceptable results within a single assay. Although the latter protocol using flow cytometry for reticulocyte counting gave more precise and reproducible results (intra-assay coefficients of variation: 5.9-14.2%, the well-characterized manual methods provide equally valid alternatives for the quality control of recombinant human erythropoietin therapeutic products.

  16. Multiple sclerosis

    Stenager, Egon; Stenager, E N; Knudsen, Lone

    1994-01-01

    In a cross-sectional study of 117 randomly selected patients (52 men, 65 women) with definite multiple sclerosis, it was found that 76 percent were married or cohabitant, 8 percent divorced. Social contacts remained unchanged for 70 percent, but outgoing social contacts were reduced for 45 percent......, need for structural changes in home and need for pension became greater with increasing physical handicap. No significant differences between gender were found. It is concluded that patients and relatives are under increased social strain, when multiple sclerosis progresses to a moderate handicap...

  17. Catalytic hydrogen recombination for nuclear containments

    Koroll, G.W.; Lau, D.W.P.; Dewit, W.A.; Graham, W.R.C.

    1994-01-01

    Catalytic recombiners appear to be a credible option for hydrogen mitigation in nuclear containments. The passive operation, versatility and ease of back fitting are appealing for existing stations and new designs. Recently, a generation of wet-proofed catalyst materials have been developed at AECL which are highly specific to H 2 -O 2 , are active at ambient temperatures and are being evaluated for containment applications. Two types of catalytic recombiners were evaluated for hydrogen removal in containments based on the AECL catalyst. The first is a catalytic combustor for application in existing air streams such as provided by fans or ventilation systems. The second is an autocatalytic recombiner which uses the enthalpy of reaction to produce natural convective flow over the catalyst elements. Intermediate-scale results obtained in 6 m 3 and 10 m 3 spherical and cylindrical vessels are given to demonstrate self-starting limits, operating limits, removal capacity, scaling parameters, flow resistance, mixing behaviour in the vicinity of an operating recombiner and sensitivity to poisoning, fouling and radiation. (author). 13 refs., 10 figs

  18. Recombinant protein blends: silk beyond natural design.

    Dinjaski, Nina; Kaplan, David L

    2016-06-01

    Recombinant DNA technology and new material concepts are shaping future directions in biomaterial science for the design and production of the next-generation biomaterial platforms. Aside from conventionally used synthetic polymers, numerous natural biopolymers (e.g., silk, elastin, collagen, gelatin, alginate, cellulose, keratin, chitin, polyhydroxyalkanoates) have been investigated for properties and manipulation via bioengineering. Genetic engineering provides a path to increase structural and functional complexity of these biopolymers, and thereby expand the catalog of available biomaterials beyond that which exists in nature. In addition, the integration of experimental approaches with computational modeling to analyze sequence-structure-function relationships is starting to have an impact in the field by establishing predictive frameworks for determining material properties. Herein, we review advances in recombinant DNA-mediated protein production and functionalization approaches, with a focus on hybrids or combinations of proteins; recombinant protein blends or 'recombinamers'. We highlight the potential biomedical applications of fibrous protein recombinamers, such as Silk-Elastin Like Polypeptides (SELPs) and Silk-Bacterial Collagens (SBCs). We also discuss the possibility for the rationale design of fibrous proteins to build smart, stimuli-responsive biomaterials for diverse applications. We underline current limitations with production systems for these proteins and discuss the main trends in systems/synthetic biology that may improve recombinant fibrous protein design and production. Copyright © 2016. Published by Elsevier Ltd.

  19. Algae-based oral recombinant vaccines

    Specht, Elizabeth A.; Mayfield, Stephen P.

    2014-01-01

    Recombinant subunit vaccines are some of the safest and most effective vaccines available, but their high cost and the requirement of advanced medical infrastructure for administration make them impractical for many developing world diseases. Plant-based vaccines have shifted that paradigm by paving the way for recombinant vaccine production at agricultural scale using an edible host. However, enthusiasm for “molecular pharming” in food crops has waned in the last decade due to difficulty in developing transgenic crop plants and concerns of contaminating the food supply. Microalgae could be poised to become the next candidate in recombinant subunit vaccine production, as they present several advantages over terrestrial crop plant-based platforms including scalable and contained growth, rapid transformation, easily obtained stable cell lines, and consistent transgene expression levels. Algae have been shown to accumulate and properly fold several vaccine antigens, and efforts are underway to create recombinant algal fusion proteins that can enhance antigenicity for effective orally delivered vaccines. These approaches have the potential to revolutionize the way subunit vaccines are made and delivered – from costly parenteral administration of purified protein, to an inexpensive oral algae tablet with effective mucosal and systemic immune reactivity. PMID:24596570

  20. Correlations in the Parton Recombination Model

    Bass, S.A. [Department of Physics, Duke University, Durham, NC 27708-0305 (United States); RIKEN BNL Research Center, Brookhaven Nat. Lab., Upton, NY 11973 (United States); Fries, R.J. [School of Physics and Astronomy, Univ. of Minnesota, Minneapolis, MN 55455 (United States); Mueller, B. [Department of Physics, Duke University, Durham, NC 27708-0305 (United States)

    2006-08-07

    We describe how parton recombination can address the recent measurement of dynamical jet-like two particle correlations. In addition we discuss the possible effect realistic light-cone wave-functions including higher Fock-states may have on the well-known elliptic flow valence-quark number scaling law.

  1. Radiative recombination of excitons in amorphous semiconductors

    Singh, Jai [School of Engineering and Logistics, Faculty Technology, B-41, Charles Darwin University, Darwin, NT 0909 (Australia)]. E-mail: jai.singh@cdu.edu.au

    2005-04-15

    A theory for calculating the radiative lifetime of excitons in amorphous semiconductors is presented. Four possibilities of excitonic radiative recombination are considered and the corresponding rates are derived at thermal equilibrium. The radiative lifetime is calculated from the inverse of the maximum rate for all the four possibilities. Results agree very well with experiments.

  2. Precise genotyping and recombination detection of Enterovirus

    2015-01-01

    Enteroviruses (EV) with different genotypes cause diverse infectious diseases in humans and mammals. A correct EV typing result is crucial for effective medical treatment and disease control; however, the emergence of novel viral strains has impaired the performance of available diagnostic tools. Here, we present a web-based tool, named EVIDENCE (EnteroVirus In DEep conception, http://symbiont.iis.sinica.edu.tw/evidence), for EV genotyping and recombination detection. We introduce the idea of using mixed-ranking scores to evaluate the fitness of prototypes based on relatedness and on the genome regions of interest. Using phylogenetic methods, the most possible genotype is determined based on the closest neighbor among the selected references. To detect possible recombination events, EVIDENCE calculates the sequence distance and phylogenetic relationship among sequences of all sliding windows scanning over the whole genome. Detected recombination events are plotted in an interactive figure for viewing of fine details. In addition, all EV sequences available in GenBank were collected and revised using the latest classification and nomenclature of EV in EVIDENCE. These sequences are built into the database and are retrieved in an indexed catalog, or can be searched for by keywords or by sequence similarity. EVIDENCE is the first web-based tool containing pipelines for genotyping and recombination detection, with updated, built-in, and complete reference sequences to improve sensitivity and specificity. The use of EVIDENCE can accelerate genotype identification, aiding clinical diagnosis and enhancing our understanding of EV evolution. PMID:26678286

  3. Theory of dielectronic recombination and plasma effects

    Yukap Hahn

    2000-01-01

    Current status of the various theoretical approaches to calculation of dielectronic recombination rates is summarized, with emphasis on the available data base and on the plasma effects of both the plasma ion (and external) fields and plasma electron collisional effects which seriously affect the rates and complicate compilation of data. (author)

  4. Optimization, purification and characterization of recombinant L ...

    We studied optimal L-asparaginase sequence from GenBank accession number X12746 encoding for Lasparaginase from Erwinia chrysanthemi NCPPB1125. The expression level of recombinant Lasparaginase was determined as 78% of the total proteins. The purified L-asparaginase had a molecular mass of 37 kDa with ...

  5. Meiotic recombination hotspots - a comparative view.

    Choi, Kyuha; Henderson, Ian R

    2015-07-01

    During meiosis homologous chromosomes pair and undergo reciprocal genetic exchange, termed crossover. Meiotic recombination has a profound effect on patterns of genetic variation and is an important tool during crop breeding. Crossovers initiate from programmed DNA double-stranded breaks that are processed to form single-stranded DNA, which can invade a homologous chromosome. Strand invasion events mature into double Holliday junctions that can be resolved as crossovers. Extensive variation in the frequency of meiotic recombination occurs along chromosomes and is typically focused in narrow hotspots, observed both at the level of DNA breaks and final crossovers. We review methodologies to profile hotspots at different steps of the meiotic recombination pathway that have been used in different eukaryote species. We then discuss what these studies have revealed concerning specification of hotspot locations and activity and the contributions of both genetic and epigenetic factors. Understanding hotspots is important for interpreting patterns of genetic variation in populations and how eukaryotic genomes evolve. In addition, manipulation of hotspots will allow us to accelerate crop breeding, where meiotic recombination distributions can be limiting. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  6. Asthma and Therapeutics: Recombinant Therapies in Asthma

    Cockcroft Donald W

    2005-03-01

    Full Text Available Abstract Numerous recombinant therapies are being investigated for the treatment of asthma. This report reviews the current status of several of these novel agents. Anti-immunoglobulin (IgE (omalizumab, Xolair markedly inhibits all aspects of the allergen challenge in subjects who have reduction of free serum IgE to undetectable levels. Several clinical studies in atopic asthma have demonstrated benefit by improved symptoms and lung function and a reduction in corticosteroid requirements. Early use in atopic asthmatics may be even more effective. Several approaches target interleukin (IL-4. Soluble IL-4 receptor has been shown to effectively replace inhaled corticosteroid; further studies are under way. Recombinant anti-IL-5 and recombinant IL-12 inhibit blood and sputum eosinophils and allergen-induced eosinophilia without any effect on airway responsiveness, allergen-induced airway responses, or allergen-induced airway hyperresponsiveness. Efalizumab, a recombinant antibody that inhibits lymphocyte trafficking, is effective in psoriasis. A bronchoprovocation study showed a reduction in allergen-induced late asthmatic response and allergen-induced eosinophilia, which suggests that it should be effective in clinical asthma. These exciting novel therapies provide not only promise of new therapies for asthma but also valuable tools for investigation of asthma mechanisms.

