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  1. A prospective longitudinal in vivo 1H MR spectroscopy study of the SIV/macaque model of neuroAIDS

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    Halpern Elkan

    2004-03-01

    Full Text Available Abstract Background The neurological complications of HIV infection remain poorly understood. Clinically, in vivo 1H magnetic resonance spectroscopy (MRS demonstrates brain injury caused by HIV infection even when the MRI is normal. Our goal was to undertsand the dynamics of cerebral injury by performing a longitudinal in vivo 1H MRS study of the SIV/macaque model of neuroAIDS. Results Eight rhesus macaques were infected with SIVmac251 and serially imaged with MRI and 1H MRS to terminal AIDS or the endpoint of 2 years. During acute infection, there were stereotypical brain MRS changes, dominated by a significant elevation of the Cho/Cr ratio in the frontal cortex. Subsequently, brain metabolic patterns diverged between animals. There was an elevation of basal ganglia Cho/Cr four weeks post-inoculation in 2 animals that developed SIV encephalitis (p = 0.022. Metabolite ratios averaged across all 8 animals were not significantly different from baseline at any time point after 2 weeks post inoculation. However, linear regression analysis on all 8 animals revealed a positive correlation between a change in frontal lobe Cho/Cr and plasma viral load (P Conclusions After infection with SIV, macaque brain metabolism changes in a complex manner that is dependent on brain region, host factors and viral load. An elevation of basal ganglia Cho/Cr 4 weeks after SIV infection may be marker of a propensity to develop SIV encephalitis. Elevations of Cho/Cr, often observed in CNS inflammation, were associated with increased plasma viral load during acute and chronic infection. Evidence of neuronal injury in the basal ganglia was associated with increased plasma viral load in the chronic stage of infection. These observations support the use of drugs capable of controlling the viral replication and trafficking of virus into the CNS, and may help explain the reduction in incidence of HIV-associated dementia in the era of HAART despite the inability of most of

  2. Variability of Bio-Clinical Parameters in Chinese-Origin Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Nonhuman Primate AIDS Model

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    Chen, Song; Lai, Chunhui; Wu, Xiaoxiang; Lu, Yaozheng; Han, Daishu; Guo, Weizhong; Fu, Linchun; Andrieu, Jean-Marie; Lu, Wei

    2011-01-01

    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 (ir) SIVmac239, intravenous (iv) SIVmac239, or iv 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 (ir or iv)-infected than in SIVmac251 (iv)-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 (ir or iv)-infected than in SIVmac251 (iv)-infected animals. No significant difference in bio-clinical endpoints was observed in animals challenged with ir or iv SIVmac239. The variability (standard deviation) in peak/set-point VL was nearly one-half lower in animals infected with SIVmac239 (ir or iv) than in those infected with SIVmac251 (iv), 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. PMID:21850259

  3. Variability of bio-clinical parameters in Chinese-origin Rhesus macaques infected with simian immunodeficiency virus: a nonhuman primate AIDS model.

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    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.

  4. Association of TLR7 variants with AIDS-like disease and AIDS vaccine efficacy in rhesus macaques.

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    Roman A Siddiqui

    Full Text Available In HIV infection, TLR7-triggered IFN-α production exerts a direct antiviral effect through the inhibition of viral replication, but may also be involved in immune pathogenesis leading to AIDS. TLR7 could also be an important mediator of vaccine efficacy. In this study, we analyzed polymorphisms in the X-linked TLR7 gene in the rhesus macaque model of AIDS. Upon resequencing of the TLR7 gene in 36 rhesus macaques of Indian origin, 12 polymorphic sites were detected. Next, we identified three tightly linked single nucleotide polymorphisms (SNP as being associated with survival time. Genotyping of 119 untreated, simian immunodeficiency virus (SIV-infected male rhesus macaques, including an 'MHC adjusted' subset, revealed that the three TLR7 SNPs are also significantly associated with set-point viral load. Surprisingly, this effect was not observed in 72 immunized SIV-infected male monkeys. We hypothesize (i that SNP c.13G>A in the leader peptide is causative for the observed genotype-phenotype association and that (ii the underlying mechanism is related to RNA secondary structure formation. Therefore, we investigated a fourth SNP (c.-17C>T, located 17 bp upstream of the ATG translation initiation codon, that is also potentially capable of influencing RNA structure. In c.13A carriers, neither set-point viral load nor survival time were related to the c.-17C>T genotype. In c.13G carriers, by contrast, the c.-17C allele was significantly associated with prolonged survival. Again, no such association was detected among immunized SIV-infected macaques. Our results highlight the dual role of TLR7 in immunodeficiency virus infection and vaccination and imply that it may be important to control human AIDS vaccine trials, not only for MHC genotype, but also for TLR7 genotype.

  5. Altered immune responses in rhesus macaques co-infected with SIV and Plasmodium cynomolgi: an animal model for coincident AIDS and relapsing malaria.

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    Jeffrey W Koehler

    Full Text Available BACKGROUND: Dual epidemics of the malaria parasite Plasmodium and HIV-1 in sub-Saharan Africa and Asia present a significant risk for co-infection in these overlapping endemic regions. Recent studies of HIV/Plasmodium falciparum co-infection have reported significant interactions of these pathogens, including more rapid CD4+ T cell loss, increased viral load, increased immunosuppression, and increased episodes of clinical malaria. Here, we describe a novel rhesus macaque model for co-infection that supports and expands upon findings in human co-infection studies and can be used to identify interactions between these two pathogens. METHODOLOGY/PRINCIPAL FINDINGS: Five rhesus macaques were infected with P. cynomolgi and, following three parasite relapses, with SIV. Compared to macaques infected with SIV alone, co-infected animals had, as a group, decreased survival time and more rapid declines in markers for SIV progression, including peripheral CD4+ T cells and CD4+/CD8+ T cell ratios. The naïve CD4+ T cell pool of the co-infected animals was depleted more rapidly than animals infected with SIV alone. The co-infected animals also failed to generate proliferative responses to parasitemia by CD4+ and CD8+ T cells as well as B cells while also having a less robust anti-parasite and altered anti-SIV antibody response. CONCLUSIONS/SIGNIFICANCE: These data suggest that infection with both SIV and Plasmodium enhances SIV-induced disease progression and impairs the anti-Plasmodium immune response. These data support findings in HIV/Plasmodium co-infection studies. This animal model can be used to further define impacts of lentivirus and Plasmodium co-infection and guide public health and therapeutic interventions.

  6. Complement-mediated virus infectivity neutralisation by HLA antibodies is associated with sterilising immunity to SIV challenge in the macaque model for HIV/AIDS.

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    Mark Page

    Full Text Available Sterilising immunity is a desired outcome for vaccination against human immunodeficiency virus (HIV and has been observed in the macaque model using inactivated simian immunodeficiency virus (SIV. This protection was attributed to antibodies specific for cell proteins including human leucocyte antigens (HLA class I and II incorporated into virions during vaccine and challenge virus preparation. We show here, using HLA bead arrays, that vaccinated macaques protected from virus challenge had higher serum antibody reactivity compared with non-protected animals. Moreover, reactivity was shown to be directed against HLA framework determinants. Previous studies failed to correlate serum antibody mediated virus neutralisation with protection and were confounded by cytotoxic effects. Using a virus entry assay based on TZM-bl cells we now report that, in the presence of complement, serum antibody titres that neutralise virus infectivity were higher in protected animals. We propose that complement-augmented virus neutralisation is a key factor in inducing sterilising immunity and may be difficult to achieve with HIV/SIV Env-based vaccines. Understanding how to overcome the apparent block of inactivated SIV vaccines to elicit anti-envelope protein antibodies that effectively engage the complement system could enable novel anti-HIV antibody vaccines that induce potent, virolytic serological response to be developed.

  7. An aerosol challenge model of tuberculosis in Mauritian cynomolgus macaques

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    Sharpe, S. A.; White, A. D.; Sibley, L.; Gleeson, F.; Hall, G. A.; Basaraba, R. J.; McIntyre, A.; Clark, S. O.; Gooch, K.; Marsh, P. D.; Williams, A.; Dennis, M. J.

    2017-01-01

    Background New interventions for tuberculosis are urgently needed. Non-human primate (NHP) models provide the most relevant pre-clinical models of human disease and play a critical role in vaccine development. Models utilising Asian cynomolgus macaque populations are well established but the restricted genetic diversity of the Mauritian cynomolgus macaques may be of added value. Methods Mauritian cynomolgus macaques were exposed to a range of doses of M. tuberculosis delivered by aerosol, and the outcome was assessed using clinical, imaging and pathology-based measures. Results All macaques developed characteristic clinical signs and disease features of tuberculosis (TB). Disease burden and the ability to control disease were dependent on exposure dose. Mauritian cynomolgus macaques showed less variation in pulmonary disease burden and total gross pathology scores within exposure dose groups than either Indian rhesus macaques or Chinese cynomolgus macaques Conclusions The genetic homogeneity of Mauritian cynomolgus macaques makes them a potentially useful model of human tuberculosis. PMID:28273087

  8. Critical Role for Monocytes/Macrophages in Rapid Progression to AIDS in Pediatric Simian Immunodeficiency Virus-Infected Rhesus Macaques.

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    Sugimoto, Chie; Merino, Kristen M; Hasegawa, Atsuhiko; Wang, Xiaolei; Alvarez, Xavier A; Wakao, Hiroshi; Mori, Kazuyasu; Kim, Woong-Ki; Veazey, Ronald S; Didier, Elizabeth S; Kuroda, Marcelo J

    2017-09-01

    Infant humans and rhesus macaques infected with the human or simian immunodeficiency virus (HIV or SIV), respectively, express higher viral loads and progress more rapidly to AIDS than infected adults. Activated memory CD4(+) T cells in intestinal tissues are major primary target cells for SIV/HIV infection, and massive depletion of these cells is considered a major cause of immunodeficiency. Monocytes and macrophages are important cells of innate immunity and also are targets of HIV/SIV infection. We reported previously that a high peripheral blood monocyte turnover rate was predictive for the onset of disease progression to AIDS in SIV-infected adult macaques. The purpose of this study was to determine if earlier or higher infection of monocytes/macrophages contributes to the more rapid progression to AIDS in infants. We observed that uninfected infant rhesus macaques exhibited higher physiologic baseline monocyte turnover than adults. Early after SIV infection, the monocyte turnover further increased, and it remained high during progression to AIDS. A high percentage of terminal deoxynucleotidyltransferase dUTP nick end label (TUNEL)-positive macrophages in the lymph nodes (LNs) and intestine corresponded with an increasing number of macrophages derived from circulating monocytes (bromodeoxyuridine positive [BrdU(+)] CD163(+)), suggesting that the increased blood monocyte turnover was required to rapidly replenish destroyed tissue macrophages. Immunofluorescence analysis further demonstrated that macrophages were a significant portion of the virus-producing cells found in LNs, intestinal tissues, and lungs. The higher baseline monocyte turnover in infant macaques and subsequent macrophage damage by SIV infection may help explain the basis of more rapid disease progression to AIDS in infants.IMPORTANCE HIV infection progresses much more rapidly in pediatric cases than in adults; however, the mechanism for this difference is unclear. Using the rhesus macaque model

  9. A critical analysis of the cynomolgus macaque, Macaca fascicularis, as a model to test HIV-1/SIV vaccine efficacy.

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    Antony, Joseph M; MacDonald, Kelly S

    2015-06-17

    The use of a number of non-rhesus macaque species, but especially cynomolgus macaques as a model for HIV-1 vaccine development has increased in recent years. Cynomolgus macaques have been used in the United Kingdom, Europe, Canada and Australia as a model for HIV vaccine development for many years. Unlike rhesus macaques, cynomolgus macaques infected with SIV show a pattern of disease pathogenesis that more closely resembles that of human HIV-1 infection, exhibiting lower peak and set-point viral loads and slower progression to disease with more typical AIDS defining illnesses. Several advances have been made recently in the use of the cynomolgus macaque SIV challenge model that allow the demonstration of vaccine efficacy using attenuated viruses and vectors that are both viral and non-viral in origin. This review aims to probe the details of various vaccination trials carried out in cynomolgus macaques in the context of our modern understanding of the highly diverse immunogenetics of this species with a view to understanding the species-specific immune correlates of protection and the efficacy of vectors that have been used to design vaccines. Copyright © 2015. Published by Elsevier Ltd.

  10. A macaque model for hantavirus infection.

    NARCIS (Netherlands)

    J. Groen (Jan); M.N. Gerding; J.P. Koeman; P.J.M. Roholl (Paul); G. van Amerongen (Geert); H.G.M. Jordans; A.D.M.E. Osterhaus (Albert); H.G.M. Niesters (Bert)

    1995-01-01

    textabstractCynomolgus macaques (Macaca fascicularis) were experimentally infected with Puumala virus (strain Hallnas), which causes nephropathia epidemica in humans in western Europe. During the first week after intratracheal inoculation, the monkeys exhibited signs of lethargy followed by mild pro

  11. Nonhuman primate models for HIV/AIDS vaccine development.

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    Sui, Yongjun; Gordon, Shari; Franchini, Genoveffa; Berzofsky, Jay A

    2013-10-01

    The development of HIV vaccines has been hampered by the lack of an animal model that can accurately predict vaccine efficacy. Chimpanzees can be infected with HIV-1 but are not practical for research. However, several species of macaques are susceptible to the simian immunodeficiency viruses (SIVs) that cause disease in macaques, which also closely mimic HIV in humans. Thus, macaque-SIV models of HIV infection have become a critical foundation for AIDS vaccine development. Here we examine the multiple variables and considerations that must be taken into account in order to use this nonhuman primate (NHP) model effectively. These include the species and subspecies of macaques, virus strain, dose and route of administration, and macaque genetics, including the major histocompatibility complex molecules that affect immune responses, and other virus restriction factors. We illustrate how these NHP models can be used to carry out studies of immune responses in mucosal and other tissues that could not easily be performed on human volunteers. Furthermore, macaques are an ideal model system to optimize adjuvants, test vaccine platforms, and identify correlates of protection that can advance the HIV vaccine field. We also illustrate techniques used to identify different macaque lymphocyte populations and review some poxvirus vaccine candidates that are in various stages of clinical trials. Understanding how to effectively use this valuable model will greatly increase the likelihood of finding a successful vaccine for HIV. Copyright © 2013 John Wiley & Sons, Inc.

