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Sample records for divergent simian t-lymphotropic

  1. Simian T Lymphotropic Virus 1 Infection of Papio anubis: tax Sequence Heterogeneity and T Cell Recognition.

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    Termini, James M; Magnani, Diogo M; Maxwell, Helen S; Lauer, William; Castro, Iris; Pecotte, Jerilyn; Barber, Glen N; Watkins, David I; Desrosiers, Ronald C

    2017-10-15

    Baboons naturally infected with simian T lymphotropic virus (STLV) are a potentially useful model system for the study of vaccination against human T lymphotropic virus (HTLV). Here we expanded the number of available full-length baboon STLV-1 sequences from one to three and related the T cell responses that recognize the immunodominant Tax protein to the tax sequences present in two individual baboons. Continuously growing T cell lines were established from two baboons, animals 12141 and 12752. Next-generation sequencing (NGS) of complete STLV genome sequences from these T cell lines revealed them to be closely related but distinct from each other and from the baboon STLV-1 sequence in the NCBI sequence database. Overlapping peptides corresponding to each unique Tax sequence and to the reference baboon Tax sequence were used to analyze recognition by T cells from each baboon using intracellular cytokine staining (ICS). Individual baboons expressed more gamma interferon and tumor necrosis factor alpha in response to Tax peptides corresponding to their own STLV-1 sequence than in response to Tax peptides corresponding to the reference baboon STLV-1 sequence. Thus, our analyses revealed distinct but closely related STLV-1 genome sequences in two baboons, extremely low heterogeneity of STLV sequences within each baboon, no evidence for superinfection within each baboon, and a ready ability of T cells in each baboon to recognize circulating Tax sequences. While amino acid substitutions that result in escape from CD8 + T cell recognition were not observed, premature stop codons were observed in 7% and 56% of tax sequences from peripheral blood mononuclear cells from animals 12141 and 12752, respectively. IMPORTANCE It has been estimated that approximately 100,000 people suffer serious morbidity and 10,000 people die each year from the consequences associated with human T lymphotropic virus (HTLV) infection. There are no antiviral drugs and no preventive vaccine. A

  2. Modes of transmission of Simian T-lymphotropic Virus Type 1 in semi-captive mandrills (Mandrillus sphinx).

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    Roussel, Marion; Pontier, Dominique; Ngoubangoye, Barthélémy; Kazanji, Mirdad; Verrier, Delphine; Fouchet, David

    2015-09-30

    Non-human primates (NHPs) often live in inaccessible areas, have cryptic behaviors, and are difficult to follow in the wild. Here, we present a study on the spread of the simian T-lymphotropic Virus Type 1 (STLV-1), the simian counterpart of the human T-lymphotropic virus type 1 (HTLV-1) in a semi-captive mandrill colony. This study combines 28 years of longitudinal monitoring, including behavioral data, with a dynamic mathematical model and Bayesian inference. Three transmission modes were suspected: aggressive, sexual and familial. Our results show that among males, STLV-1 transmission occurs preferentially via aggression. Because of their impressive aggressive behavior male mandrills can easily transmit the virus during fights. On the contrary, sexual activity seems to have little effect. Thus transmission appears to occur primarily via male-male and female-female contact. In addition, for young mandrills, familial transmission appears to play an important role in virus spread. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Bushmeat Hunting and Zoonotic Transmission of Simian T-Lymphotropic Virus 1 in Tropical West and Central Africa.

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    Mossoun, Arsène; Calvignac-Spencer, Sébastien; Anoh, Augustin E; Pauly, Maude S; Driscoll, Daniel A; Michel, Adam O; Nazaire, Lavry Grah; Pfister, Stefan; Sabwe, Pascale; Thiesen, Ulla; Vogler, Barbara R; Wiersma, Lidewij; Muyembe-Tamfum, Jean-Jacques; Karhemere, Stomy; Akoua-Koffi, Chantal; Couacy-Hymann, Emmanuel; Fruth, Barbara; Wittig, Roman M; Leendertz, Fabian H; Schubert, Grit

    2017-05-15

    Simian T-lymphotropic virus 1 (STLV-1) enters human populations through contact with nonhuman primate (NHP) bushmeat. We tested whether differences in the extent of contact with STLV-1-infected NHP bushmeat foster regional differences in prevalence of human T-lymphotropic virus 1 (HTLV-1). Using serological and PCR assays, we screened humans and NHPs at two Sub-Saharan African sites where subsistence hunting was expected to be less (Taï region, Côte d'Ivoire [CIV]) or more (Bandundu region, Democratic Republic of the Congo [DRC]) developed. Only 0.7% of human participants were infected with HTLV-1 in CIV ( n = 574), and 1.3% of humans were infected in DRC ( n = 302). Two of the Ivorian human virus sequences were closely related to simian counterparts, indicating ongoing zoonotic transmission. Multivariate analysis of human demographic parameters and behavior confirmed that participants from CIV were less often exposed to NHPs than participants from DRC through direct contact, e.g., butchering. At the same time, numbers of STLV-1-infected NHPs were higher in CIV (39%; n = 111) than in DRC (23%; n = 39). We conclude that similar ultimate risks of zoonotic STLV-1 transmission-defined as the product of prevalence in local NHP and human rates of contact to fresh NHP carcasses-contribute to the observed comparable rates of HTLV-1 infection in humans in CIV and DRC. We found that young adult men and mature women are most likely exposed to NHPs at both sites. In view of the continued difficulties in controlling zoonotic disease outbreaks, the identification of such groups at high risk of NHP exposure may guide future prevention efforts. IMPORTANCE Multiple studies report a high risk for zoonotic transmission of blood-borne pathogens like retroviruses through contact with NHPs, and this risk seems to be particularly high in tropical Africa. Here, we reveal high levels of exposure to NHP bushmeat in two regions of Western and Central tropical Africa. We provide evidence

  4. [A new variant of the simian T-lymphotropic retrovirus type I (STLV-IF) in the Sukhumi colony of hamadryas baboons].

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    Chikobaeva, M G; Schatzl, H; Rose, D; Bush, U; Iakovleva, L A; Deinhardt, F; Helm, K; Lapin, B A

    1993-01-01

    Polymerase chain reaction (PCR) was developed for the detection of simian T-lymphotropic virus type 1 (STLV-1) infection of P. hamadryas and direct sequencing using oligo-nucleotide primer pairs specific for the tax and env regions of the related human T-lymphotropic virus type 1 (HTLV-1). Excellent specificity was shown in the detection of STLV-1 provirus in infected baboons by PCR using HTLV-1-derived primers. The nucleotide sequences of env 467bp and tax 159bp of the proviral genome (env position 5700-6137, tax position 7373-7498 HTLV-1, according to Seiki et al., 1983) derived from STLV-1-infected P. hamadryas were analysed using PCR and direct sequencing techniques. Two STLV-1 isolates from different sources (Sukhumi main-SuTLV-1 and forest stocks-STLV-1F) were compared. Two variants of STLV-1 among P. hamadryas with different level of homology to HTLV-1 were wound (83.8% and 95.2%, respectively). A possible role of nucleotide changes in env and tax sequenced fragments and oncogenicity of STLV-1 variants is discussed.

  5. Divergent strains of human T-lymphotropic virus type 1 (HTLV-1) within the Cosmopolitan subtype in Argentina.

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    Eirin, Maria E; Dilernia, Dario A; Berini, Carolina A; Jones, Leandro R; Pando, Maria A; Biglione, Mirna M

    2008-10-01

    HTLV-1 Cosmopolitan subtype Transcontinental subgroup A has been described among aboriginal communities from the northwest endemic area of Argentina. Moreover, Transcontinental subgroup A and the Japanese subgroup B were reported among blood donors from the nonendemic central region of the country. We carried out the first HTLV-1 phylogenetic study in individuals residing in Buenos Aires capital city. Phylogenetic analysis performed on the LTR region showed that all 44 new strains clustered within the Cosmopolitan subtype, with 42 (95.4%) belonging to Transcontinental subgroup A. Of them, 20 (45.5%) strains grouped in the large Latin American cluster and 4 (9.1%) in the small Latin American cluster. The majority of them belonged to individuals of nonblack origin, grouped with Amerindian strains. Three (6.8%) were closely related to South African references and two monophyletic clusters including only HIV/HTLV-1 coinfected individuals were observed. Interestingly, two (4.5%) new sequences (divergent strains) branched off from all five known Cosmopolitan subgroups in a well-supported clade. In summary, these findings show that HTLV-1 Cosmopolitan subtype Transcontinental subgroup A is infecting residents of Buenos Aires, a nonendemic area of Argentina, and confirm the introduction of divergent strains in the country.

  6. Molecular investigation of the evolutionary history and diversity of primate T-lymphotropic virus types 1 and 3

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    Van Dooren, Sonia Jeanne Albertine

    2005-01-01

    The Primate T-lymphotropic viruses (PTLV) comprise a group of complex retroviruses that infect both humans (HTLV) and simians (STLV) and have been associated with leukaemia or lymphoma and with neurological disorders. PTLVs have a peculiar replication strategy: their way of life is mainly determined

  7. Molecular epidemiology of endemic human T-lymphotropic virus type 1 in a rural community in Guinea-Bissau.

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    Carla van Tienen

    Full Text Available Human T-Lymphotropic Virus Type 1 (HTLV-1 infection causes lethal adult T-cell leukemia (ATL and severely debilitating HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP in up to 5% of infected adults. HTLV-1 is endemic in parts of Africa and the highest prevalence in West Africa (5% has been reported in Caio, a rural area in the North-West of Guinea-Bissau. It is not known which HTLV-1 variants are present in this community. Sequence data can provide insights in the molecular epidemiology and help to understand the origin and spread of HTLV-1.To gain insight into the molecular diversity of HTLV-1 in West Africa.HTLV-1 infected individuals were identified in community surveys between 1990-2007. The complete Long Terminal Repeat (LTR and p24 coding region of HTLV-1 was sequenced from infected subjects. Socio-demographic data were obtained from community census and from interviews performed by fieldworkers. Phylogenetic analyses were performed to characterize the relationship between the Caio HTLV-1 and HTLV-1 from other parts of the world.LTR and p24 sequences were obtained from 72 individuals (36 LTR, 24 p24 only and 12 both. Consistent with the low evolutionary change of HTLV-1, many of the sequences from unrelated individuals showed 100% nucleotide identity. Most (45 of 46 of the LTR sequences clustered with the Cosmopolitan HTLV-1 subtype 1a, subgroup D (1aD. LTR and p24 sequences from two subjects were divergent and formed a significant cluster with HTLV-1 subtype 1g, and with the most divergent African Simian T-cell Lymphotropic Virus, Tan90.The Cosmopolitan HTLV-1 1aD predominates in this rural West African community. However, HTLV-1 subtype 1g is also present. This subtype has not been described before in West Africa and may be more widespread than previously thought. These data are in line with the hypothesis that multiple monkey-to-man zoonotic events are contributing to HTLV-1 diversity.

  8. Development of neurologic diseases in a patient with primate T lymphotropic virus type 1 (PTLV-1).

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    Enose-Akahata, Yoshimi; Caruso, Breanna; Haner, Benjamin; Charlip, Emily; Nair, Govind; Massoud, Raya; Billioux, Bridgette J; Ohayon, Joan; Switzer, William M; Jacobson, Steven

    2016-08-12

    Virus transmission from various wild and domestic animals contributes to an increased risk of emerging infectious diseases in human populations. HTLV-1 is a human retrovirus associated with acute T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 originated from ancient zoonotic transmission from nonhuman primates, although cases of zoonotic infections continue to occur. Similar to HTLV-1, the simian counterpart, STLV-1, causes chronic infection and leukemia and lymphoma in naturally infected monkeys, and combined are called primate T-lymphotropic viruses (PTLV-1). However, other clinical syndromes typically seen in humans such as a chronic progressive myelopathy have not been observed in nonhuman primates. Little is known about the development of neurologic and inflammatory diseases in human populations infected with STLV-1-like viruses following nonhuman primate exposure. We performed detailed laboratory analyses on an HTLV-1 seropositive patient with typical HAM/TSP who was born in Liberia and now resides in the United States. Using a novel droplet digital PCR for the detection of the HTLV-1 tax gene, the proviral load in PBMC and cerebrospinal fluid cells was 12.98 and 51.68 %, respectively; however, we observed a distinct difference in fluorescence amplitude of the positive droplet population suggesting possible mutations in proviral DNA. A complete PTLV-1 proviral genome was amplified from the patient's PBMC DNA using an overlapping PCR strategy. Phylogenetic analysis of the envelope and LTR sequences showed the virus was highly related to PTLV-1 from sooty mangabey monkeys (smm) and humans exposed via nonhuman primates in West Africa. These results demonstrate the patient is infected with a simian variant of PTLV-1, suggesting for the first time that PTLV-1smm infection in humans may be associated with a chronic progressive neurologic disease.

  9. Zoonotic Transmission of Two New Strains of Human T-lymphotropic Virus Type 4 in Hunters Bitten by a Gorilla in Central Africa.

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    Richard, Léa; Mouinga-Ondémé, Augustin; Betsem, Edouard; Filippone, Claudia; Nerrienet, Eric; Kazanji, Mirdad; Gessain, Antoine

    2016-09-15

    Molecular screening of 300 at-risk people from Central Africa identified 2 human T-lymphotropic virus (HTLV)-4-infected individuals. A zoonotic origin of infection was suggested, as both individuals reported being severely bitten by a gorilla during hunting activities. One strain was highly divergent and was designated as the HTLV-4 subtype-b prototype. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  10. Ancient, independent evolution and distinct molecular features of the novel human T-lymphotropic virus type 4

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    Wolfe Nathan D

    2009-02-01

    Full Text Available Abstract Background Human T-lymphotropic virus type 4 (HTLV-4 is a new deltaretrovirus recently identified in a primate hunter in Cameroon. Limited sequence analysis previously showed that HTLV-4 may be distinct from HTLV-1, HTLV-2, and HTLV-3, and their simian counterparts, STLV-1, STLV-2, and STLV-3, respectively. Analysis of full-length genomes can provide basic information on the evolutionary history and replication and pathogenic potential of new viruses. Results We report here the first complete HTLV-4 sequence obtained by PCR-based genome walking using uncultured peripheral blood lymphocyte DNA from an HTLV-4-infected person. The HTLV-4(1863LE genome is 8791-bp long and is equidistant from HTLV-1, HTLV-2, and HTLV-3 sharing only 62–71% nucleotide identity. HTLV-4 has a prototypic genomic structure with all enzymatic, regulatory, and structural proteins preserved. Like STLV-2, STLV-3, and HTLV-3, HTLV-4 is missing a third 21-bp transcription element found in the long terminal repeats of HTLV-1 and HTLV-2 but instead contains unique c-Myb and pre B-cell leukemic transcription factor binding sites. Like HTLV-2, the PDZ motif important for cellular signal transduction and transformation in HTLV-1 and HTLV-3 is missing in the C-terminus of the HTLV-4 Tax protein. A basic leucine zipper (b-ZIP region located in the antisense strand of HTLV-1 and believed to play a role in viral replication and oncogenesis, was also found in the complementary strand of HTLV-4. Detailed phylogenetic analysis shows that HTLV-4 is clearly a monophyletic viral group. Dating using a relaxed molecular clock inferred that the most recent common ancestor of HTLV-4 and HTLV-2/STLV-2 occurred 49,800 to 378,000 years ago making this the oldest known PTLV lineage. Interestingly, this period coincides with the emergence of Homo sapiens sapiens during the Middle Pleistocene suggesting that early humans may have been susceptible hosts for the ancestral HTLV-4. Conclusion The

  11. JST Thesaurus Headwords and Synonyms: human T-lymphotropic virus 1 [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term human T-lymphotropic virus 1 名詞 一...般 * * * * HTLV1 HTLV1 エイチティーエルブイイチ Thesaurus2015 200906096931199548 C LS07 UNKNOWN_2 human T - lymphotropic virus 1

  12. Molecular epidemiology of endemic human t-lymphotropic virus type 1 in a rural community in guinea-bissau

    NARCIS (Netherlands)

    C. van Tienen (Carla); T.I. de Silva (Thushan); L.C.J. Alcantara (Luiz); C. Onyango (Clayton); S. Jarju (Sheikh); N. Gonçalves (Nato); T. Vincent (Tim); P. Aaby; H. Whittle (Hilton); M. Schim van der Loeff (Maarten); M. Cotten (Matthew)

    2012-01-01

    textabstractBackground: Human T-Lymphotropic Virus Type 1 (HTLV-1) infection causes lethal adult T-cell leukemia (ATL) and severely debilitating HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in up to 5% of infected adults. HTLV-1 is endemic in parts of Africa and the highest

  13. Molecular Epidemiology of Endemic Human T-Lymphotropic Virus Type 1 in a Rural Community in Guinea-Bissau

    NARCIS (Netherlands)

    van Tienen, Carla; de Silva, Thushan I.; Alcantara, Luiz Carlos Junior; Onyango, Clayton O.; Jarju, Sheikh; Gonçalves, Nato; Vincent, Tim; Aaby, Peter; Whittle, Hilton; Schim van der Loeff, Maarten; Cotten, Matthew

    2012-01-01

    Background: Human T-Lymphotropic Virus Type 1 (HTLV-1) infection causes lethal adult T-cell leukemia (ATL) and severely debilitating HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in up to 5% of infected adults. HTLV-1 is endemic in parts of Africa and the highest prevalence in

  14. NLRP3 polymorphism is associated with protection against human T-lymphotropic virus 1 infection

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    Anselmo Jiro Kamada

    2014-11-01

    Full Text Available Inter-individual heterogeneity in the response to human T-lymphotropic virus 1 (HTLV-1 infection has been partially attributed to host genetic background. The antiviral activity of the inflammasome cytoplasmic complex recognises viral molecular patterns and regulates immune responses via the activation of interleukin (IL-1 family (IL-1, IL-18 and IL-33 members. The association between polymorphisms in the inflammasome receptors NLRP1 and NLRP3 and HTLV-1 infection was evaluated in a northeastern Brazilian population (84 HTLV-1 carriers and 155 healthy controls. NLRP3 rs10754558 G/G was associated with protection against HTLV-1 infection (p = 0.012; odds ratio = 0.37. rs10754558 affects NLRP3 mRNA stability; therefore, our results suggest that higher NLRP3 expression may augment first-line defences, leading to the effective protection against HTLV-1 infection.

  15. Effects of Physiotherapy in the Treatment of Neurogenic Bladder in Patients Infected With Human T-Lymphotropic Virus 1.

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    Andrade, Rosana C P; Neto, José A; Andrade, Luciana; Oliveira, Tatiane S; Santos, Dislene N; Oliveira, Cassius J V; Prado, Márcio J; Carvalho, Edgar M

    2016-03-01

    To evaluate the efficacy of physiotherapy for urinary manifestations in patients with human T-lymphotropic virus 1-associated lower urinary tract dysfunction. Open clinical trial was conducted with 21 patients attending the physiotherapy clinic of the Hospital Universitário, Bahia, Brazil. Combinations of behavioral therapy, perineal exercises, and intravaginal or intra-anal electrical stimulation were used. The mean age was 54 ± 12 years and 67% were female. After treatment, there was an improvement in symptoms of urinary urgency, frequency, incontinence, nocturia, and in the sensation of incomplete emptying (P Physiotherapy was effective in cases of human T-lymphotropic virus 1-associated neurogenic bladder, reducing symptoms, increasing perineal muscle strength, and improving urodynamic parameters and quality of life. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Possible etiologies for tropical spastic paraparesis and human T lymphotropic virus I-associated myelopathy

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    V. Zaninovic'

    2004-01-01

    Full Text Available The epidemiology of tropical spastic paraparesis/human T lymphotropic virus I (HTLV-I-associated myelopathy (TSP/HAM is frequently inconsistent and suggests environmental factors in the etiology of these syndromes. The neuropathology corresponds to a toxometabolic or autoimmune process and possibly not to a viral disease. Some logical hypotheses about the etiology and physiopathology of TSP and HAM are proposed. Glutamate-mediated excitotoxicity, central distal axonopathies, cassava, lathyrism and cycad toxicity may explain most cases of TSP. The damage caused to astrocytes and to the blood-brain barrier by HTLV-I plus xenobiotics may explain most cases of HAM. Analysis of the HTLV-I/xenobiotic ratio clarifies most of the paradoxical epidemiology of TSP and HAM. Modern neurotoxicology, neuroimmunology and molecular biology may explain the neuropathology of TSP and HAM. It is quite possible that there are other xenobiotics implicated in the etiology of some TSP/HAMs. The prevention of these syndromes appears to be possible today.

  17. Anti-human T-lymphotropic virus type-I antibodies in atomic-bomb survivors

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    Matsuo, Tatsuki; Nakashima, Eiji; Carter, R.L. [Radiation Effects Research Foundation, Nagasaki (Japan). Nagasaki Branch] [and others

    1995-03-01

    Adult T-cell leukemia (ATL), induced by human T-lymphotropic virus type-I (HTLV-I), is endemic in Nagasaki, Japan. To investigate the effects of atomic-bomb radiation on development of this specific type of leukemia, 6182 individuals in the Radiation Effects Research Foundation (RERF) Adult Health Study sample in Hiroshima and Nagasaki were examined for positive rate of HTLV-I antibody. Several lymphocyte parameters were also studied for 70 antibody-positive subjects in Nagasaki. The HTLV-I antibody-positive rate was higher in Nagasaki (6.36%) than in Hiroshima (0.79%) and significantly increased with increasing age, but no association was observed with radiation dose. Whether relationship existed between antibody titer levels and radiation dose among antibody-positive subjects was not clear. The frequency of abnormal lymphocytes tended to be higher in antibody-positive subjects than in antibody-negative subjects, and higher in females than in males regardless of radiation dose. The lymphocyte count was lower in antibody-positive subjects than in antibody-negative subjects and lower in female than in male subjects. No evidence was found to suggest that atomic-bomb radiation plays an important role in HTLV-I infection. (author).

  18. Human T-lymphotropic virus type I tax regulates the expression of the human lymphotoxin gene.

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    Tschachler, E; Böhnlein, E; Felzmann, S; Reitz, M S

    1993-01-01

    Human T-lymphotropic virus type-I (HTLV-I)-infected T-cell lines constitutively produce high levels of lymphotoxin (LT). To analyze the mechanisms that lead to the expression of LT in HTLV-I-infected cell lines, we studied regulatory regions of the human LT promoter involved in the activation of the human LT gene. As determined by deletional analysis, sequences between +137 and -116 (relative to the transcription initiation site) are sufficient to direct expression of a reporter gene in the HTLV-I-infected cell line MT-2. Site-directed mutation of a of the single kappa B-like motif present in the LT promoter region (positions -99 to -89) completely abrogated LT promoter activity in MT-2 cells, suggesting that this site plays a critical role in the activation of the human LT gene. Transfection of LT constructs into HTLV-I-uninfected and -unstimulated Jurkat and U937 cell lines showed little to no activity of the LT promoter. Cotransfection of the same constructs with a tax expression plasmid into Jurkat cells led to detectable promoter activity, which could be significantly increased by stimulation of the cells with phorbol myristate acetate (PMA). Similarly, cotransfection of the LT promoter constructs and the tax expression plasmid into U937 cells led to significant promoter activity upon stimulation with PMA. These data suggest that HTLV-I tax is involved in the upregulation of LT gene expression in HTLV-I-infected cells.

  19. Imaging of human T-lymphotropic virus type I-associated chronic progressive myeloneuropathies

    International Nuclear Information System (INIS)

    Alcindor, F.; Valderrama, R.; Canavaggio, M.; Lee, H.; Katz, A.; Montesinos, C.; Madrid, R.E.; Merino, R.R.; Pipia, P.A.

    1992-01-01

    We studied magnetic resonance imaging (MRI) of the head and cervical spine and CT of the head in 46 patients (14 men, 32 women) with chronic progressive myeloneuropathy. The findings were correlated with human T-lymphotropic virus type I (HTLV-I) serology, race, country of origin, and age. We found a female predominance of 2:1. Most patients were aged between 30 and 50 years, and most were Caribbean immigrants and black. There were 9 men and 17 women with blood antibody titers to HTLV-I and 7 mem and 15 women with cerebrospinal fluid (CSF) titers. All patients with virus or antibodies in blood or CSF were Caribbean immigrants or black. T2-weighted cranial MRI showed scattered areas of high signal intensity in the cerebral white matter, usually in the periventricular and subcortical areas, but not in the posterior cranial fossa. Cranial CT revealed periventricular low density areas, ventricular enlargement, and atrophy MRI of the cervical spine showed atrophy of the cord. Myelography was normal in all 15 patients examined. No imaging differences were observed between the HTLV-I-positive and -negative patients. These findings, although consistent with demyelination, are not specific. (orig.)

  20. Imaging of human T-lymphotropic virus type I-associated chronic progressive myeloneuropathies

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    Alcindor, F. (Dept. of Neurology, State Univ. of New York, Health Science Center, Brooklyn, NY (United States)); Valderrama, R. (Dept. of Neurology, State Univ. of New York, Health Science Center, Brooklyn, NY (United States)); Canavaggio, M. (Abbott Labs., North Chicago, IL (United States)); Lee, H. (Abbott Labs., North Chicago, IL (United States)); Katz, A. (Dept. of Neurology, State Univ. of New York, Health Science Center, Brooklyn, NY (United States)); Montesinos, C. (Beth Israel Medical Center, Dept. of Neurology and Clinical Electrophysiology, New York, NY (United States)); Madrid, R.E. (New York State Office of Mental Retardation and Developmental Disabilities, Inst. for Basic Research in Developmental Disabilities, NY (United States)); Merino, R.R. (Beth Israel Medical Center, Dept. of Neurology and Clinical Electrophysiology, New York, NY (United States)); Pipia, P.A. (Dept. of Neurology, State Univ. of New York, Health Science Center, Brooklyn, NY (United States))

    1992-12-01

    We studied magnetic resonance imaging (MRI) of the head and cervical spine and CT of the head in 46 patients (14 men, 32 women) with chronic progressive myeloneuropathy. The findings were correlated with human T-lymphotropic virus type I (HTLV-I) serology, race, country of origin, and age. We found a female predominance of 2:1. Most patients were aged between 30 and 50 years, and most were Caribbean immigrants and black. There were 9 men and 17 women with blood antibody titers to HTLV-I and 7 mem and 15 women with cerebrospinal fluid (CSF) titers. All patients with virus or antibodies in blood or CSF were Caribbean immigrants or black. T2-weighted cranial MRI showed scattered areas of high signal intensity in the cerebral white matter, usually in the periventricular and subcortical areas, but not in the posterior cranial fossa. Cranial CT revealed periventricular low density areas, ventricular enlargement, and atrophy MRI of the cervical spine showed atrophy of the cord. Myelography was normal in all 15 patients examined. No imaging differences were observed between the HTLV-I-positive and -negative patients. These findings, although consistent with demyelination, are not specific. (orig.)

  1. A Novel Human T-lymphotropic Virus Type 1c Molecular Variant in an Indigenous Individual from New Caledonia, Melanesia.

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    Olivier Cassar

    2017-01-01

    Full Text Available Human T-Lymphotropic Virus type 1 (HTLV-1 is endemic among people of Melanesian descent in Papua New Guinea, Solomon Islands and Vanuatu, and in Indigenous populations from Central Australia. Molecular studies revealed that these Australo-Melanesian strains constitute the highly divergent HTLV-1c subtype. New Caledonia is a French overseas territory located in the Southwest Pacific Ocean. HTLV-1 situation is poorly documented in New Caledonia and the molecular epidemiology of HTLV-1 infection remains unknown.Studying 500 older adults Melanesian natives from New Caledonia, we aim to evaluate the HTLV-1 seroprevalence and to molecularly characterize HTLV-1 proviral strains.Plasma from 262 men and 238 females (age range: 60-96 years old, mean age: 70.5 were screened for anti-HTLV-1 antibodies by particle agglutination (PA and indirect immunofluorescence assay (IFA. Serological confirmation was obtained using Western blot assay. DNAs were extracted from peripheral blood buffy coat of HTLV-1 seropositive individuals, and subjected to four series of PCR (LTR-gag; pro-pol; pol-env and tax-LTR. Primers were designed from highly common conserved regions of the major HTLV-1 subtypes to characterize the entire HTLV-1 proviral genome.Among 500 samples, 3 were PA and IFA positive. The overall seroprevalence was 0.6%. The DNA sample from 1 New Caledonian woman (NCP201 was found positive by PCR and the complete HTLV-1 proviral genome (9,033-bp was obtained. The full-length HTLV-1 genomic sequence from a native woman from Vanuatu (EM5, obtained in the frame of our previous studies, was also characterized. Both sequences belonged to the HTLV-1c Australo-Melanesian subtype. The NCP201 strain exhibited 0.3% nucleotide divergence with the EM5 strain from Vanuatu. Furthermore, divergence reached 1.1% to 2.9% with the Solomon and Australian sequences respectively. Phylogenetic analyses on a 522-bp-long fragment of the gp21-env gene showed the existence of two major

  2. Discovery and full genome characterization of two highly divergent simian immunodeficiency viruses infecting black-and-white colobus monkeys (Colobus guereza) in Kibale National Park, Uganda.

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    Lauck, Michael; Switzer, William M; Sibley, Samuel D; Hyeroba, David; Tumukunde, Alex; Weny, Geoffrey; Taylor, Bill; Shankar, Anupama; Ting, Nelson; Chapman, Colin A; Friedrich, Thomas C; Goldberg, Tony L; O'Connor, David H

    2013-10-21

    African non-human primates (NHPs) are natural hosts for simian immunodeficiency viruses (SIV), the zoonotic transmission of which led to the emergence of HIV-1 and HIV-2. However, our understanding of SIV diversity and evolution is limited by incomplete taxonomic and geographic sampling of NHPs, particularly in East Africa. In this study, we screened blood specimens from nine black-and-white colobus monkeys (Colobus guereza occidentalis) from Kibale National Park, Uganda, for novel SIVs using a combination of serology and "unbiased" deep-sequencing, a method that does not rely on genetic similarity to previously characterized viruses. We identified two novel and divergent SIVs, tentatively named SIVkcol-1 and SIVkcol-2, and assembled genomes covering the entire coding region for each virus. SIVkcol-1 and SIVkcol-2 were detected in three and four animals, respectively, but with no animals co-infected. Phylogenetic analyses showed that SIVkcol-1 and SIVkcol-2 form a lineage with SIVcol, previously discovered in black-and-white colobus from Cameroon. Although SIVkcol-1 and SIVkcol-2 were isolated from the same host population in Uganda, SIVkcol-1 is more closely related to SIVcol than to SIVkcol-2. Analysis of functional motifs in the extracellular envelope glycoprotein (gp120) revealed that SIVkcol-2 is unique among primate lentiviruses in containing only 16 conserved cysteine residues instead of the usual 18 or more. Our results demonstrate that the genetic diversity of SIVs infecting black-and-white colobus across equatorial Africa is greater than previously appreciated and that divergent SIVs can co-circulate in the same colobine population. We also show that the use of "unbiased" deep sequencing for the detection of SIV has great advantages over traditional serological approaches, especially for studies of unknown or poorly characterized viruses. Finally, the detection of the first SIV containing only 16 conserved cysteines in the extracellular envelope protein

  3. Human T-lymphotropic virus type 1-infected cells secrete exosomes that contain Tax protein.

    Science.gov (United States)

    Jaworski, Elizabeth; Narayanan, Aarthi; Van Duyne, Rachel; Shabbeer-Meyering, Shabana; Iordanskiy, Sergey; Saifuddin, Mohammed; Das, Ravi; Afonso, Philippe V; Sampey, Gavin C; Chung, Myung; Popratiloff, Anastas; Shrestha, Bindesh; Sehgal, Mohit; Jain, Pooja; Vertes, Akos; Mahieux, Renaud; Kashanchi, Fatah

    2014-08-08

    Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. The HTLV-1 transactivator protein Tax controls many critical cellular pathways, including host cell DNA damage response mechanisms, cell cycle progression, and apoptosis. Extracellular vesicles called exosomes play critical roles during pathogenic viral infections as delivery vehicles for host and viral components, including proteins, mRNA, and microRNA. We hypothesized that exosomes derived from HTLV-1-infected cells contain unique host and viral proteins that may contribute to HTLV-1-induced pathogenesis. We found exosomes derived from infected cells to contain Tax protein and proinflammatory mediators as well as viral mRNA transcripts, including Tax, HBZ, and Env. Furthermore, we observed that exosomes released from HTLV-1-infected Tax-expressing cells contributed to enhanced survival of exosome-recipient cells when treated with Fas antibody. This survival was cFLIP-dependent, with Tax showing induction of NF-κB in exosome-recipient cells. Finally, IL-2-dependent CTLL-2 cells that received Tax-containing exosomes were protected from apoptosis through activation of AKT. Similar experiments with primary cultures showed protection and survival of peripheral blood mononuclear cells even in the absence of phytohemagglutinin/IL-2. Surviving cells contained more phosphorylated Rb, consistent with the role of Tax in regulation of the cell cycle. Collectively, these results suggest that exosomes may play an important role in extracellular delivery of functional HTLV-1 proteins and mRNA to recipient cells. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Human T-lymphotropic Virus Type 1-infected Cells Secrete Exosomes That Contain Tax Protein*

    Science.gov (United States)

    Jaworski, Elizabeth; Narayanan, Aarthi; Van Duyne, Rachel; Shabbeer-Meyering, Shabana; Iordanskiy, Sergey; Saifuddin, Mohammed; Das, Ravi; Afonso, Philippe V.; Sampey, Gavin C.; Chung, Myung; Popratiloff, Anastas; Shrestha, Bindesh; Sehgal, Mohit; Jain, Pooja; Vertes, Akos; Mahieux, Renaud; Kashanchi, Fatah

    2014-01-01

    Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. The HTLV-1 transactivator protein Tax controls many critical cellular pathways, including host cell DNA damage response mechanisms, cell cycle progression, and apoptosis. Extracellular vesicles called exosomes play critical roles during pathogenic viral infections as delivery vehicles for host and viral components, including proteins, mRNA, and microRNA. We hypothesized that exosomes derived from HTLV-1-infected cells contain unique host and viral proteins that may contribute to HTLV-1-induced pathogenesis. We found exosomes derived from infected cells to contain Tax protein and proinflammatory mediators as well as viral mRNA transcripts, including Tax, HBZ, and Env. Furthermore, we observed that exosomes released from HTLV-1-infected Tax-expressing cells contributed to enhanced survival of exosome-recipient cells when treated with Fas antibody. This survival was cFLIP-dependent, with Tax showing induction of NF-κB in exosome-recipient cells. Finally, IL-2-dependent CTLL-2 cells that received Tax-containing exosomes were protected from apoptosis through activation of AKT. Similar experiments with primary cultures showed protection and survival of peripheral blood mononuclear cells even in the absence of phytohemagglutinin/IL-2. Surviving cells contained more phosphorylated Rb, consistent with the role of Tax in regulation of the cell cycle. Collectively, these results suggest that exosomes may play an important role in extracellular delivery of functional HTLV-1 proteins and mRNA to recipient cells. PMID:24939845

  5. Regulation of human T-lymphotropic virus type I latency and reactivation by HBZ and Rex.

    Directory of Open Access Journals (Sweden)

    Subha Philip

    2014-04-01

    Full Text Available Human T lymphotropic virus type I (HTLV-I infection is largely latent in infected persons. How HTLV-1 establishes latency and reactivates is unclear. Here we show that most HTLV-1-infected HeLa cells become senescent. By contrast, when NF-κB activity is blocked, senescence is averted, and infected cells continue to divide and chronically produce viral proteins. A small population of infected NF-κB-normal HeLa cells expresses low but detectable levels of Tax and Rex, albeit not Gag or Env. In these "latently" infected cells, HTLV-1 LTR trans-activation by Tax persists, but NF-κB trans-activation is attenuated due to inhibition by HBZ, the HTLV-1 antisense protein. Furthermore, Gag-Pol mRNA localizes primarily in the nuclei of these cells. Importantly, HBZ was found to inhibit Rex-mediated export of intron-containing mRNAs. Over-expression of Rex or shRNA-mediated silencing of HBZ led to viral reactivation. Importantly, strong NF-κB inhibition also reactivates HTLV-1. Hence, during HTLV-1 infection, when Tax/Rex expression is robust and dominant over HBZ, productive infection ensues with expression of structural proteins and NF-κB hyper-activation, which induces senescence. When Tax/Rex expression is muted and HBZ is dominant, latent infection is established with expression of regulatory (Tax/Rex/HBZ but not structural proteins. HBZ maintains viral latency by down-regulating Tax-induced NF-κB activation and senescence, and by inhibiting Rex-mediated expression of viral structural proteins.

  6. Human T-lymphotropic virus type 1 infection and disease in Spain.

    Science.gov (United States)

    de Mendoza, Carmen; Caballero, Estrella; Aguilera, Antonio; Requena, Silvia; de Lejarazu, Raúl Ortiz; Pirón, María; González, Rocío; Jiménez, Ana; Roc, Lourdes; Treviño, Ana; Benito, Rafael; Fernández-Alonso, Miriam; Aguinaga, Aitziber; Rodríguez, Carmen; García-Costa, Juan; Blanco, Lidia; Ramos, José M; Calderón, Enrique; Eirós, José M; Sauleda, Silvia; Barreiro, Pablo; Soriano, Vicente

    2017-07-31

    : Human T-lymphotropic virus type 1 (HTLV-1) infection is a neglected disease despite roughly 15 million people are chronically infected worldwide. Lifelong less than 10% of carriers develop life-threatening diseases, mostly a subacute myelopathy known as tropical spastic paraparesis (TSP) and a lymphoproliferative disorder named adult T-cell leukemia (ATL). HTLV-1 is efficiently transmitted perinatally (breastfeeding), sexually (more from men to women) and parenterally (transfusions, injection drug user (IDU), and transplants). To date there is neither prophylactic vaccine nor effective antiviral therapy. A total of 327 cases of HTLV-1 infection had been reported at the HTLV-1 Spanish registry until December 2016, of whom 34 had been diagnosed with TSP and 25 with ATL. Overall 62% were Latin American immigrants and 13% were persons of African origin. The incidence of HTLV-1 in Spain has remained stable for nearly a decade with 20-25 new cases yearly. Of the 21 newly diagnosed HTLV-1 cases during year 2016, one was a native Spaniard pregnant woman, and four presented with symptomatic disease, including three with ATL and one with TSP. Underdiagnosis of HTLV-1 in Spain must be high (iceberg model), which may account for the disproportionate high rate of symptomatic cases (almost 20%) and the late recognition of preventable HTLV-1 transmissions in special populations, such as newborns and transplant recipients. Our current estimate is of 10 000 persons living with HTLV-1 infection in Spain. Given the large flux of immigrants and visitors from HTLV-1 endemic regions to Spain, the expansion of HTLV-1 screening policies is warranted. At this time, it seems worth recommending HTLV testing to all donor/recipient organ transplants and pregnant women regardless place of birth. Although current leukoreduction procedures largely prevent HTLV-1 transmission by blood transfusions, HTLV testing of all first-time donors should be cost-effective contributing to unveil

  7. Family Aggregation of Human T-Lymphotropic Virus 1-Associated Diseases: a Systematic Review

    Directory of Open Access Journals (Sweden)

    Carolina Alvarez

    2016-10-01

    Full Text Available Human T-lymphotropic virus 1 (HTLV-1 is a retrovirus that produces a persistent infection. Two transmission routes (from mother to child and via sexual intercourse favor familial clustering of HTLV-1. It is yet unknown why most HTLV-1 carriers remain asymptomatic while about 10% of them develop complications. HTLV-1 associated diseases were originally described as sporadic entities, but familial presentations have been reported. To explore what is known about family aggregation of HTLV-1-associated diseases we undertook a systematic review. We aimed at answering whether, when and where family aggregation of HTLV-1-associated diseases was reported, which relatives were affected and which hypotheses were proposed to explain aggregation. We searched MEDLINE, abstract books of HTLV conferences and reference lists of selected papers. Search terms used referred to HTLV-1 infection, and HTLV-1-associated diseases, and family studies. HTLV-1-associated diseases considered are adult T-cell leukemia/lymphoma (ATLL, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP, HTLV-1-associated uveitis, and infective dermatitis. Seventy-four records reported HTLV-1-associated diseases in more than one member of the same family and were included. Most reports came from HTLV-1-endemic countries, mainly Japan (n=30 and Brazil (n=10. These reports described a total of 270 families in which more than one relative had HTLV-1-associated diseases. In most families, different family members suffered from the same disease (n=221. The diseases most frequently reported were ATLL (114 families and HAM/TSP (101 families. Most families (n=142 included two to four affected individuals. The proportion of ATLL patients with family history of ATLL ranged from 2% to 26%. The proportion of HAM/TSP patients with family history of HAM/TSP ranged from 1% to 48%. The predominant cluster types for ATLL were clusters of siblings and parent-child pairs and for HAM/TSP, an

  8. Strongyloidiasis and infective dermatitis alter human T lymphotropic virus-1 clonality in vivo.

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    Nicolas A Gillet

    Full Text Available Human T-lymphotropic Virus-1 (HTLV-1 is a retrovirus that persists lifelong by driving clonal proliferation of infected T-cells. HTLV-1 causes a neuroinflammatory disease and adult T-cell leukemia/lymphoma. Strongyloidiasis, a gastrointestinal infection by the helminth Strongyloides stercoralis, and Infective Dermatitis associated with HTLV-1 (IDH, appear to be risk factors for the development of HTLV-1 related diseases. We used high-throughput sequencing to map and quantify the insertion sites of the provirus in order to monitor the clonality of the HTLV-1-infected T-cell population (i.e. the number of distinct clones and abundance of each clone. A newly developed biodiversity estimator called "DivE" was used to estimate the total number of clones in the blood. We found that the major determinant of proviral load in all subjects without leukemia/lymphoma was the total number of HTLV-1-infected clones. Nevertheless, the significantly higher proviral load in patients with strongyloidiasis or IDH was due to an increase in the mean clone abundance, not to an increase in the number of infected clones. These patients appear to be less capable of restricting clone abundance than those with HTLV-1 alone. In patients co-infected with Strongyloides there was an increased degree of oligoclonal expansion and a higher rate of turnover (i.e. appearance and disappearance of HTLV-1-infected clones. In Strongyloides co-infected patients and those with IDH, proliferation of the most abundant HTLV-1⁺ T-cell clones is independent of the genomic environment of the provirus, in sharp contrast to patients with HTLV-1 infection alone. This implies that new selection forces are driving oligoclonal proliferation in Strongyloides co-infection and IDH. We conclude that strongyloidiasis and IDH increase the risk of development of HTLV-1-associated diseases by increasing the rate of infection of new clones and the abundance of existing HTLV-1⁺ clones.

  9. Sensitivity and specificity of four assays to detect human T-lymphotropic virus type I or type I/II antibodies

    NARCIS (Netherlands)

    Vrielink, H.; Reesink, H. W.; Zaaijer, H. L.; van der Poel, C. L.; Cuypers, H. T.; Lelie, P. N.

    1996-01-01

    BACKGROUND: Assays that detect human T-lymphotropic virus type I and type II antibody (HTLV-I/II) are widely used in the routine screening of blood donors. STUDY DESIGN AND METHODS: Four commercially available anti-HTLV-I (Fujirebio and Organon Teknika) or -HTLV-I/II assays (Murex and Ortho) were

  10. Introduction of lymphadenopathy associated virus or human T lymphotropic virus (LAV/HTLV-III) into the male homosexual community in Amsterdam

    NARCIS (Netherlands)

    Coutinho, R. A.; Krone, W. J.; Smit, L.; Albrecht-van Lent, P.; van der Noordaa, J.; Schaesberg, W.; Goudsmit, J.

    1986-01-01

    To establish when lymphadenopathy associated virus or human T lymphotropic virus (LAV/HTLV-III) was introduced into the Netherlands, we studied a cohort of homosexual men who participated in a hepatitis B vaccine efficacy study between 1980 and 1982. On entry into the study (November 1980 to

  11. Are lipid disorders involved in the predominance of human T-lymphotropic virus-1 infections in women?

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    Luciana Debortoli de Carvalho

    2015-12-01

    Full Text Available Abstract INTRODUCTION : The human T-lymphotropic virus-1 (HTLV-1 is associated with chronic inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP, a chronic inflammatory disease. Disturbances in lipid metabolism are involved in inflammatory and demyelinating diseases. METHODS : Plasma levels of triglycerides, total cholesterol, and fractions of HTLV-1-infected individuals of both sexes with different clinical progressions were determined. RESULTS : Elevated levels of triglyceride and very low-density lipoproteins (VLDL were exclusively detected in HTLV-1-infected women from asymptomatic and HAM/TSP groups compared with uninfected individuals (p = 0.02. CONCLUSIONS : Elevated triglyceride and VLDL levels in HTLV-1-infected women may be related to the predominance of HAM/TSP in women.

  12. Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome

    Energy Technology Data Exchange (ETDEWEB)

    DeFreitas, E.; Hilliard, B.; Cheney, P.R.; Bell, D.S.; Kiggundu, E.; Sankey, D.; Wroblewska, Z.; Palladino, M.; Woodward, J.P.; Koprowski, H. (Wistar Inst., Philadelphia, PA (United States))

    1991-04-01

    Chronic fatigue immune dysfunction syndrome (CFIDS) is a recently recognized illness characterized by debilitating fatigue as well as immunological and neurological abnormalities. Once thought to be caused by Epstein-Barr virus, it is now thought to have a different but unknown etiology. The authors evaluted 30 adult and pediatric CFIDS patients from six eastern states for the presence of human T-lymphotropic virus (HTLV) types I and II by Western immunoblotting, polymerase chain reaction, and in situ hybridization of blood samples. The majority of patients were positive for HTLV antibodies by Western blotting and for HTLV-II gag sequences by polymerase chain reaction and in situ hybridization. Twenty nonexposure healthy controls were negative in all assays. These data support an association between an HTLV-II-like virus and CFIDS.

  13. Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome

    International Nuclear Information System (INIS)

    DeFreitas, E.; Hilliard, B.; Cheney, P.R.; Bell, D.S.; Kiggundu, E.; Sankey, D.; Wroblewska, Z.; Palladino, M.; Woodward, J.P.; Koprowski, H.

    1991-01-01

    Chronic fatigue immune dysfunction syndrome (CFIDS) is a recently recognized illness characterized by debilitating fatigue as well as immunological and neurological abnormalities. Once thought to be caused by Epstein-Barr virus, it is now thought to have a different but unknown etiology. The authors evaluted 30 adult and pediatric CFIDS patients from six eastern states for the presence of human T-lymphotropic virus (HTLV) types I and II by Western immunoblotting, polymerase chain reaction, and in situ hybridization of blood samples. The majority of patients were positive for HTLV antibodies by Western blotting and for HTLV-II gag sequences by polymerase chain reaction and in situ hybridization. Twenty nonexposure healthy controls were negative in all assays. These data support an association between an HTLV-II-like virus and CFIDS

  14. Low prevalence of antibodies to human T-lymphotropic virus-I/II among blood donors in eastern Saudi Arabia.

    Science.gov (United States)

    Fawaz, Naglaa A; Tamim, Hala; Almawi, Wassim Y

    2005-04-01

    The seroprevalence of human T-lymphotropic virus (HTLV)-I/II was assessed in 13,443 consecutive blood donors in eastern Saudi Arabia between 1998 and 2001. Screening by enzyme-linked immunosorbent assay (ELISA) and confirmation by Western blot resulted in 8 (0.060%) positive cases, of which 5 (0.056%) belonged to Saudi and 3 (0.113%) to non-Saudi donors. The majority of the HTLV-positive donations (6/8) were for patients, and none had a history of known risk factor for HTLV-I/II transmission. Although the very low prevalence of HTLV-I/II among Saudi donors does not support routine screening, screening of donors from other nationalities may be initiated, especially those from HTLV-I/II endemic areas.

  15. Physiotherapy for human T-lymphotropic virus 1-associated myelopathy: review of the literature and future perspectives.

    Science.gov (United States)

    Sá, Katia N; Macêdo, Maíra C; Andrade, Rosana P; Mendes, Selena D; Martins, José V; Baptista, Abrahão F

    2015-01-01

    Human T-lymphotropic virus 1 (HTLV-1) infection may be associated with damage to the spinal cord - HTLV-associated myelopathy/tropical spastic paraparesis - and other neurological symptoms that compromise everyday life activities. There is no cure for this disease, but recent evidence suggests that physiotherapy may help individuals with the infection, although, as far as we are aware, no systematic review has approached this topic. Therefore, the objective of this review is to address the core problems associated with HTLV-1 infection that can be detected and treated by physiotherapy, present the results of clinical trials, and discuss perspectives on the development of knowledge in this area. Major problems for individuals with HTLV-1 are pain, sensory-motor dysfunction, and urinary symptoms. All of these have high impact on quality of life, and recent clinical trials involving exercises, electrotherapeutic modalities, and massage have shown promising effects. Although not influencing the basic pathologic disturbances, a physiotherapeutic approach seems to be useful to detect specific problems related to body structures, activity, and participation related to movement in HTLV-1 infection, as well as to treat these conditions.

  16. Viral Causes of Lymphoma: The History of Epstein-Barr Virus and Human T-Lymphotropic Virus 1.

    Science.gov (United States)

    Esau, Daniel

    2017-01-01

    In 1964, Epstein, Barr, and Achong published a report outlining their discovery of viral particles in lymphoblasts isolated from a patient with Burkitt lymphoma. The Epstein-Barr virus (EBV) was the first human cancer virus to be described, and its discovery paved the way for further investigations into the oncogenic potential of viruses. In the decades following the discovery of EBV, multinational research efforts led to the discovery of further viral causes of various human cancers. Lymphomas are perhaps the cancer type that is most closely associated with oncogenic viruses: infection with EBV, human T-lymphotropic virus 1 (HTLV-1), human immunodeficiency virus (HIV), Kaposi sarcoma-associated herpesvirus/human herpesvirus 8, and hepatitis C virus have all been associated with lymphomagenesis. Lymphomas have also played an important role in the history of oncoviruses, as both the first human oncovirus (EBV) and the first human retrovirus (HTLV-1) were discovered through isolates taken from patients with unique lymphoma syndromes. The history of the discovery of these 2 key oncoviruses is presented here, and their impact on further medical research, using the specific example of HIV research, is briefly discussed.

  17. Clinical pathophysiology of human T-lymphotropic virus-type1-associated myelopathy/tropical spastic paraparesis

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    Yoshihisa eYamano

    2012-11-01

    Full Text Available Human T-lymphotropic virus type 1 (HTLV-1, a human retrovirus, is the causative agent of a progressive neurological disease termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. HAM/TSP is a chronic inflammatory disease of the central nervous system and is characterized by unremitting myelopathic symptoms such as spastic paraparesis, lower limb sensory disturbance, and bladder/bowel dysfunction. Approximately 0.25%–3.8% of HTLV-1-infected individuals develop HAM/TSP, which is more common in women than in men. Since the discovery of HAM/TSP, significant advances have been made with respect to elucidating the virological, molecular, and immunopathological mechanisms underlying this disease. These findings suggest that spinal cord invasion by HTLV-1-infected T cells triggers a strong virus-specific immune response and increases proinflammatory cytokine and chemokine production, leading to chronic lymphocytic inflammation and tissue damage in spinal cord lesions. However, little progress has been made in the development of an optimal treatment for HAM/TSP, more specifically in the identification of biomarkers for predicting disease progression and of molecular targets for novel therapeutic strategies targeting the underlying pathological mechanisms. This review summarizes current clinical and pathophysiological knowledge on HAM/TSP and discusses future focus areas for research on this disease.

  18. Prevalence of Human T-lymphotropic virus type 1 and 2 among blood donors in Manaus, Amazonas State, Brazil

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    Márcia Poinho EncarnaçÃo de Morais

    2017-12-01

    Full Text Available ABSTRACT Introduction: Human T-lymphotropic virus type 1 and 2 (HTLV-1/2 is endemic in Brazil, but few studies have investigated the seroprevalence of HTLV and its subtypes among blood donors in the capital city Manaus, Amazonas State, Brazil. Aim: To estimate the seroprevalence of HTLV-1/2 and to identify circulating subtypes among blood donors in Manaus. Materials and Methods: Blood donors (2001-2003 were screened for HTLV-1/2 antibodies by ELISA. Positive results were confirmed and subtyped by Western blot assays. Prevalence rates were calculated and compared with demographic data. Results: Among the 87,402 individuals screened, 116 (0.13% were seropositive for HTLV-1/2. A second sample (76/116 was collected and retested by HTLV-1/2 ELISA, of which only 41/76 were positive. Western blot confirmed HTLV infection in 24/41 retested blood donors [HTLV-1 (n=16, HTLV-2 (n=5 and HTLV-untypable (n=3]. Discussion: HTLV-1 and HTLV-2 are prevalent among blood donors in Manaus. However, additional studies are needed to comprehend the epidemiology of HTLV-1/2 in Amazonas not only to understand the pathophysiology of the disease providing adequate medical assistance, but also to reduce or block virus transmission.

  19. Modulation of the Brd4/P-TEFb interaction by the human T-lymphotropic virus type 1 tax protein.

    Science.gov (United States)

    Cho, Won-Kyung; Zhou, Meisheng; Jang, Moon Kyoo; Huang, Keven; Jeong, Soo-Jin; Ozato, Keiko; Brady, John N

    2007-10-01

    Positive transcription elongation factor (P-TEFb), which is composed of CDK9 and cyclin T1, plays an important role in cellular and viral gene expression. Our lab has recently demonstrated that P-TEFb is required for Tax transactivation of the viral long terminal repeat (LTR). P-TEFb is found in two major complexes: the inactive form, which is associated with inhibitory subunits 7SK snRNA and HEXIM1, and the active form, which is associated with, at least in part, Brd4. In this study, we analyzed the effect of Brd4 on human T-lymphotropic virus type 1 (HTLV-1) transcription. Overexpression of Brd4 repressed Tax transactivation of the HTLV-1 LTR in a dose-dependent manner. In vitro binding studies suggest that Tax and Brd4 compete for binding to P-TEFb through direct interaction with cyclin T1. Tax interacts with cyclin T1 amino acids 426 to 533, which overlaps the region responsible for Brd4 binding. In vivo, overexpression of Tax decreased the amount of 7SK snRNA associated with P-TEFb and stimulates serine 2 phosphorylation of the RNA polymerase II carboxyl-terminal domain, suggesting that Tax regulates the functionality of P-TEFb. Our results suggest the possibility that Tax may compete and functionally substitute for Brd4 in P-TEFb regulation.

  20. Leukotrienes are upregulated and associated with human T-lymphotropic virus type 1 (HTLV-1-associated neuroinflammatory disease.

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    Bruno Caetano Trindade

    Full Text Available Leukotrienes (LTs are lipid mediators involved in several inflammatory disorders. We investigated the LT pathway in human T-lymphotropic virus type 1 (HTLV-1 infection by evaluating LT levels in HTLV-1-infected patients classified according to the clinical status as asymptomatic carriers (HACs and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP patients. Bioactive LTB(4 and CysLTs were both increased in the plasma and in the supernatant of peripheral blood mononuclear cell cultures of HTLV-1-infected when compared to non-infected. Interestingly, CysLT concentrations were increased in HAM/TSP patients. Also, the concentration of plasma LTB(4 and LTC(4 positively correlated with the HTLV-1 proviral load in HTLV-1-infected individuals. The gene expression levels of LT receptors were differentially modulated in CD4(+ and CD8(+ T cells of HTLV-1-infected patients. Analysis of the overall plasma signature of immune mediators demonstrated that LT and chemokine amounts were elevated during HTLV-1 infection. Importantly, in addition to CysLTs, IP-10 was also identified as a biomarker for HAM/TSP activity. These data suggest that LTs are likely to be associated with HTLV-1 infection and HAM/TSP development, suggesting their putative use for clinical monitoring.

  1. Viral Causes of Lymphoma: The History of Epstein-Barr Virus and Human T-Lymphotropic Virus 1

    Directory of Open Access Journals (Sweden)

    Daniel Esau

    2017-09-01

    Full Text Available In 1964, Epstein, Barr, and Achong published a report outlining their discovery of viral particles in lymphoblasts isolated from a patient with Burkitt lymphoma. The Epstein-Barr virus (EBV was the first human cancer virus to be described, and its discovery paved the way for further investigations into the oncogenic potential of viruses. In the decades following the discovery of EBV, multinational research efforts led to the discovery of further viral causes of various human cancers. Lymphomas are perhaps the cancer type that is most closely associated with oncogenic viruses: infection with EBV, human T-lymphotropic virus 1 (HTLV-1, human immunodeficiency virus (HIV, Kaposi sarcoma-associated herpesvirus/human herpesvirus 8, and hepatitis C virus have all been associated with lymphomagenesis. Lymphomas have also played an important role in the history of oncoviruses, as both the first human oncovirus (EBV and the first human retrovirus (HTLV-1 were discovered through isolates taken from patients with unique lymphoma syndromes. The history of the discovery of these 2 key oncoviruses is presented here, and their impact on further medical research, using the specific example of HIV research, is briefly discussed.

  2. Human T-lymphotropic virus type 1 prevalence in northeastern Iran, Sabzevar: an epidemiologic-based study and phylogenetic analysis.

    Science.gov (United States)

    Azarpazhooh, Mahmoud Reza; Hasanpour, Kazem; Ghanbari, Mohsen; Rezaee, S A Rahim; Mashkani, Baratali; Hedayati-Moghaddam, Mohammad Reza; Valizadeh, Narges; Farid Hosseini, Reza; Foroghipoor, Mohsen; Soltanifar, Azadeh; Sahebari, Maryam; Azadmanesh, Keyhan; Hassanshahi, Gholahossein; Rafatpanah, Houshang

    2012-09-01

    Human T-lymphotropic virus type 1 (HTLV-I) is an important global health problem in the world mainly in the endemic areas of HTLV-I infection. It was previously reported that Mashhad, in northeastern Iran, is a new endemic region of HTLV-I. The aim of this study was to examine the prevalence and phylogenetic analysis of HTLV-I in Sabzevar, located in the southeast of Mashhad. In this cross-sectional study 1445 individuals were selected by multistage cluster sampling. Serum samples were screened for anti-HTLV-I antibody using enzyme-linked immunosorbent assay (ELISA); all of the ELISA-positive samples were confirmed by polymerase chain reaction (PCR). Long terminal repeat (LTR) sequencing was carried out to determine the type of HTLV-I in Sabzevar. In the primary screening by ELISA, 26/1445 (1.8%) of those sampled were reactive for HTLV-I antibody. Twenty-four out of 26 samples were confirmed HTLV-I infection by PCR (24/1445). The overall prevalence of HTLV-I infection in Sabzevar is 1.66%. The prevalence of the virus infection in men and women was 2.42% (11/455) and 1.31% (13/989), respectively. Seroprevalence was associated with age, increasing significantly among those older than 30 years (p=0.015), and a history of surgery (p=0.002), imprisonment (p=0.018), and hospitalization (p=0.005). Three out of 24 positive HTLV-I samples were selected for sequencing and phylogenetic analysis of LTR. The results showed that HTLV-I in Sabzevar belonged to the cosmopolitan subtype. The present study showed Sabzevar is a new endemic area for HTLV-I infection. Our study emphasizes that systemic HTLV-I screening of blood donors in Sabzevar and other cities in Khorasan province is important and should be taken into account.

  3. Human T-lymphotropic virus type 1 infection is frequent in rural communities of the southern Andes of Peru.

    Science.gov (United States)

    Ita, Fanny; Mayer, Erick F; Verdonck, Kristien; Gonzalez, Elsa; Clark, Daniel; Gotuzzo, Eduardo

    2014-02-01

    To evaluate the presence of human T-lymphotropic virus type 1 (HTLV-1) infection in isolated rural communities in the southern Andes of Peru. We conducted a cross-sectional study in five communities located in three provinces in Ayacucho, Peru. The five communities are located at >3000 meters above sea level and are mainly rural, and more than 85% of the population speaks Quechua. Volunteers aged 12 years and older were included. Clinical and epidemiological data were collected, along with a blood sample for serological testing. We included 397 participants; their median age was 41 years (interquartile range 31-57 years) and 69% were women. According to our definitions, 98% were of Quechua origin. HTLV-1 was diagnosed in 11 people: 0/164 in Cangallo, 3/154 (2%) in Vilcashuaman, and 8/79 (10%) in Parinacochas. There were no cases of HTLV-2. All the HTLV-1-positive participants were born in Ayacucho and were of Quechua origin; they ranged in age from 29 to 87 years (median 56 years) and 10/11 were women. Ten were apparently healthy, and one woman was diagnosed with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Three out of 11 had a family member with a lower limb impairment compatible with HAM/TSP. The fact that HTLV-1 infection was present in two out of three provinces suggests that HTLV-1 could be highly endemic in the southern Andes in the Quechua population. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Long Terminal Repeat Circular DNA as Markers of Active Viral Replication of Human T Lymphotropic Virus-1 in Vivo

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    James M Fox

    2016-03-01

    Full Text Available Clonal expansion of human T-lymphotropic virus type-1 (HTLV-1 infected cells in vivo is well documented. Unlike human immunodeficiency virus type 1 (HIV-1, HTLV-1 plasma RNA is sparse. The contribution of the “mitotic” spread of HTLV-1 compared with infectious spread of the virus to HTLV-1 viral burden in established infection is uncertain. Since extrachromosomal long terminal repeat (LTR DNA circles are indicators of viral replication in HIV-1 carriers with undetectable plasma HIV RNA, we hypothesised that HTLV-1 LTR circles could indicate reverse transcriptase (RT usage and infectious activity. 1LTR and 2LTR DNA circles were measured in HTLV-1 cell lines and peripheral blood mononuclear cells (PBMC of asymptomatic carriers (ACs and patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP or adult T cell leukaemia/lymphoma (ATLL. 1LTR DNA circles were detected in 14/20 patients at a mean of 1.38/100 PBMC but did not differentiate disease status nor correlate with HTLV-1 DNA copies. 2LTR DNA circles were detected in 30/31 patients and at higher concentrations in patients with HTLV-1-associated diseases, independent of HTLV-1 DNA load. In an incident case the 2LTR DNA circle concentration increased 2.1 fold at the onset of HAM/TSP compared to baseline. Detectable and fluctuating levels of HTLV-1 DNA circles in patients indicate viral RT usage and virus replication. Our results indicate HTLV-1 viral replication capacity is maintained in chronic infection and may be associated with disease onset.

  5. Physiotherapy for human T-lymphotropic virus 1-associated myelopathy: review of the literature and future perspectives

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    Sá KN

    2015-02-01

    Full Text Available Katia N Sá,1 Maíra C Macêdo,1 Rosana P Andrade,2 Selena D Mendes,1 José V Martins,3 Abrahão F Baptista1,4 1Neuromusculoskeletal Research Group, Bahian School of Medicine and Human Health, Salvador, Brazil; 2Edgard Santos University Hospital, Federal University of Bahia, Salvador, 3Deolindo Couto Institute of Neurology, Federal University of Rio de Janeiro, Rio de Janeiro, 4Biomorphology Department, Health Sciences Institute, Federal University of Bahia, Salvador, Brazil Abstract: Human T-lymphotropic virus 1 (HTLV-1 infection may be associated with damage to the spinal cord – HTLV-associated myelopathy/tropical spastic paraparesis – and other neurological symptoms that compromise everyday life activities. There is no cure for this disease, but recent evidence suggests that physiotherapy may help individuals with the infection, although, as far as we are aware, no systematic review has approached this topic. Therefore, the objective of this review is to address the core problems associated with HTLV-1 infection that can be detected and treated by physiotherapy, present the results of clinical trials, and discuss perspectives on the development of knowledge in this area. Major problems for individuals with HTLV-1 are pain, sensory-motor dysfunction, and urinary symptoms. All of these have high impact on quality of life, and recent clinical trials involving exercises, electrotherapeutic modalities, and massage have shown promising effects. Although not influencing the basic pathologic disturbances, a physiotherapeutic approach seems to be useful to detect specific problems related to body structures, activity, and participation related to movement in HTLV-1 infection, as well as to treat these conditions. Keywords: HTLV-1, HAM/TSP, physical therapy modalities, quality of life, pain, sensory-motor dysfunction, urinary symptoms

  6. Rate of positive autoimmune markers in Human T lymphotropic virus type 1 carriers: a case-control study from Iran.

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    Ahmadi Ghezeldasht, Sanaz; Hedayati-Moghaddam, Mohammad Reza; Habibi, Meysam; Mollahosseini, Farzad; Rafatpanah, Houshang; Miri, Rahele; Hatef Fard, MohammadReza; Sahebari, Maryam

    2018-01-01

    Human T lymphotropic virus type 1 (HTLV-1) infection with high prevalence in the north-east of Iran, particularly in Mashhad, can lead to adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and a variety of autoimmune diseases. The aim of the study was to examine the presence of autoimmune markers in HTLV carries. Serum samples were obtained from blood donors in Mashhad, northeastern Iran. One hundred and five HTLV-1 positive (cases) and 104 age- and sex-matched HTLV-1 negative donors (controls) were assessed for presence of serum autoimmune markers by enzyme-linked immunosorbent assay. The mean ages of cases and controls were 40.8 ± 9.4 and 41.5 ± 9.3 years, respectively (P = 0.5). In the case group, 81.9% and in the control group 83.7% were male (P = 0.74). The frequency of positive antinuclear antibodies and anticyclic citrullinated peptide antibodies in the serum of the two groups were not significantly different (P = 0.68 and P = 0.62, respectively). Only one antineutrophil cytoplasmic antibody-positive case (1%) was observed in the group and no anti-phospholipid immunoglobulin G positivity was observed. The frequency of rheumatoid factor (RF) was greater in case group than in the control group, although the difference was not significant (P = 0.08). The amount of RF in all 12 RF positive sera were higher than normal levels (33-37 IU/mL). Because we failed to detect any significant relation between serum autoimmune markers and HTLV-1 infection, and because of the relatively low prevalence of autoimmune diseases, it could be concluded that healthy HTLV-1 carriers do not produce rheumatologic-related auto-antibodies more than the healthy population. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  7. Screening for simian foamy virus infection by using a combined antigen Western blot assay: evidence for a wide distribution among Old World primates and identification of four new divergent viruses

    International Nuclear Information System (INIS)

    Hussain, Althaf I.; Shanmugam, Vedapuri; Bhullar, Vinod B.; Beer, Brigitte E.; Vallet, Dominique; Gautier-Hion, Annie; Wolfe, Nathan D.; Karesh, William B.; Kilbourn, Annelisa M.; Tooze, Zeena; Heneine, Walid; Switzer, William M.

    2003-01-01

    Simian foamy viruses (SFVs) belong to a genetically and antigenically diverse class of retroviruses that naturally infect a wide range of nonhuman primates (NHPs) and can also be transmitted to humans occupationally exposed to NHPs. Current serologic detection of SFV infection requires separate Western blot (WB) testing by using two different SFV antigens [SFV AGM (African green monkey) and SFV CPZ (chimpanzee)]. However, this method is labor intensive and validation is limited to only small numbers of NHPs. To facilitate serologic SFV testing, we developed a WB assay that combines antigens from both SFV AGM and SFV CPZ . The combined-antigen WB (CA-WB) assay was validated with 145 serum samples from 129 NHPs (32 African and Asian species) and 16 humans, all with known SFV infection status determined by PCR. Concordant CA-WB results were obtained for all 145 PCR-positive or -negative primate and human specimens, giving the assay a 100% sensitivity and specificity. In addition, no reactivity was observed in sera from persons positive for human immunodeficiency virus or human T cell lymphotropic virus (HIV/HTLV) (n = 25) or HIV/HTLV-negative U.S. blood donors (n = 100). Using the CA-WB assay, we screened 360 sera from 43 Old World primate species and found an SFV prevalence of about 68% in both African and Asian primates. We also isolated SFV from the blood of four seropositive primates (Allenopithecus nigroviridis, Trachypithecus francoisi, Hylobates pileatus, and H. leucogenys) not previously known to be infected with SFV. Phylogenetic analysis of integrase sequences from these isolates confirmed that all four SFVs represent new, distinct, and highly divergent lineages. These results demonstrate the ability of the CA-WB assay to detect infection in a large number of NHP species, including previously uncharacterized infections with divergent SFVs

  8. Quantification of Human T-lymphotropic virus type I (HTLV-I) provirus load in a rural West African population: no enhancement of human immunodeficiency virus type 2 pathogenesis, but HTLV-I provirus load relates to mortality

    NARCIS (Netherlands)

    Ariyoshi, Koya; Berry, Neil; Cham, Fatim; Jaffar, Shabbar; Schim van der Loeff, Maarten; Jobe, Ousman; N'Gom, Pa Tamba; Larsen, Olav; Andersson, Sören; Aaby, Peter; Whittle, Hilton

    2003-01-01

    Human T-lymphotropic virus type I (HTLV-I) provirus load was examined in a cohort of a population in Guinea-Bissau among whom human immunodeficiency virus (HIV) type 2 is endemic. Geometric mean of HIV-2 RNA load among HTLV-I-coinfected subjects was significantly lower than that in subjects infected

  9. HTLV-3/4 and simian foamy retroviruses in humans: discovery, epidemiology, cross-species transmission and molecular virology.

    Science.gov (United States)

    Gessain, Antoine; Rua, Réjane; Betsem, Edouard; Turpin, Jocelyn; Mahieux, Renaud

    2013-01-05

    Non-human primates are considered to be likely sources of viruses that can infect humans and thus pose a significant threat to human population. This is well illustrated by some retroviruses, as the simian immunodeficiency viruses and the simian T lymphotropic viruses, which have the ability to cross-species, adapt to a new host and sometimes spread. This leads to a pandemic situation for HIV-1 or an endemic one for HTLV-1. Here, we present the available data on the discovery, epidemiology, cross-species transmission and molecular virology of the recently discovered HTLV-3 and HTLV-4 deltaretroviruses, as well as the simian foamy retroviruses present in different human populations at risk, especially in central African hunters. We discuss also the natural history in humans of these retroviruses of zoonotic origin (magnitude and geographical distribution, possible inter-human transmission). In Central Africa, the increase of the bushmeat trade during the last decades has opened new possibilities for retroviral emergence in humans, especially in immuno-compromised persons. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Human T-Lymphotropic Virus Type 1-Induced Overexpression of Activated Leukocyte Cell Adhesion Molecule (ALCAM) Facilitates Trafficking of Infected Lymphocytes through the Blood-Brain Barrier.

    Science.gov (United States)

    Curis, Céline; Percher, Florent; Jeannin, Patricia; Montange, Thomas; Chevalier, Sébastien A; Seilhean, Danielle; Cartier, Luis; Couraud, Pierre-Olivier; Gout, Olivier; Gessain, Antoine; Ceccaldi, Pierre-Emmanuel; Afonso, Philippe V

    2016-08-15

    Human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of a slowly progressive neurodegenerative disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This disease develops upon infiltration of HTLV-1-infected lymphocytes into the central nervous system, mostly the thoracic spinal cord. The central nervous system is normally protected by a physiological structure called the blood-brain barrier (BBB), which consists primarily of a continuous endothelium with tight junctions. In this study, we investigated the role of activated leukocyte cell adhesion molecule (ALCAM/CD166), a member of the immunoglobulin superfamily, in the crossing of the BBB by HTLV-1-infected lymphocytes. We demonstrated that ALCAM is overexpressed on the surface of HTLV-1-infected lymphocytes, both in chronically infected cell lines and in primary infected CD4(+) T lymphocytes. ALCAM overexpression results from the activation of the canonical NF-κB pathway by the viral transactivator Tax. In contrast, staining of spinal cord sections of HAM/TSP patients showed that ALCAM expression is not altered on the BBB endothelium in the context of HTLV-1 infection. ALCAM blockade or downregulation of ALCAM levels significantly reduced the migration of HTLV-1-infected lymphocytes across a monolayer of human BBB endothelial cells. This study suggests a potential role for ALCAM in HAM/TSP pathogenesis. Human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of a slowly progressive neurodegenerative disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This disease is the consequence of the infiltration of HTLV-1-infected lymphocytes into the central nervous system (CNS), mostly the thoracic spinal cord. The CNS is normally protected by a physiological structure called the blood-brain barrier (BBB), which consists primarily of a continuous endothelium with tight junctions. The mechanism of migration of lymphocytes into the CNS is unclear

  11. Human T-lymphotropic Virus-1/2 detected in drug abused men who have sex with men infected with HIV in Surakarta, Indonesia

    Science.gov (United States)

    Agung Prasetyo, Afiono; Sari, Yulia

    2018-05-01

    Human T-lymphotropic virus types 1 and 2 (HTLV-1/2) share similar routes of transmission with human immunodeficiency virus (HIV), and the HTLV-1/2 co-infection may affect the clinical course of HIV infection. The HIV/HTLV-1/2 co-infection risk higher if the patient performing the high-risk activities. This study evaluated the presentation of HTLV-1 and 2 in HIV-infected men who have sex with men with drug abused history in Surakarta Indonesia. Blood samples collected from HIV-infected men who have sex with men with drug abused history in Surakarta were tested using HTLV-1/2 enzyme-linked immunosorbent assays and confirmed by RT-PCR nested addressed the part of HTLV-1 LTR and HTLV-2 LTR region, respectively. The specificity of the molecular assays was confirmed by sequencing the amplicons. The anti HTLV-1/2 positive rate was 17.4% (8/46). All positive serological samples were confirmed by nested RT-PCR. Of these, three was HTLV-1 positive and five was HTLV-2 positive. Molecular analysis of positive PCR products revealed that all HTLV-1 isolates had a close relationship with HTLV-1 isolated in Japan while all HTLV-2 isolates with that of isolated in the USA. HTLV-1 and HTLV-2 were detected in drug abused men who have sex with men infected with HIV in Surakarta.