  7. Recombination in disordered regions at semiconductors

    Artem'ev, V.A.; Mikhnovich, V.V.

    1987-01-01

    Theoretical estimates indicate the need to allow for the heating of carriers by the electrostatic field in disordered regions when studies are made of recombination properties. An analysis is made of the experiments in which the influence of heating on the properties of disordered regions may be manifested and experimentally verifiable effects of this influence are considered

  8. Dielectronic recombination of highly ionized iron

    Griffin, D.C.; Pindzola, M.S.

    1987-01-01

    Dielectronic recombination of the iron ions Fe/sup 15+/, Fe/sup 23+/, and Fe/sup 25+/ has been studied in the isolated-resonance, distorted-wave approximation. The cross-section calculations include the dielec- tronic transitions associated with the 3s→3l and 3s→4l excitations in Fe/sup 15+/, the 2s→2p and 2s→3l excitations in Fe/sup 23+/, and the 1s→2l excitations in Fe/sup 25+/. The effects of external electric fields have been included by employing intermediate-coupled, field-mixed eigenvectors for the doubly excited Rydberg states, determined by diagonalizing a Hamiltonian matrix which includes the internal electrostatic and spin-orbit terms, as well as the Stark matrix elements. The field effects are found to be quite large in Fe/sup 15+/, relatively small in Fe/sup 23+/, and negligible in Fe/sup 25+/. The calculations indicate that there are large resonances near threshold in Fe/sup 23+/ that are unaffected by external fields and may be measurable in new experiments currently being designed. In addition, the contributions of radiative recombination and the possible interference between radiative and dielectronic recombination in low-lying resonances are considered. Even though the radiative recombination cross sections may be appreciable near threshold in Fe/sup 15+/ and Fe/sup 23+/, the interference between these processes appears to be completely negligible

  9. Expression of recombinant Streptokinase from local Egyptian ...

    We reported for the first time the expression of a recombinant SK from a local Streptococcus strain. When produced on industrial scale this r-SK may substantially contribute to reducing the costs of thrombolytic therapy in developing countries. In this study, a highly purified r-SK from Streptococcus sp. isolated from Egyptian ...

  10. Algae-based oral recombinant vaccines

    Elizabeth A Specht

    2014-02-01

    Full Text Available Recombinant subunit vaccines are some of the safest and most effective vaccines available, but their high cost and the requirement of advanced medical infrastructure for administration make them impractical for many developing world diseases. Plant-based vaccines have shifted that paradigm by paving the way for recombinant vaccine production at agricultural scale using an edible host. However, enthusiasm for molecular pharming in food crops has waned in the last decade due to difficulty in developing transgenic crop plants and concerns of contaminating the food supply. Microalgae are poised to become the next candidate in recombinant subunit vaccine production, and they present several advantages over terrestrial crop plant-based platforms including scalable and contained growth, rapid transformation, easily obtained stable cell lines, and consistent transgene expression levels. Algae have been shown to accumulate and properly fold several vaccine antigens, and efforts are underway to create recombinant algal fusion proteins that can enhance antigenicity for effective orally-delivered vaccines. These approaches have the potential to revolutionize the way subunit vaccines are made and delivered – from costly parenteral administration of purified protein, to an inexpensive oral algae tablet with effective mucosal and system immune reactivity.

  11. Resonances in dissociative recombination: Trends and patterns

    Orel, A E; Ngassam, V; Royal, J [Department of Applied Science, University of California, Davis (United States); Roos, J B; Larson, A, E-mail: aeorel@ucdavis.ed [Department of Theoretical Chemistry, Royal Institute of Technology, Stockholm (Sweden)

    2009-11-15

    In dissociative recombination, the kinetic energy of the incident electron is transferred into excitation of the electrons of the target ion and then into kinetic energy of the fragments. In general, this proceeds via a resonance where the electron is temporarily trapped by the ion, leading to efficient energy transfer. The study of dissociative recombination is the study of these resonances, Rydberg states converging to the ground and excited states of the ion. For a number of systems, we have studied the electronic states involved in dissociative recombination, including the ground and excited states of the ion, the resonant states and the bound Rydberg states of the system, by combining electron scattering calculations with multi-reference configuration interaction quantum chemistry calculations. We will report on trends and patterns in these resonance states. We will discuss studies of dissociative recombination of the rare-gas ions, moving down the periodic table from He{sup +}{sub 2} to Ne{sup +}{sub 2} to Ar{sup +}{sub 2}, where the ground electronic state of the ion is constant, but its polarizability increases. We will also present results on isoelectronic polyatomic systems, such as HCO{sup +} and HCNH{sup +}, as well as the effects of changing the electronic structure slightly such as HCN{sup +}/HNC{sup +} and H{sub 2}CO{sup +}.

  12. Expression and characterization of recombinant ecarin.

    Jonebring, A.; Lange, U.; Bucha, E.; Deinum, J.; Elg, M.; Lovgren, A.

    2012-01-01

    The snake venom protease ecarin from Echis carinatus was expressed in stable transfected CHO-S cells grown in animal component free cell culture medium. Recombinant ecarin (r-ecarin) was secreted from the suspension adapted Chinese Hamster Ovary (CHO-S) host cells as a pro-protein and activation to

  13. Recombination times in germanium under high pressure

    Kuyt, J.H.

    1975-01-01

    The influence of pressure on a well defined recombination process was studied. The centres were introduced by γirradiation and the lifetime determined by the decay time of photoconductivity. An optical pressure vessel is described which allows for a hydrostatic variation of 3000 bars. The diffusion constant and lifetime measurements are presented and analysed. (V.J.C.)

  14. Gas recombination assembly for electrochemical cells

    Levy, Isaac; Charkey, Allen

    1989-01-01

    An assembly for recombining gases generated in electrochemical cells wherein a catalyst strip is enveloped within a hydrophobic, gas-porous film which, in turn, is encased between gas-porous, metallic layers. The sandwich construction of metallic layers and film is formed into a spiral with a tab for connection to the cell.

  15. Production, purification and characterization of two recombinant ...

    STORAGESEVER

    2008-06-17

    Jun 17, 2008 ... Two recombinant DNA-derived variants of ovine growth hormone were produced, purified, characterized and compared with the authentic pituitary derived GH. The variants oGH3 and oGH5 were isolated by differential centrifugation method and were purified after refolding by ion-exchange.

  16. Managing meiotic recombination in plant breeding

    Wijnker, T.G.; Jong, de J.H.S.G.M.

    2008-01-01

    Crossover recombination is a crucial process in plant breeding because it allows plant breeders to create novel allele combnations on chromosomes that can be used for breeding superior F1 hybrids. Gaining control over this process, in terms of increasing crossover incidence, altering crossover

  17. Radiative recombination of excitons in amorphous semiconductors

    Singh, Jai

    2005-01-01

    A theory for calculating the radiative lifetime of excitons in amorphous semiconductors is presented. Four possibilities of excitonic radiative recombination are considered and the corresponding rates are derived at thermal equilibrium. The radiative lifetime is calculated from the inverse of the maximum rate for all the four possibilities. Results agree very well with experiments

  18. Circulating water pumps for nuclear power stations

    Satoh, Hiroshi; Ohmori, Tsuneaki

    1979-01-01

    Shortly, the nuclear power station with unit power output of 1100 MW will begin the operation, and the circulating water pumps manufactured recently are those of 2.4 to 4 m bore, 840 to 2170 m 3 /min discharge and 2100 to 5100 kW driving power. The circulating water pumps are one of important auxiliary machines, because if they fail, power generation capacity lowers immediately. Enormous quantity of cooling water is required to cool condensers, therefore in Japan, sea water is usually used. As siphon is formed in circulating water pipes, the total head of the pumps is not very high. The discharge of the pumps is determined so as to keep the temperature rise of discharged water lower than 7 deg. C. The quantity of cooling water for nuclear power generation is about 50% more as compared with thermal power generation because of the difference in steam conditions. The total head of the pumps is normally from 8 to 15 m. The circulating water pumps rarely stop after they started the operation, therefore it is economical to determine the motor power so that it can withstand 10% overload for a short period, instead of large power. At present, vertical shaft, oblique flow circulating water pumps are usually employed. Recently, movable blade pumps are adopted. The installation, construction and materials of the pumps and the problems are described. (Kako, I.)

  19. Cascade of circulations in fluid turbulence.

    Eyink, Gregory L

    2006-12-01

    Kelvin's theorem on conservation of circulations is an essential ingredient of Taylor's theory of turbulent energy dissipation by the process of vortex-line stretching. In previous work, we have proposed a nonlinear mechanism for the breakdown of Kelvin's theorem in ideal turbulence at infinite Reynolds number. We develop here a detailed physical theory of this cascade of circulations. Our analysis is based upon an effective equation for large-scale coarse-grained velocity, which contains a turbulent-induced vortex force that can violate Kelvin's theorem. We show that singularities of sufficient strength, which are observed to exist in turbulent flow, can lead to nonvanishing dissipation of circulation for an arbitrarily small coarse-graining length in the effective equations. This result is an analog for circulation of Onsager's theorem on energy dissipation for singular Euler solutions. The physical mechanism of the breakdown of Kelvin's theorem is diffusion of lines of large-scale vorticity out of the advected loop. This phenomenon can be viewed as a classical analog of the Josephson-Anderson phase-slip phenomenon in superfluids due to quantized vortex lines. We show that the circulation cascade is local in scale and use this locality to develop concrete expressions for the turbulent vortex force by a multiscale gradient expansion. We discuss implications for Taylor's theory of turbulent dissipation and we point out some related cascade phenomena, in particular for magnetic flux in magnetohydrodynamic turbulence.