  12. A macaque model for hantavirus infection

    NARCIS (Netherlands)

    Groen, J; Gerding, M; Koeman, J P; Roholl, P J; van Amerongen, G; Jordans, H G; Niesters, H G; Osterhaus, A D

    1995-01-01

    Cynomolgus macaques (Macaca fascicularis) were experimentally infected with Puumala virus (strain Hällnäs), which causes nephropathia epidemica in humans in western Europe. During the first week after intratracheal inoculation, the monkeys exhibited signs of lethargy followed by mild proteinuria and

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

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    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

  14. Mycobacterium avium complex in macaques with AIDS is associated with a specific strain of simian immunodeficiency virus and prolonged survival after primary infection.

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    Mansfield, K G; Pauley, D; Young, H L; Lackner, A A

    1995-10-01

    Mycobacterium avium complex (MAC) in simian immunodeficiency virus (SIV)-infected macaques is a frequent opportunistic infection that shares many features with the condition in human AIDS patients. A retrospective analysis of necropsies on 135 macaques with SIV-induced simian AIDS that received neither antiretroviral nor antimicrobial therapy revealed that 17% (23/135) were infected with MAC. MAC developed in 31.3% (21/67) of the animals inoculated with uncloned SIVmac251 versus 1.9% (1/53) and 6.7% (1/15) of the animals inoculated with the molecular clones SIVmac239 and SIVmac239/316EM, respectively (P = .001). This is the first example in which the risk of infection with a specific opportunistic organism was affected by the infecting strain of immunodeficiency virus. In addition, animals with MAC had a longer mean survival after primary infection and lower CD4 cell counts at death than animals that did not develop this opportunistic infection. The SIV-inoculated macaque is a valuable model in which to study the pathogenesis of MAC in the immunocompromised host.

  15. Evolution of SIV toward RANTES resistance in macaques rapidly progressing to AIDS upon coinfection with HHV-6A

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    Gallo Robert C

    2009-07-01

    Full Text Available Abstract Background Progression to AIDS is often associated with the evolution of HIV-1 toward increased virulence and/or pathogenicity. Evidence suggests that a virulence factor for HIV-1 is resistance to CCR5-binding chemokines, most notably RANTES, which are believed to play a role in HIV-1 control in vivo. HIV-1 can achieve RANTES resistance either by phenotypic switching from an exclusive CCR5 usage to an expanded coreceptor specificity, or by the acquisition of alternative modalities of CCR5 usage. An infectious agent that might promote the evolution of HIV-1 toward RANTES resistance is human herpesvirus 6A (HHV-6A, which is frequently reactivated in HIV-1-infected patients and is a potent RANTES inducer in lymphoid tissue. Results SIV isolates obtained from pig-tailed macaques (M. nemestrina after approximately one year of single infection with SIVsmE660 or dual infection with SIVsmE660 and HHV-6AGS were characterized for their growth capacity and sensitivity to HHV-6A- and RANTES-mediated inhibition in human or macaque lymphoid tissues ex vivo. Four out of 4 HHV-6A-coinfected macaques, all of which progressed to full-blown AIDS within 2 years of infection, were found to harbor SIV variants with a reduced sensitivity to both HHV-6A and RANTES, despite maintaining an exclusive CCR5 coreceptor specificity; viruses derived from two of these animals replicated even more vigorously in the presence of exogenous HHV-6A or RANTES. The SIV variants that emerged in HHV-6A-coinfected macaques showed an overall reduced ex vivo replication capacity that was partially reversed upon addition of exogenous RANTES, associated with suppressed IL-2 and enhanced IFN-γ production. In contrast, SIV isolates obtained from two singly-infected macaques, none of which progressed to AIDS, maintained HHV-6A/RANTES sensitivity, whereas the only AIDS progressor among singly-infected macaques developed an SIV variant with partial HHV-6A/RANTES resistance and increased

  16. AIDS Epidemiological models

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    Rahmani, Fouad Lazhar

    2010-11-01

    The aim of this paper is to present mathematical modelling of the spread of infection in the context of the transmission of the human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome (AIDS). These models are based in part on the models suggested in the field of th AIDS mathematical modelling as reported by ISHAM [6].

  17. Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques

    DEFF Research Database (Denmark)

    Yan, Guangmei; Zhang, Guojie; Fang, Xiaodong

    2011-01-01

    The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus...

  18. Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques

    DEFF Research Database (Denmark)

    Yan, Guangmei; Zhang, Guojie; Fang, Xiaodong

    2011-01-01

    The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus...

  19. Disease Progression Patterns of SHIV-KB9 in Rhesus Macaques of Chinese Origin in Comparison with Indian Macaques

    Institute of Scientific and Technical Information of China (English)

    QIANG LIU; GUI-BO YANG; HUI ZHAO; QIANG WEI; HUI XING; CHUAN QIN; YI-MING SHAO

    2008-01-01

    To develop a model of SHIV-KB9/Chinese origin rhesus (Ch Rh) macaques for vaccine research and to compare the pathogenesis of SHIV-KB9 in Ch Rh macaques with that reported in Indian rhesus (had Rh) macaques. Methods Seven mamu-A*01 negative Ch Rh macaques were inoculated intravenously with 1-10000 MID of SHIV-KB9. The monkeys were monitored for viral load, CD4, CD8, SHIV-specific antibody and virus genetic variation. The results were compared with those previously observed in Ind Rh macaques. Results As compared to that observed in Ind Rh macaques, SHIV-KB9 in Ch Rh macaques displayed three identical disease progression patterns. However, the primary pattern was not identical between the two subspecies. The level of plasma viremia differed in SHIV-KB9-infected Ch Rh macaques which exhibited different outcomes from those in Ind Rh macaques. Generally, the values of viral load and the maintenance of CD4 T cells were associated with humoral responses. Otherwise, the viral genetic distances (divergence, diversity) were larger in animals (M419, M425) with their CD4T cells profoundly depleted. Conclusion The model of SHIV-KB9/Ch Rh macaques displays a relatively slow progression to AIDS compared with Ind Rh macaques, which may more accurately reflect the potential ofcandidate vaccines in humans.

  20. Non-human primate models for HIV/AIDS vaccine development

    Science.gov (United States)

    Sui, Yongjun; Gordon, Shari; Franchini, Genoveffa; Berzofsky, Jay A.

    2013-01-01

    The development of HIV vaccines has been hampered by the lack of an animal model that can accurately predict vaccine efficacy. Chimpanzees can be infected with HIV-1 but are not practical for research. However, several species of macaques are susceptible to the Simian Immunodeficiency Viruses (SIV) that causes a disease in macaques that closely mimics HIV in humans. Thus, macaque-SIV models of HIV infection have become a critical foundation for AIDS vaccine development. Here, we examine the multiple variables and considerations that must be taken into account to use this NHP model effectively. These include the species and subspecies of macaques, virus strain, dose and route of administration and macaque genetics including Major Histocompatibility Complex molecules that affect immune responses and other virus restriction factors. We illustrate how these NHP models can be used to carry out studies of immune responses in mucosal and other tissues than could not easily be performed on human volunteers. Futhermore macaques are an ideal model system to optimize adjuvants, test vaccine platforms, and identify correlates of protection that can advance the HIV vaccine field. We also illustrate techniques used to identify different macaque lymphocyte populations and review some poxvirus vaccine candidates that are in various stages of clinical trials. Understanding how to effectively use this valuable model will greatly increase the likelihood of finding a successful vaccine for HIV. PMID:24510515

  1. Development of a Zika Virus Infection Model in Cynomolgus Macaques

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    Fusataka Koide

    2016-12-01

    Full Text Available Limited availability of Indian rhesus macaques (IRM is a bottleneck to study Zika virus (ZIKV pathogenesis and evaluation of appropriate control measures in non-human primates. To address these issues, we report here the Mauritian cynomolgus macaque (MCM model for ZIKV infection. In brief, six MCMs (seronegative for dengue and ZIKV were subdivided into 3 cohorts with a male and female each and challenged with different doses of Asian PRVABC59 (Puerto Rico or FSS13025 (Cambodia or African (IBH30656 lineage ZIKV isolates. Clinical signs were monitored; and biological fluids (serum, saliva and urine and tissues (testes and brain were assessed for viral load by quantitative RT-PCR and neutralizing antibodies (Nab by 50% Plaque Reduction Neutralization Test (PRNT50 at various times post infection (p.i. PRVABC59 induced viremia detectable up to day 10, with peak viral load at 2 to 3 days p.i. An intermittent viremia spike was observed on day 30 with titers reaching 2.5 ×103 genomes/mL. Moderate viral load was observed in testes, urine and saliva. In contrast, FSS13025 induced viremia lasting only up to 6 days and detectable viral loads in testes but not in urine and saliva. Recurrent viremia was detected but at lower titers compare to PRVABC59. Challenge with either PRVABC59 or FSS13025 resulted in 100% seroconversion; with mean PRNT50 titers ranging from 597 to 5179. IBH30656 failed to establish infection in MCM suggesting that MCM are susceptible to infection with ZIKV isolates of the Asian lineage but not from Africa. Due to the similarity of biphasic viremia and Nab responses between MCM and IRM models, MCM could be a suitable alternative for evaluation of ZIKV vaccine and therapeutic candidates.

  2. Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.

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    Deborah Heydenburg Fuller

    Full Text Available Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT, during antiretroviral therapy (ART induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans.

  3. Control of viremia and prevention of AIDS following immunotherapy of SIV-infected macaques with peptide-pulsed blood.

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    Robert De Rose

    2008-05-01

    Full Text Available Effective immunotherapies for HIV are needed. Drug therapies are life-long with significant toxicities. Dendritic-cell based immunotherapy approaches are promising but impractical for widespread use. A simple immunotherapy, reinfusing fresh autologous blood cells exposed to overlapping SIV peptides for 1 hour ex vivo, was assessed for the control of SIV(mac251 replication in 36 pigtail macaques. An initial set of four immunizations was administered under antiretroviral cover and a booster set of three immunizations administered 6 months later. Vaccinated animals were randomized to receive Gag peptides alone or peptides spanning all nine SIV proteins. High-level, SIV-specific CD4 and CD8 T-cell immunity was induced following immunization, both during antiretroviral cover and without. Virus levels were durably approximately 10-fold lower for 1 year in immunized animals compared to controls, and a significant delay in AIDS-related mortality resulted. Broader immunity resulted following immunizations with peptides spanning all nine SIV proteins, but the responses to Gag were weaker in comparison to animals only immunized with Gag. No difference in viral outcome occurred in animals immunized with all SIV proteins compared to animals immunized against Gag alone. Peptide-pulsed blood cells are an immunogenic and effective immunotherapy in SIV-infected macaques. Our results suggest Gag alone is an effective antigen for T-cell immunotherapy. Fresh blood cells pulsed with overlapping Gag peptides is proceeding into trials in HIV-infected humans.

  4. Comparative pathology of rhesus macaque and common marmoset animal models with Middle East respiratory syndrome coronavirus

    Science.gov (United States)

    Yu, Pin; Xu, Yanfeng; Deng, Wei; Bao, Linlin; Huang, Lan; Xu, Yuhuan; Yao, Yanfeng; Qin, Chuan

    2017-01-01

    Middle East respiratory syndrome (MERS), which is caused by a newly discovered coronavirus (CoV), has recently emerged. It causes severe viral pneumonia and is associated with a high fatality rate. However, the pathogenesis, comparative pathology and inflammatory cell response of rhesus macaques and common marmosets experimentally infected with MERS-CoV are unknown. We describe the histopathological, immunohistochemical, and ultrastructural findings from rhesus macaque and common marmoset animal models of MERS-CoV infection. The main histopathological findings in the lungs of rhesus macaques and common marmosets were varying degrees of pulmonary lesions, including pneumonia, pulmonary oedema, haemorrhage, degeneration and necrosis of the pneumocytes and bronchial epithelial cells, and inflammatory cell infiltration. The characteristic inflammatory cells in the lungs of rhesus macaques and common marmosets were eosinophils and neutrophils, respectively. Based on these observations, the lungs of rhesus macaques and common marmosets appeared to develop chronic and acute pneumonia, respectively. MERS-CoV antigens and viral RNA were identified in type I and II pneumocytes, alveolar macrophages and bronchial epithelial cells, and ultrastructural observations showed that viral protein was found in type II pneumocytes and inflammatory cells in both species. Correspondingly, the entry receptor DDP4 was found in type I and II pneumocytes, bronchial epithelial cells, and alveolar macrophages. The rhesus macaque and common marmoset animal models of MERS-CoV can be used as a tool to mimic the oncome of MERS-CoV infections in humans. These models can help to provide a better understanding of the pathogenic process of this virus and to develop effective medications and prophylactic treatments. PMID:28234937

  5. Low autocrine interferon beta production as a gene therapy approach for AIDS: Infusion of interferon beta-engineered lymphocytes in macaques chronically infected with SIVmac251

    Directory of Open Access Journals (Sweden)

    Dormont Dominique

    2004-09-01

    Full Text Available Abstract Background The aim of this study was to evaluate gene therapy for AIDS based on the transduction of circulating lymphocytes with a retroviral vector giving low levels of constitutive macaque interferon β production in macaques chronically infected with a pathogenic isolate of SIVmac251. Results Two groups of three animals infected for more than one year with a pathogenic primary isolate of SIVmac251 were included in this study. The macaques received three infusions of their own lymphocytes transduced ex vivo with the construct encoding macaque IFN-β (MaIFN-β or with a vector carrying a version of the MaIFN-β gene with a deletion preventing translation of the mRNA. Cellular or plasma viremia increased transiently following injection in most cases, regardless of the retroviral construct used. Transduced cells were detected only transiently after each infusion, among the peripheral blood mononuclear cells of all the animals, with copy numbers of 10 to 1000 per 106 peripheral mononuclear cells. Conclusion Long-term follow-up indicated that the transitory presence of such a small number of cells producing such small amounts of MaIFN-β did not prevent animals from the progressive decrease in CD4+ cell count typical of infection with simian immunodeficiency virus. These results reveal potential pitfalls for future developments of gene therapy strategies of HIV infection.