  12. Western blot seroindeterminate individuals for Human T-lymphotropic Virus 1/2 (HTLV-1/2 in Fortaleza (Brazil: a serological and molecular diagnostic and epidemiological approach

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    Santos Terezinha de Jesus Teixeira

    2003-01-01

    Full Text Available How to handle Western blot (WB seroindeterminate individuals for Human T-lymphotropic Virus 1/2 (HTLV-1/2 constitutes a challenge for blood banks and fam ilies. We made a cross-sectional study of 191 enzyme linked immunoassay (EIA reactive individuals from the hematological center (HEMOCE of Fortaleza (Brazil, examining their serological (WB and molecular (PCR diagnosis, and demographic profiles, as well as a possible association of their condition with other infectious pathologies and risk factors. Ethical institutional approval and personal consent were obtained. Out of 191 EIA reactive individuals, 118 were WB seroindeterminate and 73 were seropositive for HTLV-1/2. In the PCR analysis of 41 WB seroindeterminate individuals, 9 (22% were positive and 32 (78% were negative for HTLV-1/2. The demographic analysis indicated a trend towards a predominance of males among the seroindeterminate individuals and females in the seropositive ones. The seroindeterminate individuals were younger than the seropositive ones. We did not find any association of these conditions with syphilis, Chagas disease or HIV or hepatitis, and with risk factors such as breast-feeding, blood transfusion, STD (syphilis and IDU.

  13. Western blot seroindeterminate individuals for Human T-lymphotropic Virus 1/2 (HTLV-1/2 in Fortaleza (Brazil: a serological and molecular diagnostic and epidemiological approach

    Directory of Open Access Journals (Sweden)

    Terezinha de Jesus Teixeira Santos

    Full Text Available How to handle Western blot (WB seroindeterminate individuals for Human T-lymphotropic Virus 1/2 (HTLV-1/2 constitutes a challenge for blood banks and fam ilies. We made a cross-sectional study of 191 enzyme linked immunoassay (EIA reactive individuals from the hematological center (HEMOCE of Fortaleza (Brazil, examining their serological (WB and molecular (PCR diagnosis, and demographic profiles, as well as a possible association of their condition with other infectious pathologies and risk factors. Ethical institutional approval and personal consent were obtained. Out of 191 EIA reactive individuals, 118 were WB seroindeterminate and 73 were seropositive for HTLV-1/2. In the PCR analysis of 41 WB seroindeterminate individuals, 9 (22% were positive and 32 (78% were negative for HTLV-1/2. The demographic analysis indicated a trend towards a predominance of males among the seroindeterminate individuals and females in the seropositive ones. The seroindeterminate individuals were younger than the seropositive ones. We did not find any association of these conditions with syphilis, Chagas disease or HIV or hepatitis, and with risk factors such as breast-feeding, blood transfusion, STD (syphilis and IDU.

  14. Lower numbers of circulating natural killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease

    Science.gov (United States)

    Ndhlovu, L C; Snyder-Cappione, J E; Carvalho, K I; Leal, F E; Loo, C P; bruno, F R; Jha, A R; Devita, D; Hasenkrug, A M; Barbosa, H M R; Segurado, A C; Nixon, D F; Murphy, E L; Kallas, E G

    2009-01-01

    Human T lymphotropic virus type 1 (HTLV-1) infects 10–20 million people worldwide. The majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV-1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/TSP infection from two cohorts on two continents: São Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4+ and fewer CD8+ cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4+ NK T subset are associated with HTLV-1 disease progression. PMID:19778295

  15. The human T-lymphotropic virus type I tax gene can cooperate with the ras oncogene to induce neoplastic transformation of cells.

    Science.gov (United States)

    Pozzatti, R; Vogel, J; Jay, G

    1990-01-01

    Epidemiologic studies have linked infection by the human T-lymphotropic virus type I (HTLV-I) with the development of adult T-cell leukemia. The low penetrance of the virus and the long latency for disease manifestation are factors that obscure the role of HTLV-I infection in oncogenesis. We have used an in vitro transformation assay system to determine directly whether the HTLV-I tax gene has transformation potential. Transfection of the tax gene alone into early-passage rat embryo fibroblasts did not induce morphological alterations. However, cotransfection of tax with the selectable marker plasmid pRSVneo gave rise to G418-resistant colonies that could be established as immortalized cell lines. Cotransfection of tax with the ras oncogene into rat embryo fibroblasts gave rise to foci of transformed cells that were highly tumorigenic in nude mice. These data represent a direct demonstration of the oncogenic potential of the tax gene in nonlymphoid cells and establish HTLV-I as a transforming virus.

  16. Comparison of seropositivity of human T lymphotropic virus type 1 in mycosis fungoides patients and normal volunteers: A case-control study and review of literature

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    Seirafi Hassan

    2009-01-01

    Full Text Available Background: There have been controversial reports about the possible association between mycosis fungoides (MF, its leukemic variant Sιzary syndrome (SS and human T lymphotropic virus type 1 (HTLV-1 in different geographical regions. Aims: The purpose of this study was to explore any association between MF and presence of HTLV-1 infection in Iran. Methods: In a case-control setting, 150 clinically and histopathologically proven MF patients had been admitted to the tertiary referral skin center during a 10-year period and another 150 normal volunteers had been compared with each other for the presence of HTLV-1 infection. Enzyme-linked immunosorbent assay (ELISA was used to detect antibodies against HTLV-1, and positive results were confirmed with western blotting. Results: Only three MF patients had HTLV-1 infection, whereas two cases of normal subjects had the infection ( P > 0.05. The only three seropositive MF patients were male and from North-Eastern Iran . Conclusion: This study showed that MF does not correlate with HTLV-1 infection in Iran.

  17. ORIGIN AND PREVALENCE OF HUMAN T-LYMPHOTROPIC VIRUS TYPE 1 (HTLV-1 AND TYPE 2 (HTLV-2 AMONG INDIGENOUS POPULATIONS IN THE AMERICAS

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    Arthur Paiva

    2015-02-01

    Full Text Available Human T-lymphotropic virus type 1 (HTLV-1 is found in indigenous peoples of the Pacific Islands and the Americas, whereas type 2 (HTLV-2 is widely distributed among the indigenous peoples of the Americas, where it appears to be more prevalent than HTLV-1, and in some tribes of Central Africa. HTLV-2 is considered ancestral in the Americas and is transmitted to the general population and injection drug users from the indigenous population. In the Americas, HTLV-1 has more than one origin, being brought by immigrants in the Paleolithic period through the Bering Strait, through slave trade during the colonial period, and through Japanese immigration from the early 20th century, whereas HTLV-2 was only brought by immigrants through the Bering Strait. The endemicity of HTLV-2 among the indigenous people of Brazil makes the Brazilian Amazon the largest endemic area in the world for its occurrence. A review of HTLV-1 in all Brazilian tribes supports the African origin of HTLV-1 in Brazil. The risk of hyperendemicity in these epidemiologically closed populations and transmission to other populations reinforces the importance of public health interventions for HTLV control, including the recognition of the infection among reportable diseases and events.

  18. Use of anti-tumor necrosis factor biologics in the treatment of rheumatoid arthritis does not change human T-lymphotropic virus type 1 markers: a case series.

    Science.gov (United States)

    Umekita, Kunihiko; Umeki, Kazumi; Miyauchi, Shunichi; Ueno, Shiro; Kubo, Kazuyoshi; Kusumoto, Norio; Takajo, Ichiro; Nagatomo, Yasuhiro; Okayama, Akihiko

    2015-09-01

    Anti-tumor necrosis factor (anti-TNF) biologics are effective in the treatment of rheumatoid arthritis (RA); however, it is still not clear whether this treatment promotes the development of malignancies such as lymphoma. Human T-lymphotropic virus type 1 (HTLV-1), which is a causative agent of adult T-cell lymphoma (ATL), is prevalent in Japan. Many HTLV-1-positive patients with RA are assumed to exist; however, there have thus far been no reports on the effect of anti-TNF biologics on HTLV-1-positive patients. We analyzed the response to treatment with anti-TNF biologics and change of HTLV-1 markers in two cases of RA. The two cases showed no response based on the European League Against of Rheumatism response criteria 60-96 weeks after administration of anti-TNF biologics (infliximab and etanercept). No signs of ATL were observed and HTLV-1 markers, such as proviral load and clonality of HTLV-1-infected cells, showed no significant change in either of two cases. Therefore, treatment with anti-TNF biologics did not induce activation of HTLV-1, although the effect on RA was not as effective as in HTLV-1-negative patients in this limited study. Further long-term study with a greater number of patients is necessary to clarify the safety and efficacy of anti-TNF biologics in HTLV-1-positive patients with RA.

  19. Histone acetyltransferase (HAT) activity of p300 modulates human T lymphotropic virus type 1 p30II-mediated repression of LTR transcriptional activity

    International Nuclear Information System (INIS)

    Michael, Bindhu; Nair, Amrithraj M.; Datta, Antara; Hiraragi, Hajime; Ratner, Lee; Lairmore, Michael D.

    2006-01-01

    Human T-lymphotropic virus type-1 (HTLV-1) is a deltaretrovirus that causes adult T cell leukemia/lymphoma, and is implicated in a variety of lymphocyte-mediated inflammatory disorders. HTLV-1 provirus has regulatory and accessory genes in four pX open reading frames. HTLV-1 pX ORF-II encodes two proteins, p13 II and p30 II , which are incompletely defined in virus replication or pathogenesis. We have demonstrated that pX ORF-II mutations block virus replication in vivo and that ORF-II encoded p30 II , a nuclear-localizing protein that binds with CREB-binding protein (CBP)/p300, represses CREB and Tax responsive element (TRE)-mediated transcription. Herein, we have identified p30 II motifs important for p300 binding and in regulating TRE-mediated transcription in the absence and presence of HTLV-1 provirus. Within amino acids 100-179 of p30 II , a region important for repression of LTR-mediated transcription, we identified a single lysine residue at amino acid 106 (K3) that significantly modulates the ability of p30 II to repress TRE-mediated transcription. Exogenous p300, in a dose-responsive manner, reverses p30 II -dependent repression of TRE-mediated transcription, in the absence or presence of the provirus, In contrast to wild type p300, p300 HAT mutants (defective in histone acetyltransferase activity) only partially rescued p30 II -mediated LTR repression. Deacetylation by histone deacetylase-1 (HDAC-1) enhanced p30 II -mediated LTR repression, while inhibition of deacetylation by trichostatin A decreases p30 II -mediated LTR repression. Collectively, our data indicate that HTLV-1 p30 II modulates viral gene expression in a cooperative manner with p300-mediated acetylation

  20. Human T lymphotropic virus type-1 p30II alters cellular gene expression to selectively enhance signaling pathways that activate T lymphocytes

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    Feuer Gerold

    2004-11-01

    Full Text Available Abstract Background Human T-lymphotropic virus type-1 (HTLV-1 is a deltaretrovirus that causes adult T-cell leukemia/lymphoma and is implicated in a variety of lymphocyte-mediated disorders. HTLV-1 contains both regulatory and accessory genes in four pX open reading frames. pX ORF-II encodes two proteins, p13II and p30II, which are incompletely defined in the virus life cycle or HTLV-1 pathogenesis. Proviral clones of the virus with pX ORF-II mutations diminish the ability of the virus to maintain viral loads in vivo. Exogenous expression of p30II differentially modulates CREB and Tax-responsive element-mediated transcription through its interaction with CREB-binding protein/p300 and represses tax/rex RNA nuclear export. Results Herein, we further characterized the role of p30II in regulation of cellular gene expression, using stable p30II expression system employing lentiviral vectors to test cellular gene expression with Affymetrix U133A arrays, representing ~33,000 human genes. Reporter assays in Jurkat T cells and RT-PCR in Jurkat and primary CD4+ T-lymphocytes were used to confirm selected gene expression patterns. Our data reveals alterations of interrelated pathways of cell proliferation, T-cell signaling, apoptosis and cell cycle in p30II expressing Jurkat T cells. In all categories, p30II appeared to be an overall repressor of cellular gene expression, while selectively increasing the expression of certain key regulatory genes. Conclusions We are the first to demonstrate that p30II, while repressing the expression of many genes, selectively activates key gene pathways involved in T-cell signaling/activation. Collectively, our data suggests that this complex retrovirus, associated with lymphoproliferative diseases, relies upon accessory gene products to modify cellular environment to promote clonal expansion of the virus genome and thus maintain proviral loads in vivo.

  1. Human T-Lymphotropic Virus Type 1 (HTLV-1 and Regulatory T Cells in HTLV-1-Associated Neuroinflammatory Disease

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    Yoshihisa Yamano

    2011-08-01

    Full Text Available Human T-lymphotropic virus type 1 (HTLV-1 is a retrovirus that is the causative agent of adult T cell leukemia/lymphoma (ATL and associated with multiorgan inflammatory disorders, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP and uveitis. HTLV-1-infected T cells have been hypothesized to contribute to the development of these disorders, although the precise mechanisms are not well understood. HTLV-1 primarily infects CD4+ T helper (Th cells that play a central role in adaptive immune responses. Based on their functions, patterns of cytokine secretion, and expression of specific transcription factors and chemokine receptors, Th cells that are differentiated from naïve CD4+ T cells are classified into four major lineages: Th1, Th2, Th17, and T regulatory (Treg cells. The CD4+CD25+CCR4+ T cell population, which consists primarily of suppressive T cell subsets, such as the Treg and Th2 subsets in healthy individuals, is the predominant viral reservoir of HTLV-1 in both ATL and HAM/TSP patients. Interestingly, CD4+CD25+CCR4+ T cells become Th1-like cells in HAM/TSP patients, as evidenced by their overproduction of IFN-γ, suggesting that HTLV-1 may intracellularly induce T cell plasticity from Treg to IFN-γ+ T cells. This review examines the recent research into the association between HTLV-1 and Treg cells that has greatly enhanced understanding of the pathogenic mechanisms underlying immune dysregulation in HTLV-1-associated neuroinflammatory disease.

  2. Human T-lymphotropic virus type 1 Tax protein complexes with P-TEFb and competes for Brd4 and 7SK snRNP/HEXIM1 binding.

    Science.gov (United States)

    Cho, Won-Kyung; Jang, Moon Kyoo; Huang, Keven; Pise-Masison, Cynthia A; Brady, John N

    2010-12-01

    Positive transcription elongation factor b (P-TEFb) plays an important role in stimulating RNA polymerase II elongation for viral and cellular gene expression. P-TEFb is found in cells in either an active, low-molecular-weight (LMW) form or an inactive, high-molecular-weight (HMW) form. We report here that human T-lymphotropic virus type 1 (HTLV-1) Tax interacts with the cyclin T1 subunit of P-TEFb, forming a distinct Tax/P-TEFb LMW complex. We demonstrate that Tax can play a role in regulating the amount of HMW complex present in the cell by decreasing the binding of 7SK snRNP/HEXIM1 to P-TEFb. This is seen both in vitro using purified Tax protein and in vivo in cells transduced with Tax expression constructs. Further, we find that a peptide of cyclin T1 spanning the Tax binding domain inhibits the ability of Tax to disrupt HMW P-TEFb complexes. These results suggest that the direct interaction of Tax with cyclin T1 can dissociate P-TEFb from the P-TEFb/7SK snRNP/HEXIM1 complex for activation of the viral long terminal repeat (LTR). We also show that Tax competes with Brd4 for P-TEFb binding. Chromatin immunoprecipitation (ChIP) assays demonstrated that Brd4 and P-TEFb are associated with the basal HTLV-1 LTR, while Tax and P-TEFb are associated with the activated template. Furthermore, the knockdown of Brd4 by small interfering RNA (siRNA) activates the HTLV-1 LTR promoter, which results in an increase in viral expression and production. Our studies have identified Tax as a regulator of P-TEFb that is capable of affecting the balance between its association with the large inactive complex and the small active complex.

  3. Discordant human T-lymphotropic virus screening with Western blot confirmation: evaluation of the dual-test algorithm for US blood donations.

    Science.gov (United States)

    Stramer, Susan L; Townsend, Rebecca L; Foster, Gregory A; Johnson, Ramona; Weixlmann, Barbara; Dodd, Roger Y

    2018-03-01

    Human T-lymphotropic virus (HTLV) blood donation screening has used a dual-testing algorithm beginning with either a chemiluminescent immunoassay or enzyme-linked immunosorbent screening assay (ELISA). Before the availability of a licensed HTLV supplemental assay, repeat-reactive (RR) samples on a first assay (Assay 1) were retested with a second screening assay (Assay 2). Donors with RR results by Assay 2 were deferred from blood donation and further tested using an unlicensed supplemental test to confirm reactivity while nonreactive (NR) donors remained eligible for donation until RR on a subsequent donation. This "dual-test" algorithm was replaced in May 2016 with the requirement that all RRs by Assay 1 be further tested by a licensed HTLV supplemental test (Western blot [WB]). In this study, we have requalified the dual-test algorithm using the available licensed HTLV WB. We tested 100 randomly selected HTLV RRs on screening Assay 1 (Abbott PRISM chemiluminescent immunoassay) but NR on screening Assay 2 (Avioq ELISA) by a Food and Drug Administration-licensed WB (MP Biomedicals) to ensure that no confirmed positives were among those that were RR by Assay 1 but NR by Assay 2. Of the 100 samples evaluated, 79 of 100 were WB seronegative, 21 of 100 indeterminate, and 0 of 100 seropositive. Of the 79 of 100 seronegative specimens, 73 of 79 did not express any bands on WB. We demonstrated that none of the 100 samples RR on Assay 1 but NR on Assay 2 were confirmed positive. This algorithm prevents such donors from requiring further testing and from being deferred. © 2018 AABB.

  4. Importance of a Rapid and Accurate Diagnosis in Strongyloides Stercoralis and Human T-Lymphotropic Virus 1 Co-infection: A Case Report and Review of the Literature.

    Science.gov (United States)

    Quintero, Olga; Berini, Carolina A; Waldbaum, Carlos; Avagnina, Alejandra; Juarez, María; Repetto, Silvia; Sorda, Juan; Biglione, Mirna

    2017-01-01

    Strongyloides (S.) stercoralis and Human T-Lymphotropic Virus 1 (HTLV-1) share some endemic regions such as Japan, Jamaica, and South America and are mostly diagnosed elsewhere in immigrants from endemic areas. This co-infection has not been documented in Argentina although both pathogens are endemic in the Northwest. We present a case of S. stercoralis and HTLV-1 co-infection with an initial presentation due to gastrointestinal symptoms which presented neither eosinophilia nor the presence of larvae in stool samples in a non-endemic area for these infections. A young Peruvian woman living in Buenos Aires attended several emergency rooms and finally ended up admitted in a gastroenterology ward due to incoercible vomiting, diarrhea, abdominal pain, fever, and weight loss. Gastrointestinal symptoms started 3 months before she returned to Argentina from a trip to Peru. She presented malnutrition and abdominal distension parameters. HIV-1 and other immunodeficiencies were discarded. The serial coproparasitological test was negative. Computed tomography showed diffuse thickening of duodenal and jejunal walls. At the beginning, vasculitis was suspected and corticosteroid therapy was initiated. The patient worsened rapidly. Skin, new enteral biopsies, and a new set of coproparasitological samples revealed S. stercoralis . Then, HTLV-1 was suspected and infection was confirmed. Ivermectin and albendazole were administrated, until the stool sample remained negative for 2 weeks. Larvae were not observed in fresh stool, Ritchie method, and agar culture 1 week post-treatment. Although she required initial support with parenteral nutrition due to oral intolerance she slowly progressed favorably. It has been highly recommended to include a rapid and sensitive PCR strategy in the algorithm to confirm Strongyloides infection, which has demonstrated to improve early diagnosis in patients at-risk of disseminated strongyloidiasis.

  5. Importance of a Rapid and Accurate Diagnosis in Strongyloides Stercoralis and Human T-Lymphotropic Virus 1 Co-infection: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Olga Quintero

    2017-12-01

    Full Text Available Strongyloides (S. stercoralis and Human T-Lymphotropic Virus 1 (HTLV-1 share some endemic regions such as Japan, Jamaica, and South America and are mostly diagnosed elsewhere in immigrants from endemic areas. This co-infection has not been documented in Argentina although both pathogens are endemic in the Northwest. We present a case of S. stercoralis and HTLV-1 co-infection with an initial presentation due to gastrointestinal symptoms which presented neither eosinophilia nor the presence of larvae in stool samples in a non-endemic area for these infections. A young Peruvian woman living in Buenos Aires attended several emergency rooms and finally ended up admitted in a gastroenterology ward due to incoercible vomiting, diarrhea, abdominal pain, fever, and weight loss. Gastrointestinal symptoms started 3 months before she returned to Argentina from a trip to Peru. She presented malnutrition and abdominal distension parameters. HIV-1 and other immunodeficiencies were discarded. The serial coproparasitological test was negative. Computed tomography showed diffuse thickening of duodenal and jejunal walls. At the beginning, vasculitis was suspected and corticosteroid therapy was initiated. The patient worsened rapidly. Skin, new enteral biopsies, and a new set of coproparasitological samples revealed S. stercoralis. Then, HTLV-1 was suspected and infection was confirmed. Ivermectin and albendazole were administrated, until the stool sample remained negative for 2 weeks. Larvae were not observed in fresh stool, Ritchie method, and agar culture 1 week post-treatment. Although she required initial support with parenteral nutrition due to oral intolerance she slowly progressed favorably. It has been highly recommended to include a rapid and sensitive PCR strategy in the algorithm to confirm Strongyloides infection, which has demonstrated to improve early diagnosis in patients at-risk of disseminated strongyloidiasis.

  6. Human T-lymphotropic virus type-1 p30 alters cell cycle G2 regulation of T lymphocytes to enhance cell survival

    Directory of Open Access Journals (Sweden)

    Silverman Lee

    2007-07-01

    Full Text Available Abstract Background Human T-lymphotropic virus type-1 (HTLV-1 causes adult T-cell leukemia/lymphoma and is linked to a number of lymphocyte-mediated disorders. HTLV-1 contains both regulatory and accessory genes in four pX open reading frames. pX ORF-II encodes two proteins, p13 and p30, whose roles are still being defined in the virus life cycle and in HTLV-1 virus-host cell interactions. Proviral clones of HTLV-1 with pX ORF-II mutations diminish the ability of the virus to maintain viral loads in vivo. p30 expressed exogenously differentially modulates CREB and Tax-responsive element-mediated transcription through its interaction with CREB-binding protein/p300 and while acting as a repressor of many genes including Tax, in part by blocking tax/rex RNA nuclear export, selectively enhances key gene pathways involved in T-cell signaling/activation. Results Herein, we analyzed the role of p30 in cell cycle regulation. Jurkat T-cells transduced with a p30 expressing lentivirus vector accumulated in the G2-M phase of cell cycle. We then analyzed key proteins involved in G2-M checkpoint activation. p30 expression in Jurkat T-cells resulted in an increase in phosphorylation at serine 216 of nuclear cell division cycle 25C (Cdc25C, had enhanced checkpoint kinase 1 (Chk1 serine 345 phosphorylation, reduced expression of polo-like kinase 1 (PLK1, diminished phosphorylation of PLK1 at tyrosine 210 and reduced phosphorylation of Cdc25C at serine 198. Finally, primary human lymphocyte derived cell lines immortalized by a HTLV-1 proviral clone defective in p30 expression were more susceptible to camptothecin induced apoptosis. Collectively these data are consistent with a cell survival role of p30 against genotoxic insults to HTLV-1 infected lymphocytes. Conclusion Collectively, our data are the first to indicate that HTLV-1 p30 expression results in activation of the G2-M cell cycle checkpoint, events that would promote early viral spread and T

  7. Human T-lymphotropic virus type-I infection, antibody titers and cause-specific mortality among atomic-bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Arisawa, Kokichi; Soda, Midori; Akahoshi, Masazumi [Radiation Effects Research Foundation, Nagasaki (Japan). Nagasaki Lab.; Matsuo, Tatsuki; Nakashima, Eiji; Tomonaga, Masao; Saito, Hiroshi

    1998-08-01

    There have been few longitudinal studies on the long-term health effects of human T-lymphotropic virus type-I (HTLV-I) infection. The authors performed a cohort study of HTLV-I infection and cause-specific mortality in 3,090 atomic-bomb survivors in Nagasaki, Japan, who were followed from 1985-1987 to 1995. The prevalence of HTLV-I seropositivity in men and women was 99/1,196 (8.3%) and 171/1,894 (9.0%), respectively. During a median follow-up of 8.9 years, 448 deaths occurred. There was one nonfatal case of adult T-cell leukemia/lymphoma (incidence rate=0.46 cases/1,000 person-years; 95% confidence interval (CI) 0.01-2.6). After adjustment for sex, age and other potential confounders, significantly increased risk among HTLV-I carriers was observed for deaths from all causes (rate ratio (RR)=1.41), all cancers (RR=1.64), liver cancer (RR=3.04), and heart diseases (RR=2.22). The association of anti-HTLV-I seropositivity with mortality from all non-neoplastic diseases (RR=1.40) and chronic liver diseases (RR=5.03) was of borderline significance. Possible confounding by blood transfusions and hepatitis C/B (HCV/HBV) viral infections could not be precluded in this study. However, even after liver cancer and chronic liver diseases were excluded, mortality rate was still increased among HTLV-I carriers (RR=1.32, 95% CI 0.99-1.78), especially among those with high antibody titers (RR=1.56, 95% CI 0.99-2.46, P for trend=0.04). These findings may support the idea that HTLV-I infection exerts adverse effects on mortality from causes other than adult T-cell leukemia/lymphoma. Further studies on confounding by HCV/HBV infections and the interaction between HCV/HBV and HTLV-I may be required to analyze the increased mortality from liver cancer and chronic liver diseases. (author)

  8. Additional recommendations to reduce sexual and drug abuse-related transmission of human T-lymphotropic virus type III/lymphadenopathy-associated virus.

    Science.gov (United States)

    1986-03-14

    Previous US Public Health Service recommendations pertaining to sexual, IV drug abuse, and perinatal transmission of human-T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) have been published. Reduction of sexual and IV transmission of HTLV-III/LAV should be enhanced by using available serologic tests to give asymptomatic, infected individuals in high-risk groups the opportunity to know their status so they can take appropriate steps to prevent the further transmission of this virus. Since the objective of these additional recommendations is to help interrupt transmission by encouraging testing and counseling among persons in high-risk groups, careful attention must be paid to maintaining confidentiality and to protecting records from any unauthorized disclosure. The ability of health departments to assure confidentiality, and the public confidence in that ability, are crucial to efforts to increase the number of persons requesting such testing and counseling. Persons at increased risk of HTLV-III/LAV infection include: homosexual and bisexual men; present or past IV drug abusers; persons with clinical or laboratory evidence of infection, such as those with signs or symptoms compatible with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC); persons born in countries where heterosexual transmission is thought to play a major role; male or female prostitutes and their sex partners; sex partners of infected persons or persons at increased risk; all persons with hemophilia who have received clotting-factor products; and newborn infants of high-risk or infected mothers. Recommendations include: community health education programs should be aimed at members of high-risk groups to increase knowledge of AIDS, to facilitate behavioral changes to reduce risks of HTLV-III/LAV infection, and encourage voluntary testing and counseling; counseling and voluntary serologic testing for HTLV-III/LAV should be routinely offered to

  9. Quantification of Human T-lymphotropic virus type I (HTLV-I) provirus load in a rural West African population: no enhancement of human immunodeficiency virus type 2 pathogenesis, but HTLV-I provirus load relates to mortality

    DEFF Research Database (Denmark)

    Ariyoshi, K; Berry, N; Cham, F

    2003-01-01

    Human T-lymphotropic virus type I (HTLV-I) provirus load was examined in a cohort of a population in Guinea-Bissau among whom human immunodeficiency virus (HIV) type 2 is endemic. Geometric mean of HIV-2 RNA load among HTLV-I-coinfected subjects was significantly lower than that in subjects...... infected with HIV-2 alone (212 vs. 724 copies/mL; P=.02). Adjusted for age, sex, and HIV status, the risk of death increased with HTLV-I provirus load; mortality hazard ratio was 1.59 for each log10 increase in HTLV-I provirus copies (P=.038). There is no enhancing effect of HTLV-I coinfection on HIV-2...... disease, but high HTLV-I provirus loads may contribute to mortality....

  10. Loss of memory CD4+ T-cells in semi-wild mandrills (Mandrillus sphinx) naturally infected with species-specific simian immunodeficiency virus SIVmnd-1.

    Science.gov (United States)

    Greenwood, Edward J D; Schmidt, Fabian; Liégeois, Florian; Kondova, Ivanela; Herbert, Anaïs; Ngoubangoye, Barthelemy; Rouet, François; Heeney, Jonathan L

    2014-01-01

    Simian immunodeficiency virus (SIV) infection is found in a number of African primate species and is thought to be generally non-pathogenic. However, studies of wild primates are limited to two species, with SIV infection appearing to have a considerably different outcome in each. Further examination of SIV-infected primates exposed to their natural environment is therefore warranted. We performed a large cross-sectional study of a cohort of semi-wild mandrills with naturally occurring SIV infection, including 39 SIV-negative and 33 species-specific SIVmnd-1-infected animals. This study was distinguished from previous reports by considerably greater sample size, examination of exclusively naturally infected animals in semi-wild conditions and consideration of simian T-lymphotropic virus (STLV) status in addition to SIVmnd-1 infection. We found that SIVmnd-1 infection was associated with a significant and progressive loss of memory CD4(+) T-cells. Limited but significant increases in markers of immune activation in the T-cell populations, significant increases in plasma neopterin and changes to B-cell subsets were also observed in SIV-infected animals. However, no increase in plasma soluble CD14 was observed. Histological examination of peripheral lymph nodes suggested that SIVmnd-1 infection was not associated with a significant disruption of the lymph node architecture. Whilst this species has evolved numerous strategies to resist the development of AIDS, significant effects of SIV infection could be observed when examined in a natural environment. STLVmnd-1 infection also had significant effects on some markers relevant to understanding SIV infection and thus should be considered in studies of SIV infection of African primates where present.

  11. Tax secretion from peripheral blood mononuclear cells and Tax detection in plasma of patients with human T-lymphotropic virus-type 1-associated myelopathy/tropical spastic paraparesis and asymptomatic carriers.

    Science.gov (United States)

    Medina, Fernando; Quintremil, Sebastián; Alberti, Carolina; Godoy, Fabián; Pando, María E; Bustamante, Andrés; Barriga, Andrés; Cartier, Luis; Puente, Javier; Tanaka, Yuetsu; Valenzuela, María A; Ramírez, Eugenio

    2016-03-01

    Human T-lymphotropic virus-type 1 (HTLV-1) is the etiologic agent of the neurologic disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Tax viral protein plays a critical role in viral pathogenesis. Previous studies suggested that extracellular Tax might involve cytokine-like extracellular effects. We evaluated Tax secretion in 18 h-ex vivo peripheral blood mononuclear cells (PBMCs) cultures from 15 HAM/TSP patients and 15 asymptomatic carriers. Futhermore, Tax plasma level was evaluated from other 12 HAM/TSP patients and 10 asymptomatic carriers. Proviral load and mRNA encoding Tax were quantified by PCR and real-time RT-PCR, respectively. Intracellular Tax in CD4(+)CD25(+) cells occurred in 100% and 86.7% of HAM/TSP patients and asymptomatic carriers, respectively. Percentage of CD4(+)CD25(+) Tax+, proviral load and mRNA encoding Tax were significantly higher in HAM/TSP patients. Western blot analyses showed higher secretion levels of ubiquitinated Tax in HAM/TSP patients than in asymptomatic carriers. In HTLV-1-infected subjects, Western blot of plasma Tax showed higher levels in HAM/TSP patients than in asymptomatic carriers, whereas no Tax was found in non-infected subjects. Immunoprecipitated plasma Tax resolved on SDS-PAGE gave two major bands of 57 and 48 kDa allowing identification of Tax and Ubiquitin peptides by mass spectrometry. Relative percentage of either CD4(+)CD25(+) Tax+ cells, or Tax protein released from PBMCs, or plasma Tax, correlates neither with tax mRNA nor with proviral load. This fact could be explained by a complex regulation of Tax expression. Tax secreted from PBMCs or present in plasma could potentially become a biomarker to distinguish between HAM/TSP patients and asymptomatic carriers. © 2015 Wiley Periodicals, Inc.

  12. A comparison of human immunodeficiency virus, hepatitis C virus, hepatitis B virus, and human T-lymphotropic virus marker rates for directed versus volunteer blood donations to the American Red Cross during 2005 to 2010.

    Science.gov (United States)

    Dorsey, Kerri A; Moritz, Erin D; Steele, Whitney R; Eder, Anne F; Stramer, Susan L

    2013-06-01

    At most US blood centers, patients may still opt to choose specific donors to give blood for their anticipated transfusion needs. However, there is little evidence of improved safety with directed donation when compared to volunteer donation. The percentage of directed donations made to the American Red Cross (ARC) from 1995 to 2010 was determined. Infectious disease marker rates for human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), and human T-lymphotropic virus (HTLV) were calculated for volunteer and directed donations made from 2005 to 2010. Odds ratios (ORs) were calculated to compare marker-positive rates of directed donations to volunteer donations. The percentage of donations from directed donors declined from 1.6% in 1995 to 0.12% in 2010. From 2005 to 2010, the ARC collected 38,894,782 volunteer and 69,869 directed donations. Rates of HIV, HCV, HBV, and HTLV for volunteer donations were 2.9, 32.2, 12.4, and 2.5 per 100,000 donations, respectively; for directed, the rates were 7.2, 93.0, 40.1, and 18.6 per 100,000. After demographics and first-time or repeat status were adjusted for, corresponding ORs of viral marker positivity in directed versus volunteer donations were not significant for HIV, HBV, or HTLV and significant for HCV (OR, 0.7; 95% confidence interval, 0.50-0.90). Directed donations have declined by 92% at the ARC since 1995, but have higher viral marker rates than volunteer donations. The difference can be explained in part by the effects of first-time or repeat status of the donors. Patients considering directed donation should be appropriately counseled about the potential risks. © 2012 American Association of Blood Banks.

  13. Finite Divergence

    DEFF Research Database (Denmark)

    Hansen, Michael Edberg; Pandya, P. K.; Chaochen, Zhou

    1995-01-01

    the framework of duration calculus. Axioms and proof rules are given. Patterns of occurrence of divergence are classified into dense divergence, accumulative divergence and discrete divergence by appropriate axioms. Induction rules are given for reasoning about discrete divergence...

  14. In vivo fluctuation of Tax, Foxp3, CTLA-4, and GITR mRNA expression in CD4(+)CD25(+) T cells of patients with human T-lymphotropic virus type 1-associated myelopathy.

    Science.gov (United States)

    Ramirez, E; Cartier, L; Rodriguez, L; Alberti, C; Valenzuela, M A

    2010-11-01

    HTLV-1 Tax expression exerts an inhibitory effect on the Foxp3 transcription factor in CD4(+)CD25(+) T-regulatory cells (Treg). For a better understanding of the role of Tax mRNA in the gene expression of cellular markers we measured Tax, Foxp3, CTLA-4, GITR, TGF-β, and IL-10 mRNA in Treg cells of 50 patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP; 27 women and 23 men; mean age: 56.7 years). The control group consisted of 23 non-infected subjects (12 women and 11 men) with a mean age of 51.3 years. Real-time PCR was used to measure mRNA of Tax proteins and several cellular markers of Treg function. Determinations revealed a high level of Tax mRNA in HAM/TSP (124.35 copies/100 CD4(+)CD25(+) T cells). Foxp3, GITR, and CTLA-4 mRNA levels were lower in HAM/TSP patients (mean ± SD, 22.07 ± 0.78, 9.63 ± 0.36, and 4.54 ± 0.39, respectively) than in non-infected controls (47.15 ± 12.94, 22.14 ± 1.91, and 21.07 ± 2.31). Both groups had similar levels of TGF-β and IL-10. An inverse relationship was found between Tax levels and Foxp3, CTLA-4, and GITR levels. Conversely, there was a direct correlation between levels of Foxp3, GITR, and CTLA-4. Disease severity and evolution time did not correlate with Tax or Foxp3 levels. The present results suggest that Tax and Foxp3 mRNA vary with the same degree of disease severity in HAM/TSP patients. Tax fluctuations may affect CTLA-4 and GITR expression via the Foxp3 pathway, causing virus-induced dysfunction of CD4(+)CD25(+) T cells in HAM/TSP patients.

  15. In vivo fluctuation of Tax, Foxp3, CTLA-4, and GITR mRNA expression in CD4+CD25+ T cells of patients with human T-lymphotropic virus type 1-associated myelopathy

    Directory of Open Access Journals (Sweden)

    E. Ramirez

    2010-11-01

    Full Text Available HTLV-1 Tax expression exerts an inhibitory effect on the Foxp3 transcription factor in CD4+CD25+ T-regulatory cells (Treg. For a better understanding of the role of Tax mRNA in the gene expression of cellular markers we measured Tax, Foxp3, CTLA-4, GITR, TGF-β, and IL-10 mRNA in Treg cells of 50 patients with human T-lymphotropic virus type 1 (HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP; 27 women and 23 men; mean age: 56.7 years. The control group consisted of 23 non-infected subjects (12 women and 11 men with a mean age of 51.3 years. Real-time PCR was used to measure mRNA of Tax proteins and several cellular markers of Treg function. Determinations revealed a high level of Tax mRNA in HAM/TSP (124.35 copies/100 CD4+CD25+ T cells. Foxp3, GITR, and CTLA-4 mRNA levels were lower in HAM/TSP patients (mean ± SD, 22.07 ± 0.78, 9.63 ± 0.36, and 4.54 ± 0.39, respectively than in non-infected controls (47.15 ± 12.94, 22.14 ± 1.91, and 21.07 ± 2.31. Both groups had similar levels of TGF-β and IL-10. An inverse relationship was found between Tax levels and Foxp3, CTLA-4, and GITR levels. Conversely, there was a direct correlation between levels of Foxp3, GITR, and CTLA-4. Disease severity and evolution time did not correlate with Tax or Foxp3 levels. The present results suggest that Tax and Foxp3 mRNA vary with the same degree of disease severity in HAM/TSP patients. Tax fluctuations may affect CTLA-4 and GITR expression via the Foxp3 pathway, causing virus-induced dysfunction of CD4+CD25+ T cells in HAM/TSP patients.

  16. Identification of Human T-lymphotropic Virus Type I (HTLV-I Subtypes Using Restrited Fragment Length Polymorphism in a Cohort of Asymptomatic Carriers and Patients with HTLV-I-associated Myelopathy/tropical Spastic Paraparesis from São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Segurado Aluisio AC

    2002-01-01

    Full Text Available Although human T-lymphotropic virus type I (HTLV-I exhibits high genetic stability, as compared to other RNA viruses and particularly to human immunodeficiency virus (HIV, genotypic subtypes of this human retrovirus have been characterized in isolates from diverse geographical areas. These are currently believed not to be associated with different pathogenetic outcomes of infection. The present study aimed at characterizing genotypic subtypes of viral isolates from 70 HTLV-I-infected individuals from São Paulo, Brazil, including 42 asymptomatic carriers and 28 patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP, using restricted fragment length polymorphism (RFLP analysis of long terminal repeat (LTR HTLV-I proviral DNA sequences. Peripheral blood mononuclear cell lysates were amplified by nested polymerase chain reaction (PCR and amplicons submitted to enzymatic digestion using a panel of endonucleases. Among HTLV-I asymptomatic carriers, viral cosmopolitan subtypes A, B, C and E were identified in 73.8%, 7.1%, 7.1% and 12% of tested samples, respectively, whereas among HAM/TSP patients, cosmopolitan A (89.3%, cosmopolitan C (7.1% and cosmopolitan E (3.6% subtypes were detected. HTLV-I subtypes were not statistically significant associated with patients' clinical status. We also conclude that RFLP analysis is a suitable tool for descriptive studies on the molecular epidemiology of HTLV-I infections in our environment.

  17. Diverging Cohesion?

    DEFF Research Database (Denmark)

    Charron, Nicholas

    2016-01-01

    – which we define here as a combination of impartial bureaucratic practices, corruption and the rule of law – limits, and in some cases reverses the tendency towards greater divergence linked to trade. Countries with high levels of state capacity – that is, those that have greater government effectiveness......, stronger rule of law and lower corruption – experience lower levels of divergence, as they have the mechanisms to counterbalance the strong centripetal forces linked to openness. This claim is tested on countries that have experienced relatively high levels of increases in levels of economic and political......Why do increases in globalisation in the face of European expansion lead to sharp levels of regional divergences in wealth in some countries but not in others? The central crux of this paper is that convergence/divergence trends in European states are conditioned by ‘state capacity’. State capacity...

  18. Cocirculation of Two env Molecular Variants, of Possible Recombinant Origin, in Gorilla and Chimpanzee Simian Foamy Virus Strains from Central Africa.

    Science.gov (United States)

    Richard, Léa; Rua, Réjane; Betsem, Edouard; Mouinga-Ondémé, Augustin; Kazanji, Mirdad; Leroy, Eric; Njouom, Richard; Buseyne, Florence; Afonso, Philippe V; Gessain, Antoine

    2015-12-01

    Simian foamy virus (SFV) is a ubiquitous retrovirus in nonhuman primates (NHPs) that can be transmitted to humans, mostly through severe bites. In the past few years, our laboratory has identified more than 50 hunters from central Africa infected with zoonotic SFVs. Analysis of the complete sequences of five SFVs obtained from these individuals revealed that env was the most variable gene. Furthermore, recombinant SFV strains, some of which involve sequences in the env gene, were recently identified. Here, we investigated the variability of the env genes of zoonotic SFV strains and searched for possible recombinants. We sequenced the complete env gene or its surface glycoprotein region (SU) from DNA amplified from the blood of (i) a series of 40 individuals from Cameroon or Gabon infected with a gorilla or chimpanzee foamy virus (FV) strain and (ii) 1 gorilla and 3 infected chimpanzees living in the same areas as these hunters. Phylogenetic analyses revealed the existence of two env variants among both the gorilla and chimpanzee FV strains that were present in zoonotic and NHP strains. These variants differ greatly (>30% variability) in a 753-bp-long region located in the receptor-binding domain of SU, whereas the rest of the gene is very conserved. Although the organizations of the Env protein sequences are similar, the potential glycosylation patterns differ between variants. Analysis of recombination suggests that the variants emerged through recombination between different strains, although all parental strains could not be identified. SFV infection in humans is a great example of a zoonotic retroviral infection that has not spread among human populations, in contrast to human immunodeficiency viruses (HIVs) and human T-lymphotropic viruses (HTLVs). Recombination was a major mechanism leading to the emergence of HIV. Here, we show that two SFV molecular envelope gene variants circulate among ape populations in Central Africa and that both can be transmitted to

  19. Antibody to human T-lymphotropic virus in a patient with Guillain-Barré syndrome (case report Anticorpo para o vírus linfotrópico humano T em um paciente com a síndrome de Guillain-Barré

    Directory of Open Access Journals (Sweden)

    C.M. Nakauchi

    1991-08-01

    Full Text Available Serum sample obtained from a male, 12 year old patient suffering from Guillain-Barré syndrome (GBS was positive for human T-lymphotropic virus (HTLV-I antibody by the enzyme-linked immunosorbent assay (ELISA and the Western Blot analysis (WB. Attempts to isolate enteroviruses (including poliovirus from faecal material in both tissue culture and suckling mice were unsuccessful; in addition, acute and convalescent paired serum samples did not show any evidence of recent poliovirus infection when tested against the three serotypes. Specific tests for detection of Epstein-Barr virus infection were not performed; however, the Paul-Bunnel test yielded negative results. ELISA for detection of anti-cytomegalovirus IgM was also negative. The concomitant occurrence of either adult T cell leukemia (ATL or lymphoma was not recorded in this case.Amostra de soro obtida de paciente com a síndrome de Guillain-Barré revelou-se positiva quanto à presença de anticorpos para o vírus linfotrópico humano T (HTLV-I pelo método imuno-enzimático (ELISA e a análise por "Western-Blot". Resultaram negativos os testes visando à detecção de enterovírus (incluindo poliovírus a partir de material fecal, tanto em cultura de tecidos como em camundongos recém-nascidos; exames com amostras de soro aguda e convalescente não exibiram qualquer evidência de infecção recente pelos três tipos de poliovírus. O teste de Paul-Bunnel, assim como o "ELISA" para a detecção de IgM anti-citomegalovírus resultaram negativos. Não foi registrada, no presente caso, quer a leucemia adulta de células T, quer linfomas.

  20. Hepatitis C virus and human T-lymphotropic virus coinfection: epidemiological, clinical, laboratory and histopathological features Coinfecção vírus da hepatite C-vírus linfotrópico de células T humanas: aspectos epidemiológicos, clínicos, laboratoriais e histopatológicos

    Directory of Open Access Journals (Sweden)

    Flávio Augusto Pádua Milagres

    2009-08-01

    Full Text Available Twenty-four hepatitis C virus patients coinfected with human T-lymphotropic virus type 1 were compared with six coinfected with HTLV-2 and 55 with HCV alone, regarding clinical, epidemiological, laboratory and histopathological data. Fischer's discriminant analysis was applied to define functions capable of differentiating between the study groups (HCV, HCV/HTLV-1 and HCV/HTLV-2. The discriminant accuracy was evaluated by cross-validation. Alcohol consumption, use of intravenous drugs or inhaled cocaine and sexual partnership with intravenous drug users were more frequent in the HCV/HTLV-2 group, whereas patients in the HCV group more often reported abdominal pain or a sexual partner with hepatitis. Coinfected patients presented higher platelet counts, but aminotransferase and gamma-glutamyl transpeptidase levels were higher among HCV-infected subjects. No significant difference between the groups was seen regarding liver histopathological findings. Through discriminant analysis, classification functions were defined, including sex, age group, intravenous drug use and sexual partner with hepatitis. Cross-validation revealed high discriminant accuracy for the HCV group.Compararam-se 24 pacientes coinfectados pelos vírus da hepatite C/vírus linfotrópico de células T humanas do tipo 1 com 6 coinfectados por VHC/HTLV-2 e 55 infectados pelo VHC, no tocante a dados clínico-epidemiológicos, laboratoriais e histopatológicos. A análise discriminante de Fischer foi utilizada para definir funções capazes de diferenciar os grupos de estudo (VHC, VHC/HTLV-1 e VHC/HTLV-2. A acurácia discriminatória foi avaliada pelo por validação cruzada. O uso de álcool, drogas endovenosas, cocaína inalatória e a parceria sexual com UDEV foram mais freqüentes no grupo VHC/HTLV-2, enquanto queixa de dor abdominal e parceiro sexual com hepatite predominaram no grupo VHC. Os coinfectados apresentaram número maior de plaquetas, enquanto as aminotransferases e

  1. Stability of the gorilla microbiome despite simian immunodeficiency virus infection

    OpenAIRE

    Moeller, A. H.; Peeters, Martine; Ayouba, Ahidjo; Ngole, E. M.; Esteban, A.; Hahn, B. H.; Ochman, H.

    2015-01-01

    Simian immunodeficiency viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in faecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. H...

  2. Inactivation of human and simian rotaviruses by ozone

    Energy Technology Data Exchange (ETDEWEB)

    Vaughn, J.M.; Chen, Y.S.; Lindburg, K.; Morales, D.

    1987-09-01

    The inactivation of simian rotavirus Sa-11 and human rotavirus type 2 (Wa) by ozone was compared at 4/sup 0/C by using single-particle virus stocks. Although the human strain was clearly more sensitive, both virus types were rapidly inactivated by ozone concentrations of 0.25 mg/liter or greater at all pH levels tested. Comparison of the virucidal activity of ozone with that of chlorine in identical experiments indicated little significant difference in rotavirus-inactivating efficiencies when the disinfectants were used at concentrations of 0.25 mg/liter or greater.

  3. Pyrimidine dimers block simian virus 40 replication forks

    International Nuclear Information System (INIS)

    Berger, C.A.; Edenberg, H.J.

    1986-01-01

    UV light produces lesions, predominantly pyrimidine dimers, which inhibit DNA replication in mammalian cells. The mechanism of inhibition is controversial: is synthesis of a daughter strand halted at a lesion while the replication fork moves on and reinitiates downstream, or is fork progression itself blocked for some time at the site of a lesion? We directly addressed this question by using electron microscopy to examine the distances of replication forks from the origin in unirradiated and UV-irradiated simian virus 40 chromosomes. If UV lesions block replication fork progression, the forks should be asymmetrically located in a large fraction of the irradiated molecules; if replication forks move rapidly past lesions, the forks should be symmetrically located. A large fraction of the simian virus 40 replication forks in irradiated molecules were asymmetrically located, demonstrating that UV lesions present at the frequency of pyrimidine dimers block replication forks. As a mechanism for this fork blockage, we propose that polymerization of the leading strand makes a significant contribution to the energetics of fork movement, so any lesion in the template for the leading strand which blocks polymerization should also block fork movement

  4. Intracistronic complementation in the simian virus 40 A gene.

    Science.gov (United States)

    Tornow, J; Cole, C N

    1983-01-01

    A set of eight simian virus 40 mutants was constructed with lesions in the A gene, which encodes the large tumor (T) antigen. These mutants have small deletions (3-20 base pairs) at either 0.497, 0.288, or 0.243 map units. Mutants having both in-phase and frameshift mutations at each site were isolated. Neither plaque formation nor replication of the mutant DNAs could be detected after transfection of monkey kidney cells. Another nonviable mutant, dlA2459, had a 14-base-pair deletion at 0.193 map unit and was positive for viral DNA replication. Each of the eight mutants were tested for ability to form plaques after cotransfection with dlA2459 DNA. The four mutants that had in-phase deletions were able to complement dlA2459. The other four, which had frameshift deletions, did not. No plaques were formed after cotransfection of cells with any other pair of group A mutants. This suggests that the defect in dlA2459 defines a distinct functional domain of simian virus 40 T antigen. Images PMID:6312452

  5. Soroprevalência e perfil imunofenotípico de células linfóides T em indivíduos soropositivos para o vírus linfotrópico de células T humanas Seroprevalence and immunophenotypic profile of T lymphocyte cells in human T lymphotropic virus seropositive individuals

    Directory of Open Access Journals (Sweden)

    Geane F. de Sóuza

    2003-03-01

    Full Text Available O vírus linfotrópico de células T humana (HTLV é transmitido por transfusões, uso compartilhado de agulhas contaminadas, aleitamento e contato sexual. A prevalência varia de acordo com a região geográfica, grupo racial e população estudada. Cerca de 1% a 4% dos indivíduos infectados desenvolvem algum tipo de doença em decorrência da infecção. É reconhecida a associação entre o HTLV-I e leucemia de células T do adulto e paraparesia espástica tropical (PET. Embora a maioria dos portadores permaneça assintomática, existem evidências de comprometimento funcional da resposta imune celular. Os objetivos desse trabalho foram avaliar a prevalência de soropositividade para HTLV-I/II na população de doadores de sangue do HEMOCE e analisar o perfil imunofenotípico de células linfóides circulantes em 26 doadores soronegativos, 11 soropositivos para HTLV-I sintomáticos e 24 assintomáticos, comparando-os entre si. A prevalência da soropositividade para HTLV-I/II foi de 0,66%. No grupo de indivíduos contaminados pelo HTLV-I houve predomínio do sexo feminino e a maior média de idade. O grupo soropositivo apresentou menor valor de hemoglobina e o grupo sintomático evidenciou contagem de neutrófilos significativamente mais elevada. A contagem média de linfócitos não diferiu entre os grupos. A análise imunofenotípica mostrou que os valores médios de células CD3+, CD4+, CD8+ e relação CD4/CD8 não diferiram significativamente entre os grupos. Uma elevação de células CD8+ no grupo soropositivo foi observada embora não alcançasse significância estatística. A ativação de linfócitos CD8+ está envolvida na patogênese das doenças associadas ao HTLV-I. A definição do valor preditivo desse achado requer confirmação posterior.Human T lymphotropic virus (HTLV can be transmitted by transfusions of cellular blood products, shared use of contaminated syringes, breast feeding and sexual intercourse. The prevalence of

  6. String perturbation theory diverges

    International Nuclear Information System (INIS)

    Gross, D.J.; Periwal, V.

    1988-01-01

    We prove that perturbation theory for the bosonic string diverges for arbitrary values of the coupling constant and is not Borel summable. This divergence is independent of the existence of the infinities that occur in the theory due to the presence of tachyons and dilaton tadpoles. We discuss the physical implications of such a divergence

  7. Toxicity and efficacy of 2',3'-dideoxycytidine in clinical trials of pigtailed macaques infected with simian retrovirus type 2.

    OpenAIRE

    Tsai, C C; Follis, K E; Yarnall, M; Blakley, G A

    1989-01-01

    Four dosing regimens of 2',3'-dideoxycytidine (ddC) were administered intravenously for 10 to 28 days to 18 pigtailed macaques with simian acquired immunodeficiency syndrome. Ten macaques naturally infected with simian acquired immunodeficiency syndrome retrovirus serotype 2 (SRV-2), the etiologic agent of simian acquired immunodeficiency syndrome, received ddC by continuous intravenous infusion or by a daily bolus injection for 10 to 12 days. Another eight macaques that were negative for SRV...

  8. The Patchwork Divergence Theorem

    OpenAIRE

    Dray, Tevian; Hellaby, Charles

    1994-01-01

    The divergence theorem in its usual form applies only to suitably smooth vector fields. For vector fields which are merely piecewise smooth, as is natural at a boundary between regions with different physical properties, one must patch together the divergence theorem applied separately in each region. We give an elegant derivation of the resulting "patchwork divergence theorem" which is independent of the metric signature in either region, and which is thus valid if the signature changes. (PA...

  9. Divergent Cumulative Cultural Evolution

    OpenAIRE

    Marriott, Chris; Chebib, Jobran

    2016-01-01

    Divergent cumulative cultural evolution occurs when the cultural evolutionary trajectory diverges from the biological evolutionary trajectory. We consider the conditions under which divergent cumulative cultural evolution can occur. We hypothesize that two conditions are necessary. First that genetic and cultural information are stored separately in the agent. Second cultural information must be transferred horizontally between agents of different generations. We implement a model with these ...

  10. On infrared divergences

    International Nuclear Information System (INIS)

    Parisi, G.

    1979-01-01

    The structure of infrared divergences is studied in superrenormalizable interactions. It is conjectured that there is an extension of the Bogoliubov-Parasiuk-Hepp theorem which copes also with infrared divergences. The consequences of this conjecture on the singularities of the Borel transform in a massless asymptotic free field theory are discussed. The application of these ideas to gauge theories is briefly discussed. (Auth.)

  11. Replicative intermediates in UV-irradiated Simian virus 40

    International Nuclear Information System (INIS)

    Clark, J.M.; Hanawalt, P.C.

    1984-01-01

    The authors have used Simian virus 40 (SV40) as a probe to study the replication of UV-damaged DNA in mammalian cells. Viral DNA replication in infected monkey kidney cells was synchronized by incubating a mutant of SV40 (tsA58) temperature-sensitive for the initiation of DNA synthesis at the restrictive temperature and then adding aphidicolin to temporarily inhibit DNA synthesis at the permissive temperature while permitting pre-replicative events to occur. After removal of the drug, the infected cells were irradiated at 100 J/m 2 (254 nm) to produce 6-7 pyrimidine dimers per SV40 genome, and returned to the restrictive temperature to prevent reinitiation of replication from the SV40 origin. Replicative intermediates (RI) were labeled with [ 3 H]thymidine. The size distribution of daughter DNA strands in RI isolated shortly after irradiation was skewed towards lengths less than the interdimer spacing in parental DNA; this bias persisted for at least 1 h after irradiation, but disappeared within 3 h by which time the size of the newly-synthesized DNA exceeded the interdimer distance. Evidence was obtained for the generation at late times after irradiation, of Form I molecules in which the daughter DNA strand contain dimers. Thus DNA strand exchange as well as trans-dimer synthesis may be involved in the generation of supercoiled Form I DNA from 0V-damaged SV40 replicative intermediates. (Auth.)

  12. Evidence of simian retrovirus type D by polymerase chain reaction.

    Science.gov (United States)

    Hwa, Christian Z R; Tsai, Sheung Pun; Yee, JoAnn L; Van Rompay, Koen K; Roberts, Jeffrey A

    2017-06-01

    Over the past few years, there have been reports of finding Simian retrovirus type D (SRV) in macaque colonies where some animals were characterized as antibody positive but virus negative raising questions about how SRV was transmitted or whether there is a variant strain detected by antibody but not polymerase chain reaction (PCR) in current use. We developed a three-round nested PCR assay using degenerate primers targeting the pol gene to detect for SRV serotypes 1-5 and applied this newly validated PCR assay to test macaque DNA samples collected in China from 2010 to 2015. Using the nested PCR assay validated in this study, we found 0.15% of the samples archived on FTA ® cards were positive. The source of SRV infection identified within domestic colonies might have originated from imported macaques. The multiplex nested PCR assay developed here may supplement the current assays for SRV. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Physicochemical stability and inactivation of human and simian rotaviruses

    International Nuclear Information System (INIS)

    Meng, Z.D.; Birch, C.; Heath, R.; Gust, I.

    1987-01-01

    The effects of various physical and chemical treatments on the stability of a human serotype 1 rotavirus and simian agent 11 (SA11) were compared by using a fluorescence focus assay. The infectivity of both strains was retained after storage at room temperature for 14 days, 4 degree C for 22 days, and -20 degree C for 32 days; lyophilization; and treatment at pH 3 to 11. Both viruses were inactivated at pH 12, as was the human virus at pH 2, although this pH resulted in only partial inactivation of SA11. The human virus also appeared to be more sensitive than SA11 to the action of ether and chloroform. The infectivity of both viruses was lost after UV irradiation for 15 min and after treatment with 8% formaldehyde for 5 min, 70% (vol/vol) ethanol for 30 min, and 2% lysol, 2% phenol, and 1% H 2 O 2 for 1 h each

  14. Physicochemical stability and inactivation of human and simian rotaviruses

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Z.D.; Birch, C.; Heath, R.; Gust, I.

    1987-04-01

    The effects of various physical and chemical treatments on the stability of a human serotype 1 rotavirus and simian agent 11 (SA11) were compared by using a fluorescence focus assay. The infectivity of both strains was retained after storage at room temperature for 14 days, 4 degree C for 22 days, and -20 degree C for 32 days; lyophilization; and treatment at pH 3 to 11. Both viruses were inactivated at pH 12, as was the human virus at pH 2, although this pH resulted in only partial inactivation of SA11. The human virus also appeared to be more sensitive than SA11 to the action of ether and chloroform. The infectivity of both viruses was lost after UV irradiation for 15 min and after treatment with 8% formaldehyde for 5 min, 70% (vol/vol) ethanol for 30 min, and 2% lysol, 2% phenol, and 1% H/sub 2/O/sub 2/ for 1 h each.

  15. Inactivation of human and simian rotaviruses by chlorine dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yu-Shiaw (Brookhaven National Lab., Upton, NY (USA)); Vaughn, J.M. (Univ. of New England College of Medicine, Biddeford, ME (USA))

    1990-05-01

    The inactivation of single-particle stocks of human (type 2, Wa) and simian (SA-11) rotaviruses by chlorine dioxide was investigated. Experiments were conducted at 4{degree}C in a standard phosphate-carbonate buffer. Both virus types were rapidly inactivated, within 20 s under alkaline conditions, when chlorine dioxide concentrations ranging from 0.05 to 0.2 mg/liter were used. Similar reductions of 10{sup 5}-fold in infectivity required additional exposure time of 120 s at 0.2 mg/liter for Wa and at 0.5 mg/liter for SA-11, respectively, at pH 6.0. The inactivation of both virus types was moderate a neutral pH, and the sensitivities to chlorine dioxide were similar. The observed enhancement of virucidal efficiency with increasing pH was contrary to earlier findings with chlorine- and ozone-treated rotavirus particles, where efficiencies decreased with increasing alkalinity. Comparison of 99.9% virus inactivation times revealed ozone to be the most effective virucidal agent among these three disinfectants.

  16. Quantum skew divergence

    Energy Technology Data Exchange (ETDEWEB)

    Audenaert, Koenraad M. R., E-mail: koenraad.audenaert@rhul.ac.uk [Department of Mathematics, Royal Holloway University of London, Egham TW20 0EX, United Kingdom and Department of Physics and Astronomy, University of Ghent, S9, Krijgslaan 281, B-9000 Ghent (Belgium)

    2014-11-15

    In this paper, we study the quantum generalisation of the skew divergence, which is a dissimilarity measure between distributions introduced by Lee in the context of natural language processing. We provide an in-depth study of the quantum skew divergence, including its relation to other state distinguishability measures. Finally, we present a number of important applications: new continuity inequalities for the quantum Jensen-Shannon divergence and the Holevo information, and a new and short proof of Bravyi's Small Incremental Mixing conjecture.

  17. JST Thesaurus Headwords and Synonyms: simian virus 40 [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term simian virus 40 名詞 一般 * * * * SV4...0ウイルス SV40ウイルス エスブイヨンゼロウイルス Thesaurus2015 200906022865540531 C LS07 UNKNOWN_2 simian virus 4 0

  18. Stability of the gorilla microbiome despite simian immunodeficiency virus infection.

    Science.gov (United States)

    Moeller, Andrew H; Peeters, Martine; Ayouba, Ahidjo; Ngole, Eitel Mpoudi; Esteban, Amadine; Hahn, Beatrice H; Ochman, Howard

    2015-02-01

    Simian immunodeficiency viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in faecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. Here, we examine the effects of SIVgor, a close relative of SIVcpz of chimpanzees and HIV-1 of humans, on the gut bacterial communities residing within wild gorillas, revealing that gorilla gut microbiomes are exceptionally robust to SIV infection. In contrast to the microbiomes of HIV-1-infected humans and SIVcpz-infected chimpanzees, SIVgor-infected gorilla microbiomes exhibit neither rises in the frequencies of opportunistic pathogens nor elevated rates of microbial turnover within individual hosts. Regardless of SIV infection status, gorilla microbiomes assort into enterotypes, one of which is compositionally analogous to those identified in humans and chimpanzees. The other gorilla enterotype appears specialized for a leaf-based diet and is enriched in environmentally derived bacterial genera. We hypothesize that the acquisition of this gorilla-specific enterotype was enabled by lowered immune system control over the composition of the microbiome. Our results indicate differences between the pathology of SIVgor and SIVcpz/HIV-1 infections, demonstrating the utility of investigating host microbial ecology as a means for studying disease in wild primates of high conservation priority. © 2014 John Wiley & Sons Ltd.

  19. Association between simian virus 40 and non-Hodgkin lymphoma

    Science.gov (United States)

    Vilchez, Regis A.; Madden, Charles R.; Kozinetz, Claudia A.; Halvorson, Steven J.; White, Zoe S.; Jorgensen, Jeffrey L.; Finch, Chris J.; Butel, Janet S.

    2002-01-01

    BACKGROUND: Non-Hodgkin lymphoma has increased in frequency over the past 30 years, and is a common cancer in HIV-1-infected patients. Although no definite risk factors have emerged, a viral cause has been postulated. Polyomaviruses are known to infect human beings and to induce tumours in laboratory animals. We aimed to identify which one of the three polyomaviruses able to infect human beings (simian virus 40 [SV40], JC virus, and BK virus) was associated with non-Hodgkin lymphoma. METHODS: We analysed systemic non-Hodgkin lymphoma from 76 HIV-1-infected and 78 HIV-1-uninfected patients, and non-malignant lymphoid samples from 79 HIV-1-positive and 107 HIV-1-negative patients without tumours; 54 colon and breast carcinoma samples served as cancer controls. We used PCR followed by Southern blot hybridisation and DNA sequence analysis to detect DNAs of polyomaviruses and herpesviruses. FINDINGS: Polyomavirus T antigen sequences, all of which were SV40-specific, were detected in 64 (42%) of 154 non-Hodgkin lymphomas, none of 186 non-malignant lymphoid samples, and none of 54 control cancers. This difference was similar for HIV-1-infected patients and HIV-1-uninfected patients alike. Few tumours were positive for both SV40 and Epstein-Barr virus. Human herpesvirus type 8 was not detected. SV40 sequences were found most frequently in diffuse large B-cell and follicular-type lymphomas. INTERPRETATION: SV40 is significantly associated with some types of non-Hodgkin lymphoma. These results add lymphomas to the types of human cancers associated with SV40.

  20. Simian virus 40 vectors for pulmonary gene therapy

    Directory of Open Access Journals (Sweden)

    Oppenheim Ariella

    2007-10-01

    Full Text Available Abstract Background Sepsis remains the leading cause of death in critically ill patients. One of the primary organs affected by sepsis is the lung, presenting as the Acute Respiratory Distress Syndrome (ARDS. Organ damage in sepsis involves an alteration in gene expression, making gene transfer a potential therapeutic modality. This work examines the feasibility of applying simian virus 40 (SV40 vectors for pulmonary gene therapy. Methods Sepsis-induced ARDS was established by cecal ligation double puncture (2CLP. SV40 vectors carrying the luciferase reporter gene (SV/luc were administered intratracheally immediately after sepsis induction. Sham operated (SO as well as 2CLP rats given intratracheal PBS or adenovirus expressing luciferase served as controls. Luc transduction was evaluated by in vivo light detection, immunoassay and luciferase mRNA detection by RT-PCR in tissue harvested from septic rats. Vector abundance and distribution into alveolar cells was evaluated using immunostaining for the SV40 VP1 capsid protein as well as by double staining for VP1 and for the surfactant protein C (proSP-C. Immunostaining for T-lymphocytes was used to evaluate the cellular immune response induced by the vector. Results Luc expression measured by in vivo light detection correlated with immunoassay from lung tissue harvested from the same rats. Moreover, our results showed vector presence in type II alveolar cells. The vector did not induce significant cellular immune response. Conclusion In the present study we have demonstrated efficient uptake and expression of an SV40 vector in the lungs of animals with sepsis-induced ARDS. These vectors appear to be capable of in vivo transduction of alveolar type II cells and may thus become a future therapeutic tool.

  1. Genomic evidence that simian virus 2 and six other simian picornaviruses represent a new genus in Picornaviridae

    International Nuclear Information System (INIS)

    Oberste, M. Steven; Maher, Kaija; Pallansch, Mark A.

    2003-01-01

    Analysis of the VP1 capsid protein coding region of simian virus (SV) 2, SV16, SV18, SV42, SV44, SV45, and SV49 demonstrates that they are clearly distinct from members of the Enterovirus genus and from members of other existing picornavirus genera. To further characterize this group of viruses and to clarify their classification within the Picornaviridae, we have determined the complete genomic sequence of SV2 (8126 nucleotides). The genome was typical of members of Picornaviridae, encoding a single open reading frame. The putative polyprotein contained typical picornavirus protease cleavage sites, yielding mature proteins homologous to each of the known picornavirus proteins. SV2 contained an amino-terminal extension of the reading frame, which was analogous to the leader protein of members of the Aphthovirus, Cardiovirus, Erbovirus, Kobuvirus, and Teschovirus genera, but there was no significant amino acid homology with any of these known leader proteins. The 2A protein also aligned poorly with the 2A proteins of other picornaviruses. The deduced amino acid sequences of the SV2 structural and nonstructural proteins were related to but phylogenetically distinct from those of enteroviruses and human rhinoviruses. The major distinguishing features of SV2 were the presence of a type 2 internal ribosome entry site in the 5'-NTR, a putative leader protein encoded upstream of the structural proteins, and an unusually large 2A protein. On the basis of the molecular analysis, we propose that SV2, SV16, SV18, SV42, SV44, SV45, SV49, and porcine enterovirus 8 be classified as members of a new genus in Picornaviridae and that SV2 (strain 2383) be designated as the type strain

  2. SIVdrl detection in captive mandrills: are mandrills infected with a third strain of simian immunodeficiency virus?

    NARCIS (Netherlands)

    van der Kuyl, Antoinette C.; van den Burg, Remco; Hoyer, Mark J.; Gruters, Rob A.; Osterhaus, Albert D. M. E.; Berkhout, Ben

    2004-01-01

    A pol-fragment of simian immunodeficiency virus (SIV) that is highly related to SIVdrl-pol from drill monkeys (Mandrillus leucophaeus) was detected in two mandrills (Mandrillus sphinx) from Amsterdam Zoo. These captivity-born mandrills had never been in contact with drill monkeys, and were unlikely

  3. Converging or Diverging Lens?

    Science.gov (United States)

    Branca, Mario

    2013-01-01

    Why does a lens magnify? Why does it shrink objects? Why does this happen? The activities that we propose here are useful in helping us to understand how lenses work, and they show that the same lens can have different magnification capabilities. A converging lens can also act as a diverging lens. (Contains 4 figures.)

  4. Local divergence and curvature divergence in first order optics

    Science.gov (United States)

    Mafusire, Cosmas; Krüger, Tjaart P. J.

    2018-06-01

    The far-field divergence of a light beam propagating through a first order optical system is presented as a square root of the sum of the squares of the local divergence and the curvature divergence. The local divergence is defined as the ratio of the beam parameter product to the beam width whilst the curvature divergence is a ratio of the space-angular moment also to the beam width. It is established that the beam’s focusing parameter can be defined as a ratio of the local divergence to the curvature divergence. The relationships between the two divergences and other second moment-based beam parameters are presented. Their various mathematical properties are presented such as their evolution through first order systems. The efficacy of the model in the analysis of high power continuous wave laser-based welding systems is briefly discussed.

  5. Convergence from divergence

    Science.gov (United States)

    Costin, Ovidiu; Dunne, Gerald V.

    2018-01-01

    We show how to convert divergent series, which typically occur in many applications in physics, into rapidly convergent inverse factorial series. This can be interpreted physically as a novel resummation of perturbative series. Being convergent, these new series allow rigorous extrapolation from an asymptotic region with a large parameter, to the opposite region where the parameter is small. We illustrate the method with various physical examples, and discuss how these convergent series relate to standard methods such as Borel summation, and also how they incorporate the physical Stokes phenomenon. We comment on the relation of these results to Dyson’s physical argument for the divergence of perturbation theory. This approach also leads naturally to a wide class of relations between bosonic and fermionic partition functions, and Klein-Gordon and Dirac determinants.

  6. JST Thesaurus Headwords and Synonyms: simian immunodeficiency virus [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term simian immunodeficiency virus 名詞 ...一般 * * * * サル免疫不全ウイルス サルメンエキフゼンウイルス サルメンエキフゼンウイルス Thesaurus2015 200906068937985410 C LS07 UNKNOWN_2 simian immunodeficiency virus

  7. Regularization of divergent integrals

    OpenAIRE

    Felder, Giovanni; Kazhdan, David

    2016-01-01

    We study the Hadamard finite part of divergent integrals of differential forms with singularities on submanifolds. We give formulae for the dependence of the finite part on the choice of regularization and express them in terms of a suitable local residue map. The cases where the submanifold is a complex hypersurface in a complex manifold and where it is a boundary component of a manifold with boundary, arising in string perturbation theory, are treated in more detail.