  20. Circulation as Assessment: Collection Development Policies Evaluated in Terms of Circulation at a Small Academic Library.

    Dinkins, Debbi

    2003-01-01

    Discusses the use of academic library circulation statistics to assess whether user needs are being met and describes a study at Stetson University that investigated collection development practices by comparing circulation statistics for books selected by faculty in support of departmental curricula with those of librarian selections. (Author/LRW)

  1. A neural network for the analysis of DIII-D charge exchange recombination data

    Baker, D.R.; Groebner, R.J.; Burrell, K.H.

    1994-01-01

    A neural network of the multiple-layer perceptron (MLP) type, named CERNEUR, has been created for the task of analysing the charge exchange recombination data from DIII-D for the purpose of providing control-room ion temperatures and rotation velocities between shots and, in the future, to provide initial guesses for the standard curve-fitting code. CERNEUR provides very useful 'control-room' in-between shot analysis of the rotation velocity and ion temperature profiles. (author)

  2. MODEST: a web-based design tool for oligonucleotide-mediated genome engineering and recombineering

    Bonde, Mads; Klausen, Michael Schantz; Anderson, Mads Valdemar

    2014-01-01

    Recombineering and multiplex automated genome engineering (MAGE) offer the possibility to rapidly modify multiple genomic or plasmid sites at high efficiencies. This enables efficient creation of genetic variants including both single mutants with specifically targeted modifications as well......, which confers the corresponding genetic change, is performed manually. To address these challenges, we have developed the MAGE Oligo Design Tool (MODEST). This web-based tool allows designing of MAGE oligos for (i) tuning translation rates by modifying the ribosomal binding site, (ii) generating...

  3. Some recent developments in the recombination model

    Hwa, R.C.

    1979-01-01

    A critical review of the recombination model for hadron production at low P/sub T/ is first given, emphasizing not so much the successes as unanswered questions that the model faces. A systematic program to answer some of the basic questions is then developed. The theoretical framework is quantum chromodynamics. First, in what may appear as a digression, the possibility of formation of valence quark clusters (called valons) in a nucleon due to gluon bremsstrahlung and quark-pair creation is considered. Evidences are found not only for the valons in neutrino scattering data, but also indications for their momentum distribution in a nucleon. When similar considerations are applied to a meson, the meaning of the recombination function is discussed and its normalization as well as its shape are determined. Next, the problem of quark decay in a hard scattering process (e.g., pion production in e + e - annihilation) is considered. The joint distribution of partons in a quark jet is determined in QCD. The quark decay function for pions in the recombination model is then obtained with excellent fit to the data. Similar investigation is applied to the problem of photoproduction of pions in the fragmentation region; again good agreement with data is achieved. The results indicate the reliability of the recombination model when the two-parton distributions can be calculated in QCD. Finally, hadron initiated reactions are considered. A duality between quark recombination and valon fragmentation is suggested. The picture is consistent with dual Regge model. A possible way to determine the inclusive distribution in the context of QCD is suggested

  4. Multiple myeloma

    Sohn, Jeong Ick; Ha, Choon Ho; Choi, Karp Shik

    1994-01-01

    Multiple myeloma is a malignant plasma cell tumor that is thought to originate proliferation of a single clone of abnormal plasma cell resulting production of a whole monoclonal paraprotein. The authors experienced a case of multiple myeloma with severe mandibular osteolytic lesions in 46-year-old female. As a result of careful analysis of clinical, radiological, histopathological features, and laboratory findings, we diagnosed it as multiple myeloma, and the following results were obtained. 1. Main clinical symptoms were intermittent dull pain on the mandibular body area, abnormal sensation of lip and pain due to the fracture on the right clavicle. 2. Laboratory findings revealed M-spike, reversed serum albumin-globulin ratio, markedly elevated ESR and hypercalcemia. 3. Radiographically, multiple osteolytic punched-out radiolucencies were evident on the skull, zygoma, jaw bones, ribs, clavicle and upper extremities. Enlarged liver and increased uptakes on the lesional sites in RN scan were also observed. 4. Histopathologically, markedly hypercellular marrow with sheets of plasmoblasts and megakaryocytes were also observed.

  5. Multiple sclerosis

    Stenager, E; Jensen, K

    1988-01-01

    Forty-two (12%) of a total of 366 patients with multiple sclerosis (MS) had psychiatric admissions. Of these, 34 (81%) had their first psychiatric admission in conjunction with or after the onset of MS. Classification by psychiatric diagnosis showed that there was a significant positive correlation...

  6. Multiple sclerosis

    Stenager, E; Knudsen, L; Jensen, K

    1991-01-01

    In a cross-sectional investigation of 116 patients with multiple sclerosis, the social and sparetime activities of the patient were assessed by both patient and his/her family. The assessments were correlated to physical disability which showed that particularly those who were moderately disabled...

  7. Multiple sclerosis

    Stenager, E; Jensen, K

    1990-01-01

    An investigation on the correlation between ability to read TV subtitles and the duration of visual evoked potential (VEP) latency in 14 patients with definite multiple sclerosis (MS), indicated that VEP latency in patients unable to read the TV subtitles was significantly delayed in comparison...

  8. Multiple sclerosis

    Stenager, E; Knudsen, L; Jensen, K

    1994-01-01

    In a cross-sectional study of 94 patients (42 males, 52 females) with definite multiple sclerosis (MS) in the age range 25-55 years, the correlation of neuropsychological tests with the ability to read TV-subtitles and with the use of sedatives is examined. A logistic regression analysis reveals...

  9. Multiple Sclerosis.

    Plummer, Nancy; Michael, Nancy, Ed.

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

  10. Parenting Multiples

    ... when your babies do. Though it can be hard to let go of the thousand other things you need to do, remember that your well-being is key to your ability to take care of your babies. What Problems Can Happen? It may be hard to tell multiple babies apart when they first ...

  11. Metabolite profiling of recombinant CHO cells: Designing tailored feeding regimes that enhance recombinant antibody production.

    Sellick, C.A.; Croxford, A.S.; Maqsood, A.R.; Stephens, G.; Westerhoff, H.V.; Goodacre, R.; Dickson, A.J.

    2011-01-01

    Chinese hamster ovary (CHO) cells are the primary platform for commercial expression of recombinant therapeutic proteins. Obtaining maximum production from the expression platform requires optimal cell culture medium (and associated nutrient feeds). We have used metabolite profiling to define the

  12. Metabolite profiling of recombinant CHO cells: designing tailored feeding regimes that enhance recombinant antibody production.

    Sellick, C.A.; Croxford, A.S.; Maqsood, A.R.; Stephens, G.; Westerhoff, H.V.; Goodacre, R.; Dickson, A.J.

    2011-01-01

    Chinese hamster ovary (CHO) cells are the primary platform for commercial expression of recombinant therapeutic proteins. Obtaining maximum production from the expression platform requires optimal cell culture medium (and associated nutrient feeds). We have used metabolite profiling to define the

  13. Sequence and recombination analyses of the geminivirus replication

    Prakash

    2006-09-18

    Sep 18, 2006 ... Recombination can provide selective advantage in the evolution of viruses .... Program (v 1.08): Recombination Detection Program (RDP). (Martin and Rybicki ..... Sweet potato leaf curl virus - [US:Louisiana:1994]. AF104036.

  14. New rifamycins produced by a recombinant strain of Nocardia mediterranei.

    Schupp, T; Traxler, P; Auden, J A

    1981-08-01

    A recombinant strain of Nocardia mediterranei was found to produce a number of new rifamycins which are structurally related to rifamycin S, rifamycin W and rifamycin G. This strain was derived from two Nocardia mediterranei mutants by intraspecific recombination.

  15. High recombination rate in natural populations of Plasmodium falciparum

    Conway, D. J.; Roper, C.; Oduola, A. M.; Arnot, D. E.; Kremsner, P. G.; Grobusch, M. P.; Curtis, C. F.; Greenwood, B. M.

    1999-01-01

    Malaria parasites are sexually reproducing protozoa, although the extent of effective meiotic recombination in natural populations has been debated. If meiotic recombination occurs frequently, compared with point mutation and mitotic rearrangement, linkage disequilibrium between polymorphic sites is

  16. Experimental study of the natural circulation phenomena

    Sabundjian, Gaiane; Andrade, Delvonei Alves de; Umbehaun, Pedro E.; Torres, Walmir M.; Castro, Alfredo Jose Alvim de; Belchior Junior, Antonio; Rocha, Ricardo Takeshi Vieira da; Damy, Osvaldo Luiz de Almeida; Torres, Eduardo

    2006-01-01

    The objective of this paper is to study the natural circulation in experimental loops and extend the results to nuclear facilities. New generation of compact nuclear power plants use the natural circulation as cooling and residual heat removal systems in case of accidents or shutdown. Lately the interest in this phenomenon, by scientific community, has increased. The experimental loop, described in this paper, was assembled at Escola Politecnica - USP at the Chemical Engineering Department. It is the goal to generate information to help with the understanding of the one and two phase natural circulation phenomena. Some experiments were performed with different levels of heat power and different flow of the cooling water at the secondary circuit. The data generated from these experiments are going to be used to validate some computational thermal hydraulic codes. Experimental results for one and two phase regimes are presented as well as the proposed model to simulate the flow regimes with the RELAP5 code. (author)

  17. Systems engineering requirements impacting MHTGR circulator design

    Chi, H.W.; Baccaglini, G.M.; Potter, R.C.; Shenoy, A.S.