  6. Computer-Aided Modeling Framework

    DEFF Research Database (Denmark)

    Fedorova, Marina; Sin, Gürkan; Gani, Rafiqul

    development and application. The proposed work is a part of the project for development of methods and tools that will allow systematic generation, analysis and solution of models for various objectives. It will use the computer-aided modeling framework that is based on a modeling methodology, which combines....... In this contribution, the concept of template-based modeling is presented and application is highlighted for the specific case of catalytic membrane fixed bed models. The modeling template is integrated in a generic computer-aided modeling framework. Furthermore, modeling templates enable the idea of model reuse...... are generated through the template in ICAS-MoT and translated into a model object. Once in ICAS-MoT, the model is numerical analyzed, solved and identified. A computer-aided modeling framework integrating systematic model derivation and development tools has been developed. It includes features for model...

  7. Development and Characterization of a Macaque Model of Focal Internal Capsular Infarcts.

    Directory of Open Access Journals (Sweden)

    Yumi Murata

    Full Text Available Several studies have used macaque monkeys with lesions induced in the primary motor cortex (M1 to investigate the recovery of motor function after brain damage. However, in human stroke patients, the severity and outcome of motor impairments depend on the degree of damage to the white matter, especially that in the posterior internal capsule, which carries corticospinal tracts. To bridge the gap between results obtained in M1-lesioned macaques and the development of clinical intervention strategies, we established a method of inducing focal infarcts at the posterior internal capsule of macaque monkeys by injecting endothelin-1 (ET-1, a vasoconstrictor peptide. The infarcts expanded between 3 days and 1 week after ET-1 injection. The infarct volume in each macaque was negatively correlated with precision grip performance 3 days and 1 week after injection, suggesting that the degree of infarct expansion may have been a cause of the impairment in hand movements during the early stage. Although the infarct volume decreased and gross movement improved, impairment of dexterous hand movements remained until the end of the behavioral and imaging experiments at 3 months after ET-1 injection. A decrease in the abundance of large neurons in M1, from which the descending motor tracts originate, was associated with this later-stage impairment. The present model is useful not only for studying neurological changes underlying deficits and recovery but also for testing therapeutic interventions after white matter infarcts in primates.

  8. Model-observer similarity, error modeling and social learning in rhesus macaques.

    Science.gov (United States)

    Monfardini, Elisabetta; Hadj-Bouziane, Fadila; Meunier, Martine

    2014-01-01

    Monkeys readily learn to discriminate between rewarded and unrewarded items or actions by observing their conspecifics. However, they do not systematically learn from humans. Understanding what makes human-to-monkey transmission of knowledge work or fail could help identify mediators and moderators of social learning that operate regardless of language or culture, and transcend inter-species differences. Do monkeys fail to learn when human models show a behavior too dissimilar from the animals' own, or when they show a faultless performance devoid of error? To address this question, six rhesus macaques trained to find which object within a pair concealed a food reward were successively tested with three models: a familiar conspecific, a 'stimulus-enhancing' human actively drawing the animal's attention to one object of the pair without actually performing the task, and a 'monkey-like' human performing the task in the same way as the monkey model did. Reward was manipulated to ensure that all models showed equal proportions of errors and successes. The 'monkey-like' human model improved the animals' subsequent object discrimination learning as much as a conspecific did, whereas the 'stimulus-enhancing' human model tended on the contrary to retard learning. Modeling errors rather than successes optimized learning from the monkey and 'monkey-like' models, while exacerbating the adverse effect of the 'stimulus-enhancing' model. These findings identify error modeling as a moderator of social learning in monkeys that amplifies the models' influence, whether beneficial or detrimental. By contrast, model-observer similarity in behavior emerged as a mediator of social learning, that is, a prerequisite for a model to work in the first place. The latter finding suggests that, as preverbal infants, macaques need to perceive the model as 'like-me' and that, once this condition is fulfilled, any agent can become an effective model.

  9. A Review of Plasmodium coatneyi-Macaque Models of Severe Malaria.

    Science.gov (United States)

    Lombardini, E D; Gettayacamin, M; Turner, G D H; Brown, A E

    2015-11-01

    Malaria remains one of the most significant public health concerns in the world today. Approximately half the human population is at risk for infection, with children and pregnant women being most vulnerable. More than 90% of the total human malaria burden, which numbers in excess of 200 million annually, is due to Plasmodium falciparum. Lack of an effective vaccine and a dwindling stockpile of antimalarial drugs due to increased plasmodial resistance underscore the critical need for valid animal models. Plasmodium coatneyi was described in Southeast Asia 50 years ago. This plasmodium of nonhuman primates has been used sporadically as a model for severe malaria, as it mimics many of the pathophysiologic features of human disease. This review covers the reported macroscopic, microscopic, ultrastructural, and molecular pathology of P. coatneyi infection in macaques, specifically focusing on the rhesus macaque, as well as describing the critical needs still outstanding in the validation of this crucial model of human disease.

  10. The most common Chinese rhesus macaque MHC class I molecule shares peptide binding repertoire with the HLA-B7 supertype

    DEFF Research Database (Denmark)

    Solomon, C.; Southwood, S.; Hoof, Ilka;

    2010-01-01

    macaque potentially being a more relevant model for AIDS outcomes than the Indian rhesus macaque, the Chinese-origin rhesus macaques have not been well-characterized for their major histocompatibility complex (MHC) composition and function, reducing their greater utilization. In this study, we...... characterized a total of 50 unique Chinese rhesus macaques from several varying origins for their entire MHC class I allele composition and identified a total of 58 unique complete MHC class I sequences. Only nine of the sequences had been associated with Indian rhesus macaques, and 28/58 (48...... binding characteristics with the HLA-B7 supertype, the most frequent supertype in human populations. These studies provide the first functional characterization of an MHC class I molecule in the context of Chinese rhesus macaques and the first instance of HLA-B7 analogy for rhesus macaques....

  11. Computer-Aided Modeling Framework

    DEFF Research Database (Denmark)

    Fedorova, Marina; Sin, Gürkan; Gani, Rafiqul

    with them. As the required models may be complex and require multiple time and/or length scales, their development and application for product-process design is not trivial. Therefore, a systematic modeling framework can contribute by significantly reducing the time and resources needed for model...... development and application. The proposed work is a part of the project for development of methods and tools that will allow systematic generation, analysis and solution of models for various objectives. It will use the computer-aided modeling framework that is based on a modeling methodology, which combines....... In this contribution, the concept of template-based modeling is presented and application is highlighted for the specific case of catalytic membrane fixed bed models. The modeling template is integrated in a generic computer-aided modeling framework. Furthermore, modeling templates enable the idea of model reuse...

  12. A macaque model of mesial temporal lobe epilepsy induced by unilateral intrahippocampal injection of kainic Acid.

    Directory of Open Access Journals (Sweden)

    Ning Chen

    Full Text Available OBJECTIVE: In order to better investigate the cause/effect relationships of human mesial temporal lobe epilepsy (mTLE, we hereby describe a new non-human primate model of mTLE. METHODS: Ten macaques were studied and divided into 2 groups: saline control group (n = 4 and kainic acid (KA injection group (n = 6. All macaques were implanted bilaterally with subdural electrodes over temporal cortex and depth electrodes in CA3 hippocampal region. KA was stereotaxically injected into the right hippocampus of macaques. All animals were monitored by video and electrocorticography (ECoG to assess status epilepticus (SE and subsequent spontaneous recurrent seizures (SRS. Additionally, in order to evaluate brain injury produced by SE or SRS, we used both neuroimaging, including magnetic resonance image (MRI & magnetic resonance spectroscopy (MRS, and histological pathology, including Nissl stainning and glial fibrillary acid protein (GFAP immunostaining. RESULTS: The typical seizures were observed in the KA-injected animal model. Hippocampal sclerosis could be found by MRI & MRS. Hematoxylin and eosin (H&E staining and GFAP immunostaining showed neuronal loss, proliferation of glial cells, formation of glial scars, and hippocampal atrophy. Electron microscopic analysis of hippocampal tissues revealed neuronal pyknosis, partial ribosome depolymerization, an abnormal reduction in rough endoplasmic reticulum size, expansion of Golgi vesicles and swollen star-shaped cells. Furthermore, we reported that KA was able to induce SE followed by SRS after a variable period of time. Similar to human mTLE, brain damage is confined to the hippocampus. Accordingly, hippocampal volume is in positive correlations with the neuronal cells count in the CA3, especially the ratio of neuron/glial cell. CONCLUSIONS: The results suggest that a model of mTLE can be developed in macaques by intra-hippocampal injection of KA. Brain damage is confined to the hippocampus which

  13. Lymphocytic choriomeningitis virus (LCMV) infection of macaques: a model for Lassa fever.

    Science.gov (United States)

    Zapata, Juan C; Pauza, C David; Djavani, Mahmoud M; Rodas, Juan D; Moshkoff, Dmitry; Bryant, Joseph; Ateh, Eugene; Garcia, Cybele; Lukashevich, Igor S; Salvato, Maria S

    2011-11-01

    Arenaviruses such as Lassa fever virus (LASV) and lymphocytic choriomeningitis virus (LCMV) are benign in their natural reservoir hosts, and can occasionally cause severe viral hemorrhagic fever (VHF) in non-human primates and in human beings. LCMV is considerably more benign for human beings than Lassa virus, however certain strains, like the LCMV-WE strain, can cause severe disease when the virus is delivered as a high-dose inoculum. Here we describe a rhesus macaque model for Lassa fever that employs a virulent strain of LCMV. Since LASV must be studied within Biosafety Level-4 (BSL-4) facilities, the LCMV-infected macaque model has the advantage that it can be used at BSL-3. LCMV-induced disease is rarely as severe as other VHF, but it is similar in cases where vascular leakage leads to lethal systemic failure. The LCMV-infected macaque has been valuable for describing the course of disease with differing viral strains, doses and routes of infection. By monitoring system-wide changes in physiology and gene expression in a controlled experimental setting, it is possible to identify events that are pathognomonic for developing VHF and potential treatment targets.

  14. Lymphocytic choriomeningitis virus (LCMV) infection of macaques: a model for Lassa fever

    Science.gov (United States)

    Zapata, Juan C.; Pauza, C. David; Djavani, Mahmoud M.; Rodas, Juan D.; Moshkoff, Dmitry; Bryant, Joseph; Ateh, Eugene; Garcia, Cybele; Lukashevich, Igor S.; Salvato, Maria S.

    2011-01-01

    Arenaviruses such as Lassa fever virus (LASV) and lymphocytic choriomeningitis virus (LCMV) are benign in their natural reservoir hosts, and can occasionally cause severe viral hemorrhagic fever (VHF) in non-human primates and in human beings. LCMV is considerably more benign for human beings than Lassa virus, however certain strains, like the LCMV-WE strain, can cause severe disease when the virus is delivered as a high-dose inoculum. Here we describe a rhesus macaque model for Lassa fever that employs a virulent strain of LCMV. Since LASV must be studied within Biosafety Level-4 (BSL-4) facilities, the LCMV-infected macaque model has the advantage that it can be used at BSL-3. LCMV-induced disease is rarely as severe as other VHF, but it is similar in cases where vascular leakage leads to lethal systemic failure. The LCMV-infected macaque has been valuable for describing the course of disease with differing viral strains, doses and routes of infection. By monitoring system-wide changes in physiology and gene expression in a controlled experimental setting, it is possible to identify events that are pathognomonic for developing VHF and potential treatment targets. PMID:21820469

  15. Amblyomma maculatum Feeding Augments Rickettsia parkeri Infection in a Rhesus Macaque Model: A Pilot Study.

    Science.gov (United States)

    Banajee, Kaikhushroo H; Embers, Monica E; Langohr, Ingeborg M; Doyle, Lara A; Hasenkampf, Nicole R; Macaluso, Kevin R

    2015-01-01

    Rickettsia parkeri is an emerging eschar-causing human pathogen in the spotted fever group of Rickettsia and is transmitted by the Gulf coast tick, Amblyomma maculatum. Tick saliva has been shown to alter both the cellular and humoral components of the innate and adaptive immune systems. However, the effect of this immunomodulation on Rickettsia transmission and pathology in an immunocompetent vertebrate host has not been fully examined. We hypothesize that, by modifying the host immune response, tick feeding enhances infection and pathology of pathogenic spotted fever group Rickettsia sp. In order to assess this interaction in vivo, a pilot study was conducted using five rhesus macaques that were divided into three groups. One group was intradermally inoculated with low passage R. parkeri (Portsmouth strain) alone (n = 2) and another group was inoculated during infestation by adult, R. parkeri-free A. maculatum (n = 2). The final macaque was infested with ticks alone (tick feeding control group). Blood, lymph node and skin biopsies were collected at several time points post-inoculation/infestation to assess pathology and quantify rickettsial DNA. As opposed to the tick-only animal, all Rickettsia-inoculated macaques developed inflammatory leukograms, elevated C-reactive protein concentrations, and elevated TH1 (interferon-γ, interleukin-15) and acute phase inflammatory cytokines (interleukin-6) post-inoculation, with greater neutrophilia and interleukin-6 concentrations in the tick plus R. parkeri group. While eschars formed at all R. parkeri inoculation sites, larger and slower healing eschars were observed in the tick feeding plus R. parkeri group. Furthermore, dissemination of R. parkeri to draining lymph nodes early in infection and increased persistence at the inoculation site were observed in the tick plus R. parkeri group. This study indicates that rhesus macaques can be used to model R. parkeri rickettsiosis, and suggests that immunomodulatory factors

  16. Biologically-directed modeling reflects cytolytic clearance of SIV-infected cells in vivo in macaques.

    Directory of Open Access Journals (Sweden)

    W David Wick

    Full Text Available The disappointing outcomes of cellular immune-based vaccines against HIV-1 despite strong evidence for the protective role of CD8⁺ T lymphocytes (CTLs has prompted revisiting the mechanisms of cellular immunity. Prior data from experiments examining the kinetics of Simian Immunodeficiency Virus (SIV clearance in infected macaques with or without in vivo CD8 depletion were interpreted as refuting the concept that CTLs suppress SIV/HIV by direct killing of infected cells. Here we briefly review the biological evidence for CTL cytolytic activity in viral infections, and utilize biologically-directed modeling to assess the possibility of a killing mechanism for the antiviral effect of CTLs, taking into account the generation, proliferation, and survival of activated CD4⁺ and CD8⁺ T lymphocytes, as well as the life cycle of the virus. Our analyses of the published macaque data using these models support a killing mechanism, when one considers T lymphocyte and HIV-1 lifecycles, and factors such as the eclipse period before release of virions by infected cells, an exponential pattern of virion production by infected cells, and a variable lifespan for acutely infected cells. We conclude that for SIV/HIV pathogenesis, CTLs deserve their reputation as being cytolytic.