  8. Geographic distribution of human T-lymphotropic virus types 1 and 2 among mothers of newborns tested during neonatal screening, Minas Gerais, Brazil Distribución geográfica del virus linfotrópico de células T humanas tipos 1 y 2 en madres de recién nacidos estudiados en el tamizaje neonatal en Minas Gerais, Brasil

    Directory of Open Access Journals (Sweden)

    Maísa Aparecida Ribeiro

    2010-05-01

    Full Text Available OBJECTIVE: To evaluate the geographic distribution of human T-lymphotropic virus types 1 and 2 (HTLV-1/2 in the State of Minas Gerais, Brazil, in puerperal women whose newborns were tested for HTLV-1/2 during neonatal screening, and to overlap seropositivity with social and economic status determinants. METHODS: During September-November 2007, the dry-blood samples taken from newborns on filter paper for routine screening were also tested for maternal IgG anti-HTLV-1/2 antibodies. For reactive samples, the mothers of the newborns had blood drawn to test for these viruses. RESULTS: The study analyzed 55 293 specimens taken from newborns. Of these, 52 (9.4 per 10 000 were reactive and 42 mothers (7.6 per 10 000 were confirmed with HTLV-1/2 infection. HTLV-1/2 geographic distribution was heterogeneous, with a tendency to be higher in the North and North-East parts of Minas Gerais. The highest rates of seropositivity were observed in Vale do Mucuri (55.9 per 10 000 and in Jequitinhonha (16.0 per 10 000, overlapping with the State's worst social and economic indicators. CONCLUSIONS: To our knowledge this was the first time that neonatal screening for HTLV-1/2 was performed in Brazil. This model could be used in other areas with high HTLV-1/2 prevalence rates. The detection of carrier mothers can enable intervention measures, such as providing infant formula to newborns, to be implemented expeditiously to reduce vertical transmission.OBJETIVOS: Evaluar la distribución geográfica del virus linfotrópico de células T humanas tipos 1 y 2 (HTLV-1/2 en el estado de Minas Gerais (Brasil, en mujeres puérperas en cuyos recién nacidos se analizó la presencia del HTLV-1/2 durante las pruebas neonatales de detección sistemática, y superponer la seropositividad con determinantes del estado socioeconómico. MÉTODOS: Entre septiembre y noviembre de 2007, en las muestras de sangre seca extraída a los recién nacidos en papel de filtro para un tamizaje

  9. Induction of Mucosal Homing Virus-Specific CD8+ T Lymphocytes by Attenuated Simian Immunodeficiency Virus

    OpenAIRE

    Cromwell, Mandy A.; Veazey, Ronald S.; Altman, John D.; Mansfield, Keith G.; Glickman, Rhona; Allen, Todd M.; Watkins, David I.; Lackner, Andrew A.; Johnson, R. Paul

    2000-01-01

    Induction of virus-specific T-cell responses in mucosal as well as systemic compartments of the immune system is likely to be a critical feature of an effective AIDS vaccine. We investigated whether virus-specific CD8+ lymphocytes induced in rhesus macaques by immunization with attenuated simian immunodeficiency virus (SIV), an approach that is highly effective in eliciting protection against mucosal challenge, express the mucosa-homing receptor α4β7 and traffic to the intestinal mucosa. SIV-...

  10. CCR5 Signal Transduction in Macrophages by Human Immunodeficiency Virus and Simian Immunodeficiency Virus Envelopes

    OpenAIRE

    Arthos, James; Rubbert, Andrea; Rabin, Ronald L.; Cicala, Claudia; Machado, Elizabeth; Wildt, Kathryne; Hanbach, Meredith; Steenbeke, Tavis D.; Swofford, Ruth; Farber, Joshua M.; Fauci, Anthony S.

    2000-01-01

    The capacity of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) envelopes to transduce signals through chemokine coreceptors on macrophages was examined by measuring the ability of recombinant envelope proteins to mobilize intracellular calcium stores. Both HIV and SIV envelopes mobilized calcium via interactions with CCR5. The kinetics of these responses were similar to those observed when macrophages were treated with MIP-1β. Distinct differences in the capacity o...

  11. Characterization of components released by alkali disruption of simian virus 40

    DEFF Research Database (Denmark)

    Christiansen, Gunna; Landers, T; Griffith, J

    1977-01-01

    Treatment of simian virus 40 (SV40) particles at pH 9.8 in the presence of 1 mM dithiothreitol for 5 min at 37 degrees C disrupted the virions into a 60S DNA-protein complex and DNA-free 7S protein particles. The DNA-protein complex contained approximately equal amounts of DNA and protein, and ap...

  12. Vaccination of rhesus macaques with a vif-deleted simian immunodeficiency virus proviral DNA vaccine

    International Nuclear Information System (INIS)

    Sparger, Ellen E.; Dubie, Robert A.; Shacklett, Barbara L.; Cole, Kelly S.; Chang, W.L.; Luciw, Paul A.

    2008-01-01

    Studies in non-human primates, with simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) have demonstrated that live-attenuated viral vaccines are highly effective; however these vaccine viruses maintain a low level of pathogenicity. Lentivirus attenuation associated with deletion of the viral vif gene carries a significantly reduced risk for pathogenicity, while retaining the potential for virus replication of low magnitude in the host. This report describes a vif-deleted simian immunodeficiency virus (SIV)mac239 provirus that was tested as an attenuated proviral DNA vaccine by inoculation of female rhesus macaques. SIV-specific interferon-γ enzyme-linked immunospot responses of low magnitude were observed after immunization with plasmid containing the vif-deleted SIV provirus. However, vaccinated animals displayed strong sustained virus-specific T cell proliferative responses and increasing antiviral antibody titers. These immune responses suggested either persistent vaccine plasmid expression or low level replication of vif-deleted SIV in the host. Immunized and unvaccinated macaques received a single high dose vaginal challenge with pathogenic SIVmac251. A transient suppression of challenge virus load and a greater median survival time was observed for vaccinated animals. However, virus loads for vaccinated and unvaccinated macaques were comparable by twenty weeks after challenge and overall survival curves for the two groups were not significantly different. Thus, a vif-deleted SIVmac239 proviral DNA vaccine is immunogenic and capable of inducing a transient suppression of pathogenic challenge virus, despite severe attenuation of the vaccine virus

  13. Divergent Perturbation Series

    International Nuclear Information System (INIS)

    Suslov, I.M.

    2005-01-01

    Various perturbation series are factorially divergent. The behavior of their high-order terms can be determined by Lipatov's method, which involves the use of instanton configurations of appropriate functional integrals. When the Lipatov asymptotic form is known and several lowest order terms of the perturbation series are found by direct calculation of diagrams, one can gain insight into the behavior of the remaining terms of the series, which can be resummed to solve various strong-coupling problems in a certain approximation. This approach is demonstrated by determining the Gell-Mann-Low functions in φ 4 theory, QED, and QCD with arbitrary coupling constants. An overview of the mathematical theory of divergent series is presented, and interpretation of perturbation series is discussed. Explicit derivations of the Lipatov asymptotic form are presented for some basic problems in theoretical physics. A solution is proposed to the problem of renormalon contributions, which hampered progress in this field in the late 1970s. Practical perturbation-series summation schemes are described both for a coupling constant of order unity and in the strong-coupling limit. An interpretation of the Borel integral is given for 'non-Borel-summable' series. Higher order corrections to the Lipatov asymptotic form are discussed

  14. Functional simian immunodeficiency virus Gag-specific CD8+ intraepithelial lymphocytes in the mucosae of SIVmac251- or simian-human immunodeficiency virus KU2-infected macaques

    International Nuclear Information System (INIS)

    Stevceva, Liljana; Moniuszko, Marcin; Alvarez, Xavier; Lackner, Andrew A.; Franchini, Genoveffa

    2004-01-01

    The vaginal and rectal mucosae are the first line of cellular immune defense to sexually transmitted human immunodeficiency virus type 1 (HIV-1) entry. Thus, intraepithelial lymphocytes (IELs) may be important in the immune response to HIV infection. Here we investigated whether functional IELs in mucosal compartments could be visualized by direct staining with a tetrameric complex specific for the simian immunodeficiency virus (SIV) immunodominant Gag epitope in either separated IEL cells or tissues of macaques infected with SIVmac251. Of the 15 Mamu-A*01-positive macaques studied here, eight were chronically infected with either SIVmac251 or simian-human immunodeficiency virus (SHIV) KU2 and the remaining seven were exposed mucosally to SIVmac251 and sacrificed within 48 h to assess the local immune response. Gag-specific CD8+ T-cells were found in separated IELs from the rectum, colon, jejunum, and vagina of most infected animals. Direct staining of tetramers also revealed their presence in intact tissue. These Gag-specific IELs expressed the activation marker CD69 and produced IFN-γ, suggesting an active immune response in this locale

  15. Quadratic divergences and dimensional regularisation

    International Nuclear Information System (INIS)

    Jack, I.; Jones, D.R.T.

    1990-01-01

    We present a detailed analysis of quadratic and quartic divergences in dimensionally regulated renormalisable theories. We perform explicit three-loop calculations for a general theory of scalars and fermions. We find that the higher-order quartic divergences are related to the lower-order ones by the renormalisation group β-functions. (orig.)

  16. Molecular Determinants of Human T-lymphotropic Virus Type 1 Transmission and Spread

    Directory of Open Access Journals (Sweden)

    Patrick L. Green

    2011-07-01

    Full Text Available Human T-lymphotrophic virus type-1 (HTLV-1 infects approximately 15 to 20 million people worldwide, with endemic areas in Japan, the Caribbean, and Africa. The virus is spread through contact with bodily fluids containing infected cells, most often from mother to child through breast milk or via blood transfusion. After prolonged latency periods, approximately 3 to 5% of HTLV-1 infected individuals will develop either adult T-cell leukemia/lymphoma (ATL, or other lymphocyte-mediated disorders such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. The genome of this complex retrovirus contains typical gag, pol, and env genes, but also unique nonstructural proteins encoded from the pX region. These nonstructural genes encode the Tax and Rex regulatory proteins, as well as novel proteins essential for viral spread in vivo such as, p30, p12, p13 and the antisense encoded HBZ. While progress has been made in the understanding of viral determinants of cell transformation and host immune responses, host and viral determinants of HTLV-1 transmission and spread during the early phases of infection are unclear. Improvements in the molecular tools to test these viral determinants in cellular and animal models have provided new insights into the early events of HTLV-1 infection. This review will focus on studies that test HTLV-1 determinants in context to full length infectious clones of the virus providing insights into the mechanisms of transmission and spread of HTLV-1.

  17. High prevalence of human T-lymphotropic virus infection in indigenous women from the peruvian Amazon.

    Science.gov (United States)

    Blas, Magaly M; Alva, Isaac E; García, Patricia J; Cárcamo, Cesar; Montano, Silvia M; Mori, Nicanor; Muñante, Ricardo; Zunt, Joseph R

    2013-01-01

    In an earlier study, we detected an association between human T-cell lymphotropic virus (HTLV) infection and cervical human papillomavirus (HPV) in indigenous Amazonian Peruvian women of the Shipibo-Konibo ethnic group. As both HTLV and HPV can be transmitted sexually, we now report a population-based study examining the prevalence and risk factors for HTLV-1 and HTLV-2 infection in this population. Between July and December 2010, we conducted a comprehensive screening for HTLV among Shipibo-Konibo women 15 to 39 years of age living in two communities located in Lima and in 17 communities located within four hours by car or boat from the Amazonian city of Pucallpa in Peru. We screened 1,253 Shipibo-Konibo women for HTLV infection 74 (5.9%) tested positive for HTLV-1, 47 (3.8%) for HTLV-2 infection, and 4 (0.3%) had indeterminate results. In the multivariate analysis, factors associated with HTLV-1 infection included: older age (Prevalence Ratio (PR): 1.04, 95% CI 1.00-1.08), primary education or less (PR: 2.01, 95% CI: 1.25-3.24), younger or same age most recent sex partner (PR: 1.66, 95% CI: 1.00-2.74), and having a most recent sex partner who worked at a logging camp (PR: 1.73, 95% CI: 1.09-2.75). The only factor associated with HTLV-2 infection was older age (PR: 1.08, 95% CI: 1.03-1.12). HTLV infection is endemic among Shipibo-Konibo women. Two characteristics of the sexual partner (younger age and labor history) were associated with infection in women. These results suggest the need for implementation of both HTLV screening during the antenatal healthcare visits of Shipibo-Konibo women, and counseling about the risk of HTLV transmission through prolonged breastfeeding in infected women. We also recommend the implementation of prevention programs to reduce sexual transmission of these viruses.

  18. High prevalence of human T-lymphotropic virus infection in indigenous women from the peruvian Amazon.

    Directory of Open Access Journals (Sweden)

    Magaly M Blas

    Full Text Available In an earlier study, we detected an association between human T-cell lymphotropic virus (HTLV infection and cervical human papillomavirus (HPV in indigenous Amazonian Peruvian women of the Shipibo-Konibo ethnic group. As both HTLV and HPV can be transmitted sexually, we now report a population-based study examining the prevalence and risk factors for HTLV-1 and HTLV-2 infection in this population.Between July and December 2010, we conducted a comprehensive screening for HTLV among Shipibo-Konibo women 15 to 39 years of age living in two communities located in Lima and in 17 communities located within four hours by car or boat from the Amazonian city of Pucallpa in Peru.We screened 1,253 Shipibo-Konibo women for HTLV infection 74 (5.9% tested positive for HTLV-1, 47 (3.8% for HTLV-2 infection, and 4 (0.3% had indeterminate results. In the multivariate analysis, factors associated with HTLV-1 infection included: older age (Prevalence Ratio (PR: 1.04, 95% CI 1.00-1.08, primary education or less (PR: 2.01, 95% CI: 1.25-3.24, younger or same age most recent sex partner (PR: 1.66, 95% CI: 1.00-2.74, and having a most recent sex partner who worked at a logging camp (PR: 1.73, 95% CI: 1.09-2.75. The only factor associated with HTLV-2 infection was older age (PR: 1.08, 95% CI: 1.03-1.12.HTLV infection is endemic among Shipibo-Konibo women. Two characteristics of the sexual partner (younger age and labor history were associated with infection in women. These results suggest the need for implementation of both HTLV screening during the antenatal healthcare visits of Shipibo-Konibo women, and counseling about the risk of HTLV transmission through prolonged breastfeeding in infected women. We also recommend the implementation of prevention programs to reduce sexual transmission of these viruses.

  19. Human T-Lymphotropic virus (HTLV type I in vivo integration in oral keratinocytes

    Directory of Open Access Journals (Sweden)

    Martha C Domínguez

    2011-03-01

    Full Text Available Although the infection of HTLV-1 to cell components of the mouth have been previously reported, there was not until this report, a detailed study to show the characteristics of such infection. From 14 Tropical Spastic Paraparesis/ HTLV-1-Associated Myelopathy (HAM/TSP patients and 11 asymptomatic carrier individuals (AC coming from HTLV-1 endemic areas of southwest Pacific of Colombia, infected oral mucosa cells were primary cultured during five days. These cell cultures were immunophenotyped by dual color fluorescence cell assortment using different lymphocyte CD markers and also were immunohistochemically processed using a polyclonal anti-keratin antibody. Five days old primary cultures were characterized as oral keratinocytes, whose phenotype was CD3- /CD4-/CD8-/CD19-/CD14-/CD45-/A575-keratin+. From DNA extracted of primary cultures LTR, pol, env and tax HTLV-1 proviral DNA regions were differentially amplified by PCR showing proviral integration. Using poly A+ RNA obtained of these primary cultures, we amplify by RT-PCR cDNA of tax and pol in 57.14% (8/14 HAM/TSP patients and 27.28% (3/11 AC. Tax and pol poly A+ RNA were expressed only in those sIgA positive subjects. Our results showed that proviral integration and viral gene expression in oral keratinocytes are associated with a HTLV-1 specific local mucosal immune response only in those HTLV-1 infected individuals with detectable levels of sIgA in their oral fluids. Altogether the results gave strong evidence that oral mucosa infection would be parte of the systemic spreading of HTLV-1 infection.

  20. Reactivation of herpes simplex virus in a cell line inducible for simian virus 40 synthesis

    International Nuclear Information System (INIS)

    Zamansky, G.B.; Kleinman, L.F.; Black, P.H.; Kaplan, J.C.

    1980-01-01

    The reactivation of UV-irradiated herpes simplex virus (HSV) was investigated in irradiated and unirradiated transformed hamster cells in which infectious simian virus 40(SV40) can be induced. Reactivation was enhanced when the cells were treated with UV light or mitomycin C prior to infection with HSV. The UV dose-response curve of this enhanced reactivation was strikingly similar to that found for induction of SV40 virus synthesis in cells treated under identical conditions. This is the first time that two SOS functions described in bacteria have been demonstrated in a single mammalian cell line. (orig.)

  1. Linear energy divergences in Coulomb gauge QCD

    OpenAIRE

    Andrasi, A.

    2011-01-01

    The structure of linear energy divergences is analysed on the example of one graph to 3-loop order. Such dangerous divergences do cancel when all graphs are added, but next to leading divergences do not cancel out.

  2. Boiling flow through diverging microchannel

    Indian Academy of Sciences (India)

    such systems, for small pressure drop penalty and with good flow stability. .... ied the effect of divergence angle on mean and transient pressure/temperature distribution and .... supplying a fixed voltage and current using a power source meter.

  3. Atmospheric horizontal divergence and diffusion

    International Nuclear Information System (INIS)

    Castans, M.

    1981-01-01

    The action of horizontal divergence on diffusion near the ground is established through.a very simple flow model. The shape of the well-known Pasquill-Gifford-Turner curves, that apparently take account in some way of divergence, is justified. The possibility of explaining the discre--pancies between the conventional straight line model and experimental results, mainly under low-wind-speed satable conditions, is considered. Some hints for further research are made. (auth.)

  4. String loop divergences and effective lagrangians

    International Nuclear Information System (INIS)

    Fischler, W.; Klebanov, I.; Susskind, L.

    1988-01-01

    We isolate logarithmic divergences from bosonic string amplitudes on a disc. These divergences are compared with 'tadpole' divergences in the effective field theory, with a covariant cosmological term implied by the counting of string coupling constants. We find an inconsistency between the two. This might be a problem in eliminating divergences from the bosonic string. (orig.)

  5. Semantic search during divergent thinking.

    Science.gov (United States)

    Hass, Richard W

    2017-09-01

    Divergent thinking, as a method of examining creative cognition, has not been adequately analyzed in the context of modern cognitive theories. This article casts divergent thinking responding in the context of theories of memory search. First, it was argued that divergent thinking tasks are similar to semantic fluency tasks, but are more constrained, and less well structured. Next, response time distributions from 54 participants were analyzed for temporal and semantic clustering. Participants responded to two prompts from the alternative uses test: uses for a brick and uses for a bottle, for two minutes each. Participants' cumulative response curves were negatively accelerating, in line with theories of search of associative memory. However, results of analyses of semantic and temporal clustering suggested that clustering is less evident in alternative uses responding compared to semantic fluency tasks. This suggests either that divergent thinking responding does not involve an exhaustive search through a clustered memory trace, but rather that the process is more exploratory, yielding fewer overall responses that tend to drift away from close associates of the divergent thinking prompt. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Replication of simian virus 40 in simian virus 40-transformed hamster kidney cells induced by mitomycin C or 60Co γ irradiation

    International Nuclear Information System (INIS)

    Rakusanova, T.; Smales, W.P.; Kaplan, J.C.; Black, P.H.

    1978-01-01

    Several clones of simian virus 40 (SV40)-transformed hamster kidney cells, which are heterogeneous for induction of infectious SV40, have been studied. SV40 yields are low after induction with 60 Co γ irradiation or mitomycin C. In order to clarify the mechanism(s) by which virus is produced in induced cells, we analyzed the replication of viral DNA and production of virion (V) antigen and infectious virus after induction in various clones as well as in lytically infected permissive cells. Cells replicating SV40 DNA or synthesizing V antigen were visualized by in situ hybridization and immunofluorescence techniques, respectively. Only some cells in induced cultures were found to produce SV40 and those which did were less efficient than lytically infected monkey cells. Mitomycin C or 60 Co γ irradiation acted by inducing more cells to replicate virus rather than by increasing the amount of SV40 released from individual cells. A greater proportion of cells could be induced to replicate SV40 DNA than to synthesize V antigen in all induced clones studied. Also, SV40 DNA replication was induced at lower doses of γ irradiation than the production of either V antigen or infectious virus suggesting that synthesis of late virus protein is more restricted in induced cells than is replication of SV40 DNA. These findings indicate that one of the effects of induction treatments on SV40-transformed hamster cells is an enhancement of the cells' capacity to support SV40 replication

  7. Hyperreal Numbers for Infinite Divergent Series

    OpenAIRE

    Bartlett, Jonathan

    2018-01-01

    Treating divergent series properly has been an ongoing issue in mathematics. However, many of the problems in divergent series stem from the fact that divergent series were discovered prior to having a number system which could handle them. The infinities that resulted from divergent series led to contradictions within the real number system, but these contradictions are largely alleviated with the hyperreal number system. Hyperreal numbers provide a framework for dealing with divergent serie...

  8. Chained Kullback-Leibler Divergences

    Science.gov (United States)

    Pavlichin, Dmitri S.; Weissman, Tsachy

    2017-01-01

    We define and characterize the “chained” Kullback-Leibler divergence minw D(p‖w) + D(w‖q) minimized over all intermediate distributions w and the analogous k-fold chained K-L divergence min D(p‖wk−1) + … + D(w2‖w1) + D(w1‖q) minimized over the entire path (w1,…,wk−1). This quantity arises in a large deviations analysis of a Markov chain on the set of types – the Wright-Fisher model of neutral genetic drift: a population with allele distribution q produces offspring with allele distribution w, which then produce offspring with allele distribution p, and so on. The chained divergences enjoy some of the same properties as the K-L divergence (like joint convexity in the arguments) and appear in k-step versions of some of the same settings as the K-L divergence (like information projections and a conditional limit theorem). We further characterize the optimal k-step “path” of distributions appearing in the definition and apply our findings in a large deviations analysis of the Wright-Fisher process. We make a connection to information geometry via the previously studied continuum limit, where the number of steps tends to infinity, and the limiting path is a geodesic in the Fisher information metric. Finally, we offer a thermodynamic interpretation of the chained divergence (as the rate of operation of an appropriately defined Maxwell’s demon) and we state some natural extensions and applications (a k-step mutual information and k-step maximum likelihood inference). We release code for computing the objects we study. PMID:29130024

  9. The nonnucleoside reverse transcription inhibitor MIV-160 delivered from an intravaginal ring, but not from a carrageenan gel, protects against simian/human immunodeficiency virus-RT Infection.

    Science.gov (United States)

    Aravantinou, Meropi; Singer, Rachel; Derby, Nina; Calenda, Giulia; Mawson, Paul; Abraham, Ciby J; Menon, Radhika; Seidor, Samantha; Goldman, Daniel; Kenney, Jessica; Villegas, Guillermo; Gettie, Agegnehu; Blanchard, James; Lifson, Jeffrey D; Piatak, Michael; Fernández-Romero, José A; Zydowsky, Thomas M; Teleshova, Natalia; Robbiani, Melissa

    2012-11-01

    We previously showed that a carrageenan (CG) gel containing 50 μM MIV-150 (MIV-150/CG) reduced vaginal simian/human immunodeficiency virus (SHIV)-RT infection of macaques (56%, p>0.05) when administered daily for 2 weeks with the last dose given 8 h before challenge. Additionally, when 100 mg of MIV-150 was loaded into an intravaginal ring (IVR) inserted 24 h before challenge and removed 2 weeks after challenge, >80% protection was observed (p<0.03). MIV-160 is a related NNRTI with a similar IC(50), greater aqueous solubility, and a shorter synthesis. To objectively compare MIV-160 with MIV-150, herein we evaluated the antiviral effects of unformulated MIV-160 in vitro as well as the in vivo protection afforded by MIV-160 delivered in CG (MIV-160/CG gel) and in an IVR under regimens used with MIV-150 in earlier studies. Like MIV-150, MIV-160 exhibited potent antiviral activity against SHIV-RT in macaque vaginal explants. However, formulated MIV-160 exhibited divergent effects in vivo. The MIV-160/CG gel offered no protection compared to CG alone, whereas the MIV-160 IVRs protected significantly. Importantly, the results of in vitro release studies of the MIV-160/CG gel and the MIV-160 IVR suggested that in vivo efficacy paralleled the amount of MIV-160 released in vitro. Hundreds of micrograms of MIV-160 were released daily from IVRs while undetectable amounts of MIV-160 were released from the CG gel. Our findings highlight the importance of testing different modalities of microbicide delivery to identify the optimal formulation for efficacy in vivo.

  10. SIVdrl detection in captive mandrills: are mandrills infected with a third strain of simian immunodeficiency virus?

    Directory of Open Access Journals (Sweden)

    Osterhaus Albert DME

    2004-11-01

    Full Text Available Abstract A pol-fragment of simian immunodeficiency virus (SIV that is highly related to SIVdrl-pol from drill monkeys (Mandrillus leucophaeus was detected in two mandrills (Mandrillus sphinx from Amsterdam Zoo. These captivity-born mandrills had never been in contact with drill monkeys, and were unlikely to be hybrids. Their mitochondrial haplotype suggested that they descended from founder animals in Cameroon or northern Gabon, close to the habitat of the drill. SIVdrl has once before been found in a wild-caught mandrill from the same region, indicating that mandrills are naturally infected with a SIVdrl-like virus. This suggests that mandrills are the first primate species to be infected with three strains of SIV: SIVmnd1, SIVmnd2, and SIVdrl.

  11. Understanding the Process of Envelope Glycoprotein Incorporation into Virions in Simian and Feline Immunodeficiency Viruses

    Directory of Open Access Journals (Sweden)

    José L. Affranchino

    2014-01-01

    Full Text Available The lentiviral envelope glycoproteins (Env mediate virus entry by interacting with specific receptors present at the cell surface, thereby determining viral tropism and pathogenesis. Therefore, Env incorporation into the virions formed by assembly of the viral Gag polyprotein at the plasma membrane of the infected cells is a key step in the replication cycle of lentiviruses. Besides being useful models of human immunodeficiency virus (HIV infections in humans and valuable tools for developing AIDS therapies and vaccines, simian and feline immunodeficiency viruses (SIV and FIV, respectively are relevant animal retroviruses; the study of which provides important information on how lentiviral replication strategies have evolved. In this review, we discuss the molecular mechanisms underlying the incorporation of the SIV and FIV Env glycoproteins into viral particles.

  12. Effect of uv-irradiation on genetic recombination of Simian virus 40 mutants

    International Nuclear Information System (INIS)

    Gentil, A.; Margot, A.; Sarasin, A.

    1983-01-01

    Genetic recombination in monkey kidney cells has been studied using Simian virus 40 (SV40) as a molecular probe. Control or uv-irradiated cells have been co-infected with two thermosensitive mutants of SV40, tsA58 and tsA30. Recombination between the two viral genomes gives rise to a wild type virus phenotype, able to grow at the restrictive temperature of 41 0 C, which was taken as a measure of the recombination activity of the host cells. Results show that recombination takes place at a low frequency when viruses are not uv-irradiated. Irradiation of one or both viruses increases drastically recombination frequency. Pretreatment of the host cells with uv-light or mitomycin C 24 hours before being infected does not increase recombination frequency measured in our experimental conditions. 23 references, 5 tables

  13. Influence of cell dissociation procedures on the tumorigenicity of Simian Virus 40 transformed fibroblasts

    International Nuclear Information System (INIS)

    Tenforde, T.S.; Risius, J.; Beckmann, A.; Tobias, C.A.; Gurney, E.

    1975-11-01

    Mouse fibroblasts transformed by Simian Virus 40 (SV40) were examined for tumor forming ability in syngeneic BALB/c mice following dissociation from tissue culture dishes by two procedures. A significantly greater in vivo proliferative capacity was observed for cells dissociated by the tryspin-EDTA procedure, with the injected cell dose for tumor production in 50 percent of recipient mice (the TPD 50 ) being 16-fold lower than the TPD 50 for cells dissociated by the EDTA procedure. Host immunosuppression with 300 rad whole-body γ irradiation led to a significant 7-fold decrease in the TPD 50 for cells dissociated by the EDTA procedure, while no significant decrease in TPD 50 was observed for cells dissociated by the tryspin-EDTA procedure

  14. Formation of pyrimidine dimers in Simian virus 40 chromosomes and DNA in vitro: effects of salt

    International Nuclear Information System (INIS)

    Edenberg, H.J.

    1984-01-01

    Simian virus 40 chromosomes were used to determine whether packaging of DNA into chromatin affected the yield of cylcobutane pyrimidine dimers introduced by ultraviolet light (254 nm). SV40 chromatin and purified SV40 DNA (radioactively labeled with different isotopes) were mixed and irradiated in vitro. The proteins were extracted and pyrimidine dimers detected as sites sensitive to the UV-endonuclease encoded by bacteriophage T4. When irradiation was carried out in the presence of at least 0.05 M NaCl the same number of dimers were formed in chromatin as in free DNA. Irradiation in the absence of NaCl, however, reduced the relative yield of dimers in chromatin to 89% of that in free DNA. Different methods of chromatin preparation did not influence these results. (author)

  15. Induction of Mucosal and Systemic Immunity to a Recombinant Simian Immunodeficiency Viral Protein

    Science.gov (United States)

    Lehner, T.; Bergmeier, L. A.; Panagiotidi, C.; Tao, L.; Brookes, R.; Klavinskis, L. S.; Walker, P.; Walker, J.; Ward, R. G.; Hussain, L.; Gearing, A. J. H.; Adams, S. E.

    1992-11-01

    Heterosexual transmission through the cervico-vaginal mucosa is the principal route of human immunodeficiency virus (HIV) infection in Africa and is increasing in the United States and Europe. Vaginal immunization with simian immunodeficiency virus (SIV) had not yet been studied in nonhuman primates. Immune responses in macaques were investigated by stimulation of the genital and gut-associated lymphoid tissue with a recombinant, particulate SIV antigen. Vaginal, followed by oral, administration of the vaccine elicited three types of immunity: (i) gag protein p27-specific, secretory immunoglobulin A (IgA) and immunoglobulin G (IgG) in the vaginal fluid, (ii) specific CD4^+ T cell proliferation and helper function in B cell p27-specific IgA synthesis in the genital lymph nodes, and (iii) specific serum IgA and IgG, with CD4^+ T cell proliferative and helper functions in the circulating blood.

  16. Cell and molecular biology of simian virus 40: implications for human infections and disease

    Science.gov (United States)

    Butel, J. S.; Lednicky, J. A.

    1999-01-01

    Simian virus 40 (SV40), a polyomavirus of rhesus macaque origin, was discovered in 1960 as a contaminant of polio vaccines that were distributed to millions of people from 1955 through early 1963. SV40 is a potent DNA tumor virus that induces tumors in rodents and transforms many types of cells in culture, including those of human origin. This virus has been a favored laboratory model for mechanistic studies of molecular processes in eukaryotic cells and of cellular transformation. The viral replication protein, named large T antigen (T-ag), is also the viral oncoprotein. There is a single serotype of SV40, but multiple strains of virus exist that are distinguishable by nucleotide differences in the regulatory region of the viral genome and in the part of the T-ag gene that encodes the protein's carboxyl terminus. Natural infections in monkeys by SV40 are usually benign but may become pathogenic in immunocompromised animals, and multiple tissues can be infected. SV40 can replicate in certain types of simian and human cells. SV40-neutralizing antibodies have been detected in individuals not exposed to contaminated polio vaccines. SV40 DNA has been identified in some normal human tissues, and there are accumulating reports of detection of SV40 DNA and/or T-ag in a variety of human tumors. This review presents aspects of replication and cell transformation by SV40 and considers their implications for human infections and disease pathogenesis by the virus. Critical assessment of virologic and epidemiologic data suggests a probable causative role for SV40 in certain human cancers, but additional studies are necessary to prove etiology.

  17. Electrostatic potential of human immunodeficiency virus type 2 and rhesus macaque simian immunodeficiency virus capsid proteins

    Directory of Open Access Journals (Sweden)

    Katarzyna eBozek

    2012-06-01

    Full Text Available Human immunodeficiency virus type 2 (HIV-2 and simian immunodeficiency virus isolated from a macaque monkey (SIVmac are assumed to have originated from simian immunodeficiency virus isolated from sooty mangabey (SIVsm. Despite their close similarity in genome structure, HIV-2 and SIVmac show different sensitivities to TRIM5α, a host restriction factor against retroviruses. The replication of HIV-2 strains is potently restricted by rhesus (Rh monkey TRIM5α, while that of SIVmac strain 239 (SIVmac239 is not. Viral capsid protein is the determinant of this differential sensitivity to TRIM5α, as the HIV-2 mutant carrying SIVmac239 capsid protein evaded Rh TRIM5α-mediated restriction. However, the molecular determinants of this restriction mechanism are unknown. Electrostatic potential on the protein-binding site is one of the properties regulating protein-protein interactions. In this study, we investigated the electrostatic potential on the interaction surface of capsid protein of HIV-2 strain GH123 and SIVmac239. Although HIV-2 GH123 and SIVmac239 capsid proteins share more than 87% amino acid identity, we observed a large difference between the two molecules with the HIV-2 GH123 molecule having predominantly positive and SIVmac239 predominantly negative electrostatic potential on the surface of the loop between α-helices 4 and 5 (L4/5. As L4/5 is one of the major determinants of Rh TRIM5α sensitivity of these viruses, the present results suggest that the binding site of the Rh TRIM5α may show complementarity to the HIV-2 GH123 capsid surface charge distribution.

  18. Seroprevalence of simian immunodeficiency virus in wild and captive born Sykes' monkeys (Cercopithecus mitis) in Kenya

    OpenAIRE

    Otsyula Moses G; Robinson James; Elliott Debra; Munene Elephas; Ellis Brett R; Michael Scott F

    2004-01-01

    Abstract Background The Sykes' monkey and related forms (Cercopithecus mitis) make up an abundant, widespread and morphologically diverse species complex in eastern Africa that naturally harbors a distinct simian immunodeficiency virus (SIVsyk). We carried out a retrospective serological survey of SIV infection from both wild and captive Sykes' monkeys from Kenya. We compared two commercially available, cross-reactive ELISA tests using HIV antigens with a novel SIVsyk antigen-specific Western...

  19. On Hölder Projective Divergences

    KAUST Repository

    Nielsen, Frank

    2017-03-16

    We describe a framework to build distances by measuring the tightness of inequalities and introduce the notion of proper statistical divergences and improper pseudo-divergences. We then consider the Holder ordinary and reverse inequalities and present two novel classes of Holder divergences and pseudo-divergences that both encapsulate the special case of the Cauchy-Schwarz divergence. We report closed-form formulas for those statistical dissimilarities when considering distributions belonging to the same exponential family provided that the natural parameter space is a cone (e.g., multivariate Gaussians) or affine (e.g., categorical distributions). Those new classes of Holder distances are invariant to rescaling and thus do not require distributions to be normalized. Finally, we show how to compute statistical Holder centroids with respect to those divergences and carry out center-based clustering toy experiments on a set of Gaussian distributions which demonstrate empirically that symmetrized Holder divergences outperform the symmetric Cauchy-Schwarz divergence.

  20. On Hölder Projective Divergences

    KAUST Repository

    Nielsen, Frank; Sun, Ke; Marchand-Maillet, Stephane

    2017-01-01

    We describe a framework to build distances by measuring the tightness of inequalities and introduce the notion of proper statistical divergences and improper pseudo-divergences. We then consider the Holder ordinary and reverse inequalities and present two novel classes of Holder divergences and pseudo-divergences that both encapsulate the special case of the Cauchy-Schwarz divergence. We report closed-form formulas for those statistical dissimilarities when considering distributions belonging to the same exponential family provided that the natural parameter space is a cone (e.g., multivariate Gaussians) or affine (e.g., categorical distributions). Those new classes of Holder distances are invariant to rescaling and thus do not require distributions to be normalized. Finally, we show how to compute statistical Holder centroids with respect to those divergences and carry out center-based clustering toy experiments on a set of Gaussian distributions which demonstrate empirically that symmetrized Holder divergences outperform the symmetric Cauchy-Schwarz divergence.

  1. Genetic Divergence in Sugarcane Genotypes

    OpenAIRE

    Tahir, Mohammad; Rahman, Hidayatur; Gul, Rahmani; Ali, Amjad; Khalid, Muhammad

    2012-01-01

    To assess genetic divergence of sugarcane germplasm, an experiment comprising 25 sugarcane genotypes was conducted at Sugar Crops Research Institute (SCRI), Mardan, Khyber Pakhtunkhwa, Pakistan, in quadruple lattice design during 2008-09. Among the 14 parameters evaluated, majority exhibited significant differences while some showed nonsignificant mean squares. The initial correlation matrix revealed medium to high correlations. Principal Component Analysis (PCA) showed that there were two pr...

  2. Computer recognition of divergences in Feynman graphs

    Energy Technology Data Exchange (ETDEWEB)

    Calmet, J

    1973-05-01

    The program described recognizes whether or not a graph is divergent. It determines the kind of the divergences found: vacuum polarizations, electron self energies and vertices. it does not consider infrared divergences. The programming language used is REDUCE. A LISP version is also available. The nature of the divergences and their counter terms was extensively used to write down this program, therefore it is limited to the case of quantum electrodynamics. (auth)

  3. Genetic divergence of tomato subsamples

    Directory of Open Access Journals (Sweden)

    André Pugnal Mattedi

    2014-02-01

    Full Text Available Understanding the genetic variability of a species is crucial for the progress of a genetic breeding program and requires characterization and evaluation of germplasm. This study aimed to characterize and evaluate 101 tomato subsamples of the Salad group (fresh market and two commercial controls, one of the Salad group (cv. Fanny and another of the Santa Cruz group (cv. Santa Clara. Four experiments were conducted in a randomized block design with three replications and five plants per plot. The joint analysis of variance was performed and characteristics with significant complex interaction between control and experiment were excluded. Subsequently, the multicollinearity diagnostic test was carried out and characteristics that contributed to severe multicollinearity were excluded. The relative importance of each characteristics for genetic divergence was calculated by the Singh's method (Singh, 1981, and the less important ones were excluded according to Garcia (1998. Results showed large genetic divergence among the subsamples for morphological, agronomic and organoleptic characteristics, indicating potential for genetic improvement. The characteristics total soluble solids, mean number of good fruits per plant, endocarp thickness, mean mass of marketable fruit per plant, total acidity, mean number of unmarketable fruit per plant, internode diameter, internode length, main stem thickness and leaf width contributed little to the genetic divergence between the subsamples and may be excluded in future studies.

  4. Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia.

    Science.gov (United States)

    Reeves, Daniel B; Peterson, Christopher W; Kiem, Hans-Peter; Schiffer, Joshua T

    2017-07-01

    Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts the plasma viral load set point and the rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load but an unchanged viral set point during viral rebound. The addition of an autologous stem cell transplant before cART withdrawal alters viral dynamics: we found a higher rebound set point but similar peak viral loads compared to the primary infection. Mathematical modeling of the data that accounts for fundamental immune parameters achieves excellent fit to heterogeneous viral loads. Analysis of model output suggests that the rapid memory immune response following treatment interruption does not ultimately lead to better viral containment. Transplantation decreases the durability of the adaptive immune response following cART withdrawal and viral rebound. Our model's results highlight the impact of the endogenous adaptive immune response during primary SHIV infection. Moreover, because we capture adaptive immune memory and the impact of transplantation, this model will provide insight into further studies of cure strategies inspired by the Berlin patient. IMPORTANCE HIV patients who interrupt combination antiretroviral therapy (cART) eventually experience viral rebound, the return of viral loads to pretreatment levels. However, the "Berlin patient" remained free of HIV rebound over a decade after stopping cART. His cure is attributed to leukemia treatment that included an HIV-resistant stem cell transplant. Inspired by this case, we studied the impact

  5. Macaque homologs of EBV and KSHV show uniquely different associations with simian AIDS-related lymphomas.

    Directory of Open Access Journals (Sweden)

    A Gregory Bruce

    Full Text Available Two gammaherpesviruses, Epstein-Barr virus (EBV (Lymphocryptovirus genus and Kaposi's sarcoma-associated herpesvirus (KSHV (Rhadinovirus genus have been implicated in the etiology of AIDS-associated lymphomas. Homologs of these viruses have been identified in macaques and other non-human primates. In order to assess the association of these viruses with non-human primate disease, archived lymphoma samples were screened for the presence of macaque lymphocryptovirus (LCV homologs of EBV, and macaque rhadinoviruses belonging to the RV1 lineage of KSHV homologs or the more distant RV2 lineage of Old World primate rhadinoviruses. Viral loads were determined by QPCR and infected cells were identified by immunolabeling for different viral proteins. The lymphomas segregated into three groups. The first group (n = 6 was associated with SIV/SHIV infections, contained high levels of LCV (1-25 genomes/cell and expressed the B-cell antigens CD20 or BLA.36. A strong EBNA-2 signal was detected in the nuclei of the neoplastic cells in one of the LCV-high lymphomas, indicative of a type III latency stage. None of the lymphomas in this group stained for the LCV viral capsid antigen (VCA lytic marker. The second group (n = 5 was associated with D-type simian retrovirus-2 (SRV-2 infections, contained high levels of RV2 rhadinovirus (9-790 genomes/cell and expressed the CD3 T-cell marker. The third group (n = 3 was associated with SIV/SHIV infections, contained high levels of RV2 rhadinovirus (2-260 genomes/cell and was negative for both CD20 and CD3. In both the CD3-positive and CD3/CD20-negative lymphomas, the neoplastic cells stained strongly for markers of RV2 lytic replication. None of the lymphomas had detectable levels of retroperitoneal fibromatosis herpesvirus (RFHV, the macaque RV1 homolog of KSHV. Our data suggest etiological roles for both lymphocryptoviruses and RV2 rhadinoviruses in the development of simian AIDS-associated lymphomas and indicate that

  6. Molecular ecology and natural history of simian foamy virus infection in wild-living chimpanzees.

    Directory of Open Access Journals (Sweden)

    Weimin Liu

    2008-07-01

    Full Text Available Identifying microbial pathogens with zoonotic potential in wild-living primates can be important to human health, as evidenced by human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2 and Ebola virus. Simian foamy viruses (SFVs are ancient retroviruses that infect Old and New World monkeys and apes. Although not known to cause disease, these viruses are of public health interest because they have the potential to infect humans and thus provide a more general indication of zoonotic exposure risks. Surprisingly, no information exists concerning the prevalence, geographic distribution, and genetic diversity of SFVs in wild-living monkeys and apes. Here, we report the first comprehensive survey of SFVcpz infection in free-ranging chimpanzees (Pan troglodytes using newly developed, fecal-based assays. Chimpanzee fecal samples (n = 724 were collected at 25 field sites throughout equatorial Africa and tested for SFVcpz-specific antibodies (n = 706 or viral nucleic acids (n = 392. SFVcpz infection was documented at all field sites, with prevalence rates ranging from 44% to 100%. In two habituated communities, adult chimpanzees had significantly higher SFVcpz infection rates than infants and juveniles, indicating predominantly horizontal rather than vertical transmission routes. Some chimpanzees were co-infected with simian immunodeficiency virus (SIVcpz; however, there was no evidence that SFVcpz and SIVcpz were epidemiologically linked. SFVcpz nucleic acids were recovered from 177 fecal samples, all of which contained SFVcpz RNA and not DNA. Phylogenetic analysis of partial gag (616 bp, pol-RT (717 bp, and pol-IN (425 bp sequences identified a diverse group of viruses, which could be subdivided into four distinct SFVcpz lineages according to their chimpanzee subspecies of origin. Within these lineages, there was evidence of frequent superinfection and viral recombination. One chimpanzee was infected by a foamy virus from a Cercopithecus monkey

  7. Statistical inference based on divergence measures

    CERN Document Server

    Pardo, Leandro

    2005-01-01

    The idea of using functionals of Information Theory, such as entropies or divergences, in statistical inference is not new. However, in spite of the fact that divergence statistics have become a very good alternative to the classical likelihood ratio test and the Pearson-type statistic in discrete models, many statisticians remain unaware of this powerful approach.Statistical Inference Based on Divergence Measures explores classical problems of statistical inference, such as estimation and hypothesis testing, on the basis of measures of entropy and divergence. The first two chapters form an overview, from a statistical perspective, of the most important measures of entropy and divergence and study their properties. The author then examines the statistical analysis of discrete multivariate data with emphasis is on problems in contingency tables and loglinear models using phi-divergence test statistics as well as minimum phi-divergence estimators. The final chapter looks at testing in general populations, prese...

  8. Ultraviolet divergences and supersymmetric theories

    International Nuclear Information System (INIS)

    Sagnotti, A.

    1984-09-01

    This article is closely related to the one by Ferrara in these same Proceedings. It deals with what is perhaps the most fascinating property of supersymmetric theories, their improved ultraviolet behavior. My aim here is to present a survey of the state of the art as of August, 1984, and a somewhat more detailed discussion of the breakdown of the superspace power-counting beyond N = 2 superfields. A method is also described for simplifying divergence calculations that uses the locality of subtracted Feynman integrals. 74 references

  9. Ultraviolet divergences of Einstein gravity

    International Nuclear Information System (INIS)

    Goroff, M.H.

    1986-01-01

    The author discuss a two-loop calculation showing that the S matrix of Einstein's theory of gravity contains nonrenormalizable ultraviolet divergences in four dimension. The author discusses the calculation in both background field and normal field theory. The author describes a new method for dealing with ghost fields in gauge theories by combining them with suitable extensions of the gauge fields in higher dimensions. The author shows how using subtracted integrals in the calculation of higher loop graphs simplifies the calculation in the background field method by eliminating the need for mixed counterterms. Finally, the author makes some remarks about the implications of the result for supergravity theories

  10. Mesothelioma mortality in Europe: impact of asbestos consumption and simian virus 40

    Directory of Open Access Journals (Sweden)

    Rehak Peter

    2006-11-01

    Full Text Available Abstract Background It is well established that asbestos is the most important cause of mesothelioma. The role of simian virus 40 (SV40 in mesothelioma development, on the other hand, remains controversial. This potential human oncogene has been introduced into various populations through contaminated polio vaccines. The aim of this study was to investigate whether the possible presence of SV40 in various European countries, as indicated either by molecular genetic evidence or previous exposure to SV40-contaminated vaccines, had any effect on pleural cancer rates in the respective countries. Methods We conducted a Medline search that covered the period from January 1969 to August 2005 for reports on the detection of SV40 DNA in human tissue samples. In addition, we collected all available information about the types of polio vaccines that had been used in these European countries and their SV40 contamination status. Results Our ecological analysis confirms that pleural cancer mortality in males, but not in females, correlates with the extent of asbestos exposure 25 – 30 years earlier. In contrast, neither the presence of SV40 DNA in tumor samples nor a previous vaccination exposure had any detectable influence on the cancer mortality rate in neither in males (asbestos-corrected rates nor in females. Conclusion Using the currently existing data on SV40 prevalence, no association between SV40 prevalence and asbestos-corrected male pleural cancer can be demonstrated.

  11. Immunovirological analyses of chronically simian immunodeficiency virus SIVmnd-1- and SIVmnd-2-infected mandrills (Mandrillus sphinx).

    Science.gov (United States)

    Apetrei, Cristian; Sumpter, Beth; Souquiere, Sandrine; Chahroudi, Ann; Makuwa, Maria; Reed, Patricia; Ribeiro, Ruy M; Pandrea, Ivona; Roques, Pierre; Silvestri, Guido

    2011-12-01

    Simian immunodeficiency virus (SIV) infection in African nonhuman primate (NHP) natural hosts is usually nonpathogenic, despite high levels of virus replication. We have previously shown that chronic SIV infection in sooty mangabeys (SMs) and African green monkeys (AGMs) is associated with low levels of immune activation and bystander T cell apoptosis. To compare these features with those observed in another natural host, the mandrill (MND), we conducted a cross-sectional survey of the 23 SIV-infected and 25 uninfected MNDs from the only semifree colony of mandrills available worldwide. Viral loads (VLs) were determined and phenotypic and functional analysis of peripheral blood- and lymph node-derived lymphocytes was performed. We found that mandrills chronically infected with SIVmnd-1 or SIVmnd-2 have similar levels of viral replication, and we observed a trend toward lower CD4+ T cell counts in chronically SIVmnd-2-infected MNDs than SIVmnd-1-infected MNDs. No correlation between CD4+ T cell counts and VLs in SIV-infected MNDs could be established. Of note, the levels of T cell activation, proliferation, and apoptosis were comparable between SIVmnd-1- and SIVmnd-2-infected MNDs and to those observed in uninfected animals, with the only exception being an increase in tumor necrosis factor alpha-producing CD8+ T cells in SIVmnd-2-infected MNDs. Overall, these findings recapitulate previous observations in SIV-infected SMs and AGMs and lend further evidence to the hypothesis that low levels of immune activation protect natural SIV hosts from disease progression.

  12. Nef Secretion into Extracellular Vesicles or Exosomes Is Conserved across Human and Simian Immunodeficiency Viruses

    Directory of Open Access Journals (Sweden)

    Ryan P. McNamara

    2018-02-01

    Full Text Available Extracellular vesicles (EVs or exosomes have been implicated in the pathophysiology of infections and cancer. The negative regulatory factor (Nef encoded by simian immunodeficiency virus (SIV and human immunodeficiency virus (HIV plays a critical role in the progression to AIDS and impairs endosomal trafficking. Whether HIV-1 Nef can be loaded into EVs has been the subject of controversy, and nothing is known about the connection between SIV Nef and EVs. We find that both SIV and HIV-1 Nef proteins are present in affinity-purified EVs derived from cultured cells, as well as in EVs from SIV-infected macaques. Nef-positive EVs were functional, i.e., capable of membrane fusion and depositing their content into recipient cells. The EVs were able to transfer Nef into recipient cells. This suggests that Nef readily enters the exosome biogenesis pathway, whereas HIV virions are assembled at the plasma membrane. It suggests a novel mechanism by which lentiviruses can influence uninfected and uninfectable, i.e., CD4-negative, cells.

  13. Simian virus 40, poliovirus vaccines, and human cancer: research progress versus media and public interests

    Science.gov (United States)

    Butel, J. S.

    2000-01-01

    From 1955 through early 1963, millions of people were inadvertently exposed to simian virus 40 (SV40) as a contaminant of poliovirus vaccines; the virus had been present in the monkey kidney cultures used to prepare the vaccines and had escaped detection. SV40 was discovered in 1960 and subsequently eliminated from poliovirus vaccines. This article reviews current knowledge about SV40 and considers public responses to reports in the media. SV40 is a potent tumour virus with broad tissue tropism that induces tumours in rodents and transforms cultured cells from many species. It is also an important laboratory model for basic studies of molecular processes in eukaryotic cells and mechanisms of neoplastic transformation. SV40 neutralizing antibodies have been detected in individuals not exposed to contaminated poliovirus vaccines. There have been many reports of detection of SV40 DNA in human tumours, especially mesotheliomas, brain tumours and osteosarcomas; and DNA sequence analyses have ruled out the possibility that the viral DNA in tumours was due to laboratory contamination or that the virus had been misidentified. However, additional studies are necessary to prove that SV40 is the cause of certain human cancers. A recently published review article evaluated the status of the field and received much media attention. The public response emphasized that there is great interest in the possibility of health risks today from vaccinations received in the past.

  14. Enhanced replication of UV-damaged Simian virus 40 DNA in carcinogen-treated mammalian cells

    International Nuclear Information System (INIS)

    Maga, J.A.

    1983-01-01

    The replication of UV-damaged Simian virus 40 (SV40) in carcinogen-treated monkey cells has been studied to elucidate the mechanism of carcinogen-enhanced reactivation. Carcinogen enhanced reactivation is the observed increase in UV-irradiated virus survival in host cells treated with low doses of carcinogen compared to UV-irradiated virus survival in untreated hosts. Carcinogen treatment of monkey kidney cells with either N-acetoxy-2-acetylaminofluorene (AAAF) or UV radiation leads to an enhanced capacity to replicate UV-damaged virus during the first round of infection. To further define the mechanism leading to enhanced replication, a detailed biochemical analysis of replication intermediates in carcinogen-treated cells was performed. Several conclusions can be drawn. First enhanced replication can be observed in the first four rounds of replication after UV irradiation of viral templates. The second major finding is that the relaxed circular intermediate model proposed for the replication of UV-damaged templates in untreated cells appears valid for replication of UV-damaged templates in carcinogen-treated cells. Possible mechanisms and the supporting evidence are discussed and future experiments outlined

  15. Seroprevalence of simian immunodeficiency virus in wild and captive born Sykes' monkeys (Cercopithecus mitis in Kenya

    Directory of Open Access Journals (Sweden)

    Otsyula Moses G

    2004-10-01

    Full Text Available Abstract Background The Sykes' monkey and related forms (Cercopithecus mitis make up an abundant, widespread and morphologically diverse species complex in eastern Africa that naturally harbors a distinct simian immunodeficiency virus (SIVsyk. We carried out a retrospective serological survey of SIV infection from both wild and captive Sykes' monkeys from Kenya. We compared two commercially available, cross-reactive ELISA tests using HIV antigens with a novel SIVsyk antigen-specific Western blot assay and analyzed the data by origin, subspecies, age and sex. Results The SIVsyk antigen-specific Western blot assay detected more serum samples as positive than either of the cross-reactive ELISA assays. Using this assay, we found that seroprevalence is higher than previously reported, but extremely variable in wild populations (from 0.0 to 90.9%. Females were infected more often than males in both wild and captive populations. Seropositive infants were common. However, no seropositive juveniles were identified. Conclusion We have developed a specific and sensitive Western blot assay for anti-SIVsyk antibody detection. Sykes' monkeys are commonly infected with SIVsyk, but with extremely variable prevalence in the wild. Higher infection prevalence in females suggests predominantly sexual transmission. High infection prevalence in infants, but none in juveniles, suggests maternal antibodies, but little or no vertical transmission.

  16. Simian virus 40 inhibits differentiation and maturation of rhesus macaque DC-SIGN+-dendritic cells

    Directory of Open Access Journals (Sweden)

    Changyong G

    2010-09-01

    Full Text Available Abstract Dendritic cells (DC are the initiators and modulators of the immune responses. Some species of pathogenic microorganisms have developed immune evasion strategies by controlling antigen presentation function of DC. Simian virus 40 (SV40 is a DNA tumor virus of rhesus monkey origin. It can induce cell transformation and tumorigenesis in many vertebrate species, but often causes no visible effects and persists as a latent infection in rhesus monkeys under natural conditions. To investigate the interaction between SV40 and rhesus monkey DC, rhesus monkey peripheral blood monocyte-derived DC were induced using recombinant human Interleukin-4 (rhIL-4 and infective SV40, the phenotype and function of DC-specific intracellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN+ DC were analyzed by flow cytometry (FCM and mixed lymphocyte reaction (MLR. Results showed that SV40 can down-regulate the expression of CD83 and CD86 on DC and impair DC-induced activation of T cell proliferation. These findings suggest that SV40 might also cause immune suppression by influencing differentiation and maturation of DC.

  17. B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers.

    Science.gov (United States)

    Fukazawa, Yoshinori; Lum, Richard; Okoye, Afam A; Park, Haesun; Matsuda, Kenta; Bae, Jin Young; Hagen, Shoko I; Shoemaker, Rebecca; Deleage, Claire; Lucero, Carissa; Morcock, David; Swanson, Tonya; Legasse, Alfred W; Axthelm, Michael K; Hesselgesser, Joseph; Geleziunas, Romas; Hirsch, Vanessa M; Edlefsen, Paul T; Piatak, Michael; Estes, Jacob D; Lifson, Jeffrey D; Picker, Louis J

    2015-02-01

    Chronic-phase HIV and simian immunodeficiency virus (SIV) replication is reduced by as much as 10,000-fold in elite controllers (ECs) compared with typical progressors (TPs), but sufficient viral replication persists in EC tissues to allow viral sequence evolution and induce excess immune activation. Here we show that productive SIV infection in rhesus monkey ECs, but not TPs, is markedly restricted to CD4(+) follicular helper T (TFH) cells, suggesting that these EC monkeys' highly effective SIV-specific CD8(+) T cells can effectively clear productive SIV infection from extrafollicular sites, but their relative exclusion from B cell follicles prevents their elimination of productively infected TFH cells. CD8(+) lymphocyte depletion in EC monkeys resulted in a dramatic re-distribution of productive SIV infection to non-TFH cells, with restriction of productive infection to TFH cells resuming upon CD8(+) T cell recovery. Thus, B cell follicles constitute 'sanctuaries' for persistent SIV replication in the presence of potent anti-viral CD8(+) T cell responses, potentially complicating efforts to cure HIV infection with therapeutic vaccination or T cell immunotherapy.

  18. Distribution of ultraviolet-induced lesions in Simian Virus 40 DNA

    International Nuclear Information System (INIS)

    Bourre, F.; Renault, G.; Sarasin, A.; Seawell, P.C.

    1985-01-01

    In order to analyze the molecular mechanisms of mutagenesis in mammalian cells, we devised an analytical assay using Simian Virus 40 as biological probe. To study the possible correlations between the distribution of the lesions on the treated DNA and the distribution of mutations, we have located and quantified the lesions induced by ultraviolet light (254 nm) on a SV40 DNA fragment. At a fluence of 2,000J/m 2 , our results show that the formation frequency of thymine-thymine dimers (TT) is three to four times higher than the formation frequency of the other types of dimers (TC, CT, CC). On the other hand, the formation frequency of a dimer is influenced by the adjacent sequence. In particular, a pyrimidine in the 5' position of a thymine-thymine dimer enhances its formation frequency. At the dose used the formation frequency of the pyrimidine (6-4) pyrimidone photoproducts is twenty times less than the formation frequency of pyrimidine dimers. This paper shows the distribution of the major lesions induced by UV-light on a defined fragment of SV40 genome after UV irradiation. This work is necessary to get an insight in the molecular mechanisms of UV-mutagenesis

  19. Divergent thinking and constructing episodic simulations.

    Science.gov (United States)

    Addis, Donna Rose; Pan, Ling; Musicaro, Regina; Schacter, Daniel L

    2016-01-01

    Divergent thinking likely plays an important role in simulating autobiographical events. We investigated whether divergent thinking is differentially associated with the ability to construct detailed imagined future and imagined past events as opposed to recalling past events. We also examined whether age differences in divergent thinking might underlie the reduced episodic detail generated by older adults. The richness of episodic detail comprising autobiographical events in young and older adults was assessed using the Autobiographical Interview. Divergent thinking abilities were measured using the Alternative Uses Task. Divergent thinking was significantly associated with the amount of episodic detail for imagined future events. Moreover, while age was significantly associated with imagined episodic detail, this effect was strongly related to age-related changes in episodic retrieval rather than divergent thinking.

  20. Characterization of a transcriptional promoter of human papillomavirus 18 and modulation of its expression by simian virus 40 and adenovirus early antigens

    International Nuclear Information System (INIS)

    Thierry, F.; Heard, J.M.; Dartmann, K.; Yaniv, M.

    1987-01-01

    RNA present in cells derived from cervical carcinoma that contained human papillomavirus 18 genomes was initiated in the 1.053-kilobase BamHI fragment that covered the complete noncoding region of this virus. When cloned upstream of the chloramphenicol acetyltransferase gene, this viral fragment directed the expression of the bacterial enzyme only in the sense orientation. Initiation sites were mapped around the ATG of open reading frame E6. This promoter was active in some human and simian cell lines, and its expression was modulated positively by simian virus 40 large T antigen and negatively by adenovirus type 5 E1a antigen

  1. Genetic divergence analysis in pumpkin

    International Nuclear Information System (INIS)

    Quamruzzaman, A.M.; Moniruzzaman, M.

    2013-01-01

    Genetic divergence among 18 punpkin genotypes was estimated using Mahalanohis's 1) statistic. Altogether lour clusters were formed where cluster I contained the highest number of genotypes (8) and cluster II contained the lowest (I). The highest intra-cluster distance was observed h.ir cluster I (0.83 I) and the lowest for clustcr IV (0.65 I). The highest inter-cluster distance was observed between cluster I and 11(24.346). Cluster II recorded the highest mean for fruit number/plant, TSS, fruit yield and niinitnuiii III cavity length and cavity diameter. Cluster III had the second highest mean for fruit diameter, fruit number/plant, individual unit weight, fruit yield and the fewest number of days to 1st Female flowering, earliness being a desirable trait. These crosses may produce new recombinants with desirable traits. (author)

  2. Divergence operator and related inequalities

    CERN Document Server

    Acosta, Gabriel

    2017-01-01

    This Brief is mainly devoted to two classical and related results: the existence of a right inverse of the divergence operator and the so-called Korn Inequalities. It is well known that both results are fundamental tools in the analysis of some classic differential equations, particularly in those arising in fluid dynamics and elasticity. Several connections between these two topics and improved Poincaré inequalities are extensively treated. From simple key ideas the book is growing smoothly in complexity. Beginning with the study of these problems on star-shaped domains the arguments are extended first to John domains and then to Hölder α domains where the need of weighted spaces arises naturally. In this fashion, the authors succeed in presenting in an unified and concise way several classic and recent developments in the field. These features certainly makes this Brief useful for students, post-graduate students, and researchers as well.

  3. Ramanujan summation of divergent series

    CERN Document Server

    Candelpergher, Bernard

    2017-01-01

    The aim of this monograph is to give a detailed exposition of the summation method that Ramanujan uses in Chapter VI of his second Notebook. This method, presented by Ramanujan as an application of the Euler-MacLaurin formula, is here extended using a difference equation in a space of analytic functions. This provides simple proofs of theorems on the summation of some divergent series. Several examples and applications are given. For numerical evaluation, a formula in terms of convergent series is provided by the use of Newton interpolation. The relation with other summation processes such as those of Borel and Euler is also studied. Finally, in the last chapter, a purely algebraic theory is developed that unifies all these summation processes. This monograph is aimed at graduate students and researchers who have a basic knowledge of analytic function theory.

  4. Beam divergence scaling in neutral beam injectors

    International Nuclear Information System (INIS)

    Holmes, A.J.T.

    1976-01-01

    One of the main considerations in the design of neutral beam injectors is to monimize the divergence of the primary ion beam and hence maximize the beam transport and minimize the input of thermal gas. Experimental measurements of the divergence of a cylindrical ion beam are presented and these measurements are used to analyze the major components of ion beam divergence, namely: space charge expansion, gas-ion scattering, emittance and optical aberrations. The implication of these divergence components in the design of a neutral beam injector system is discussed and a method of maximizing the beam current is described for a given area of source plasma

  5. Guises and disguises of quadratic divergences

    Energy Technology Data Exchange (ETDEWEB)

    Cherchiglia, A.L., E-mail: adriano@fisica.ufmg.br [Departamento de Física, ICEx, Universidade Federal de Minas Gerais, P.O. BOX 702, 30.161-970, Belo Horizonte, MG (Brazil); Vieira, A.R., E-mail: arvieira@fisica.ufmg.br [Departamento de Física, ICEx, Universidade Federal de Minas Gerais, P.O. BOX 702, 30.161-970, Belo Horizonte, MG (Brazil); Hiller, Brigitte, E-mail: brigitte@teor.fis.uc.pt [Departamento de Física, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, 3004-516 Coimbra (Portugal); Baêta Scarpelli, A.P., E-mail: scarpelli.apbs@dpf.gov.br [Setor Técnico-Científico, Departamento de Polícia Federal, Rua Hugo D’Antola, 95 - Lapa, São Paulo (Brazil); Sampaio, Marcos, E-mail: marcos.sampaio@durham.ac.uk [Departamento de Física, ICEx, Universidade Federal de Minas Gerais, P.O. BOX 702, 30.161-970, Belo Horizonte, MG (Brazil); Centre for Particle Theory, Department of Mathematical Sciences, Durham University, South Road Durham DH1 3LE (United Kingdom)

    2014-12-15

    In this contribution, we present a new perspective on the control of quadratic divergences in quantum field theory, in general, and in the Higgs naturalness problem, in particular. Our discussion is essentially based on an approach where UV divergences are parameterized, after being reduced to basic divergent integrals (BDI) in one internal momentum, as functions of a cutoff and a renormalization group scale λ. We illustrate our proposal with well-known examples, such as the gluon vacuum self energy of QCD and the Higgs decay in two photons within this approach. We also discuss frameworks in effective low-energy QCD models, where quadratic divergences are indeed fundamental.

  6. Divergence Palsy due to Divalproex and Oxcarbazepine.

    Science.gov (United States)

    Bouffard, Marc Albert; Caplan, Louis R; Torun, Nurhan

    This case series is the first to describe divergence palsy as an adverse effect of antiepileptic drug use. Diplopia is a common adverse effect of antiepileptic drugs, but no explanatory motility deficit has ever been reported. We present 2 patients, 1 on oxcarbazepine and 1 on divalproex, each with a normal examination result between spells and divergency palsy when symptomatic. Discontinuation of the antiepileptic medication led to resolution of the episodes in both cases. Rechallenge with the offending agent after washout in one patient resulted in recurrence of diplopia and divergence palsy, both resolving after subsequent withdrawal of the antiepileptic. Antiepileptic drugs may cause divergence palsy.

  7. Use of a simian virus 40-based shuttle vector to analyze enhanced mutagenesis in mitomycin C-treated monkey cells

    International Nuclear Information System (INIS)

    Roilides, E.; Munson, P.J.; Levine, A.S.; Dixon, K.

    1988-01-01

    When monkey cells were treated with mitomycin C 24 h before transfection with UV-irradiated pZ189 (a simian virus 40-based shuttle vector), there was a twofold increase in the frequency of mutations in the supF gene of the vector. These results suggest the existence of an enhancible mutagenesis pathway in mammalian cells. However, DNA sequence analysis of the SupF- mutants suggested no dramatic changes in the mechanisms of mutagenesis due to mitomycin C treatment of the cells

  8. A brief history of the discovery of natural simian immunodeficiency virus (SIV) infections in captive sooty mangabey monkeys.

    Science.gov (United States)

    Gormus, Bobby J; Martin, Louis N; Baskin, Gary B

    2004-01-01

    Experimental leprosy studies using Mycobacterium leprae inoculum isolated from a sooty mangabey monkey (SMM) resulted in the accidental discovery that SMM's asymptomatically carry simian immunodeficiency virus (SIV) that is pathogenic in macaques. We showed that the SMM virus, SIVDelta, was antigenically related to SIVmac, which had been identified in macaques, and to the human immunodeficiency virus (HIV). Similar asymptomatic natural SIV infections had been reported in African green monkeys (AGM). Our results together with observations of others led us to propose that both SIVmac and SIVDelta originated in SMM and that SIV emerged in humans as a result of early African nonhuman primate SIV trans-species infections in humans.

  9. Evaluation of recombinant influenza virus-simian immunodeficiency virus vaccines in macaques.

    Science.gov (United States)

    Sexton, Amy; De Rose, Robert; Reece, Jeanette C; Alcantara, Sheilajen; Loh, Liyen; Moffat, Jessica M; Laurie, Karen; Hurt, Aeron; Doherty, Peter C; Turner, Stephen J; Kent, Stephen J; Stambas, John

    2009-08-01

    There is an urgent need for human immunodeficiency virus (HIV) vaccines that induce robust mucosal immunity. Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques. Influenza virus was readily detected from respiratory tract secretions, although the infections were asymptomatic. Animals seroconverted to influenza virus and generated CD8 and CD4 T-cell responses to influenza virus proteins. SIV-specific CD8 T-cell responses bearing the mucosal homing marker beta7 integrin were induced by vaccination of naïve animals. Further, SIV-specific CD8 T-cell responses could be boosted by recombinant influenza virus-SIV vaccination of animals with already-established SIV infection. Sequential vaccination with influenza virus-SIV recombinants of different subtypes (H1N1 followed by H3N2 or vice versa) produced only a limited boost in immunity, probably reflecting T-cell immunity to conserved internal proteins of influenza A virus. SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T-cell response, but immune escape rapidly ensued and there was no impact on chronic SIV viremia. Although our results suggest that influenza virus-HIV vaccines hold promise for the induction of mucosal immunity to HIV, broader antigen cover will be needed to limit cytotoxic T-lymphocyte escape.

  10. Primary simian immunodeficiency virus SIVmnd-2 infection in mandrills (Mandrillus sphinx).

    Science.gov (United States)

    Onanga, Richard; Souquière, Sandrine; Makuwa, Maria; Mouinga-Ondeme, Augustin; Simon, François; Apetrei, Cristian; Roques, Pierre

    2006-04-01

    Mandrills are the only nonhuman primate (NHP) naturally infected by two types of simian immunodeficiency virus (SIV): SIVmnd-1 and SIVmnd-2. We have already reported that the high SIVmnd-1 replication during primary infection contrasts with only transient changes in CD4+ and CD8+ cell counts. Since early virus-host interactions predict viral control and disease progression in human immunodeficiency virus-infected patients, we investigated the dynamics of SIVmnd-2 primary infection in mandrills to examine the impact on immune effectors in blood and lymph nodes (LNs). To avoid in vitro strain selection, all mandrills in this study received plasma from SIVmnd-2-infected mandrills. SIVmnd-2 plasma viremia peaked at 10(7) to 10(8) RNA copies/ml between days 7 and 10. This peak was followed in all four monkeys by a decline in virus replication, with a set point level of 10(5) to 10(6) RNA copies/ml at day 42 postinfection (p.i.). Viral DNA load in PBMC and LNs also peaked between days 7 and 10 (10(5) to 10(6) DNA copies/10(6) cells) and stabilized at 10(3) to 10(4) DNA copies/10(6) cells during the chronic phase. Anti-SIVmnd-2 antibodies were detected starting from days 28 to 32. A transitory decline of CD3+ CD4+ cells in the LNs occurred in animals with high peak VLs. CD4+ and CD8+ T-cell activation in blood and LNs was noted between days 5 and 17 p.i., surrounding the peak of viral replication. This was most significant in the LNs. Activation markers then returned to preinfection values despite continuous and active viral replication during the chronic infection. The dynamics of SIVmnd-2 infection in mandrills showed a pattern similar to that of SIVmnd-1 infection. This might be a general feature of nonpathogenic SIV natural African NHP models.

  11. Adaptive evolution of simian immunodeficiency viruses isolated from two conventional progressor macaques with neuroaids

    Energy Technology Data Exchange (ETDEWEB)

    Foley, Brian T [Los Alamos National Laboratory; Korber, Bette T [Los Alamos National Laboratory

    2008-01-01

    Simian immunodeficiency virus infection of macaques may result in neuroAIDS, a feature more commonly observed in macaques with rapid progressive disease than in those with conventional disease. This is the first report of two conventional progressors (H631 and H636) with encephalitis in rhesus macaques inoculated with a derivative of SIVsmES43-3. Phylogenetic analyses of viruses isolated from the cerebral spinal fluid (CSF) and plasma from both animals demonstrated tissue compartmentalization. Additionally, virus from the central nervous system (CNS) was able to infect primary macaque monocyte-derived macrophages more efficiently than virus from plasma. Conversely, virus isolated from plasma was able to replicate better in peripheral blood mononuclear cells than virus from CNS. We speculate that these viruses were under different selective pressures in their separate compartments. Furthermore, these viruses appear to have undergone adaptive evolution to preferentially replicate in their respective cell targets. Analysis of the number of potential N-linked glycosylation sites (PNGS) in gp160 showed that there was a statistically significant loss of PNGS in viruses isolated from CNS in both macaques compared to SIVsmE543-3. Moreover, virus isolated from the brain in H631, had statistically significant loss of PNGS compared to virus isolated from CSF and plasma of the same animal. It is possible that the brain isolate may have adapted to decrease the number of PNGS given that humoral immune selection pressure is less likely to be encountered in the brain. These viruses provide a relevant model to study the adaptations required for SIV to induce encephalitis.

  12. Wide distribution and ancient evolutionary history of simian foamy viruses in New World primates.

    Science.gov (United States)

    Ghersi, Bruno M; Jia, Hongwei; Aiewsakun, Pakorn; Katzourakis, Aris; Mendoza, Patricia; Bausch, Daniel G; Kasper, Matthew R; Montgomery, Joel M; Switzer, William M

    2015-10-29

    Although simian foamy viruses (SFV) are the only exogenous retroviruses to infect New World monkeys (NWMs), little is known about their evolutionary history and epidemiology. Previous reports show distinct SFVs among NWMs but were limited to small numbers of captive or wild monkeys from five (Cebus, Saimiri, Ateles, Alouatta, and Callithrix) of the 15 NWM genera. Other studies also used only PCR testing or serological assays with limited validation and may have missed infection in some species. We developed and validated new serological and PCR assays to determine the prevalence of SFV in blood specimens from a large number of captive NWMs in the US (n = 274) and in captive and wild-caught NWMs (n = 236) in Peruvian zoos, rescue centers, and illegal trade markets. Phylogenetic and co-speciation reconciliation analyses of new SFV polymerase (pol) and host mitochondrial cytochrome B sequences, were performed to infer SFV and host co-evolutionary histories. 124/274 (45.2 %) of NWMs captive in the US and 59/157 (37.5 %) of captive and wild-caught NWMs in Peru were SFV WB-positive representing 11 different genera (Alouatta, Aotus, Ateles, Cacajao, Callithrix, Cebus, Lagothrix, Leontopithecus, Pithecia, Saguinus and Saimiri). Seroprevalences were lower at rescue centers (10/53, 18.9 %) compared to zoos (46/97, 47.4 %) and illegal trade markets (3/7, 8/19, 42.9 %) in Peru. Analyses showed that the trees of NWM hosts and SFVs have remarkably similar topologies at the level of species and sub-populations suggestive of co-speciation. Phylogenetic reconciliation confirmed 12 co-speciation events (p history of SFV in NWMs at the species level. Additional studies are necessary to further explore the epidemiology and natural history of SFV infection of NWMs and to determine the zoonotic potential for persons exposed to infected monkeys in captivity and in the wild.