    1988-01-01

    At the initiation of the MHTGR program, an important task involved translating the plant users' requirements into design conditions. This was particularly true in the case of the heat transport and shutdown cooling systems since these embody many components. This paper addresses the two helium circulators in these systems. An integrated approach is being used in the development of design and design documentation for the MHTGR plant. It is an organized and systematic development of plant functions and requirements, determined by top-down design, performance, and cost trade-off studies and analyses, to define the overall plant systems, subsystems, components, and human actions. These studies, that led to the identification of the major design parameters for the two circulators, are discussed in this paper. This includes the performance information, steady state and transient data, and the various interface requirements. The design of the circulators used in the MHTGR is presented. (author). 1 ref., 17 figs

  18. Circulating microRNAs in breast cancer

    Hamam, Rimi; Hamam, Dana; Alsaleh, Khalid A

    2017-01-01

    Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence in ...... circulating miRNAs as diagnostic, prognostic or predictive biomarkers in breast cancer management.......Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence...... in the past several years has highlighted the potential use of peripheral blood circulating nucleic acids such as DNA, mRNA and micro (mi)RNA in breast cancer diagnosis, prognosis and for monitoring response to anticancer therapy. Among these, circulating miRNA is increasingly recognized as a promising...

  19. Adjustable speed drives improve circulating water system

    Dent, R.A.; Dicic, Z.

    1994-01-01

    This paper illustrates the integration of electrical and mechanical engineering requirements to produce a solution to past problems and future operating demands. The application of adjustable speed drives in the modifications of the circulating water system at Indian Point No. 3 Nuclear Power Plant provided increased operating flexibility, efficiency and avoided otherwise costly renovations to the plant electrical systems. Rectification of the original inadequate design of the circulating water system, in addition to maximizing plant efficiency consistent with environmental considerations, formed the basis for this modification. This entailed replacement of all six circulating water pumps and motors and physical modifications to the intake system. This paper details the methodology used in this engineering task. The new system was installed successfully and has been operating reliably and economically for the past eight years

  20. Caenorhabditis briggsae recombinant inbred line genotypes reveal inter-strain incompatibility and the evolution of recombination.

    Joseph A Ross

    2011-07-01

    Full Text Available The nematode Caenorhabditis briggsae is an emerging model organism that allows evolutionary comparisons with C. elegans and exploration of its own unique biological attributes. To produce a high-resolution C. briggsae recombination map, recombinant inbred lines were generated from reciprocal crosses between two strains and genotyped at over 1,000 loci. A second set of recombinant inbred lines involving a third strain was also genotyped at lower resolution. The resulting recombination maps exhibit discrete domains of high and low recombination, as in C. elegans, indicating these are a general feature of Caenorhabditis species. The proportion of a chromosome's physical size occupied by the central, low-recombination domain is highly correlated between species. However, the C. briggsae intra-species comparison reveals striking variation in the distribution of recombination between domains. Hybrid lines made with the more divergent pair of strains also exhibit pervasive marker transmission ratio distortion, evidence of selection acting on hybrid genotypes. The strongest effect, on chromosome III, is explained by a developmental delay phenotype exhibited by some hybrid F2 animals. In addition, on chromosomes IV and V, cross direction-specific biases towards one parental genotype suggest the existence of cytonuclear epistatic interactions. These interactions are discussed in relation to surprising mitochondrial genome polymorphism in C. briggsae, evidence that the two strains diverged in allopatry, the potential for local adaptation, and the evolution of Dobzhansky-Muller incompatibilities. The genetic and genomic resources resulting from this work will support future efforts to understand inter-strain divergence as well as facilitate studies of gene function, natural variation, and the evolution of recombination in Caenorhabditis nematodes.

  1. Evolution of recombination in eutherian mammals: insights into mechanisms that affect recombination rates and crossover interference

    Segura, Joana; Ferretti, Luca; Ramos-Onsins, Sebastián; Capilla, Laia; Farré, Marta; Reis, Fernanda; Oliver-Bonet, Maria; Fernández-Bellón, Hugo; Garcia, Francisca; Garcia-Caldés, Montserrat; Robinson, Terence J.; Ruiz-Herrera, Aurora

    2013-01-01

    Recombination allows faithful chromosomal segregation during meiosis and contributes to the production of new heritable allelic variants that are essential for the maintenance of genetic diversity. Therefore, an appreciation of how this variation is created and maintained is of critical importance to our understanding of biodiversity and evolutionary change. Here, we analysed the recombination features from species representing the major eutherian taxonomic groups Afrotheria, Rodentia, Primat...

  2. A systematic investigation of production of synthetic prions from recombinant prion protein.

    Schmidt, Christian; Fizet, Jeremie; Properzi, Francesca; Batchelor, Mark; Sandberg, Malin K; Edgeworth, Julie A; Afran, Louise; Ho, Sammy; Badhan, Anjna; Klier, Steffi; Linehan, Jacqueline M; Brandner, Sebastian; Hosszu, Laszlo L P; Tattum, M Howard; Jat, Parmjit; Clarke, Anthony R; Klöhn, Peter C; Wadsworth, Jonathan D F; Jackson, Graham S; Collinge, John

    2015-12-01

    According to the protein-only hypothesis, infectious mammalian prions, which exist as distinct strains with discrete biological properties, consist of multichain assemblies of misfolded cellular prion protein (PrP). A critical test would be to produce prion strains synthetically from defined components. Crucially, high-titre 'synthetic' prions could then be used to determine the structural basis of infectivity and strain diversity at the atomic level. While there have been multiple reports of production of prions from bacterially expressed recombinant PrP using various methods, systematic production of high-titre material in a form suitable for structural analysis remains a key goal. Here, we report a novel high-throughput strategy for exploring a matrix of conditions, additives and potential cofactors that might generate high-titre prions from recombinant mouse PrP, with screening for infectivity using a sensitive automated cell-based bioassay. Overall, approximately 20,000 unique conditions were examined. While some resulted in apparently infected cell cultures, this was transient and not reproducible. We also adapted published methods that reported production of synthetic prions from recombinant hamster PrP, but again did not find evidence of significant infectious titre when using recombinant mouse PrP as substrate. Collectively, our findings are consistent with the formation of prion infectivity from recombinant mouse PrP being a rare stochastic event and we conclude that systematic generation of prions from recombinant PrP may only become possible once the detailed structure of authentic ex vivo prions is solved. © 2015 The Authors.

  3. A Rapid and Improved Method to Generate Recombinant Dengue Virus Vaccine Candidates.

    Govindarajan, Dhanasekaran; Guan, Liming; Meschino, Steven; Fridman, Arthur; Bagchi, Ansu; Pak, Irene; ter Meulen, Jan; Casimiro, Danilo R; Bett, Andrew J

    2016-01-01

    Dengue is one of the most important mosquito-borne infections accounting for severe morbidity and mortality worldwide. Recently, the tetravalent chimeric live attenuated Dengue vaccine Dengvaxia® was approved for use in several dengue endemic countries. In general, live attenuated vaccines (LAV) are very efficacious and offer long-lasting immunity against virus-induced disease. Rationally designed LAVs can be generated through reverse genetics technology, a method of generating infectious recombinant viruses from full length cDNA contained in bacterial plasmids. In vitro transcribed (IVT) viral RNA from these infectious clones is transfected into susceptible cells to generate recombinant virus. However, the generation of full-length dengue virus cDNA clones can be difficult due to the genetic instability of viral sequences in bacterial plasmids. To circumvent the need for a single plasmid containing a full length cDNA, in vitro ligation of two or three cDNA fragments contained in separate plasmids can be used to generate a full-length dengue viral cDNA template. However, in vitro ligation of multiple fragments often yields low quality template for IVT reactions, resulting in inconsistent low yield RNA. These technical difficulties make recombinant virus recovery less efficient. In this study, we describe a simple, rapid and efficient method of using LONG-PCR to recover recombinant chimeric Yellow fever dengue (CYD) viruses as potential dengue vaccine candidates. Using this method, we were able to efficiently generate several viable recombinant viruses without introducing any artificial mutations into the viral genomes. We believe that the techniques reported here will enable rapid and efficient recovery of recombinant flaviviruses for evaluation as vaccine candidates and, be applicable to the recovery of other RNA viruses.

  4. A Rapid and Improved Method to Generate Recombinant Dengue Virus Vaccine Candidates.

    Dhanasekaran Govindarajan

    Full Text Available Dengue is one of the most important mosquito-borne infections accounting for severe morbidity and mortality worldwide. Recently, the tetravalent chimeric live attenuated Dengue vaccine Dengvaxia® was approved for use in several dengue endemic countries. In general, live attenuated vaccines (LAV are very efficacious and offer long-lasting immunity against virus-induced disease. Rationally designed LAVs can be generated through reverse genetics technology, a method of generating infectious recombinant viruses from full length cDNA contained in bacterial plasmids. In vitro transcribed (IVT viral RNA from these infectious clones is transfected into susceptible cells to generate recombinant virus. However, the generation of full-length dengue virus cDNA clones can be difficult due to the genetic instability of viral sequences in bacterial plasmids. To circumvent the need for a single plasmid containing a full length cDNA, in vitro ligation of two or three cDNA fragments contained in separate plasmids can be used to generate a full-length dengue viral cDNA template. However, in vitro ligation of multiple fragments often yields low quality template for IVT reactions, resulting in inconsistent low yield RNA. These technical difficulties make recombinant virus recovery less efficient. In this study, we describe a simple, rapid and efficient method of using LONG-PCR to recover recombinant chimeric Yellow fever dengue (CYD viruses as potential dengue vaccine candidates. Using this method, we were able to efficiently generate several viable recombinant viruses without introducing any artificial mutations into the viral genomes. We believe that the techniques reported here will enable rapid and efficient recovery of recombinant flaviviruses for evaluation as vaccine candidates and, be applicable to the recovery of other RNA viruses.