  17. Distribution of SIV infection in the gastrointestinal tract of rhesus macaques at early and terminal stages of AIDS.

    Science.gov (United States)

    Heise, C; Vogel, P; Miller, C J; Lackner, A; Dandekar, S

    1993-01-01

    Intestinal tissues from SIV-infected rhesus macaques with subclinical as well as with terminal SIV disease were evaluated for SIV infection. SIV-infected mononuclear cells were detected throughout the gastrointestinal tract in all animals. In early infection, SIV-infected cells were diffusely distributed in lymphoid tissue and lamina propria, whereas in late stages of the disease, the viral infection was more severe and widely disseminated. Lymphoid cells of the lamina propria and gut-associated lymphoid tissue were the primary targets of SIV.

  18. Measles immune suppression: lessons from the macaque model.

    Directory of Open Access Journals (Sweden)

    Rory D de Vries

    Full Text Available Measles remains a significant childhood disease, and is associated with a transient immune suppression. Paradoxically, measles virus (MV infection also induces robust MV-specific immune responses. Current hypotheses for the mechanism underlying measles immune suppression focus on functional impairment of lymphocytes or antigen-presenting cells, caused by infection with or exposure to MV. We have generated stable recombinant MVs that express enhanced green fluorescent protein, and remain virulent in non-human primates. By performing a comprehensive study of virological, immunological, hematological and histopathological observations made in animals euthanized at different time points after MV infection, we developed a model explaining measles immune suppression which fits with the "measles paradox". Here we show that MV preferentially infects CD45RA(- memory T-lymphocytes and follicular B-lymphocytes, resulting in high infection levels in these populations. After the peak of viremia MV-infected lymphocytes were cleared within days, followed by immune activation and lymph node enlargement. During this period tuberculin-specific T-lymphocyte responses disappeared, whilst strong MV-specific T-lymphocyte responses emerged. Histopathological analysis of lymphoid tissues showed lymphocyte depletion in the B- and T-cell areas in the absence of apoptotic cells, paralleled by infiltration of T-lymphocytes into B-cell follicles and reappearance of proliferating cells. Our findings indicate an immune-mediated clearance of MV-infected CD45RA(- memory T-lymphocytes and follicular B-lymphocytes, which causes temporary immunological amnesia. The rapid oligoclonal expansion of MV-specific lymphocytes and bystander cells masks this depletion, explaining the short duration of measles lymphopenia yet long duration of immune suppression.

  19. Depo-provera treatment does not abrogate protection from intravenous SIV challenge in female macaques immunized with an attenuated AIDS virus.

    Directory of Open Access Journals (Sweden)

    Meritxell Genescà

    Full Text Available BACKGROUND: In a previous study, progesterone treatment of female monkeys immunized with live, attenuated SHIV89.6 abrogated the generally consistent protection from vaginal simian immunodeficiency virus (SIV challenge. The mechanisms responsible for the loss of protection remain to be defined. The objective of the present study was to determine whether Depo-Provera administration alters protection from intravenous SIV challenge in SHIV-immunized female macaques. METHODS AND FINDINGS: Two groups of female macaques were immunized with attenuated SHIV89.6 and then challenged intravenously with SIVmac239. Four weeks before challenge, one animal group was treated with Depo-Provera, a commonly used injectable contraceptive progestin. As expected, SHIV-immunized monkeys had significantly lower peak and set-point plasma viral RNA levels compared to naïve controls, but in contrast to previously published findings with vaginal SIV challenge, the Depo-Provera SHIV-immunized animals controlled SIV replication to a similar, or even slightly greater, degree than did the untreated SHIV-immunized animals. Control of viral replication from week 4 to week 20 after challenge was more consistent in the progesterone-treated, SHIV-immunized animals than in untreated, SHIV-immunized animals. Although levels of interferon-gamma production were similar, the SIV-specific CD8(+ T cells of progesterone-treated animals expressed more functions than the anti-viral CD8(+ T cells from untreated animals. CONCLUSIONS: Depo-Provera did not diminish the control of viral replication after intravenous SIV challenge in female macaques immunized with a live-attenuated lentivirus. This result contrasts with the previously reported effect of Depo-Provera(R on protection from vaginal SIV challenge and strongly implies that the decreased protection from vaginal challenge is due to effects of progesterone on the genital tract rather than to systemic effects. Further, these results

  20. Identification of rhesus macaque genital microbiota by 16S pyrosequencing shows similarities to human bacterial vaginosis: implications for use as an animal model for HIV vaginal infection.

    Science.gov (United States)

    Spear, Gregory T; Gilbert, Douglas; Sikaroodi, Masoumeh; Doyle, Lara; Green, Linda; Gillevet, Patrick M; Landay, Alan L; Veazey, Ronald S

    2010-02-01

    The composition of the lower genital tract microbiota in women is believed to affect the risk of sexually acquiring HIV. Since macaque genital microbiota could similarly impact vaginal infection with SIV we identified microbiota in 11 rhesus macaques using multitag pyrosequencing of the 16S rRNA gene. The microbiota was polymicrobial with a median of nine distinct bacterial taxa per macaque (range 3-16 taxa, each constituting 1% or more of the sequences). Taxa frequently found included Peptoniphilus, Sneathia, Porphyromonas, Mobiluncus, Atopobacter, Dialister, Thioreductor, Prevotella, and Streptococcus, many of which are also frequently found in women with bacterial vaginosis. Lactobacillus sequences (mostly L. johnsonii) were found in only four macaques but were not predominant in any (median of 0% of sequences, range 0-39%). All macaques were resampled 6 months after the first time point to determine the stability of the microbiota. The microbiota remained polymicrobial with a median of 10 taxa (range 6-18). Microbial patterns remained similar for six of the macaques, changed substantially in two, and had a mixed pattern in three. Significant sialidase enzyme activity, a marker of bacteria vaginosis in women, was detected in genital fluid from 9/11 and 8/11 macaques from the first and second time points, respectively. These results show that the macaque lower genital microbiota resembled a bacteria vaginosis-type microbiota in women and suggest that the microbiota of macaques in captivity promote rather than protect against vaginal infection with SIV. These results also suggest macaques could be used as an animal model to study some aspects of bacterial vaginosis.

  1. Does the macaque monkey provide a good model for studying human executive control? A comparative behavioral study of task switching.

    Directory of Open Access Journals (Sweden)

    Luana Caselli

    Full Text Available The ability to swiftly and smoothly switch from one task set to another is central to intelligent behavior, because it allows an organism to flexibly adapt to ever changing environmental conditions and internal needs. For this reason, researchers interested in executive control processes have often relied on task-switching paradigms as powerful tools to uncover the underlying cognitive and brain architecture. In order to gather fundamental information at the single-cell level, it would be greatly helpful to demonstrate that non-human primates, especially the macaque monkey, share with us similar behavioral manifestations of task-switching and therefore, in all likelihood, similar underlying brain mechanisms. Unfortunately, prior attempts have provided negative results (e.g., Stoet & Snyder, 2003b, in that it was reported that macaques do not show the typical signature of task-switching operations at the behavioral level, represented by switch costs. If confirmed, this would indicate that the macaque cannot be used as a model approach to explore human executive control mechanisms by means of task-switching paradigms. We have therefore decided to re-explore this issue, by conducting a comparative experiment on a group of human participants and two macaque monkeys, whereby we measured and compared performance costs linked to task switching and resistance to interference across the two species. Contrary to what previously reported, we found that both species display robust task switching costs, thus supporting the claim that macaque monkeys provide an exquisitely suitable model to study the brain mechanisms responsible for maintaining and switching task sets.

  2. Does the macaque monkey provide a good model for studying human executive control? A comparative behavioral study of task switching.

    Science.gov (United States)

    Caselli, Luana; Chelazzi, Leonardo

    2011-01-01

    The ability to swiftly and smoothly switch from one task set to another is central to intelligent behavior, because it allows an organism to flexibly adapt to ever changing environmental conditions and internal needs. For this reason, researchers interested in executive control processes have often relied on task-switching paradigms as powerful tools to uncover the underlying cognitive and brain architecture. In order to gather fundamental information at the single-cell level, it would be greatly helpful to demonstrate that non-human primates, especially the macaque monkey, share with us similar behavioral manifestations of task-switching and therefore, in all likelihood, similar underlying brain mechanisms. Unfortunately, prior attempts have provided negative results (e.g., Stoet & Snyder, 2003b), in that it was reported that macaques do not show the typical signature of task-switching operations at the behavioral level, represented by switch costs. If confirmed, this would indicate that the macaque cannot be used as a model approach to explore human executive control mechanisms by means of task-switching paradigms. We have therefore decided to re-explore this issue, by conducting a comparative experiment on a group of human participants and two macaque monkeys, whereby we measured and compared performance costs linked to task switching and resistance to interference across the two species. Contrary to what previously reported, we found that both species display robust task switching costs, thus supporting the claim that macaque monkeys provide an exquisitely suitable model to study the brain mechanisms responsible for maintaining and switching task sets.

  3. Poster: the macaque genome.

    Science.gov (United States)

    2007-04-13

    The rhesus macaque (Macaca mulatta) facilitates an extraordinary range of biomedical and basic research, and the publication of the genome only makes it a more powerful model for studies of human disease; moreover, the macaque's position relative to humans and chimpanzees affords the opportunity to learn about the processes that have shaped the last 25 million years of primate evolution. To allow users to explore these themes of the macaque genome, Science has created a special interactive version of the poster published in the print edition of the 13 April 2007 issue. The interactive version includes additional text and exploration, as well as embedded video featuring seven scientists discussing the importance of the macaque and its genome sequence in studies of biomedicine and evolution. We have also created an accompanying teaching resource, including a lesson plan aimed at teachers of advanced high school life science students, for exploring what a comparison of the macaque and human genomes can tell us about human biology and evolution. These items are free to all site visitors.

  4. Cynomolgus macaque as an animal model for severe acute respiratory syndrome.

    Directory of Open Access Journals (Sweden)

    James V Lawler

    2006-05-01

    Full Text Available The emergence of severe acute respiratory syndrome (SARS in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs infected with SARS-CoV.In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain.SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children.

  5. Protection of stem cell-derived lymphocytes in a primate AIDS gene therapy model after in vivo selection.

    Directory of Open Access Journals (Sweden)

    Grant D Trobridge

    Full Text Available BACKGROUND: There is currently no effective AIDS vaccine, emphasizing the importance of developing alternative therapies. Recently, a patient was successfully transplanted with allogeneic, naturally resistant CCR5-negative (CCR5Delta32 cells, setting the stage for transplantation of naturally resistant, or genetically modified stem cells as a viable therapy for AIDS. Hematopoietic stem cell (HSC gene therapy using vectors that express various anti-HIV transgenes has also been attempted in clinical trials, but inefficient gene transfer in these studies has severely limited the potential of this approach. Here we evaluated HSC gene transfer of an anti-HIV vector in the pigtailed macaque (Macaca nemestrina model, which closely models human transplantation. METHODS AND FINDINGS: We used lentiviral vectors that inhibited both HIV-1 and simian immunodeficiency virus (SIV/HIV-1 (SHIV chimera virus infection, and also expressed a P140K mutant methylguanine methyltransferase (MGMT transgene to select gene-modified cells by adding chemotherapy drugs. Following transplantation and MGMT-mediated selection we demonstrated transgene expression in over 7% of stem-cell derived lymphocytes. The high marking levels allowed us to demonstrate protection from SHIV in lymphocytes derived from gene-modified macaque long-term repopulating cells that expressed an HIV-1 fusion inhibitor. We observed a statistically significant 4-fold increase of gene-modified cells after challenge of lymphocytes from one macaque that received stem cells transduced with an anti-HIV vector (p<0.02, Student's t-test, but not in lymphocytes from a macaque that received a control vector. We also established a competitive repopulation assay in a second macaque for preclinical testing of promising anti-HIV vectors. The vectors we used were HIV-based and thus efficiently transduce human cells, and the transgenes we used target HIV-1 genes that are also in SHIV, so our findings can be rapidly

  6. Use of (18)F-fluorodeoxyglucose positron emission tomography-computed tomography to aid in diagnosing intestinal adenocarcinoma in 2 rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Caporizzo, Debra J; Kwiatkowski, Anna E; Chen, Ming-Kai; Beck, Amanda P; Booth, Carmen J; Zeiss, Caroline; Smith, Peter C; Carlson Scholz, Jodi A; Wilson, Steven R

    2014-06-01

    Two aged female rhesus macaques (Macaca mulatta) presented with weight loss and intermittent inappetence. The signalment and constellation of clinical signs led clinicians to suspect the presence of intestinal adenocarcinoma. Because of each animal's advanced age and inconclusive radiographic findings, a noninvasive diagnostic tool was preferred over exploratory laparotomy to assist in determining a diagnosis. Consequently, 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography-CT (FDG-PET-CT) was chosen to aid in confirming a suspicion of gastrointestinal adenocarcinoma in both animals. FDG is a glucose analogue labeled with fluorine-18 and is taken up by highly metabolically active cells, as observed in many cancers. Tomography revealed an annular constriction of the small intestine with focal FDG uptake in one animal, and an FDG avid transmural mass in the ascending colon of the second animal. Necropsy later confirmed both sites to be adenocarcinomas. This report supports the use of FDG-PET-CT as an adjunct to conventional radiography in the diagnosis of intestinal adenocarcinoma in nonhuman primates.