  13. Frequent and recent human acquisition of simian foamy viruses through apes' bites in central Africa.

    Directory of Open Access Journals (Sweden)

    Edouard Betsem

    2011-10-01

    Full Text Available Human infection by simian foamy viruses (SFV can be acquired by persons occupationally exposed to non-human primates (NHP or in natural settings. This study aimed at getting better knowledge on SFV transmission dynamics, risk factors for such a zoonotic infection and, searching for intra-familial dissemination and the level of peripheral blood (proviral loads in infected individuals. We studied 1,321 people from the general adult population (mean age 49 yrs, 640 women and 681 men and 198 individuals, mostly men, all of whom had encountered a NHP with a resulting bite or scratch. All of these, either Pygmies (436 or Bantus (1085 live in villages in South Cameroon. A specific SFV Western blot was used and two nested PCRs (polymerase, and LTR were done on all the positive/borderline samples by serology. In the general population, 2/1,321 (0.2% persons were found to be infected. In the second group, 37/198 (18.6% persons were SFV positive. They were mostly infected by apes (37/39 FV (mainly gorilla. Infection by monkey FV was less frequent (2/39. The viral origin of the amplified sequences matched with the history reported by the hunters, most of which (83% are aged 20 to 40 years and acquired the infection during the last twenty years. The (proviral load in 33 individuals infected by a gorilla FV was quite low (<1 to 145 copies per 10(5 cells in the peripheral blood leucocytes. Of the 30 wives and 12 children from families of FV infected persons, only one woman was seropositive in WB without subsequent viral DNA amplification. We demonstrate a high level of recent transmission of SFVs to humans in natural settings specifically following severe gorilla bites during hunting activities. The virus was found to persist over several years, with low SFV loads in infected persons. Secondary transmission remains an open question.

  14. Role of the hydrophilic channels of simian virus 40 T-antigen helicase in DNA replication.

    Science.gov (United States)

    Wang, Weiping; Manna, David; Simmons, Daniel T

    2007-05-01

    The simian virus 40 (SV40) hexameric helicase consists of a central channel and six hydrophilic channels located between adjacent large tier domains within each hexamer. To study the function of the hydrophilic channels in SV40 DNA replication, a series of single-point substitutions were introduced at sites not directly involved in protein-protein contacts. The mutants were characterized biochemically in various ways. All mutants oligomerized normally in the absence of DNA. Interestingly, 8 of the 10 mutants failed to unwind an origin-containing DNA fragment and nine of them were totally unable to support SV40 DNA replication in vitro. The mutants fell into four classes based on their biochemical properties. Class A mutants bound DNA normally and had normal ATPase and helicase activities but failed to unwind origin DNA and support SV40 DNA replication. Class B mutants were compromised in single-stranded DNA and origin DNA binding at low protein concentrations. They were defective in helicase activity and unwinding of the origin and in supporting DNA replication. Class C and D mutants possessed higher-than-normal single-stranded DNA binding activity at low protein concentrations. The class C mutants failed to separate origin DNA and support DNA replication. The class D mutants unwound origin DNA normally but were compromised in their ability to support DNA replication. Taken together, these results suggest that the hydrophilic channels have an active role in the unwinding of SV40 DNA from the origin and the placement of the resulting single strands within the helicase.

  15. Increased cellular immune responses and CD4+ T-cell proliferation correlate with reduced plasma viral load in SIV challenged recombinant simian varicella virus - simian immunodeficiency virus (rSVV-SIV vaccinated rhesus macaques

    Directory of Open Access Journals (Sweden)

    Pahar Bapi

    2012-08-01

    Full Text Available Abstract Background An effective AIDS vaccine remains one of the highest priorities in HIV-research. Our recent study showed that vaccination of rhesus macaques with recombinant simian varicella virus (rSVV vector – simian immunodeficiency virus (SIV envelope and gag genes, induced neutralizing antibodies and cellular immune responses to SIV and also significantly reduced plasma viral loads following intravenous pathogenic challenge with SIVMAC251/CX1. Findings The purpose of this study was to define cellular immunological correlates of protection in rSVV-SIV vaccinated and SIV challenged animals. Immunofluorescent staining and multifunctional assessment of SIV-specific T-cell responses were evaluated in both Experimental and Control vaccinated animal groups. Significant increases in the proliferating CD4+ T-cell population and polyfunctional T-cell responses were observed in all Experimental-vaccinated animals compared with the Control-vaccinated animals. Conclusions Increased CD4+ T-cell proliferation was significantly and inversely correlated with plasma viral load. Increased SIV-specific polyfunctional cytokine responses and increased proliferation of CD4+ T-cell may be crucial to control plasma viral loads in vaccinated and SIVMAC251/CX1 challenged macaques.

  16. k-Means Clustering with Hölder Divergences

    KAUST Repository

    Nielsen, Frank; Sun, Ke; Marchand-Maillet, Sté phane

    2017-01-01

    We introduced two novel classes of Hölder divergences and Hölder pseudo-divergences that are both invariant to rescaling, and that both encapsulate the Cauchy-Schwarz divergence and the skew Bhattacharyya divergences. We review the elementary concepts of those parametric divergences, and perform a clustering analysis on two synthetic datasets. It is shown experimentally that the symmetrized Hölder divergences consistently outperform significantly the Cauchy-Schwarz divergence in clustering tasks.

  17. k-Means Clustering with Hölder Divergences

    KAUST Repository

    Nielsen, Frank

    2017-10-24

    We introduced two novel classes of Hölder divergences and Hölder pseudo-divergences that are both invariant to rescaling, and that both encapsulate the Cauchy-Schwarz divergence and the skew Bhattacharyya divergences. We review the elementary concepts of those parametric divergences, and perform a clustering analysis on two synthetic datasets. It is shown experimentally that the symmetrized Hölder divergences consistently outperform significantly the Cauchy-Schwarz divergence in clustering tasks.

  18. Lexicographic presentation of grammatical divergence in Sesotho ...

    African Journals Online (AJOL)

    Relying on existing insights from the field of theoretical lexicography this article gives an innovative application to the relation of divergence by introducing the notion of grammatical divergence. In bilingual dictionaries with English and Sesotho sa Leboa as language pair lexicographers are confronted with a real challenge ...

  19. Divergent Thinking and Age-Related Changes

    Science.gov (United States)

    Palmiero, Massimiliano; Di Giacomo, Dina; Passafiume, Domenico

    2014-01-01

    Aging can affect cognition in different ways. The extent to which aging affects divergent thinking is unclear. In this study, younger and older adults were compared at the performance on the Torrance Test of Creative Thinking in visual and verbal form. Results showed that older adults can think divergently as younger participants, although they…

  20. Initial stage of transformation of permissive cells by simian virus 40: development of resistance to productive infection.

    Science.gov (United States)

    Hahn, E C; Sauer, G

    1971-07-01

    A quantitative assay has been used to determine the conditions leading to acquisition of resistance of permissive cells to lytic infection. The number of cell colonies surviving infection depends on the occurrence of several cell divisions after infection. High yields of resistant colonies were obtained when infected, confluent cultures were released from contact inhibition 10 to 14 hr after infection. Infection of actively growing cells produced similar results, but halting further division by seeding these growing cells on confluent monolayers prevented the development of colonies. Colony formation was a direct function of multiplicities lower than 5. An inverse killing response was observed with higher multiplicities, yet colonies were produced at a multiplicity of infection as high as 50. Brief exposure of input simian virus 40 to ultraviolet light stimulated colony formation. Irradiation of the virus for longer periods of time led to reduction of colony formation at a rate slower than the rate of inactivation of viral infectivity. It was concluded that resistance is induced by simian virus 40 and that this alteration represents one of the earliest detectable characteristics of the transformation of permissive cells.

  1. High throughput generation and characterization of replication-competent clade C transmitter-founder simian human immunodeficiency viruses.

    Directory of Open Access Journals (Sweden)

    Debashis Dutta

    Full Text Available Traditional restriction endonuclease-based cloning has been routinely used to generate replication-competent simian-human immunodeficiency viruses (SHIV and simian tropic HIV (stHIV. This approach requires the existence of suitable restriction sites or the introduction of nucleotide changes to create them. Here, using an In-Fusion cloning technique that involves homologous recombination, we generated SHIVs and stHIVs based on epidemiologically linked clade C transmitted/founder HIV molecular clones from Zambia. Replacing vif from these HIV molecular clones with vif of SIVmac239 resulted in chimeric genomes used to generate infectious stHIV viruses. Likewise, exchanging HIV env genes and introducing N375 mutations to enhance macaque CD4 binding site and cloned into a SHIVAD8-EO backbone. The generated SHIVs and stHIV were infectious in TZMbl and ZB5 cells, as well as macaque PBMCs. Therefore, this method can replace traditional methods and be a valuable tool for the rapid generation and testing of molecular clones of stHIV and SHIV based on primary clinical isolates will be valuable to generate rapid novel challenge viruses for HIV vaccine/cure studies.

  2. Optimization of the doxycycline-dependent simian immunodeficiency virus through in vitro evolution

    Directory of Open Access Journals (Sweden)

    Piatak Mike

    2008-06-01

    Full Text Available Abstract Background Vaccination of macaques with live attenuated simian immunodeficiency virus (SIV provides significant protection against the wild-type virus. The use of a live attenuated human immunodeficiency virus (HIV as AIDS vaccine in humans is however considered unsafe because of the risk that the attenuated virus may accumulate genetic changes during persistence and evolve to a pathogenic variant. We earlier presented a conditionally live HIV-1 variant that replicates exclusively in the presence of doxycycline (dox. Replication of this vaccine strain can be limited to the time that is needed to provide full protection through transient dox administration. Since the effectiveness and safety of such a conditionally live virus vaccine should be tested in macaques, we constructed a similar dox-dependent SIV variant. The Tat-TAR transcription control mechanism in this virus was inactivated through mutation and functionally replaced by the dox-inducible Tet-On regulatory system. This SIV-rtTA variant replicated in a dox-dependent manner in T cell lines, but not as efficiently as the parental SIVmac239 strain. Since macaque studies will likely require an efficiently replicating variant, we set out to optimize SIV-rtTA through in vitro viral evolution. Results Upon long-term culturing of SIV-rtTA, additional nucleotide substitutions were observed in TAR that affect the structure of this RNA element but that do not restore Tat binding. We demonstrate that the bulge and loop mutations that we had introduced in the TAR element of SIV-rtTA to inactivate the Tat-TAR mechanism, shifted the equilibrium between two alternative conformations of TAR. The additional TAR mutations observed in the evolved variants partially or completely restored this equilibrium, which suggests that the balance between the two TAR conformations is important for efficient viral replication. Moreover, SIV-rtTA acquired mutations in the U3 promoter region. We demonstrate

  3. Simian virus 40 infection in humans and association with human diseases: results and hypotheses

    International Nuclear Information System (INIS)

    Barbanti-Brodano, Giuseppe; Sabbioni, Silvia; Martini, Fernanda; Negrini, Massimo; Corallini, Alfredo; Tognon, Mauro

    2004-01-01

    Simian virus 40 (SV40) is a monkey virus that was introduced in the human population by contaminated poliovaccines, produced in SV40-infected monkey cells, between 1955 and 1963. Epidemiological evidence now suggests that SV40 may be contagiously transmitted in humans by horizontal infection, independent of the earlier administration of SV40-contaminated poliovaccines. This evidence includes detection of SV40 DNA sequences in human tissues and of SV40 antibodies in human sera, as well as rescue of infectious SV40 from a human tumor. Detection of SV40 DNA sequences in blood and sperm and of SV40 virions in sewage points to the hematic, sexual, and orofecal routes as means of virus transmission in humans. The site of latent infection in humans is not known, but the presence of SV40 in urine suggests the kidney as a possible site of latency, as it occurs in the natural monkey host. SV40 in humans is associated with inflammatory kidney diseases and with specific tumor types: mesothelioma, lymphoma, brain, and bone. These human tumors correspond to the neoplasms that are induced by SV40 experimental inoculation in rodents and by generation of transgenic mice with the SV40 early region gene directed by its own early promoter-enhancer. The mechanisms of SV40 tumorigenesis in humans are related to the properties of the two viral oncoproteins, the large T antigen (Tag) and the small t antigen (tag). Tag acts mainly by blocking the functions of p53 and RB tumor suppressor proteins, as well as by inducing chromosomal aberrations in the host cell. These chromosome alterations may hit genes important in oncogenesis and generate genetic instability in tumor cells. The clastogenic activity of Tag, which fixes the chromosome damage in the infected cells, may explain the low viral load in SV40-positive human tumors and the observation that Tag is expressed only in a fraction of tumor cells. 'Hit and run' seems the most plausible mechanism to support this situation. The small tag

  4. Suppression of a Natural Killer Cell Response by Simian Immunodeficiency Virus Peptides.

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    Jamie L Schafer

    2015-09-01

    Full Text Available Natural killer (NK cell responses in primates are regulated in part through interactions between two highly polymorphic molecules, the killer-cell immunoglobulin-like receptors (KIRs on NK cells and their major histocompatibility complex (MHC class I ligands on target cells. We previously reported that the binding of a common MHC class I molecule in the rhesus macaque, Mamu-A1*002, to the inhibitory receptor Mamu-KIR3DL05 is stabilized by certain simian immunodeficiency virus (SIV peptides, but not by others. Here we investigated the functional implications of these interactions by testing SIV peptides bound by Mamu-A1*002 for the ability to modulate Mamu-KIR3DL05+ NK cell responses. Twenty-eight of 75 SIV peptides bound by Mamu-A1*002 suppressed the cytolytic activity of primary Mamu-KIR3DL05+ NK cells, including three immunodominant CD8+ T cell epitopes previously shown to stabilize Mamu-A1*002 tetramer binding to Mamu-KIR3DL05. Substitutions at C-terminal positions changed inhibitory peptides into disinhibitory peptides, and vice versa, without altering binding to Mamu-A1*002. The functional effects of these peptide variants on NK cell responses also corresponded to their effects on Mamu-A1*002 tetramer binding to Mamu-KIR3DL05. In assays with mixtures of inhibitory and disinhibitory peptides, low concentrations of inhibitory peptides dominated to suppress NK cell responses. Consistent with the inhibition of Mamu-KIR3DL05+ NK cells by viral epitopes presented by Mamu-A1*002, SIV replication was significantly higher in Mamu-A1*002+ CD4+ lymphocytes co-cultured with Mamu-KIR3DL05+ NK cells than with Mamu-KIR3DL05- NK cells. These results demonstrate that viral peptides can differentially affect NK cell responses by modulating MHC class I interactions with inhibitory KIRs, and provide a mechanism by which immunodeficiency viruses may evade NK cell responses.

  5. Genetic divergence of common bean cultivars.

    Science.gov (United States)

    Veloso, J S; Silva, W; Pinheiro, L R; Dos Santos, J B; Fonseca, N S; Euzebio, M P

    2015-09-22

    The aim of this study was to evaluate genetic divergence in the 'Carioca' (beige with brown stripes) common bean cultivar used by different institutions and in 16 other common bean cultivars used in the Rede Cooperativa de Pesquisa de Feijão (Cooperative Network of Common Bean Research), by using simple sequence repeats associated with agronomic traits that are highly distributed in the common bean genome. We evaluated 22 polymorphic loci using bulks containing DNA from 30 plants. There was genetic divergence among the Carioca cultivar provided by the institutions. Nevertheless, there was lower divergence among them than among the other cultivars. The cultivar used by Instituto Agronômico do Paraná was the most divergent in relation to the Carioca samples. The least divergence was observed among the samples used by Universidade Federal de Lavras and by Embrapa Arroz e Feijão. Of all the cultivars, 'CNFP 10104' and 'BRSMG Realce' showed the greatest dissimilarity. The cultivars were separated in two groups of greatest similarity using the Structure software. Genetic variation among cultivars was greater than the variation within or between the groups formed. This fact, together with the high estimate of heterozygosity observed and the genetic divergence of the samples of the Carioca cultivar in relation to the original provided by Instituto Agronômico de Campinas, indicates a mixture of cultivars. The high divergence among cultivars provides potential for the utilization of this genetic variability in plant breeding.

  6. The estimation of genetic divergence

    Science.gov (United States)

    Holmquist, R.; Conroy, T.

    1981-01-01

    Consideration is given to the criticism of Nei and Tateno (1978) of the REH (random evolutionary hits) theory of genetic divergence in nucleic acids and proteins, and to their proposed alternative estimator of total fixed mutations designated X2. It is argued that the assumption of nonuniform amino acid or nucleotide substitution will necessarily increase REH estimates relative to those made for a model where each locus has an equal likelihood of fixing mutations, thus the resulting value will not be an overestimation. The relative values of X2 and measures calculated on the basis of the PAM and REH theories for the number of nucleotide substitutions necessary to explain a given number of observed amino acid differences between two homologous proteins are compared, and the smaller values of X2 are attributed to (1) a mathematical model based on the incorrect assumption that an entire structural gene is free to fix mutations and (2) the assumptions of different numbers of variable codons for the X2 and REH calculations. Results of a repeat of the computer simulations of Nei and Tateno are presented which, in contrast to the original results, confirm the REH theory. It is pointed out that while a negative correlation is observed between estimations of the fixation intensity per varion and the number of varions for a given pair of sequences, the correlation between the two fixation intensities and varion numbers of two different pairs of sequences need not be negative. Finally, REH theory is used to resolve a paradox concerning the high rate of covarion turnover and the nature of general function sites as permanent covarions.

  7. Verbal and visual divergent thinking in aging.

    Science.gov (United States)

    Palmiero, Massimiliano; Nori, Raffaella; Piccardi, Laura

    2017-04-01

    According to the peak and decline model divergent thinking declines at a specific age (in or after middle age). However, if divergent thinking declines steadily in aging still has to be clarified. In order to explore the age-related changes in verbal and visual divergent thinking, in the present study a sample of 159 participants was divided in five age groups: young adults (18-35 years), middle-aged adults (36-55), young old (56-74), old (75-85) and the oldest-old (86-98). Two divergent thinking tasks were administered: the alternative uses for cardboard boxes, aimed at assessing verbal ideational fluency, flexibility and originality; the completion drawing task, aimed at assessing visual ideational fluency, flexibility and originality. Results showed that after peaking in the young adult group (20-35 years) all components of verbal and visual divergent thinking stabilized in the middle-aged adult group (36-55 years) and then started declining in the young old group (56-75). Interestingly, all components were found to be preserved after declining. Yet, verbal and visual divergent thinking were found at the same extent across age groups, with the exception of visual ideational fluency, that was higher in the young old group, the old group and the oldest-old group than verbal ideational fluency. These results support the idea that divergent thinking does not decline steadily in the elderly. Given that older people can preserve to some extent verbal and visual divergent thinking, these findings have important implications for active aging, that is, divergent thinking might be fostered in aging in order to prevent the cognitive decline.

  8. Two separable functional domains of simian virus 40 large T antigen: carboxyl-terminal region of simian virus 40 large T antigen is required for efficient capsid protein synthesis.

    Science.gov (United States)

    Tornow, J; Polvino-Bodnar, M; Santangelo, G; Cole, C N

    1985-01-01

    The carboxyl-terminal portion of simian virus 40 large T antigen is essential for productive infection of CV-1 and CV-1p green monkey kidney cells. Mutant dlA2459, lacking 14 base pairs at 0.193 map units, was positive for viral DNA replication, but unable to form plaques in CV-1p cells (J. Tornow and C.N. Cole, J. Virol. 47:487-494, 1983). In this report, the defect of dlA2459 is further defined. Simian virus 40 late mRNAs were transcribed, polyadenylated, spliced, and transported in dlA2459-infected cells, but the level of capsid proteins produced in infected CV-1 green monkey kidney cells was extremely low. dlA2459 large T antigen lacks those residues known to be required for adenovirus helper function, and the block to productive infection by dlA2459 occurs at the same stage of infection as the block to productive adenovirus infection of CV-1 cells. These results suggest that the adenovirus helper function is required for productive infection by simian virus 40. Mutant dlA2459 was able to grow on the Vero and BSC-1 lines of African green monkey kidney cells. Additional mutants affecting the carboxyl-terminal portion of large T were prepared. Mutant inv2408 contains an inversion of the DNA between the BamHI and BclI sites (0.144 to 0.189 map units). This inversion causes transposition of the carboxyl-terminal 26 amino acids of large T antigen and the carboxyl-terminal 18 amino acids of VP1. This mutant was viable, even though the essential information absent from dlA2459 large T antigen has been transferred to the carboxyl terminus of VP1 of inv2408. The VP1 polypeptide carrying this carboxyl-terminal portion of large T could overcome the defect of dlA2459. This indicates that the carboxyl terminus of large T antigen is a separate and separable functional domain. Images PMID:2982029

  9. Two New Measures of Fuzzy Divergence and Their Properties

    Directory of Open Access Journals (Sweden)

    Om Parkash

    2006-06-01

    Full Text Available Several measures of directed divergence and their corresponding measures of fuzzy divergence are available in the exiting literature. Two new measures of fuzzy divergence have been developed and their desirable properties have been discussed.

  10. MAIT cells are reduced in frequency and functionally impaired in human T lymphotropic virus type 1 infection: Potential clinical implications.

    Science.gov (United States)

    Paquin-Proulx, Dominic; Greenspun, Benjamin C; Costa, Emanuela A S; Segurado, Aluisio C; Kallas, Esper G; Nixon, Douglas F; Leal, Fabio E

    2017-01-01

    HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develop HAM/TSP. The cellular immune response has been implicated in the development of inflammatory alterations in these patients; however the pathogenic mechanisms for disease progression remain unclear. Furthermore, HTLV-1-infected individuals have an increase incidence of Mycobacterium tuberculosis (Mtb) infection, suggesting that immunological defect are associated with HTLV-1 infection. Evidence suggests an important role for Mucosal-associated invariant T (MAIT) cells in the early control of Mtb infection. Chronic viral infections like HIV and HCV have been associated with decreased frequency and functionality of MAIT cells. We hypothesized that HTLV-1 infection is associated with similar perturbations in MAIT cells. We investigated MAIT cell frequency, phenotype, and function by flow cytometry in a cohort of 10 asymptomatic and 10 HAM/TSP HTLV-1 infected patients. We found that MAIT cells from HTLV-1-infected subjects were reduced and showed high co-expression of the activation markers CD38 and HLA-DR but normal levels of CCR6 and CD127. MAIT cells had a lower expression of the transcription factor PLZF in HAM/TSP patients. Unlike Tax-specific CD8+T cells, which are hyperfunctional, MAIT cells from HTLV-1-infected subjects had a poor IFNγ response following antigen stimulation. MAIT cell perturbations in HTLV-1 infection were not associated with HTLV-1 proviral load and MAIT cells were not infected by HTLV-1 in vivo. Rather, MAIT cells loss was associated with immune activation. Overall, our results do not support a role for MAIT cells in HAM/TSP pathogenesis but reduced numbers of MAIT cells, together with their poor functionality, could contribute to the increased susceptibility of HTLV-1-infected individuals to other infectious agents.

  11. MAIT cells are reduced in frequency and functionally impaired in human T lymphotropic virus type 1 infection: Potential clinical implications.

    Directory of Open Access Journals (Sweden)

    Dominic Paquin-Proulx

    Full Text Available HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. It is unclear why a minority of infected subjects develop HAM/TSP. The cellular immune response has been implicated in the development of inflammatory alterations in these patients; however the pathogenic mechanisms for disease progression remain unclear. Furthermore, HTLV-1-infected individuals have an increase incidence of Mycobacterium tuberculosis (Mtb infection, suggesting that immunological defect are associated with HTLV-1 infection. Evidence suggests an important role for Mucosal-associated invariant T (MAIT cells in the early control of Mtb infection. Chronic viral infections like HIV and HCV have been associated with decreased frequency and functionality of MAIT cells. We hypothesized that HTLV-1 infection is associated with similar perturbations in MAIT cells. We investigated MAIT cell frequency, phenotype, and function by flow cytometry in a cohort of 10 asymptomatic and 10 HAM/TSP HTLV-1 infected patients. We found that MAIT cells from HTLV-1-infected subjects were reduced and showed high co-expression of the activation markers CD38 and HLA-DR but normal levels of CCR6 and CD127. MAIT cells had a lower expression of the transcription factor PLZF in HAM/TSP patients. Unlike Tax-specific CD8+T cells, which are hyperfunctional, MAIT cells from HTLV-1-infected subjects had a poor IFNγ response following antigen stimulation. MAIT cell perturbations in HTLV-1 infection were not associated with HTLV-1 proviral load and MAIT cells were not infected by HTLV-1 in vivo. Rather, MAIT cells loss was associated with immune activation. Overall, our results do not support a role for MAIT cells in HAM/TSP pathogenesis but reduced numbers of MAIT cells, together with their poor functionality, could contribute to the increased susceptibility of HTLV-1-infected individuals to other infectious agents.

  12. [Autoimmune syndrome in the tropical spastic paraparesis/myelopathy associated with human T-lymphotropic virus infections].

    Science.gov (United States)

    Domínguez, Martha C; Torres, Miyerlandi; Tamayo, Oscar; Criollo, William; Quintana, Milton; Sánchez, Adalberto; García, Felipe

    2008-12-01

    Previous reports have given evidence that in tropical spastic paraparesis (TSP)/human T-lymphotrophic virus (HTLV-I)-associated myelopathy (HAM), an autoimmune process occurs as part of its pathogenesis. The roles of autoimmunity and the molecular mimicry was evaluated in TSP/HAM patients. Plasma samples were characterized from patients in the Pacific coastal region of Colombia. Thirty-seven were identified as TSP/HAM, 10 were diagnosed with adult T-cell leukemia virus, 22 were asymptomatic carriers but seropositive for HTLV-I and 20 were seronegative and served as negative controls. Plasmatic levels of the following were determined: antinuclear antibody (ANA) levels, anticardiolipine-2 (ACL-2), interferon- (IFN-gamma) and interleukin-4 (IL-4). Using Western blot, the crossreactivity of the seropositive and seronegative samples was evaluated against proteins extracted from several central nervous system components of non infected Wistar rats. The HTLV-I seropositive plasmas were crossreacted with a monoclonal tax (LT4 anti-taxp40) from spinal cord neurons of non infected Wistar rats. Of the TSP/HAM patients, 70.2% were reactive against ANA and 83.8% against ACL-2, in contrast with those ATL and asymptomatic seropositives subjects that were not reactive (P<0.001). Moreover, 70.3% had detectable levels of IFN and 43.2% had detectable IL-4. LT4 anti-taxp40 and plasma of TSP/HAM exhibited cross reactivity with a MW 33-35 kDa protein from the rat spinal cord nuclei. Support was provided for the existence of an autoimmune syndrome mediated by molecular mimicry; the syndrome was responsible for some of the axonal degeneration observed in TSP/HAM patients.

  13. Infection with human T-lymphotropic virus types-1 and -2 (HTLV-1 and -2): Implications for blood transfusion safety.

    Science.gov (United States)

    Murphy, E L

    2016-02-01

    Many countries currently perform antibody screening for HTLV-1 infection in blood donors, and this intervention is likely cost-effective in preventing HTLV-1 related diseases in high prevalence countries. However, a number of high-income countries with low prevalence of HTLV-1 infection also perform universal HTLV-1 screening and debate has arisen regarding the cost-effectiveness of these strategies. Filter-based leukoreduction is likely to substantially reduce HTLV-1 transmission by removing infected lymphocytes, but actual laboratory data on its efficacy is currently lacking. Similarly, cost-effectiveness research on HTLV-1 prevention strategies is limited by poor data on prevalence, transmission efficacy and the cost of treating HTLV1 diseases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. Prevalence of human T-lymphotropic virus type I and type II antibody among blood donors in Eastern Saudi Arabia.

    Science.gov (United States)

    Ul-Hassan, Zahoor; Al-Bahrani, Ahmad T; Panhotra, Bodh R

    2004-10-01

    Human T-cell leukemia/lymphoma virus type I and type II (HTLV-I/II) infections can be transfusion associated, leading to tropical paraparesis, myelopathy and other neurological disorders. The aim of this study is to circumvent the risk of transmission through blood transfusion and to describe the prevalence of HTLV-I/II antibody among blood donors of Al-Hasa region and the cost effectiveness of screening blood donors. The study was conducted at the Department of Laboratory and Blood Bank, King Fahad Hospital, Al-Hofuf, Al-Hasa, Kingdom of Saudi Arabia during the period of 1997 to 2003. A total of 47426 blood donors were screened for HTLV-I/II antibody by enzyme-linked immunosorbent assay test, during the 7 years of study period. The positive samples were confirmed by western blot analysis. Overall, HTLV-I antibody positivity (confirmed by western blot) was 3/47426 (0.006%). Out of 3 donors positive for HTLV-I antibody during 1997 to 1998, 2 were expatriates (Indian) and one was native Saudi donor. Human T-cell leukemia/lymphoma virus type I antibody positivity among the native Saudi donors was 1/47426 (0.002%) (2/100000 blood donors). None of the donor were positive for HTLV-II antibody. During the last 5 consecutive years of the study period (1999-2003), none of the donor was positive for HTLV-I/II antibody. Al-Hasa region is non-endemic for HTLV-I/II virus infections. Screening of native Saudi blood donors for these viruses does not appear to be cost effective.

  15. Differentiation of a medulloblastoma cell line towards an astrocytic lineage using the human T lymphotropic retrovirus-1.

    Science.gov (United States)

    Giraudon, P; Dufay, N; Hardin, H; Reboul, A; Tardy, M; Belin, M F

    1993-02-01

    Constituent cells of medulloblastoma, the most common brain tumor occurring in childhood, resemble the primitive neuroepithelial cells normally found in the developing nervous system. However, mutational events prevent their further differentiation. We used the human T cell lymphotrophic virus type 1 to activate these deregulated immature cells by means of its transactivating protein Tax. Concomitant with viral infection was a decrease in cell proliferation characterized by inhibition of [3H]thymidine incorporation and in the number of cells in the G2/M phase of the cell cycle. Morphological changes suggested that medulloblastoma cells differentiated along the astrocytic lineage. The glial phenotype was confirmed by the induction of the glial fibrillary acidic protein and the glial enzyme glutamine synthetase. A direct viral effect and/or secondary effects to viral infection via paracrine/autocrine pathways could counterbalance the maturational defect in these medulloblastoma cells.

  16. Treatment of divergent expansions in scattering theory

    International Nuclear Information System (INIS)

    Gersten, A.; Malin, S.

    1978-01-01

    One of the biggest obstacles in applying quantum field theory to realistic scattering problems are the divergencies of pertubation expansions for large coupling constants and the divergencies of partial wave expansions for massless particles exchanges. There exist, however, methods of summation of the divergent expansions which can lead to significant application in physics. In this paper we treat the problem of summing such expansions using three methods: (i) a generalization of the Pade approximation to the multivariable case. The suggested definition is unique and preserves unitarity. (ii) The summation of divergent partial waves for arbitrary spins. (iii) A successful application of a series inversion to the 3 P 1 nucleon-nucleon phase shift up to 200 MeV. (orig./WL) [de

  17. Divergence and convergence in nutrition science

    NARCIS (Netherlands)

    Penders, Bart; Spruit, Shannon L.; Sikkema, Jan; Maat, Jan; Schuurbiers, Daan

    2015-01-01

    Nutrigenomics diverged from mainstream nutrition science, ideologically, instrumentally and culturally, due to the establishment of a protective niche. That protection is fading. This article chronicles a case in which convergence between nutrigenomics and nutrition science is pursued. Here we

  18. Decoding divergent series in nonparaxial optics.

    Science.gov (United States)

    Borghi, Riccardo; Gori, Franco; Guattari, Giorgio; Santarsiero, Massimo

    2011-03-15

    A theoretical analysis aimed at investigating the divergent character of perturbative series involved in the study of free-space nonparaxial propagation of vectorial optical beams is proposed. Our analysis predicts a factorial divergence for such series and provides a theoretical framework within which the results of recently published numerical experiments concerning nonparaxial propagation of vectorial Gaussian beams find a meaningful interpretation in terms of the decoding operated on such series by the Weniger transformation.

  19. Collinearity, convergence and cancelling infrared divergences

    International Nuclear Information System (INIS)

    Lavelle, Martin; McMullan, David

    2006-01-01

    The Lee-Nauenberg theorem is a fundamental quantum mechanical result which provides the standard theoretical response to the problem of collinear and infrared divergences. Its argument, that the divergences due to massless charged particles can be removed by summing over degenerate states, has been successfully applied to systems with final state degeneracies such as LEP processes. If there are massless particles in both the initial and final states, as will be the case at the LHC, the theorem requires the incorporation of disconnected diagrams which produce connected interference effects at the level of the cross-section. However, this aspect of the theory has never been fully tested in the calculation of a cross-section. We show through explicit examples that in such cases the theorem introduces a divergent series of diagrams and hence fails to cancel the infrared divergences. It is also demonstrated that the widespread practice of treating soft infrared divergences by the Bloch-Nordsieck method and handling collinear divergences by the Lee-Nauenberg method is not consistent in such cases

  20. Evolution of nef variants in gut associated lymphoid tissue of rhesus macaques during primary simian immunodeficiency virus infection

    International Nuclear Information System (INIS)

    Ndolo, Thomas; Syvanen, Michael; Ellison, Thomas; Dandekar, Satya

    2005-01-01

    We utilized the simian immunodeficiency virus model of AIDS to examine evolution of nef gene in gut-associated lymphoid tissue (GALT) during primary and early asymptomatic stages of infection. Macaques were infected with a cloned virus, SIVmac239/nef-stop harboring a premature stop codon in the nef gene. Restoration of the nef open reading frame occurred in GALT early at 3 days post-infection. Analysis of nef sequences by phylogenetic tools showed that evolution of nef was neutral thereafter, as evidenced by the ratio of synonymous to nonsynonymous substitutions, a star pattern in unrooted trees and distribution of amino acid replacements fitting a simple Poisson process. Two regions encoding for a nuclear localization signal and a CTL epitope were conserved. Thus, GALT was a site for strong positive selection of functional nef during initial stages of infection. However, evolution of the nef gene thereafter was neutral during early asymptomatic stage of infection

  1. Transformation of ultraviolet-irradiated human fibroblasts by simian virus 40 is enhanced by cellular DNA repair functions

    International Nuclear Information System (INIS)

    Hall, J.D.

    1981-01-01

    Human fibroblasts irradiated with ultraviolet light were either tested for survival (colony formation) or infected with simian virus 40 and examined for transformation (foci formation). For normal cell cultures, the fractions of surviving colonies which were also transformed increased with increasing irradiation dose. In contrast, little increase in the transformation of ultraviolet-irradiated repair-deficient (xeroderma pigmentosum and xeroderma pigmentosum variant) cells was observed. Similar experiments with xeroderma pigmentosum variant cells treated with caffeine following irradiation indicated that, under these conditions, the deficient cells produced more transformants among the survivors of ultraviolet irradiation than did unirradiated cells. These results suggest (1) that DNA repair functions, not DNA damage per se, are required for enhanced viral transformation in normal cells; (2) that functions involved in excision repair and functions needed for replication of ultraviolet-damaged DNA appear necessary for this stimulation; and (3) that blocking DNA replication in ultraviolet-irradiated xeroderma pigmentosum variant cells by caffeine enhances viral transformation. (Auth.)

  2. A casein-kinase-2-related protein kinase is tightly associated with the large T antigen of simian virus 40

    DEFF Research Database (Denmark)

    Götz, C; Koenig, M G; Issinger, O G

    1995-01-01

    by the addition of protein kinase CK2 suggest that at least one of the T-antigen-associated protein kinases is CK2 or a protein-kinase-CK2-related enzyme. The association of recombinant CK2 with T antigen was strongly confirmed by in vitro binding studies. Experiments with temperature-sensitive SV40-transformed......The simian virus 40 (SV40) large T antigen is a multifunctional protein involved in SV40 cell transformation and lytic virus infection. Some of its activities are regulated by interaction with cellular proteins and/or by phosphorylation of T antigen by various protein kinases. In this study, we...... show that immuno-purified T antigen from SV40-transformed cells and from baculovirus-infected insect cells is tightly associated with a protein kinase that phosphorylates T antigen in vitro. In the presence of heparin or a peptide resembling a protein kinase CK2 recognition site, the phosphorylation...

  3. Pathogenic infection of Macaca nemestrina with a CCR5-tropic subtype-C simian-human immunodeficiency virus

    Directory of Open Access Journals (Sweden)

    Song Ruijiang

    2009-07-01

    Full Text Available Abstract Background Although pig-tailed macaques (Macaca nemestrina have been used in AIDS research for years, less is known about the early immunopathogenic events in this species, as compared to rhesus macaques (Macaca mulatta. Similarly, the events in early infection are well-characterized for simian immunodeficiency viruses (SIV, but less so for chimeric simian-human immunodeficiency viruses (SHIV, although the latter have been widely used in HIV vaccine studies. Here, we report the consequences of intrarectal infection with a CCR5-tropic clade C SHIV-1157ipd3N4 in pig-tailed macaques. Results Plasma and cell-associated virus was detectable in peripheral blood and intestinal tissues of all four pig-tailed macaques following intrarectal inoculation with SHIV-1157ipd3N4. We also observed a rapid and irreversible loss of CD4+ T cells at multiple mucosal sites, resulting in a marked decrease of CD4:CD8 T cell ratios 0.5–4 weeks after inoculation. This depletion targeted subsets of CD4+ T cells expressing the CCR5 coreceptor and having a CD28-CD95+ effector memory phenotype, consistent with the R5-tropism of SHIV-1157ipd3N4. All three animals that were studied beyond the acute phase seroconverted as early as week 4, with two developing cross-clade neutralizing antibody responses by week 24. These two animals also demonstrated persistent plasma viremia for >48 weeks. One of these animals developed AIDS, as shown by peripheral blood CD4+ T-cell depletion starting at 20 weeks post inoculation. Conclusion These findings indicate that SHIV-1157ipd3N4-induced pathogenesis in pig-tailed macaques followed a similar course as SIV-infected rhesus macaques. Thus, R5 SHIV-C-infection of pig-tailed macaques could provide a useful and relevant model for AIDS vaccine and pathogenesis research.

  4. Structural improvement of unliganded simian immunodeficiency virus gp120 core by normal-mode-based X-ray crystallographic refinement

    International Nuclear Information System (INIS)

    Chen, Xiaorui; Lu, Mingyang; Poon, Billy K.; Wang, Qinghua; Ma, Jianpeng

    2009-01-01

    The structural model of the unliganded and fully glycosylated simian immunodeficiency virus gp120 core determined to 4.0 Å resolution was substantially improved using a recently developed normal-mode-based anisotropic B-factor refinement method. The envelope protein gp120/gp41 of simian and human immunodeficiency viruses plays a critical role in viral entry into host cells. However, the extraordinarily high structural flexibility and heavy glycosylation of the protein have presented enormous difficulties in the pursuit of high-resolution structural investigation of some of its conformational states. An unliganded and fully glycosylated gp120 core structure was recently determined to 4.0 Å resolution. The rather low data-to-parameter ratio limited refinement efforts in the original structure determination. In this work, refinement of this gp120 core structure was carried out using a normal-mode-based refinement method that has been shown in previous studies to be effective in improving models of a supramolecular complex at 3.42 Å resolution and of a membrane protein at 3.2 Å resolution. By using only the first four nonzero lowest-frequency normal modes to construct the anisotropic thermal parameters, combined with manual adjustments and standard positional refinement using REFMAC5, the structural model of the gp120 core was significantly improved in many aspects, including substantial decreases in R factors, better fitting of several flexible regions in electron-density maps, the addition of five new sugar rings at four glycan chains and an excellent correlation of the B-factor distribution with known structural flexibility. These results further underscore the effectiveness of this normal-mode-based method in improving models of protein and nonprotein components in low-resolution X-ray structures

  5. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques

    Science.gov (United States)

    Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A.; Veazey, Ronald S.

    2015-01-01

    Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit+IL-7Rα+ (CD117+CD127+) cells. These ILC3 cells highly expressed CD90 (∼63%) and aryl hydrocarbon receptor and produced IL-17 (∼63%), IL-22 (∼36%), and TNF-α (∼72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4+ T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues.—Xu, H., Wang, X., Lackner, A. A., Veazey, R. S. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques. PMID:26283536

  6. Brain Macrophages in Simian Immunodeficiency Virus-Infected, Antiretroviral-Suppressed Macaques: a Functional Latent Reservoir.

    Science.gov (United States)

    Avalos, Claudia R; Abreu, Celina M; Queen, Suzanne E; Li, Ming; Price, Sarah; Shirk, Erin N; Engle, Elizabeth L; Forsyth, Ellen; Bullock, Brandon T; Mac Gabhann, Feilim; Wietgrefe, Stephen W; Haase, Ashley T; Zink, M Christine; Mankowski, Joseph L; Clements, Janice E; Gama, Lucio

    2017-08-15

    A human immunodeficiency virus (HIV) infection cure requires an understanding of the cellular and anatomical sites harboring virus that contribute to viral rebound upon treatment interruption. Despite antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) are reported in HIV-infected individuals on ART. Biomarkers for macrophage activation and neuronal damage in cerebrospinal fluid (CSF) of HIV-infected individuals demonstrate continued effects of HIV in brain and suggest that the central nervous system (CNS) may serve as a viral reservoir. Using a simian immunodeficiency virus (SIV)/macaque model for HIV encephalitis and AIDS, we evaluated whether infected cells persist in brain despite ART. Eight SIV-infected pig-tailed macaques were virally suppressed with ART, and plasma and CSF viremia levels were analyzed longitudinally. To assess whether virus persisted in brain macrophages (BrMΦ) in these macaques, we used a macrophage quantitative viral outgrowth assay (MΦ-QVOA), PCR, and in situ hybridization (ISH) to measure the frequency of infected cells and the levels of viral RNA and DNA in brain. Viral RNA in brain tissue of suppressed macaques was undetectable, although viral DNA was detected in all animals. The MΦ-QVOA demonstrated that the majority of suppressed animals contained latently infected BrMΦ. We also showed that virus produced in the MΦ-QVOAs was replication competent, suggesting that latently infected BrMΦ are capable of reestablishing productive infection upon treatment interruption. This report provides the first confirmation of the presence of replication-competent SIV in BrMΦ of ART-suppressed macaques and suggests that the highly debated issue of viral latency in macrophages, at least in brain, has been addressed in SIV-infected macaques treated with ART. IMPORTANCE Resting CD4 + T cells are currently the only cells that fit the definition of a latent reservoir. However, recent evidence suggests that HIV

  7. Functional analyses of the three simian hemorrhagic fever virus nonstructural protein 1 papain-like proteases.

    Science.gov (United States)

    Vatter, Heather A; Di, Han; Donaldson, Eric F; Radu, Gertrud U; Maines, Taronna R; Brinton, Margo A

    2014-08-01

    The N-terminal region of simian hemorrhagic fever virus (SHFV) nonstructural polyprotein 1a is predicted to encode three papain-like proteases (PLP1α, PLP1β, and PLP1γ). Catalytic residues and cleavage sites for each of the SHFV PLP1s were predicted by alignment of the SHFV PLP1 region sequences with each other as well as with those of other arteriviruses, and the predicted catalytic residues were shown to be proximal by homology modeling of the SHFV nsp1s on porcine respiratory and reproductive syndrome virus (PRRSV) nsp1 crystal structures. The functionality of the predicted catalytic Cys residues and cleavage sites was tested by analysis of the autoproteolytic products generated in in vitro transcription/translation reactions done with wild-type or mutant SHFV nsp1 constructs. Cleavage sites were also analyzed by mass spectroscopy analysis of selected immunoprecipitated cleavage products. The data showed that each of the three SHFV PLP1s is an active protease. Cys63 was identified as the catalytic Cys of SHFV PLP1α and is adjacent to an Ala instead of the canonical Tyr observed in other arterivirus PLP1s. SHFV PLP1γ is able to cleave at both downstream and upstream nsp1 junction sites. Although intermediate precursor polyproteins as well as alternative products generated by each of the SHFV PLP1s cleaving at sites within the N-terminal region of nsp1β were produced in the in vitro reactions, Western blotting of SHFV-infected, MA104 cell lysates with SHFV nsp1 protein-specific antibodies detected only the three mature nsp1 proteins. SHFV is unique among arteriviruses in having three N-terminal papain-like protease 1 (PLP1) domains. Other arteriviruses encode one or two active PLP1s. This is the first functional study of the SHFV PLP1s. Analysis of the products of in vitro autoprocessing of an N-terminal SHFV nonstructural 1a polypeptide fragment showed that each of the three SHFV PLP1s is active, and the predicted catalytic Cys residues and cleavage sites

  8. Properties of classical and quantum Jensen-Shannon divergence

    NARCIS (Netherlands)

    J. Briët (Jop); P. Harremoës (Peter)

    2009-01-01

    htmlabstractJensen-Shannon divergence (JD) is a symmetrized and smoothed version of the most important divergence measure of information theory, Kullback divergence. As opposed to Kullback divergence it determines in a very direct way a metric; indeed, it is the square of a metric. We consider a

  9. Beam Angular Divergence Effects in Ion Implantation

    International Nuclear Information System (INIS)

    Horsky, T. N.; Hahto, S. K.; Bilbrough, D. G.; Jacobson, D. C.; Krull, W. A.; Goldberg, R. D.; Current, M. I.; Hamamoto, N.; Umisedo, S.

    2008-01-01

    An important difference between monomer ion beams and heavy molecular beams is a significant reduction in beam angular divergence and increased on-wafer angular accuracy for molecular beams. This advantage in beam quality stems from a reduction in space-charge effects within the beam. Such improved angular accuracy has been shown to have a significant impact on the quality and yield of transistor devices [1,12]. In this study, B 18 H x + beam current and angular divergence data collected on a hybrid scanned beam line that magnetically scans the beam across the wafer is presented. Angular divergence is kept below 0.5 deg from an effective boron energy of 200 eV to 3000 eV. Under these conditions, the beam current is shown analytically to be limited by space charge below about 1 keV, but by the matching of the beam emittance to the acceptance of the beam line above 1 keV. In addition, results of a beam transport model which includes variable space charge compensation are presented, in which a drift mode B 18 H x + beam is compared to an otherwise identical boron beam after deceleration. Deceleration is shown to introduce significant space-charge blow up resulting in a large on-wafer angular divergence. The divergence effects introduced by wafer charging are also discussed.

  10. Ion divergence in magnetically insulated diodes

    International Nuclear Information System (INIS)

    Slutz, S.A.; Lemke, R.W.; Pointon, T.D.; Desjarlais, M.P.; Johnson, D.J.; Mehlhorn, T.A.; Filuk, A.; Bailey, J.

    1995-01-01

    Magnetically insulated ion diodes are being developed to drive inertial confinement fusion. Ion beam microdivergence must be reduced to achieve the very high beam intensities required to achieve this goal. Three-dimensional particle-in-cell simulations indicate that instability induced fluctuations can produce significant ion divergence during acceleration. These simulations exhibit a fast growing mode early in time, which has been identified as the diocotron instability. The divergence generated by this mode is modest due to the relatively high frequency (>1GHz). Later, a low-frequency low-phase-velocity instability develops. This instability couples effectively to the ions, since the frequency is approximately the reciprocal of the ion transit time, and can generate unacceptably large ion divergences (>30 mrad). Linear stability theory reveals that this mode requires perturbations parallel to the applied magnetic field and is related to the modified two stream instability. Measurements of ion density fluctuations and energy-momentum correlations have confirmed that instabilities develop in ion diodes and contribute to the ion divergence. In addition, spectroscopic measurements indicate that the ions have a significant transverse temperature very close to the emission surface. Passive lithium fluoride (LiF) anodes have larger transverse beam temperatures than laser irradiated active sources. Calculations of source divergence expected from the roughness of LiF surfaces and the possible removal of this layer is presented

  11. The divergence theorem for divergence measure vectorfields on sets with fractal boundaries

    Czech Academy of Sciences Publication Activity Database

    Šilhavý, Miroslav

    2009-01-01

    Roč. 14, č. 5 (2009), s. 445-455 ISSN 1081-2865 Institutional research plan: CEZ:AV0Z10190503 Keywords : divergence measure vectorfields * fractal s * divergence theorem Subject RIV: BA - General Mathematics Impact factor: 1.065, year: 2009

  12. Pre-crisis mouse cells show strain-specific covariation in the amount of 54-kilodalton phosphoprotein and in susceptibility to transformation by simian virus 40.

    Science.gov (United States)

    Chen, S; Blanck, G; Pollack, R E

    1983-09-01

    We have used several inbred mouse strains to examine the role of the 54-kilodalton (kDa) cellular phosphoprotein in transformation by the papovavirus simian virus 40. We have measured the endogenous 54-kDa phosphoprotein in cells obtained from these inbred mouse strains. To study the effect of passage, cell cultures were measured for amount of the 54-kDa phosphoprotein at the 2nd and 12th passages. In the absence of any transforming agent, the amount of endogenous 54-kDa phosphoprotein in early pre-crisis mouse cells varied in a strain-specific way. Transformation frequency varied coordinately with endogenous 54-kDa expression. Mouse strains whose cells produced a high level of endogenous 54-kDa phosphoprotein on passage did not further increase its expression after simian virus 40 transformation.

  13. Vibhakti Divergence between Sanskrit and Hindi

    Science.gov (United States)

    Shukla, Preeti; Shukl, Devanand; Kulkarni, Amba

    Translation divergence at various levels between languages arises due to the different conventions followed by different languages for coding the information of grammatical relations. Though Sanskrit and Hindi belong to the same Indo-Aryan family and structurally as well as lexically Hindi inherits a lot from Sanskrit, yet divergences are observed at the level of function words such as vibhaktis. Pāṇini in his Aṣṭādhyāyī has assigned a default vibhakti to kārakas alongwith many scopes for exceptions. He handles these exceptions either by imposing a new kāraka role or by assigning a special vibhakti. However, these methods are not acceptable in Hindi in toto. Based on the nature of deviation, we propose seven cases of divergences in this paper.

  14. Simian Hemorrhagic Fever Virus Cell Entry Is Dependent on CD163 and Uses a Clathrin-Mediated Endocytosis-Like Pathway

    OpenAIRE

    Caì, Yíngyún; Postnikova, Elena N.; Bernbaum, John G.; Yú, Shuǐqìng; Mazur, Steven; Deiuliis, Nicole M.; Radoshitzky, Sheli R.; Lackemeyer, Matthew G.; McCluskey, Adam; Robinson, Phillip J.; Haucke, Volker; Wahl-Jensen, Victoria; Bailey, Adam L.; Lauck, Michael; Friedrich, Thomas C.

    2014-01-01

    Simian hemorrhagic fever virus (SHFV) causes a severe and almost uniformly fatal viral hemorrhagic fever in Asian macaques but is thought to be nonpathogenic for humans. To date, the SHFV life cycle is almost completely uncharacterized on the molecular level. Here, we describe the first steps of the SHFV life cycle. Our experiments indicate that SHFV enters target cells by low-pH-dependent endocytosis. Dynamin inhibitors, chlorpromazine, methyl-β-cyclodextrin, chloroquine, and concanamycin A ...

  15. Diverging expectations in buyer-seller relationships

    DEFF Research Database (Denmark)

    Andersen, Poul Houman; Christensen, Poul Rind; Damgaard, Torben

    2009-01-01

    Many firms assume that outsourcing partnerships may allow them to strengthen their overall competitiveness. Lured by its intuitive appeal, several enter into such partnerships, only to realize that they represent a marginal rather than a magical solution to their quest for increasing market...... performance. We explore the proposed impact of diverging relationship norms on relationship expectations using data from an ongoing field study of Danish buyers and Chinese suppliers. We link these diverging expectations to the business practices of Danish buyers and Chinese and their institutional contexts...

  16. Universal portfolios generated by the Bregman divergence

    Science.gov (United States)

    Tan, Choon Peng; Kuang, Kee Seng

    2017-04-01

    The Bregman divergence of two probability vectors is a stronger form of the f-divergence introduced by Csiszar. Two versions of the Bregman universal portfolio are presented by exploiting the mean-value theorem. The explicit form of the Bregman universal portfolio generated by a function of a convex polynomial is derived and studied empirically. This portfolio can be regarded as another generalized of the well-known Helmbold portfolio. By running the portfolios on selected stock-price data sets from the local stock exchange, it is shown that it is possible to increase the wealth of the investor by using the portfolios in investment.

  17. Stora's fine notion of divergent amplitudes

    Directory of Open Access Journals (Sweden)

    Joseph C. Várilly

    2016-11-01

    Full Text Available Stora and coworkers refined the notion of divergent quantum amplitude, somewhat upsetting the standard power-counting recipe. This unexpectedly clears the way to new prototypes for free and interacting field theories of bosons of any mass and spin.

  18. Taming infrared divergences in the effective potential

    Energy Technology Data Exchange (ETDEWEB)

    Elias-Miro, J. [IFAE, Univ. Autonoma de Barcelona (Spain); Universitat Autonoma de Barcelona (Spain). Dept. de Fisica; Espinosa, J.R. [IFAE, Univ. Autonoma de Barcelona (Spain); ICREA, Institucio Catalana de Recerca i Estudis Avancats, Barcelona (Spain); Konstandin, T. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2014-06-15

    The Higgs effective potential in the Standard Model (SM), calculated perturbatively, generically suffers from infrared (IR) divergences when the (field-dependent) tree-level mass of the Goldstone bosons goes to zero. Such divergences can affect both the potential and its first derivative and become worse with increasing loop order. In this paper we show that these IR divergences are spurious, we perform a simple resummation of all IR-problematic terms known (up to three loops) and explain how to extend the resummation to cure all such divergences to any order. The method is of general applicability and would work in scenarios other than the SM. Our discussion has some bearing on a scenario recently proposed as a mechanism for gauge mediation of scale breaking in the ultraviolet, in which it is claimed that the low-energy Higgs potential is non-standard. We argue that all non-decoupling effects from the heavy sector can be absorbed in the renormalization of low-energy parameters leading to a SM-like effective theory.

  19. Bounding the bias of contrastive divergence learning

    DEFF Research Database (Denmark)

    Fischer, Anja; Igel, Christian

    2011-01-01

    Optimization based on k-step contrastive divergence (CD) has become a common way to train restricted Boltzmann machines (RBMs). The k-step CD is a biased estimator of the log-likelihood gradient relying on Gibbs sampling. We derive a new upper bound for this bias. Its magnitude depends on k...

  20. Behavioural divergence, interfertility and speciation: a review.

    Science.gov (United States)

    Pillay, Neville; Rymer, Tasmin L

    2012-11-01

    Behavioural compatibility between mates is fundamental for maintaining species boundaries and is achieved through appropriate communication between males and females. A breakdown in communication will lead to behavioural divergence and reduced interfertility. In this review, we summarise the current knowledge on male signals and female perception of these signals, integrating the literature from several taxa. We advocate that signaller-perceiver coevolution, which is usually under strong stabilising selection to enable mating, forms the basis of species-specific mate recognition systems. The mechanisms (phylogeny, geography, ecology, biology) shaping signaller-perceiver systems are briefly discussed to demonstrate the factors underpinning the evolution of signaller-perceiver couplings. Since divergence and diversification of communication systems is driven by changes in the mechanical properties of sensory pathways and morphology of sensory organs, we highlight signal modalities (auditory, olfactory, visual, tactile) and their importance in communication, particularly in mate selection. Next, using available examples and generating a stylised model, we suggest how disruption (biological, ecological, stochastic) of signaller-perceiver systems drives behavioural divergence and consequently results in reduced interfertility and speciation. Future studies should adopt an integrative approach, combining multiple parameters (phylogeny, adaptive utility of communication systems, genetics and biomechanical/biochemical properties of signals and perception) to explore how disruption of signaller-perceiver systems results in behavioural divergence and reduced interfertility. Finally, we question the impact that rapid environmental change will have on disruption of communication systems, potentially interfering with signaller-perceiver couplings. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Hamiltonian representation of divergence-free fields

    International Nuclear Information System (INIS)

    Boozer, A.H.

    1984-11-01

    Globally divergence-free fields, such as the magnetic field and the vorticity, can be described by a two degree of freedom Hamiltonian. The Hamiltonian function provides a complete topological description of the field lines. The formulation also separates the dissipative and inertial time scale evolution of the magnetic and the vorticity fields

  2. Viewpoint Environmental Slogans: Memes with Diverging ...

    African Journals Online (AJOL)

    Environmental slogans can be seen as memes, i.e. cultural constructs that, not unlike genes, replicate themselves from one generation to the next. Memes may, however, be divergently interpreted and some memes can even have unwanted side-effects. We wanted to find out how supporters of an environmental ...

  3. The divergence theorem for unbounded vector fields

    OpenAIRE

    De Pauw, Thierry; Pfeffer, Washek F.

    2007-01-01

    In the context of Lebesgue integration, we derive the divergence theorem for unbounded vector. elds that can have singularities at every point of a compact set whose Minkowski content of codimension greater than two is. nite. The resulting integration by parts theorem is applied to removable sets of holomorphic and harmonic functions.

  4. Divergent Priors and well Behaved Bayes Factors

    NARCIS (Netherlands)

    R.W. Strachan (Rodney); H.K. van Dijk (Herman)

    2011-01-01

    textabstractDivergent priors are improper when defined on unbounded supports. Bartlett's paradox has been taken to imply that using improper priors results in ill-defined Bayes factors, preventing model comparison by posterior probabilities. However many improper priors have attractive properties

  5. The Harmonic Series Diverges Again and Again

    Science.gov (United States)

    Kifowit, Steven J.; Stamps, Terra A.

    2006-01-01

    The harmonic series is one of the most celebrated infinite series of mathematics. A quick glance at a variety of modern calculus textbooks reveals that there are two very popular proofs of the divergence of the harmonic series. In this article, the authors survey these popular proofs along with many other proofs that are equally simple and…

  6. Design of a divergence and alignment indicator

    International Nuclear Information System (INIS)

    Brenizer, J.S. Jr.; Raine, D.A.; Gao, J.; Chen, J.

    1996-01-01

    The divergence and alignment indicator (DAI) is an extension of the ASTM E803 L/D thermal neutron radiography L/D device that allows the user to determine both the beam centerline and the beam divergence. The DAI was made using aluminium plate and rods, and incorporated cadmium wire for contrast. Circular symmetry was utilized to simplify manufacture. The DAI was placed with the five posts against the film cassette or radioscopic imaging device in the physical center of the beam. The DAI was perpendicular to the selected beam radius when the front and back center Cd wire images overlap. The degree of misalignment was indicated by their image positions. After the DAI was aligned, analysis of the cadmium wire ''+'' image spacing yielded the beam divergence. The DAI was tested in a neutron beam which has an L/D of 30 but a small degree of divergence. The DAI was also imaged using an X-ray source. The point source predictions of Cd wire image locations showed good agreement with those measured from the X-ray radiograph. The neutron radiographic locations could be predicted using the point source equations, even though the neutron beam was a complex distributed source. (orig.)

  7. Enhancing Divergent Search through Extinction Events

    DEFF Research Database (Denmark)

    Lehman, Joel; Miikkulainen, Risto

    2015-01-01

    for the capacity to evolve. This hypothesis is tested through experiments in two evolutionary robotics domains. The results show that combining extinction events with divergent search increases evolvability, while combining them with convergent search offers no similar benefit. The conclusion is that extinction...

  8. Taming infrared divergences in the effective potential

    International Nuclear Information System (INIS)

    Elias-Miro, J.; Konstandin, T.

    2014-06-01

    The Higgs effective potential in the Standard Model (SM), calculated perturbatively, generically suffers from infrared (IR) divergences when the (field-dependent) tree-level mass of the Goldstone bosons goes to zero. Such divergences can affect both the potential and its first derivative and become worse with increasing loop order. In this paper we show that these IR divergences are spurious, we perform a simple resummation of all IR-problematic terms known (up to three loops) and explain how to extend the resummation to cure all such divergences to any order. The method is of general applicability and would work in scenarios other than the SM. Our discussion has some bearing on a scenario recently proposed as a mechanism for gauge mediation of scale breaking in the ultraviolet, in which it is claimed that the low-energy Higgs potential is non-standard. We argue that all non-decoupling effects from the heavy sector can be absorbed in the renormalization of low-energy parameters leading to a SM-like effective theory.

  9. Two distinct variants of simian foamy virus in naturally infected mandrills (Mandrillus sphinx and cross-species transmission to humans

    Directory of Open Access Journals (Sweden)

    Marx Preston

    2010-12-01

    Full Text Available Abstract Background Each of the pathogenic human retroviruses (HIV-1/2 and HTLV-1 has a nonhuman primate counterpart, and the presence of these retroviruses in humans results from interspecies transmission. The passage of another simian retrovirus, simian foamy virus (SFV, from apes or monkeys to humans has been reported. Mandrillus sphinx, a monkey species living in central Africa, is naturally infected with SFV. We evaluated the natural history of the virus in a free-ranging colony of mandrills and investigated possible transmission of mandrill SFV to humans. Results We studied 84 semi-free-ranging captive mandrills at the Primate Centre of the Centre International de Recherches Médicales de Franceville (Gabon and 15 wild mandrills caught in various areas of the country. The presence of SFV was also evaluated in 20 people who worked closely with mandrills and other nonhuman primates. SFV infection was determined by specific serological (Western blot and molecular (nested PCR of the integrase region in the polymerase gene assays. Seropositivity for SFV was found in 70/84 (83% captive and 9/15 (60% wild-caught mandrills and in 2/20 (10% humans. The 425-bp SFV integrase fragment was detected in peripheral blood DNA from 53 captive and 8 wild-caught mandrills and in two personnel. Sequence and phylogenetic studies demonstrated the presence of two distinct strains of mandrill SFV, one clade including SFVs from mandrills living in the northern part of Gabon and the second consisting of SFV from animals living in the south. One man who had been bitten 10 years earlier by a mandrill and another bitten 22 years earlier by a macaque were found to be SFV infected, both at the Primate Centre. The second man had a sequence close to SFVmac sequences. Comparative sequence analysis of the virus from the first man and from the mandrill showed nearly identical sequences, indicating genetic stability of SFV over time. Conclusion Our results show a high

  10. Two distinct variants of simian foamy virus in naturally infected mandrills (Mandrillus sphinx) and cross-species transmission to humans.

    Science.gov (United States)

    Mouinga-Ondémé, Augustin; Betsem, Edouard; Caron, Mélanie; Makuwa, Maria; Sallé, Bettina; Renault, Noemie; Saib, Ali; Telfer, Paul; Marx, Preston; Gessain, Antoine; Kazanji, Mirdad

    2010-12-14

    Each of the pathogenic human retroviruses (HIV-1/2 and HTLV-1) has a nonhuman primate counterpart, and the presence of these retroviruses in humans results from interspecies transmission. The passage of another simian retrovirus, simian foamy virus (SFV), from apes or monkeys to humans has been reported. Mandrillus sphinx, a monkey species living in central Africa, is naturally infected with SFV. We evaluated the natural history of the virus in a free-ranging colony of mandrills and investigated possible transmission of mandrill SFV to humans. We studied 84 semi-free-ranging captive mandrills at the Primate Centre of the Centre International de Recherches Médicales de Franceville (Gabon) and 15 wild mandrills caught in various areas of the country. The presence of SFV was also evaluated in 20 people who worked closely with mandrills and other nonhuman primates. SFV infection was determined by specific serological (Western blot) and molecular (nested PCR of the integrase region in the polymerase gene) assays. Seropositivity for SFV was found in 70/84 (83%) captive and 9/15 (60%) wild-caught mandrills and in 2/20 (10%) humans. The 425-bp SFV integrase fragment was detected in peripheral blood DNA from 53 captive and 8 wild-caught mandrills and in two personnel. Sequence and phylogenetic studies demonstrated the presence of two distinct strains of mandrill SFV, one clade including SFVs from mandrills living in the northern part of Gabon and the second consisting of SFV from animals living in the south. One man who had been bitten 10 years earlier by a mandrill and another bitten 22 years earlier by a macaque were found to be SFV infected, both at the Primate Centre. The second man had a sequence close to SFVmac sequences. Comparative sequence analysis of the virus from the first man and from the mandrill showed nearly identical sequences, indicating genetic stability of SFV over time. Our results show a high prevalence of SFV infection in a semi-free-ranging colony

  11. Cancellation of soft and collinear divergences in noncommutative QED

    International Nuclear Information System (INIS)

    Mirza, B.; Zarei, M.

    2006-01-01

    In this paper, we investigate the behavior of noncommutative IR divergences and will also discuss their cancellation in the physical cross sections. The commutative IR (soft) divergences existing in the nonplanar diagrams will be examined in order to prove an all-order cancellation of these divergences using the Weinberg's method. In noncommutative QED, collinear divergences due to triple photon splitting vertex, were encountered, which are shown to be canceled out by the noncommutative version of KLN theorem. This guarantees that there is no mixing between the Collinear, soft divergences and noncommutative IR divergences

  12. Human immunodeficiency virus type 1 neutralization epitope with conserved architecture elicits early type-specific antibodies in experimentally infected chimpanzees

    NARCIS (Netherlands)

    Goudsmit, J.; Debouck, C.; Meloen, R. H.; Smit, L.; Bakker, M.; Asher, D. M.; Wolff, A. V.; Gibbs, C. J.; Gajdusek, D. C.

    1988-01-01

    Chimpanzees are susceptible to infection by divergent strains of human immunodeficiency virus type 1 (HIV-1), none of which cause clinical or immunological abnormalities. Chimpanzees were inoculated with one of four strains of HIV-1: human T-lymphotropic virus (HTLV) type IIIB, lymphadenopathy virus

  13. Soluble human CD4 elicits an antibody response in rhesus monkeys that inhibits simian immunodeficiency virus replication

    International Nuclear Information System (INIS)

    Watanabe, Mamoru; Chen, Zheng W.; Tsubota, Hiroshi; Lord, C.I.; Levine, C.G.; Letvin, N.L.

    1991-01-01

    Rhesus monkeys infected with the simian immunodeficiency virus of macaques (SIV mac ) demonstrate significant virologic and clinical improvement as a result of treatment with human recombinant soluble CD4 (rsCD4). The authors show that human rsCD4 does not efficiently inhibit SIV mac replication in bone marrow macrophages of rhesus monkeys and does not significantly augment bone marrow hematopoietic colony formation in vitro. However, plasma of human rsCD4-treated rhesus monkeys does exhibit significant anti-SIV mac activity in vitro. Plasma of these animals efficiently blocks SIV mac replicaton in peripheral blood lymphocytes and bone marrow macrophages. It also increases granulocyte/macrophage colony formation in vitro by bone marrow cells of SIV mac -infected monkeys. This plasma and the IgG fraction of plasma from a rhesus monkey immunized with human rsCD4 in adjuvant demonstrate reactivity with a soluble form of the rhesus monkey CD4 molecule, exhibit binding to CD4 + but not CD8 + concanavalin A-activated rhesus monkey peripheral blood lymphocytes, and precipitate the CD4 molecule from surface-labeled activated rhesus monkey peripheral blood lymphocytes. Moreover, anti-viral activity is demonstrable in the IgG fraction of plasma from a human rsCD4-immunized monkey. These studies raise the possibility that a modified human CD4 molecule serving as an immunogen might elicit an antibody response that could potentially induce a beneficial therapeutic response in human immunodeficiency virus-infected individuals

  14. Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved in Immunity and Neurogenesis in Simian Immunodeficiency Virus-Infected Macaques

    Directory of Open Access Journals (Sweden)

    John K. Maxi

    2016-11-01

    Full Text Available Alcohol use disorders (AUD exacerbate neurocognitive dysfunction in Human Immunodeficiency Virus (HIV+ patients. We have shown that chronic binge alcohol (CBA administration (13–14 g EtOH/kg/wk prior to and during simian immunodeficiency virus (SIV infection in rhesus macaques unmasks learning deficits in operant learning and memory tasks. The underlying mechanisms of neurocognitive alterations due to alcohol and SIV are not known. This exploratory study examined the CBA-induced differential expression of hippocampal genes in SIV-infected (CBA/SIV+; n = 2 macaques in contrast to those of sucrose administered, SIV-infected (SUC/SIV+; n = 2 macaques. Transcriptomes of hippocampal samples dissected from brains obtained at necropsy (16 months post-SIV inoculation were analyzed to determine differentially expressed genes. MetaCore from Thomson Reuters revealed enrichment of genes involved in inflammation, immune responses, and neurodevelopment. Functional relevance of these alterations was examined in vitro by exposing murine neural progenitor cells (NPCs to ethanol (EtOH and HIV trans-activator of transcription (Tat protein. EtOH impaired NPC differentiation as indicated by decreased βIII tubulin expression. These findings suggest a role for neuroinflammation and neurogenesis in CBA/SIV neuropathogenesis and warrant further investigation of their potential contribution to CBA-mediated neurobehavioral deficits.

  15. Simian varicella virus infection of rhesus macaques recapitulates essential features of varicella zoster virus infection in humans.

    Directory of Open Access Journals (Sweden)

    Ilhem Messaoudi

    2009-11-01

    Full Text Available Simian varicella virus (SVV, the etiologic agent of naturally occurring varicella in primates, is genetically and antigenically closely related to human varicella zoster virus (VZV. Early attempts to develop a model of VZV pathogenesis and latency in nonhuman primates (NHP resulted in persistent infection. More recent models successfully produced latency; however, only a minority of monkeys became viremic and seroconverted. Thus, previous NHP models were not ideally suited to analyze the immune response to SVV during acute infection and the transition to latency. Here, we show for the first time that intrabronchial inoculation of rhesus macaques with SVV closely mimics naturally occurring varicella (chickenpox in humans. Infected monkeys developed varicella and viremia that resolved 21 days after infection. Months later, viral DNA was detected only in ganglia and not in non-ganglionic tissues. Like VZV latency in human ganglia, transcripts corresponding to SVV ORFs 21, 62, 63 and 66, but not ORF 40, were detected by RT-PCR. In addition, as described for VZV, SVV ORF 63 protein was detected in the cytoplasm of neurons in latently infected monkey ganglia by immunohistochemistry. We also present the first in depth analysis of the immune response to SVV. Infected animals produced a strong humoral and cell-mediated immune response to SVV, as assessed by immunohistology, serology and flow cytometry. Intrabronchial inoculation of rhesus macaques with SVV provides a novel model to analyze viral and immunological mechanisms of VZV latency and reactivation.

  16. Revisiting a quarter of a century of simian immunodeficiency virus (SIV-associated cardiovascular diseases at the German Primate Center

    Directory of Open Access Journals (Sweden)

    M. Mietsch

    2017-06-01

    Full Text Available Human immunodeficiency virus (HIV comorbidities have become clinically more important due to antiretroviral therapy. Although therapy increases life expectancy, it does not completely suppress immune activation and its associated complications. The simian immunodeficiency virus (SIV-infected rhesus macaque (Macaca mulatta represents a valuable model for the investigation of SIV-associated diseases. Although cardiovascular (CV changes are common in HIV-infected patients, there are only a few reports on the incidence of CV findings in SIV-infected animals. In addition, potential associations between pathohistological findings and hematological parameters are still unclear. We therefore conducted a retrospective analysis of 195 SIV-infected rhesus macaques that were euthanized with AIDS-related symptoms at the German Primate Center, Goettingen, over a 25-year period. Pathological findings were correlated with hematological data. The main findings included myocarditis (12.8 %, endocarditis (9.7 %, and arteriopathy (10.3 % in various organs. Thrombocytopenia occurred more frequently in macaques with endocarditis or arteriopathy than in macaques without CV disease (80 % in animals with endocarditis, 60 % in animals with arteriopathy, p < 0. 0001 and p = 0. 0016, respectively. Further investigations of the interaction between coagulation markers, proinflammatory cytokines, and biomarkers associated with endothelial dysfunction (e.g., D-dimers and histological data (vascular wall structure may unravel the mechanisms underlying HIV/SIV-associated CV comorbidities.