  5. A new set of BXD recombinant inbred lines from advanced intercross populations in mice

    Gu Jing

    2004-04-01

    Full Text Available Abstract Background Recombinant inbred (RI strains are an important resource for mapping complex traits in many species. While large RI panels are available for Arabidopsis, maize, C. elegans, and Drosophila, mouse RI panels typically consist of fewer than 30 lines. This is a severe constraint on the power and precision of mapping efforts and greatly hampers analysis of epistatic interactions. Results In order to address these limitations and to provide the community with a more effective collaborative RI mapping panel we generated new BXD RI strains from two independent advanced intercrosses (AI between C57BL/6J (B6 and DBA/2J (D2 progenitor strains. Progeny were intercrossed for 9 to 14 generations before initiating inbreeding, which is still ongoing for some strains. Since this AI base population is highly recombinant, the 46 advanced recombinant inbred (ARI strains incorporate approximately twice as many recombinations as standard RI strains, a fraction of which are inevitably shared by descent. When combined with the existing BXD RI strains, the merged BXD strain set triples the number of previously available unique recombinations and quadruples the total number of recombinations in the BXD background. Conclusion The combined BXD strain set is the largest mouse RI mapping panel. It is a powerful tool for collaborative analysis of quantitative traits and gene function that will be especially useful to study variation in transcriptome and proteome data sets under multiple environments. Additional strains also extend the value of the extensive phenotypic characterization of the previously available strains. A final advantage of expanding the BXD strain set is that both progenitors have been sequenced, and approximately 1.8 million SNPs have been characterized. This provides unprecedented power in screening candidate genes and can reduce the effective length of QTL intervals. It also makes it possible to reverse standard mapping strategies and

  6. A functional analysis of the spacer of V(DJ recombination signal sequences.

    Alfred Ian Lee

    2003-10-01

    Full Text Available During lymphocyte development, V(DJ recombination assembles antigen receptor genes from component V, D, and J gene segments. These gene segments are flanked by a recombination signal sequence (RSS, which serves as the binding site for the recombination machinery. The murine Jbeta2.6 gene segment is a recombinationally inactive pseudogene, but examination of its RSS reveals no obvious reason for its failure to recombine. Mutagenesis of the Jbeta2.6 RSS demonstrates that the sequences of the heptamer, nonamer, and spacer are all important. Strikingly, changes solely in the spacer sequence can result in dramatic differences in the level of recombination. The subsequent analysis of a library of more than 4,000 spacer variants revealed that spacer residues of particular functional importance are correlated with their degree of conservation. Biochemical assays indicate distinct cooperation between the spacer and heptamer/nonamer along each step of the reaction pathway. The results suggest that the spacer serves not only to ensure the appropriate distance between the heptamer and nonamer but also regulates RSS activity by providing additional RAG:RSS interaction surfaces. We conclude that while RSSs are defined by a "digital" requirement for absolutely conserved nucleotides, the quality of RSS function is determined in an "analog" manner by numerous complex interactions between the RAG proteins and the less-well conserved nucleotides in the heptamer, the nonamer, and, importantly, the spacer. Those modulatory effects are accurately predicted by a new computational algorithm for "RSS information content." The interplay between such binary and multiplicative modes of interactions provides a general model for analyzing protein-DNA interactions in various biological systems.

  7. A functional analysis of the spacer of V(D)J recombination signal sequences.

    Lee, Alfred Ian; Fugmann, Sebastian D; Cowell, Lindsay G; Ptaszek, Leon M; Kelsoe, Garnett; Schatz, David G

    2003-10-01

    During lymphocyte development, V(D)J recombination assembles antigen receptor genes from component V, D, and J gene segments. These gene segments are flanked by a recombination signal sequence (RSS), which serves as the binding site for the recombination machinery. The murine Jbeta2.6 gene segment is a recombinationally inactive pseudogene, but examination of its RSS reveals no obvious reason for its failure to recombine. Mutagenesis of the Jbeta2.6 RSS demonstrates that the sequences of the heptamer, nonamer, and spacer are all important. Strikingly, changes solely in the spacer sequence can result in dramatic differences in the level of recombination. The subsequent analysis of a library of more than 4,000 spacer variants revealed that spacer residues of particular functional importance are correlated with their degree of conservation. Biochemical assays indicate distinct cooperation between the spacer and heptamer/nonamer along each step of the reaction pathway. The results suggest that the spacer serves not only to ensure the appropriate distance between the heptamer and nonamer but also regulates RSS activity by providing additional RAG:RSS interaction surfaces. We conclude that while RSSs are defined by a "digital" requirement for absolutely conserved nucleotides, the quality of RSS function is determined in an "analog" manner by numerous complex interactions between the RAG proteins and the less-well conserved nucleotides in the heptamer, the nonamer, and, importantly, the spacer. Those modulatory effects are accurately predicted by a new computational algorithm for "RSS information content." The interplay between such binary and multiplicative modes of interactions provides a general model for analyzing protein-DNA interactions in various biological systems.

  8. Natural circulation in a scaled PWR integral test facility

    Kiang, R.L.; Jeuck, P.R. III

    1987-01-01

    Natural circulation is an important mechanism for cooling a nuclear power plant under abnormal operating conditions. To study natural circulation, we modeled a type of pressurized water reactor (PWR) that incorporates once-through steam generators. We conducted tests of single-phase natural circulations, two-phase natural circulations, and a boiler condenser mode. Because of complex geometry, the natural circulations observed in this facility exhibit some phenomena not commonly seen in a simple thermosyphon loop

  9. Experimental study of natural circulation circuit

    Lemos, Wanderley F.; Su, Jian, E-mail: wlemos@lasme.coppe.ufrj.br, E-mail: sujian@lasme.coppe.ufrj.br [Coordenacao dos Programas de Pos-Graduacao de Engenharia (LASME/COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Lab. de Simulacao e Metodos Numericos; Faccini, Jose L.H., E-mail: faccini@ien.gov.br [Instituto de Engenharia Nuclear (LTE/IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Lab. de Termo-Hidraulica Experimental

    2011-07-01

    This work presents an experimental study about fluid flows behavior in natural circulation, under conditions of single-phase flow. The experiment was performed through experimental thermal-hydraulic circuit built at IEN. This test equipment has performance similar to passive system of residual heat removal present in Advanced Pressurized Water Reactors (APWR). This experimental study aims to observing and analyzing the natural circulation phenomenon, using this experimental circuit that was dimensioned and built based on concepts of similarity and scale. This philosophy allows the analysis of natural circulation behavior in single-phase flow conditions proportionally to the functioning real conditions of a nuclear reactor. The experiment was performed through procedures to initialization of hydraulic feeding of primary and secondary circuits and electrical energizing of resistors installed inside heater. Power controller has availability to adjust values of electrical power to feeding resistors, in order to portray several conditions of energy decay of nuclear reactor in a steady state. Data acquisition system allows the measurement and monitoring of the evolution of the temperature in various points through thermocouples installed in strategic points along hydraulic circuit. The behavior of the natural circulation phenomenon was monitored by graphical interface on computer screen, showing the temperature evolutions of measuring points and results stored in digital spreadsheets. The results stored in digital spreadsheets allowed the getting of data to graphic construction and discussion about natural circulation phenomenon. Finally, the calculus of Reynolds number allowed the establishment for a correlation of friction in function of geometric scales of length, heights and cross section of tubing, considering a natural circulation flow throughout in the region of hot leg. (author)

  10. Fort St. Vrain circulator operating experience

    Brey, H. L.

    1988-08-15

    Fort St. Vrain, on the system of Public Service Company of Colorado, is the only high-temperature gas-cooled power reactor in the United States. Four helium circulators are utilized in this plant to transfer heat from the reactor to the steam generators. These unique machines have a single stage axial flow helium compressor driven by a single stage steam turbine. A single stage water driven (pelton wheel) turbine is the back-up drive utilizing either feed water, condensate, or fire water as the driving fluid. Developmental testing of the circulators was accomplished prior to installation into Fort St. Vrain. A combined machine operating history of approximately 250,000 hours has shown these machines to be of conservative design and proven mechanical integrity. However, many problems have been encountered in operating the complex auxiliaries which are necessary for successful circulator and plant operation. It has been 15 years since initial installation of the circulators occurred at Fort St. Vrain. During this time, a number of significant issues had to be resolved dealing specifically with machine performance. These events include cavitation damage of the pelton wheels during the initial plant hot functional testing, cracks in the water turbine buckets and cervic coupling, static shutdown seal bellows failure, and, most recently, degradation of components within the steam drive assembly. Unreliable operation particularly with the circulator auxiliaries has been a focus of attention by Public Service Company of Colorado. Actions to replace or significantly modify the existing circulators and their auxiliaries are currently awaiting decisions concerning the long-term future of the Fort St. Vrain plant. (author). 10 refs, 7 figs, 2 tabs.

  11. Experimental study of natural circulation circuit

    Lemos, Wanderley F.; Su, Jian; Faccini, Jose L.H.

    2011-01-01

    This work presents an experimental study about fluid flows behavior in natural circulation, under conditions of single-phase flow. The experiment was performed through experimental thermal-hydraulic circuit built at IEN. This test equipment has performance similar to passive system of residual heat removal present in Advanced Pressurized Water Reactors (APWR). This experimental study aims to observing and analyzing the natural circulation phenomenon, using this experimental circuit that was dimensioned and built based on concepts of similarity and scale. This philosophy allows the analysis of natural circulation behavior in single-phase flow conditions proportionally to the functioning real conditions of a nuclear reactor. The experiment was performed through procedures to initialization of hydraulic feeding of primary and secondary circuits and electrical energizing of resistors installed inside heater. Power controller has availability to adjust values of electrical power to feeding resistors, in order to portray several conditions of energy decay of nuclear reactor in a steady state. Data acquisition system allows the measurement and monitoring of the evolution of the temperature in various points through thermocouples installed in strategic points along hydraulic circuit. The behavior of the natural circulation phenomenon was monitored by graphical interface on computer screen, showing the temperature evolutions of measuring points and results stored in digital spreadsheets. The results stored in digital spreadsheets allowed the getting of data to graphic construction and discussion about natural circulation phenomenon. Finally, the calculus of Reynolds number allowed the establishment for a correlation of friction in function of geometric scales of length, heights and cross section of tubing, considering a natural circulation flow throughout in the region of hot leg. (author)

  12. Fort St. Vrain circulator operating experience

    Brey, H.L.