  7. Job Aiding/Training Decision Process Model

    Science.gov (United States)

    1992-09-01

    I[ -, . 1’, oo Ii AL-CR-i1992-0004 AD-A256 947lEE = IIEI ifl ll 1l I JOB AIDING/TRAINING DECISION PROCESS MODEL A R M John P. Zenyuh DTIC S Phillip C...March 1990 - April 1990 4. TITLE AND SUBTITLE S. FUNDING NUMBERS C - F33615-86-C-0545 Job Aiding/Training Decision Process Model PE - 62205F PR - 1121 6...Components to Process Model Decision and Selection Points ........... 32 13. Summary of Subject Recommendations for Aiding Approaches

  8. Pathophysiologic and transcriptomic analyses of viscerotropic yellow fever in a rhesus macaque model.

    Science.gov (United States)

    Engelmann, Flora; Josset, Laurence; Girke, Thomas; Park, Byung; Barron, Alex; Dewane, Jesse; Hammarlund, Erika; Lewis, Anne; Axthelm, Michael K; Slifka, Mark K; Messaoudi, Ilhem

    2014-01-01

    Infection with yellow fever virus (YFV), an explosively replicating flavivirus, results in viral hemorrhagic disease characterized by cardiovascular shock and multi-organ failure. Unvaccinated populations experience 20 to 50% fatality. Few studies have examined the pathophysiological changes that occur in humans during YFV infection due to the sporadic nature and remote locations of outbreaks. Rhesus macaques are highly susceptible to YFV infection, providing a robust animal model to investigate host-pathogen interactions. In this study, we characterized disease progression as well as alterations in immune system homeostasis, cytokine production and gene expression in rhesus macaques infected with the virulent YFV strain DakH1279 (YFV-DakH1279). Following infection, YFV-DakH1279 replicated to high titers resulting in viscerotropic disease with ∼72% mortality. Data presented in this manuscript demonstrate for the first time that lethal YFV infection results in profound lymphopenia that precedes the hallmark changes in liver enzymes and that although tissue damage was noted in liver, kidneys, and lymphoid tissues, viral antigen was only detected in the liver. These observations suggest that additional tissue damage could be due to indirect effects of viral replication. Indeed, circulating levels of several cytokines peaked shortly before euthanasia. Our study also includes the first description of YFV-DakH1279-induced changes in gene expression within peripheral blood mononuclear cells 3 days post-infection prior to any clinical signs. These data show that infection with wild type YFV-DakH1279 or live-attenuated vaccine strain YFV-17D, resulted in 765 and 46 differentially expressed genes (DEGs), respectively. DEGs detected after YFV-17D infection were mostly associated with innate immunity, whereas YFV-DakH1279 infection resulted in dysregulation of genes associated with the development of immune response, ion metabolism, and apoptosis. Therefore, WT-YFV infection

  9. Function and innervation of the locus ceruleus in a macaque model of Functional Hypothalamic Amenorrhea.

    Science.gov (United States)

    Bethea, Cynthia L; Kim, Aaron; Cameron, Judy L

    2013-02-01

    A body of knowledge implicates an increase in output from the locus ceruleus (LC) during stress. We questioned the innervation and function of the LC in our macaque model of Functional Hypothalamic Amenorrhea, also known as Stress-Induced Amenorrhea. Cohorts of macaques were initially characterized as highly stress resilient (HSR) or stress-sensitive (SS) based upon the presence or absence of ovulation during a protocol involving 2 menstrual cycles with psychosocial and metabolic stress. Afterwards, the animals were rested until normal menstrual cycles resumed and then euthanized on day 5 of a new menstrual cycle [a] in the absence of further stress; or [b] after 5 days of resumed psychosocial and metabolic stress. In this study, parameters of the LC were examined in HSR and SS animals in the presence and absence of stress (2×2 block design) using ICC and image analysis. Tyrosine hydroxylase (TH) is the rate-limiting enzyme for the synthesis of catecholamines; and the TH level was used to assess by inference, NE output. The pixel area of TH-positive dendrites extending outside the medial border of the LC was significantly increased by stress to a similar degree in both HSR and SS animals (p<0.0001). There is a significant CRF innervation of the LC. The positive pixel area of CRF boutons, lateral to the LC, was higher in SS than HSR animals in the absence of stress. Five days of moderate stress significantly increased the CRF-positive bouton pixel area in the HSR group (p<0.02), but not in the SS group. There is also a significant serotonin innervation of the LC. A marked increase in medial serotonin dendrite swelling and beading was observed in the SS+stress group, which may be a consequence of excitotoxicity. The dendrite beading interfered with analysis of axonal boutons. However, at one anatomical level, the serotonin-positive bouton area was obtained between the LC and the superior cerebellar peduncle. Serotonin-positive bouton pixel area was significantly

  10. Computer Aided Continuous Time Stochastic Process Modelling

    DEFF Research Database (Denmark)

    Kristensen, N.R.; Madsen, Henrik; Jørgensen, Sten Bay

    2001-01-01

    A grey-box approach to process modelling that combines deterministic and stochastic modelling is advocated for identification of models for model-based control of batch and semi-batch processes. A computer-aided tool designed for supporting decision-making within the corresponding modelling cycle...

  11. Computer Aided Modelling – Opportunities and Challenges

    DEFF Research Database (Denmark)

    2011-01-01

    This chapter considers the opportunities that are present in developing, extending and applying aspects of computer-aided modelling principles and practice. What are the best tasks to be done by modellers and what needs the application of CAPE tools? How do we efficiently develop model-based solu......This chapter considers the opportunities that are present in developing, extending and applying aspects of computer-aided modelling principles and practice. What are the best tasks to be done by modellers and what needs the application of CAPE tools? How do we efficiently develop model...

  12. Computer-Aided Modelling Methods and Tools

    DEFF Research Database (Denmark)

    Cameron, Ian; Gani, Rafiqul

    2011-01-01

    The development of models for a range of applications requires methods and tools. In many cases a reference model is required that allows the generation of application specific models that are fit for purpose. There are a range of computer aided modelling tools available that help to define...... a taxonomy of aspects around conservation, constraints and constitutive relations. Aspects of the ICAS-MoT toolbox are given to illustrate the functionality of a computer aided modelling tool, which incorporates an interface to MS Excel....

  13. Behavioural profiles in captive-bred cynomolgus macaques: towards monkey models of mental disorders?

    Directory of Open Access Journals (Sweden)

    Sandrine M J Camus

    Full Text Available BACKGROUND: To date, experimental and preclinical studies on neuropsychiatric conditions have almost exclusively been performed in experimentally-induced animal models and have only rarely relied upon an ethological approach where animals have been observed in more naturalistic settings. The laboratory species of choice has been the rodent while the potential of more closely-related non-human primates have remained largely underexplored. METHODS: The present study, therefore, aimed at investigating the possible existence of spontaneous atypical/abnormal behaviours displayed by 40 cynomolgus macaques in captive conditions using an unbiased ethological scan-sampling analysis followed by multifactorial correspondence analysis and a hierarchical clustering. RESULTS: The study identified five distinct profiles (groups A to E that significantly differed on several behaviours, body postures, body orientations, gaze directions and locations in the cage environment. We suggest that animals from the low n groups (D and E present depressive-like and anxious-like symptoms, reminiscent of depressive and generalized anxiety disorders. Inter-individual differences were highlighted through unbiased ethological observations of spontaneous behaviours and associated parameters, although these were not associated with differences in plasma or cerebrospinal fluid levels of either stress-related hormones or monoamines, i.e. in accordance with the human situation. CONCLUSIONS: No interventional behavioural testing was required to discriminate between 3 typical and 2 atypical ethologically-defined behavioural profiles, reminiscent of certain depressive-like and anxiety-like symptoms. The use of unbiased behavioural observations might, thus, allow the identification of animal models of human mental/behavioural disorders and their most appropriate control groups.

  14. Behavioural Profiles in Captive-Bred Cynomolgus Macaques: Towards Monkey Models of Mental Disorders?

    Science.gov (United States)

    Camus, Sandrine M. J.; Blois-Heulin, Catherine; Li, Qin; Hausberger, Martine; Bezard, Erwan

    2013-01-01

    Background To date, experimental and preclinical studies on neuropsychiatric conditions have almost exclusively been performed in experimentally-induced animal models and have only rarely relied upon an ethological approach where animals have been observed in more naturalistic settings. The laboratory species of choice has been the rodent while the potential of more closely-related non-human primates have remained largely underexplored. Methods The present study, therefore, aimed at investigating the possible existence of spontaneous atypical/abnormal behaviours displayed by 40 cynomolgus macaques in captive conditions using an unbiased ethological scan-sampling analysis followed by multifactorial correspondence analysis and a hierarchical clustering. Results The study identified five distinct profiles (groups A to E) that significantly differed on several behaviours, body postures, body orientations, gaze directions and locations in the cage environment. We suggest that animals from the low n groups (D and E) present depressive-like and anxious-like symptoms, reminiscent of depressive and generalized anxiety disorders. Inter-individual differences were highlighted through unbiased ethological observations of spontaneous behaviours and associated parameters, although these were not associated with differences in plasma or cerebrospinal fluid levels of either stress-related hormones or monoamines, i.e. in accordance with the human situation. Conclusions No interventional behavioural testing was required to discriminate between 3 typical and 2 atypical ethologically-defined behavioural profiles, reminiscent of certain depressive-like and anxiety-like symptoms. The use of unbiased behavioural observations might, thus, allow the identification of animal models of human mental/behavioural disorders and their most appropriate control groups. PMID:23658620

  15. Generation of lineage-related, mucosally transmissible subtype C R5 simian-human immunodeficiency viruses capable of AIDS development, induction of neurological disease, and coreceptor switching in rhesus macaques.

    Science.gov (United States)

    Ren, Wuze; Mumbauer, Alexandra; Gettie, Agegnehu; Seaman, Michael S; Russell-Lodrigue, Kasi; Blanchard, James; Westmoreland, Susan; Cheng-Mayer, Cecilia

    2013-06-01

    Most human immunodeficiency virus (HIV) transmissions are initiated with CCR5 (R5)-using viruses across mucosal surfaces, with the majority in regions where HIV type 1 (HIV-1) clade C predominates. Mucosally transmissible, highly replication competent, pathogenic R5 simian-human immunodeficiency viruses (SHIVs) encoding biologically relevant clade C envelopes are therefore needed as challenge viruses in vaccine efficacy studies with nonhuman primates. Here we describe the generation of three lineage-related subtype C SHIVs through four successive rapid transfers in rhesus macaques of SHIVC109F.PB4, a molecular clone expressing the soluble-CD4 (sCD4)-sensitive CCR5-tropic clade C envelope of a recently infected subject in Zambia. The viruses differed in their monkey passage histories and neutralization sensitivities but remained R5 tropic. SHIVC109P3 and SHIVC109P3N were recovered from a passage-3 rapid-progressor animal during chronic infection (24 weeks postinfection [wpi]) and at end-stage disease (34 wpi), respectively, and are classified as tier 1B strains, whereas SHIVC109P4 was recovered from a passage-4 normal-progressor macaque at 22 wpi and is a tier 2 virus, more difficult to neutralize. All three viruses were transmitted efficiently via intrarectal inoculation, reaching peak viral loads of 10(7) to 10(9) RNA copies/ml plasma and establishing viremia at various set points. Notably, one of seven (GC98) and two of six (CL31, FI08) SHIVC109P3- and SHIVC109P3N-infected macaques, respectively, progressed to AIDS, with neuropathologies observed in GC98 and FI08, as well as coreceptor switching in the latter. These findings support the use of these new SHIVC109F.PB4-derived viruses to study the immunopathology of HIV-1 clade C infection and to evaluate envelope-based AIDS vaccines in nonhuman primates.

  16. AIDS models grow in use -- and controversy.

    Science.gov (United States)

    Barron, T

    1992-01-01

    Policy and program planners use information gained from computer-based statistical models to develop interventions against AIDS. Models of the epidemic's effect, however, show widely differing impacts on population. With the recent entry of a British researcher's view of the impact of AIDS on the population of Africa, the debate between researchers has only intensified. While the World Health Organization (WHO) has conservatively estimated that 40 million people will be infected with HIV by the year 2000, Roy Anderson of the University of London and Robert May of Oxford University expect AIDS to cause population decline in Africa after the year 2002. Major donors and researchers feel that while population growth rates will decline, growth rates will not turn negative due to AIDS. The British researchers, however, do not consider their views to differ greatly from those of US researchers, but they do have problems with overly conservative WHO projections. Their research assumes a higher degree of transmission between core groups of HIV-positive people, including prostitutes, IV drug users, and general populations in Africa's hardest hit areas. They project infection prevalence to reach 50% or more in some areas. Greater levels of prostitution and poverty, as well as the tendency for males to have sex with increasingly younger females, will lead to higher HIV incidence and prevalence in Africa. Family planning experts are voicing their concern over the integrity of these models and question whether they are more than simply educated guesses of what the future holds. Even though projections are uncertain and extremely data-dependent, family planning efforts must continue. Whether or not the AIDS pandemic eventually levels off in certain areas, critics must remember that family planning improves maternal and child health in addition to contributing to lower growth rates and prevent AIDS.

  17. Computer Aided Modelling – Opportunities and Challenges

    DEFF Research Database (Denmark)

    Cameron, Ian; Gani, Rafiqul

    2011-01-01

    -based solutions to significant problems? The important issues of workflow and data flow are discussed together with fit-for-purpose model development. As well, the lack of tools around multiscale modelling provides opportunities for the development of efficient tools to address such challenges. The ability......This chapter considers the opportunities that are present in developing, extending and applying aspects of computer-aided modelling principles and practice. What are the best tasks to be done by modellers and what needs the application of CAPE tools? How do we efficiently develop model...... and opportunities are discussed for such systems....

  18. Development of a Rotavirus-Shedding Model in Rhesus Macaques, Using a Homologous Wild-Type Rotavirus of a New P Genotype

    Science.gov (United States)

    McNeal, Monica M.; Sestak, Karol; Choi, Anthony H.-C.; Basu, Mitali; Cole, Michael J.; Aye, Pyone P.; Bohm, Rudolf P.; Ward, Richard L.