  17. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus-infected macaques.

    Science.gov (United States)

    Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A; Veazey, Ronald S

    2015-12-01

    Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit(+)IL-7Rα(+) (CD117(+)CD127(+)) cells. These ILC3 cells highly expressed CD90 (∼ 63%) and aryl hydrocarbon receptor and produced IL-17 (∼ 63%), IL-22 (∼ 36%), and TNF-α (∼ 72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4(+) T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues. © FASEB.

  18. Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1 Nef Proteins Show Distinct Patterns and Mechanisms of Src Kinase Activation

    Science.gov (United States)

    Greenway, Alison L.; Dutartre, Hélène; Allen, Kelly; McPhee, Dale A.; Olive, Daniel; Collette, Yves

    1999-01-01

    The nef gene from human and simian immunodeficiency viruses (HIV and SIV) regulates cell function and viral replication, possibly through binding of the nef product to cellular proteins, including Src family tyrosine kinases. We show here that the Nef protein encoded by SIVmac239 interacts with and also activates the human Src kinases Lck and Hck. This is in direct contrast to the inhibitory effect of HIV type 1 (HIV-1) Nef on Lck catalytic activity. Unexpectedly, however, the interaction of SIV Nef with human Lck or Hck is not mediated via its consensus proline motif, which is known to mediate HIV-1 Nef binding to Src homology 3 (SH3) domains, and various experimental analyses failed to show significant interaction of SIV Nef with the SH3 domain of either kinase. Instead, SIV Nef can bind Lck and Hck SH2 domains, and its N-terminal 50 amino acid residues are sufficient for Src kinase binding and activation. Our results provide evidence for multiple mechanisms by which Nef binds to and regulates Src kinases. PMID:10364375

  19. Assignment of simian rotavirus SA11 temperature-sensitive mutant groups B and E to genome segments

    International Nuclear Information System (INIS)

    Gombold, J.L.; Estes, M.K.; Ramig, R.F.

    1985-01-01

    Recombinant (reassortant) viruses were selected from crosses between temperature-sensitive (ts) mutants of simian rotavirus SA11 and wild-type human rotavirus Wa. The double-stranded genome RNAs of the reassortants were examined by electrophoresis in Tris-glycine-buffered polyacrylamide gels and by dot hybridization with a cloned DNA probe for genome segment 2. Analysis of replacements of genome segments in the reassortants allowed construction of a map correlating genome segments providing functions interchangeable between SA11 and Wa. The reassortants revealed a functional correspondence in order of increasing electrophoretic mobility of genome segments. Analysis of the parental origin of genome segments in ts+ SA11/Wa reassortants derived from the crosses SA11 tsB(339) X Wa and SA11 tsE(1400) X Wa revealed that the group B lesion of tsB(339) was located on genome segment 3 and the group E lesion of tsE(1400) was on segment 8

  20. Assignment of simian rotavirus SA11 temperature-sensitive mutant groups B and E to genome segments

    Energy Technology Data Exchange (ETDEWEB)

    Gombold, J.L.; Estes, M.K.; Ramig, R.F.

    1985-05-01

    Recombinant (reassortant) viruses were selected from crosses between temperature-sensitive (ts) mutants of simian rotavirus SA11 and wild-type human rotavirus Wa. The double-stranded genome RNAs of the reassortants were examined by electrophoresis in Tris-glycine-buffered polyacrylamide gels and by dot hybridization with a cloned DNA probe for genome segment 2. Analysis of replacements of genome segments in the reassortants allowed construction of a map correlating genome segments providing functions interchangeable between SA11 and Wa. The reassortants revealed a functional correspondence in order of increasing electrophoretic mobility of genome segments. Analysis of the parental origin of genome segments in ts+ SA11/Wa reassortants derived from the crosses SA11 tsB(339) X Wa and SA11 tsE(1400) X Wa revealed that the group B lesion of tsB(339) was located on genome segment 3 and the group E lesion of tsE(1400) was on segment 8.

  1. Phenotypic Divergence in the Reproductive Traits of Marbled ...

    African Journals Online (AJOL)

    Overall, the results indicated some level of phenotypic divergence of the fish ... divergence cannot be partitioned between fishing mortality, genetic .... female fish was estimated from the egg counts ..... that greatly improved the quality of the.

  2. Endemic infrared divergences in QED3 at finite temperature

    International Nuclear Information System (INIS)

    Lo, Pok Man; Swanson, Eric S.

    2011-01-01

    We demonstrate that massless QED in three dimensions contains endemic infrared divergences. It is argued that these divergences do not affect observables; furthermore, it is possible to choose a gauge that renders the theory finite.

  3. Divergent Geophysical Evolution of Vesta and Ceres

    Science.gov (United States)

    Raymond, C. A.; Ermakov, A.; Castillo, J. C.; Fu, R. R.; McSween, H. Y., Jr.; McCord, T. B.; Park, R. S.; Russell, C. T.; De Sanctis, M. C.; Jaumann, R.; Konopliv, A. S.

    2017-12-01

    The Dawn mission explored two massive protoplanets in the main asteroid belt, Vesta and Ceres, that are fossils from the earliest epoch of solar system formation. Dawn's data provide evidence that these bodies formed very early, within the first few million years after CAIs, yet they followed divergent evolutionary paths. Vesta formed globally homogeneous distribution of minerals across the surface indicates that Ceres' interior experienced pervasive alteration. Topography and morphology of the surface reveals smoother, apparently resurfaced areas, generally at lower elevation, and rougher areas with greater relief. Local morphology such as crater floor deposits, isolated mountains, and enigmatic bright areas indicate recently active processes on Ceres, likely driven by brine cryovolcanism. Causes of the divergent evolution of these bodies include their accretionary environment, timing of accretion and size. Acknowledgements: Part of this research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under contract to the National Aeronautics and Space Administration.

  4. PUBLIC INTEGRITY AND THE DIVERGENCE FROM IT

    Directory of Open Access Journals (Sweden)

    Simona‐Roxana ULMAN

    2013-12-01

    Full Text Available Public Integrity is one of the public sector’s essential objectives to attain. In contradiction, as a divergence from it, corruption is one of the persistent problems of the societies over years and it affects the credibility of public institutions and its ambassadors in front of the citizens and of the other related countries. All nations complain of corruption and, as it is observed in the Corruption Perception Index 2012, no country has a maximum score which shows that a country is totally clean. In this context, the study of the most important elements of the public integrity concept, the identification of what causes the divergence from it and the solutions detection become a relevant option for economic literature. In this context, the main objective of this paper is to emphasize the public integrity concept and its main aspects and to make a comparison between countries to achieve a large perspective of the world’s public integrity juncture.

  5. Flow over convergent and divergent wall riblets

    Energy Technology Data Exchange (ETDEWEB)

    Koeltzsch, K.; Dinkelacker, A.; Grundmann, R. [Institut fuer Luft- und Raumfahrttechnik, Technische Universitaet Dresden, 36460 Merkers (Germany)

    2002-08-01

    Fast swimming sharks have small riblets on their skin, which are assumed to improve the swimming performance of the fish. Fluid dynamic experiments in water as well as in air confirm this assumption. With riblet surfaces as compared to smooth surfaces, drag reductions up to about 10% were measured. The overall riblet pattern on sharks shows parallel riblets directed from head to tail, but besides this overall pattern fast swimming sharks have also small areas with converging riblets and others with diverging riblets. In the present study the velocity field over convergent and divergent riblet patterns is investigated by hot-wire measurements in turbulent pipe flow. Significant changes in the near wall velocity field were found. (orig.)

  6. Gluon mass generation without seagull divergences

    International Nuclear Information System (INIS)

    Aguilar, Arlene C.; Papavassiliou, Joannis

    2010-01-01

    Dynamical gluon mass generation has been traditionally plagued with seagull divergences, and all regularization procedures proposed over the years yield finite but scheme-dependent gluon masses. In this work we show how such divergences can be eliminated completely by virtue of a characteristic identity, valid in dimensional regularization. The ability to trigger the aforementioned identity hinges crucially on the particular Ansatz employed for the three-gluon vertex entering into the Schwinger-Dyson equation governing the gluon propagator. The use of the appropriate three-gluon vertex brings about an additional advantage: one obtains two separate (but coupled) integral equations, one for the effective charge and one for the gluon mass. This system of integral equations has a unique solution, which unambiguously determines these two quantities. Most notably, the effective charge freezes in the infrared, and the gluon mass displays power-law running in the ultraviolet, in agreement with earlier considerations.

  7. Increasing interpersonal trust through divergent thinking

    Directory of Open Access Journals (Sweden)

    Roberta eSellaro

    2014-06-01

    Full Text Available Interpersonal trust is an essential ingredient of many social relationships but how stable is it actually, and how is it controlled? There is evidence that the degree of trust into others might be rather volatile and can be affected by manipulations like drawing attention to personal interdependence or independence. Here we investigated whether the degree of interpersonal trust can be biased by inducing either a more integrative or a more cognitive-control mode by means of a creativity task requiring divergent or convergent thinking, respectively. Participants then performed the Trust Game, which provides an index of interpersonal trust by assessing the money units one participant (the trustor transfers to another participant (the trustee. As expected, participants transferred significantly more money to the trustee after engaging in divergent thinking as compared to convergent thinking. This observation provides support for the idea that interpersonal trust is controlled by domain-general (i.e., not socially dedicated cognitive states.

  8. High temperature phase transitions without infrared divergences

    International Nuclear Information System (INIS)

    Tetradis, N.; Wetterich, C.

    1993-09-01

    The most commonly used method for the study of high temperature phase transitions is based on the perturbative evaluation of the temperature dependent effective potential. This method becomes unreliable in the case of a second order or weakly first order phase transition, due to the appearance of infrared divergences. These divergences can be controlled through the method of the effective average action which employs renormalization group ideas. We report on the study of the high temperature phase transition for the N-component φ 4 theory. A detailed quantitative picture of the second order phase transition is presented, including the critical exponents for the behaviour in the vicinity of the critical temperature. An independent check of the results is obtained in the large N limit, and contact with the perturbative approach is established through the study of the Schwinger-Dyson equations. (orig.)

  9. Molecular evidence for deep phylogenetic divergence in Mandrillus sphinx.

    Science.gov (United States)

    Telfer, P T; Souquière, S; Clifford, S L; Abernethy, K A; Bruford, M W; Disotell, T R; Sterner, K N; Roques, P; Marx, P A; Wickings, E J

    2003-07-01

    Mandrills (Mandrillus sphinx) are forest primates indigenous to western central Africa. Phylogenetic analysis of 267 base pairs (bp) of the cytochrome b gene from 53 mandrills of known and 17 of unknown provenance revealed two phylogeographical groups, with haplotypes differentiated by 2.6% comprising seven synonymous transitions. The distribution of the haplotypes suggests that the Ogooué River, Gabon, which bisects their range, separates mandrill populations in Cameroon and northern Gabon from those in southern Gabon. The haplotype distribution is also concordant with that of two known mandrill simian immunodeficiency viruses, suggesting that these two mandrill phylogroups have followed different evolutionary trajectories since separation.

  10. COMPARATIVE FINANCIAL STATEMENTS. CONVERGENCE VERSUS DIVERGENCE

    Directory of Open Access Journals (Sweden)

    Nicolae ECOBICI

    2010-09-01

    Full Text Available In this paper I compared the Romanian financial statements with the US GAAP financial statements in terms of two criteria: first the reference period and secondly the shape, structure and content of financial statements. Nowadays the two accounting systems, the French and Anglo-Saxon, tend to harmonize. I will present the convergences and the divergences between the financial statements of Romania, subject to OMFP 3055/2009, in parallel with the Anglo-Saxon accounting system.

  11. Divergent Effects of Dendritic Cells on Pancreatitis

    Science.gov (United States)

    2015-09-01

    role of dendritic cells in pancreatitis. Dendritic cells are professional antigen presenting cells which initiate innate and adaptive immune... Lymphoid -tissue-specific homing of bone- marrow-derived dendritic cells . Blood. 113:6638–6647. http://dx.doi .org/10.1182/blood-2009-02-204321 Dapito...Award Number: W81XWH-12-1-0313 TITLE: Divergent Effects of Dendritic Cells on Pancreatitis PRINCIPAL INVESTIGATOR: Dr. George Miller

  12. Initial States: IR and Collinear Divergences

    International Nuclear Information System (INIS)

    Lavelle, Martin; McMullan, David

    2007-01-01

    The standard approach to the infra-red problem is to use the Bloch-Nordsieck trick to handle soft divergences and the Lee-Nauenberg (LN) theorem for collinear singularities. We show that this is inconsistent in the presence of massless initial particles. Furthermore, we show that using the LN theorem with such initial states introduces a non-convergent infinite series of diagrams at any fixed order in perturbation theory

  13. Carnot efficiency at divergent power output

    Science.gov (United States)

    Polettini, Matteo; Esposito, Massimiliano

    2017-05-01

    The widely debated feasibility of thermodynamic machines achieving Carnot efficiency at finite power has been convincingly dismissed. Yet, the common wisdom that efficiency can only be optimal in the limit of infinitely slow processes overlooks the dual scenario of infinitely fast processes. We corroborate that efficient engines at divergent power output are not theoretically impossible, framing our claims within the theory of Stochastic Thermodynamics. We inspect the case of an electronic quantum dot coupled to three particle reservoirs to illustrate the physical rationale.

  14. Fast algorithms for computing phylogenetic divergence time.

    Science.gov (United States)

    Crosby, Ralph W; Williams, Tiffani L

    2017-12-06

    The inference of species divergence time is a key step in most phylogenetic studies. Methods have been available for the last ten years to perform the inference, but the performance of the methods does not yet scale well to studies with hundreds of taxa and thousands of DNA base pairs. For example a study of 349 primate taxa was estimated to require over 9 months of processing time. In this work, we present a new algorithm, AncestralAge, that significantly improves the performance of the divergence time process. As part of AncestralAge, we demonstrate a new method for the computation of phylogenetic likelihood and our experiments show a 90% improvement in likelihood computation time on the aforementioned dataset of 349 primates taxa with over 60,000 DNA base pairs. Additionally, we show that our new method for the computation of the Bayesian prior on node ages reduces the running time for this computation on the 349 taxa dataset by 99%. Through the use of these new algorithms we open up the ability to perform divergence time inference on large phylogenetic studies.

  15. Two families of astrophysical diverging lens models

    Science.gov (United States)

    Er, Xinzhong; Rogers, Adam

    2018-03-01

    In the standard gravitational lensing scenario, rays from a background source are bent in the direction of a foreground lensing mass distribution. Diverging lens behaviour produces deflections in the opposite sense to gravitational lensing, and is also of astrophysical interest. In fact, diverging lensing due to compact distributions of plasma has been proposed as an explanation for the extreme scattering events that produce frequency-dependent dimming of extragalactic radio sources, and may also be related to the refractive radio wave phenomena observed to affect the flux density of pulsars. In this work we study the behaviour of two families of astrophysical diverging lenses in the geometric optics limit, the power law, and the exponential plasma lenses. Generally, the members of these model families show distinct behaviour in terms of image formation and magnification, however the inclusion of a finite core for certain power-law lenses can produce a caustic and critical curve morphology that is similar to the well-studied Gaussian plasma lens. Both model families can produce dual radial critical curves, a novel distinction from the tangential distortion usually produced by gravitational (converging) lenses. The deflection angle and magnification of a plasma lens vary with the observational frequency, producing wavelength-dependent magnifications that alter the amplitudes and the shape of the light curves. Thus, multiwavelength observations can be used to physically constrain the distribution of the electron density in such lenses.

  16. An Exponential Regulator for Rapidity Divergences

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ye [Fermilab; Neill, Duff [MIT, Cambridge, CTP; Zhu, Hua Xing [MIT, Cambridge, CTP

    2016-04-01

    Finding an efficient and compelling regularization of soft and collinear degrees of freedom at the same invariant mass scale, but separated in rapidity is a persistent problem in high-energy factorization. In the course of a calculation, one encounters divergences unregulated by dimensional regularization, often called rapidity divergences. Once regulated, a general framework exists for their renormalization, the rapidity renormalization group (RRG), leading to fully resummed calculations of transverse momentum (to the jet axis) sensitive quantities. We examine how this regularization can be implemented via a multi-differential factorization of the soft-collinear phase-space, leading to an (in principle) alternative non-perturbative regularization of rapidity divergences. As an example, we examine the fully-differential factorization of a color singlet's momentum spectrum in a hadron-hadron collision at threshold. We show how this factorization acts as a mother theory to both traditional threshold and transverse momentum resummation, recovering the classical results for both resummations. Examining the refactorization of the transverse momentum beam functions in the threshold region, we show that one can directly calculate the rapidity renormalized function, while shedding light on the structure of joint resummation. Finally, we show how using modern bootstrap techniques, the transverse momentum spectrum is determined by an expansion about the threshold factorization, leading to a viable higher loop scheme for calculating the relevant anomalous dimensions for the transverse momentum spectrum.

  17. The direct Flow parametric Proof of Gauss' Divergence Theorem revisited

    DEFF Research Database (Denmark)

    Markvorsen, Steen

    The standard proof of the divergence theorem in undergraduate calculus courses covers the theorem for static domains between two graph surfaces. We show that within first year undergraduate curriculum, the flow proof of the dynamic version of the divergence theorem - which is usually considered...... we apply the key instrumental concepts and verify the various steps towards this alternative proof of the divergence theorem....

  18. Origin of HTLV-1 in hunters of nonhuman primates in Central Africa.

    Science.gov (United States)

    Kazanji, Mirdad; Mouinga-Ondémé, Augustin; Lekana-Douki-Etenna, Sonia; Caron, Mélanie; Makuwa, Maria; Mahieux, Renaud; Gessain, Antoine

    2015-02-01

    Of 78 Gabonese individuals who had received bites from nonhuman primates (NHPs) while hunting, 7 were infected with human T lymphotropic virus (HTLV-1). Five had been bitten by gorillas and were infected with subtype B strains; however, a 12-year-old girl who was severely bitten by a Cercopithecus nictitans was infected with a subtype D strain that was closely related to the simian T lymphotropic virus (STLV-1) that infects this monkey species. Her mother was infected with a subtype B strain. These data confirm that hunters in Africa can be infected by HTLV-1 that is closely related to the strains circulating among local NHP game. Our findings strongly suggest that a severe bite represent a risk factor for STLV-1 acquisition. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Variational divergence in wave scattering theory with Kirchhoffean trial functions

    Science.gov (United States)

    Bird, J. F.

    1986-01-01

    In a recent study of variational improvement of the Kirchhoff approximation for electromagnetic scattering by rough surfaces, a key ingredient in the variational principle was found to diverge for important configurations (e.g., backscatter) if the polarization had any vertical component. The cause and a cure of this divergence are discussed here. The divergence is demonstrated to occur for arbitrary perfectly conducting scatterers and its universal characterstics are determined, by means of a general divergence criterion that is derived. A variational cure for the divergence is prescribed, and it is tested successfully on a standard scattering model.

  20. Targeting α4β7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection.

    Science.gov (United States)

    Byrareddy, Siddappa N; Kallam, Brianne; Arthos, James; Cicala, Claudia; Nawaz, Fatima; Hiatt, Joseph; Kersh, Ellen N; McNicholl, Janet M; Hanson, Debra; Reimann, Keith A; Brameier, Markus; Walter, Lutz; Rogers, Kenneth; Mayne, Ann E; Dunbar, Paul; Villinger, Tara; Little, Dawn; Parslow, Tristram G; Santangelo, Philip J; Villinger, Francois; Fauci, Anthony S; Ansari, Aftab A

    2014-12-01

    α4β7 integrin-expressing CD4(+) T cells preferentially traffic to gut-associated lymphoid tissue (GALT) and have a key role in HIV and simian immunodeficiency virus (SIV) pathogenesis. We show here that the administration of an anti-α4β7 monoclonal antibody just prior to and during acute infection protects rhesus macaques from transmission following repeated low-dose intravaginal challenges with SIVmac251. In treated animals that became infected, the GALT was significantly protected from infection and CD4(+) T cell numbers were maintained in both the blood and the GALT. Thus, targeting α4β7 reduces mucosal transmission of SIV in macaques.

  1. Tolerance to Chronic Delta-9-Tetrahydrocannabinol (Δ9-THC) in Rhesus Macaques Infected With Simian Immunodeficiency Virus

    Science.gov (United States)

    Winsauer, Peter J.; Molina, Patricia E.; Amedee, Angela M.; Filipeanu, Catalin M.; McGoey, Robin R.; Troxclair, Dana A.; Walker, Edith M.; Birke, Leslie L.; Stouwe, Curtis Vande; Howard, Jessica M.; Leonard, Stuart T.; Moerschbaecher, Joseph M.; Lewis, Peter B.

    2011-01-01

    Although Δ9-THC has been approved to treat anorexia and weight loss associated with AIDS, it may also reduce well-being by disrupting complex behavioral processes or enhancing HIV replication. To investigate these possibilities, four groups of male rhesus macaques were trained to respond under an operant acquisition and performance procedure, and administered vehicle or Δ9-THC before and after inoculation with simian immunodeficiency virus(SIVmac251, 100 TCID50/ml, i.v.). Prior to chronic Δ9-THC and SIV inoculation, 0.032– 0.32 mg/kg of Δ9-THC produced dose-dependent rate-decreasing effects and small, sporadic error-increasing effects in the acquisition and performance components in each subject. Following 28 days of chronic Δ9-THC (0.32 mg/kg, i.m.) or vehicle twice daily, delta-9-THC-treated subjects developed tolerance to the rate-decreasing effects, and this tolerance was maintained during the initial 7–12 months irrespective of SIV infection (i.e., +THC/−SIV, +THC/+SIV). Full necropsy was performed on all SIV subjects an average of 329 days post-SIV inoculation, with postmortem histopathology suggestive of a reduced frequency of CNS pathology as well as opportunistic infections in delta-9-THC-treated subjects. Chronic Δ9-THC also significantly reduced CB-1 and CB-2 receptor levels in the hippocampus, attenuated the expression of a proinflammatory cytokine (MCP-1), and did not increase viral load in plasma, cerebrospinal fluid, or brain tissue compared to vehicle-treated subjects with SIV. Together, these data indicate that chronic Δ9-THC produces tolerance to its behaviorally disruptive effects on complex tasks while not adversely affecting viral load or other markers of disease progression during the early stages of infection. PMID:21463073

  2. Detection of polyomavirus simian virus 40 tumor antigen DNA in AIDS-related systemic non-Hodgkin lymphoma

    Science.gov (United States)

    Vilchez, Regis A.; Lednicky, John A.; Halvorson, Steven J.; White, Zoe S.; Kozinetz, Claudia A.; Butel, Janet S.

    2002-01-01

    Systemic non-Hodgkin lymphoma (S-NHL) is a common malignancy during HIV infection, and it is hypothesized that infectious agents may be involved in the etiology. Epstein-Barr virus DNA is found in <40% of patients with AIDS-related S-NHL, suggesting that other oncogenic viruses, such as polyomaviruses, may play a role in pathogenesis. We analyzed AIDS-related S-NHL samples, NHL samples from HIV-negative patients, peripheral blood leukocytes from HIV-infected and -uninfected patients without NHL, and lymph nodes without tumors from HIV-infected patients. Specimens were examined by polymerase chain reaction analysis with use of primers specific for an N-terminal region of the oncoprotein large tumor antigen ( T-ag ) gene conserved among all three polyomaviruses (simian virus 40 [SV40], JC virus, and BK virus). Polyomavirus T-ag DNA sequences, proven to be SV40-specific, were detected more frequently in AIDS-related S-NHL samples (6 of 26) than in peripheral blood leukocytes from HIV-infected patients (6 of 26 vs. 0 of 69; p =.0001), NHL samples from HIV-negative patients (6 of 26 vs. 0 of 10; p =.09), or lymph nodes (6 of 26 vs. 0 of 7; p =.16). Sequences of C-terminal T-ag DNA from SV40 were amplified from two AIDS-related S-NHL samples. Epstein-Barr virus DNA sequences were detected in 38% (10 of 26) AIDS-related S-NHL samples, 50% (5 of 10) HIV-negative S-NHL samples, and 57% (4 of 7) lymph nodes. None of the S-NHL samples were positive for both Epstein-Barr virus DNA and SV40 DNA. Further studies of the possible role of SV40 in the pathogenesis of S-NHL are warranted.

  3. Caffeine toxicity is inversely related to DNA repair in simian virus 40-transformed xeroderma pigmentosum cells irradiated with ultraviolet light

    International Nuclear Information System (INIS)

    Cleaver, J.E.

    1989-01-01

    Human cells transformed by simian virus 40 (SV40) are more sensitive to killing by ultraviolet light when grown in caffeine after irradiation. The degree of sensitization at 2 mM caffeine (expressed as the ratio of the 37% survival dose for control cells divided by the 37% survival dose for cells grown in caffeine, i.e., the dose modification factor) was approximately 1.9 in transformed normal cells and 3.8-5.8 in excision-defective xeroderma pigmentosum (XP) groups A, C, and D cells. A large dose modification factor of 12 was observed in a transformed XP variant cell line. Chinese hamster ovary cells were not significantly different from transformed normal human cells, with a maximum dose modification factor of 1.5. Two radioresistant XP revertants that do not excise cyclobutane dimers gave different responses; one resembled its group A parent in being sensitized by caffeine, and one did not. These results can be interpreted on the basis of a single hypothesis that cells are killed as a result of attempts to replicate damaged DNA. Increased replication rates caused by transformation, increased numbers of replication forks in DNA caused by caffeine, and increased numbers of damaged sites ahead of replication forks in excision-defective cells are all processes that will consequently increase killing according to this hypothesis. A corollary is that the XP variant may be highly sensitized to caffeine because of excision defects at the DNA replication forks, an idea that may be important in designing cloning strategies for the XP variant gene

  4. Caffeine toxicity is inversely related to DNA repair in simian virus 40-transformed xeroderma pigmentosum cells irradiated with ultraviolet light

    Energy Technology Data Exchange (ETDEWEB)

    Cleaver, J.E. (Univ. of California, San Francisco (USA))

    1989-01-01

    Human cells transformed by simian virus 40 (SV40) are more sensitive to killing by ultraviolet light when grown in caffeine after irradiation. The degree of sensitization at 2 mM caffeine (expressed as the ratio of the 37% survival dose for control cells divided by the 37% survival dose for cells grown in caffeine, i.e., the dose modification factor) was approximately 1.9 in transformed normal cells and 3.8-5.8 in excision-defective xeroderma pigmentosum (XP) groups A, C, and D cells. A large dose modification factor of 12 was observed in a transformed XP variant cell line. Chinese hamster ovary cells were not significantly different from transformed normal human cells, with a maximum dose modification factor of 1.5. Two radioresistant XP revertants that do not excise cyclobutane dimers gave different responses; one resembled its group A parent in being sensitized by caffeine, and one did not. These results can be interpreted on the basis of a single hypothesis that cells are killed as a result of attempts to replicate damaged DNA. Increased replication rates caused by transformation, increased numbers of replication forks in DNA caused by caffeine, and increased numbers of damaged sites ahead of replication forks in excision-defective cells are all processes that will consequently increase killing according to this hypothesis. A corollary is that the XP variant may be highly sensitized to caffeine because of excision defects at the DNA replication forks, an idea that may be important in designing cloning strategies for the XP variant gene.

  5. Topical tenofovir protects against vaginal simian HIV infection in macaques coinfected with Chlamydia trachomatis and Trichomonas vaginalis.

    Science.gov (United States)

    Makarova, Natalia; Henning, Tara; Taylor, Andrew; Dinh, Chuong; Lipscomb, Jonathan; Aubert, Rachael; Hanson, Debra; Phillips, Christi; Papp, John; Mitchell, James; McNicholl, Janet; Garcia-Lerma, Gerardo J; Heneine, Walid; Kersh, Ellen; Dobard, Charles

    2017-03-27

    Chlamydia trachomatis and Trichomonas vaginalis, two prevalent sexually transmitted infections, are known to increase HIV risk in women and could potentially diminish preexposure prophylaxis efficacy, particularly for topical interventions that rely on local protection. We investigated in macaques whether coinfection with Chlamydia trachomatis/Trichomonas vaginalis reduces protection by vaginal tenofovir (TFV) gel. Vaginal TFV gel dosing previously shown to provide 100 or 74% protection when applied either 30 min or 3 days before simian HIV(SHIV) challenge was assessed in pigtailed macaques coinfected with Chlamydia trachomatis/Trichomonas vaginalis and challenged twice weekly with SHIV162p3 for up to 10 weeks (two menstrual cycles). Three groups of six macaques received either placebo or 1% TFV gel 30 min or 3 days before each SHIV challenge. We additionally assessed TFV and TFV diphosphate concentrations in plasma and vaginal tissues in Chlamydia trachomatis/Trichomonas vaginalis coinfected (n = 4) and uninfected (n = 4) macaques. Chlamydia trachomatis/Trichomonas vaginalis coinfections were maintained during the SHIV challenge period. All macaques that received placebo gel were SHIV infected after a median of seven challenges (one menstrual cycle). In contrast, no infections were observed in macaques treated with TFV gel 30 min before SHIV challenge (P vaginal lymphocytes were significantly higher in Chlamydia trachomatis/Trichomonas vaginalis coinfected compared with Chlamydia trachomatis/Trichomonas vaginalis uninfected macaques. Our findings in this model suggest that Chlamydia trachomatis/Trichomonas vaginalis coinfection may have little or no impact on the efficacy of highly effective topical TFV modalities and highlight a significant modulation of TFV pharmacokinetics.

  6. The Eurozone Dynamic Cohesion: Convergence or Divergence

    Directory of Open Access Journals (Sweden)

    Antonin Rusek

    2013-08-01

    Full Text Available The long term economic dynamics of the Eurozone’s original 12 countries (Greece, Italy, Spain, Portugal, Ireland, Germany, Netherlands, Luxembourg, Belgium, Austria, Finland, France is analyzed and compared. It is today increasingly recognized that the diverging competitiveness between the Eurozone members is at the root of the current crisis. But the competitiveness dynamics and its impact on the crucial fiscal and financial variables during the common currency existence is seldom analyzed and compared, especially as far as the different groups of countries (and/or different areas within the Eurozone are concerned.

  7. Diverging patterns with endogenous labor migration.

    Science.gov (United States)

    Reichlin, P; Rustichini, A

    1998-05-05

    "The standard neoclassical model cannot explain persistent migration flows and lack of cross-country convergence when capital and labor are mobile. Here we present a model where both phenomena may take place.... Our model is based on the Arrow-Romer approach to endogenous growth theory. We single out the importance of a (however weak) scale effect from the size of the workforce.... The main conclusion of this simple model is that lack of convergence, or even divergence, among countries is possible, even with perfect capital mobility and labor mobility." excerpt

  8. Projection Pursuit Through ϕ-Divergence Minimisation

    Directory of Open Access Journals (Sweden)

    Jacques Touboul

    2010-06-01

    Full Text Available In his 1985 article (“Projection pursuit”, Huber demonstrates the interest of his method to estimate a density from a data set in a simple given case. He considers the factorization of density through a Gaussian component and some residual density. Huber’s work is based on maximizing Kullback–Leibler divergence. Our proposal leads to a new algorithm. Furthermore, we will also consider the case when the density to be factorized is estimated from an i.i.d. sample. We will then propose a test for the factorization of the estimated density. Applications include a new test of fit pertaining to the elliptical copulas.

  9. Divergence-based tests for model diagnostic

    Czech Academy of Sciences Publication Activity Database

    Hobza, Tomáš; Esteban, M. D.; Morales, D.; Marhuenda, Y.

    2008-01-01

    Roč. 78, č. 13 (2008), s. 1702-1710 ISSN 0167-7152 R&D Projects: GA MŠk 1M0572 Grant - others:Instituto Nacional de Estadistica (ES) MTM2006-05693 Institutional research plan: CEZ:AV0Z10750506 Keywords : goodness of fit * devergence statistics * GLM * model checking * bootstrap Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 0.445, year: 2008 http://library.utia.cas.cz/separaty/2008/SI/hobza-divergence-based%20tests%20for%20model%20diagnostic.pdf

  10. Diverging expectations in buyer-seller relationships

    DEFF Research Database (Denmark)

    Andersen, Poul Houman; Christensen, Poul Rind; Damgaard, Torben

    2009-01-01

    Many firms assume that outsourcing partnerships may allow them to strengthen their overall competitiveness. Lured by its intuitive appeal, several enter into such partnerships, only to realize that they represent a marginal rather than a magical solution to their quest for increasing market...... SMEs. We discuss four relational expectations derived from the B2B literature on relational norms for addressing these divergences: Quality, frequency and scope of communication, role specifications and coordination of work nature of planning horizons, and trustworthiness and link these to relationship...

  11. World health inequality: convergence, divergence, and development.

    Science.gov (United States)

    Clark, Rob

    2011-02-01

    Recent studies characterize the last half of the twentieth century as an era of cross-national health convergence, with some attributing welfare gains in the developing world to economic growth. In this study, I examine the extent to which welfare outcomes have actually converged and the extent to which economic development is responsible for the observed trends. Drawing from estimates covering 195 nations during the 1955-2005 period, I find that life expectancy averages converged during this time, but that infant mortality rates continuously diverged. I develop a narrative that implicates economic development in these contrasting trends, suggesting that health outcomes follow a "welfare Kuznets curve." Among poor countries, economic development improves life expectancy more than it reduces infant mortality, whereas the situation is reversed among wealthier nations. In this way, development has contributed to both convergence in life expectancy and divergence in infant mortality. Drawing from 674 observations across 163 countries during the 1980-2005 period, I find that the positive effect of GDP PC on life expectancy attenuates at higher levels of development, while the negative effect of GDP PC on infant mortality grows stronger. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Growth divergence: a challenging opportunity for dendrochronology

    Science.gov (United States)

    Buras, Allan; Sass-Klaassen, Ute; Wilmking, Martin

    2017-04-01

    Dendrochronology is an essential cornerstone of paleoclimatology and the evaluation of climate change impacts on forest ecosystems. However, a growing body of literature indicates that the standard dendrochronological approach may too rigorously neglect individualistic tree-growth (e.g. Wilmking et al., 2004, Buras et al., 2016). Amongst others, these studies showed convincing evidence that individual trees of the same species sampled at one site expressed different long-term growth patterns and therefore differing climate-growth relationships. This phenomenon is commonly termed growth divergence (GD) and possibly weakens our ability to correctly estimate past climate variability as discussed in the context of the so-called divergence phenomenon (D'Arrigo et al., 2008). In this context, climate change may naturally select for trees on the stand-level which are better adapted to future conditions. Although GD has been reported for several sites, the standard dendrochronological approach yet does not consider the existence of GD. A possible reason for this methodological persistence is the lack of detailed information on the frequency, magnitude, and impact of GD occurrence. To assess GD occurrence and related tree-individual variations in climate-growth response we conducted a global GD study by using 134 ring-width data representing 52 tree species and 16 genera distributed over 115 sites across 22 countries. Our analyses clearly reveal GD to be a common phenomenon as occurring in 85 % of all sites. GD was clearly related to the degree of tree-individual differences in climate-growth response. Respective transfer functions which appropriately accounted for GD by selection of tree-cohorts with a high share of long-term variance on average increased the precision and stability of tree-ring based climate reconstructions. Concluding, incorporation of GD assessments into the dendrochronological approach has a strong potential to improve the precision of our predictions

  13. A Separation between Divergence and Holevo Information for Ensembles

    OpenAIRE

    Jain, Rahul; Nayak, Ashwin; Su, Yi

    2007-01-01

    The notion of divergence information of an ensemble of probability distributions was introduced by Jain, Radhakrishnan, and Sen in the context of the ``substate theorem''. Since then, divergence has been recognized as a more natural measure of information in several situations in quantum and classical communication. We construct ensembles of probability distributions for which divergence information may be significantly smaller than the more standard Holevo information. As a result, we establ...

  14. Exact cancellation of quadratic divergences in top condensation models

    International Nuclear Information System (INIS)

    Blumhofer, A.

    1995-01-01

    We discuss the hierarchy problem and the corresponding quadratic divergences in the top mode Standard Model. Quadratic divergences appear at each order 1/N c since fermionic and bosonic contributions are of different order 1/N c . It is shown that the full dynamical system to all orders in 1/N c admits a solution, where the sum of all quadratic divergent contributions disappears. ((orig.))

  15. Culturally divergent responses to mortality salience.

    Science.gov (United States)

    Ma-Kellams, Christine; Blascovich, Jim

    2011-08-01

    Two experiments compared the effects of death thoughts, or mortality salience, on European and Asian Americans. Research on terror management theory has demonstrated that in Western cultural groups, individuals typically employ self-protective strategies in the face of death-related thoughts. Given fundamental East-West differences in self-construal (i.e., the independent vs. interdependent self), we predicted that members of Eastern cultural groups would affirm other people, rather than defend and affirm the self, after encountering conditions of mortality salience. We primed European Americans and Asian Americans with either a death or a control prime and examined the effect of this manipulation on attitudes about a person who violates cultural norms (Study 1) and on attributions about the plight of an innocent victim (Study 2). Mortality salience promoted culturally divergent responses, leading European Americans to defend the self and Asian Americans to defend other people.

  16. Process model simulations of the divergence effect

    Science.gov (United States)

    Anchukaitis, K. J.; Evans, M. N.; D'Arrigo, R. D.; Smerdon, J. E.; Hughes, M. K.; Kaplan, A.; Vaganov, E. A.

    2007-12-01

    We explore the extent to which the Vaganov-Shashkin (VS) model of conifer tree-ring formation can explain evidence for changing relationships between climate and tree growth over recent decades. The VS model is driven by daily environmental forcing (temperature, soil moisture, and solar radiation), and simulates tree-ring growth cell-by-cell as a function of the most limiting environmental control. This simplified representation of tree physiology allows us to examine using a selection of case studies whether instances of divergence may be explained in terms of changes in limiting environmental dependencies or transient climate change. Identification of model-data differences permits further exploration of the effects of tree-ring standardization, atmospheric composition, and additional non-climatic factors.

  17. Hamiltonian mechanics and divergence-free fields

    International Nuclear Information System (INIS)

    Boozer, A.H.

    1986-08-01

    The field lines, or integral curves, of a divergence-free field in three dimensions are shown to be topologically equivalent to the trajectories of a Hamiltonian with two degrees of freedom. The consideration of fields that depend on a parameter allow the construction of a canonical perturbation theory which is valid even if the perturbation is large. If the parametric dependence of the magnetic, or the vorticity field is interpreted as time dependence, evolution equations are obtained which give Kelvin's theorem or the flux conservation theorem for ideal fluids and plasmas. The Hamiltonian methods prove especially useful for study of fields in which the field lines must be known throughout a volume of space

  18. Some Divergence Properties of Asset Price Models

    Directory of Open Access Journals (Sweden)

    Wolfgang Stummer

    2001-12-01

    Full Text Available Abstract: We consider asset price processes Xt which are weak solutions of one-dimensional stochastic differential equations of the form (equation (2 Such price models can be interpreted as non-lognormally-distributed generalizations of the geometric Brownian motion. We study properties of the Iα-divergence between the law of the solution Xt and the corresponding drift-less measure (the special case α=1 is the relative entropy. This will be applied to some context in statistical information theory as well as to arbitrage theory and contingent claim valuation. For instance, the seminal option pricing theorems of Black-Scholes and Merton appear as a special case.

  19. DIVERGING DISCOURSES ON THE SYR DARYA

    Directory of Open Access Journals (Sweden)

    Eelke Kraak

    2012-01-01

    Full Text Available The hydraulic mission of the Soviet Union has transformed Central Asia’s Syr Darya River into a governable entity. After the dissolution of the Soviet Union the river system disintegrated and conflict arose over the operation of the main dam and reservoir of the river: the Toktogul. Uzbekistan and Kyrgyzstan have widely different and diverging sanctioned discourses on how the dam should be operated and on the nature of the water itself. These discourses have had a significant impact on the hydro-politics of the river basin and the operation of the dam. The central argument of this paper is that both the decline of the Aral Sea, and the potential conflict between the states are driven by the same modernist governmentality of the river.

  20. Divergent clonal selection dominates medulloblastoma at recurrence

    Science.gov (United States)

    Morrissy, A. Sorana; Garzia, Livia; Shih, David J. H.; Zuyderduyn, Scott; Huang, Xi; Skowron, Patryk; Remke, Marc; Cavalli, Florence M. G.; Ramaswamy, Vijay; Lindsay, Patricia E.; Jelveh, Salomeh; Donovan, Laura K.; Wang, Xin; Luu, Betty; Zayne, Kory; Li, Yisu; Mayoh, Chelsea; Thiessen, Nina; Mercier, Eloi; Mungall, Karen L.; Ma, Yusanne; Tse, Kane; Zeng, Thomas; Shumansky, Karey; Roth, Andrew J. L.; Shah, Sohrab; Farooq, Hamza; Kijima, Noriyuki; Holgado, Borja L.; Lee, John J. Y.; Matan-Lithwick, Stuart; Liu, Jessica; Mack, Stephen C.; Manno, Alex; Michealraj, K. A.; Nor, Carolina; Peacock, John; Qin, Lei; Reimand, Juri; Rolider, Adi; Thompson, Yuan Y.; Wu, Xiaochong; Pugh, Trevor; Ally, Adrian; Bilenky, Mikhail; Butterfield, Yaron S. N.; Carlsen, Rebecca; Cheng, Young; Chuah, Eric; Corbett, Richard D.; Dhalla, Noreen; He, An; Lee, Darlene; Li, Haiyan I.; Long, William; Mayo, Michael; Plettner, Patrick; Qian, Jenny Q.; Schein, Jacqueline E.; Tam, Angela; Wong, Tina; Birol, Inanc; Zhao, Yongjun; Faria, Claudia C.; Pimentel, José; Nunes, Sofia; Shalaby, Tarek; Grotzer, Michael; Pollack, Ian F.; Hamilton, Ronald L.; Li, Xiao-Nan; Bendel, Anne E.; Fults, Daniel W.; Walter, Andrew W.; Kumabe, Toshihiro; Tominaga, Teiji; Collins, V. Peter; Cho, Yoon-Jae; Hoffman, Caitlin; Lyden, David; Wisoff, Jeffrey H.; Garvin, James H.; Stearns, Duncan S.; Massimi, Luca; Schüller, Ulrich; Sterba, Jaroslav; Zitterbart, Karel; Puget, Stephanie; Ayrault, Olivier; Dunn, Sandra E.; Tirapelli, Daniela P. C.; Carlotti, Carlos G.; Wheeler, Helen; Hallahan, Andrew R.; Ingram, Wendy; MacDonald, Tobey J.; Olson, Jeffrey J.; Van Meir, Erwin G.; Lee, Ji-Yeoun; Wang, Kyu-Chang; Kim, Seung-Ki; Cho, Byung-Kyu; Pietsch, Torsten; Fleischhack, Gudrun; Tippelt, Stephan; Ra, Young Shin; Bailey, Simon; Lindsey, Janet C.; Clifford, Steven C.; Eberhart, Charles G.; Cooper, Michael K.; Packer, Roger J.; Massimino, Maura; Garre, Maria Luisa; Bartels, Ute; Tabori, Uri; Hawkins, Cynthia E.; Dirks, Peter; Bouffet, Eric; Rutka, James T.; Wechsler-Reya, Robert J.; Weiss, William A.; Collier, Lara S.; Dupuy, Adam J.; Korshunov, Andrey; Jones, David T. W.; Kool, Marcel; Northcott, Paul A.; Pfister, Stefan M.; Largaespada, David A.; Mungall, Andrew J.; Moore, Richard A.; Jabado, Nada; Bader, Gary D.; Jones, Steven J. M.; Malkin, David; Marra, Marco A.; Taylor, Michael D.

    2016-01-01

    The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon–driven, functional genomic mouse model of medulloblastoma with ‘humanized’ in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy. PMID:26760213

  1. Differential Impact of In Vivo CD8+ T Lymphocyte Depletion in Controller versus Progressor Simian Immunodeficiency Virus-Infected Macaques.

    Science.gov (United States)

    Chowdhury, Ankita; Hayes, Timothy L; Bosinger, Steven E; Lawson, Benton O; Vanderford, Thomas; Schmitz, Joern E; Paiardini, Mirko; Betts, Michael; Chahroudi, Ann; Estes, Jacob D; Silvestri, Guido

    2015-09-01

    Numerous studies have demonstrated that CD8(+) T lymphocytes suppress virus replication during human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection. However, the mechanisms underlying this activity of T cells remain incompletely understood. Here, we conducted CD8(+) T lymphocyte depletion in 15 rhesus macaques (RMs) infected intravenously (i.v.) with SIVmac239. At day 70 postinfection, the animals (10 progressors with high viremia and 5 controllers with low viremia) were CD8 depleted by i.v. administration of the antibody M-T807R1. As expected, CD8 depletion resulted in increased virus replication, more prominently in controllers than progressors, which correlated inversely with predepletion viremia. Of note, the feature of CD8(+) T lymphocyte predepletion that correlated best with the increase in viremia postdepletion was the level of CD8(+) T-bet(+) lymphocytes. We next found that CD8 depletion resulted in a homogenous increase of SIV RNA in superficial and mesenteric lymph nodes, spleen, and the gastrointestinal tract of both controllers and progressors. Interestingly, the level of SIV DNA increased postdepletion in both CD4(+) central memory T lymphocytes (TCM) and CD4(+) effector memory T lymphocytes (TEM) in progressor RMs but decreased in the CD4(+) TCM of 4 out of 5 controllers. Finally, we found that CD8 depletion is associated with a greater increase in CD4(+) T lymphocyte activation (measured by Ki-67 expression) in controllers than in progressors. Overall, these data reveal a differential impact of CD8(+) T lymphocyte depletion between controller and progressor SIV-infected RMs, emphasizing the complexity of the in vivo antiviral role of CD8(+) T lymphocytes. In this study, we further dissect the impact of CD8(+) T lymphocytes on HIV/SIV replication during SIV infection. CD8(+) T lymphocyte depletion leads to a relatively homogenous increase in viral replication in peripheral blood and tissues. CD8(+) T lymphocyte depletion

  2. Detection of Simian Immunodeficiency Virus in Semen, Urethra, and Male Reproductive Organs during Efficient Highly Active Antiretroviral Therapy

    Science.gov (United States)

    Matusali, G.; Dereuddre-Bosquet, N.; Le Tortorec, A.; Moreau, M.; Satie, A.-P.; Mahé, D.; Roumaud, P.; Bourry, O.; Sylla, N.; Bernard-Stoecklin, S.; Pruvost, A.; Le Grand, R.

    2015-01-01

    ABSTRACT A number of men receiving prolonged suppressive highly active antiretroviral therapy (HAART) still shed human immunodeficiency virus (HIV) in semen. To investigate whether this seminal shedding may be due to poor drug penetration and/or viral production by long-lived cells within male genital tissues, we analyzed semen and reproductive tissues from macaques chronically infected with simian immunodeficiency virus mac251 (SIVmac251) who were treated for 4 months with HAART, which was intensified over the last 7 weeks with an integrase inhibitor. We showed that a subset of treated animals continued shedding SIV in semen despite efficient HAART. This shedding was not associated with low antiretroviral drug concentrations in semen or in testis, epididymis, seminal vesicles, and prostate. HAART had no significant impact on SIV RNA in the urethra, whereas it drastically reduced SIV RNA levels in the prostate and vas deferens and to a lesser extent in the epididymis and seminal vesicle. The only detectable SIV RNA-positive cells within the male genital tract after HAART were urethral macrophages. SIV DNA levels in genital tissues were not decreased by HAART, suggesting the presence throughout the male genital tract of nonproductively infected cells. In conclusion, our results demonstrate that 4 months of HAART induced variable and limited control of viral infection in the male reproductive organs, particularly in the urethra, and suggest that infected long-lived cells in the male genital tract may be involved in persistent seminal shedding during HAART. These results pave the way for further investigations of male genital organ infection in long-term-treated infected individuals. IMPORTANCE A substantial subset of men receiving prolonged HAART suppressing viral loads in the blood still harbor HIV in semen, and cases of sexual transmission have been reported. To understand the origin of this persistence, we analyzed the semen and male reproductive tissues from SIV

  3. Structure of Simian Immunodeficiency Virus Envelope Spikes Bound with CD4 and Monoclonal Antibody 36D5.

    Science.gov (United States)

    Hu, Guiqing; Liu, Jun; Roux, Kenneth H; Taylor, Kenneth A

    2017-08-15

    The human immunodeficiency virus type 1 (HIV-1)/simian immunodeficiency virus (SIV) envelope spike (Env) mediates viral entry into host cells. The V3 loop of the gp120 component of the Env trimer contributes to the coreceptor binding site and is a target for neutralizing antibodies. We used cryo-electron tomography to visualize the binding of CD4 and the V3 loop monoclonal antibody (MAb) 36D5 to gp120 of the SIV Env trimer. Our results show that 36D5 binds gp120 at the base of the V3 loop and suggest that the antibody exerts its neutralization effect by blocking the coreceptor binding site. The antibody does this without altering the dynamics of the spike motion between closed and open states when CD4 is bound. The interaction between 36D5 and SIV gp120 is similar to the interaction between some broadly neutralizing anti-V3 loop antibodies and HIV-1 gp120. Two conformations of gp120 bound with CD4 are revealed, suggesting an intrinsic dynamic nature of the liganded Env trimer. CD4 binding substantially increases the binding of 36D5 to gp120 in the intact Env trimer, consistent with CD4-induced changes in the conformation of gp120 and the antibody binding site. Binding by MAb 36D5 does not substantially alter the proportions of the two CD4-bound conformations. The position of MAb 36D5 at the V3 base changes little between conformations, indicating that the V3 base serves as a pivot point during the transition between these two states. IMPORTANCE Glycoprotein spikes on the surfaces of SIV and HIV are the sole targets available to the immune system for antibody neutralization. Spikes evade the immune system by a combination of a thick layer of polysaccharide on the surface (the glycan shield) and movement between spike domains that masks the epitope conformation. Using SIV virions whose spikes were "decorated" with the primary cellular receptor (CD4) and an antibody (36D5) at part of the coreceptor binding site, we visualized multiple conformations trapped by the

  4. Reconstitution of wild type viral DNA in simian cells transfected with early and late SV40 defective genomes.

    Science.gov (United States)

    O'Neill, F J; Gao, Y; Xu, X

    1993-11-01

    The DNAs of polyomaviruses ordinarily exist as a single circular molecule of approximately 5000 base pairs. Variants of SV40, BKV and JCV have been described which contain two complementing defective DNA molecules. These defectives, which form a bipartite genome structure, contain either the viral early region or the late region. The defectives have the unique property of being able to tolerate variable sized reiterations of regulatory and terminus region sequences, and portions of the coding region. They can also exchange coding region sequences with other polyomaviruses. It has been suggested that the bipartite genome structure might be a stage in the evolution of polyomaviruses which can uniquely sustain genome and sequence diversity. However, it is not known if the regulatory and terminus region sequences are highly mutable. Also, it is not known if the bipartite genome structure is reversible and what the conditions might be which would favor restoration of the monomolecular genome structure. We addressed the first question by sequencing the reiterated regulatory and terminus regions of E- and L-SV40 DNAs. This revealed a large number of mutations in the regulatory regions of the defective genomes, including deletions, insertions, rearrangements and base substitutions. We also detected insertions and base substitutions in the T-antigen gene. We addressed the second question by introducing into permissive simian cells, E- and L-SV40 genomes which had been engineered to contain only a single regulatory region. Analysis of viral DNA from transfected cells demonstrated recombined genomes containing a wild type monomolecular DNA structure. However, the complete defectives, containing reiterated regulatory regions, could often compete away the wild type genomes. The recombinant monomolecular genomes were isolated, cloned and found to be infectious. All of the DNA alterations identified in one of the regulatory regions of E-SV40 DNA were present in the recombinant

  5. Using Dendritic Heat Maps to Simultaneously Display Genotype Divergence with Phenotype Divergence.

    Science.gov (United States)

    Kellom, Matthew; Raymond, Jason

    2016-01-01

    The advancement of techniques to visualize and analyze large-scale sequencing datasets is an area of active research and is rooted in traditional techniques such as heat maps and dendrograms. We introduce dendritic heat maps that display heat map results over aligned DNA sequence clusters for a range of clustering cutoffs. Dendritic heat maps aid in visualizing the effects of group differences on clustering hierarchy and relative abundance of sampled sequences. Here, we artificially generate two separate datasets with simplified mutation and population growth procedures with GC content group separation to use as example phenotypes. In this work, we use the term phenotype to represent any feature by which groups can be separated. These sequences were clustered in a fractional identity range of 0.75 to 1.0 using agglomerative minimum-, maximum-, and average-linkage algorithms, as well as a divisive centroid-based algorithm. We demonstrate that dendritic heat maps give freedom to scrutinize specific clustering levels across a range of cutoffs, track changes in phenotype inequity across multiple levels of sequence clustering specificity, and easily visualize how deeply rooted changes in phenotype inequity are in a dataset. As genotypes diverge in sample populations, clusters are shown to break apart into smaller clusters at higher identity cutoff levels, similar to a dendrogram. Phenotype divergence, which is shown as a heat map of relative abundance bin response, may or may not follow genotype divergences. This joined view highlights the relationship between genotype and phenotype divergence for treatment groups. We discuss the minimum-, maximum-, average-, and centroid-linkage algorithm approaches to building dendritic heat maps and make a case for the divisive "top-down" centroid-based clustering methodology as being the best option visualize the effects of changing factors on clustering hierarchy and relative abundance.

  6. Using Dendritic Heat Maps to Simultaneously Display Genotype Divergence with Phenotype Divergence.

    Directory of Open Access Journals (Sweden)

    Matthew Kellom

    Full Text Available The advancement of techniques to visualize and analyze large-scale sequencing datasets is an area of active research and is rooted in traditional techniques such as heat maps and dendrograms. We introduce dendritic heat maps that display heat map results over aligned DNA sequence clusters for a range of clustering cutoffs. Dendritic heat maps aid in visualizing the effects of group differences on clustering hierarchy and relative abundance of sampled sequences. Here, we artificially generate two separate datasets with simplified mutation and population growth procedures with GC content group separation to use as example phenotypes. In this work, we use the term phenotype to represent any feature by which groups can be separated. These sequences were clustered in a fractional identity range of 0.75 to 1.0 using agglomerative minimum-, maximum-, and average-linkage algorithms, as well as a divisive centroid-based algorithm. We demonstrate that dendritic heat maps give freedom to scrutinize specific clustering levels across a range of cutoffs, track changes in phenotype inequity across multiple levels of sequence clustering specificity, and easily visualize how deeply rooted changes in phenotype inequity are in a dataset. As genotypes diverge in sample populations, clusters are shown to break apart into smaller clusters at higher identity cutoff levels, similar to a dendrogram. Phenotype divergence, which is shown as a heat map of relative abundance bin response, may or may not follow genotype divergences. This joined view highlights the relationship between genotype and phenotype divergence for treatment groups. We discuss the minimum-, maximum-, average-, and centroid-linkage algorithm approaches to building dendritic heat maps and make a case for the divisive "top-down" centroid-based clustering methodology as being the best option visualize the effects of changing factors on clustering hierarchy and relative abundance.

  7. Testing evolutionary hypotheses for phenotypic divergence using landscape genetics.

    Science.gov (United States)

    Funk, W Chris; Murphy, Melanie A

    2010-02-01

    Understanding the evolutionary causes of phenotypic variation among populations has long been a central theme in evolutionary biology. Several factors can influence phenotypic divergence, including geographic isolation, genetic drift, divergent natural or sexual selection, and phenotypic plasticity. But the relative importance of these factors in generating phenotypic divergence in nature is still a tantalizing and unresolved problem in evolutionary biology. The origin and maintenance of phenotypic divergence is also at the root of many ongoing debates in evolutionary biology, such as the extent to which gene flow constrains adaptive divergence (Garant et al. 2007) and the relative importance of genetic drift, natural selection, and sexual selection in initiating reproductive isolation and speciation (Coyne & Orr 2004). In this issue, Wang & Summers (2010) test the causes of one of the most fantastic examples of phenotypic divergence in nature: colour pattern divergence among populations of the strawberry poison frog (Dendrobates pumilio) in Panama and Costa Rica (Fig. 1). This study provides a beautiful example of the use of the emerging field of landscape genetics to differentiate among hypotheses for phenotypic divergence. Using landscape genetic analyses, Wang & Summers were able to reject the hypotheses that colour pattern divergence is due to isolation-by-distance (IBD) or landscape resistance. Instead, the hypothesis left standing is that colour divergence is due to divergent selection, in turn driving reproductive isolation among populations with different colour morphs. More generally, this study provides a wonderful example of how the emerging field of landscape genetics, which has primarily been applied to questions in conservation and ecology, now plays an essential role in evolutionary research.

  8. Conformal anomaly and elimination of infrared divergences in curved spacetime

    International Nuclear Information System (INIS)

    Grib, A.A.; Nesteruk, A.V.; Pritomanov, S.A.

    1984-01-01

    The relation between the problem of eliminating the infrared divergences and the conformal anomaly of the regularized energy-momentum tensor is studied in homogeneous isotropic and anisotropic spacetime. It is shown that elimination of the infrared divergence by means of a cutoff or the introduction of a conformally invariant mass of the field leads to the absence of the conformal anomaly

  9. Performance analysis of alpha divergence in nonnegative matrix ...

    African Journals Online (AJOL)

    This is achieved by using a suitable cost function to determine the optimal factorization. Most work in this field has focused on the use of Euclidean and Kullback-Liebler (KL) divergence. This study looks into the use of α-divergence based non negative factorization in the context of single channel musical sound separation.

  10. Convergent and Divergent Thinking in the Context of Narrative Mysteries

    Science.gov (United States)

    Wenzel, William G.; Gerrig, Richard J.

    2015-01-01

    This project demonstrates how narrative mysteries provide a context in which readers engage in creative cognition. Drawing on the concepts of convergent and divergent thinking, we wrote stories that had either convergent or divergent outcomes. For example, one story had a character give his girlfriend a ring (a convergent outcome), whereas the…

  11. Transcriptome-wide patterns of divergence during allopatric evolution.

    Science.gov (United States)

    Pereira, Ricardo J; Barreto, Felipe S; Pierce, N Tessa; Carneiro, Miguel; Burton, Ronald S

    2016-04-01

    Recent studies have revealed repeated patterns of genomic divergence associated with species formation. Such patterns suggest that natural selection tends to target a set of available genes, but is also indicative that closely related taxa share evolutionary constraints that limit genetic variability. Studying patterns of genomic divergence among populations within the same species may shed light on the underlying evolutionary processes. Here, we examine transcriptome-wide divergence and polymorphism in the marine copepod Tigriopus californicus, a species where allopatric evolution has led to replicate sets of populations with varying degrees of divergence and hybrid incompatibility. Our analyses suggest that relatively small effective population sizes have resulted in an exponential decline of shared polymorphisms during population divergence and also facilitated the fixation of slightly deleterious mutations within allopatric populations. Five interpopulation comparisons at three different stages of divergence show that nonsynonymous mutations tend to accumulate in a specific set of proteins. These include proteins with central roles in cellular metabolism, such as those encoded in mtDNA, but also include an additional set of proteins that repeatedly show signatures of positive selection during allopatric divergence. Although our results are consistent with a contribution of nonadaptive processes, such as genetic drift and gene expression levels, generating repeatable patterns of genomic divergence in closely related taxa, they also indicate that adaptive evolution targeting a specific set of genes contributes to this pattern. Our results yield insights into the predictability of evolution at the gene level. © 2016 John Wiley & Sons Ltd.

  12. Ultraviolet divergences in 1/N expansions of quantum field theories

    International Nuclear Information System (INIS)

    Rim, C.

    1984-01-01

    For asymptotically free theories, ultraviolet divergencies computed in 1/N expansion with dimensional regularization reduces to simple poles plus powers of Inelement of or finite terms. All divergences are determined by the two loop perturbative renormalization group functions. In an infrared free theory, however, element of = 0 becomes an essential singularity in the 1/N expansion

  13. Multiloop divergences in the closed bosonic string theory

    International Nuclear Information System (INIS)

    Gava, E.; Iengo, R.; Jayaraman, T.; Ramachandran, R.

    1985-12-01

    We discuss the structure of the divergences in the multiloop vacuum diagrams for the closed bosonic strings in the framework of the Polyakov covariant formalism. We find, by an explicit computation, that all the divergences in the theory may be interpreted as due to tadpole diagrams in which the dilation goes into the vacuum. (author)

  14. Evidence of multiple divergent mitochondrial lineages within the ...

    African Journals Online (AJOL)

    On this basis, the mitochondrial cytochrome c oxidase subunit 1 (COI) was used to reconstruct the phylogeny of Bicoxidens and reveal divergent lineages within the genus. Maximum likelihood and Bayesian inference analyses recovered a paraphyletic Bicoxidens phylogram with divergent lineages present in three species ...

  15. Vorticity and divergence in the high-latitude upper thermosphere

    International Nuclear Information System (INIS)

    Thayer, J.P.; Killeen, T.L.

    1991-01-01

    Measurements made from the Dynamics Explorer-2 satellite in November 1981 through January 1982 and November 1982 through January 1983 have been analyzed to determine the divergence and vertical component of vorticity of the high-latitude neutral wind field in the upper thermosphere for quiet (kp≤6) geomagnetic conditions and for both northern (winter) and southern (summer) hemispheres in the polar thermosphere and provides insight into the relative strengths of the different sources of momentum and energy responsible for driving the winds. The principal findings from this work include the following: The mean neutral wind pattern is dominated by rotational flow rather than by divergent flow, with a typical vorticity: divergence ratio of ∼ 2:1 for active conditions and ∼ 4:1 for quiet conditions. Comparison of the divergence and vorticity patterns for quiet and active conditions indicates that the divergent component of the neutral flow intensifies more significantly with increasing geomagnetic activity than does the rotational component

  16. Escort entropies and divergences and related canonical distribution

    International Nuclear Information System (INIS)

    Bercher, J.-F.

    2011-01-01

    We discuss two families of two-parameter entropies and divergences, derived from the standard Renyi and Tsallis entropies and divergences. These divergences and entropies are found as divergences or entropies of escort distributions. Exploiting the nonnegativity of the divergences, we derive the expression of the canonical distribution associated to the new entropies and a observable given as an escort-mean value. We show that this canonical distribution extends, and smoothly connects, the results obtained in nonextensive thermodynamics for the standard and generalized mean value constraints. -- Highlights: → Two-parameter entropies are derived from q-entropies and escort distributions. → The related canonical distribution is derived. → This connects and extends known results in nonextensive statistics.

  17. One-loop divergences in the quantum theory of supergravity

    International Nuclear Information System (INIS)

    Nieuwenhuizen, P. van; Vermaseren, J.A.M.

    1976-01-01

    Supergravity does not lead to a finite quantum theory of gravitation when coupled to the spin 1, 1/2 matter multiplet. The S-matrix of photon-photon scattering diverges; its divergences are proportional to the square of the photon energy-momentum tensor, in agreement with electro-magnetic duality and chiral invariance. The graviton self-energy corrections are divergent in pure supergravity as well as in the coupled Maxwell-Einstein system and satisfy their Ward identity because the supersymmetry ghost field is commuting. The photon-graviton vertex corrections diverge, as expected from the non-invariance of the action under local scale transformations, and satisfy the equivalence principle at the quantum level. The photon self-energy is divergent. (Auth.)

  18. Active learning for noisy oracle via density power divergence.

    Science.gov (United States)

    Sogawa, Yasuhiro; Ueno, Tsuyoshi; Kawahara, Yoshinobu; Washio, Takashi

    2013-10-01

    The accuracy of active learning is critically influenced by the existence of noisy labels given by a noisy oracle. In this paper, we propose a novel pool-based active learning framework through robust measures based on density power divergence. By minimizing density power divergence, such as β-divergence and γ-divergence, one can estimate the model accurately even under the existence of noisy labels within data. Accordingly, we develop query selecting measures for pool-based active learning using these divergences. In addition, we propose an evaluation scheme for these measures based on asymptotic statistical analyses, which enables us to perform active learning by evaluating an estimation error directly. Experiments with benchmark datasets and real-world image datasets show that our active learning scheme performs better than several baseline methods. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Divergent mortality trends by ethnicity in Fiji.

    Science.gov (United States)

    Taylor, Richard; Carter, Karen; Naidu, Shivnay; Linhart, Christine; Azim, Syed; Rao, Chalapati; Lopez, Alan D

    2013-12-01

    To examine trends in infant mortality rate (IMR), adult mortality and life expectancy (LE) in the two major Fijian ethnic groups since 1975. Estimates of IMR, adult mortality (15-59 years) and LE by ethnicity are calculated from previously unreported Fiji Ministry of Health data and extracted from published sources. Over 1975-2008: IMR decreased from 33 to 20 deaths/1,000 live births in i-Taukei (Fiji Melanesians); and 38 to 18 in Fijians of Indian descent. Increased adult male mortality among i-Taukei and decline among Fijians of Indian descent led to an equal probability of dying in 2007 of 29%; while in female adults the probability trended upwards in i-Taukei to 25%, and declined in Fijians of Indian descent to 17%. Life expectancy in both ethnicities increased until 1985 (to 64 years for males; 68 for females) then forming a plateau in males of both ethnicities, and Fijian females of Indian descent, but declining in i-Taukei females to 66 years in 2007. Despite IMR declines over 1975-2008, LE for i-Taukei and Fijians of Indian descent has not increased since 1985, and has actually decreased in i-Taukei women, consistent with trends in adult mortality (15-59 years). Mortality analyses in Fiji that consider the entire population mask divergent trends in the major ethnic groups. This situation is most likely a consequence of non-communicable disease mortality, requiring further assessment and a strengthened response.

  20. On the divergences of inflationary superhorizon perturbations

    Energy Technology Data Exchange (ETDEWEB)

    Enqvist, K; Nurmi, S [Physics Department, University of Helsinki, PO Box 64, Helsinki, FIN-00014 (Finland); Podolsky, D; Rigopoulos, G I, E-mail: kari.enqvist@helsinki.fi, E-mail: sami.nurmi@helsinki.fi, E-mail: dmitry.podolsky@helsinki.fi, E-mail: gerasimos.rigopoulos@helsinki.fi [Helsinki Institute of Physics, University of Helsinki, PO Box 64, Helsinki, FIN-00014 (Finland)

    2008-04-15

    We discuss the infrared divergences that appear to plague cosmological perturbation theory. We show that, within the stochastic framework, they are regulated by eternal inflation so that the theory predicts finite fluctuations. Using the {Delta}N formalism to one loop, we demonstrate that the infrared modes can be absorbed into additive constants and the coefficients of the diagrammatic expansion for the connected parts of two-and three-point functions of the curvature perturbation. As a result, the use of any infrared cutoff below the scale of eternal inflation is permitted, provided that the background fields are appropriately redefined. The natural choice for the infrared cutoff would, of course, be the present horizon; other choices manifest themselves in the running of the correlators. We also demonstrate that it is possible to define observables that are renormalization-group-invariant. As an example, we derive a non-perturbative, infrared finite and renormalization point-independent relation between the two-point correlators of the curvature perturbation for the case of the free single field.

  1. Remarkable ancient divergences amongst neglected lorisiform primates

    Science.gov (United States)

    Nekaris, K. Anne‐Isola; Perkin, Andrew; Bearder, Simon K.; Pimley, Elizabeth R.; Schulze, Helga; Streicher, Ulrike; Nadler, Tilo; Kitchener, Andrew; Zischler, Hans; Zinner, Dietmar; Roos, Christian

    2015-01-01

    Lorisiform primates (Primates: Strepsirrhini: Lorisiformes) represent almost 10% of the living primate species and are widely distributed in sub‐Saharan Africa and South/South‐East Asia; however, their taxonomy, evolutionary history, and biogeography are still poorly understood. In this study we report the largest molecular phylogeny in terms of the number of represented taxa. We sequenced the complete mitochondrial cytochrome b gene for 86 lorisiform specimens, including ∼80% of all the species currently recognized. Our results support the monophyly of the Galagidae, but a common ancestry of the Lorisinae and Perodicticinae (family Lorisidae) was not recovered. These three lineages have early origins, with the Galagidae and the Lorisinae diverging in the Oligocene at about 30 Mya and the Perodicticinae emerging in the early Miocene. Our mitochondrial phylogeny agrees with recent studies based on nuclear data, and supports Euoticus as the oldest galagid lineage and the polyphyletic status of Galagoides. Moreover, we have elucidated phylogenetic relationships for several species never included before in a molecular phylogeny. The results obtained in this study suggest that lorisiform diversity remains substantially underestimated and that previously unnoticed cryptic diversity might be present within many lineages, thus urgently requiring a comprehensive taxonomic revision of this primate group. © 2015 The Linnean Society of London PMID:26900177

  2. Antifibrotic Therapy in Simian Immunodeficiency Virus Infection Preserves CD4+ T-Cell Populations and Improves Immune Reconstitution With Antiretroviral Therapy

    Science.gov (United States)

    Estes, Jacob D.; Reilly, Cavan; Trubey, Charles M.; Fletcher, Courtney V.; Cory, Theodore J.; Piatak, Michael; Russ, Samuel; Anderson, Jodi; Reimann, Thomas G.; Star, Robert; Smith, Anthony; Tracy, Russell P.; Berglund, Anna; Schmidt, Thomas; Coalter, Vicky; Chertova, Elena; Smedley, Jeremy; Haase, Ashley T.; Lifson, Jeffrey D.; Schacker, Timothy W.

    2015-01-01

    Even with prolonged antiretroviral therapy (ART), many human immunodeficiency virus-infected individuals have <500 CD4+ T cells/µL, and CD4+ T cells in lymphoid tissues remain severely depleted, due in part to fibrosis of the paracortical T-cell zone (TZ) that impairs homeostatic mechanisms required for T-cell survival. We therefore used antifibrotic therapy in simian immunodeficiency virus-infected rhesus macaques to determine whether decreased TZ fibrosis would improve reconstitution of peripheral and lymphoid CD4+ T cells. Treatment with the antifibrotic drug pirfenidone preserved TZ architecture and was associated with significantly larger populations of CD4+ T cells in peripheral blood and lymphoid tissues. Combining pirfenidone with an ART regimen was associated with greater preservation of CD4+ T cells than ART alone and was also associated with higher pirfenidone concentrations. These data support a potential role for antifibrotic drug treatment as adjunctive therapy with ART to improve immune reconstitution. PMID:25246534

  3. Initiation of simian virus 40 DNA replication in vitro: Pulse-chase experiments identify the first labeled species as topologically unwound

    International Nuclear Information System (INIS)

    Bullock, P.A.; Seo, Yeon Soo; Hurwitz, J.

    1989-01-01

    A distinct unwound form of DNA containing the simian virus 40 (SV40) origin is produced in replication reactions carried out in mixtures containing crude fractions prepared from HeLa cells. This species, termed form U R , comigrates on chloroquine-containing agarose gels with the upper part of the previously described heterogeneous highly unwound circular DNA, form U. As with form U, formation of form U R is dependent upon the SV40 tumor (T) antigen. Pulse-chase experiments demonstrate that the first species to incorporate labeled deoxyribonucleotides comigrates with form U R . Restriction analyses of the products of the pulse-chase experiments show that initiation occurs at the SV40 origin and then proceeds outward in a bidirectional manner. These experiments establish form U R as the earliest detectable substrate for SV40 DNA replication and suggest that SV40 DNA replication initiates on an unwound species

  4. The vertical dispersión of Anopheles (Kerteszia cruzi in a forest in southern Brazil suggests that human cases of malaria of simian origin might be expected

    Directory of Open Access Journals (Sweden)

    Leonidas M. Deane

    1984-12-01

    Full Text Available By staining females of Anopheles cruzi with fluorescent coloured powders in a forest in the State of Santa Catarina, we showed that they move from canopy to ground and vice-versa to feed. This suggests that in areas where this mosquito is a vector of human and simian malarias sporadic infections of man with monkey plasmodia might be expected.Pintando fêmeas de Anopheles cruzi com pós fluorescentes coloridos, numa floresta de Santa Catarina, mostramos que elas movimentam-se da copa ao solo e vice-versa para se alimentar de sangue. Isso sugere que em áreas onde esse mosquito for tansmissor das malárias humana e simiana pode-se esperar que ocorram infecções humanas esporádicas por plasmódios de macacos.

  5. Simian hemorrhagic fever virus cell entry is dependent on CD163 and uses a clathrin-mediated endocytosis-like pathway.