    1988-01-01

    Fort St. Vrain, on the system of Public Service Company of Colorado, is the only high-temperature gas-cooled power reactor in the United States. Four helium circulators are utilized in this plant to transfer heat from the reactor to the steam generators. These unique machines have a single stage axial flow helium compressor driven by a single stage steam turbine. A single stage water driven (pelton wheel) turbine is the back-up drive utilizing either feed water, condensate, or fire water as the driving fluid. Developmental testing of the circulators was accomplished prior to installation into Fort St. Vrain. A combined machine operating history of approximately 250,000 hours has shown these machines to be of conservative design and proven mechanical integrity. However, many problems have been encountered in operating the complex auxiliaries which are necessary for successful circulator and plant operation. It has been 15 years since initial installation of the circulators occurred at Fort St. Vrain. During this time, a number of significant issues had to be resolved dealing specifically with machine performance. These events include cavitation damage of the pelton wheels during the initial plant hot functional testing, cracks in the water turbine buckets and cervic coupling, static shutdown seal bellows failure, and, most recently, degradation of components within the steam drive assembly. Unreliable operation particularly with the circulator auxiliaries has been a focus of attention by Public Service Company of Colorado. Actions to replace or significantly modify the existing circulators and their auxiliaries are currently awaiting decisions concerning the long-term future of the Fort St. Vrain plant. (author). 10 refs, 7 figs, 2 tabs

  13. Controlling meiotic recombinational repair - specifying the roles of ZMMs, Sgs1 and Mus81/Mms4 in crossover formation.

    Ashwini Oke

    2014-10-01

    Full Text Available Crossovers (COs play a critical role in ensuring proper alignment and segregation of homologous chromosomes during meiosis. How the cell balances recombination between CO vs. noncrossover (NCO outcomes is not completely understood. Further lacking is what constrains the extent of DNA repair such that multiple events do not arise from a single double-strand break (DSB. Here, by interpreting signatures that result from recombination genome-wide, we find that synaptonemal complex proteins promote crossing over in distinct ways. Our results suggest that Zip3 (RNF212 promotes biased cutting of the double Holliday-junction (dHJ intermediate whereas surprisingly Msh4 does not. Moreover, detailed examination of conversion tracts in sgs1 and mms4-md mutants reveal distinct aberrant recombination events involving multiple chromatid invasions. In sgs1 mutants, these multiple invasions are generally multichromatid involving 3-4 chromatids; in mms4-md mutants the multiple invasions preferentially resolve into one or two chromatids. Our analysis suggests that Mus81/Mms4 (Eme1, rather than just being a minor resolvase for COs is crucial for both COs and NCOs in preventing chromosome entanglements by removing 3'- flaps to promote second-end capture. Together our results force a reevaluation of how key recombination enzymes collaborate to specify the outcome of meiotic DNA repair.

  14. Recombination Is a Major Driving Force of Genetic Diversity in the Anaplasmataceae Ehrlichia ruminantium.

    Cangi, Nídia; Gordon, Jonathan L; Bournez, Laure; Pinarello, Valérie; Aprelon, Rosalie; Huber, Karine; Lefrançois, Thierry; Neves, Luís; Meyer, Damien F; Vachiéry, Nathalie

    2016-01-01

    The disease, Heartwater, caused by the Anaplasmataceae E. ruminantium , represents a major problem for tropical livestock and wild ruminants. Up to now, no effective vaccine has been available due to a limited cross protection of vaccinal strains on field strains and a high genetic diversity of Ehrlichia ruminantium within geographical locations. To address this issue, we inferred the genetic diversity and population structure of 194 E. ruminantium isolates circulating worldwide using Multilocus Sequence Typing based on lipA, lipB, secY, sodB , and sucA genes . Phylogenetic trees and networks were generated using BEAST and SplitsTree, respectively, and recombination between the different genetic groups was tested using the PHI test for recombination. Our study reveals the repeated occurrence of recombination between E. ruminantium strains, suggesting that it may occur frequently in the genome and has likely played an important role in the maintenance of genetic diversity and the evolution of E. ruminantium . Despite the unclear phylogeny and phylogeography, E. ruminantium isolates are clustered into two main groups: Group 1 (West Africa) and a Group 2 (worldwide) which is represented by West, East, and Southern Africa, Indian Ocean, and Caribbean strains. Some sequence types are common between West Africa and Caribbean and between Southern Africa and Indian Ocean strains. These common sequence types highlight two main introduction events due to the movement of cattle: from West Africa to Caribbean and from Southern Africa to the Indian Ocean islands. Due to the long branch lengths between Group 1 and Group 2, and the propensity for recombination between these groups, it seems that the West African clusters of Subgroup 2 arrived there more recently than the original divergence of the two groups, possibly with the original waves of domesticated ruminants that spread across the African continent several thousand years ago.

  15. Quenching phenomena in natural circulation loop

    Umekawa, Hisashi; Ozawa, Mamoru; Ishida, Naoki

    1995-01-01

    Quenching phenomena has been investigated experimentally using circulation loop of liquid nitrogen. During the quenching under natural circulation, the heat transfer mode changes from film boiling to nucleate boiling, and at the same time flux changes with time depending on the vapor generation rate and related two-phase flow characteristics. Moreover, density wave oscillations occur under a certain operating condition, which is closely related to the dynamic behavior of the cooling curve. The experimental results indicates that the occurrence of the density wave oscillation induces the deterioration of effective cooling of the heat surface in the film and the transition boiling regions, which results in the decrease in the quenching velocity

  16. Labour circulation and the urban labour process.

    Standing, G

    1986-01-01

    The author investigates aspects of labor circulation, which he defines as "temporary movement between geographical areas for work or in search of work....[He attempts to determine] what roles have been played by labour circulation in the development of urban-industrial labour forces in the transition to industrial capitalism." Factors considered include the exploitation and oppression of labor migrants; the industrial-urban labor reserve; urban socioeconomic stratification and discrimination by age, sex, or race; the division of labor; and policy options. excerpt

  17. An elementary model of money circulation

    Pokrovskii, Vladimir N.; Schinckus, Christophe

    2016-12-01

    This paper investigates money circulation for a system, consisting of a production system, the government, a central bank, commercial banks and many customers of the commercial banks. A set of equations for the system is written; the theory determines the main features of interaction between production and money circulation. Investigation of the equations in a steady-state situation reveals some relationship among output of the production system and monetary variables. The relation of quantity theory of money is confirmed, whereas a new concept of the efficiency of the system is introduced.

  18. Engineering Judgment and Natural Circulation Calculations

    Ferreri, J.C.; Ferreri, J.C.

    2011-01-01

    The analysis performed to establish the validity of computer code results in the particular field of natural circulation flow stability calculations is presented in the light of usual engineering practice. The effects of discretization and closure correlations are discussed and some hints to avoid undesired mistakes in the evaluations performed are given. Additionally, the results are presented for an experiment relevant to the way in which a (small) number of skilled, nuclear safety analysts and researchers react when facing the solution of a natural circulation problem. These results may be also framed in the concept of Engineering Judgment and are potentially useful for Knowledge Management activities.

  19. First circulating beam in the AA

    CERN PhotoLab

    1980-01-01

    On 3 July 1980, two years after project authorization, beam circulated for the first time in the AA. It was a 3.56 GeV/c proton test beam. We see an expecting crowd, minutes before the happy event. The persons are too numerous to name them all, but the 3 most prominent ones are at the centre (left to right): Roy Billinge (Joint AA Project Leader, with his hand on the control box), Eifionydd Jones (white shirt), Simon van der Meer (spiritus rector and Joint AA Project Leader). The first antiprotons were injected, made to circulate and cooled soon after, on 14 July 1980.

  20. Quenching phenomena in natural circulation loop

    Umekawa, Hisashi; Ozawa, Mamoru [Kansai Univ., Osaka (Japan); Ishida, Naoki [Daihatsu Motor Company, Osaka (Japan)

    1995-09-01

    Quenching phenomena has been investigated experimentally using circulation loop of liquid nitrogen. During the quenching under natural circulation, the heat transfer mode changes from film boiling to nucleate boiling, and at the same time flux changes with time depending on the vapor generation rate and related two-phase flow characteristics. Moreover, density wave oscillations occur under a certain operating condition, which is closely related to the dynamic behavior of the cooling curve. The experimental results indicates that the occurrence of the density wave oscillation induces the deterioration of effective cooling of the heat surface in the film and the transition boiling regions, which results in the decrease in the quenching velocity.

  1. Immunogenicity of mumps virus vaccine candidates matching circulating genotypes in the United States and China.

    Zengel, James; Phan, Shannon I; Pickar, Adrian; Xu, Pei; He, Biao

    2017-07-13

    Mumps virus (MuV) causes acute infection in humans with characteristic swelling of the parotid gland. While vaccination has greatly reduced the incidence of MuV infection, there have been multiple large outbreaks of mumps virus (MuV) in highly vaccinated populations. The most common vaccine strain, Jeryl Lynn, belongs to genotype A, which is no longer a circulating genotype. We have developed two vaccine candidates that match the circulating genotypes in the United States (genotype G) and China (genotype F). We found that there was a significant decrease in the ability of the Jeryl Lynn vaccine to produce neutralizing antibody responses to non-matched viruses, when compared to either of our vaccine candidates. Our data suggests that an updated vaccine may allow for better immunity against the circulating MuV genotypes G and F. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Atmospheric Diabatic Heating in Different Weather States and the General Circulation

    Rossow, William B.; Zhang, Yuanchong; Tselioudis, George

    2016-01-01

    Analysis of multiple global satellite products identifies distinctive weather states of the atmosphere from the mesoscale pattern of cloud properties and quantifies the associated diabatic heating/cooling by radiative flux divergence, precipitation, and surface sensible heat flux. The results show that the forcing for the atmospheric general circulation is a very dynamic process, varying strongly at weather space-time scales, comprising relatively infrequent, strong heating events by ''stormy'' weather and more nearly continuous, weak cooling by ''fair'' weather. Such behavior undercuts the value of analyses of time-averaged energy exchanges in observations or numerical models. It is proposed that an analysis of the joint time-related variations of the global weather states and the general circulation on weather space-time scales might be used to establish useful ''feedback like'' relationships between cloud processes and the large-scale circulation.