    2005-01-01

    Although there are several reports on rotavirus inoculation of nonhuman primates, no reliable model exists. Therefore, this study was designed to develop a rhesus macaque model for rotavirus studies. The goals were to obtain a wild-type macaque rotavirus and evaluate it as a challenge virus for model studies. Once rotavirus was shown to be endemic within the macaque colony at the Tulane National Primate Research Center, stool specimens were collected from juvenile animals (2.6 to 5.9 months of age) without evidence of previous rotavirus infection and examined for rotavirus antigen. Six of 10 animals shed rotavirus during the 10-week collection period, and the electropherotypes of all isolates were identical to each other but distinct from those of prototype simian rotaviruses. These viruses were characterized as serotype G3 and subgroup 1, properties typical of many animal rotaviruses, including simian strains. Nucleotide sequence analysis of the VP4 gene was performed with a culture-grown isolate from the stool of one animal, designated the TUCH strain. Based on both genotypic and phylogenetic comparisons between TUCH VP4 and cognate proteins of representatives of the reported 22 P genotypes, the TUCH virus belongs to a new genotype, P[23]. A pool of wild-type TUCH was prepared and intragastrically administered to eight cesarean section-derived, specific-pathogen-free macaques 14 to 42 days of age. All animals were kept in a biocontainment level 2 facility. Although no diarrhea was observed and the animals remained clinically normal, all animals shed large quantities of rotavirus antigen in their feces after inoculation, which resolved by the end of the 14-day observation period. Therefore, TUCH infection of macaques provides a useful nonhuman primate model for studies on rotavirus protection. PMID:15613323

  19. Exome screening to identify loss-of-function mutations in the rhesus macaque for development of preclinical models of human disease.

    Science.gov (United States)

    Cornish, Adam S; Gibbs, Robert M; Norgren, Robert B

    2016-03-02

    Exome sequencing has been utilized to identify genetic variants associated with disease in humans. Identification of loss-of-function mutations with exome sequencing in rhesus macaques (Macaca mulatta) could lead to valuable animal models of genetic disease. Attempts have been made to identify variants in rhesus macaques by aligning exome data against the rheMac2 draft genome. However, such efforts have been impaired due to the incompleteness and annotation errors associated with rheMac2. We wished to determine whether aligning exome reads against our new, improved rhesus genome, MacaM, could be used to identify high impact, loss-of-function mutations in rhesus macaques that would be relevant to human disease. We compared alignments of exome reads from four rhesus macaques, the reference animal and three unrelated animals, against rheMac2 and MacaM. Substantially more reads aligned against MacaM than rheMac2. We followed the Broad Institute's Best Practice guidelines for variant discovery which utilizes the Genome Analysis Toolkit to identify high impact mutations. When rheMac2 was used as the reference genome, a large number of apparent false positives were identified. When MacaM was used as the reference genome, the number of false positives was greatly reduced. After examining the variant analyses conducted with MacaM as reference genome, we identified two putative loss-of-function mutations, in the heterozygous state, in genes related to human health. Sanger sequencing confirmed the presence of these mutations. We followed the transmission of one of these mutations (in the butyrylthiocholine gene) through three generations of rhesus macaques. Further, we demonstrated a functional decrease in butyrylthiocholinesterase activity similar to that observed in human heterozygotes with loss-of-function mutations in the same gene. The new MacaM genome can be effectively utilized to identify loss-of-function mutations in rhesus macaques without generating a high level of

  20. CD4+ T-cell-independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection.

    Science.gov (United States)

    Foreman, Taylor W; Mehra, Smriti; LoBato, Denae N; Malek, Adel; Alvarez, Xavier; Golden, Nadia A; Bucşan, Allison N; Didier, Peter J; Doyle-Meyers, Lara A; Russell-Lodrigue, Kasi E; Roy, Chad J; Blanchard, James; Kuroda, Marcelo J; Lackner, Andrew A; Chan, John; Khader, Shabaana A; Jacobs, William R; Kaushal, Deepak

    2016-09-20

    The synergy between Mycobacterium tuberculosis (Mtb) and HIV in coinfected patients has profoundly impacted global mortality because of tuberculosis (TB) and AIDS. HIV significantly increases rates of reactivation of latent TB infection (LTBI) to active disease, with the decline in CD4(+) T cells believed to be the major causality. In this study, nonhuman primates were coinfected with Mtb and simian immunodeficiency virus (SIV), recapitulating human coinfection. A majority of animals exhibited rapid reactivation of Mtb replication, progressing to disseminated TB and increased SIV-associated pathology. Although a severe loss of pulmonary CD4(+) T cells was observed in all coinfected macaques, a subpopulation of the animals was still able to prevent reactivation and maintain LTBI. Investigation of pulmonary immune responses and pathology in this cohort demonstrated that increased CD8(+) memory T-cell proliferation, higher granzyme B production, and expanded B-cell follicles correlated with protection from reactivation. Our findings reveal mechanisms that control SIV- and TB-associated pathology. These CD4-independent protective immune responses warrant further studies in HIV coinfected humans able to control their TB infection. Moreover, these findings will provide insight into natural immunity to Mtb and will guide development of novel vaccine strategies and immunotherapies.

  1. Minipig and beagle animal model genomes aid species selection in pharmaceutical discovery and development

    Energy Technology Data Exchange (ETDEWEB)

    Vamathevan, Jessica J., E-mail: jessica.j.vamathevan@gsk.com [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Stevenage (United Kingdom); Hall, Matthew D.; Hasan, Samiul; Woollard, Peter M. [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Stevenage (United Kingdom); Xu, Meng; Yang, Yulan; Li, Xin; Wang, Xiaoli [BGI-Shenzen, Shenzhen (China); Kenny, Steve [Safety Assessment, PTS, GlaxoSmithKline, Ware (United Kingdom); Brown, James R. [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Collegeville, PA (United States); Huxley-Jones, Julie [UK Platform Technology Sciences (PTS) Operations and Planning, PTS, GlaxoSmithKline, Stevenage (United Kingdom); Lyon, Jon; Haselden, John [Safety Assessment, PTS, GlaxoSmithKline, Ware (United Kingdom); Min, Jiumeng [BGI-Shenzen, Shenzhen (China); Sanseau, Philippe [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Stevenage (United Kingdom)

    2013-07-15

    Improving drug attrition remains a challenge in pharmaceutical discovery and development. A major cause of early attrition is the demonstration of safety signals which can negate any therapeutic index previously established. Safety attrition needs to be put in context of clinical translation (i.e. human relevance) and is negatively impacted by differences between animal models and human. In order to minimize such an impact, an earlier assessment of pharmacological target homology across animal model species will enhance understanding of the context of animal safety signals and aid species selection during later regulatory toxicology studies. Here we sequenced the genomes of the Sus scrofa Göttingen minipig and the Canis familiaris beagle, two widely used animal species in regulatory safety studies. Comparative analyses of these new genomes with other key model organisms, namely mouse, rat, cynomolgus macaque, rhesus macaque, two related breeds (S. scrofa Duroc and C. familiaris boxer) and human reveal considerable variation in gene content. Key genes in toxicology and metabolism studies, such as the UGT2 family, CYP2D6, and SLCO1A2, displayed unique duplication patterns. Comparisons of 317 known human drug targets revealed surprising variation such as species-specific positive selection, duplication and higher occurrences of pseudogenized targets in beagle (41 genes) relative to minipig (19 genes). These data will facilitate the more effective use of animals in biomedical research. - Highlights: • Genomes of the minipig and beagle dog, two species used in pharmaceutical studies. • First systematic comparative genome analysis of human and six experimental animals. • Key drug toxicology genes display unique duplication patterns across species. • Comparison of 317 drug targets show species-specific evolutionary patterns.

  2. Animal models for HIV/AIDS research

    Science.gov (United States)

    Hatziioannou, Theodora; Evans, David T.

    2015-01-01

    The AIDS pandemic continues to present us with unique scientific and public health challenges. Although the development of effective antiretroviral therapy has been a major triumph, the emergence of drug resistance requires active management of treatment regimens and the continued development of new antiretroviral drugs. Moreover, despite nearly 30 years of intensive investigation, we still lack the basic scientific knowledge necessary to produce a safe and effective vaccine against HIV-1. Animal models offer obvious advantages in the study of HIV/AIDS, allowing for a more invasive investigation of the disease and for preclinical testing of drugs and vaccines. Advances in humanized mouse models, non-human primate immunogenetics and recombinant challenge viruses have greatly increased the number and sophistication of available mouse and simian models. Understanding the advantages and limitations of each of these models is essential for the design of animal studies to guide the development of vaccines and antiretroviral therapies for the prevention and treatment of HIV-1 infection. PMID:23154262

  3. Influenza A Virus Challenge Models in Cynomolgus Macaques Using the Authentic Inhaled Aerosol and Intra-Nasal Routes of Infection.

    Directory of Open Access Journals (Sweden)

    Anthony C Marriott

    Full Text Available Non-human primates are the animals closest to humans for use in influenza A virus challenge studies, in terms of their phylogenetic relatedness, physiology and immune systems. Previous studies have shown that cynomolgus macaques (Macaca fascicularis are permissive for infection with H1N1pdm influenza virus. These studies have typically used combined challenge routes, with the majority being intra-tracheal delivery, and high doses of virus (> 107 infectious units. This paper describes the outcome of novel challenge routes (inhaled aerosol, intra-nasal instillation and low to moderate doses (103 to 106 plaque forming units of H1N1pdm virus in cynomolgus macaques. Evidence of virus replication and sero-conversion were detected in all four challenge groups, although the disease was sub-clinical. Intra-nasal challenge led to an infection confined to the nasal cavity. A low dose (103 plaque forming units did not lead to detectable infectious virus shedding, but a 1000-fold higher dose led to virus shedding in all intra-nasal challenged animals. In contrast, aerosol and intra-tracheal challenge routes led to infections throughout the respiratory tract, although shedding from the nasal cavity was less reproducible between animals compared to the high-dose intra-nasal challenge group. Intra-tracheal and aerosol challenges induced a transient lymphopaenia, similar to that observed in influenza-infected humans, and greater virus-specific cellular immune responses in the blood were observed in these groups in comparison to the intra-nasal challenge groups. Activation of lung macrophages and innate immune response genes was detected at days 5 to 7 post-challenge. The kinetics of infection, both virological and immunological, were broadly in line with human influenza A virus infections. These more authentic infection models will be valuable in the determination of anti-influenza efficacy of novel entities against less severe (and thus more common influenza

  4. Interferon-β therapy prolongs survival in rhesus macaque models of Ebola and Marburg hemorrhagic fever.

    Science.gov (United States)

    Smith, Lauren M; Hensley, Lisa E; Geisbert, Thomas W; Johnson, Joshua; Stossel, Andrea; Honko, Anna; Yen, Judy Y; Geisbert, Joan; Paragas, Jason; Fritz, Elizabeth; Olinger, Gene; Young, Howard A; Rubins, Kathleen H; Karp, Christopher L

    2013-07-15

    There is a clear need for novel, effective therapeutic approaches to hemorrhagic fever due to filoviruses. Ebola virus hemorrhagic fever is associated with robust interferon (IFN)-α production, with plasma concentrations of IFN-α that greatly (60- to 100-fold) exceed those seen in other viral infections, but little IFN-β production. While all of the type I IFNs signal through the same receptor complex, both quantitative and qualitative differences in biological activity are observed after stimulation of the receptor complex with different type I IFNs. Taken together, this suggested potential for IFN-β therapy in filovirus infection. Here we show that early postexposure treatment with IFN-β significantly increased survival time of rhesus macaques infected with a lethal dose of Ebola virus, although it failed to alter mortality. Early treatment with IFN-β also significantly increased survival time after Marburg virus infection. IFN-β may have promise as an adjunctive postexposure therapy in filovirus infection.

  5. Rhesus macaque theta defensins suppress inflammatory cytokines and enhance survival in mouse models of bacteremic sepsis.

    Directory of Open Access Journals (Sweden)

    Justin B Schaal

    Full Text Available Theta-defensins (θ-defensins are macrocyclic antimicrobial peptides expressed in leukocytes of Old World monkeys. The peptides are broad spectrum microbicides in vitro and numerous θ-defensin isoforms have been identified in granulocytes of rhesus macaques and Olive baboons. Several mammalian α- and β-defensins, genetically related to θ-defensins, have proinflammatory and immune-activating properties that bridge innate and acquired immunity. In the current study we analyzed the immunoregulatory properties of rhesus θ-defensins 1-5 (RTDs 1-5. RTD-1, the most abundant θ-defensin in macaques, reduced the levels of TNF, IL-1α, IL-1β, IL-6, and IL-8 secreted by blood leukocytes stimulated by several TLR agonists. RTDs 1-5 suppressed levels of soluble TNF released by bacteria- or LPS-stimulated blood leukocytes and THP-1 monocytes. Despite their highly conserved conformation and amino acid sequences, the anti-TNF activities of RTDs 1-5 varied by as much as 10-fold. Systemically administered RTD-1 was non-toxic for BALB/c mice, and escalating intravenous doses were well tolerated and non-immunogenic in adult chimpanzees. The peptide was highly stable in serum and plasma. Single dose administration of RTD-1 at 5 mg/kg significantly improved survival of BALB/c mice with E. coli peritonitis and cecal ligation-and-puncture induced polymicrobial sepsis. Peptide treatment reduced serum levels of several inflammatory cytokines/chemokines in bacteremic animals. Collectively, these results indicate that the anti-inflammatory properties of θ-defensins in vitro and in vivo are mediated by the suppression of numerous proinflammatory cytokines and blockade of TNF release may be a primary effect.

  6. Computer Aided Design Modeling for Heterogeneous Objects

    CERN Document Server

    Gupta, Vikas; Tandon, Puneet

    2010-01-01

    Heterogeneous object design is an active research area in recent years. The conventional CAD modeling approaches only provide geometry and topology of the object, but do not contain any information with regard to the materials of the object and so can not be used for the fabrication of heterogeneous objects (HO) through rapid prototyping. Current research focuses on computer-aided design issues in heterogeneous object design. A new CAD modeling approach is proposed to integrate the material information into geometric regions thus model the material distributions in the heterogeneous object. The gradient references are used to represent the complex geometry heterogeneous objects which have simultaneous geometry intricacies and accurate material distributions. The gradient references helps in flexible manipulability and control to heterogeneous objects, which guarantees the local control over gradient regions of developed heterogeneous objects. A systematic approach on data flow, processing, computer visualizat...