    Science.gov (United States)

    Caì, Yíngyún; Postnikova, Elena N; Bernbaum, John G; Yú, Shu Qìng; Mazur, Steven; Deiuliis, Nicole M; Radoshitzky, Sheli R; Lackemeyer, Matthew G; McCluskey, Adam; Robinson, Phillip J; Haucke, Volker; Wahl-Jensen, Victoria; Bailey, Adam L; Lauck, Michael; Friedrich, Thomas C; O'Connor, David H; Goldberg, Tony L; Jahrling, Peter B; Kuhn, Jens H

    2015-01-01

    Simian hemorrhagic fever virus (SHFV) causes a severe and almost uniformly fatal viral hemorrhagic fever in Asian macaques but is thought to be nonpathogenic for humans. To date, the SHFV life cycle is almost completely uncharacterized on the molecular level. Here, we describe the first steps of the SHFV life cycle. Our experiments indicate that SHFV enters target cells by low-pH-dependent endocytosis. Dynamin inhibitors, chlorpromazine, methyl-β-cyclodextrin, chloroquine, and concanamycin A dramatically reduced SHFV entry efficiency, whereas the macropinocytosis inhibitors EIPA, blebbistatin, and wortmannin and the caveolin-mediated endocytosis inhibitors nystatin and filipin III had no effect. Furthermore, overexpression and knockout study and electron microscopy results indicate that SHFV entry occurs by a dynamin-dependent clathrin-mediated endocytosis-like pathway. Experiments utilizing latrunculin B, cytochalasin B, and cytochalasin D indicate that SHFV does not hijack the actin polymerization pathway. Treatment of target cells with proteases (proteinase K, papain, α-chymotrypsin, and trypsin) abrogated entry, indicating that the SHFV cell surface receptor is a protein. Phospholipases A2 and D had no effect on SHFV entry. Finally, treatment of cells with antibodies targeting CD163, a cell surface molecule identified as an entry factor for the SHFV-related porcine reproductive and respiratory syndrome virus, diminished SHFV replication, identifying CD163 as an important SHFV entry component. Simian hemorrhagic fever virus (SHFV) causes highly lethal disease in Asian macaques resembling human illness caused by Ebola or Lassa virus. However, little is known about SHFV's ecology and molecular biology and the mechanism by which it causes disease. The results of this study shed light on how SHFV enters its target cells. Using electron microscopy and inhibitors for various cellular pathways, we demonstrate that SHFV invades cells by low-pH-dependent, actin

  6. Candidiasis in Simians

    Science.gov (United States)

    Candidiasis was diagnosed in six monkeys over a 10-month period. Most cases had been on antibiotic therapy for enterocolitis. Fungal invasion was...seen in epithelium of the tongue, oral cavity, esophagus, and colon, and in hard keratin of the nails. Gross lesions of the anterior alimentary tract

  7. Jensen divergence based on Fisher’s information

    International Nuclear Information System (INIS)

    Sánchez-Moreno, P; Zarzo, A; Dehesa, J S

    2012-01-01

    The measure of Jensen–Fisher divergence between probability distributions is introduced and its theoretical grounds set up. This quantity, in contrast to the remaining Jensen divergences, grasps the fluctuations of the probability distributions because it is controlled by the (local) Fisher information, which is a gradient functional of the distribution. So it is appropriate and informative when studying the similarity of distributions, mainly for those having oscillatory character. The new Jensen–Fisher divergence shares with the Jensen–Shannon divergence the following properties: non-negativity, additivity when applied to an arbitrary number of probability densities, symmetry under exchange of these densities, vanishing under certain conditions and definiteness even when these densities present non-common zeros. Moreover, the Jensen–Fisher divergence is shown to be expressed in terms of the relative Fisher information as the Jensen–Shannon divergence does in terms of the Kullback–Leibler or relative Shannon entropy. Finally, the Jensen–Shannon and Jensen–Fisher divergences are compared for the following three large, non-trivial and qualitatively different families of probability distributions: the sinusoidal, generalized gamma-like and Rakhmanov–Hermite distributions, which are closely related to the quantum-mechanical probability densities of numerous physical systems. (paper)

  8. Total Bregman Divergence and its Applications to Shape Retrieval.

    Science.gov (United States)

    Liu, Meizhu; Vemuri, Baba C; Amari, Shun-Ichi; Nielsen, Frank

    2010-01-01

    Shape database search is ubiquitous in the world of biometric systems, CAD systems etc. Shape data in these domains is experiencing an explosive growth and usually requires search of whole shape databases to retrieve the best matches with accuracy and efficiency for a variety of tasks. In this paper, we present a novel divergence measure between any two given points in [Formula: see text] or two distribution functions. This divergence measures the orthogonal distance between the tangent to the convex function (used in the definition of the divergence) at one of its input arguments and its second argument. This is in contrast to the ordinate distance taken in the usual definition of the Bregman class of divergences [4]. We use this orthogonal distance to redefine the Bregman class of divergences and develop a new theory for estimating the center of a set of vectors as well as probability distribution functions. The new class of divergences are dubbed the total Bregman divergence (TBD). We present the l 1 -norm based TBD center that is dubbed the t-center which is then used as a cluster center of a class of shapes The t-center is weighted mean and this weight is small for noise and outliers. We present a shape retrieval scheme using TBD and the t-center for representing the classes of shapes from the MPEG-7 database and compare the results with other state-of-the-art methods in literature.

  9. Interspecific genetic divergence in grey mullets from the Goa region

    Digital Repository Service at National Institute of Oceanography (India)

    Menezes, M.R.; Martins, M.; Naik, S.

    Genetic divergence and phylogenetic relationships among Mugil cephalus, Liza subviridis and Valamugil cunnesius were investigated by examining the electrophoretic patterns of ten enzymes and sarcoplasmic proteins. Among the 19 loci detected, eight...

  10. Role of mantle flow in Nubia-Somalia plate divergence

    Science.gov (United States)

    Stamps, D. S.; Iaffaldano, G.; Calais, E.

    2015-01-01

    Present-day continental extension along the East African Rift System (EARS) has often been attributed to diverging sublithospheric mantle flow associated with the African Superplume. This implies a degree of viscous coupling between mantle and lithosphere that remains poorly constrained. Recent advances in estimating present-day opening rates along the EARS from geodesy offer an opportunity to address this issue with geodynamic modeling of the mantle-lithosphere system. Here we use numerical models of the global mantle-plates coupled system to test the role of present-day mantle flow in Nubia-Somalia plate divergence across the EARS. The scenario yielding the best fit to geodetic observations is one where torques associated with gradients of gravitational potential energy stored in the African highlands are resisted by weak continental faults and mantle basal drag. These results suggest that shear tractions from diverging mantle flow play a minor role in present-day Nubia-Somalia divergence.

  11. Diverging diamond interchange performance evaluation (I-44 and Route 13)

    Science.gov (United States)

    2011-02-01

    Performance evaluation was conducted on the first diverging diamond interchange (DDI) or double : crossover interchange (DCD) constructed in the United States. This evaluation assessed traffic operations, safety and : public perceptions t...

  12. A divergence theorem for pseudo-Finsler spaces

    OpenAIRE

    Minguzzi, E.

    2015-01-01

    We study the divergence theorem on pseudo-Finsler spaces and obtain a completely Finslerian version for spaces having a vanishing mean Cartan torsion. This result helps to clarify the problem of energy-momentum conservation in Finsler gravity theories.

  13. Stora's fine notion of divergent amplitudes

    International Nuclear Information System (INIS)

    Várilly, Joseph C.; Gracia-Bondía, José M.

    2016-01-01

    Stora and coworkers refined the notion of divergent quantum amplitude, somewhat upsetting the standard power-counting recipe. This unexpectedly clears the way to new prototypes for free and interacting field theories of bosons of any mass and spin.

  14. Principal Curves for Statistical Divergences and an Application to Finance

    Directory of Open Access Journals (Sweden)

    Ana Flávia P. Rodrigues

    2018-05-01

    Full Text Available This paper proposes a method for the beta pricing model under the consideration of non-Gaussian returns by means of a generalization of the mean-variance model and the use of principal curves to define a divergence model for the optimization of the pricing model. We rely on the q-exponential model so consider the properties of the divergences which are used to describe the statistical model and fully characterize the behavior of the assets. We derive the minimum divergence portfolio, which generalizes the Markowitz’s (mean-divergence approach and relying on the information geometrical aspects of the distributions the Capital Asset Pricing Model (CAPM is then derived under the geometrical characterization of the distributions which model the data, all by the consideration of principal curves approach. We discuss the possibility of integration of our model into an adaptive procedure that can be used for the search of optimum points on finance applications.

  15. NATO Technology: From Gap to Divergence? (Defense Horizons, July 2004)

    National Research Council Canada - National Science Library

    Daniel, Donald

    2004-01-01

    .... Over several decades, great disparities in the funding of defense research and technology by NATO members has produced a widening technological gap that threatens to become a divergence a condition...

  16. Camouflage target detection via hyperspectral imaging plus information divergence measurement

    Science.gov (United States)

    Chen, Yuheng; Chen, Xinhua; Zhou, Jiankang; Ji, Yiqun; Shen, Weimin

    2016-01-01

    Target detection is one of most important applications in remote sensing. Nowadays accurate camouflage target distinction is often resorted to spectral imaging technique due to its high-resolution spectral/spatial information acquisition ability as well as plenty of data processing methods. In this paper, hyper-spectral imaging technique together with spectral information divergence measure method is used to solve camouflage target detection problem. A self-developed visual-band hyper-spectral imaging device is adopted to collect data cubes of certain experimental scene before spectral information divergences are worked out so as to discriminate target camouflage and anomaly. Full-band information divergences are measured to evaluate target detection effect visually and quantitatively. Information divergence measurement is proved to be a low-cost and effective tool for target detection task and can be further developed to other target detection applications beyond spectral imaging technique.

  17. Impact of urothelial carcinoma with divergent differentiation on tumor stage

    Directory of Open Access Journals (Sweden)

    S Chalise

    2016-03-01

    Full Text Available Background: Urinary bladder cancer is classified as urothelial or non-urothelial. Ninenty percent of bladder cancer are urothelial and has propensity for divergent differentiation. Squamous differentiation is associated with unfavourable prognostic features. The aim of this study is to determine the significance of urothelial carcinoma with divergent differentiation in relation to tumor stage and lymphovascular as well as perineural invasion in radical cystectomy and partial cystectomy specimen.Materials and methods: This prospective study was done among 51 patients who underwent radical cystectomy or partial cystectomy at Bhaktapur Cancer Hospital from 1st August 2013 to 31st December 2015. Received specimen was grossed following standard protocol and histopathological evaluation was done in relation to tumor type, depth of invasion, Lymphovascular and perineural invasion.Results: Pure urothelial carcinoma comprises 47.1% of cases. Among the divergent differentiation, urothelial carcinoma with squamous differentiation was the commonest one (39.2% followed by glandular differentiation (5.9%, sarcomatoid differentiation (3.9%, clear cell variant (2.0% and squamous along with sarcomatoid variant (2.0%. Statistical significant correlation was found between urothelial carcinoma with divergent differentiation and tumor stage (p<0.012. Statistically significant correlation was also found between urothelial carcinoma with divergent differentiation and lymphovascular invasion (p=0.012 as well as perineural invasion (p=0.037.Conclusion:  Most common divergent differentiation was squamous differentiation. Urothelial carcinoma with divergent differentiation was associated with higher stage and lymphovascular as well as perineural invasion. So it is mandatory to search for the divergent differentiation in urothelial carcinoma as this may be associated with unfavourable prognosis.

  18. The direct Flow parametric Proof of Gauss' Divergence Theorem revisited

    OpenAIRE

    Markvorsen, Steen

    2006-01-01

    The standard proof of the divergence theorem in undergraduate calculus courses covers the theorem for static domains between two graph surfaces. We show that within first year undergraduate curriculum, the flow proof of the dynamic version of the divergence theorem - which is usually considered only much later in more advanced math courses - is comprehensible with only a little extension of the first year curriculum. Moreover, it is more intuitive than the static proof. We support this intuit...

  19. Dimensional regularization and infrared divergences in quantum electrodynamics

    International Nuclear Information System (INIS)

    Marculescu, S.

    1979-01-01

    Dimensional continuation was devised as a powerful regularization method for ultraviolet divergences in quantum field theories. Recently it was clear, at least for quantum electrodynamics, that such a method could be employed for factorizing out infrared divergences from the on-shell S-matrix elements. This provides a renormalization scheme on the electron mass-shell without using a gauge violating ''photon mass''. (author)

  20. Diverging Trade Strategies in Latin America: An Analytical Framework

    OpenAIRE

    Aggarwal, Vinod K.; Espach, Ralph H.

    2003-01-01

    Although there is increasing divergence among the trade policies of various Latin American nations, overall the last twenty years have seen a dramatic shift away from protectionism towards liberalization. Focusing on case studies of four Latin American nations — Brazil, Mexico, Chile and Argentina — the authors use an analytical framework to explain the rationales behind divergent policies. The analytical approach used considers the combination of economic, political and strategic objectives ...

  1. Robust bounds on risk-sensitive functionals via Renyi divergence

    OpenAIRE

    Atar, Rami; Chowdhary, Kamaljit; Dupuis, Paul

    2013-01-01

    We extend the duality between exponential integrals and relative entropy to a variational formula for exponential integrals involving the Renyi divergence. This formula characterizes the dependence of risk-sensitive functionals and related quantities determined by tail behavior to perturbations in the underlying distributions, in terms of the Renyi divergence. The characterization gives rise to upper and lower bounds that are meaningful for all values of a large deviation scaling parameter, a...

  2. Neural Mechanisms of Episodic Retrieval Support Divergent Creative Thinking.

    Science.gov (United States)

    Madore, Kevin P; Thakral, Preston P; Beaty, Roger E; Addis, Donna Rose; Schacter, Daniel L

    2017-11-17

    Prior research has indicated that brain regions and networks that support semantic memory, top-down and bottom-up attention, and cognitive control are all involved in divergent creative thinking. Kernels of evidence suggest that neural processes supporting episodic memory-the retrieval of particular elements of prior experiences-may also be involved in divergent thinking, but such processes have typically been characterized as not very relevant for, or even a hindrance to, creative output. In the present study, we combine functional magnetic resonance imaging with an experimental manipulation to test formally, for the first time, episodic memory's involvement in divergent thinking. Following a manipulation that facilitates detailed episodic retrieval, we observed greater neural activity in the hippocampus and stronger connectivity between a core brain network linked to episodic processing and a frontoparietal brain network linked to cognitive control during divergent thinking relative to an object association control task that requires little divergent thinking. Stronger coupling following the retrieval manipulation extended to a subsequent resting-state scan. Neural effects of the episodic manipulation were consistent with behavioral effects of enhanced idea production on divergent thinking but not object association. The results indicate that conceptual frameworks should accommodate the idea that episodic retrieval can function as a component process of creative idea generation, and highlight how the brain flexibly utilizes the retrieval of episodic details for tasks beyond simple remembering. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Riverscape genetics identifies replicated ecological divergence across an Amazonian ecotone.

    Science.gov (United States)

    Cooke, Georgina M; Landguth, Erin L; Beheregaray, Luciano B

    2014-07-01

    Ecological speciation involves the evolution of reproductive isolation and niche divergence in the absence of a physical barrier to gene flow. The process is one of the most controversial topics of the speciation debate, particularly in tropical regions. Here, we investigate ecologically based divergence across an Amazonian ecotone in the electric fish, Steatogenys elegans. We combine phylogenetics, genome scans, and population genetics with a recently developed individual-based evolutionary landscape genetics approach that incorporates selection. This framework is used to assess the relative contributions of geography and divergent natural selection between environments as biodiversity drivers. We report on two closely related and sympatric lineages that exemplify how divergent selection across a major Amazonian aquatic ecotone (i.e., between rivers with markedly different hydrochemical properties) may result in replicated ecologically mediated speciation. The results link selection across an ecological gradient with reproductive isolation and we propose that assortative mating based on water color may be driving the divergence. Divergence resulting from ecologically driven selection highlights the importance of considering environmental heterogeneity in studies of speciation in tropical regions. Furthermore, we show that framing ecological speciation in a spatially explicit evolutionary landscape genetics framework provides an important first step in exploring a wide range of the potential effects of spatial dependence in natural selection. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  4. The nuclear import of the human T lymphotropic virus type I (HTLV-1) tax protein is carrier- and energy-independent.

    Science.gov (United States)

    Tsuji, Takahiro; Sheehy, Noreen; Gautier, Virginie W; Hayakawa, Hitoshi; Sawa, Hirofumi; Hall, William W

    2007-05-04

    HTLV-1 is the etiologic agent of the adult T cell leukemialymphoma (ATLL). The viral regulatory protein Tax plays a central role in leukemogenesis as a transcriptional transactivator of both viral and cellular gene expression, and this requires Tax activity in both the cytoplasm and the nucleus. In the present study, we have investigated the mechanisms involved in the nuclear localization of Tax. Employing a GFP fusion expression system and a range of Tax mutants, we could confirm that the N-terminal 60 amino acids, and specifically residues within the zinc finger motif in this region, are important for nuclear localization. Using an in vitro nuclear import assay, it could be demonstrated that the transportation of Tax to the nucleus required neither energy nor carrier proteins. Specific and direct binding between Tax and p62, a nucleoporin with which the importin beta family of proteins have been known to interact was also observed. The nuclear import activity of wild type Tax and its mutants and their binding affinity for p62 were also clearly correlated, suggesting that the entry of Tax into the nucleus involves a direct interaction with nucleoporins within the nuclear pore complex (NPC). The nuclear export of Tax was also shown to be carrier independent. It could be also demonstrated that Tax it self may have a carrier function and that the NF-kappaB subunit p65 could be imported into the nucleus by Tax. These studies suggest that Tax could alter the nucleocytoplasmic distribution of cellular proteins, and this could contribute to the deregulation of cellular processes observed in HTLV-1 infection.

  5. Effects of Physiotherapy in the Treatment of Neurogenic Bladder in Patients Infected with Human T-Lymphotropic Virus 1 (HTLV-1)

    Science.gov (United States)

    Andrade, Rosana C.P.; Neto, José A.; Andrade, Luciana; Oliveira, Tatiane S. S.; Santos, Dislene N.; Oliveira, Cassius J.V.; Prado, Márcio J.; Carvalho, Edgar M.

    2016-01-01

    Objective To evaluate the efficacy of physiotherapy for urinary manifestations in patients with HTLV-1-associated lower urinary tract dysfunction. Methods Open clinical trial with 21 patients attending the physiotherapy clinic of the Hospital Universitário, Bahia, Brazil. Combinations of behavioral therapy, perineal exercises and intravaginal/intra-anal electrical stimulation were used. Results The mean age was 54±12 years and 67% were female. After treatment, there was an improvement in symptoms of urinary urgency, frequency, incontinence, nocturia and in the sensation of incomplete emptying (pPhysiotherapy was effective in cases of HTLV-1-associated neurogenic bladder, reducing symptoms, increasing perineal muscle strength, improving urodynamic parameters and quality of life. PMID:26724409

  6. Radioimmunoassay and enzyme-linked immunoassay of antibodies to the core protein (P24) of human T-lymphotropic virus (HTLV III). [Acquired immunodeficiency syndrome (AIDS)

    Energy Technology Data Exchange (ETDEWEB)

    Neurath, A R; Strick, N; Sproul, P

    1985-05-01

    Human T-cell lymphotropic viruses designated HTLV III or LAV are considered to represent the causative agents of the acquired immunodeficiency syndrome (AIDS). Therefore a simple direct RIA or ELISA method for antibodies to distinct epitopes of HTLV III/LAV structural components would be of great value. The authors describe RIA and ELISA assays which obviate the need for purified virus or virus proteins, do not utilize infected cells and thus do not diminish the source for continuous production of viral antigens and are specific for a major core protein of HTLV III/LAV.

  7. Human T-lymphotropic virus-1/2 detected in drug abused men who have sex with men in Surakarta Indonesia

    Science.gov (United States)

    Prasetyo, Afiono Agung; Sari, Yulia

    2017-02-01

    Human T-cell lymphotropic virus types 1 and 2 (HTLV-1/2) are retroviruses that probably among the most neglected blood-borne pathogens. The molecular epidemiology data of HTLV-1/2 in Indonesia is very rare. This study evaluated the prevalence of HTLV-1 and 2 in men who have sex with men with drug abused history in Surakarta Indonesia, to track the presentation of HTLV-1/2 in Indonesia. All blood samples collected from men who have sex with men with drug abused history in Surakarta in 2009-2013 were tested using enzyme linked immunosorbent assays and confirmed by RT-PCR nested addressed the part of HTLV-1 LTR and HTLV-2 LTR region, respectively. The specificity of the molecular assays was confirmed by sequencing the amplicons. The anti HTLV-1/2 positive rate was 4.8% (6/126). All positive serological samples were confirmed by nested RT-PCR. Of these, two was HTLV-1 positive and four was HTLV-2 positive. Molecular analysis of positive PCR products revealed that all HTLV-1 isolate had close relationship with HTLV-1 isolated in Japan while all HTLV-2 isolate with that of isolated in USA. HTLV-1 and HTLV-2 were detected in men who have sex with men with drug abused history in Surakarta indicated that these viruses were circulated in Indonesia, especially in the high risk communities

  8. The cause of urinary symptoms among Human T Lymphotropic Virus Type I (HLTV-I infected patients: a cross sectional study

    Directory of Open Access Journals (Sweden)

    Salgado Katia

    2007-03-01

    Full Text Available Abstract Background HTLV-I infected patients often complain of urinary symptomatology. Epidemiological studies have suggested that these individuals have a higher prevalence and incidence of urinary tract infection (UTI than seronegative controls. However, the diagnosis of UTI in these studies relied only on patient information and did not require confirmation by urine culture. The purpose of this study was to investigate the role of urinary tract infection (UTI as the cause of urinary symptoms in HTLV-I infected patients. Methods In this cross sectional study we interviewed, and cultured urine from, 157 HTLV-I seropositive individuals followed regularly at a specialized clinic. All patients were evaluated by a neurologist and classified according to the Expanded Disability Status Scale (EDSS. Urodynamic studies were performed at the discretion of the treating physician. Results Sixty-four patients complained of at least one active urinary symptom but UTI was confirmed by a positive urine culture in only 12 of these patients (19%; the majority of symptomatic patients (81% had negative urine cultures. To investigate the mechanism behind the urinary complaints in symptomatic individuals with negative urine cultures, we reviewed the results of urodynamic studies performed in 21 of these patients. Most of them (90.5% had abnormal findings. The predominant abnormalities were detrusor sphincter hyperreflexia and dyssynergia, findings consistent with HTLV-I-induced neurogenic bladder. On a multivariate logistic regression, an abnormal EDSS score was the strongest predictor of urinary symptomatology (OR 9.87, 95% CI 3.465 to 28.116, P Conclusion Urinary symptomatology suggestive of UTI is highly prevalent among HTLV-I seropositive individuals but true UTI is responsible for the minority of cases. We posit that the main cause of urinary symptoms in this population is neurogenic bladder. Our data imply that HLTV-I infected patients with urinary symptomatology should not be empirically treated for UTI but rather undergo urine culture; if a UTI is excluded, further investigation with urodynamic studies should be considered.

  9. Lineage-specific positive selection at the merozoite surface protein 1 (msp1 locus of Plasmodium vivax and related simian malaria parasites

    Directory of Open Access Journals (Sweden)

    Kawai Satoru

    2010-02-01

    Full Text Available Abstract Background The 200 kDa merozoite surface protein 1 (MSP-1 of malaria parasites, a strong vaccine candidate, plays a key role during erythrocyte invasion and is a target of host protective immune response. Plasmodium vivax, the most widespread human malaria parasite, is closely related to parasites that infect Asian Old World monkeys, and has been considered to have become a parasite of man by host switch from a macaque malaria parasite. Several Asian monkey parasites have a range of natural hosts. The same parasite species shows different disease manifestations among host species. This suggests that host immune responses to P. vivax-related malaria parasites greatly differ among host species (albeit other factors. It is thus tempting to invoke that a major immune target parasite protein such as MSP-1 underwent unique evolution, depending on parasite species that exhibit difference in host range and host specificity. Results We performed comparative phylogenetic and population genetic analyses of the gene encoding MSP-1 (msp1 from P. vivax and nine P. vivax-related simian malaria parasites. The inferred phylogenetic tree of msp1 significantly differed from that of the mitochondrial genome, with a striking displacement of P. vivax from a position close to P. cynomolgi in the mitochondrial genome tree to an outlier of Asian monkey parasites. Importantly, positive selection was inferred for two ancestral branches, one leading to P. inui and P. hylobati and the other leading to P. vivax, P. fieldi and P. cynomolgi. This ancestral positive selection was estimated to have occurred three to six million years ago, coinciding with the period of radiation of Asian macaques. Comparisons of msp1 polymorphisms between P. vivax, P. inui and P. cynomolgi revealed that while some positively selected amino acid sites or regions are shared by these parasites, amino acid changes greatly differ, suggesting that diversifying selection is acting species

  10. Growth regulation of simian and human AIDS-related non-Hodgkin's lymphoma cell lines by TGF-β1 and IL-6

    Directory of Open Access Journals (Sweden)

    Levy Laura S

    2007-02-01

    Full Text Available Abstract Background AIDS-related non-Hodgkin's lymphoma (AIDS-NHL is the second most frequent cancer associated with AIDS, and is a frequent cause of death in HIV-infected individuals. Experimental analysis of AIDS-NHL has been facilitated by the availability of an excellent animal model, i.e., simian Acquired Immunodeficiency Syndrome (SAIDS in the rhesus macaque consequent to infection with simian immunodeficiency virus. A recent study of SAIDS-NHL demonstrated a lymphoma-derived cell line to be sensitive to the growth inhibitory effects of the ubiquitous cytokine, transforming growth factor-beta (TGF-beta. The authors concluded that TGF-beta acts as a negative growth regulator of the lymphoma-derived cell line and, potentially, as an inhibitory factor in the regulatory network of AIDS-related lymphomagenesis. The present study was conducted to assess whether other SAIDS-NHL and AIDS-NHL cell lines are similarly sensitive to the growth inhibitory effects of TGF-beta, and to test the hypothesis that interleukin-6 (IL-6 may represent a counteracting positive influence in their growth regulation. Methods Growth stimulation or inhibition in response to cytokine treatment was quantified using trypan blue exclusion or colorimetric MTT assay. Intracellular flow cytometry was used to analyze the activation of signaling pathways and to examine the expression of anti-apoptotic proteins and distinguishing hallmarks of AIDS-NHL subclass. Apoptosis was quantified by flow cytometric analysis of cell populations with sub-G1 DNA content and by measuring activated caspase-3. Results Results confirmed the sensitivity of LCL8664, an immunoblastic SAIDS-NHL cell line, to TGF-beta1-mediated growth inhibition, and further demonstrated the partial rescue by simultaneous treatment with IL-6. IL-6 was shown to activate STAT3, even in the presence of TGF-beta1, and thereby to activate proliferative and anti-apoptotic pathways. By comparison, human AIDS-NHL cell lines

  11. The archetype enhancer of simian virus 40 DNA is duplicated during virus growth in human cells and rhesus monkey kidney cells but not in green monkey kidney cells

    International Nuclear Information System (INIS)

    O'Neill, Frank J.; Greenlee, John E.; Carney, Helen

    2003-01-01

    Archetype SV40, obtained directly from its natural host, is characterized by a single 72-bp enhancer element. In contrast, SV40 grown in cell culture almost invariably exhibits partial or complete duplication of the enhancer region. This distinction has been considered important in studies of human tumor material, since SV40-associated tumor isolates have been described having a single enhancer region, suggesting natural infection as opposed to possible contamination by laboratory strains of virus. However, the behavior of archetypal SV40 in cultured cells has never been methodically studied. In this study we reengineered nonarchetypal 776-SV40 to contain a single 72-bp enhancer region and used this reengineered archetypal DNA to transfect a number of simian and human cell lines. SV40 DNA recovered from these cells was analyzed by restriction endonuclease analysis, PCR, and DNA sequencing. Reengineered archetype SV40 propagated in green monkey TC-7 or BSC-1 kidney cells remained without enhancer region duplication even after extensive serial virus passage. Archetype SV40 grown in all but one of the rhesus or human cell lines initially appeared exclusively archetypal. However, when virus from these cell types was transferred to green monkey cells, variants with partial enhancer duplication appeared after as little as a single passage. These findings suggest (1) that virus with a single 72-bp enhancer may persist in cultured cells of simian and human origin; (2) that variants with partially duplicated enhancer regions may arise within cell lines in quantities below limits of detection; (3) that these variants may enjoy a selective advantage in cell types other than those from which they arose (e.g., green monkey kidney cells); and (4) that certain cell lines may support a selective growth advantage for the variants without supporting their formation. Our data indicate that enhancer duplication may also occur in human as well as rhesus kidney cells. Thus, detection of

  12. Superior Efficacy of a Human Immunodeficiency Virus Vaccine Combined with Antiretroviral Prevention in Simian-Human Immunodeficiency Virus-Challenged Nonhuman Primates.

    Science.gov (United States)

    Le Grand, Roger; Dereuddre-Bosquet, Nathalie; Dispinseri, Stefania; Gosse, Leslie; Desjardins, Delphine; Shen, Xiaoying; Tolazzi, Monica; Ochsenbauer, Christina; Saidi, Hela; Tomaras, Georgia; Prague, Mélanie; Barnett, Susan W; Thiebaut, Rodolphe; Cope, Alethea; Scarlatti, Gabriella; Shattock, Robin J

    2016-06-01

    Although vaccines and antiretroviral (ARV) prevention have demonstrated partial success against human immunodeficiency virus (HIV) infection in clinical trials, their combined introduction could provide more potent protection. Furthermore, combination approaches could ameliorate the potential increased risk of infection following vaccination in the absence of protective immunity. We used a nonhuman primate model to determine potential interactions of combining a partially effective ARV microbicide with an envelope-based vaccine. The vaccine alone provided no protection from infection following 12 consecutive low-dose intravaginal challenges with simian-HIV strain SF162P3, with more animals infected compared to naive controls. The microbicide alone provided a 68% reduction in the risk of infection relative to that of the vaccine group and a 45% reduction relative to that of naive controls. The vaccine-microbicide combination provided an 88% reduction in the per-exposure risk of infection relative to the vaccine alone and a 79% reduction relative to that of the controls. Protected animals in the vaccine-microbicide group were challenged a further 12 times in the absence of microbicide and demonstrated a 98% reduction in the risk of infection. A total risk reduction of 91% was observed in this group over 24 exposures (P = 0.004). These important findings suggest that combined implementation of new biomedical prevention strategies may provide significant gains in HIV prevention. There is a pressing need to maximize the impact of new biomedical prevention tools in the face of the 2 million HIV infections that occur each year. Combined implementation of complementary biomedical approaches could create additive or synergistic effects that drive improved reduction of HIV incidence. Therefore, we assessed a combination of an untested vaccine with an ARV-based microbicide in a nonhuman primate vaginal challenge model. The vaccine alone provided no protection (and may have

  13. DAST in Flight Showing Diverging Wingtip Oscillations

    Science.gov (United States)

    1980-01-01

    normal stiffness. This was done because stiffness requires structural weight but ensures freedom from flutter-an uncontrolled, divergent oscillation of the structure, driven by aerodynamic forces and resulting in structural failure. The program used refined theoretical tools to predict at what speed flutter would occur. It then designed a high-response control system to counteract the motion and permit a much lighter wing structure. The wing had, in effect, 'electronic stiffness.' Flight research with this concept was extremely hazardous because an error in either the flutter prediction or control system implementation would result in wing structural failure and the loss of the vehicle. Because of this, flight demonstration of a sub-scale vehicle made sense from the standpoint of both safety and cost. The program anticipated structural failure during the course of the flight research. The Firebee II was a supersonic drone selected as the DAST testbed because its wing could be easily replaced, it used only tail-mounted control surfaces, and it was available as surplus from the U. S. Air Force. It was capable of 5-g turns (that is, turns producing acceleration equal to 5 times that of gravity). Langley outfitted a drone with an aeroelastic, supercritical research wing suitable for a Mach 0.98 cruise transport with a predicted flutter speed of Mach 0.95 at an altitude of 25,000 feet. Dryden and Langley, in conjunction with Boeing, designed and fabricated a digital flutter suppression system (FSS). Dryden developed an RPRV (remotely piloted research vehicle) flight control system; integrated the wing, FSS, and vehicle systems; and conducted the flight program. In addition to a digital flight control system and aeroelastic wings, each DAST drone had research equipment mounted in its nose and a mid-air retrieval system in its tail. The drones were originally launched from the NASA B-52 bomber and later from a DC-130. The DAST vehicle's flight was monitored from the sky by an F

  14. Rotational and divergent kinetic energy in the mesoscale model ALADIN

    Directory of Open Access Journals (Sweden)

    V. Blažica

    2013-03-01

    Full Text Available Kinetic energy spectra from the mesoscale numerical weather prediction (NWP model ALADIN with horizontal resolution 4.4 km are split into divergent and rotational components which are then compared at horizontal scales below 300 km and various vertical levels. It is shown that about 50% of kinetic energy in the free troposphere in ALADIN is divergent energy. The percentage increases towards 70% near the surface and in the upper troposphere towards 100 hPa. The maximal percentage of divergent energy is found at stratospheric levels around 100 hPa and at scales below 100 km which are not represented by the global models. At all levels, the divergent energy spectra are characterised by shallower slopes than the rotational energy spectra, and the difference increases as horizontal scales become larger. A very similar vertical distribution of divergent energy is obtained by using the standard ALADIN approach for the computation of spectra based on the extension zone and by applying detrending approach commonly used in mesoscale NWP community.

  15. Sufficient Statistics for Divergence and the Probability of Misclassification

    Science.gov (United States)

    Quirein, J.

    1972-01-01

    One particular aspect is considered of the feature selection problem which results from the transformation x=Bz, where B is a k by n matrix of rank k and k is or = to n. It is shown that in general, such a transformation results in a loss of information. In terms of the divergence, this is equivalent to the fact that the average divergence computed using the variable x is less than or equal to the average divergence computed using the variable z. A loss of information in terms of the probability of misclassification is shown to be equivalent to the fact that the probability of misclassification computed using variable x is greater than or equal to the probability of misclassification computed using variable z. First, the necessary facts relating k-dimensional and n-dimensional integrals are derived. Then the mentioned results about the divergence and probability of misclassification are derived. Finally it is shown that if no information is lost (in x = Bz) as measured by the divergence, then no information is lost as measured by the probability of misclassification.

  16. Concrete ensemble Kalman filters with rigorous catastrophic filter divergence.

    Science.gov (United States)

    Kelly, David; Majda, Andrew J; Tong, Xin T

    2015-08-25

    The ensemble Kalman filter and ensemble square root filters are data assimilation methods used to combine high-dimensional, nonlinear dynamical models with observed data. Ensemble methods are indispensable tools in science and engineering and have enjoyed great success in geophysical sciences, because they allow for computationally cheap low-ensemble-state approximation for extremely high-dimensional turbulent forecast models. From a theoretical perspective, the dynamical properties of these methods are poorly understood. One of the central mysteries is the numerical phenomenon known as catastrophic filter divergence, whereby ensemble-state estimates explode to machine infinity, despite the true state remaining in a bounded region. In this article we provide a breakthrough insight into the phenomenon, by introducing a simple and natural forecast model that transparently exhibits catastrophic filter divergence under all ensemble methods and a large set of initializations. For this model, catastrophic filter divergence is not an artifact of numerical instability, but rather a true dynamical property of the filter. The divergence is not only validated numerically but also proven rigorously. The model cleanly illustrates mechanisms that give rise to catastrophic divergence and confirms intuitive accounts of the phenomena given in past literature.

  17. Sandwiched Rényi divergence satisfies data processing inequality

    International Nuclear Information System (INIS)

    Beigi, Salman

    2013-01-01

    Sandwiched (quantum) α-Rényi divergence has been recently defined in the independent works of Wilde et al. [“Strong converse for the classical capacity of entanglement-breaking channels,” preprint http://arxiv.org/abs/arXiv:1306.1586 (2013)] and Müller-Lennert et al. [“On quantum Rényi entropies: a new definition, some properties and several conjectures,” preprint http://arxiv.org/abs/arXiv:1306.3142v1 (2013)]. This new quantum divergence has already found applications in quantum information theory. Here we further investigate properties of this new quantum divergence. In particular, we show that sandwiched α-Rényi divergence satisfies the data processing inequality for all values of α > 1. Moreover we prove that α-Holevo information, a variant of Holevo information defined in terms of sandwiched α-Rényi divergence, is super-additive. Our results are based on Hölder's inequality, the Riesz-Thorin theorem and ideas from the theory of complex interpolation. We also employ Sion's minimax theorem

  18. Ayahuasca enhances creative divergent thinking while decreasing conventional convergent thinking.

    Science.gov (United States)

    Kuypers, K P C; Riba, J; de la Fuente Revenga, M; Barker, S; Theunissen, E L; Ramaekers, J G

    2016-09-01

    Ayahuasca is a South American psychotropic plant tea traditionally used in Amazonian shamanism. The tea contains the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT), plus β-carboline alkaloids with monoamine oxidase-inhibiting properties. Increasing evidence from anecdotal reports and open-label studies indicates that ayahuasca may have therapeutic effects in treatment of substance use disorders and depression. A recent study on the psychological effects of ayahuasca found that the tea reduces judgmental processing and inner reactivity, classic goals of mindfulness psychotherapy. Another psychological facet that could potentially be targeted by ayahuasca is creative divergent thinking. This mode of thinking can enhance and strengthen psychological flexibility by allowing individuals to generate new and effective cognitive, emotional, and behavioral strategies. The present study aimed to assess the potential effects of ayahuasca on creative thinking. We visited two spiritual ayahuasca workshops and invited participants to conduct creativity tests before and during the acute effects of ayahuasca. In total, 26 participants consented. Creativity tests included the "pattern/line meanings test" (PLMT) and the "picture concept test" (PCT), both assessing divergent thinking and the latter also assessing convergent thinking. While no significant effects were found for the PLMT, ayahuasca intake significantly modified divergent and convergent thinking as measured by the PCT. While convergent thinking decreased after intake, divergent thinking increased. The present data indicate that ayahuasca enhances creative divergent thinking. They suggest that ayahuasca increases psychological flexibility, which may facilitate psychotherapeutic interventions and support clinical trial initiatives.

  19. Computational Investigations in Rectangular Convergent and Divergent Ribbed Channels

    Science.gov (United States)

    Sivakumar, Karthikeyan; Kulasekharan, N.; Natarajan, E.

    2018-05-01

    Computational investigations on the rib turbulated flow inside a convergent and divergent rectangular channel with square ribs of different rib heights and different Reynolds numbers (Re=20,000, 40,000 and 60,000). The ribs were arranged in a staggered fashion between the upper and lower surfaces of the test section. Computational investigations are carried out using computational fluid dynamic software ANSYS Fluent 14.0. Suitable solver settings like turbulence models were identified from the literature and the boundary conditions for the simulations on a solution of independent grid. Computations were carried out for both convergent and divergent channels with 0 (smooth duct), 1.5, 3, 6, 9 and 12 mm rib heights, to identify the ribbed channel with optimal performance, assessed using a thermo hydraulic performance parameter. The convergent and divergent rectangular channels show higher Nu values than the standard correlation values.

  20. Frequencies of digits, divergence points, and Schmidt games

    International Nuclear Information System (INIS)

    Olsen, L.

    2009-01-01

    Sets of divergence points, i.e. numbers x (or tuples of numbers) for which the limiting frequency of a given string of N-adic digits of x fails to exist, have recently attracted huge interest in the literature. In this paper we consider sets of simultaneous divergence points, i.e. numbers x (or tuples of numbers) for which the limiting frequencies of all strings of N-adic digits of x fail to exist. We show that many natural sets of simultaneous divergence points are (α, β)-wining sets in the sense of the Schmidt game. As an application we obtain lower bounds for the Hausdorff dimension of these sets.

  1. Structure of UV divergences in maximally supersymmetric gauge theories

    Science.gov (United States)

    Kazakov, D. I.; Borlakov, A. T.; Tolkachev, D. M.; Vlasenko, D. E.

    2018-06-01

    We consider the UV divergences up to sub-subleading order for the four-point on-shell scattering amplitudes in D =8 supersymmetric Yang-Mills theory in the planar limit. We trace how the leading, subleading, etc divergences appear in all orders of perturbation theory. The structure of these divergences is typical for any local quantum field theory independently on renormalizability. We show how the generalized renormalization group equations allow one to evaluate the leading, subleading, etc. contributions in all orders of perturbation theory starting from one-, two-, etc. loop diagrams respectively. We focus then on subtraction scheme dependence of the results and show that in full analogy with renormalizable theories the scheme dependence can be absorbed into the redefinition of the couplings. The only difference is that the role of the couplings play dimensionless combinations like g2s2 or g2t2, where s and t are the Mandelstam variables.

  2. To be liked versus respected: Divergent goals in interracial interactions.

    Science.gov (United States)

    Bergsieker, Hilary B; Shelton, J Nicole; Richeson, Jennifer A

    2010-08-01

    Pervasive representations of Blacks and Latinos as unintelligent and of Whites as racist may give rise to divergent impression management goals in interracial interactions. We present studies showing that in interracial interactions racial minorities seek to be respected and seen as competent more than Whites do, whereas Whites seek to be liked and seen as moral more than racial minorities do. These divergent impression management goals are reflected in Whites' and racial minorities' self-report responses (Studies 1a, 1b, 2, and 4) and behaviors (Studies 3a and 3b). Divergent goals are observed in pre-existing relationships (Study 2), as well as in live interactions (Studies 3a, 3b, and 4), and are associated with higher levels of negative other-directed affect (Study 4). Implications of these goals for interracial communication and misunderstandings are discussed.

  3. Genetic divergence in sesame based on morphological and agronomic traits

    Directory of Open Access Journals (Sweden)

    Nair Helena Castro Arriel

    2007-01-01

    Full Text Available The evaluation of diversity in germplasm collections is important for both plant breeders and germplasmcurators to optimize the use of the variability available. Diversity can be estimated by different genetic markers. The purposeof this study was to estimate the genetic divergence of 30 morphological and agronomic traits in 108 sesame genotypes bymultivariate analysis. The Cole-Rodgers index was used to establish the dissimilarity matrices. The principal componentanalysis identified the traits that contributed most to the divergence and the genotypes were clustered by Tocher’s optimization.Despite the narrow genetic basis, the markers were efficient to characterize the genotypes and identify the most similar groupsor duplicate and divergent genotypes. Greatest variation was found for the traits number of capsules per plant and grain yield.

  4. Does niche divergence accompany allopatric divergence in Aphelocoma jays as predicted under ecological speciation? Insights from tests with niche models.

    Science.gov (United States)

    McCormack, John E; Zellmer, Amanda J; Knowles, L Lacey

    2010-05-01

    The role of ecology in the origin of species has been the subject of long-standing interest to evolutionary biologists. New sources of spatially explicit ecological data allow for large-scale tests of whether speciation is associated with niche divergence or whether closely related species tend to be similar ecologically (niche conservatism). Because of the confounding effects of spatial autocorrelation of environmental variables, we generate null expectations for niche divergence for both an ecological-niche modeling and a multivariate approach to address the question: do allopatrically distributed taxa occupy similar niches? In a classic system for the study of niche evolution--the Aphelocoma jays--we show that there is little evidence for niche divergence among Mexican Jay (A. ultramarina) lineages in the process of speciation, contrary to previous results. In contrast, Aphelocoma species that exist in partial sympatry in some regions show evidence for niche divergence. Our approach is widely applicable to the many cases of allopatric lineages in the beginning stages of speciation. These results do not support an ecological speciation model for Mexican Jay lineages because, in most cases, the allopatric environments they occupy are not significantly more divergent than expected under a null model.

  5. Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques.

    Science.gov (United States)

    Simon, Liz; Song, Keijing; Vande Stouwe, Curtis; Hollenbach, Andrew; Amedee, Angela; Mohan, Mahesh; Winsauer, Peter; Molina, Patricia

    2016-03-01

    Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques. To determine if the neuroimmunomodulation of Δ9-THC involved differential microRNA (miR) expression, miR expression in the striatum of uninfected macaques receiving vehicle (VEH) or Δ9-THC (THC) and SIV-infected macaques administered either vehicle (VEH/SIV) or Δ9-THC (THC/SIV) was profiled using next generation deep sequencing. Among the 24 miRs that were differentially expressed among the four groups, 16 miRs were modulated by THC in the presence of SIV. These 16 miRs were classified into four categories and the biological processes enriched by the target genes determined. Our results indicate that Δ9-THC modulates miRs that regulate mRNAs of proteins involved in 1) neurotrophin signaling, 2) MAPK signaling, and 3) cell cycle and immune response thus promoting an overall neuroprotective environment in the striatum of SIV-infected macaques. This is also reflected by increased Brain Derived Neurotrophic Factor (BDNF) and decreased proinflammatory cytokine expression compared to the VEH/SIV group. Whether Δ9-THC-mediated modulation of epigenetic mechanisms provides neuroprotection in other regions of the brain and during chronic SIV-infection remains to be determined.

  6. Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus

    International Nuclear Information System (INIS)

    Kaur, Amitinder; Sanford, Hannah B.; Garry, Deirdre; Lang, Sabine; Klumpp, Sherry A.; Watanabe, Daisuke; Bronson, Roderick T.; Lifson, Jeffrey D.; Rosati, Margherita; Pavlakis, George N.; Felber, Barbara K.; Knipe, David M.; Desrosiers, Ronald C.

    2007-01-01

    The immunogenicity and protective capacity of replication-defective herpes simplex virus (HSV) vector-based vaccines were examined in rhesus macaques. Three macaques were inoculated with recombinant HSV vectors expressing Gag, Env, and a Tat-Rev-Nef fusion protein of simian immunodeficiency virus (SIV). Three other macaques were primed with recombinant DNA vectors expressing Gag, Env, and a Pol-Tat-Nef-Vif fusion protein prior to boosting with the HSV vectors. Robust anti-Gag and anti-Env cellular responses were detected in all six macaques. Following intravenous challenge with wild-type, cloned SIV239, peak and 12-week plasma viremia levels were significantly lower in vaccinated compared to control macaques. Plasma SIV RNA in vaccinated macaques was inversely correlated with anti-Rev ELISPOT responses on the day of challenge (P value < 0.05), anti-Tat ELISPOT responses at 2 weeks post challenge (P value < 0.05) and peak neutralizing antibody titers pre-challenge (P value 0.06). These findings support continued study of recombinant herpesviruses as a vaccine approach for AIDS

  7. The impact of early immune destruction on the kinetics of postacute viral replication in rhesus monkey infected with the simian-human immunodeficiency virus 89.6P

    International Nuclear Information System (INIS)

    Zhang Zhiqiang; Schleif, William A.; Casimiro, Danilo R.; Handt, Larry; Chen, Minchun; Davies, Mary-Ellen; Liang Xiaoping; Fu Tongming; Tang Aimin; Wilson, Keith A.; McElhaugh, Michael; Carella, Anthony; Tan, Charles; Connolly, Brett; Hill, Susan; Klein, Hilton; Emini, Emilio A.; Shiver, John W.

    2004-01-01

    Set-point viral load is positively correlated with the extent of initial viral replication in pathogenic simian-human immunodeficiency virus (SHIV) infection. To elucidate the mechanisms underlying the correlation, we conducted a systematic investigation in rhesus monkeys infected with the highly pathogenic SHIV 89.6P. This model is widely used in the preclinical evaluation of AIDS vaccine candidates and a thorough understanding of the model's biology is important to the proper interpretation of these evaluations. We found that the levels of peak viremia were positively correlated not only with the levels of set-point viremia but, importantly, with the extent of initial overall immune destruction as indicated by the degree of CD4 + T cell depletion and lymph node germinal center (GC) formation. The extent of initial overall immune destruction was inversely correlated with subsequent development and maintenance of virus-specific cellular and humoral immune responses. Thus, these data suggest that the extent of early immune damage determines the development and durability of virus-specific immunity, thereby playing a critical role in establishing the levels of set-point viral replication in SHIV infection. Vaccines that limit both the initial viral replication and the extent of early immune damage will therefore mediate long-term virus replication control and mitigation of long-term immune destruction in this model of immunodeficiency virus infection

  8. High-throughput gene expression profiling indicates dysregulation of intestinal cell cycle mediators and growth factors during primary simian immunodeficiency virus infection

    Energy Technology Data Exchange (ETDEWEB)

    George, Michael D; Sankaran, Sumathi; Reay, Elizabeth; Gelli, Angie C; Dandekar, Satya

    2003-07-20

    During primary simian immunodeficiency virus (SIV) infection, CD4+ T cells are severely depleted in gut-associated lymphoid tissue (GALT), while CD8+ T-cell numbers dramatically increase. To gain an understanding of the molecular basis of this disruption in T-cell homeostasis, host gene expression was monitored in longitudinal jejunum tissue biopsies from SIV-infected rhesus macaques by DNA microarray analysis. Transcription of cyclin E1, CDC2, retinoblastoma, transforming growth factor (TGF), fibroblast growth factor (FGF), and interleukin-2 was repressed while cyclins B1 and D2 and transcription factor E2F were upregulated, indicating a complex dysregulation of growth and proliferation within the intestinal mucosa. Innate, cell-mediated, and humoral immune responses were markedly upregulated in animals that significantly reduced their viral loads and retained more intestinal CD4+ T cells. We conclude that the alterations in intestinal gene expression during primary SIV infection were characteristic of a broad-range immune response, and reflective of the efficacy of viral suppression.

  9. High-throughput gene expression profiling indicates dysregulation of intestinal cell cycle mediators and growth factors during primary simian immunodeficiency virus infection

    International Nuclear Information System (INIS)

    George, Michael D.; Sankaran, Sumathi; Reay, Elizabeth; Gelli, Angie C.; Dandekar, Satya

    2003-01-01

    During primary simian immunodeficiency virus (SIV) infection, CD4+ T cells are severely depleted in gut-associated lymphoid tissue (GALT), while CD8+ T-cell numbers dramatically increase. To gain an understanding of the molecular basis of this disruption in T-cell homeostasis, host gene expression was monitored in longitudinal jejunum tissue biopsies from SIV-infected rhesus macaques by DNA microarray analysis. Transcription of cyclin E1, CDC2, retinoblastoma, transforming growth factor (TGF), fibroblast growth factor (FGF), and interleukin-2 was repressed while cyclins B1 and D2 and transcription factor E2F were upregulated, indicating a complex dysregulation of growth and proliferation within the intestinal mucosa. Innate, cell-mediated, and humoral immune responses were markedly upregulated in animals that significantly reduced their viral loads and retained more intestinal CD4+ T cells. We conclude that the alterations in intestinal gene expression during primary SIV infection were characteristic of a broad-range immune response, and reflective of the efficacy of viral suppression

  10. Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatability complex class I-mediated control

    Science.gov (United States)

    Beck, Sarah E.; Queen, Suzanne E.; Viscidi, Raphael; Johnson, Darius; Kent, Stephen J.; Adams, Robert J.; Tarwater, Patrick M.; Mankowski, Joseph L.

    2016-01-01

    In the fourth decade of the HIV epidemic, the relationship between host immunity and HIV central nervous system (CNS) disease remains incompletely understood. Using a simian immunodeficiency virus (SIV)/macaque model, we examined CNS outcomes in pigtailed macaques expressing the MHC class I allele Mane-A1*084:01 which confers resistance to SIV-induced CNS disease and induces the prototypic viral escape mutation Gag K165R. Insertion of gag K165R into the neurovirulent clone SIV/17E-Fr reduced viral replication in vitro compared to SIV/17E-Fr. We also found lower CSF, but not plasma, viral loads in macaques inoculated with SIV/17E-Fr K165R versus those inoculated with wildtype. Although escape mutation K165R was genotypically stable in plasma, it rapidly reverted to wildtype Gag KP9 in both CSF and in microglia cultures. We induced robust Gag KP9-specific CTL tetramer responses by vaccinating Mane-A*084:01-positive pigtailed macaques with a Gag KP9 virus-like particle (VLP) vaccine. Upon SIV/17E-Fr challenge, vaccinated animals had lower SIV RNA in CSF compared to unvaccinated controls, but showed no difference in plasma viral loads. These data clearly demonstrate that viral fitness in the CNS is distinct from the periphery and underscores the necessity of understanding the consequences of viral escape in CNS disease with the advent of new therapeutic vaccination strategies. PMID:26727909

  11. Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid

    Science.gov (United States)

    Boyer, Jean D.; Robinson, Tara M.; Kutzler, Michele A.; Vansant, Gordon; Hokey, David A.; Kumar, Sanjeev; Parkinson, Rose; Wu, Ling; Sidhu, Maninder K.; Pavlakis, George N.; Felber, Barbara K.; Brown, Charles; Silvera, Peter; Lewis, Mark G.; Monforte, Joseph; Waldmann, Thomas A.; Eldridge, John; Weiner, David B.

    2007-01-01

    The cell-mediated immune profile induced by a recombinant DNA vaccine was assessed in the simian/HIV (SHIV) and macaque model. The vaccine strategy included coimmunization of a DNA-based vaccine alone or in combination with an optimized plasmid encoding macaque IL-15 (pmacIL-15). We observed strong induction of vaccine-specific IFN-γ-producing CD8+ and CD4+ effector T cells in the vaccination groups. Animals were subsequently challenged with 89.6p. The vaccine groups were protected from ongoing infection, and the IL-15 covaccinated group showed a more rapidly controlled infection than the group treated with DNA vaccine alone. Lymphocytes isolated from the group covaccinated with pmacIL-15 had higher cellular proliferative responses than lymphocytes isolated from the macaques that received SHIV DNA alone. Vaccine antigen activation of lymphocytes was also studied for a series of immunological molecules. Although mRNA for IFN-γ was up-regulated after antigen stimulation, the inflammatory molecules IL-8 and MMP-9 were down-regulated. These observed immune profiles are potentially reflective of the ability of the different groups to control SHIV replication. This study demonstrates that an optimized IL-15 immune adjuvant delivered with a DNA vaccine can impact the cellular immune profile in nonhuman primates and lead to enhanced suppression of viral replication. PMID:18000037

  12. [Inheritable phenotypic normalization of rodent cells transformed by simian adenovirus SA7 E1 oncogenes by singled-stranded oligonucleotides complementary to a long region of integrated oncogenes].

    Science.gov (United States)

    Grineva, N I; Borovkova, T V; Sats, N V; Kurabekova, R M; Rozhitskaia, O S; Solov'ev, G Ia; Pantin, V I

    1995-08-01

    G11 mouse cells and SH2 rat cells transformed with simian adenovirus SA7 DNA showed inheritable oncogen-specific phenotypic normalization when treated with sense and antisense oligonucleotides complementary to long RNA sequences, plus or minus strands of the integrated adenovirus oncogenes E1A and E1B. Transitory treatment of the cells with the oligonucleotides in the absence of serum was shown to cause the appearance of normalized cell lines with fibroblastlike morphology, slower cell proliferation, and lack of ability to form colonies in soft agar. Proliferative activity and adhesion of the normalized cells that established cell lines were found to depend on the concentration of growth factors in the cultural medium. In some of the cell lines, an inhibition of transcription of the E1 oncogenes was observed. The normalization also produced cells that divided 2 - 5 times and died and cells that reverted to a transformed phenotype in 2 - 10 days. The latter appeared predominantly upon the action of the antisense oligonucleotides.

  13. A Macaque Model for Rectal Lymphogranuloma Venereum and Non-Lymphogranuloma Venereum Chlamydia trachomatis: Impact on Rectal Simian/Human Immunodeficiency Virus Acquisition.

    Science.gov (United States)

    Vishwanathan, Sundaram Ajay; Aubert, Rachael D; Morris, Monica R; Zhao, Chunxia; Philips, Christi; Khalil, George M; Deyounks, Frank; Kelley, Kristen; Ritter, Jana M; Chen, C Y; Kersh, Ellen N; McNicholl, Janet M

    2017-09-01

    Sustained genital tract inflammation caused by sexually transmitted infections (STIs) is known to increase risk of vaginal human immunodeficiency virus (HIV) infections but, to our knowledge, there are no nonhuman primate studies that have evaluated its link to rectal HIV acquisition. Rhesus macaques inoculated with Chlamydia trachomatis (CT) (serovars LGV-L2 and CT-E; n = 7) or saline (n = 7) received up to 20 rectal challenges twice a week of simian/HIV immunodeficiency virus (SHIVSF162p3). SHIV viremia was determined by real-time PCR and Chlamydia infection by APTIMA Combo 2 testing. The rectal cytokine-chemokine levels were evaluated by multiplex bead assays. Rectal Chlamydia infection was maintained throughout the study. We did not observe significant differences (P = 1.0) in frequency of SHIV acquisition between the STI and control arms. It took fewer SHIV challenges to infect the STI animals although the difference was not significant (P = 0.59). There were no significant differences in peak plasma viremia between STI and control arms (P = 0.63). The association of plasma viremia with rectal shedding was significantly different by arm (P = 0.038). In the first such study in a macaque model, we did not observe an increased risk of SHIV acquisition due to rectal Chlamydia coinfection. This macaque model can be further developed and expanded to better investigate the impact of different rectal STIs on HIV acquisition.

  14. Simian immunodeficiency virus infection induces severe loss of intestinal central memory T cells which impairs CD4+ T-cell restoration during antiretroviral therapy.

    Science.gov (United States)

    Verhoeven, D; Sankaran, S; Dandekar, S

    2007-08-01

    Simian immunodeficiency virus (SIV) infection leads to severe loss of intestinal CD4(+) T cells and, as compared to peripheral blood, restoration of these cells is slow during antiretroviral therapy (ART). Mechanisms for this delay have not been examined in context of which specific CD4(+) memory subsets or lost and fail to regenerate during ART. Fifteen rhesus macaques were infected with SIV, five of which received ART (FTC/PMPA) for 30 weeks. Viral loads were measured by real-time PCR. Flow cytometric analysis determined changes in T-cell subsets and their proliferative state. Changes in proliferative CD4(+) memory subsets during infection accelerated their depletion. This reduced the central memory CD4(+) T-cell pool and contributed to slow CD4(+) T-cell restoration during ART. There was a lack of restoration of the CD4(+) central memory and effector memory T-cell subsets in gut-associated lymphoid tissue during ART, which may contribute to the altered intestinal T-cell homeostasis in SIV infection.

  15. Robust Covariance Estimators Based on Information Divergences and Riemannian Manifold

    Directory of Open Access Journals (Sweden)

    Xiaoqiang Hua

    2018-03-01

    Full Text Available This paper proposes a class of covariance estimators based on information divergences in heterogeneous environments. In particular, the problem of covariance estimation is reformulated on the Riemannian manifold of Hermitian positive-definite (HPD matrices. The means associated with information divergences are derived and used as the estimators. Without resorting to the complete knowledge of the probability distribution of the sample data, the geometry of the Riemannian manifold of HPD matrices is considered in mean estimators. Moreover, the robustness of mean estimators is analyzed using the influence function. Simulation results indicate the robustness and superiority of an adaptive normalized matched filter with our proposed estimators compared with the existing alternatives.

  16. Bubble Divergences: Sorting out Topology from Cell Structure

    Science.gov (United States)

    Bonzom, Valentin; Smerlak, Matteo

    2012-02-01

    We conclude our analysis of bubble divergences in the flat spinfoam model. In [arXiv:1008.1476] we showed that the divergence degree of an arbitrary two-complex Gamma can be evaluated exactly by means of twisted cohomology. Here, we specialize this result to the case where Gamma is the two-skeleton of the cell decomposition of a pseudomanifold, and sharpen it with a careful analysis of the cellular and topological structures involved. Moreover, we explain in detail how this approach reproduces all the previous powercounting results for the Boulatov-Ooguri (colored) tensor models, and sheds light on algebraic-topological aspects of Gurau's 1/N expansion.

  17. Zimmermann's forest formula, infrared divergences and the QCD beta function

    Directory of Open Access Journals (Sweden)

    Franz Herzog

    2018-01-01

    Full Text Available We review Zimmermann's forest formula, which solves Bogoliubov's recursive R-operation for the subtraction of ultraviolet divergences in perturbative Quantum Field Theory. We further discuss a generalisation of the R-operation which subtracts besides ultraviolet also Euclidean infrared divergences. This generalisation, which goes under the name of the R⁎-operation, can be used efficiently to compute renormalisation constants. We will discuss several results obtained by this method with focus on the QCD beta function at five loops as well as the application to hadronic Higgs boson decay rates at N4LO. This article summarizes a talk given at the Wolfhart Zimmermann Memorial Symposium.

  18. Divergence from factorizable distributions and matroid representations by partitions

    Czech Academy of Sciences Publication Activity Database

    Matúš, František

    2009-01-01

    Roč. 55, č. 12 (2009), s. 5375-5381 ISSN 0018-9448 R&D Projects: GA AV ČR IAA100750603; GA ČR GA201/04/0393 Institutional research plan: CEZ:AV0Z10750506 Keywords : Information divergence * relative entropy * Shannon entropy * exponential family * hierarchical model * log-linear model * contingency table * Gibbs distribution * matroid representation * secret sharing scheme * maximum likelihood. Subject RIV: BA - General Mathematics Impact factor: 2.357, year: 2009 http://library.utia.cas.cz/separaty/2009/MTR/matus-divergence from factorizable distributions and matroid representations by partitions.pdf

  19. O Cabimento dos Embargos de Divergência

    OpenAIRE

    LOURENCO, S. R.

    2012-01-01

    A presente pesquisa objetiva demonstrar os embargos de divergência com enfoque nos elementos processuais do cabimento de tal modalidade recursal em nosso ordenamento jurídico. Para tanto, investigaremos os aspectos gerais dos embargos de divergência, a partir da análise dos elementos históricos enquanto a criação do instituto, como também sua finalidade e classificação no ordenamento jurídico brasileiro. Após, analisaremos o requisito de admissibilidade do cabimento dos embargo...

  20. Ultraviolet divergences in higher dimensional supersymmetric Yang-Mills theories

    International Nuclear Information System (INIS)

    Howe, P.S.; Stelle, K.S.

    1984-01-01

    We determine the loop orders for the onset of allowed ultra-violet divergences in higher dimensional supersymmetric Yang-Mills theories. Cancellations are controlled by the non-renormalization theorems for the linearly realizable supersymmetries and by the requirement that counterterms display the full non-linear supersymmetries when the classical equations of motion are imposed. The first allowed divergences in the maximal super Yang-Mills theories occur at four loops in five dimensions, three loops in six dimensions and two loops in seven dimensions. (orig.)

  1. Asymptotic states and infrared divergences in gauge theories

    International Nuclear Information System (INIS)

    Butler, D.R.

    1981-01-01

    The gauge theories, Gravity and QCD are shown to be infrared finite to a non-trival order by a generalization of the coherent state approach. The asymptotic Hamiltonian operator is used, along with a mathematical theorem by Magnus, to specify a S-operator and to show cancellation of infrared divergences at the amplitude level. This procedure is exemplified in Gravity to third order and applied to QCD for leading order divergences to fifth order in the coupling constant. Dimensional regularization is used to isolate the infrared singularities in QCD. The sections on Gravity include a derivation of the infrared structure of the propagators for a massive particle and the graviton

  2. An ancient divergence among the bacteria. [methanogenic phylogeny

    Science.gov (United States)

    Balch, W. E.; Magrum, L. J.; Fox, G. E.; Wolfe, R. S.; Woese, C. R.

    1977-01-01

    The 16S ribosomal RNZs from two species of met methanogenic bacteria, the mesophile Methanobacterium ruminantium and the thermophile Methanobacterium thermoautotrophicum, have been characterized in terms of the oligonucleotides produced by digestion with T1 ribonuclease. These two organisms are found to be sufficiently related that they can be considered members of the same genus or family. However, they bear only slight resemblance to 'typical' Procaryotic genera; such as Escherichia, Bacillus and Anacystis. The divergence of the methanogenic bacteria from other bacteria may be the most ancient phylogenetic event yet detected - antedating considerably the divergence of the blue green algal line for example, from the main bacterial line.

  3. Rates of genomic divergence in humans, chimpanzees and their lice.

    Science.gov (United States)

    Johnson, Kevin P; Allen, Julie M; Olds, Brett P; Mugisha, Lawrence; Reed, David L; Paige, Ken N; Pittendrigh, Barry R

    2014-02-22

    The rate of DNA mutation and divergence is highly variable across the tree of life. However, the reasons underlying this variation are not well understood. Comparing the rates of genetic changes between hosts and parasite lineages that diverged at the same time is one way to begin to understand differences in genetic mutation and substitution rates. Such studies have indicated that the rate of genetic divergence in parasites is often faster than that of their hosts when comparing single genes. However, the variation in this relative rate of molecular evolution across different genes in the genome is unknown. We compared the rate of DNA sequence divergence between humans, chimpanzees and their ectoparasitic lice for 1534 protein-coding genes across their genomes. The rate of DNA substitution in these orthologous genes was on average 14 times faster for lice than for humans and chimpanzees. In addition, these rates were positively correlated across genes. Because this correlation only occurred for substitutions that changed the amino acid, this pattern is probably produced by similar functional constraints across the same genes in humans, chimpanzees and their ectoparasites.

  4. Micropolar Fluids Using B-spline Divergence Conforming Spaces

    KAUST Repository

    Sarmiento, Adel; Garcia, Daniel; Dalcin, Lisandro; Collier, Nathan; Calo, Victor M.

    2014-01-01

    The divergence free formulation was used to guarantee an accurate solution of the flow. This formulation was implemented using the framework PetIGA as a basis, using its parallel stuctures to achieve high scalability. The results of the square heat driven cavity test case are in good agreement with those reported earlier.

  5. Divergent apparent temperature sensitivity of terrestrial ecosystem respiration

    Science.gov (United States)

    Bing Song; Shuli Niu; Ruise Luo; Yiqi Luo; Jiquan Chen; Guirui Yu; Janusz Olejnik; Georg Wohlfahrt; Gerard Kiely; Ako Noormets; Leonardo Montagnani; Alessandro Cescatti; Vincenzo Magliulo; Beverly Elizabeth Law; Magnus Lund; Andrej Varlagin; Antonio Raschi; Matthias Peichl; Mats B. Nilsson; Lutz Merbold

    2014-01-01

    Recent studies revealed convergent temperature sensitivity of ecosystem respiration (Re) within aquatic ecosystems and between terrestrial and aquatic ecosystems. We do not know yet whether various terrestrial ecosystems have consistent or divergent temperature sensitivity. Here, we synthesized 163 eddy covariance flux sites across the world and...

  6. Gauge-invariance and infrared divergences in the luminosity distance

    Energy Technology Data Exchange (ETDEWEB)

    Biern, Sang Gyu; Yoo, Jaiyul, E-mail: sgbiern@physik.uzh.ch, E-mail: jyoo@physik.uzh.ch [Center for Theoretical Astrophysics and Cosmology, Institute for Computational Science, University of Zürich, Winterthurerstrasse 190, CH-8057, Zürich (Switzerland)

    2017-04-01

    Measurements of the luminosity distance have played a key role in discovering the late-time cosmic acceleration. However, when accounting for inhomogeneities in the Universe, its interpretation has been plagued with infrared divergences in its theoretical predictions, which are in some cases used to explain the cosmic acceleration without dark energy. The infrared divergences in most calculations are artificially removed by imposing an infrared cut-off scale. We show that a gauge-invariant calculation of the luminosity distance is devoid of such divergences and consistent with the equivalence principle, eliminating the need to impose a cut-off scale. We present proper numerical calculations of the luminosity distance using the gauge-invariant expression and demonstrate that the numerical results with an ad hoc cut-off scale in previous calculations have negligible systematic errors as long as the cut-off scale is larger than the horizon scale. We discuss the origin of infrared divergences and their cancellation in the luminosity distance.

  7. Mass generation and the problem of seagull divergences

    International Nuclear Information System (INIS)

    Figueiredo, C. T.; Aguilar, A. C.

    2016-01-01

    The gluon mass generation is a purely non-perturbative effect, and the natural framework to study it in the continuum are the Schwinger-Dyson equations (SDEs) of the theory. At the level of the SDEs the generation of such a mass is associated with the existence of infrared finite solutions for the gluon propagator. From the theoretical point of view, the dynamical gluon mass generation has been traditionally plagued with seagull divergences. In this work, we will review how such divergences can be eliminated completely by virtue of a characteristic identity, valid in dimensional regularization. As a pedagogical example, we will first discuss in the context of scalar QED how it is possible to eliminate all seagull divergences, by triggering the aforementioned special identity, which enforces the masslessness of the photon. Then, we will discuss what happens in QCD and present an Ansatz for the three gluon vertex, which completely eliminates all seagull divergences and at same time allows for the possibility of a dynamical gluon mass generation. (paper)

  8. Sand-mediated divergence between shallow reef communities on ...

    African Journals Online (AJOL)

    Sand-mediated divergence between shallow reef communities on horizontal and vertical substrata in the western Indian Ocean. SN Porter, GM Branch, KJ Sink. Abstract. Distinctions are rarely made between vertical and horizontal surfaces when assessing reef community composition, yet physical differences are expected ...

  9. Speciation in rapidly diverging systems: lessons from Lake Malawi.

    Science.gov (United States)

    Danley, P D; Kocher, T D

    2001-05-01

    Rapid evolutionary radiations provide insight into the fundamental processes involved in species formation. Here we examine the diversification of one such group, the cichlid fishes of Lake Malawi, which have radiated from a single ancestor into more than 400 species over the past 700 000 years. The phylogenetic history of this group suggests: (i) that their divergence has proceeded in three major bursts of cladogenesis; and (ii) that different selective forces have dominated each cladogenic event. The first episode resulted in the divergence of two major lineages, the sand- and rock-dwellers, each adapted to a major benthic macrohabitat. Among the rock-dwellers, competition for trophic resources then drove a second burst of cladogenesis, which resulted in the differentiation of trophic morphology. The third episode of cladogenesis is associated with differentiation of male nuptial colouration, most likely in response to divergent sexual selection. We discuss models of speciation in relation to this observed pattern. We advocate a model, divergence with gene flow, which reconciles the disparate selective forces responsible for the diversification of this group and suggest that the nonadaptive nature of the tertiary episode has significantly contributed to the extraordinary species richness of this group.

  10. Determining divergence times with a protein clock: update and reevaluation

    Science.gov (United States)

    Feng, D. F.; Cho, G.; Doolittle, R. F.; Bada, J. L. (Principal Investigator)

    1997-01-01

    A recent study of the divergence times of the major groups of organisms as gauged by amino acid sequence comparison has been expanded and the data have been reanalyzed with a distance measure that corrects for both constraints on amino acid interchange and variation in substitution rate at different sites. Beyond that, the availability of complete genome sequences for several eubacteria and an archaebacterium has had a great impact on the interpretation of certain aspects of the data. Thus, the majority of the archaebacterial sequences are not consistent with currently accepted views of the Tree of Life which cluster the archaebacteria with eukaryotes. Instead, they are either outliers or mixed in with eubacterial orthologs. The simplest resolution of the problem is to postulate that many of these sequences were carried into eukaryotes by early eubacterial endosymbionts about 2 billion years ago, only very shortly after or even coincident with the divergence of eukaryotes and archaebacteria. The strong resemblances of these same enzymes among the major eubacterial groups suggest that the cyanobacteria and Gram-positive and Gram-negative eubacteria also diverged at about this same time, whereas the much greater differences between archaebacterial and eubacterial sequences indicate these two groups may have diverged between 3 and 4 billion years ago.

  11. Divergent Explanatory Production (DEP): The Relationship between Resilience and Creativity

    Science.gov (United States)

    Hernández, Óscar Sánchez; Méndez, Francisco Xavier; Garber, Judy

    2015-01-01

    Introduction: The aim of the study is to describe and analyze a new test and construct, Divergent Explanatory Production (DEP), defined as the ability to observe adverse situations from various points of view. At the theoretical level, it is a bridge between the reformulated model of learned helplessness (as a resilience model), and creative…

  12. Gauge-invariance and infrared divergences in the luminosity distance

    International Nuclear Information System (INIS)

    Biern, Sang Gyu; Yoo, Jaiyul

    2017-01-01

    Measurements of the luminosity distance have played a key role in discovering the late-time cosmic acceleration. However, when accounting for inhomogeneities in the Universe, its interpretation has been plagued with infrared divergences in its theoretical predictions, which are in some cases used to explain the cosmic acceleration without dark energy. The infrared divergences in most calculations are artificially removed by imposing an infrared cut-off scale. We show that a gauge-invariant calculation of the luminosity distance is devoid of such divergences and consistent with the equivalence principle, eliminating the need to impose a cut-off scale. We present proper numerical calculations of the luminosity distance using the gauge-invariant expression and demonstrate that the numerical results with an ad hoc cut-off scale in previous calculations have negligible systematic errors as long as the cut-off scale is larger than the horizon scale. We discuss the origin of infrared divergences and their cancellation in the luminosity distance.