  3. Development of a lectin binding assay to differentiate between recombinant and endogenous proteins in pharmacokinetic studies of protein-biopharmaceuticals.

    Weber, Alfred; Minibeck, Eva; Scheiflinger, Friedrich; Turecek, Peter L

    2015-04-10

    Human glycoproteins, expressed in hamster cell lines, show similar glycosylation patterns to naturally occurring human molecules except for a minute difference in the linkage of terminal sialic acid: both cell types lack α2,6-galactosyl-sialyltransferase, abundantly expressed in human hepatocytes and responsible for the α2,6-sialylation of circulating glycoproteins. This minute difference, which is currently not known to have any physiological relevance, was the basis for the selective measurement of recombinant glycoproteins in the presence of their endogenous counterparts. The assay is based on using the lectin Sambucus nigra agglutinin (SNA), selectively binding to α2,6-sialylated N-glycans. Using von Willebrand factor (VWF), factor IX (FIX), and factor VIIa (FVIIa), it was demonstrated that (i) the plasma-derived proteins, but not the corresponding recombinant proteins, specifically bind to SNA and (ii) this binding can be used to deplete the plasma-derived proteins. The feasibility of this approach was confirmed in spike-recovery studies for all three recombinant coagulation proteins in human plasma and for recombinant VWF (rVWF) in macaque plasma. Analysis of plasma samples from macaques after administration of recombinant and a plasma-derived VWF demonstrated the suitability and robustness of this approach. Data showed that rVWF could be selectively measured without changing the ELISAs and furthermore revealed the limitations of baseline adjustment using a single measurement of the predose concentration only. The SNA gel-based depletion procedure can easily be integrated in existing procedures as a specific sample pre-treatment step. While ELISA-based methods were used to measure the recombinant coagulation proteins in the supernatants obtained by depletion, this procedure is applicable for all biochemical analyses. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Phylogenetic evidence for intratypic recombinant events in a novel human adenovirus C that causes severe acute respiratory infection in children.

    Wang, Yanqun; Li, Yamin; Lu, Roujian; Zhao, Yanjie; Xie, Zhengde; Shen, Jun; Tan, Wenjie

    2016-03-10

    Human adenoviruses (HAdVs) are prevalent in hospitalized children with severe acute respiratory infection (SARI). Here, we report a unique recombinant HAdV strain (CBJ113) isolated from a HAdV-positive child with SARI. The whole-genome sequence was determined using Sanger sequencing and high-throughput sequencing. A phylogenetic analysis of the complete genome indicated that the CBJ113 strain shares a common origin with HAdV-C2, HAdV-C6, HAdV-C1, HAdV-C5, and HAdV-C57 and formed a novel subclade on the same branch as other HAdV-C subtypes. BootScan and single nucleotide polymorphism analyses showed that the CBJ113 genome has an intra-subtype recombinant structure and comprises gene regions mainly originating from two circulating viral strains: HAdV-1 and HAdV-2. The parental penton base, pVI, and DBP genes of the recombinant strain clustered with the HAdV-1 prototype strain, and the E1B, hexon, fiber, and 100 K genes of the recombinant clustered within the HAdV-2 subtype, meanwhile the E4orf1 and DNA polymerase genes of the recombinant shared the greatest similarity with those of HAdV-5 and HAdV-6, respectively. All of these findings provide insight into our understanding of the dynamics of the complexity of the HAdV-C epidemic. More extensive studies should address the pathogenicity and clinical characteristics of the novel recombinant.

  5. Circulating osteogentic precursor cells in non-hereditary heterotopic ossification.

    Egan, Kevin P; Duque, Gustavo; Keenan, Mary Ann; Pignolo, Robert J

    2018-04-01

    Non-hereditary heterotopic ossification (NHHO) may occur after musculoskeletal trauma, central nervous system (CNS) injury, or surgery. We previously described circulating osteogenic precursor (COP) cells as a bone marrow-derived type 1 collagen + CD45 + subpopulation of mononuclear adherent cells that are able of producing extraskeletal ossification in a murine in vivo implantation assay. In the current study, we performed a tissue analysis of COP cells in NHHO secondary to defined conditions, including traumatic brain injury, spinal cord injury, cerebrovascular accident, trauma without neurologic injury, and joint arthroplasty. All bone specimens revealed the presence of COP cells at 2-14 cells per high power field. COP cells were localized to early fibroproliferative and neovascular lesions of NHHO with evidence for their circulatory status supported by their presence near blood vessels in examined lesions. This study provides the first systematic evaluation of COP cells as a contributory histopathological finding associated with multiple forms of NHHO. These data support that circulating, hematopoietic-derived cells with osteogenic potential can seed inflammatory sites, such as those subject to soft tissue injury, and due to their migratory nature, may likely be involved in seeding sites distant to CNS injury. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Money creation and circulation in a credit economy

    Xiong, Wanting; Fu, Han; Wang, Yougui

    2017-01-01

    This paper presents a multi-agent model describing the main mechanisms of money creation and money circulation in a credit economy. Our special attention is paid to the role of debt in the two processes. With the agent-based modeling approach, macro phenomena are well founded in micro-based causalities. A hypothetical economy composed of a banking system and multiple traders is proposed. Instead of being a pure financial intermediary, the banking system is viewed as the center of money creation and an accelerator of money circulation. Agents finance their expenditures not only by their own savings but also through bank loans. Through mathematical calculations and numerical simulation, we identify the determinants of money multiplier and those of velocity of money. In contrast to the traditional money creation model, the money multiplier is determined not only by the behavior of borrowing but also by the behavior of repayment as well. The velocity of money is found to be influenced by both money-related factors such as the expenditure habits of agents with respect to their income and wealth and debt-related factors such as borrowing and repayment behaviors of debtors and the reserve requirements faced by banks.

  7. Harmonic currents circulation in electrical networks simulation and analysis

    Em-Mamlouk, W.M. [MEP, Cairo (Egypt); El-Sharkawy, M.A. [Shams Univ., Cairo (Egypt). Dept. of Electrical Power and Machines; Mostafa, H.E. [Jazan Univ., Jazan (Saudi Arabia). Electrical Dept.

    2009-07-01

    A detailed harmonic flow analysis for a 13-bus balanced industrial distribution system was presented. The aim of the study was to determine the influence of harmonic sources in various branches of the system on voltage and current waveforms before disruptions to the utility supply system occurred. The current harmonic contents of an adjustable speed drive (ASD) were studied under various loading conditions. The test system was simulated using a standard study test system. Harmonic effects from multiple sources were investigated, and voltage distortion on the different buses was monitored. The study demonstrated that while the harmonic loads circulated harmonic currents in all system branches, no harmonic source was directly connected to the system buses. Many of the investigated cases exceeded allowable voltage total harmonic distortion and or current total harmonic distortion standards set by the Institute of Electrical and Electronic Engineers (IEEE). It was concluded that active harmonic filters should be used to prevent the effects of harmonic current circulation at different buses on neighbouring loads within a system. 8 refs., 11 tabs., 15 figs.

  8. Nonrandom distribution of iron in circulating human transferrin.

    Zak, O; Aisen, P

    1986-07-01

    By combining the urea gel electrophoresis technique of Makey and Seal with Western immunoblotting, a method has been developed for analyzing the distribution of iron between the two sites of circulating human transferrin. The new method avoids exposure of samples to a nonphysiologic pH that may promote removal or redistribution of iron from the protein; this facilitates examination of multiple samples at one time. Analysis of 21 freshly drawn specimens from normal human subjects confirms previous reports that iron is not randomly distributed in the specific sites of transferrin. Rather, there is a considerable range in the ratio of occupancies of N-terminal and C-terminal sites (N:C ratio), from 0.31 to 6.87 in the present study, with the N-terminal site predominantly occupied in most subjects. The N:C ratio correlates modestly with serum iron concentration (r = .54). Possible flaws in studies indicating a random occupancy of the specific sites of circulating transferrin may lie in the low pH to which samples may be exposed during procedures based on isoelectric focusing or in drawing inferences from data considering only total monoferric transferrin rather than the two distinguishable monoferric species.

  9. Routinely used immunoassays do not detect circulating anti-GBM antibodies against native NC1 hexamer and EA epitope of the α3 chain of type IV collagen.

    Clavarino, Giovanna; Gauthier, Arnaud; Hellmark, Thomas; Carron, Pierre-Louis; Giovannini, Diane; Colliard, Sophie; Dragon-Durey, Marie-Agnès; Segelmark, Mårten; Cesbron, Jean-Yves; Dumestre-Pérard, Chantal

    2018-04-12

    Detection of circulating anti-GBM antibodies has a key role for the diagnosis of Goodpasture syndrome but immunoassays using purified or recombinant alpha3(IV)NC1 as antigen do not recognize all anti-GBM antibodies. We show that anti-GBM antibodies directed against epitopes in their native conformation or cryptic epitopes are detected by indirect immunofluorescence. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Recombinant zoster (shingles) vaccine, RZV - what you need to know

    ... year in the United States get shingles. Shingles vaccine (recombinant) Recombinant shingles vaccine was approved by FDA in 2017 for the ... life-threatening allergic reaction after a dose of recombinant shingles vaccine, or has a severe allergy to any component ...

  11. Bimolecular recombination in ambipolar organic field effect transistors

    Charrier, D.S.H.; Vries, T. de; Mathijssen, S.G.J.; Geluk, E.-J.; Smits, E.C.P.; Kemerink, M.; Janssen, R.A.J.