  7. Using a Shape Model in the Design of Hearing Aids

    DEFF Research Database (Denmark)

    Paulsen, Rasmus Reinhold; Nielsen, Claus; Laugesen, Søren;

    2004-01-01

    Today the design of custom completely-in-the-canal hearing aids is a manual process and therefore there is a variation in the quality of the finished hearing aids. Especially the placement of the so-called faceplate on the hearing aid strongly influences the size and shape of the hearing aid. Since...... the future hearing aid production will be less manual there is a need for algorithms that mimic the craftsmanship of skilled operators. In this paper it is described how a statistical shape model of the ear canal can be used to predict the placement of the faceplate on a hearing aid made for a given ear...

  8. Simian hemorrhagic fever virus infection of rhesus macaques as a model of viral hemorrhagic fever: clinical characterization and risk factors for severe disease.

    Science.gov (United States)

    Johnson, Reed F; Dodd, Lori E; Yellayi, Srikanth; Gu, Wenjuan; Cann, Jennifer A; Jett, Catherine; Bernbaum, John G; Ragland, Dan R; St Claire, Marisa; Byrum, Russell; Paragas, Jason; Blaney, Joseph E; Jahrling, Peter B

    2011-12-20

    Simian Hemorrhagic Fever Virus (SHFV) has caused sporadic outbreaks of hemorrhagic fevers in macaques at primate research facilities. SHFV is a BSL-2 pathogen that has not been linked to human disease; as such, investigation of SHFV pathogenesis in non-human primates (NHPs) could serve as a model for hemorrhagic fever viruses such as Ebola, Marburg, and Lassa viruses. Here we describe the pathogenesis of SHFV in rhesus macaques inoculated with doses ranging from 50 PFU to 500,000 PFU. Disease severity was independent of dose with an overall mortality rate of 64% with signs of hemorrhagic fever and multiple organ system involvement. Analyses comparing survivors and non-survivors were performed to identify factors associated with survival revealing differences in the kinetics of viremia, immunosuppression, and regulation of hemostasis. Notable similarities between the pathogenesis of SHFV in NHPs and hemorrhagic fever viruses in humans suggest that SHFV may serve as a suitable model of BSL-4 pathogens.

  9. An evaluation of istradefylline treatment on Parkinsonian motor and cognitive deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaque models.

    Science.gov (United States)

    Ko, Wai Kin D; Camus, Sandrine M; Li, Qin; Yang, Jianzhong; McGuire, Steve; Pioli, Elsa Y; Bezard, Erwan

    2016-11-01

    Istradefylline (KW-6002), an adenosine A2A receptor antagonist, is used adjunct with optimal doses of L-3,4-dihydroxyphenylalanine (l-DOPA) to extend on-time in Parkinson's disease (PD) patients experiencing motor fluctuations. Clinical application of istradefylline for the management of other l-DOPA-induced complications, both motor and non-motor related (i.e. dyskinesia and cognitive impairments), remains to be determined. In this study, acute effects of istradefylline (60-100 mg/kg) alone, or with optimal and sub-optimal doses of l-DOPA, were evaluated in two monkey models of PD (i) the gold-standard 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaque model of parkinsonian and dyskinetic motor symptoms and (ii) the chronic low dose (CLD) MPTP-treated macaque model of cognitive (working memory and attentional) deficits. Behavioural analyses in l-DOPA-primed MPTP-treated macaques showed that istradefylline alone specifically alleviated postural deficits. When combined with an optimal l-DOPA treatment dose, istradefylline increased on-time, enhanced therapeutic effects on bradykinesia and locomotion, but exacerbated dyskinesia. Istradefylline treatment at specific doses with sub-optimal l-DOPA specifically alleviated bradykinesia. Cognitive assessments in CLD MPTP-treated macaques showed that the attentional and working memory deficits caused by l-DOPA were lowered after istradefylline administration. Taken together, these data support a broader clinical use of istradefylline as an adjunct treatment in PD, where specific treatment combinations can be utilised to manage various l-DOPA-induced complications, which importantly, maintain a desired anti-parkinsonian response.

  10. Characterization of an in vitro Rhesus Macaque Blood-Brain Barrier

    Science.gov (United States)

    MacLean, Andrew G.; Orandle, Marlene S.; MacKey, John; Williams, Kenneth C.; Alvarez, Xavier; Lackner, Andrew A.

    2013-01-01

    The blood-brain barrier has been modeled in vitro in a number of species, including rat, cow and human. Coculture of multiple cell types is required for the correct expression of tight junction proteins by microvascular brain endothelial cells (MBEC). Markers of inflammation, especially MHC-II, and cell adhesion molecules, such as VCAM-1, are not expressed on the luminal surface of the barrier under resting conditions. The rhesus macaque model has been used to study early events of HIV-neuropathogenesis in vivo, but a suitable in vitro model has not been available for detailed mechanistic studies. Here we describe an in vitro rhesus macaque blood-brain barrier (BBB) that utilizes autologous MBEC and astrocytes. We believe that this model is highly relevant for examining immunological events at the blood-brain barrier and demonstrate its potential usefulness for examining early events in AIDS neuropathogenesis. PMID:12458041

  11. Surgical technique for allogeneic uterus transplantation in macaques

    OpenAIRE

    Hideaki Obara; Iori Kisu; Yojiro Kato; Yohei Yamada; Kentaro Matsubara; Katsura Emoto; Masataka Adachi; Yusuke Matoba; Kiyoko Umene; Yuya Nogami; Kouji Banno; Hideaki Tsuchiya; Iori Itagaki; Ikuo Kawamoto; Takahiro Nakagawa

    2016-01-01

    No study has reported an animal model of uterus transplantation (UTx) using cynomolgus macaques. We aimed to establish a surgical technique of allogeneic UTx assuming the recovery of a uterus from a deceased donor in cynomolgus macaques. Four allogeneic UTxs were performed in female cynomolgus macaques. Donor surgeries comprised en bloc recovery of organs with iliac vessels on both sides, and/or abdominal aorta/vena cava after sufficient perfusion from one femoral artery or external iliac art...

  12. Characterization of a Cynomolgus Macaque Model of Pneumonic Plague for Evaluation of Vaccine Efficacy.

    Science.gov (United States)

    Fellows, Patricia; Price, Jessica; Martin, Shannon; Metcalfe, Karen; Krile, Robert; Barnewall, Roy; Hart, Mary Kate; Lockman, Hank

    2015-09-01

    The efficacy of a recombinant plague vaccine (rF1V) was evaluated in cynomolgus macaques (CMs) to establish the relationship among vaccine doses, antibody titers, and survival following an aerosol challenge with a lethal dose of Yersinia pestis strain Colorado 92. CMs were vaccinated with a range of rF1V doses on a three-dose schedule (days 0, 56, and 121) to provide a range of survival outcomes. The humoral immune response following vaccination was evaluated with anti-rF1, anti-rV, and anti-rF1V bridge enzyme-linked immunosorbent assays (ELISAs). Animals were challenged via aerosol exposure on day 149. Vaccine doses and antibody responses were each significantly associated with the probability of CM survival (P plague in a dose-dependent manner. There were statistically significant correlations between the vaccine dose and the time to onset of fever (P < 0.0001), the time from onset of fever to death (P < 0.0001), the time to onset of elevated respiratory rate (P = 0.0003), and the time to onset of decreased activity (P = 0.0251) postinfection in animals exhibiting these clinical signs. Delays in the onset of these clinical signs of disease were associated with larger doses of rF1V. Immunization with ≥ 12 μg of rF1V resulted in 100% CM survival. Since both the vaccine dose and anti-rF1V antibody titers correlate with survival, rF1V bridge ELISA titers can be used as a correlate of protection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  13. AIDS

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000594.htm HIV/AIDS To use the sharing features on this page, ... immunodeficiency virus (HIV) is the virus that causes AIDS. When a person becomes infected with HIV, the ...

  14. Computer-aided design–computer-aided engineering associative feature-based heterogeneous object modeling

    Directory of Open Access Journals (Sweden)

    Jikai Liu

    2015-12-01

    Full Text Available Conventionally, heterogeneous object modeling methods paid limited attention to the concurrent modeling of geometry design and material composition distribution. Procedural method was normally employed to generate the geometry first and then determine the heterogeneous material distribution, which ignores the mutual influence. Additionally, limited capability has been established about irregular material composition distribution modeling with strong local discontinuities. This article overcomes these limitations by developing the computer-aided design–computer-aided engineering associative feature-based heterogeneous object modeling method. Level set functions are applied to model the geometry within computer-aided design module, which enables complex geometry modeling. Finite element mesh is applied to store the local material compositions within computer-aided engineering module, which allows any local discontinuities. Then, the associative feature concept builds the correspondence relationship between these modules. Additionally, the level set geometry and material optimization method are developed to concurrently generate the geometry and material information which fills the contents of the computer-aided design–computer-aided engineering associative feature model. Micro-geometry is investigated as well, instead of only the local material composition. A few cases are studied to prove the effectiveness of this new heterogeneous object modeling method.

  15. Computer-aided modeling framework – a generic modeling template

    DEFF Research Database (Denmark)

    Fedorova, Marina; Sin, Gürkan; Gani, Rafiqul

    This work focuses on the development of a computer-aided modeling framework. The framework is a knowledge-based system that is built on a generic modeling language and structured on workflows for different modeling tasks. The overall objective is to support model developers and users to generate...... and test models systematically, efficiently and reliably. In this way, development of products and processes can be made faster, cheaper and more efficient. In this contribution, as part of the framework, a generic modeling template for the systematic derivation of problem specific models is presented....... The application of the modeling template is highlighted with a case study related to the modeling of a catalytic membrane reactor coupling dehydrogenation of ethylbenzene with hydrogenation of nitrobenzene...

  16. Modelling Niche Differentiation of Co-Existing, Elusive and Morphologically Similar Species: A Case Study of Four Macaque Species in Nakai-Nam Theun National Protected Area, Laos

    Directory of Open Access Journals (Sweden)

    Camille N. Z. Coudrat

    2013-01-01

    Full Text Available Species misidentification often occurs when dealing with co-existing and morphologically similar species such as macaques, making the study of their ecology challenging. To overcome this issue, we use reliable occurrence data from camera-trap images and transect survey data to model their respective ecological niche and potential distribution locally in Nakai-Nam Theun National Protected Area (NNT NPA, central-Eastern Laos. We investigate niche differentiation of morphologically similar species using four sympatric macaque species in NNT NPA, as our model species: rhesus Macaca mulatta (Taxonomic Serial Number, TSN 180099, Northern pig-tailed M. leonina (TSN not listed; Assamese M. assamensis (TSN 573018 and stump-tailed M. arctoides (TSN 573017. We examine the implications for their conservation. We obtained occurrence data of macaque species from systematic 2006–2011 camera-trapping surveys and 2011–2012 transect surveys and model their niche and potential distribution with MaxEnt software using 25 environmental and topographic variables. The respective suitable habitat predicted for each species reveals niche segregation between the four species with a gradual geographical distribution following an environmental gradient within the study area. Camera-trapping positioned at many locations can increase elusive-species records with a relatively reduced and more systematic sampling effort and provide reliable species occurrence data. These can be used for environmental niche modelling to study niche segregation of morphologically similar species in areas where their distribution remains uncertain. Examining unresolved species' niches and potential distributions can have crucial implications for future research and species' management and conservation even in the most remote regions and for the least-known species.

  17. Modelling Niche Differentiation of Co-Existing, Elusive and Morphologically Similar Species: A Case Study of Four Macaque Species in Nakai-Nam Theun National Protected Area, Laos.

    Science.gov (United States)

    Coudrat, Camille N Z; Nekaris, K Anne-Isola

    2013-01-30

    Species misidentification often occurs when dealing with co-existing and morphologically similar species such as macaques, making the study of their ecology challenging. To overcome this issue, we use reliable occurrence data from camera-trap images and transect survey data to model their respective ecological niche and potential distribution locally in Nakai-Nam Theun National Protected Area (NNT NPA), central-Eastern Laos. We investigate niche differentiation of morphologically similar species using four sympatric macaque species in NNT NPA, as our model species: rhesus Macaca mulatta (Taxonomic Serial Number, TSN 180099), Northern pig-tailed M. leonina (TSN not listed); Assamese M. assamensis (TSN 573018) and stump-tailed M. arctoides (TSN 573017). We examine the implications for their conservation. We obtained occurrence data of macaque species from systematic 2006-2011 camera-trapping surveys and 2011-2012 transect surveys and model their niche and potential distribution with MaxEnt software using 25 environmental and topographic variables. The respective suitable habitat predicted for each species reveals niche segregation between the four species with a gradual geographical distribution following an environmental gradient within the study area. Camera-trapping positioned at many locations can increase elusive-species records with a relatively reduced and more systematic sampling effort and provide reliable species occurrence data. These can be used for environmental niche modelling to study niche segregation of morphologically similar species in areas where their distribution remains uncertain. Examining unresolved species' niches and potential distributions can have crucial implications for future research and species' management and conservation even in the most remote regions and for the least-known species.

  18. Proton magnetic resonance spectroscopy reveals neuroprotection by oral minocycline in a nonhuman primate model of accelerated NeuroAIDS.