  13. The equational theory of prebisimilarity over basic CCS with divergence

    NARCIS (Netherlands)

    Aceto, L.; Capobianco, S.; Ingólfsdóttir, A.; Luttik, B.

    2008-01-01

    This paper studies the equational theory of prebisimilarity, a bisimulation-based preorder introduced by Hennessy and Milner in the early 1980s, over basic CCS with the divergent process O. It is well known that prebisimilarity affords a finite ground-complete axiomatization over this language; this

  14. Stimulating Divergent Thinking in Junior High Career Education.

    Science.gov (United States)

    Ranke, Charlotte; Champoux, Ellen M.

    1981-01-01

    Describes a middle school career-oriented teaching unit with emphasis on teaching for divergent thinking. The unit provides hands-on opportunities for eighth-grade students to explore careers using the knowledge and skills developed in their home economics class. The careers are restaurant management, hospitality service, and interior design. (CT)

  15. Divergence time estimates of mammals from molecular clocks and ...

    Indian Academy of Sciences (India)

    Prakash

    2009-10-30

    Oct 30, 2009 ... In the last decade and a half, mammalian phylogeny and lineage divergence .... not the sudden availability of ecological niches following the KTB mass .... fish fauna, ostracods, and palynofossils (Singh et al. 2006;. Prasad et al. ... tendons and hence the functional adaptations of the animal during its life and ...

  16. Transcutaneous vagus nerve stimulation (tVNS) enhances divergent thinking.

    Science.gov (United States)

    Colzato, Lorenza S; Ritter, Simone M; Steenbergen, Laura

    2018-03-01

    Creativity is one of the most important cognitive skills in our complex and fast-changing world. Previous correlative evidence showed that gamma-aminobutyric acid (GABA) is involved in divergent but not convergent thinking. In the current study, a placebo/sham-controlled, randomized between-group design was used to test a causal relation between vagus nerve and creativity. We employed transcutaneous vagus nerve stimulation (tVNS), a novel non-invasive brain stimulation technique to stimulate afferent fibers of the vagus nerve and speculated to increase GABA levels, in 80 healthy young volunteers. Creative performance was assessed in terms of divergent thinking (Alternate Uses Task) and convergent thinking tasks (Remote Associates Test, Creative Problem Solving Task, Idea Selection Task). Results demonstrate active tVNS, compared to sham stimulation, enhanced divergent thinking. Bayesian analysis reported the data to be inconclusive regarding a possible effect of tVNS on convergent thinking. Therefore, our findings corroborate the idea that the vagus nerve is causally involved in creative performance. Even thought we did not directly measure GABA levels, our results suggest that GABA (likely to be increased in active tVNS condition) supports the ability to select among competing options in high selection demand (divergent thinking) but not in low selection demand (convergent thinking). Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. The loop expansion as a divergent-power-series expansion

    International Nuclear Information System (INIS)

    Murai, N.

    1981-01-01

    The loop expansion should be divergent, possibly an asymptotic one, in the Euclidean path integral formulation. This consideration is important in applications of the symmetric and mass-independent renormalization. The [1,1] Pade approximant is calculated in a PHI 4 model. Its classical vacua may be not truely stable for nonzero coupling constant. (author)

  18. Ground state energies from converging and diverging power series expansions

    International Nuclear Information System (INIS)

    Lisowski, C.; Norris, S.; Pelphrey, R.; Stefanovich, E.; Su, Q.; Grobe, R.

    2016-01-01

    It is often assumed that bound states of quantum mechanical systems are intrinsically non-perturbative in nature and therefore any power series expansion methods should be inapplicable to predict the energies for attractive potentials. However, if the spatial domain of the Schrödinger Hamiltonian for attractive one-dimensional potentials is confined to a finite length L, the usual Rayleigh–Schrödinger perturbation theory can converge rapidly and is perfectly accurate in the weak-binding region where the ground state’s spatial extension is comparable to L. Once the binding strength is so strong that the ground state’s extension is less than L, the power expansion becomes divergent, consistent with the expectation that bound states are non-perturbative. However, we propose a new truncated Borel-like summation technique that can recover the bound state energy from the diverging sum. We also show that perturbation theory becomes divergent in the vicinity of an avoided-level crossing. Here the same numerical summation technique can be applied to reproduce the energies from the diverging perturbative sums.

  19. An asymptotic formula of the divergent bilateral basic hypergeometric series

    OpenAIRE

    Morita, Takeshi

    2012-01-01

    We show an asymptotic formula of the divergent bilateral basic hypergeometric series ${}_1\\psi_0 (a;-;q,\\cdot)$ with using the $q$-Borel-Laplace method. We also give the limit $q\\to 1-0$ of our asymptotic formula.

  20. Ground state energies from converging and diverging power series expansions

    Energy Technology Data Exchange (ETDEWEB)

    Lisowski, C.; Norris, S.; Pelphrey, R.; Stefanovich, E., E-mail: eugene-stefanovich@usa.net; Su, Q.; Grobe, R.

    2016-10-15

    It is often assumed that bound states of quantum mechanical systems are intrinsically non-perturbative in nature and therefore any power series expansion methods should be inapplicable to predict the energies for attractive potentials. However, if the spatial domain of the Schrödinger Hamiltonian for attractive one-dimensional potentials is confined to a finite length L, the usual Rayleigh–Schrödinger perturbation theory can converge rapidly and is perfectly accurate in the weak-binding region where the ground state’s spatial extension is comparable to L. Once the binding strength is so strong that the ground state’s extension is less than L, the power expansion becomes divergent, consistent with the expectation that bound states are non-perturbative. However, we propose a new truncated Borel-like summation technique that can recover the bound state energy from the diverging sum. We also show that perturbation theory becomes divergent in the vicinity of an avoided-level crossing. Here the same numerical summation technique can be applied to reproduce the energies from the diverging perturbative sums.

  1. Divergent synthesis and optoelectronic properties of oligodiacetylene building blocks

    NARCIS (Netherlands)

    Pilzak, G.S.; Lagen, van B.; Sudhölter, E.J.R.; Zuilhof, H.

    2008-01-01

    A new and divergent synthetic route to oligodiacetylene (ODA) building blocks has been developed via Sonogashira reactions under a reductive atmosphere. These central building blocks provide a new way for rapid preparation of long ODAs. In addition, we report on their optoelectronic properties which

  2. Navier–Stokes flow in converging–diverging distensible tubes

    Directory of Open Access Journals (Sweden)

    Taha Sochi

    2015-09-01

    Full Text Available We use a method based on the lubrication approximation in conjunction with a residual-based mass-continuity iterative solution scheme to compute the flow rate and pressure field in distensible converging–diverging tubes for Navier–Stokes fluids. We employ an analytical formula derived from a one-dimensional version of the Navier–Stokes equations to describe the underlying flow model that provides the residual function. This formula correlates the flow rate to the boundary pressures in straight cylindrical elastic tubes with constant-radius. We validate our findings by the convergence toward a final solution with fine discretization as well as by comparison to the Poiseuille-type flow in its convergence toward analytic solutions found earlier in rigid converging–diverging tubes. We also tested the method on limiting special cases of cylindrical elastic tubes with constant-radius where the numerical solutions converged to the expected analytical solutions. The distensible model has also been endorsed by its convergence toward the rigid Poiseuille-type model with increasing the tube wall stiffness. Lubrication-based one-dimensional finite element method was also used for verification. In this investigation five converging–diverging geometries are used for demonstration, validation and as prototypes for modeling converging–diverging geometries in general.

  3. Functional Analysis of HIV/AIDS Stigma: Consensus or Divergence?

    Science.gov (United States)

    Hosseinzadeh, Hassan; Hossain, Syeda Zakia

    2011-01-01

    Functional theory proposes that attitudes may serve a variety of purposes for individuals. This study aimed to determine whether stigmatized attitudes toward HIV/AIDS serve the same function for all (consensus function) or serve different functions for different individuals (divergence function) by assessing various aspects of HIV/AIDS stigma…

  4. When can stress facilitate divergence by altering time to flowering?

    OpenAIRE

    Jordan, Crispin Y.; Ally, Dilara; Hodgins, Kathryn A.

    2015-01-01

    Abstract Stressors and heterogeneity are ubiquitous features of natural environments, and theory suggests that when environmental qualities alter flowering schedules through phenotypic plasticity, assortative mating can result that promotes evolutionary divergence. Therefore, it is important to determine whether common ecological stressors induce similar changes in flowering time. We review previous studies to determine whether two important stressors, water restriction and herbivory, induce ...

  5. When can stress facilitate divergence by altering time to flowering?

    Science.gov (United States)

    Jordan, Crispin Y; Ally, Dilara; Hodgins, Kathryn A

    2015-12-01

    Stressors and heterogeneity are ubiquitous features of natural environments, and theory suggests that when environmental qualities alter flowering schedules through phenotypic plasticity, assortative mating can result that promotes evolutionary divergence. Therefore, it is important to determine whether common ecological stressors induce similar changes in flowering time. We review previous studies to determine whether two important stressors, water restriction and herbivory, induce consistent flowering time responses among species; for example, how often do water restriction and herbivory both delay flowering? We focus on the direction of change in flowering time, which affects the potential for divergence in heterogeneous environments. We also tested whether these stressors influenced time to flowering and nonphenology traits using Mimulus guttatus. The literature review suggests that water restriction has variable effects on flowering time, whereas herbivory delays flowering with exceptional consistency. In the Mimulus experiment, low water and herbivory advanced and delayed flowering, respectively. Overall, our results temper theoretical predictions for evolutionary divergence due to habitat-induced changes in flowering time; in particular, we discuss how accounting for variation in the direction of change in flowering time can either increase or decrease the potential for divergence. In addition, we caution against adaptive interpretations of stress-induced phenology shifts.

  6. Genetic Divergence in Ducks for Economic Traits | Kalita | Animal ...

    African Journals Online (AJOL)

    D2 Statistics was used to identify the genetic divergence in 4 groups of duck, namely Khaki Campbell (KC), Desi (D), Khaki Campbell x Desi (KC x D) and Desi x Khaki Campbell (D x KC) reared under rural conditions at the Siphajar, Darrang District, Assam, India. The study showed that both Khaki Campbell and Desi or ...

  7. Micropolar Fluids Using B-spline Divergence Conforming Spaces

    KAUST Repository

    Sarmiento, Adel

    2014-06-06

    We discretized the two-dimensional linear momentum, microrotation, energy and mass conservation equations from micropolar fluids theory, with the finite element method, creating divergence conforming spaces based on B-spline basis functions to obtain pointwise divergence free solutions [8]. Weak boundary conditions were imposed using Nitsche\\'s method for tangential conditions, while normal conditions were imposed strongly. Once the exact mass conservation was provided by the divergence free formulation, we focused on evaluating the differences between micropolar fluids and conventional fluids, to show the advantages of using the micropolar fluid model to capture the features of complex fluids. A square and an arc heat driven cavities were solved as test cases. A variation of the parameters of the model, along with the variation of Rayleigh number were performed for a better understanding of the system. The divergence free formulation was used to guarantee an accurate solution of the flow. This formulation was implemented using the framework PetIGA as a basis, using its parallel stuctures to achieve high scalability. The results of the square heat driven cavity test case are in good agreement with those reported earlier.

  8. The odd couple: Diverging paths in language policy and educational ...

    African Journals Online (AJOL)

    This paper examines the divergences between what educational policy calls for in South African schools with regard to language and learning and what takes place in schools. It argues that South African constitutional and education policy statements employ an idea of languages as bound entities and systems, and ...

  9. Analysis of growth characteristics in short-term divergently selected ...

    African Journals Online (AJOL)

    weeks of age body weight in divergent lines of Japanese quail. Growth curves for both sexes within each selection group resembled the general sigmoid shape of a typical growth curve. Gompertz model curves and the observed growth curves were ...

  10. Divergence-Free Wavelets on the Hypercube : General Boundary Conditions

    NARCIS (Netherlands)

    Stevenson, R.

    2016-01-01

    On the n-dimensional hypercube, for given k∈N, wavelet Riesz bases are constructed for the subspace of divergence-free vector fields of the Sobolev space Hk((0,1)n)n with general homogeneous Dirichlet boundary conditions, including slip or no-slip boundary conditions. Both primal and suitable dual

  11. Factor analysis models via I-divergence optimization

    NARCIS (Netherlands)

    Finesso, L.; Spreij, P.

    2016-01-01

    Given a positive definite covariance matrix Σˆ of dimension n, we approximate it with a covariance of the form HH⊤+D, where H has a prescribed number k0 is diagonal. The quality of the approximation is gauged by the I-divergence between the zero mean normal laws with covariances

  12. Divergência genética em linhagens de melancia Genetic divergence in watermelon lines

    Directory of Open Access Journals (Sweden)

    Flávio de França Souza

    2005-06-01

    Full Text Available A divergência genética entre 31 genótipos de melancia foi avaliada por meio da análise de variáveis canônicas e de técnicas de agrupamento (Tocher e método hierárquico de Ward baseadas na distância generalizada de Mahalanobis (D²ii'. Trinta linhagens, obtidas a partir de acessos coletados no Nordeste brasileiro e a cultivar 'Crimson Sweet' foram avaliadas quanto ao número de dias para o aparecimento da primeira flor masculina e da primeira flor feminina (NDM e NDF; número do nó da primeira flor masculina e da primeira flor feminina (NGM e NGF; número de frutos por planta (NFP; comprimento de rama principal (CRP; peso médio de fruto (PMF; teor de sólidos solúveis (TSS; diâmetro transversal e longitudinal do fruto (DTF e DLF e espessura média de casca (EMC. O experimento foi realizado em delineamento de blocos ao acaso com três repetições, compostas por parcelas de sete plantas. As características que mais contribuíram para a divergência entre as linhagens foram número de frutos por planta, diâmetro longitudinal, teor de sólidos solúveis e peso médio de fruto. Foram formados três grupos por meio do método de otimização de Tocher, três por meio do método hierárquico de Ward e quatro grupos pela dispersão gráfica baseada nas duas primeiras variáveis canônicas. Neste caso, o grupo I compôs-se de sete linhagens de Pernambuco e uma da Bahia; o grupo II reuniu todas as 21 linhagens do Maranhão; os grupos III e IV foram compostos pela linhagem 97-0247.008 (Pernambuco e pela cultivar Crimson Sweet, respectivamente. As linhagens 87-019.021 e 87-019.022 foram as mais semelhantes, enquanto a linhagem 87-019.023 e 'Crimson Sweet' apresentaram maior dissimilaridade pela distância generalizada Mahalanobis (D²ii'. Os cruzamentos mais promissores serão aqueles realizados entre Crimson Sweet e as linhagens do grupo II. Cruzamentos entre Crimson Sweet e as linhagens do grupo I serão interessantes para a obtenção de

  13. Lentiviral Gag assembly analyzed through the functional characterization of chimeric simian immunodeficiency viruses expressing different domains of the feline immunodeficiency virus capsid protein.

    Directory of Open Access Journals (Sweden)

    María J Esteva

    Full Text Available To gain insight into the functional relationship between the capsid (CA domains of the Gag polyproteins of simian and feline immunodeficiency viruses (SIV and FIV, respectively, we constructed chimeric SIVs in which the CA-coding region was partially or totally replaced by the equivalent region of the FIV CA. The phenotypic characterization of the chimeras allowed us to group them into three categories: the chimeric viruses that, while being assembly-competent, exhibit a virion-associated unstable FIV CA; a second group represented only by the chimeric SIV carrying the N-terminal domain (NTD of the FIV CA which proved to be assembly-defective; and a third group constituted by the chimeric viruses that produce virions exhibiting a mature and stable FIV CA protein, and which incorporate the envelope glycoprotein and contain wild-type levels of viral genome RNA and reverse transcriptase. Further analysis of the latter group of chimeric SIVs demonstrated that they are non-infectious due to a post-entry impairment, such as uncoating of the viral core, reverse transcription or nuclear import of the preintegration complex. Furthermore, we show here that the carboxyl-terminus domain (CTD of the FIV CA has an intrinsic ability to dimerize in vitro and form high-molecular-weight oligomers, which, together with our finding that the FIV CA-CTD is sufficient to confer assembly competence to the resulting chimeric SIV Gag polyprotein, provides evidence that the CA-CTD exhibits more functional plasticity than the CA-NTD. Taken together, our results provide relevant information on the biological relationship between the CA proteins of primate and nonprimate lentiviruses.

  14. Enhanced mutagenesis of UV-irradiated simian virus 40 occurs in mitomycin C-treated host cells only at a low multiplicity of infection

    International Nuclear Information System (INIS)

    Sarasin, A.; Benoit, A.

    1986-01-01

    Treatment of monkey kidney cells with mitomycin C (MMC) 24 h prior to infection with UV-irradiated simian virus 40 (SV40) enhanced both virus survival and virus mutagenesis. The use of SV40 as a biological probe has been taken as an easy method to analyse SOS response of mammalian cells to the stress caused by DNA damage or inhibition of DNA replication. The mutation assay we used was based on the reversion from a temperature-sensitive phenotype (tsA58 mutant) to a wild-type phenotype. The optimal conditions for producing enhanced survival and mutagenesis in the virus progeny were determined with regard to the multiplicity of infection (MOI). Results showed that the level of enhanced mutagenesis observed for UV-irradiated virus grown in MMC-treated cells was an inverse function of the MOI, while enhanced survival was observed at nearly the same level regardless of the MOI. For the unirradiated virus, almost no increase in the mutation of virus progeny issued from MMC-treated cells was observed, while a small amount of enhanced virus survival was obtained. These results show that enhanced virus mutagenesis and enhanced virus survival can be dissociated under some experimental conditions. Enhanced virus mutagenesis, analogous to the error-prone replication of phages in SOS-induced bacteria, was observed, at least for SV40, only when DNA of both virus and host cells was damaged and when infection occurred with a small number of viral particles. We therefore hypothesize that an error-prone replication mode of UV-damaged templates is observed in induced monkey kidney cells

  15. Simian rhesus rotavirus is a unique heterologous (non-lapine) rotavirus strain capable of productive replication and horizontal transmission in rabbits.

    Science.gov (United States)

    Ciarlet, M; Estes, M K; Conner, M E

    2000-05-01

    Simian rhesus rotavirus (RRV) is the only identified heterologous (non-lapine) rotavirus strain capable of productive replication at a high inoculum dose of virus (>10(8) p.f.u.) in rabbits. To evaluate whether lower doses of RRV would productively infect rabbits and to obtain an estimate of the 50% infectious dose, rotavirus antibody-free rabbits were inoculated orally with RRV at inoculum doses of 10(3), 10(5) or 10(7) p.f.u. Based on faecal virus antigen or infectious virus shedding, RRV replication was observed with inoculum doses of 10(7) and 10(5) p.f.u., but not 10(3) p.f.u. Horizontal transmission of RRV to one of three mock-inoculated rabbits occurred 4-5 days after onset of virus antigen shedding in RRV-infected rabbits. Rabbits infected at 10(7) and 10(5), but not 10(3), p.f.u. of RRV developed rotavirus-specific immune responses and were completely (100%) protected from lapine ALA rotavirus challenge. These data confirm that RRV can replicate productively and spread horizontally in rabbits. In attempts to elucidate the genetic basis of the unusual replication efficacy of RRV in rabbits, the sequence of the gene encoding the lapine non-structural protein NSP1 was determined. Sequence analysis of the NSP1 of three lapine rotaviruses revealed a high degree of amino acid identity (85-88%) with RRV. Since RRV and lapine strains also share similar VP7s (96-97%) and VP4s (69-70%), RRV might replicate efficiently in rabbits because of the high relatedness of these three gene products, each implicated in host range restriction.

  16. Activation of ATPase activity of simian virus 40 large T antigen by the covalent affinity analog of ATP, fluorosulfonylbenzoyl 5'-adenosine.

    Science.gov (United States)

    Bradley, M K

    1990-01-01

    Fluorosulfonylbenzoyl 5'-adenosine (FSBA) bound to one site in simian virus 40 large T antigen (T) and covalently modified greater than 95% of the molecules in a complete reaction. This analog for ATP specifically cross-links to the Mg-phosphate pocket in ATP-binding sites. Cyanogen bromide cleavage and tryptic digestion of [14C]FSBA-labeled protein, paired with T-specific monoclonal antibody analyses, were used to map the site in T to a tryptic peptide just C terminal to the PAb204 epitope. The location of the FSBA linkage was consistent with the predicted tertiary structure of the ATP-binding region in T described previously (M. K. Bradley, T. F. Smith, R. H. Lathrop, D. M. Livingston, and T. A. Webster, Proc. Natl. Acad. Sci. USA 84:4026-4030, 1987). Binding of FSBA to T was cooperative, implying an interaction between two binding sites. This could occur if the protein formed a dimer, and it is known that the ATPase activity is associated with a dimeric T. Most interesting was the activation of the ATPase when up to 50% of T was bound by the analog. The effect was also produced by preincubation with millimolar concentrations of ATP or the nonhydrolyzable analog gamma beta-methylene 5'-adenosine diphosphate at elevated temperatures. When greater than 50% of T was modified by FSBA, the ATPase was inhibited as the analog cross-linked to the second, previously activated, binding site. These data support a dual function for the one ATP-binding site in T as both regulatory and catalytic. Images PMID:1697910

  17. Structure-based design of a disulfide-linked oligomeric form of the simian virus 40 (SV40) large T antigen DNA-binding domain

    International Nuclear Information System (INIS)

    Meinke, Gretchen; Phelan, Paul; Fradet-Turcotte, Amélie; Archambault, Jacques; Bullock, Peter A.

    2011-01-01

    With the aim of forming the ‘lock-washer’ conformation of the origin-binding domain of SV40 large T antigen in solution, using structure-based analysis an intermolecular disulfide bridge was engineered into the origin-binding domain to generate higher order oligomers in solution. The 1.7 Å resolution structure shows that the mutant forms a spiral in the crystal and has the de novo disulfide bond at the protein interface, although structural rearrangements at the interface are observed relative to the wild type. The modular multifunctional protein large T antigen (T-ag) from simian virus 40 orchestrates many of the events needed for replication of the viral double-stranded DNA genome. This protein assembles into single and double hexamers on specific DNA sequences located at the origin of replication. This complicated process begins when the origin-binding domain of large T antigen (T-ag ODB) binds the GAGGC sequences in the central region (site II) of the viral origin of replication. While many of the functions of purified T-ag OBD can be studied in isolation, it is primarily monomeric in solution and cannot assemble into hexamers. To overcome this limitation, the possibility of engineering intermolecular disulfide bonds in the origin-binding domain which could oligomerize in solution was investigated. A recent crystal structure of the wild-type T-ag OBD showed that this domain forms a left-handed spiral in the crystal with six subunits per turn. Therefore, we analyzed the protein interface of this structure and identified two residues that could potentially support an intermolecular disulfide bond if changed to cysteines. SDS–PAGE analysis established that the mutant T-ag OBD formed higher oligomeric products in a redox-dependent manner. In addition, the 1.7 Å resolution crystal structure of the engineered disulfide-linked T-ag OBD is reported, which establishes that oligomerization took place in the expected manner

  18. Durable protection from vaginal simian-human immunodeficiency virus infection in macaques by tenofovir gel and its relationship to drug levels in tissue.

    Science.gov (United States)

    Dobard, Charles; Sharma, Sunita; Martin, Amy; Pau, Chou-Pong; Holder, Angela; Kuklenyik, Zsuzsanna; Lipscomb, Jonathan; Hanson, Debra L; Smith, James; Novembre, Francis J; García-Lerma, J Gerardo; Heneine, Walid

    2012-01-01

    A vaginal gel containing 1% tenofovir (TFV) was found to be safe and effective in reducing HIV infection in women when used pericoitally. Because of the long intracellular half-life of TFV and high drug exposure in vaginal tissues, we hypothesized that a vaginal gel containing TFV may provide long-lasting protection. Here, we performed delayed-challenge experiments and showed that vaginal 1% TFV gel protected 4/6 macaques against vaginal simian-human immunodeficiency virus (SHIV) exposures occurring 3 days after gel application, demonstrating long-lasting protection. Despite continued gel dosing postinfection, neither breakthrough infection had evidence of drug resistance by ultrasensitive testing of SHIV in plasma and vaginal lavage. Analysis of the active intracellular tenofovir diphosphate (TFV-DP) in vaginal lymphocytes collected 4 h to 3 days after gel dosing persistently showed high TFV-DP levels (median, 1,810 fmol/10(6) cells) between 4 and 24 h that exceed the 95% inhibitory concentration (IC(95)), reflecting rapid accumulation and long persistence. In contrast to those in peripheral blood mononuclear cells (PBMCs) following oral dosing, TFV-DP levels in vaginal lymphocytes decreased approximately 7-fold by 3 days, exhibiting a much higher rate of decay. We observed a strong correlation between intracellular TFV-DP in vaginal lymphocytes, in vitro antiviral activity, and in vivo protection, suggesting that TFV-DP above the in vitro IC(95) in vaginal lymphocytes is a good predictor of high efficacy. Data from this model reveal an extended window of protection by TFV gel that supports coitus-independent use. The identification of protective TFV-DP concentrations in vaginal lymphocytes may facilitate the evaluation of improved delivery methods of topical TFV and inform clinical studies.

  19. Immunogenicity of NYVAC Prime-Protein Boost Human Immunodeficiency Virus Type 1 Envelope Vaccination and Simian-Human Immunodeficiency Virus Challenge of Nonhuman Primates.

    Science.gov (United States)

    Saunders, Kevin O; Santra, Sampa; Parks, Robert; Yates, Nicole L; Sutherland, Laura L; Scearce, Richard M; Balachandran, Harikrishnan; Bradley, Todd; Goodman, Derrick; Eaton, Amanda; Stanfield-Oakley, Sherry A; Tartaglia, James; Phogat, Sanjay; Pantaleo, Giuseppe; Esteban, Mariano; Gomez, Carmen E; Perdiguero, Beatriz; Jacobs, Bertram; Kibler, Karen; Korber, Bette; Montefiori, David C; Ferrari, Guido; Vandergrift, Nathan; Liao, Hua-Xin; Tomaras, Georgia D; Haynes, Barton F

    2018-04-15

    A preventive human immunodeficiency virus type 1 (HIV-1) vaccine is an essential part of the strategy to eradicate AIDS. A critical question is whether antibodies that do not neutralize primary isolate (tier 2) HIV-1 strains can protect from infection. In this study, we investigated the ability of an attenuated poxvirus vector (NYVAC) prime-envelope gp120 boost to elicit potentially protective antibody responses in a rhesus macaque model of mucosal simian-human immunodeficiency virus (SHIV) infection. NYVAC vector delivery of a group M consensus envelope, trivalent mosaic envelopes, or a natural clade B isolate B.1059 envelope elicited antibodies that mediated neutralization of tier 1 viruses, cellular cytotoxicity, and phagocytosis. None of the macaques made neutralizing antibodies against the tier 2 SHIV SF162P3 used for mucosal challenge. Significant protection from infection was not observed for the three groups of vaccinated macaques compared to unvaccinated macaques, although binding antibody to HIV-1 Env correlated with decreased viremia after challenge. Thus, NYVAC Env prime-gp120 boost vaccination elicited polyfunctional, nonneutralizing antibody responses with minimal protective activity against tier 2 SHIV mucosal challenge. IMPORTANCE The antibody responses that confer protection against HIV-1 infection remain unknown. Polyfunctional antibody responses correlated with time to infection in previous macaque studies. Determining the ability of vaccines to induce these types of responses is critical for understanding how to improve upon the one efficacious human HIV-1 vaccine trial completed thus far. We characterized the antibody responses induced by a NYVAC-protein vaccine and determined the protective capacity of polyfunctional antibody responses in an R5, tier 2 mucosal SHIV infection model. Copyright © 2018 American Society for Microbiology.

  20. Simian Immunodeficiency Virus (SIV-Specific Chimeric Antigen Receptor-T Cells Engineered to Target B Cell Follicles and Suppress SIV Replication

    Directory of Open Access Journals (Sweden)

    Kumudhini Preethi Haran

    2018-03-01

    Full Text Available There is a need to develop improved methods to treat and potentially cure HIV infection. During chronic HIV infection, replication is concentrated within T follicular helper cells (Tfh located within B cell follicles, where low levels of virus-specific CTL permit ongoing viral replication. We previously showed that elevated levels of simian immunodeficiency virus (SIV-specific CTL in B cell follicles are linked to both decreased levels of viral replication in follicles and decreased plasma viral loads. These findings provide the rationale to develop a strategy for targeting follicular viral-producing (Tfh cells using antiviral chimeric antigen receptor (CAR T cells co-expressing the follicular homing chemokine receptor CXCR5. We hypothesize that antiviral CAR/CXCR5-expressing T cells, when infused into an SIV-infected animal or an HIV-infected individual, will home to B cell follicles, suppress viral replication, and lead to long-term durable remission of SIV and HIV. To begin to test this hypothesis, we engineered gammaretroviral transduction vectors for co-expression of a bispecific anti-SIV CAR and rhesus macaque CXCR5. Viral suppression by CAR/CXCR5-transduced T cells was measured in vitro, and CXCR5-mediated migration was evaluated using both an in vitro transwell migration assay, as well as a novel ex vivo tissue migration assay. The functionality of the CAR/CXCR5 T cells was demonstrated through their potent suppression of SIVmac239 and SIVE660 replication in in vitro and migration to the ligand CXCL13 in vitro, and concentration in B cell follicles in tissues ex vivo. These novel antiviral immunotherapy products have the potential to provide long-term durable remission (functional cure of HIV and SIV infections.

  1. Herpes simplex virus-1 infection or Simian virus 40-mediated immortalization of corneal cells causes permanent translocation of NLRP3 to the nuclei

    Directory of Open Access Journals (Sweden)

    Shu-Long Wang

    2015-01-01

    Full Text Available AIM: To investigate into the potential involvement of pyrin containing 3 gene (NLRP3, a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses. METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1 (HSV-1. Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40 (SV40-immortalized human corneal epithelial cell line were also examined. Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β. RESULTS: The NLRP3 activation induced by HSV-1 infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore, in the SV40-immortalized human corneal epithelial cells, NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium (known as an inhibitor of NLRP3 activation effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot. CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.

  2. Structure of rapidity divergences in multi-parton scattering soft factors

    Science.gov (United States)

    Vladimirov, Alexey

    2018-04-01

    We discuss the structure of rapidity divergences that are presented in the soft factors of transverse momentum dependent (TMD) factorization theorems. To provide the discussion on the most general level we consider soft factors for multi-parton scattering. We show that the rapidity divergences are result of the gluon exchanges with the distant transverse plane, and are structurally equivalent to the ultraviolet divergences. It allows to formulate and to prove the renormalization theorem for rapidity divergences. The proof is made with the help the conformal transformation which maps rapidity divergences to ultraviolet divergences. The theorem is the systematic form of the factorization of rapidity divergences, which is required for the definition of TMD parton distributions. In particular, the definition of multi parton distributions is presented. The equivalence of ultraviolet and rapidity divergences leads to the exact relation between soft and rapidity anomalous dimensions. Using this relation we derive the rapidity anomalous dimension at the three-loop order.

  3. Divergence of perturbation theory in large scale structures

    Science.gov (United States)

    Pajer, Enrico; van der Woude, Drian

    2018-05-01

    We make progress towards an analytical understanding of the regime of validity of perturbation theory for large scale structures and the nature of some non-perturbative corrections. We restrict ourselves to 1D gravitational collapse, for which exact solutions before shell crossing are known. We review the convergence of perturbation theory for the power spectrum, recently proven by McQuinn and White [1], and extend it to non-Gaussian initial conditions and the bispectrum. In contrast, we prove that perturbation theory diverges for the real space two-point correlation function and for the probability density function (PDF) of the density averaged in cells and all the cumulants derived from it. We attribute these divergences to the statistical averaging intrinsic to cosmological observables, which, even on very large and "perturbative" scales, gives non-vanishing weight to all extreme fluctuations. Finally, we discuss some general properties of non-perturbative effects in real space and Fourier space.

  4. Little evidence for dynamic divergences in ultraviscous molecular liquids

    DEFF Research Database (Denmark)

    Hecksher, Tina; Nielsen, Albena; Olsen, Niels Boye

    2008-01-01

    The physics of the ultraviscous liquid phase preceding glass formation continues to pose major problems that remain unsolved. It is actively debated, for instance, whether the marked increase of the relaxation time reflects an underlying phase transition to a state of infinite relaxation time....... To elucidate the empirical evidence for this intriguing scenario, some of the most accurate relaxationtime data available for any class of ultraviscous liquids-those obtained by dielectric relaxation experiments on organic liquids just above the glass transition-were compiled. Analysis of data for 42 liquids...... shows that there is no compelling evidence for the Vogel-Fulcher-Tammann (VFT) prediction that the relaxation time diverges at a finite temperature.We conclude that theories with a dynamic divergence of the VFT formlack a direct experimental basis....

  5. Convergence and divergence, a concept for explaining drug actions.

    Science.gov (United States)

    Watanabe, Takehiko; Kamisaki, Yoshinori; Timmerman, Henk

    2004-10-01

    For the teaching and/or learning about drug actions and for the discovery and development of new drugs, it is important to understand how drugs act on living bodies. So far, there has been no clear description on the general principle of drug action in pharmacology textbooks. We propose two principles to depict the action mechanism of drugs. The first is that most, if not all, drugs act on proteins at the molecular level, that is, enzymes, receptors, ion channels, and transporters. The second is that a drug may cause divergent or convergent responses, resulting in changes of a physiological or pathological function of the human body. The concept of divergence and convergence can be used to explain the complex individuality of drug actions.

  6. Divergent biparietal diameter growth rates in twin pregnancies.

    Science.gov (United States)

    Houlton, M C

    1977-05-01

    Twenty-eight twin pregnancies were monitored by serial ultrasonic cephalometry from 30 or 31 weeks' gestation. The rates of growth of the individual twins as determined by biparietal diameters were similar in 11 cases (39%) and divergent in 17 (61%). When the rates of growth were divergent, the lesser rate was always below the mean for singleton pregnancies, and the incidence of small-for-gestational-age babies was 18 of 34 (53%). It was apparent that the greater the difference in biparietal diameters within the 2 weeks preceding delivery, the higher the risk of a small-for-gestation-age baby being delivered. No comment could be made on the growth rate prior to 28 weeks except that at diagnosis there was little or no difference in biparietal diameters.

  7. Divergent unprotected peptide macrocyclisation by palladium-mediated cysteine arylation.

    Science.gov (United States)

    Rojas, Anthony J; Zhang, Chi; Vinogradova, Ekaterina V; Buchwald, Nathan H; Reilly, John; Pentelute, Bradley L; Buchwald, Stephen L

    2017-06-01

    Macrocyclic peptides are important therapeutic candidates due to their improved physicochemical properties in comparison to their linear counterparts. Here we detail a method for a divergent macrocyclisation of unprotected peptides by crosslinking two cysteine residues with bis-palladium organometallic reagents. These synthetic intermediates are prepared in a single step from commercially available aryl bis-halides. Two bioactive linear peptides with cysteine residues at i , i + 4 and i , i + 7 positions, respectively, were cyclised to introduce a diverse array of aryl and bi-aryl linkers. These two series of macrocyclic peptides displayed similar linker-dependent lipophilicity, phospholipid affinity, and unique volume of distributions. Additionally, one of the bioactive peptides showed target binding affinity that was predominantly affected by the length of the linker. Collectively, this divergent strategy allowed rapid and convenient access to various aryl linkers, enabling the systematic evaluation of the effect of appending unit on the medicinal properties of macrocyclic peptides.

  8. Summation of Divergent Series and Zeldovich's Regularization Method

    International Nuclear Information System (INIS)

    Mur, V.D.; Pozdnyakov, S.G.; Popruzhenko, S.V.; Popov, V.S.

    2005-01-01

    A method for summing divergent series, including perturbation-theory series, is considered. This method is an analog of Zeldovich's regularization method in the theory of quasistationary states. It is shown that the method in question is more powerful than the well-known Abel and Borel methods, but that it is compatible with them (that is, it leads to the same value for the sum of a series). The constraints on the parameter domain that arise upon the removal of the regularization of divergent integrals by this method are discussed. The dynamical Stark shifts and widths of loosely bound s states in the field of a circularly polarized electromagnetic wave are calculated at various values of the Keldysh adiabaticity parameter and the multiquantum parameter

  9. Divergence-free MHD Simulations with the HERACLES Code

    Directory of Open Access Journals (Sweden)

    Vides J.

    2013-12-01

    Full Text Available Numerical simulations of the magnetohydrodynamics (MHD equations have played a significant role in plasma research over the years. The need of obtaining physical and stable solutions to these equations has led to the development of several schemes, all requiring to satisfy and preserve the divergence constraint of the magnetic field numerically. In this paper, we aim to show the importance of maintaining this constraint numerically. We investigate in particular the hyperbolic divergence cleaning technique applied to the ideal MHD equations on a collocated grid and compare it to the constrained transport technique that uses a staggered grid to maintain the property. The methods are implemented in the software HERACLES and several numerical tests are presented, where the robustness and accuracy of the different schemes can be directly compared.

  10. Relations between heat exchange and Rényi divergences

    Science.gov (United States)

    Wei, Bo-Bo

    2018-04-01

    In this work, we establish an exact relation which connects the heat exchange between two systems initialized in their thermodynamic equilibrium states at different temperatures and the Rényi divergences between the initial thermodynamic equilibrium state and the final nonequilibrium state of the total system. The relation tells us that the various moments of the heat statistics are determined by the Renyi divergences between the initial equilibrium state and the final nonequilibrium state of the global system. In particular the average heat exchange is quantified by the relative entropy between the initial equilibrium state and the final nonequilibrium state of the global system. The relation is applicable to both finite classical systems and finite quantum systems.

  11. Divergent series, summability and resurgence II simple and multiple summability

    CERN Document Server

    Loday-Richaud, Michèle

    2016-01-01

    Addressing the question how to “sum” a power series in one variable when it diverges, that is, how to attach to it analytic functions, the volume gives answers by presenting and comparing the various theories of k-summability and multisummability. These theories apply in particular to all solutions of ordinary differential equations. The volume includes applications, examples and revisits, from a cohomological point of view, the group of tangent-to-identity germs of diffeomorphisms of C studied in volume 1. With a view to applying the theories to solutions of differential equations, a detailed survey of linear ordinary differential equations is provided which includes Gevrey asymptotic expansions, Newton polygons, index theorems and Sibuya’s proof of the meromorphic classification theorem that characterizes the Stokes phenomenon for linear differential equations. This volume is the second of a series of three entitled Divergent Series, Summability and Resurgence. It is aimed at graduate students and res...

  12. Divergence of Cs-137 sources fluence used in brachytherapy

    International Nuclear Information System (INIS)

    Vianello, E.A.; Almeida, C.E. de

    1998-01-01

    In this work the experimental determination of correction factor for fluence divergence (kln) of linear Cs-137 sources CDCS J4, with Farmer ionization chamber model 2571 in a central and perpendicular plan to source axis, for distances range from 1 to 7 cm., has been presented. The experimental results were compared to calculating by Kondo and Randolph (1960) isotropic theory and Bielajew (1990) anisotropic theory. (Author)

  13. Real and metaphorical hunger: the case of The Divergent Trilogy

    OpenAIRE

    Paravano, Cristina

    2015-01-01

    The present contribution investigates how the issue of hunger becomes a means of expressing and communicating personal and social identity in Veronica Roth’s best seller trilogy Divergent (2011-13). Roth portrays a dystopian future developing a multifaceted concept of hunger, both real and figurative, and using food as a cultural metaphor. The trilogy is set in a post-apocalyptic Chicago, whose population is divided into five allegorical factions, according to a number of personal and social ...

  14. Divergence, recombination and retention of functionality during protein evolution

    Directory of Open Access Journals (Sweden)

    Xu Yanlong O

    2005-09-01

    Full Text Available Abstract We have only a vague idea of precisely how protein sequences evolve in the context of protein structure and function. This is primarily because structural and functional contexts are not easily predictable from the primary sequence, and evaluating patterns of evolution at individual residue positions is also difficult. As a result of increasing biodiversity in genomics studies, progress is being made in detecting context-dependent variation in substitution processes, but it remains unclear exactly what context-dependent patterns we should be looking for. To address this, we have been simulating protein evolution in the context of structure and function using lattice models of proteins and ligands (or substrates. These simulations include thermodynamic features of protein stability and population dynamics. We refer to this approach as 'ab initio evolution' to emphasise the fact that the equilibrium details of fitness distributions arise from the physical principles of the system and not from any preconceived notions or arbitrary mathematical distributions. Here, we present results on the retention of functionality in homologous recombinants following population divergence. A central result is that protein structure characteristics can strongly influence recombinant functionality. Exceptional structures with many sequence options evolve quickly and tend to retain functionality -- even in highly diverged recombinants. By contrast, the more common structures with fewer sequence options evolve more slowly, but the fitness of recombinants drops off rapidly as homologous proteins diverge. These results have implications for understanding viral evolution, speciation and directed evolutionary experiments. Our analysis of the divergence process can also guide improved methods for accurately approximating folding probabilities in more complex but realistic systems.

  15. [Phylogeny and divergence time estimation of Schizothoracinae fishes in Xinjiang].

    Science.gov (United States)

    Ayelhan, Haysa; Guo, Yan; Meng, Wei; Yang, Tianyan; Ma, Yanwu

    2014-10-01

    Based on combined data of mitochondrial COI, ND4 and 16S RNA genes, molecular phylogeny of 4 genera, 10 species or subspecies of Schizothoracinae fishes distributed in Xinjiang were analyzed. The molecular clock was calibrated by divergence time of Cyprininae and geological segregation event between the upper Yellow River and Qinghai Lake. Divergence time of Schizothoracinae fishes was calculated, and its relationship with the major geological events and the climate changes in surrounding areas of Tarim Basin was discussed. The results showed that genus Aspiorhynchus did not form an independent clade, but clustered with Schizothorax biddulphi and S. irregularis. Kimura 2-parameter model was used to calculate the genetic distance of COI gene, the genetic distance between genus Aspiorhynchus and Schizothorax did not reach genus level, and Aspiorhynchus laticeps might be a specialized species of genus Schizothorax. Cluster analysis showed a different result with morphological classification method, and it did not support the subgenus division of Schizothorax fishes. Divergence of two groups of primitive Schizothoracinae (8.18Ma) and divergence of Gymnodiptychus dybowskii and Diptychus maculates (7.67Ma) occurred in late Miocene, which might be related with the separation of Kunlun Mountain and north Tianshan Mountain River system that was caused by the uplift of Qinghai-Tibet Plateau and Tianshan Mountain, and the aridification of Tarim Basin. The terrain of Tarim Basin that was affected by Quaternary Himalayan movement was high in west but low in east, as a result, Lop Nor became the center of surrounding mountain rivers in Tarim Basin, which shaped the distribution pattern of genus Schizothorax.

  16. Existence and multiplicity of solutions for divergence type elliptic equations

    Directory of Open Access Journals (Sweden)

    Lin Zhao

    2011-03-01

    Full Text Available We establish the existence and multiplicity of weak solutions of a problem involving a uniformly convex elliptic operator in divergence form. We find one nontrivial solution by the mountain pass lemma, when the nonlinearity has a $(p-1$-superlinear growth at infinity, and two nontrivial solutions by minimization and mountain pass when the nonlinear term has a $(p-1$-sublinear growth at infinity.

  17. Infra-red divergences and Regge behaviour in QCD

    International Nuclear Information System (INIS)

    Jaroszewicz, T.

    1980-01-01

    We analyze high energy behaviour of multi-gluon exchange amplitudes in the leading-lns approximation in perturbation theory. Working in the Coulomb gauge and employing Ward identities we derive an integral equation for the n-gluon system in the exchange channel. We find that the Regge behaviour is associated with exponentiation of leading infrared divergences, and the position of the j-plane singularities is determined by the colour quantum numbers of the exchanged system. (author)

  18. Schroedinger propagation of initial discontinuities leads to divergence of moments

    International Nuclear Information System (INIS)

    Marchewka, A.; Schuss, Z.

    2009-01-01

    We show that the large phase expansion of the Schroedinger propagation of an initially discontinuous wave function leads to the divergence of average energy, momentum, and displacement, rendering them unphysical states. If initially discontinuous wave functions are considered to be approximations to continuous ones, the determinant of the spreading rate of these averages is the maximal gradient of the initial wave function. Therefore a dilemma arises between the inclusion of discontinuous wave functions in quantum mechanics and the requirement of finite moments.

  19. Schroedinger propagation of initial discontinuities leads to divergence of moments

    Energy Technology Data Exchange (ETDEWEB)

    Marchewka, A., E-mail: avi.marchewka@gmail.co [Ruppin Academic Center, Emek-Hefer 40250 (Israel); Schuss, Z., E-mail: schuss@post.tau.ac.i [Department of Mathematics, Tel-Aviv University, Ramat-Aviv, 69978 Tel-Aviv (Israel)

    2009-09-21

    We show that the large phase expansion of the Schroedinger propagation of an initially discontinuous wave function leads to the divergence of average energy, momentum, and displacement, rendering them unphysical states. If initially discontinuous wave functions are considered to be approximations to continuous ones, the determinant of the spreading rate of these averages is the maximal gradient of the initial wave function. Therefore a dilemma arises between the inclusion of discontinuous wave functions in quantum mechanics and the requirement of finite moments.

  20. Chloroplast Genome Evolution in Early Diverged Leptosporangiate Ferns

    OpenAIRE

    Kim, Hyoung Tae; Chung, Myong Gi; Kim, Ki-Joong

    2014-01-01

    In this study, the chloroplast (cp) genome sequences from three early diverged leptosporangiate ferns were completed and analyzed in order to understand the evolution of the genome of the fern lineages. The complete cp genome sequence of Osmunda cinnamomea (Osmundales) was 142,812 base pairs (bp). The cp genome structure was similar to that of eusporangiate ferns. The gene/intron losses that frequently occurred in the cp genome of leptosporangiate ferns were not found in the cp genome of O. c...

  1. A limit of the quantum Rényi divergence

    International Nuclear Information System (INIS)

    Datta, Nilanjana; Leditzky, Felix

    2014-01-01

    Recently, an interesting quantity called the quantum Rényi divergence (or ‘sandwiched’ Rényi relative entropy) was defined for pairs of positive semi-definite operators ρ and σ. It depends on a parameter α and acts as a parent quantity for other relative entropies which have important operational significance in quantum information theory: the quantum relative entropy and the min- and max-relative entropies. There is, however, another relative entropy, called the 0-relative Rényi entropy, which plays a key role in the analysis of various quantum information-processing tasks in the one-shot setting. We prove that the 0-relative Rényi entropy is obtainable from the quantum Rényi divergence only if ρ and σ have equal supports. This, along with existing results in the literature, suggests that it suffices to consider two essential parent quantities from which operationally relevant entropic quantities can be derived—the quantum Rényi divergence with parameter α ⩾ 1/2, and the α-relative Rényi entropy with α ∈ [0, 1). (paper)

  2. Infrared divergences for free quantum fields in cosmological spacetimes

    Science.gov (United States)

    Higuchi, Atsushi; Rendell, Nicola

    2018-06-01

    We investigate the nature of infrared divergences for the free graviton and inflaton two-point functions in flat Friedman–Lemaître–Robertson–Walker spacetime. These divergences arise because the momentum integral for these two-point functions diverges in the infrared. It is straightforward to see that the power of the momentum in the integrand can be increased by 2 in the infrared using large gauge transformations, which are sufficient for rendering these two-point functions infrared finite for slow-roll inflation. In other words, if the integrand of the momentum integral for these two-point functions behaves like , where p is the momentum, in the infrared, then it can be made to behave like by large gauge transformations. On the other hand, it is known that, if one smears these two-point functions in a gauge-invariant manner, the power of the momentum in the integrand is changed from to . This fact suggests that the power of the momentum in the integrand for these two-point functions can be increased by 4 using large gauge transformations. In this paper we show that this is indeed the case. Thus, the two-point functions for the graviton and inflaton fields can be made finite by large gauge transformations for a large class of potentials and states in single-field inflation.

  3. A vadose zone water fluxmeter with divergence control

    Science.gov (United States)

    Gee, G.W.; Ward, A.L.; Caldwell, T.G.; Ritter, J.C.

    2002-01-01

    Unsaturated water flux densities are needed to quantify water and contaminant transfer within the vadose zone. However, water flux densities are seldom measured directly and often are predicted with uncertainties of an order or magnitude or more. A water fluxmeter was designed, constructed, and tested to directly measure drainage fluxes in field soils. The fluxmeter was designed to minimize divergence. It concentrates flow into a narrow sensing region filled with a fiberglass wick. The wick applies suction, proportional to its length, and passively drains the meter. The meter can be installed in an augured borehole at almost any depth below the root zone. Water flux through the meter is measured with a self‐calibrating tipping bucket, with a sensitivity of ∼4 mL tip−1. For our meter this is equivalent to detection limit of ∼0.1 mm. Passive‐wick devices previously have not properly corrected for flow divergence. Laboratory measurements supported predictions of a two‐dimensional (2‐D) numerical model, which showed that control of the collector height H and knowledge of soil hydraulic properties are required for improving divergence control, particularly at fluxes below 1000 mm yr−1. The water fluxmeter is simple in concept, is inexpensive, and has the capability of providing continuous and reliable monitoring of unsaturated water fluxes ranging from less than 1 mm yr−1 to more than 1000 mm yr−1.

  4. Divergence of iron metabolism in wild Malaysian yeast.

    Science.gov (United States)

    Lee, Hana N; Mostovoy, Yulia; Hsu, Tiffany Y; Chang, Amanda H; Brem, Rachel B

    2013-12-09

    Comparative genomic studies have reported widespread variation in levels of gene expression within and between species. Using these data to infer organism-level trait divergence has proven to be a key challenge in the field. We have used a wild Malaysian population of S. cerevisiae as a test bed in the search to predict and validate trait differences based on observations of regulatory variation. Malaysian yeast, when cultured in standard medium, activated regulatory programs that protect cells from the toxic effects of high iron. Malaysian yeast also showed a hyperactive regulatory response during culture in the presence of excess iron and had a unique growth defect in conditions of high iron. Molecular validation experiments pinpointed the iron metabolism factors AFT1, CCC1, and YAP5 as contributors to these molecular and cellular phenotypes; in genome-scale sequence analyses, a suite of iron toxicity response genes showed evidence for rapid protein evolution in Malaysian yeast. Our findings support a model in which iron metabolism has diverged in Malaysian yeast as a consequence of a change in selective pressure, with Malaysian alleles shifting the dynamic range of iron response to low-iron concentrations and weakening resistance to extreme iron toxicity. By dissecting the iron scarcity specialist behavior of Malaysian yeast, our work highlights the power of expression divergence as a signpost for biologically and evolutionarily relevant variation at the organismal level. Interpreting the phenotypic relevance of gene expression variation is one of the primary challenges of modern genomics.

  5. Flutter and divergence instability of supported piezoelectric nanotubes conveying fluid

    Science.gov (United States)

    Bahaadini, Reza; Hosseini, Mohammad; Jamali, Behnam

    2018-01-01

    In this paper, divergence and flutter instabilities of supported piezoelectric nanotubes containing flowing fluid are investigated. To take the size effects into account, the nonlocal elasticity theory is implemented in conjunction with the Euler-Bernoulli beam theory incorporating surface stress effects. The Knudsen number is applied to investigate the slip boundary conditions between the flow and wall of nanotube. The nonlocal governing equations of nanotube are obtained using Newtonian method, including the influence of piezoelectric voltage, surface effects, Knudsen number and nonlocal parameter. Applying Galerkin approach to transform resulting equations into a set of eigenvalue equations under the simple-simple (S-S) and clamped-clamped (C-C) boundary conditions. The effects of the piezoelectric voltage, surface effects, Knudsen number, nonlocal parameter and boundary conditions on the divergence and flutter boundaries of nanotubes are discussed. It is observed that the fluid-conveying nanotubes with both ends supported lose their stability by divergence first and then by flutter with increase in fluid velocity. Results indicate the importance of using piezoelectric voltage, nonlocal parameter and Knudsen number in decrease of critical flow velocities of system. Moreover, the surface effects have a significant role on the eigenfrequencies and critical fluid velocity.

  6. Predictors for reproductive isolation in a ring species complex following genetic and ecological divergence.

    Science.gov (United States)

    Pereira, Ricardo J; Monahan, William B; Wake, David B

    2011-07-06

    Reproductive isolation (RI) is widely accepted as an important "check point" in the diversification process, since it defines irreversible evolutionary trajectories. Much less consensus exists about the processes that might drive RI. Here, we employ a formal quantitative analysis of genetic interactions at several stages of divergence within the ring species complex Ensatina eschscholtzii in order to assess the relative contribution of genetic and ecological divergence for the development of RI. By augmenting previous genetic datasets and adding new ecological data, we quantify levels of genetic and ecological divergence between populations and test how they correlate with a restriction of genetic admixture upon secondary contact. Our results indicate that the isolated effect of ecological divergence between parental populations does not result in reproductively isolated taxa, even when genetic transitions between parental taxa are narrow. Instead, processes associated with overall genetic divergence are the best predictors of reproductive isolation, and when parental taxa diverge in nuclear markers we observe a complete cessation of hybridization, even to sympatric occurrence of distinct evolutionary lineages. Although every parental population has diverged in mitochondrial DNA, its degree of divergence does not predict the extent of RI. These results show that in Ensatina, the evolutionary outcomes of ecological divergence differ from those of genetic divergence. While evident properties of taxa may emerge via ecological divergence, such as adaptation to local environment, RI is likely to be a byproduct of processes that contribute to overall genetic divergence, such as time in geographic isolation, rather than being a direct outcome of local adaptation.

  7. Simian virus 40 small t antigen is not required for the maintenance of transformation but may act as a promoter (cocarcinogen) during establishment of transformation in resting rat cells.

    Science.gov (United States)

    Seif, R; Martin, R G

    1979-12-01

    Simian virus 40 deletion mutants affecting the 20,000-dalton (20K) t antigen and tsA mutants rendering the 90K T antigen temperature sensitive, as well as double mutants containing both mutations, induced host DNA synthesis in resting rat cells at the restrictive temperature. Nonetheless, the deletion mutants and double mutants did not induce transformation in resting cells even at the permissive temperature. On the other hand, the deletion mutants did induce full transformants when actively growing rat cells were infected; the transformants grew efficiently in agar and to high saturation densities on platic. The double mutants did not induce T-antigen-independent (temperature-insensitive) transformants which were shown previously to arise preferentially from resting cells. Thus, small t antigen was dispensable for the maintenance of the transformed phenotype in T-antigen-dependent rat transformants (transformants derived from growing cells) and may play a role in the establishment of T-antigen-independent transformants. We attempt to establish a parallel between transformation induced by chemical carcinogens and simian virus 40-induced transformation.

  8. Selection is stronger in early-versus-late stages of divergence in a Neotropical livebearing fish.

    Science.gov (United States)

    Ingley, Spencer J; Johnson, Jerald B

    2016-03-01

    How selection acts to drive trait evolution at different stages of divergence is of fundamental importance in our understanding of the origins of biodiversity. Yet, most studies have focused on a single point along an evolutionary trajectory. Here, we provide a case study evaluating the strength of divergent selection acting on life-history traits at early-versus-late stages of divergence in Brachyrhaphis fishes. We find that the difference in selection is stronger in the early-diverged population than the late-diverged population, and that trait differences acquired early are maintained over time. © 2016 The Author(s).

  9. Variability of bio-clinical parameters in Chinese-origin Rhesus macaques infected with simian immunodeficiency virus: a nonhuman primate AIDS model.

    Directory of Open Access Journals (Sweden)

    Song Chen

    Full Text Available BACKGROUND: Although Chinese-origin Rhesus macaques (Ch RhMs infected with simian immunodeficiency virus (SIV have been used for many years to evaluate the efficacy of AIDS vaccines and therapeutics, the bio-clinical variability of such a nonhuman primate AIDS model was so far not established. METHODOLOGY/PRINCIPAL FINDINGS: By randomizing 150 (78 male and 72 female Ch RhMs with diverse MHC class I alleles into 3 groups (50 animals per group challenged with intrarectal (i.r. SIVmac239, intravenous (i.v. SIVmac239, or i.v. SIVmac251, we evaluated variability in bio-clinical endpoints for 118 weeks. All SIV-challenged Ch RhMs became seropositive for SIV during 1-2 weeks. Plasma viral load (VL peaked at weeks 1-2 and then declined to set-point levels as from week 5. The set-point VL was 30 fold higher in SIVmac239 (i.r. or i.v.-infected than in SIVmac251 (i.v.-infected animals. This difference in plasma VL increased overtime (>100 fold as from week 68. The rates of progression to AIDS or death were more rapid in SIVmac239 (i.r. or i.v.-infected than in SIVmac251 (i.v.-infected animals. No significant difference in bio-clinical endpoints was observed in animals challenged with i.r. or i.v. SIVmac239. The variability (standard deviation in peak/set-point VL was nearly one-half lower in animals infected with SIVmac239 (i.r. or i.v. than in those infected with SIVmac251 (i.v., allowing that the same treatment-related difference can be detected with one-half fewer animals using SIVmac239 than using SIVmac251. CONCLUSION/SIGNIFICANCE: These results provide solid estimates of variability in bio-clinical endpoints needed when designing studies using the Ch RhM SIV model and contribute to the improving quality and standardization of preclinical studies.

  10. Bionomics of Anopheles latens in Kapit, Sarawak, Malaysian Borneo in relation to the transmission of zoonotic simian malaria parasite Plasmodium knowlesi

    Directory of Open Access Journals (Sweden)

    Matusop Asmad

    2008-03-01

    Full Text Available Abstract Background A large focus of human infections with Plasmodium knowlesi, a simian parasite naturally found in long-tailed and pig-tailed macaques was discovered in the Kapit Division of Sarawak, Malaysian Borneo. A study was initiated to identify the vectors of malaria, to elucidate where transmission is taking place and to understand the bionomics of the vectors in Kapit. Methods Three different ecological sites in the forest, farm and longhouse in the Kapit district were selected for the study. Mosquitoes were collected by human landing collection at all sites and at the forest also by monkey-baited-traps situated on three different levels. All mosquitoes were identified and salivary glands and midguts of anopheline mosquitoes were dissected to determine the presence of malaria parasites. Results and Discussions Over an 11-month period, a total of 2,504 Anopheles mosquitoes comprising 12 species were caught; 1,035 at the farm, 774 at the forest and 425 at the longhouse. Anopheles latens (62.3% and Anopheles watsonii (30.6% were the predominant species caught in the forested ecotypes, while in the farm Anopheles donaldi (49.9% and An. latens (35.6% predominated. In the long house, An. latens (29.6% and An. donaldi (22.8% were the major Anopheline species. However, An. latens was the only mosquito positive for sporozoites and it was found to be attracted to both human and monkey hosts. In monkey-baited net traps, it preferred to bite monkeys at the canopy level than at ground level. An. latens was found biting early as 18.00 hours. Conclusion Anopheles latens is the main vector for P. knowlesi malaria parasites in the Kapit District of Sarawak, Malaysian Borneo. The study underscores the relationship between ecology, abundance and bionomics of anopheline fauna. The simio-anthropophagic and acrodendrophilic behaviour of An. latens makes it an efficient vector for the transmission of P. knowlesi parasites to both human and monkey hosts.

  11. A highly intensified ART regimen induces long-term viral suppression and restriction of the viral reservoir in a simian AIDS model.

    Directory of Open Access Journals (Sweden)

    Iart Luca Shytaj

    Full Text Available Stably suppressed viremia during ART is essential for establishing reliable simian models for HIV/AIDS. We tested the efficacy of a multidrug ART (highly intensified ART in a wide range of viremic conditions (10³-10⁷ viral RNA copies/mL in SIVmac251-infected rhesus macaques, and its impact on the viral reservoir. Eleven macaques in the pre-AIDS stage of the disease were treated with a multidrug combination (highly intensified ART consisting of two nucleosidic/nucleotidic reverse transcriptase inhibitors (emtricitabine and tenofovir, an integrase inhibitor (raltegravir, a protease inhibitor (ritonavir-boosted darunavir and the CCR5 blocker maraviroc. All animals stably displayed viral loads below the limit of detection of the assay (i.e. <40 RNA copies/mL after starting highly intensified ART. By increasing the sensitivity of the assay to 3 RNA copies/mL, viral load was still below the limit of detection in all subjects tested. Importantly, viral DNA resulted below the assay detection limit (<2 copies of DNA/5*10⁵ cells in PBMCs and rectal biopsies of all animals at the end of the follow-up, and in lymph node biopsies from the majority of the study subjects. Moreover, highly intensified ART decreased central/transitional memory, effector memory and activated (HLA-DR⁺ effector memory CD4⁺ T-cells in vivo, in line with the role of these subsets as the main cell subpopulations harbouring the virus. Finally, treatment with highly intensified ART at viral load rebound following suspension of a previous anti-reservoir therapy eventually improved the spontaneous containment of viral load following suspension of the second therapeutic cycle, thus leading to a persistent suppression of viremia in the absence of ART. In conclusion, we show, for the first time, complete suppression of viral load by highly intensified ART and a likely associated restriction of the viral reservoir in the macaque AIDS model, making it a useful platform for testing

  12. Bionomics of Anopheles latens in Kapit, Sarawak, Malaysian Borneo in relation to the transmission of zoonotic simian malaria parasite Plasmodium knowlesi

    Science.gov (United States)

    Tan, Cheong H; Vythilingam, Indra; Matusop, Asmad; Chan, Seng T; Singh, Balbir

    2008-01-01

    Background A large focus of human infections with Plasmodium knowlesi, a simian parasite naturally found in long-tailed and pig-tailed macaques was discovered in the Kapit Division of Sarawak, Malaysian Borneo. A study was initiated to identify the vectors of malaria, to elucidate where transmission is taking place and to understand the bionomics of the vectors in Kapit. Methods Three different ecological sites in the forest, farm and longhouse in the Kapit district were selected for the study. Mosquitoes were collected by human landing collection at all sites and at the forest also by monkey-baited-traps situated on three different levels. All mosquitoes were identified and salivary glands and midguts of anopheline mosquitoes were dissected to determine the presence of malaria parasites. Results and Discussions Over an 11-month period, a total of 2,504 Anopheles mosquitoes comprising 12 species were caught; 1,035 at the farm, 774 at the forest and 425 at the longhouse. Anopheles latens (62.3%) and Anopheles watsonii (30.6%) were the predominant species caught in the forested ecotypes, while in the farm Anopheles donaldi (49.9%) and An. latens (35.6%) predominated. In the long house, An. latens (29.6%) and An. donaldi (22.8%) were the major Anopheline species. However, An. latens was the only mosquito positive for sporozoites and it was found to be attracted to both human and monkey hosts. In monkey-baited net traps, it preferred to bite monkeys at the canopy level than at ground level. An. latens was found biting early as 18.00 hours. Conclusion Anopheles latens is the main vector for P. knowlesi malaria parasites in the Kapit District of Sarawak, Malaysian Borneo. The study underscores the relationship between ecology, abundance and bionomics of anopheline fauna. The simio-anthropophagic and acrodendrophilic behaviour of An. latens makes it an efficient vector for the transmission of P. knowlesi parasites to both human and monkey hosts. PMID:18377652

  13. Transgene Expression and Repression in Transgenic Rats Bearing the Phosphoenolpyruvate Carboxykinase-Simian Virus 40 T Antigen or the Phosphoenolpyruvate Carboxykinase-Transforming Growth Factor-α Constructs

    Science.gov (United States)

    Haas, Michael J.; Dragan, Yvonne P.; Hikita, Hiroshi; Shimel, Randee; Takimoto, Koichi; Heath, Susan; Vaughan, Jennifer; Pitot, Henry C.

    1999-01-01

    Transgenic Sprague-Dawley rats expressing either human transforming growth factor-α (TGFα) or simian virus 40 large and small T antigen (TAg), each under the control of the phosphoenolpyruvate carboxykinase (PEPCK) promoter, were developed as an approach to the study of the promotion of hepatocarcinogenesis in the presence of a transgene regulatable by diet and/or hormones. Five lines of PEPCK-TGFα transgenic rats were established, each genetic line containing from one to several copies of the transgene per haploid genome. Two PEPCK-TAg transgenic founder rats were obtained, each with multiple copies of the transgene. Expression of the transgene was undetectable in the TGFα transgenic rats and could not be induced when the animals were placed on a high-protein, low-carbohydrate diet. The transgene was found to be highly methylated in all of these lines. No pathological alterations in the liver and intestine were observed at any time (up to 2 years) during the lives of these rats. One line of transgenic rats expressing the PEPCK-TAg transgene developed pancreatic islet cell hyperplasias and carcinomas, with few normal islets evident in the pancreas. This transgene is integrated as a hypomethylated tandem array of 10 to 12 copies on chromosome 8q11. Expression of large T antigen is highest in pancreatic neoplasms, but is also detectable in the normal brain, kidney, and liver. Mortality is most rapid in males, starting at 5 months of age and reaching 100% by 8 months. Morphologically, islet cell differentiation in the tumors ranges from poor to well differentiated, with regions of necrosis and fibrosis. Spontaneous metastasis of TAg-positive tumor cells to regional lymph nodes was observed. These studies indicate the importance of DNA methylation in the repression of specific transgenes in the rat. However, the expression of the PEPCK-TAg induces neoplastic transformation in islet cells, probably late in neuroendocrine cell differentiation. T antigen expression

  14. Anti-retroviral therapy fails to restore the severe Th-17: Tc-17 imbalance observed in peripheral blood during simian immunodeficiency virus infection.

    Science.gov (United States)

    Kader, M; Bixler, S; Piatak, M; Lifson, J; Mattapallil, J J

    2009-10-01

    Human immuno deficiency virus and simian immunodeficiency virus infections are characterized by a severe loss of Th-17 cells (IL-17(+)CD4(+) T cells) that has been associated with disease progression and systemic dissemination of bacterial infections. Anti-retroviral therapy (ART) has led to repopulation of CD4(+) T cells in peripheral tissues with little sustainable repopulation in mucosal tissues. Given the central importance of Th-17 cells in mucosal homeostasis, it is not known if the failure of ART to permanently repopulate mucosal tissues is associated with a failure to restore Th-17 cells that are lost during infection. Dynamics of alpha4(+)beta7(hi) CD4(+) T cells in peripheral blood of SIV infected rhesus macaques were evaluated and compared to animals that were treated with ART. The frequency of Th-17 and Tc-17 cells was determined following infection and after therapy. Relative expression of IL-21, IL-23, and TGFbeta was determined using Taqman PCR. Treatment of SIV infected rhesus macaques with anti-retroviral therapy was associated with a substantial repopulation of mucosal homing alpha4(+)beta7(hi)CD4(+) T cells in peripheral blood. This repopulation, however, was not accompanied by a restoration of Th-17 responses. Interestingly, SIV infection was associated with an increase in Tc-17 responses (IL-17(+)CD8(+) T cells) suggesting to a skewing in the ratio of Th-17: Tc-17 cells from a predominantly Th-17 phenotype to a predominantly Tc-17 phenotype. Surprisingly, Tc-17 responses remained high during the course of therapy suggesting that ART failed to correct the imbalance in Th-17 : Tc-17 responses induced following SIV infection. ART was associated with substantial repopulation of alpha4(+)beta7(hi) CD4(+) T cells in peripheral blood with little or no rebound of Th-17 cells. On the other hand, repopulation of alpha4(+)beta7(hi) CD4(+) T cells was accompanied by persistence of high levels of Tc-17 cells in peripheral blood. The dysregulation of Th-17

  15. Properties of the simian virus 40 (SV40) large T antigens encoded by SV40 mutants with deletions in gene A.

    Science.gov (United States)

    Cole, C N; Tornow, J; Clark, R; Tjian, R

    1986-01-01

    The biochemical properties of the large T antigens encoded by simian virus 40 (SV40) mutants with deletions at DdeI sites in the SV40 A gene were determined. Mutant large T antigens containing only the first 138 to 140 amino acids were unable to bind to the SV40 origin of DNA replication as were large T antigens containing at their COOH termini 96 or 97 amino acids encoded by the long open reading frame located between 0.22 and 0.165 map units (m.u.). All other mutant large T antigens were able to bind to the SV40 origin of replication. Mutants with in-phase deletions at 0.288 and 0.243 m.u. lacked ATPase activity, but ATPase activity was normal in mutants lacking origin-binding activity. The 627-amino acid large T antigen encoded by dlA2465, with a deletion at 0.219 m.u., was the smallest large T antigen displaying ATPase activity. Mutant large T antigens with the alternate 96- or 97-amino acid COOH terminus also lacked ATPase activity. All mutant large T antigens were found in the nuclei of infected cells; a small amount of large T with the alternate COOH terminus was also located in the cytoplasm. Mutant dlA2465 belonged to the same class of mutants as dlA2459. It was unable to form plaques on CV-1p cells at 37 or 32 degrees C but could form plaques on BSC-1 monolayers at 37 degrees C but not at 32 degrees C. It was positive for viral DNA replication and showed intracistronic complementation with any group A mutant whose large T antigen contained a normal carboxyl terminus. These findings and those of others suggest that both DNA binding and ATPase activity are required for the viral DNA replication function of large T antigen, that these two activities must be located on the same T antigen monomer, and that these two activities are performed by distinct domains of the polypeptide. These domains are distinct and separable from the domain affected by the mutation of dlA2465 and indicate that SV40 large T antigen is made up of at least three separate functional

  16. Chloroplast genome evolution in early diverged leptosporangiate ferns.

    Science.gov (United States)

    Kim, Hyoung Tae; Chung, Myong Gi; Kim, Ki-Joong

    2014-05-01

    In this study, the chloroplast (cp) genome sequences from three early diverged leptosporangiate ferns were completed and analyzed in order to understand the evolution of the genome of the fern lineages. The complete cp genome sequence of Osmunda cinnamomea (Osmundales) was 142,812 base pairs (bp). The cp genome structure was similar to that of eusporangiate ferns. The gene/intron losses that frequently occurred in the cp genome of leptosporangiate ferns were not found in the cp genome of O. cinnamomea. In addition, putative RNA editing sites in the cp genome were rare in O. cinnamomea, even though the sites were frequently predicted to be present in leptosporangiate ferns. The complete cp genome sequence of Diplopterygium glaucum (Gleicheniales) was 151,007 bp and has a 9.7 kb inversion between the trnL-CAA and trnVGCA genes when compared to O. cinnamomea. Several repeated sequences were detected around the inversion break points. The complete cp genome sequence of Lygodium japonicum (Schizaeales) was 157,142 bp and a deletion of the rpoC1 intron was detected. This intron loss was shared by all of the studied species of the genus Lygodium. The GC contents and the effective numbers of codons (ENCs) in ferns varied significantly when compared to seed plants. The ENC values of the early diverged leptosporangiate ferns showed intermediate levels between eusporangiate and core leptosporangiate ferns. However, our phylogenetic tree based on all of the cp gene sequences clearly indicated that the cp genome similarity between O. cinnamomea (Osmundales) and eusporangiate ferns are symplesiomorphies, rather than synapomorphies. Therefore, our data is in agreement with the view that Osmundales is a distinct early diverged lineage in the leptosporangiate ferns.