    2009-01-01

    In ambipolar organic field effect transistors (OFET) the shape of the channel potential is intimately related to the recombination zone width W, and hence to the electron–hole recombination strength. Experimentally, the recombination profile can be assessed by scanning Kelvin probe microscopy

  12. Intrinsic and experimental quasiparticle recombination times in superconducting films

    Eisenmenger, W.; Lassmann, K.; Trumpp, H.J.; Krauss, R.

    1977-01-01

    Experimental quasiparticle recombination lifetime data for superconducting Al, Sn, and Pb films are compared with calculations based on a ray acoustic model taking account of the film thickness dependence of the reabsorption of recombination phonons. Information on the true or intrinsic quasiparticle recombination lifetime obtained from these and other data is discussed. (orig.) [de

  13. Bimolecular recombination in ambipolar organic field effect transistors

    Charrier, D. S. H.; de Vries, T.; Mathijssen, S. G. J.; Geluk, E. -J.; Smits, E. C. P.; Kemerink, M.; Janssen, R. A. J.

    In ambipolar organic field effect transistors (OFET) the shape of the channel potential is intimately related to the recombination zone width W, and hence to the electron-hole recombination strength. Experimentally, the recombination profile can be assessed by scanning Kelvin probe microscopy

  14. Anti-proliferative activity of recombinant melittin expressed in ...

    Recombinant melittin was then successfully expressed in Escherichia coli. The activity of affinity-purified recombinant melittin was determined in human leukemic U937 cells. Results show that the recombinant melittin had the same anti-proliferative activity in human leukemic U937 cells in vitro as natural one. This shows the ...

  15. Homologous recombination in mammalian cells: effect of p53 and Bcl-2 proteins, replication inhibition and ionizing radiations

    Saintigny, Yannick

    1999-01-01

    The control of cell cycle, associated with the mechanisms of replication, DNA repair/recombination allows the cells to maintain their genetic integrity. The p53 protein ensures the control of G1/S transition. Its inactivation would allow to initial replication on damaged matrix and lead to the block of replication forks followed by DNA strand breaks, good substrates for recombination. This work shows that the expression of mutant p53 protein stimulates both spontaneous and radio-induced homologous recombination, independently of the control of cell cycle. Moreover, the use of a set of replication inhibitors show that inhibition of the replication elongation stimulates recombination more strongly than the initiation inhibition. Replication arrest by these inhibitors also significantly increases the number of DNA strand breaks. These results highlighted a point of action of p53 protein on the ultimate stages of the homologous recombination mechanism. Lastly, the expression of Bcl-2 protein inhibits apoptosis and increases survival, but specifically inhibits conservative recombination, after radiation as well as in absence of apoptotic stress. The extinction of this mechanism of DNA repair is associated with an increase of mutagenesis. Taken together, these results allow ta consider the maintenance of the genetic stability as a cellular network involving different pathways. A multiple stages model for tumoral progression can be deduced. (author) [fr

  16. First report of an HIV-1 triple recombinant of subtypes B, C and F in Buenos Aires, Argentina

    Weissenbacher Mercedes

    2006-09-01

    Full Text Available Abstract We describe the genetic diversity of currently transmitted strains of HIV-1 in men who have sex with men (MSM in Buenos Aires, Argentina between 2000 and 2004. Nearly full-length sequence analysis of 10 samples showed that 6 were subtype B, 3 were BF recombinant and 1 was a triple recombinant of subtypes B, C and F. The 3 BF recombinants were 3 different unique recombinant forms. Full genome analysis of one strain that was subtype F when sequenced in pol was found to be a triple recombinant. Gag and pol were predominantly subtype F, while gp120 was subtype B; there were regions of subtype C interspersed throughout. The young man infected with this strain reported multiple sexual partners and sero-converted between May and November of 2004. This study reported for the first time the full genome analysis of a triple recombinant between subtypes B, C and F, that combines in one virus the three most common subtypes in South America.

  17. Local Chromatin Features Including PU.1 and IKAROS Binding and H3K4 Methylation Shape the Repertoire of Immunoglobulin Kappa Genes Chosen for V(DJ Recombination

    Louise S. Matheson

    2017-11-01

    Full Text Available V(DJ recombination is essential for the generation of diverse antigen receptor (AgR repertoires. In B cells, immunoglobulin kappa (Igκ light chain recombination follows immunoglobulin heavy chain (Igh recombination. We recently developed the DNA-based VDJ-seq assay for the unbiased quantitation of Igh VH and DH repertoires. Integration of VDJ-seq data with genome-wide datasets revealed that two chromatin states at the recombination signal sequence (RSS of VH genes are highly predictive of recombination in mouse pro-B cells. It is unknown whether local chromatin states contribute to Vκ gene choice during Igκ recombination. Here we adapt VDJ-seq to profile the Igκ VκJκ repertoire and present a comprehensive readout in mouse pre-B cells, revealing highly variable Vκ gene usage. Integration with genome-wide datasets for histone modifications, DNase hypersensitivity, transcription factor binding and germline transcription identified PU.1 binding at the RSS, which was unimportant for Igh, as highly predictive of whether a Vκ gene will recombine or not, suggesting that it plays a binary, all-or-nothing role, priming genes for recombination. Thereafter, the frequency with which these genes recombine was shaped both by the presence and level of enrichment of several other chromatin features, including H3K4 methylation and IKAROS binding. Moreover, in contrast to the Igh locus, the chromatin landscape of the promoter, as well as of the RSS, contributes to Vκ gene recombination. Thus, multiple facets of local chromatin features explain much of the variation in Vκ gene usage. Together, these findings reveal shared and divergent roles for epigenetic features and transcription factors in AgR V(DJ recombination and provide avenues for further investigation of chromatin signatures that may underpin V(DJ-mediated chromosomal translocations.

  18. [Genetic evidence for recombination and mutation in the emergence of human enterovirus 71].

    Liu, Ai-Ping; Tan, Hui; Xie, Qun; Chen, Bai-Tang; Liu, Xiao-Feng; Zhang, Yong

    2014-09-01

    We wished to understand the genetic recombination and phylogenetic characteristics of human en- terovirus A71 (EV-A71) and to explore its potential virulence-related sites. Full-length genomes of three EV-A71 strains isolated from patients in Chenzhou City (China) were sequenced and analyzed. Possible re- combination events and crossover sites were analyzed with Recombination Detection Program v4. 1. 6 by comparison with the complete genome sequences of 231 strains of EV-A71. Similarly, plot and bootscanning analyses were undertaken with SimPlot v3. 5. 1. Phylogenetic trees based on the sequences of VP1 regions were constructed with MEGA v5. 2 using the Kimura two-parameter model and neighbor-joining method. Results suggested that recombination events were detected among the three EV-A71 isolates from Chenzhou City. The common main parent sequence was from JF799986 isolated from samples in Guang- zhou City (China) in 2009, and the minor parent sequence was TW/70516/08. Intertypic recombination e- vents were found in the C4b strain (strain SHZH98 isolated in 1998) and C4a strain (Fuyang strain isola- ted in 2008) with the prototype strains of CVA4 and CVA14 in the 3D region. The chi-square test was used to screen-out potential virulence-related sites with nucleotide substitutions of different types of hand, foot, and mouth disease (HFMD) cases using SPSS v19.0. Results suggested that there were no significant nucleotide substitutions between death cases and severe-HFMD cases. Eighteen significant nucleotide substitutions were found between death/severe-HFMD cases and mild-HFMD cases, and all these 18 substitutions were distributed only in P2 and P3 regions. Intertypic recombination among the predominant circulating EV-A71 strains in the Chinese mainland and other EV-A strains probably dates before 1998, and intratypic recombination might have occurred frequently in the HFMD outbreak from 2008 to 2012. Substitutions in the non-capsid region may be correlated with the

  19. Substitutions in PBP3 confer resistance to both ampicillin and extended-spectrum cephalosporins in Haemophilus parainfluenzae as revealed by site-directed mutagenesis and gene recombinants

    Wienholtz, Nanna H; Ciechanowski, Aynur Barut; Nørskov-Lauritsen, Niels

    2017-01-01

    using site-directed mutagenesis. Recombinants were also generated using PCR-amplified ftsI from clinical strains encoding multiple amino acid substitutions. MICs of ampicillin, cefuroxime, cefotaxime and ceftriaxone were determined using Etest ® . Results: Transformation of a susceptible strain with fts...... for recombinants were lower than those for the donor strains. Using site-directed mutagenesis, no single substitution conferred resistance to the tested β-lactams, although V511A increased the MIC of cefuroxime to the intermediate category for intravenous administration. Recombinants encoding N526K...

  20. Multiple sclerosis

    Sadashima, Hiromichi; Kusaka, Hirofumi; Imai, Terukuni; Takahashi, Ryosuke; Matsumoto, Sadayuki; Yamamoto, Toru; Yamasaki, Masahiro; Maya, Kiyomi

    1986-01-01

    Eleven patients with a definite diagnosis of multiple sclerosis were examined in terms of correlations between the clinical features and the results of cranial computed tomography (CT), and magnetic resonance imaging (MRI). Results: In 5 of the 11 patients, both CT and MRI demonstrated lesions consistent with a finding of multiple sclerosis. In 3 patients, only MRI demonstrated lesions. In the remaining 3 patients, neither CT nor MRI revealed any lesion in the brain. All 5 patients who showed abnormal findings on both CT and MRI had clinical signs either of cerebral or brainstem - cerebellar lesions. On the other hand, two of the 3 patients with normal CT and MRI findings had optic-nerve and spinal-cord signs. Therefore, our results suggested relatively good correlations between the clinical features, CT, and MRI. MRI revealed cerebral lesions in two of the four patients with clinical signs of only optic-nerve and spinal-cord lesions. MRI demonstrated sclerotic lesions in 3 of the 6 patients whose plaques were not detected by CT. In conclusion, MRI proved to be more helpful in the demonstration of lesions attributable to chronic multiple sclerosis. (author)