  17. Evolution of cichlid vision via trans-regulatory divergence

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    O’Quin Kelly E

    2012-12-01

    Full Text Available Abstract Background Phenotypic evolution may occur through mutations that affect either the structure or expression of protein-coding genes. Although the evolution of color vision has historically been attributed to structural mutations within the opsin genes, recent research has shown that opsin regulatory mutations can also tune photoreceptor sensitivity and color vision. Visual sensitivity in African cichlid fishes varies as a result of the differential expression of seven opsin genes. We crossed cichlid species that express different opsin gene sets and scanned their genome for expression Quantitative Trait Loci (eQTL responsible for these differences. Our results shed light on the role that different structural, cis-, and trans-regulatory mutations play in the evolution of color vision. Results We identified 11 eQTL that contribute to the divergent expression of five opsin genes. On three linkage groups, several eQTL formed regulatory “hotspots” associated with the expression of multiple opsins. Importantly, however, the majority of the eQTL we identified (8/11 or 73% occur on linkage groups located trans to the opsin genes, suggesting that cichlid color vision has evolved primarily via trans-regulatory divergence. By modeling the impact of just two of these trans-regulatory eQTL, we show that opsin regulatory mutations can alter cichlid photoreceptor sensitivity and color vision at least as much as opsin structural mutations can. Conclusions Combined with previous work, we demonstrate that the evolution of cichlid color vision results from the interplay of structural, cis-, and especially trans-regulatory loci. Although there are numerous examples of structural and cis-regulatory mutations that contribute to phenotypic evolution, our results suggest that trans-regulatory mutations could contribute to phenotypic divergence more commonly than previously expected, especially in systems like color vision, where compensatory changes in the

  18. Sympatric and allopatric divergence of MHC genes in threespine stickleback.

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    Blake Matthews

    2010-06-01

    Full Text Available Parasites can strongly affect the evolution of their hosts, but their effects on host diversification are less clear. In theory, contrasting parasite communities in different foraging habitats could generate divergent selection on hosts and promote ecological speciation. Immune systems are costly to maintain, adaptable, and an important component of individual fitness. As a result, immune system genes, such as those of the Major Histocompatibility Complex (MHC, can change rapidly in response to parasite-mediated selection. In threespine stickleback (Gasterosteus aculeatus, as well as in other vertebrates, MHC genes have been linked with female mating preference, suggesting that divergent selection acting on MHC genes might influence speciation. Here, we examined genetic variation at MHC Class II loci of sticklebacks from two lakes with a limnetic and benthic species pair, and two lakes with a single species. In both lakes with species pairs, limnetics and benthics differed in their composition of MHC alleles, and limnetics had fewer MHC alleles per individual than benthics. Similar to the limnetics, the allopatric population with a pelagic phenotype had few MHC alleles per individual, suggesting a correlation between MHC genotype and foraging habitat. Using a simulation model we show that the diversity and composition of MHC alleles in a sympatric species pair depends on the amount of assortative mating and on the strength of parasite-mediated selection in adjacent foraging habitats. Our results indicate parallel divergence in the number of MHC alleles between sympatric stickleback species, possibly resulting from the contrasting parasite communities in littoral and pelagic habitats of lakes.

  19. Conductive solar wind models in rapidly diverging flow geometries

    International Nuclear Information System (INIS)

    Holzer, T.E.; Leer, E.

    1980-01-01

    A detailed parameter study of conductive models of the solar wind has been carried out, extending the previous similar studies of Durney (1972) and Durney and Hundhausen (1974) by considering collisionless inhibition of thermal conduction, rapidly diverging flow geometries, and the structure of solutions for the entire n 0 -T 0 plane (n 0 and T 0 are the coronal base density and temperature). Primary emphasis is placed on understanding the complex effects of the physical processes operative in conductive solar wind models. There are five points of particular interest that have arisen from the study: (1) neither collisionless inhibition of thermal conduction nor rapidly diverging flow geometries can significantly increase the solar wind speed at 1 AU; (2) there exists a firm upper limit on the coronal base temperature consistent with observed values of the coronal base pressure and solar wind mass flux density; (3) the principal effect of rapidly diverging flow geometries is a decrease in the solar wind mass flux density at 1 AU and an increase in the mass flux density at the coronal base; (4) collisionless inhibition of thermal conduction can lead to a solar wind flow speed that either increases or decreases with increasing coronal base density (n 0 ) and temperature (T 0 , depending on the region of the n 0 -T 0 plane considered; (5) there is a region of the n 0 -T/sub o/ plane at high coronal base densities where low-speed, high-mass-flux, transonic solar wind flows exist: a region not previously considered

  20. Divergent trophic levels in two cryptic sibling bat species.

    Science.gov (United States)

    Siemers, Björn M; Greif, Stefan; Borissov, Ivailo; Voigt-Heucke, Silke L; Voigt, Christian C

    2011-05-01

    Changes in dietary preferences in animal species play a pivotal role in niche specialization. Here, we investigate how divergence of foraging behaviour affects the trophic position of animals and thereby their role for ecosystem processes. As a model, we used two closely related bat species, Myotis myotis and M. blythii oxygnathus, that are morphologically very similar and share the same roosts, but show clear behavioural divergence in habitat selection and foraging. Based on previous dietary studies on synanthropic populations in Central Europe, we hypothesised that M. myotis would mainly prey on predatory arthropods (i.e., secondary consumers) while M. blythii oxygnathus would eat herbivorous insects (i.e., primary consumers). We thus expected that the sibling bats would be at different trophic levels. We first conducted a validation experiment with captive bats in the laboratory and measured isotopic discrimination, i.e., the stepwise enrichment of heavy in relation to light isotopes between consumer and diet, in insectivorous bats for the first time. We then tested our trophic level hypothesis in the field at an ancient site of natural coexistence for the two species (Bulgaria, south-eastern Europe) using stable isotope analyses. As predicted, secondary consumer arthropods (carabid beetles; Coleoptera) were more enriched in (15)N than primary consumer arthropods (tettigoniids; Orthoptera), and accordingly wing tissue of M. myotis was more enriched in (15)N than tissue of M. blythii oxygnathus. According to a Bayesian mixing model, M. blythii oxygnathus indeed fed almost exclusively on primary consumers (98%), while M. myotis ate a mix of secondary (50%), but also, and to a considerable extent, primary consumers (50%). Our study highlights that morphologically almost identical, sympatric sibling species may forage at divergent trophic levels, and, thus may have different effects on ecosystem processes.

  1. Symbolic interactionism and critical perspective: divergent or synergistic?

    Science.gov (United States)

    Burbank, Patricia M; Martins, Diane C

    2010-01-01

    Throughout their history, symbolic interactionism and critical perspective have been viewed as divergent theoretical perspectives with different philosophical underpinnings. A review of their historical and philosophical origins reveals both points of divergence and areas of convergence. Their underlying philosophies of science and views of human freedom are different as is their level of focus with symbolic interactionism having a micro perspective and critical perspective using a macro perspective. This micro/macro difference is reflected in the divergence of their major concepts, goals and basic tenets. While their underlying philosophies are different, however, they are not necessarily contradictory and areas of convergence may include the concepts of reference groups and looking glass self within symbolic interactionism and ideological hegemony within critical perspective. By using a pragmatic approach and combining symbolic interactionism and critical perspectives, both micro and macro levels come into focus and strategies for change across individual and societal levels can be developed and applied. Application of both symbolic interactionism and critical perspective to nursing research and scholarship offers exciting new opportunities for theory development and research methodologies. In nursing education, these two perspectives can give students added insight into patients' and families' problems at the micro level while, at the same time, giving them a lens to see and tools to apply to problems at the macro level in health care. In nursing practice, a combined symbolic interactionism/critical perspective approach assists nurses to give high-quality care at the individual level while also working at the macro level to address the manufacturers of illness. New research questions emerge from this combination of perspectives with new possibilities for theory development, a transformation in nursing education, and the potential for new practice strategies that

  2. On the Critical Role of Divergent Selection in Evolvability

    Directory of Open Access Journals (Sweden)

    Joel Lehman

    2016-08-01

    Full Text Available An ambitious goal in evolutionary robotics is to evolve increasingly complex robotic behaviors with minimal human design effort. Reaching this goal requires evolutionary algorithms that can unlock from genetic encodings their latent potential for evolvability. One issue clouding this goal is conceptual confusion about evolvability, which often obscures the aspects of evolvability that are important or desirable. The danger from such confusion is that it may establish unrealistic goals for evolvability that prove unproductive in practice. An important issue separate from conceptual confusion is the common misalignment between selection and evolvability in evolutionary robotics. While more expressive encodings can represent higher-level adaptations (e.g. sexual reproduction or developmental systems that increase long-term evolutionary potential (i.e. evolvability, realizing such potential requires gradients of fitness and evolvability to align. In other words, selection is often a critical factor limiting increasing evolvability. Thus, drawing from a series of recent papers, this article seeks to both (1 clarify and focus the ways in which the term evolvability is used within artificial evolution, and (2 argue for the importance of one type of selection, i.e. divergent selection, for enabling evolvability. The main argument is that there is a fundamental connection between divergent selection and evolvability (on both the individual and population level that does not hold for typical goal-oriented selection. The conclusion is that selection pressure plays a critical role in realizing the potential for evolvability, and that divergent selection in particular provides a principled mechanism for encouraging evolvability in artificial evolution.

  3. Rethinking conformity and imitation: divergence, convergence, and social understanding

    Directory of Open Access Journals (Sweden)

    Bert eHodges

    2014-07-01

    Full Text Available Social and developmental psychologists have stressed the pervasiveness and strength of humans’ tendencies to conform and to imitate, and social anthropologists have argued that these tendencies are crucial to the formation of cultures. Research from four domains is reviewed and elaborated to show that divergence is also pervasive and potent, and is interwoven with convergence in a complex set of dynamics that is often unnoticed or minimized. First, classic research in social conformity is reinterpreted in terms of truth, trust, and social solidarity, revealing that dissent is its most salient feature. Second, recent studies of children’s use of testimony to guide action reveal a surprisingly sophisticated balance of trust and prudence, and a concern for truth and charity. Third, new experiments indicate that people diverge from others even under conditions where conformity seems assured. Fourth, current studies of imitation provide strong evidence that children are both selective and faithful in who, what, and why they follow others. All of the evidence reviewed points toward children and adults as being engaged, embodied partners with others, motivated to learn and understand the world, others, and themselves in ways that go beyond goals and rules, prediction and control. Even young children act as if they are in a dialogical relationship with others and the world, rather than acting as if they are solo explorers or blind followers. Overall, the evidence supports the hypothesis that social understanding cannot be reduced to convergence or divergence, but includes ongoing activities that seek greater comprehensiveness and complexity in the ability to act and interact effectively, appropriately, and with integrity.

  4. Rethinking conformity and imitation: divergence, convergence, and social understanding.

    Science.gov (United States)

    Hodges, Bert H

    2014-01-01

    Social and developmental psychologists have stressed the pervasiveness and strength of humans' tendencies to conform and to imitate, and social anthropologists have argued that these tendencies are crucial to the formation of cultures. Research from four domains is reviewed and elaborated to show that divergence is also pervasive and potent, and it is interwoven with convergence in a complex set of dynamics that is often unnoticed or minimized. First, classic research in social conformity is reinterpreted in terms of truth, trust, and social solidarity, revealing that dissent is its most salient feature. Second, recent studies of children's use of testimony to guide action reveal a surprisingly sophisticated balance of trust and prudence, and a concern for truth and charity. Third, new experiments indicate that people diverge from others even under conditions where conformity seems assured. Fourth, current studies of imitation provide strong evidence that children are both selective and faithful in who, what, and why they follow others. All of the evidence reviewed points toward children and adults as being engaged, embodied partners with others, motivated to learn and understand the world, others, and themselves in ways that go beyond goals and rules, prediction and control. Even young children act as if they are in a dialogical relationship with others and the world, rather than acting as if they are solo explorers or blind followers. Overall, the evidence supports the hypothesis that social understanding cannot be reduced to convergence or divergence, but includes ongoing activities that seek greater comprehensiveness and complexity in the ability to act and interact effectively, appropriately, and with integrity.

  5. IR divergences in QCD and Kinoshita-Lee-Nauenberg theorem

    International Nuclear Information System (INIS)

    Ito, Ikuo

    1982-01-01

    It is shown that the infrared divergences in quark-quark scattering process with a hard photon in the final state vanish in the cross section summed over degenerate initial states as well as final ones. All the diagrams with an arbitrary number of disconnected soft gluons must be taken into account, but the contributions of disconnected parts can be factored out by a rearrangement of the infinite series. A finite number of connected diagrams are added to give an infrared finite result. (author)

  6. Infrared divergence cancellation in pure Yang-Mills theory

    International Nuclear Information System (INIS)

    Alvarez, A.G.

    1977-01-01

    Virtual and real corrections to massless external lines in pure Yang-Mills theory are considered in order to look for general features of the infrared divergence cancellation. Use of the Ward identities and sums over transverse polarization states give rise to terms formally corresponding to real ghost emission, cancelling ghost loop singularities, and to a factorisation of the hard narrow single gauge boson emission. Other virtual corrections are examined in the soft region and a graph by graph cancellation is also found. An illustrative explicit calculation of scattering of a gauge particle in an external scalar potential, including hard narrow angle emission is presented. (Auth.)

  7. Scattering theory of infrared divergent Pauli-Fierz Hamiltonians

    CERN Document Server

    Derezinski, J

    2003-01-01

    We consider in this paper the scattering theory of infrared divergent massless Pauli-Fierz Hamiltonians. We show that the CCR representations obtained from the asymptotic field contain so-called {\\em coherent sectors} describing an infinite number of asymptotically free bosons. We formulate some conjectures leading to mathematically well defined notion of {\\em inclusive and non-inclusive scattering cross-sections} for Pauli-Fierz Hamiltonians. Finally we give a general description of the scattering theory of QFT models in the presence of coherent sectors for the asymptotic CCR representations.

  8. Kernel and divergence techniques in high energy physics separations

    Science.gov (United States)

    Bouř, Petr; Kůs, Václav; Franc, Jiří

    2017-10-01

    Binary decision trees under the Bayesian decision technique are used for supervised classification of high-dimensional data. We present a great potential of adaptive kernel density estimation as the nested separation method of the supervised binary divergence decision tree. Also, we provide a proof of alternative computing approach for kernel estimates utilizing Fourier transform. Further, we apply our method to Monte Carlo data set from the particle accelerator Tevatron at DØ experiment in Fermilab and provide final top-antitop signal separation results. We have achieved up to 82 % AUC while using the restricted feature selection entering the signal separation procedure.

  9. Behaviour modelling of two aluminas in divergent spherical pyrotechnical experiments

    International Nuclear Information System (INIS)

    Malaise, F.; Tranchet, J.Y.; Collombet, F.

    1997-01-01

    Two pure aluminas of different characteristics have been subjected to the propagation of a longitudinal divergent spherical shock wave through pyrotechnical experiments. An approach combining a phenomenological analysis and numerical 1D-calculations is proposed to study the behaviour of these aluminas submitted to that type of wave loading. The modelling, proposed in a previous paper, is refined and gives satisfying experimentation-calculation correlations. An analysis of the influence exerted by the various encountered phenomena (plastic activity, pore closure, microcracking) is performed. The significant consequence of the activation of damage with an extension criterion is also underlined. (orig.)

  10. The impact of selection, gene flow and demographic history on heterogeneous genomic divergence: three-spine sticklebacks in divergent environments.

    Science.gov (United States)

    Ferchaud, Anne-Laure; Hansen, Michael M

    2016-01-01

    Heterogeneous genomic divergence between populations may reflect selection, but should also be seen in conjunction with gene flow and drift, particularly population bottlenecks. Marine and freshwater three-spine stickleback (Gasterosteus aculeatus) populations often exhibit different lateral armour plate morphs. Moreover, strikingly parallel genomic footprints across different marine-freshwater population pairs are interpreted as parallel evolution and gene reuse. Nevertheless, in some geographic regions like the North Sea and Baltic Sea, different patterns are observed. Freshwater populations in coastal regions are often dominated by marine morphs, suggesting that gene flow overwhelms selection, and genomic parallelism may also be less pronounced. We used RAD sequencing for analysing 28 888 SNPs in two marine and seven freshwater populations in Denmark, Europe. Freshwater populations represented a variety of environments: river populations accessible to gene flow from marine sticklebacks and large and small isolated lakes with and without fish predators. Sticklebacks in an accessible river environment showed minimal morphological and genomewide divergence from marine populations, supporting the hypothesis of gene flow overriding selection. Allele frequency spectra suggested bottlenecks in all freshwater populations, and particularly two small lake populations. However, genomic footprints ascribed to selection could nevertheless be identified. No genomic regions were consistent freshwater-marine outliers, and parallelism was much lower than in other comparable studies. Two genomic regions previously described to be under divergent selection in freshwater and marine populations were outliers between different freshwater populations. We ascribe these patterns to stronger environmental heterogeneity among freshwater populations in our study as compared to most other studies, although the demographic history involving bottlenecks should also be considered in the

  11. Adaptive divergence in resistance to herbivores in Datura stramonium

    Directory of Open Access Journals (Sweden)

    Guillermo Castillo

    2015-11-01

    Full Text Available Defensive traits exhibited by plants vary widely across populations. Heritable phenotypic differentiation is likely to be produced by genetic drift and spatially restricted gene flow between populations. However, spatially variable selection exerted by herbivores may also give rise to differences among populations. To explore to what extent these factors promote the among-population differentiation of plant resistance of 13 populations of Datura stramonium, we compared the degree of phenotypic differentiation (PST of leaf resistance traits (trichome density, atropine and scopolamine concentration against neutral genetic differentiation (FST at microsatellite loci. Results showed that phenotypic differentiation in defensive traits among-population is not consistent with divergence promoted by genetic drift and restricted gene flow alone. Phenotypic differentiation in scopolamine concentration was significantly higher than FST across the range of trait heritability values. In contrast, genetic differentiation in trichome density was different from FST only when heritability was very low. On the other hand, differentiation in atropine concentration differed from the neutral expectation when heritability was less than or equal to 0.3. In addition, we did not find a significant correlation between pair-wise neutral genetic distances and distances of phenotypic resistance traits. Our findings reinforce previous evidence that divergent natural selection exerted by herbivores has promoted the among-population phenotypic differentiation of defensive traits in D. stramonium.

  12. Fossils, molecules, divergence times, and the origin of lissamphibians.

    Science.gov (United States)

    Marjanović, David; Laurin, Michel

    2007-06-01

    A review of the paleontological literature shows that the early dates of appearance of Lissamphibia recently inferred from molecular data do not favor an origin of extant amphibians from temnospondyls, contrary to recent claims. A supertree is assembled using new Mesquite modules that allow extinct taxa to be incorporated into a time-calibrated phylogeny with a user-defined geological time scale. The supertree incorporates 223 extinct species of lissamphibians and has a highly significant stratigraphic fit. Some divergences can even be dated with sufficient precision to serve as calibration points in molecular divergence date analyses. Fourteen combinations of minimal branch length settings and 10 random resolutions for each polytomy give much more recent minimal origination times of lissamphibian taxa than recent studies based on a phylogenetic analyses of molecular sequences. Attempts to replicate recent molecular date estimates show that these estimates depend strongly on the choice of calibration points, on the dating method, and on the chosen model of evolution; for instance, the estimate for the date of the origin of Lissamphibia can lie between 351 and 266 Mya. This range of values is generally compatible with our time-calibrated supertree and indicates that there is no unbridgeable gap between dates obtained using the fossil record and those using molecular evidence, contrary to previous suggestions.

  13. Coherence and Divergence of Megatrends in Science and Engineering

    Science.gov (United States)

    Roco, M. C.

    2002-04-01

    Scientific discoveries and technological innovations are at the core of human endeavor, and it is estimated that their role will only increase in time. Such advancements evolve in coherence, with areas of confluence and temporary divergences, which bring synergism and that stimulate further developments following in average an exponential growth. Six increasingly interconnected megatrends are perceived as dominating the scene for the next decades: (a) information and computing, (b) nanoscale science and engineering (S&E), (c) biology and bio-environmental approaches, (d) medical sciences and enhancing human physical capabilities, (e) cognitive sciences and enhancing intellectual abilities, and (f) collective behavior and system approach. This paper presents a perspective on the process of identification, planning and program implementation of S&E megatrends, with illustration for the US research initiative on nanoscale science, engineering, and technology. The interplay between coherence and divergence, leading to unifying science and converging technologies, does not develop only among simultaneous scientific trends but also along time and across geopolitical boundaries. There is no single way of development of S&E, and here is the role of taking visionary measures. Societal implication scientists need to be involved from the conceptual phase of a program responding to a S&E megatrend.

  14. Redundancy and divergence in the amyloid precursor protein family.

    Science.gov (United States)

    Shariati, S Ali M; De Strooper, Bart

    2013-06-27

    Gene duplication provides genetic material required for functional diversification. An interesting example is the amyloid precursor protein (APP) protein family. The APP gene family has experienced both expansion and contraction during evolution. The three mammalian members have been studied quite extensively in combined knock out models. The underlying assumption is that APP, amyloid precursor like protein 1 and 2 (APLP1, APLP2) are functionally redundant. This assumption is primarily supported by the similarities in biochemical processing of APP and APLPs and on the fact that the different APP genes appear to genetically interact at the level of the phenotype in combined knockout mice. However, unique features in each member of the APP family possibly contribute to specification of their function. In the current review, we discuss the evolution and the biology of the APP protein family with special attention to the distinct properties of each homologue. We propose that the functions of APP, APLP1 and APLP2 have diverged after duplication to contribute distinctly to different neuronal events. Our analysis reveals that APLP2 is significantly diverged from APP and APLP1. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  15. Divergence of activity expansions: Is it actually a problem?

    Science.gov (United States)

    Ushcats, M. V.; Bulavin, L. A.; Sysoev, V. M.; Ushcats, S. Yu.

    2017-12-01

    For realistic interaction models, which include both molecular attraction and repulsion (e.g., Lennard-Jones, modified Lennard-Jones, Morse, and square-well potentials), the asymptotic behavior of the virial expansions for pressure and density in powers of activity has been studied taking power terms of high orders into account on the basis of the known finite-order irreducible integrals as well as the recent approximations of infinite irreducible series. Even in the divergence region (at subcritical temperatures), this behavior stays thermodynamically adequate (in contrast to the behavior of the virial equation of state with the same set of irreducible integrals) and corresponds to the beginning of the first-order phase transition: the divergence yields the jump (discontinuity) in density at constant pressure and chemical potential. In general, it provides a statistical explanation of the condensation phenomenon, but for liquid or solid states, the physically proper description (which can turn the infinite discontinuity into a finite jump of density) still needs further study of high-order cluster integrals and, especially, their real dependence on the system volume (density).

  16. Gene duplication and divergence affecting drug content in Cannabis sativa.

    Science.gov (United States)

    Weiblen, George D; Wenger, Jonathan P; Craft, Kathleen J; ElSohly, Mahmoud A; Mehmedic, Zlatko; Treiber, Erin L; Marks, M David

    2015-12-01

    Cannabis sativa is an economically important source of durable fibers, nutritious seeds, and psychoactive drugs but few economic plants are so poorly understood genetically. Marijuana and hemp were crossed to evaluate competing models of cannabinoid inheritance and to explain the predominance of tetrahydrocannabinolic acid (THCA) in marijuana compared with cannabidiolic acid (CBDA) in hemp. Individuals in the resulting F2 population were assessed for differential expression of cannabinoid synthase genes and were used in linkage mapping. Genetic markers associated with divergent cannabinoid phenotypes were identified. Although phenotypic segregation and a major quantitative trait locus (QTL) for the THCA/CBDA ratio were consistent with a simple model of codominant alleles at a single locus, the diversity of THCA and CBDA synthase sequences observed in the mapping population, the position of enzyme coding loci on the map, and patterns of expression suggest multiple linked loci. Phylogenetic analysis further suggests a history of duplication and divergence affecting drug content. Marijuana is distinguished from hemp by a nonfunctional CBDA synthase that appears to have been positively selected to enhance psychoactivity. An unlinked QTL for cannabinoid quantity may also have played a role in the recent escalation of drug potency. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  17. Divergence from, and Convergence to, Uniformity of Probability Density Quantiles

    Directory of Open Access Journals (Sweden)

    Robert G. Staudte

    2018-04-01

    Full Text Available We demonstrate that questions of convergence and divergence regarding shapes of distributions can be carried out in a location- and scale-free environment. This environment is the class of probability density quantiles (pdQs, obtained by normalizing the composition of the density with the associated quantile function. It has earlier been shown that the pdQ is representative of a location-scale family and carries essential information regarding shape and tail behavior of the family. The class of pdQs are densities of continuous distributions with common domain, the unit interval, facilitating metric and semi-metric comparisons. The Kullback–Leibler divergences from uniformity of these pdQs are mapped to illustrate their relative positions with respect to uniformity. To gain more insight into the information that is conserved under the pdQ mapping, we repeatedly apply the pdQ mapping and find that further applications of it are quite generally entropy increasing so convergence to the uniform distribution is investigated. New fixed point theorems are established with elementary probabilistic arguments and illustrated by examples.

  18. WORMHOLE: Novel Least Diverged Ortholog Prediction through Machine Learning.

    Directory of Open Access Journals (Sweden)

    George L Sutphin

    2016-11-01

    Full Text Available The rapid advancement of technology in genomics and targeted genetic manipulation has made comparative biology an increasingly prominent strategy to model human disease processes. Predicting orthology relationships between species is a vital component of comparative biology. Dozens of strategies for predicting orthologs have been developed using combinations of gene and protein sequence, phylogenetic history, and functional interaction with progressively increasing accuracy. A relatively new class of orthology prediction strategies combines aspects of multiple methods into meta-tools, resulting in improved prediction performance. Here we present WORMHOLE, a novel ortholog prediction meta-tool that applies machine learning to integrate 17 distinct ortholog prediction algorithms to identify novel least diverged orthologs (LDOs between 6 eukaryotic species-humans, mice, zebrafish, fruit flies, nematodes, and budding yeast. Machine learning allows WORMHOLE to intelligently incorporate predictions from a wide-spectrum of strategies in order to form aggregate predictions of LDOs with high confidence. In this study we demonstrate the performance of WORMHOLE across each combination of query and target species. We show that WORMHOLE is particularly adept at improving LDO prediction performance between distantly related species, expanding the pool of LDOs while maintaining low evolutionary distance and a high level of functional relatedness between genes in LDO pairs. We present extensive validation, including cross-validated prediction of PANTHER LDOs and evaluation of evolutionary divergence and functional similarity, and discuss future applications of machine learning in ortholog prediction. A WORMHOLE web tool has been developed and is available at http://wormhole.jax.org/.

  19. WORMHOLE: Novel Least Diverged Ortholog Prediction through Machine Learning

    Science.gov (United States)

    Sutphin, George L.; Mahoney, J. Matthew; Sheppard, Keith; Walton, David O.; Korstanje, Ron

    2016-01-01

    The rapid advancement of technology in genomics and targeted genetic manipulation has made comparative biology an increasingly prominent strategy to model human disease processes. Predicting orthology relationships between species is a vital component of comparative biology. Dozens of strategies for predicting orthologs have been developed using combinations of gene and protein sequence, phylogenetic history, and functional interaction with progressively increasing accuracy. A relatively new class of orthology prediction strategies combines aspects of multiple methods into meta-tools, resulting in improved prediction performance. Here we present WORMHOLE, a novel ortholog prediction meta-tool that applies machine learning to integrate 17 distinct ortholog prediction algorithms to identify novel least diverged orthologs (LDOs) between 6 eukaryotic species—humans, mice, zebrafish, fruit flies, nematodes, and budding yeast. Machine learning allows WORMHOLE to intelligently incorporate predictions from a wide-spectrum of strategies in order to form aggregate predictions of LDOs with high confidence. In this study we demonstrate the performance of WORMHOLE across each combination of query and target species. We show that WORMHOLE is particularly adept at improving LDO prediction performance between distantly related species, expanding the pool of LDOs while maintaining low evolutionary distance and a high level of functional relatedness between genes in LDO pairs. We present extensive validation, including cross-validated prediction of PANTHER LDOs and evaluation of evolutionary divergence and functional similarity, and discuss future applications of machine learning in ortholog prediction. A WORMHOLE web tool has been developed and is available at http://wormhole.jax.org/. PMID:27812085

  20. Weighted divergence correction scheme and its fast implementation

    Science.gov (United States)

    Wang, ChengYue; Gao, Qi; Wei, RunJie; Li, Tian; Wang, JinJun

    2017-05-01

    Forcing the experimental volumetric velocity fields to satisfy mass conversation principles has been proved beneficial for improving the quality of measured data. A number of correction methods including the divergence correction scheme (DCS) have been proposed to remove divergence errors from measurement velocity fields. For tomographic particle image velocimetry (TPIV) data, the measurement uncertainty for the velocity component along the light thickness direction is typically much larger than for the other two components. Such biased measurement errors would weaken the performance of traditional correction methods. The paper proposes a variant for the existing DCS by adding weighting coefficients to the three velocity components, named as the weighting DCS (WDCS). The generalized cross validation (GCV) method is employed to choose the suitable weighting coefficients. A fast algorithm for DCS or WDCS is developed, making the correction process significantly low-cost to implement. WDCS has strong advantages when correcting velocity components with biased noise levels. Numerical tests validate the accuracy and efficiency of the fast algorithm, the effectiveness of GCV method, and the advantages of WDCS. Lastly, DCS and WDCS are employed to process experimental velocity fields from the TPIV measurement of a turbulent boundary layer. This shows that WDCS achieves a better performance than DCS in improving some flow statistics.

  1. Quantum networks in divergence-free circuit QED

    Science.gov (United States)

    Parra-Rodriguez, A.; Rico, E.; Solano, E.; Egusquiza, I. L.

    2018-04-01

    Superconducting circuits are one of the leading quantum platforms for quantum technologies. With growing system complexity, it is of crucial importance to develop scalable circuit models that contain the minimum information required to predict the behaviour of the physical system. Based on microwave engineering methods, divergent and non-divergent Hamiltonian models in circuit quantum electrodynamics have been proposed to explain the dynamics of superconducting quantum networks coupled to infinite-dimensional systems, such as transmission lines and general impedance environments. Here, we study systematically common linear coupling configurations between networks and infinite-dimensional systems. The main result is that the simple Lagrangian models for these configurations present an intrinsic natural length that provides a natural ultraviolet cutoff. This length is due to the unavoidable dressing of the environment modes by the network. In this manner, the coupling parameters between their components correctly manifest their natural decoupling at high frequencies. Furthermore, we show the requirements to correctly separate infinite-dimensional coupled systems in local bases. We also compare our analytical results with other analytical and approximate methods available in the literature. Finally, we propose several applications of these general methods to analogue quantum simulation of multi-spin-boson models in non-perturbative coupling regimes.

  2. Vertical divergence of fogwater fluxes above a spruce forest

    Science.gov (United States)

    Burkard, R.; Eugster, W.; Wrzesinsky, T.; Klemm, O.

    Two almost identical eddy covariance measurement setups were used to measure the fogwater fluxes to a forest ecosystem in the "Fichtelgebirge" mountains (Waldstein research site, 786 m a.s.l.) in Germany. During the first experiment, an intercomparison was carried out with both setups running simultaneously at the same measuring height on a meteorological tower, 12.5 m above the forest canopy. The results confirmed a close agreement of the turbulent fluxes between the two setups, and allowed to intercalibrate liquid water content (LWC) and gravitational fluxes. During the second experiment, the setups were mounted at a height of 12.5 and 3 m above the canopy, respectively. For the 22 fog events, a persistent negative flux divergence was observed with a greater downward flux at the upper level. To extrapolate the turbulent liquid water fluxes measured at height z to the canopy of height hc, a conversion factor 1/[1+0.116( z- hc)] was determined. For the fluxes of nonvolatile ions, no such correction is necessary since the net evaporation of the fog droplets appears to be the primary cause of the vertical flux divergence. Although the net evaporation reduces the liquid water flux reaching the canopy, it is not expected to change the absolute amount of ions dissolved in fogwater.

  3. Happy creativity: Listening to happy music facilitates divergent thinking.

    Science.gov (United States)

    Ritter, Simone M; Ferguson, Sam

    2017-01-01

    Creativity can be considered one of the key competencies for the twenty-first century. It provides us with the capacity to deal with the opportunities and challenges that are part of our complex and fast-changing world. The question as to what facilitates creative cognition-the ability to come up with creative ideas, problem solutions and products-is as old as the human sciences, and various means to enhance creative cognition have been studied. Despite earlier scientific studies demonstrating a beneficial effect of music on cognition, the effect of music listening on creative cognition has remained largely unexplored. The current study experimentally tests whether listening to specific types of music (four classical music excerpts systematically varying on valance and arousal), as compared to a silence control condition, facilitates divergent and convergent creativity. Creativity was higher for participants who listened to 'happy music' (i.e., classical music high on arousal and positive mood) while performing the divergent creativity task, than for participants who performed the task in silence. No effect of music was found for convergent creativity. In addition to the scientific contribution, the current findings may have important practical implications. Music listening can be easily integrated into daily life and may provide an innovative means to facilitate creative cognition in an efficient way in various scientific, educational and organizational settings when creative thinking is needed.

  4. Genome-nutrition divergence: evolving understanding of the malnutrition spectrum.

    Science.gov (United States)

    Eaton, Jacob C; Iannotti, Lora L

    2017-11-01

    Humans adapted over a period of 2.3 million years to a diet high in quality and diversity. Genome-nutrition divergence describes the misalignment between modern global diets and the genome formed through evolution. A survey of hominin diets over time shows that humans have thrived on a broad range of foods. Earlier diets were highly diverse and nutrient dense, in contrast to modern food systems in which monotonous diets of staple cereals and ultraprocessed foods play a more prominent role. Applying the lens of genome-nutrition divergence to malnutrition reveals shared risk factors for undernutrition and overnutrition at nutrient, food, and environmental levels. Mechanisms for food system shifts, such as crop-neutral agricultural policy, agroecology, and social policy, are explored as a means to realign modern diets with the nutritional patterns to which humans may be better adapted to thrive. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Coherence and Divergence of Megatrends in Science and Engineering

    International Nuclear Information System (INIS)

    Roco, M.C.

    2002-01-01

    Scientific discoveries and technological innovations are at the core of human endeavor, and it is estimated that their role will only increase in time. Such advancements evolve in coherence, with areas of confluence and temporary divergences, which bring synergism and that stimulate further developments following in average an exponential growth. Six increasingly interconnected megatrends are perceived as dominating the scene for the next decades: (a) information and computing, (b) nanoscale science and engineering (S and E), (c) biology and bio-environmental approaches, (d) medical sciences and enhancing human physical capabilities, (e) cognitive sciences and enhancing intellectual abilities, and (f) collective behavior and system approach.This paper presents a perspective on the process of identification, planning and program implementation of S and E megatrends, with illustration for the US research initiative on nanoscale science, engineering, and technology. The interplay between coherence and divergence, leading to unifying science and converging technologies, does not develop only among simultaneous scientific trends but also along time and across geopolitical boundaries. There is no single way of development of S and E, and here is the role of taking visionary measures. Societal implication scientists need to be involved from the conceptual phase of a program responding to a S and E megatrend

  6. Genomic islands of divergence are not affected by geography of speciation in sunflowers.

    Science.gov (United States)

    Renaut, S; Grassa, C J; Yeaman, S; Moyers, B T; Lai, Z; Kane, N C; Bowers, J E; Burke, J M; Rieseberg, L H

    2013-01-01

    Genomic studies of speciation often report the presence of highly differentiated genomic regions interspersed within a milieu of weakly diverged loci. The formation of these speciation islands is generally attributed to reduced inter-population gene flow near loci under divergent selection, but few studies have critically evaluated this hypothesis. Here, we report on transcriptome scans among four recently diverged pairs of sunflower (Helianthus) species that vary in the geographical context of speciation. We find that genetic divergence is lower in sympatric and parapatric comparisons, consistent with a role for gene flow in eroding neutral differences. However, genomic islands of divergence are numerous and small in all comparisons, and contrary to expectations, island number and size are not significantly affected by levels of interspecific gene flow. Rather, island formation is strongly associated with reduced recombination rates. Overall, our results indicate that the functional architecture of genomes plays a larger role in shaping genomic divergence than does the geography of speciation.

  7. Island biology and morphological divergence of the Skyros wall lizard Podarcis gaigeae: a combined role for local selection and genetic drift on color morph frequency divergence?

    Directory of Open Access Journals (Sweden)

    Runemark Anna

    2010-09-01

    Full Text Available Abstract Background Patterns of spatial variation in discrete phenotypic traits can be used to draw inferences about the adaptive significance of traits and evolutionary processes, especially when compared to patterns of neutral genetic variation. Population divergence in adaptive traits such as color morphs can be influenced by both local ecology and stochastic factors such as genetic drift or founder events. Here, we use quantitative color measurements of males and females of Skyros wall lizard, Podarcis gaigeae, to demonstrate that this species is polymorphic with respect to throat color, and the morphs form discrete phenotypic clusters with limited overlap between categories. We use divergence in throat color morph frequencies and compare that to neutral genetic variation to infer the evolutionary processes acting on islet- and mainland populations. Results Geographically close islet- and mainland populations of the Skyros wall lizard exhibit strong divergence in throat color morph frequencies. Population variation in throat color morph frequencies between islets was higher than that between mainland populations, and the effective population sizes on the islets were small (Ne:s ST for throat color morph frequencies fell within the neutral FST-distribution estimated from microsatellite markers, and genetic drift could thus not be rejected as an explanation for the pattern. Moreover, for both comparisons among mainland-mainland population pairs and between mainland-islet population pairs, morph frequency divergence was significantly correlated with neutral divergence, further pointing to some role for genetic drift in divergence also at the phenotypic level of throat color morphs. Conclusions Genetic drift could not be rejected as an explanation for the pattern of population divergence in morph frequencies. In spite of an expected stabilising selection, throat color frequencies diverged in the islet populations. These results suggest that

  8. New STLV-3 strains and a divergent SIVmus strain identified in non-human primate bushmeat in Gabon

    Directory of Open Access Journals (Sweden)

    Liégeois Florian

    2012-03-01

    Full Text Available Abstract Background Human retroviral infections such as Human Immunodeficiency Virus (HIV or Human T-cell Lymphotropic Virus (HTLV are the result of simian zoonotic transmissions through handling and butchering of Non-Human Primates (NHP or by close contact with pet animals. Recent studies on retroviral infections in NHP bushmeat allowed for the identification of numerous Simian Immunodeficiency Viruses (SIV and Simian T-cell Lymphotropic Viruses (STLV to which humans are exposed. Nevertheless, today, data on simian retroviruses at the primate/hunter interface remain scarce. We conducted a pilot study on 63 blood and/or tissues samples derived from NHP bushmeat seized by the competent authorities in different locations across the country. Results SIV and STLV were detected by antibodies to HIV and HTLV antigens, and PCRs were performed on samples with an HIV or/and HTLV-like or indeterminate profile. Fourteen percent of the samples cross-reacted with HIV antigens and 44% with HTLV antigens. We reported STLV-1 infections in five of the seven species tested. STLV-3 infections, including a new STLV-3 subtype, STLV-1 and -3 co-infections, and triple SIV, STLV-1, STLV-3 infections were observed in red-capped mangabeys (C.torquatus. We confirmed SIV infections by PCR and sequence analyses in mandrills, red-capped mangabeys and showed that mustached monkeys in Gabon are infected with a new SIV strain basal to the SIVgsn/mus/mon lineage that did not fall into the previously described SIVmus lineages reported from the corresponding species in Cameroon. The same monkey (subspecies can thus be carrier of, at least, three distinct SIVs. Overall, the minimal prevalence observed for both STLV and SIV natural infections were 26.9% and 11.1% respectively. Conclusions Overall, these data, obtained from a restricted sampling, highlight the need for further studies on simian retroviruses in sub-Saharan Africa to better understand their evolutionary history and to

  9. On the Borel summability of divergent solutions of the heat equation

    OpenAIRE

    Lutz, D. A.; Miyake, M.; Schäfke, R.

    1999-01-01

    In recent years, the theory of Borel summability or multisummability of divergent power series of one variable has been established and it has been proved that every formal solution of an ordinary differential equation with irregular singular point is multisummable. For partial differential equations the summability problem for divergent solutions has not been studied so well, and in this paper we shall try to develop the Borel summability of divergent solutions of the Cauch...

  10. ON A PROLONGATION CONSTRUCTION FOR LOCAL NON-DIVERGENT VECTOR FIELDS ON Rn

    Directory of Open Access Journals (Sweden)

    A. M. Lukatsky

    2015-01-01

    Full Text Available The problem of a prolongation of non-divergent vector field, defined in a vicinity of zero in Rn t, to a finite non-divergent vector field on Rn is considered. Explicit formulas for the elements of the simple Lie algebra of non-divergent vector from the well-known Cartan series are obtained. This construction allows to move from the Euler equations for the ideal incompressible fluid to the Euler equations on finite-dimensional Lie groups.

  11. Divergence of gene body DNA methylation and evolution of plant duplicate genes.

    Directory of Open Access Journals (Sweden)

    Jun Wang

    Full Text Available It has been shown that gene body DNA methylation is associated with gene expression. However, whether and how deviation of gene body DNA methylation between duplicate genes can influence their divergence remains largely unexplored. Here, we aim to elucidate the potential role of gene body DNA methylation in the fate of duplicate genes. We identified paralogous gene pairs from Arabidopsis and rice (Oryza sativa ssp. japonica genomes and reprocessed their single-base resolution methylome data. We show that methylation in paralogous genes nonlinearly correlates with several gene properties including exon number/gene length, expression level and mutation rate. Further, we demonstrated that divergence of methylation level and pattern in paralogs indeed positively correlate with their sequence and expression divergences. This result held even after controlling for other confounding factors known to influence the divergence of paralogs. We observed that methylation level divergence might be more relevant to the expression divergence of paralogs than methylation pattern divergence. Finally, we explored the mechanisms that might give rise to the divergence of gene body methylation in paralogs. We found that exonic methylation divergence more closely correlates with expression divergence than intronic methylation divergence. We show that genomic environments (e.g., flanked by transposable elements and repetitive sequences of paralogs generated by various duplication mechanisms are associated with the methylation divergence of paralogs. Overall, our results suggest that the changes in gene body DNA methylation could provide another avenue for duplicate genes to develop differential expression patterns and undergo different evolutionary fates in plant genomes.

  12. On the summability of divergent power series solutions for certain first-order linear PDEs

    Directory of Open Access Journals (Sweden)

    Masaki Hibino

    2015-01-01

    Full Text Available This article is concerned with the study of the Borel summability of divergent power series solutions for certain singular first-order linear partial differential equations of nilpotent type. Our main purpose is to obtain conditions which coefficients of equations should satisfy in order to ensure the Borel summability of divergent solutions. We will see that there is a close affinity between the Borel summability of divergent solutions and global analytic continuation properties for coefficients of equations.

  13. Cytotoxic T-Lymphocyte Escape Does Not Always Explain the Transient Control of Simian Immunodeficiency Virus SIVmac239 Viremia in Adenovirus-Boosted and DNA-Primed Mamu-A*01-Positive Rhesus Macaques

    Science.gov (United States)

    McDermott, Adrian B.; O'Connor, David H.; Fuenger, Sarah; Piaskowski, Shari; Martin, Sarah; Loffredo, John; Reynolds, Matthew; Reed, Jason; Furlott, Jessica; Jacoby, Timothy; Riek, Cara; Dodds, Elizabeth; Krebs, Kendall; Davies, Mary-Ellen; Schleif, William A.; Casimiro, Danilo R.; Shiver, John W.; Watkins, D. I.

    2005-01-01

    Adenovirus 5 (Ad5) vectors show promise as human immunodeficiency virus vaccine candidates. Indian rhesus macaques vaccinated with Ad5-gag controlled simian-human immunodeficiency virus SHIV89.6P viral replication in the absence of Env immunogens that might elicit humoral immunity. Here we immunized 15 macaques using either a homologous Ad5-gag/Ad5-gag (Ad5/Ad5) or a heterologous DNA-gag/Ad5-gag (DNA/Ad5) prime-boost regimen and challenged them with a high dose of simian immunodeficiency virus SIVmac239. Macaques vaccinated with the DNA/Ad5 regimen experienced a brief viral load nadir of less than 10,000 viral copies per ml blood plasma that was not seen in Mamu-A*01-negative DNA/Ad5 vaccinees, Mamu-A*01-positive Ad5/Ad5 vaccinees, or vaccine-naive controls. Interestingly, most of these animals were not durably protected from disease progression when challenged with SIVmac239. To investigate the reasons underlying this short-lived vaccine effect, we investigated breadth of the T-cell response, immunogenetic background, and viral escape from CD8+ lymphocytes that recognize immunodominant T-cell epitopes. We show that these animals do not mount unusually broad cellular immune response, nor do they express unusual major histocompatibility complex class I alleles. Viral recrudescence occurred in four of the five Mamu-A*01-positive vaccinated macaques. However, only a single animal in this group demonstrated viral escape in the immunodominant Gag181-189CM9 response. These results suggest that viral “breakthrough” in vaccinated animals and viral escape are not inextricably linked and underscore the need for additional research into the mechanisms of vaccine failure. PMID:16306626

  14. Changes in soluble factor-mediated CD8+ cell-derived antiviral activity in cynomolgus macaques infected with simian immunodeficiency virus SIVmac251: relationship to biological markers of progression.

    Science.gov (United States)

    Dioszeghy, Vincent; Benlhassan-Chahour, Kadija; Delache, Benoit; Dereuddre-Bosquet, Nathalie; Aubenque, Celine; Gras, Gabriel; Le Grand, Roger; Vaslin, Bruno

    2006-01-01

    Cross-sectional studies have shown that the capacity of CD8+ cells from human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV) SIVmac-infected macaques to suppress the replication of human and simian immunodeficiency viruses in vitro depends on the clinical stage of disease, but little is known about changes in this antiviral activity over time in individual HIV-infected patients or SIV-infected macaques. We assessed changes in the soluble factor-mediated noncytolytic antiviral activity of CD8+ cells over time in eight cynomolgus macaques infected with SIVmac251 to determine the pathophysiological role of this activity. CD8+ cell-associated antiviral activity increased rapidly in the first week after viral inoculation and remained detectable during the early phase of infection. The net increase in antiviral activity of CD8+ cells was correlated with plasma viral load throughout the 15 months of follow-up. CD8+ cells gradually lost their antiviral activity over time and acquired virus replication-enhancing capacity. Levels of antiviral activity correlated with CD4+ T-cell counts after viral set point. Concentrations of beta-chemokines and interleukin-16 in CD8+ cell supernatants were not correlated with this antiviral activity, and alpha-defensins were not detected. The soluble factor-mediated antiviral activity of CD8+ cells was neither cytolytic nor restricted to major histocompatibility complex. This longitudinal study strongly suggests that the increase in noncytolytic antiviral activity from baseline and the maintenance of this increase over time in cynomolgus macaques depend on both viral replication and CD4+ T cells.

  15. Changes in Soluble Factor-Mediated CD8+ Cell-Derived Antiviral Activity in Cynomolgus Macaques Infected with Simian Immunodeficiency Virus SIVmac251: Relationship to Biological Markers of Progression†

    Science.gov (United States)

    Dioszeghy, Vincent; Benlhassan-Chahour, Kadija; Delache, Benoit; Dereuddre-Bosquet, Nathalie; Aubenque, Celine; Gras, Gabriel; Le Grand, Roger; Vaslin, Bruno

    2006-01-01

    Cross-sectional studies have shown that the capacity of CD8+ cells from human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV) SIVmac-infected macaques to suppress the replication of human and simian immunodeficiency viruses in vitro depends on the clinical stage of disease, but little is known about changes in this antiviral activity over time in individual HIV-infected patients or SIV-infected macaques. We assessed changes in the soluble factor-mediated noncytolytic antiviral activity of CD8+ cells over time in eight cynomolgus macaques infected with SIVmac251 to determine the pathophysiological role of this activity. CD8+ cell-associated antiviral activity increased rapidly in the first week after viral inoculation and remained detectable during the early phase of infection. The net increase in antiviral activity of CD8+ cells was correlated with plasma viral load throughout the 15 months of follow-up. CD8+ cells gradually lost their antiviral activity over time and acquired virus replication-enhancing capacity. Levels of antiviral activity correlated with CD4+ T-cell counts after viral set point. Concentrations of β-chemokines and interleukin-16 in CD8+ cell supernatants were not correlated with this antiviral activity, and α-defensins were not detected. The soluble factor-mediated antiviral activity of CD8+ cells was neither cytolytic nor restricted to major histocompatibility complex. This longitudinal study strongly suggests that the increase in noncytolytic antiviral activity from baseline and the maintenance of this increase over time in cynomolgus macaques depend on both viral replication and CD4+ T cells. PMID:16352548

  16. Simian Immunodeficiency Virus Targeting of CXCR3+ CD4+ T Cells in Secondary Lymphoid Organs Is Associated with Robust CXCL10 Expression in Monocyte/Macrophage Subsets.

    Science.gov (United States)

    Fujino, Masayuki; Sato, Hirotaka; Okamura, Tomotaka; Uda, Akihiko; Takeda, Satoshi; Ahmed, Nursarat; Shichino, Shigeyuki; Shiino, Teiichiro; Saito, Yohei; Watanabe, Satoru; Sugimoto, Chie; Kuroda, Marcelo J; Ato, Manabu; Nagai, Yoshiyuki; Izumo, Shuji; Matsushima, Kouji; Miyazawa, Masaaki; Ansari, Aftab A; Villinger, Francois; Mori, Kazuyasu

    2017-07-01

    Glycosylation of Env defines pathogenic properties of simian immunodeficiency virus (SIV). We previously demonstrated that pathogenic SIVmac239 and a live-attenuated, quintuple deglycosylated Env mutant (Δ5G) virus target CD4 + T cells residing in different tissues during acute infection. SIVmac239 and Δ5G preferentially infected distinct CD4 + T cells in secondary lymphoid organs (SLOs) and within the lamina propria of the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Here, we studied the host responses relevant to SIV targeting of CXCR3 + CCR5 + CD4 + T cells in SLOs. Genome-wide transcriptome analyses revealed that Th1-polarized inflammatory responses, defined by expression of CXCR3 chemokines, were distinctly induced in the SIVmac239-infected animals. Consistent with robust expression of CXCL10, CXCR3 + T cells were depleted from blood in the SIVmac239-infected animals. We also discovered that elevation of CXCL10 expression in blood and SLOs was secondary to the induction of CD14 + CD16 + monocytes and MAC387 + macrophages, respectively. Since the significantly higher levels of SIV infection in SLOs occurred with a massive accumulation of infiltrated MAC387 + macrophages, T cells, dendritic cells (DCs), and residential macrophages near high endothelial venules, the results highlight critical roles of innate/inflammatory responses in SIVmac239 infection. Restricted infection in SLOs by Δ5G also suggests that glycosylation of Env modulates innate/inflammatory responses elicited by cells of monocyte/macrophage/DC lineages. IMPORTANCE We previously demonstrated that a pathogenic SIVmac239 virus and a live-attenuated, deglycosylated mutant Δ5G virus infected distinct CD4 + T cell subsets in SLOs and the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Accordingly, infections with SIVmac239, but not with Δ5G, deplete CXCR3

  17. The Global Monsoon as Seen through the Divergent Atmospheric Circulation.

    Science.gov (United States)

    Trenberth, Kevin E.; Stepaniak, David P.; Caron, Julie M.

    2000-11-01

    A comprehensive description is given of the global monsoon as seen through the large-scale overturning in the atmosphere that changes with the seasons, and it provides a basis for delimiting the monsoon regions of the world. The analysis focuses on the mean annual cycle of the divergent winds and associated vertical motions, as given by the monthly mean fields for 1979-93 reanalyses from the National Centers for Environmental Prediction-National Center for Atmospheric Research (NCEP-NCAR) and European Centre for Medium-Range Weather Forecasts (ECMWF), which are able to reproduce the dominant modes. A complex empirical orthogonal function analysis of the divergent circulation brings out two dominant modes with essentially the same vertical structures in all months of the year. The first mode, which depicts the global monsoon, has a simple vertical structure with a maximum in vertical motion at about 400 mb, divergence in the upper troposphere that is strongest at 150 mb and decays to zero amplitude above 70 mb, and convergence in the lower troposphere with a maximum at 925 mb (ECMWF) or 850 mb (NCEP). However, this mode has a rich three-dimensional spatial structure that evolves with the seasons. It accounts for 60% of the annual cycle variance of the divergent mass circulation and dominates the Hadley circulation as well as three overturning transverse cells. These include the Pacific Walker circulation; an Americas-Atlantic Walker circulation, both of which comprise rising motion in the west and sinking in the east; and a transverse cell over Asia, the Middle East, North Africa, and the Indian Ocean that has rising motion in the east and sinking toward the west. These exist year-round but migrate and evolve considerably with the seasons and have about a third to half of the mass flux of the peak Hadley cell. The annual cycle of the two Hadley cells reveals peak strength in early February and early August in both reanalyses.A second monsoon mode, which accounts for

  18. Activation Detection in fMRI Using Jeffrey Divergence

    Science.gov (United States)

    Seghouane, Abd-Krim

    2009-12-01

    A statistical test for detecting activated pixels in functional MRI (fMRI) data is proposed. For the derivation of this test, the fMRI time series measured at each voxel is modeled as the sum of a response signal which arises due to the experimentally controlled activation-baseline pattern, a nuisance component representing effects of no interest, and Gaussian white noise. The test is based on comparing the dimension of the voxels fMRI time series fitted data models with and without controlled activation-baseline pattern. The Jeffrey divergence is used for this comparison. The test has the advantage of not requiring a level of significance or a threshold to be provided.

  19. Regularized κ-distributions with non-diverging moments

    Science.gov (United States)

    Scherer, K.; Fichtner, H.; Lazar, M.

    2017-12-01

    For various plasma applications the so-called (non-relativistic) κ-distribution is widely used to reproduce and interpret the suprathermal particle populations exhibiting a power-law distribution in velocity or energy. Despite its reputation the standard κ-distribution as a concept is still disputable, mainly due to the velocity moments M l which make a macroscopic characterization possible, but whose existence is restricted only to low orders l definition of the κ-distribution itself is conditioned by the existence of the moment of order l = 2 (i.e., kinetic temperature) satisfied only for κ > 3/2 . In order to resolve these critical limitations we introduce the regularized κ-distribution with non-diverging moments. For the evaluation of all velocity moments a general analytical expression is provided enabling a significant step towards a macroscopic (fluid-like) description of space plasmas, and, in general, any system of κ-distributed particles.

  20. Ultraviolet divergences in non-renormalizable supersymmetric theories

    International Nuclear Information System (INIS)

    Smilga, A.

    2017-01-01

    We present a pedagogical review of our current understanding of the ultraviolet structure of N =(1, 1) 6D supersymmetric Yang-Mills theory and of N = 8 4D supergravity. These theories are not renormalizable, they involve power ultraviolet divergences and, in all probability, an infinite set of higher-dimensional counterterms that contribute to on-mass-shell scattering amplitudes. A specific feature of supersymmetric theories (especially of extended supersymmetric theories) is that these counterterms may not be invariant off-shell under the full set of supersymmetry transformations. The lowest-dimensional nontrivial counterterm is supersymmetric on-shell. Still higher counterterms may lose even the on-shell invariance. On the other hand, the full effective Lagrangian, generating the amplitudes and representing an infinite sum of counterterms, still enjoys the complete symmetry of original theory. We also discuss simple supersymmetric quantum-mechanical models that exhibit the same behavior.

  1. Little Divergence Among Mitochondrial Lineages of Prochilodus (Teleostei, Characiformes

    Directory of Open Access Journals (Sweden)

    Bruno F. Melo

    2018-04-01

    Full Text Available Evidence that migration prevents population structure among Neotropical characiform fishes has been reported recently but the effects upon species diversification remain unclear. Migratory species of Prochilodus have complex species boundaries and intrincate taxonomy representing a good model to address such questions. Here, we analyzed 147 specimens through barcode sequences covering all species of Prochilodus across a broad geographic area of South America. Species delimitation and population genetic methods revealed very little genetic divergence among mitochondrial lineages suggesting that extensive gene flow resulted likely from the highly migratory behavior, natural hybridization or recent radiation prevent accumulation of genetic disparity among lineages. Our results clearly delimit eight genetic lineages in which four of them contain a single species and four contain more than one morphologically problematic taxon including a trans-Andean species pair and species of the P. nigricans group. Information about biogeographic distribution of haplotypes presented here might contribute to further research on the population genetics and taxonomy of Prochilodus.

  2. Research Performance Progress Report: Diverging Supernova Explosion Experiments on NIF

    Energy Technology Data Exchange (ETDEWEB)

    Plewa, Tomasz [Florida State Univ., Tallahassee, FL (United States)

    2016-10-25

    The aim of this project was to design a series of blast-wave driven Rayleigh-Taylor (RT) experiments on the National Ignition Facility (NIF). The experiments of this kind are relevant to mixing in core-collapse supernovae (ccSNe) and have the potential to address previously unanswered questions in high-energy density physics (HEDP) and astrophysics. The unmatched laser power of the NIF laser offers a unique chance to observe and study “new physics” like the mass extensions observed in HEDP RT experiments performed on the Omega laser [1], which might be linked to self-generated magnetic fields [2] and so far could not be reproduced by numerical simulations. Moreover, NIF is currently the only facility that offers the possibility to execute a diverging RT experiment, which would allow to observe processes such as inter-shell penetration via turbulent mixing and shock-proximity effects (distortion of the shock by RT spikes).

  3. Approaches to the summability of divergent multidimensional integrals

    International Nuclear Information System (INIS)

    Vainikko, G M; Lifanov, I K

    2003-01-01

    Under discussion are various approaches to the concept of summability (finding the finite part - (f.p.)) of divergent integrals with integrand represented as a product of two functions, one with a parameter-dependent non-integrable singularity at one point of the integration and the other absolutely integrable. A study is made of summability methods which are based on the expansion of the absolutely integrable function in a Taylor series with centre at the singular point (f.p.), on the analytic continuation with respect to the parameter of the singularity (a.f.p.), and on integration by parts (f.p.p.). Formulae of changes of variables in such integrals are presented

  4. A Divergence Statistics Extension to VTK for Performance Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Pebay, Philippe Pierre [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bennett, Janine Camille [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-02-01

    This report follows the series of previous documents ([PT08, BPRT09b, PT09, BPT09, PT10, PB13], where we presented the parallel descriptive, correlative, multi-correlative, principal component analysis, contingency, k -means, order and auto-correlative statistics engines which we developed within the Visualization Tool Kit ( VTK ) as a scalable, parallel and versatile statistics package. We now report on a new engine which we developed for the calculation of divergence statistics, a concept which we hereafter explain and whose main goal is to quantify the discrepancy, in a stasticial manner akin to measuring a distance, between an observed empirical distribution and a theoretical, "ideal" one. The ease of use of the new diverence statistics engine is illustrated by the means of C++ code snippets. Although this new engine does not yet have a parallel implementation, it has already been applied to HPC performance analysis, of which we provide an example.

  5. The constancy of gene conservation across divergent bacterial orders

    Directory of Open Access Journals (Sweden)

    Ackermann Martin

    2009-01-01

    Full Text Available Abstract Background Orthologous genes are frequently presumed to perform similar functions. However, outside of model organisms, this is rarely tested. One means of inferring changes in function is if there are changes in the level of gene conservation and selective constraint. Here we compare levels of gene conservation across three bacterial groups to test for changes in gene functionality. Findings The level of gene conservation for different orthologous genes is highly correlated across clades, even for highly divergent groups of bacteria. These correlations do not arise from broad differences in gene functionality (e.g. informational genes vs. metabolic genes, but instead seem to result from very specific differences in gene function. Furthermore, these functional differences appear to be maintained over very long periods of time. Conclusion These results suggest that even over broad time scales, most bacterial genes are under a nearly constant level of purifying selection, and that bacterial evolution is thus dominated by selective and functional stasis.

  6. DIVERGENT OR CONVERGENT TRENDS IN PROFESSIONAL MILITARY EDUCATION IN SLOVENIA?

    Directory of Open Access Journals (Sweden)

    Maja Garb

    2017-11-01

    Full Text Available There is a decade long discussion about the professional military education in Slovenia. The country has developed its own military force after the independence in 1991. Since the lack of the professional officers corps there was a decision adopted to have a convergent system of staffing the military with the officers. The future officers have to obtain high school or university degree at civilian education institutions, after that they get the military training and education provided by the Slovenian Armed Forces. However, there have been some insufficiencies in the system and therefore the ideas how to change the system of professional military education in Slovenia have been constantly raised. There are several questions on military education in Slovenia that are presented and discussed in the paper in the framework of divergence and convergence of the military and its parent society.

  7. Divergent Synthesis of Solanidine and 22-epi-Solanidine.

    Science.gov (United States)

    Hou, Ling-Li; Shi, Yong; Zhang, Zhi-Dan; Wu, Jing-Jing; Yang, Qing-Xiong; Tian, Wei-Sheng

    2017-07-21

    A divergent synthesis of solanidine and 22-epi-solanidine, two 25S natural steroidal alkaloids, from 25R-configured diosgenin acetate, is described. Initially, solanidine was synthesized through a series of transformations including a cascade ring-switching process of furostan-26-acid, an epimerization of C25 controlled by the conformation of six-membered lactone ring, an intramolecular Schmidt reaction, and an imine reduction/intramolecular aminolysis process. To address the epimerization issue during Schmidt reaction, an improved synthesis was developed, which also led to a synthesis of 22-epi-solanidine. In this synthesis, selective transformation of azido lactone to azido diol and amino diol was realized through a reduction relay tactic. The azido diol was transformed to solanidine via an intramolecular Schmidt reaction/N-alkylation/reduction process and to 22-epi-solanidine via an intramolecular double N-alkylation process.

  8. Summation of divergent series and Zel'dovich's regularization method

    International Nuclear Information System (INIS)

    Mur, V.D.; Pozdnyakov, S.G.; Popruzhenko, S.V.; Popov, V.S.

    2005-01-01

    The method of summation of divergent series, including series of a perturbation theory, which is an analog of the Zel'dovich regularization procedure in the theory of quasistationary states is considered. It is shown that this method is more powerful than the well-known Abel and Borel methods, but compatible with them (i. e., gives the same value for the sum of the series). The restrictions to the range of parameters which appear after removal of the regularization of integrals by this method are discussed. The dynamical Stark shifts and widths of weakly bound s states in a field of circularly polarized electromagnetic wave are calculated at different values of the Keldysh adiabaticity parameter and multiquantum parameter [ru

  9. Kullback-Leibler divergence and the Pareto-Exponential approximation.

    Science.gov (United States)

    Weinberg, G V

    2016-01-01

    Recent radar research interests in the Pareto distribution as a model for X-band maritime surveillance radar clutter returns have resulted in analysis of the asymptotic behaviour of this clutter model. In particular, it is of interest to understand when the Pareto distribution is well approximated by an Exponential distribution. The justification for this is that under the latter clutter model assumption, simpler radar detection schemes can be applied. An information theory approach is introduced to investigate the Pareto-Exponential approximation. By analysing the Kullback-Leibler divergence between the two distributions it is possible to not only assess when the approximation is valid, but to determine, for a given Pareto model, the optimal Exponential approximation.

  10. Increasing self-other integration through divergent thinking.

    Science.gov (United States)

    Colzato, Lorenza S; van den Wildenberg, Wery P M; Hommel, Bernhard

    2013-10-01

    Increasing evidence suggests that people may cognitively represent themselves and others just like any other, nonsocial event. Here, we provide evidence that the degree of self-other integration (as reflected by the joint Simon effect; JSE) is systematically affected by the control characteristics of temporally overlapping but unrelated and nonsocial creativity tasks. In particular, the JSE was found to be larger in the context of a divergent-thinking task (alternate uses task) than in the context of a convergent-thinking task (remote association task). This suggests that self-other integration and action corepresentation are controlled by domain-general cognitive-control parameters that regulate the integrativeness (strong vs. weak top-down control and a resulting narrow vs. broad attentional focus) of information processing irrespective of its social implications.

  11. Divergent Synthesis of Diastereomeric Sphingosines from a Chiral Aziridine

    Energy Technology Data Exchange (ETDEWEB)

    Kang, On-Yu; Shin, Mi-Ri; Kang, Han-Young [Chungbuk National University, Gongju (Korea, Republic of)

    2016-07-15

    All four stereoisomers of sphingosines were synthesized starting from a single intermediate, chiral aziridine (2), which was efficiently prepared by enzymatic desymmetrization in an enatiopure form. Aziridine (2) was converted to 3, which was used for the synthesis of 4. Both the advanced key intermediates, vinylaziridines 3 and 4, were successfully converted to threo-sphingosines 1a and 1b, respectively. Ring-closing metathesis (RCM) using the Grubbs II catalyst was the key reaction in the synthesis. Two erythro-sphingosines 1c and 1d were synthesized by the ring-expansion reactions of vinylaziridines 3 and 4, followed by RCM reactions. The successful divergent synthesis confirmed that chiral vinylaziridine 2 can be used as a key intermediate for the synthesis of sphingosine-related natural products.

  12. Kullback-Leibler divergence measure of intermittency: Application to turbulence

    Science.gov (United States)

    Granero-Belinchón, Carlos; Roux, Stéphane G.; Garnier, Nicolas B.

    2018-01-01

    For generic systems exhibiting power law behaviors, and hence multiscale dependencies, we propose a simple tool to analyze multifractality and intermittency, after noticing that these concepts are directly related to the deformation of a probability density function from Gaussian at large scales to non-Gaussian at smaller scales. Our framework is based on information theory and uses Shannon entropy and Kullback-Leibler divergence. We provide an extensive application to three-dimensional fully developed turbulence, seen here as a paradigmatic complex system where intermittency was historically defined and the concepts of scale invariance and multifractality were extensively studied and benchmarked. We compute our quantity on experimental Eulerian velocity measurements, as well as on synthetic processes and phenomenological models of fluid turbulence. Our approach is very general and does not require any underlying model of the system, although it can probe the relevance of such a model.

  13. A detector for localizing diverging beams of ionizing radiations

    International Nuclear Information System (INIS)

    Allemand, Robert.

    1974-01-01

    Description is given of a detector for localizing diverging radiation beams, adapted to provide the angular distribution of nuclear events. That detector comprises a casing filled with a fluid adapted to produce electric charges under radiations and provided with a front-side and a rear-side, means for generating an electric field at right angles to portions of parallel surfaces of revolution having in common an axis of revolution contained in the place of symmetry, and a plane unit for localizing electric charges mounted at the rear of said means, the initial portion of the beam being on the axis of revolution. This can be applied to X-ray diffraction and to neutron diffraction [fr

  14. Divergent series, summability and resurgence I monodromy and resurgence

    CERN Document Server

    Mitschi, Claude

    2016-01-01

    Providing an elementary introduction to analytic continuation and monodromy, the first part of this volume applies these notions to the local and global study of complex linear differential equations, their formal solutions at singular points, their monodromy and their differential Galois groups. The Riemann-Hilbert problem is discussed from Bolibrukh’s point of view. The second part expounds 1-summability and Ecalle’s theory of resurgence under fairly general conditions. It contains numerous examples and presents an analysis of the singularities in the Borel plane via “alien calculus”, which provides a full description of the Stokes phenomenon for linear or non-linear differential or difference equations. The first of a series of three, entitled Divergent Series, Summability and Resurgence, this volume is aimed at graduate students, mathematicians and theoretical physicists interested in geometric, algebraic or local analytic properties of dynamical systems. It includes useful exercises with solution...

  15. Hypergeometric continuation of divergent perturbation series: I. Critical exponents of the Bose–Hubbard model

    International Nuclear Information System (INIS)

    Sanders, Sören; Holthaus, Martin

    2017-01-01

    We study the connection between the exponent of the order parameter of the Mott insulator-to-superfluid transition occurring in the two-dimensional Bose–Hubbard model, and the divergence exponents of its one- and two-particle correlation functions. We find that at the multicritical points all divergence exponents are related to each other, allowing us to express the critical exponent in terms of one single divergence exponent. This approach correctly reproduces the critical exponent of the three-dimensional XY universality class. Because divergence exponents can be computed in an efficient manner by hypergeometric analytic continuation, our strategy is applicable to a wide class of systems. (paper)

  16. Hypergeometric continuation of divergent perturbation series: I. Critical exponents of the Bose-Hubbard model

    Science.gov (United States)

    Sanders, Sören; Holthaus, Martin

    2017-10-01

    We study the connection between the exponent of the order parameter of the Mott insulator-to-superfluid transition occurring in the two-dimensional Bose-Hubbard model, and the divergence exponents of its one- and two-particle correlation functions. We find that at the multicritical points all divergence exponents are related to each other, allowing us to express the critical exponent in terms of one single divergence exponent. This approach correctly reproduces the critical exponent of the three-dimensional XY universality class. Because divergence exponents can be computed in an efficient manner by hypergeometric analytic continuation, our strategy is applicable to a wide class of systems.

  17. Creative Cognition in Secondary Science: An exploration of divergent thinking in science among adolescents

    Science.gov (United States)

    Antink-Meyer, Allison; Lederman, Norman G.

    2015-07-01

    The divergent thinking skills in science of 282 US high school students were investigated across 16 weeks of instruction in order to determine whether typical academic time periods can significantly influence changes in thinking skills. Students' from 6 high school science classrooms completed the Scientific Structures Creativity Measure (SSCM) before and after a semester of instruction. Even the short time frame of a typical academic term was found to be sufficient to promote both improvements in divergent thinking skills as well as declining divergent thinking. Declining divergent thinking skills were more common in this time frame than were improvements. The nature of student performance on the SSCM and implications are discussed.

  18. Acidic ribosomal proteins and histone H3 from Leishmania present a high rate of divergence

    Directory of Open Access Journals (Sweden)

    Ysabel Montoya

    2000-08-01

    Full Text Available Another additional peculiarity in Leishmania will be discussed about of the amino acid divergence rate of three structural proteins: acidic ribosomal P1 and P2b proteins, and histone H3 by using multiple sequence alignment and dendrograms. These structural proteins present a high rate of divergence regarding to their homologous protein in Trypanosoma cruzi. At this regard, L. (V. peruviana P1 and T. cruzi P1 showed 57.4% of divergence rate. Likewise, L. (V. braziliensis histone H3 and acidic ribosomal P2 protein exhibited 31.8% and 41.7% respectively of rate of divergence in comparison with their homologous in T. cruzi.

  19. Segmenting the human genome based on states of neutral genetic divergence.

    Science.gov (United States)

    Kuruppumullage Don, Prabhani; Ananda, Guruprasad; Chiaromonte, Francesca; Makova, Kateryna D

    2013-09-03

    Many studies have demonstrated that divergence levels generated by different mutation types vary and covary across the human genome. To improve our still-incomplete understanding of the mechanistic basis of this phenomenon, we analyze several mutation types simultaneously, anchoring their variation to specific regions of the genome. Using hidden Markov models on insertion, deletion, nucleotide substitution, and microsatellite divergence estimates inferred from human-orangutan alignments of neutrally evolving genomic sequences, we segment the human genome into regions corresponding to different divergence states--each uniquely characterized by specific combinations of divergence levels. We then parsed the mutagenic contributions of various biochemical processes associating divergence states with a broad range of genomic landscape features. We find that high divergence states inhabit guanine- and cytosine (GC)-rich, highly recombining subtelomeric regions; low divergence states cover inner parts of autosomes; chromosome X forms its own state with lowest divergence; and a state of elevated microsatellite mutability is interspersed across the genome. These general trends are mirrored in human diversity data from the 1000 Genomes Project, and departures from them highlight the evolutionary history of primate chromosomes. We also find that genes and noncoding functional marks [annotations from the Encyclopedia of DNA Elements (ENCODE)] are concentrated in high divergence states. Our results provide a powerful tool for biomedical data analysis: segmentations can be used to screen personal genome variants--including those associated with cancer and other diseases--and to improve computational predictions of noncoding functional elements.

  20. Divergence and Conservative Evolution of XTNX Genes in Land Plants

    Directory of Open Access Journals (Sweden)

    Yan-Mei Zhang

    2017-10-01

    Full Text Available The Toll-interleukin-1 receptor (TIR and Nucleotide-binding site (NBS domains are two major components of the TIR-NBS-leucine-rich repeat family plant disease resistance genes. Extensive functional and evolutionary studies have been performed on these genes; however, the characterization of a small group of genes that are composed of atypical TIR and NBS domains, namely XTNX genes, is limited. The present study investigated this specific gene family by conducting genome-wide analyses of 59 green plant genomes. A total of 143 XTNX genes were identified in 51 of the 52 land plant genomes, whereas no XTNX gene was detected in any green algae genomes, which indicated that XTNX genes originated upon emergence of land plants. Phylogenetic analysis revealed that the ancestral XTNX gene underwent two rounds of ancient duplications in land plants, which resulted in the formation of clades I/II and clades IIa/IIb successively. Although clades I and IIb have evolved conservatively in angiosperms, the motif composition difference and sequence divergence at the amino acid level suggest that functional divergence may have occurred since the separation of the two clades. In contrast, several features of the clade IIa genes, including the absence in the majority of dicots, the long branches in the tree, the frequent loss of ancestral motifs, and the loss of expression in all detected tissues of Zea mays, all suggest that the genes in this lineage might have undergone pseudogenization. This study highlights that XTNX genes are a gene family originated anciently in land plants and underwent specific conservative pattern in evolution.