    Directory of Open Access Journals (Sweden)

    Eva-Maria Ratai

    Full Text Available BACKGROUND: Despite the advent of highly active anti-retroviral therapy (HAART, HIV-associated neurocognitive disorders continue to be a significant problem. In efforts to understand and alleviate neurocognitive deficits associated with HIV, we used an accelerated simian immunodeficiency virus (SIV macaque model of NeuroAIDS to test whether minocycline is neuroprotective against lentiviral-induced neuronal injury. METHODOLOGY/PRINCIPAL FINDINGS: Eleven rhesus macaques were infected with SIV, depleted of CD8+ lymphocytes, and studied until eight weeks post inoculation (wpi. Seven animals received daily minocycline orally beginning at 4 wpi. Neuronal integrity was monitored in vivo by proton magnetic resonance spectroscopy and post-mortem by immunohistochemistry for synaptophysin (SYN, microtubule-associated protein 2 (MAP2, and neuronal counts. Astrogliosis and microglial activation were quantified by measuring glial fibrillary acidic protein (GFAP and ionized calcium binding adaptor molecule 1 (IBA-1, respectively. SIV infection followed by CD8+ cell depletion induced a progressive decline in neuronal integrity evidenced by declining N-acetylaspartate/creatine (NAA/Cr, which was arrested with minocycline treatment. The recovery of this ratio was due to increases in NAA, indicating neuronal recovery, and decreases in Cr, likely reflecting downregulation of glial cell activation. SYN, MAP2, and neuronal counts were found to be higher in minocycline-treated animals compared to untreated animals while GFAP and IBA-1 expression were decreased compared to controls. CSF and plasma viral loads were lower in MN-treated animals. CONCLUSIONS/SIGNIFICANCE: In conclusion, oral minocycline alleviates neuronal damage induced by the AIDS virus.

  19. 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.

  20. The establishment of macaque models of temporal lobe epilepsy%恒河猴颞叶癫痫模型的建立

    Institute of Scientific and Technical Information of China (English)

    陈宁; 孟凡刚; 张建国; 张凯; 刘焕光; 孟大伟; 刘崇; 葛燕

    2013-01-01

    目的 应用立体定向方法单侧海马内注射海人酸,建立恒河猴颞叶癫痫模型,并评价其生物学特性.方法 通过立体定向手术,恒河猴右侧海马注射海人酸,观察恒河猴行为学、神经电生理、影像学、组织病理及超微结构改变.结果 海人酸注射后恒河猴出现典型的颞叶癫痫发作表现,脑电图表现为棘波、慢波、棘慢波、尖波发放.MRI、MRS可见海马硬化的表现,组织学标本显示颞角扩大、海马硬化,HE染色可见神经元缺失、胶质细胞增生、瘢痕萎缩,电镜显示神经元固缩、血脑屏障破坏、星形细胞肿胀、细胞器受损.结论 立体定向单侧注入海人酸后恒河猴癫痫发作明显,其行为学、神经电生理、影像学、神经病理改变符合颞叶内侧型癫痫表现,可作为癫痫模型.%Objective To establish the animal model of temporal lobe epilepsy in macaques and to observe the changes of biological characteristics.Methods Kainic acid (KA) was injected into the right intra-hippocampus of macaques with the stereotacic technique.Video recording,iconology,hisopathology,and ultrastructural changes of the macaques were observed to evaluate the biological characteristics.Electrocorticography (EcoG)was used to detect the electrophysiological changes.Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS)were performed.Then macaques were sacrificed and brains were removed for ultrastructural examination using electron microscopes after 3 months post-injection.Results Typical seizures were observed in the models.Epileptic discharge,such as spike,slow,spike-slow,and sharp appeared in electroencephalograms (EEG).Hippocampal sclerosis could be found by MRI and MRS.HE staining of samples from the macaques injected with KA showed neuronal loss,proliferation of glial cells,formation of glial scar,and hippocampal atrophy.Electron microscopic analysis of hippocampal tissues revealed pyknosis of neurons

  1. New, More Authentic Model for AIDS Will Accelerate Studies | Poster

    Science.gov (United States)

    By Frank Blanchard, Staff Writer, and Jeff Lifson, Guest Writer Researchers are working to develop a more authentic animal model of human immunodeficiency virus (HIV) infection and AIDS that is expected to speed up studies of experimental treatments and vaccines.

  2. Modelling AIDS epidemic and treatment with difference equations

    Directory of Open Access Journals (Sweden)

    Ramani A

    2004-01-01

    Full Text Available We propose two models for the description of the dynamics of an AIDS epidemic and of the effect of a combined-drugs AIDS treatment based on difference equations. We show that our interacting population model, despite its extreme simplicity, describes adequately the evolution of an AIDS epidemic. A cellular-automaton analogue of the discrete system of equations is presented as well. In the case of drug treatment, we identify two different regimes corresponding to efficient and inefficient medication. The effect of the discreteness of the equations is also studied.

  3. Modelling AIDS epidemic and treatment with difference equations

    Directory of Open Access Journals (Sweden)

    A. S. Carstea

    2004-07-01

    Full Text Available We propose two models for the description of the dynamics of an AIDS epidemic and of the effect of a combined-drugs AIDS treatment based on difference equations. We show that our interacting population model, despite its extreme simplicity, describes adequately the evolution of an AIDS epidemic. A cellular-automaton analogue of the discrete system of equations is presented as well. In the case of drug treatment, we identify two different regimes corresponding to efficient and inefficient medication. The effect of the discreteness of the equations is also studied.

  4. Deleterious impact of feto-maternal MHC compatibility on the success of pregnancy in a macaque model.

    Science.gov (United States)

    Aarnink, Alice; Mee, Edward T; Savy, Nicolas; Congy-Jolivet, Nicolas; Rose, Nicola J; Blancher, Antoine

    2014-02-01

    The impact of feto-maternal histocompatibility on reproduction has inspired long-lasting debates. However, after the review of numerous articles, the impact of HLA allele sharing within couples on fecundity remains questionable. We decided to explore the impact of major histocompatibility complex (MHC) feto-maternal compatibility on reproduction in a cynomolgus macaque facility composed of animals of Mauritian descent. The Mauritian-derived macaque population presents a very restricted MHC polymorphism (only seven founding haplotypes) due to a strong founding bottleneck effect. The MHC polymorphism was investigated in 237 trios (male, female and offspring) using 17 microsatellite markers distributed across the MHC. Haplotypes were confirmed by segregation analysis. We evaluated the relative frequencies of MHC-compatible and MHC-semi-compatible offspring with the mothers. Among the 237 trios, we selected 42 trios for which the identity of the father is certain and for which the theoretical probabilities of fully compatible and semi-compatible offspring were equal. We found 11 offspring fully compatible and 31 offspring semi-compatible with their respective mother. The observed proportions were clearly outside the interval of confidence of 99 % and therefore most probably resulted from a selection of the semi-compatible offspring during pregnancy. We concluded that MHC fully compatible cynomolgus macaque offspring have a selective survival disadvantage in comparison with offspring inheriting a paternal MHC haplotype differing from maternal haplotypes.

  5. Functional analysis of frequently expressed Chinese rhesus macaque MHC class I molecules Mamu-A1*02601 and Mamu-B*08301 reveals HLA-A2 and HLA-A3 supertypic specificities

    DEFF Research Database (Denmark)

    Southwood, Scott; Solomon, Christopher; Hoof, Ilka

    2011-01-01

    The Simian immunodeficiency virus (SIV)-infected Indian rhesus macaque (Macaca mulatta) is the most established model of HIV infection and AIDS-related research, despite the potential that macaques of Chinese origin is a more relevant model. Ongoing efforts to further characterize the Chinese...... rhesus macaques’ major histocompatibility complex (MHC) for composition and function should facilitate greater utilization of the species. Previous studies have demonstrated that Chinese-origin M. mulatta (Mamu) class I alleles are more polymorphic than their Indian counterparts, perhaps inferring...... a model more representative of human MHC, human leukocyte antigen (HLA). Furthermore, the Chinese rhesus macaque class I allele Mamu-A1*02201, the most frequent allele thus far identified, has recently been characterized and shown to be an HLA-B7 supertype analog, the most frequent supertype in human...

  6. Can we spend our way out of the AIDS epidemic? A world halting AIDS model

    Science.gov (United States)

    2009-01-01

    Background There has been a sudden increase in the amount of money donors are willing to spend on the worldwide HIV/AIDS epidemic. Present plans are to hold most of the money in reserve and spend it slowly. However, rapid spending may be the best strategy for halting this disease. Methods We develop a mathematical model that predicts eradication or persistence of HIV/AIDS on a world scale. Dividing the world into regions (continents, countries etc), we develop a linear differential equation model of infectives which has the same eradication properties as more complex models. Results We show that, even if HIV/AIDS can be eradicated in each region independently, travel/immigration of infectives could still sustain the epidemic. We use a continent-level example to demonstrate that eradication is possible if preventive intervention methods (such as condoms or education) reduced the infection rate to two fifths of what it is currently. We show that, for HIV/AIDS to be eradicated within five years, the total cost would be ≈ $63 billion, which is within the existing $60 billion (plus interest) amount raised by the donor community. However, if this action is spread over a twenty year period, as currently planned, then eradication is no longer possible, due to population growth, and the costs would exceed $90 billion. Conclusion Eradication of AIDS is feasible, using the tools that we have currently to hand, but action needs to occur immediately. If not, then HIV/AIDS will race beyond our ability to afford it. PMID:19922685

  7. Comparing acceleration and speed tuning in macaque MT: physiology and modeling.

    Science.gov (United States)

    Price, N S C; Ono, S; Mustari, M J; Ibbotson, M R

    2005-11-01

    Studies of individual neurons in area MT have traditionally investigated their sensitivity to constant speeds. We investigated acceleration sensitivity in MT neurons by comparing their responses to constant steps and linear ramps in stimulus speed. Speed ramps constituted constant accelerations and decelerations between 0 and 240 degrees /s. Our results suggest that MT neurons do not have explicit acceleration sensitivity, although speed changes affected their responses in three main ways. First, accelerations typically evoked higher responses than the corresponding deceleration rate at all rates tested. We show that this can be explained by adaptation mechanisms rather than differential processing of positive and negative speed gradients. Second, we inferred a cell's preferred speed from the responses to speed ramps by finding the stimulus speed at the latency-adjusted time when response amplitude peaked. In most cells, the preferred speeds inferred from deceleration were higher than those for accelerations of the same rate or from steps in stimulus speed. Third, neuron responses to speed ramps were not well predicted by the transient or sustained responses to steps in stimulus speed. Based on these findings, we developed a model incorporating adaptation and a neuron's speed tuning that predicted the higher inferred speeds and lower spike rates for deceleration responses compared with acceleration responses. This model did not predict acceleration-specific responses, in accordance with the lack of acceleration sensitivity in the neurons. The outputs of this single-cell model were passed to a population-vector-based model used to estimate stimulus speed and acceleration. We show that such a model can accurately estimate relative speed and acceleration using information from the population of neurons in area MT.

  8. 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

  9. Computational modelling of the impact of AIDS on business.

    Science.gov (United States)

    Matthews, Alan P

    2007-07-01

    An overview of computational modelling of the impact of AIDS on business in South Africa, with a detailed description of the AIDS Projection Model (APM) for companies, developed by the author, and suggestions for further work. Computational modelling of the impact of AIDS on business in South Africa requires modelling of the epidemic as a whole, and of its impact on a company. This paper gives an overview of epidemiological modelling, with an introduction to the Actuarial Society of South Africa (ASSA) model, the most widely used such model for South Africa. The APM produces projections of HIV prevalence, new infections, and AIDS mortality on a company, based on the anonymous HIV testing of company employees, and projections from the ASSA model. A smoothed statistical model of the prevalence test data is computed, and then the ASSA model projection for each category of employees is adjusted so that it matches the measured prevalence in the year of testing. FURTHER WORK: Further techniques that could be developed are microsimulation (representing individuals in the computer), scenario planning for testing strategies, and models for the business environment, such as models of entire sectors, and mapping of HIV prevalence in time and space, based on workplace and community data.

  10. Tracking the Emergence of Host-Specific Simian Immunodeficiency Virus env and nef Populations Reveals nef Early Adaptation and Convergent Evolution in Brain of Naturally Progressing Rhesus Macaques.

    Science.gov (United States)

    Lamers, Susanna L; Nolan, David J; Rife, Brittany D; Fogel, Gary B; McGrath, Michael S; Burdo, Tricia H; Autissier, Patrick; Williams, Kenneth C; Goodenow, Maureen M; Salemi, Marco

    2015-08-01

    While a clear understanding of the events leading to successful establishment of host-specific viral populations and productive infection in the central nervous system (CNS) has not yet been reached, the simian immunodeficiency virus (SIV)-infected rhesus macaque provides a powerful model for the study of human immunodeficiency virus (HIV) intrahost evolution and neuropathogenesis. The evolution of the gp120 and nef genes, which encode two key proteins required for the establishment and maintenance of infection, was assessed in macaques that were intravenously inoculated with the same viral swarm and allowed to naturally progress to simian AIDS and potential SIV-associated encephalitis (SIVE). Longitudinal plasma samples and immune markers were monitored until terminal illness. Single-genome sequencing was employed to amplify full-length env through nef transcripts from plasma over time and from brain tissues at necropsy. nef sequences diverged from the founder virus faster than gp120 diverged. Host-specific sequence populations were detected in nef (~92 days) before they were detected in gp120 (~182 days). At necropsy, similar brain nef sequences were found in different macaques, indicating convergent evolution, while gp120 brain sequences remained largely host specific. Molecular clock and selection analyses showed weaker clock-like behavior and stronger selection pressure in nef than in gp120, with the strongest nef selection in the macaque with SIVE. Rapid nef diversification, occurring prior to gp120 diversification, indicates that early adaptation of nef in the new host is essential for successful infection. Moreover, the convergent evolution of nef sequences in the CNS suggests a significant role for nef in establishing neurotropic strains. The SIV-infected rhesus macaque model closely resembles HIV-1 immunopathogenesis, neuropathogenesis, and disease progression in humans. Macaques were intravenously infected with identical viral swarms to investigate

  11. Waveguide model of the hearing aid earmold system

    Directory of Open Access Journals (Sweden)

    Kostek Bozena

    2006-05-01

    Full Text Available Abstract Background The earmold system of the Behind-The-Ear hearing aid is an acoustic system that modifies the spectrum of the propagated sound waves. Improper selection of the earmold system may result in deterioration of sound quality and speech intelligibility. Computer modeling methods may be useful in the process of hearing aid fitting, allowing physician to examine various earmold system configurations and choose the optimum one for the hearing aid user. Methods In this paper, a computer model adequate for this task is proposed. This model is based on the waveguide modeling method. The waveguide model simulates the propagation of sound waves in the system of cylindrical tubes. Frequency response of the hearing aid receiver is simulated in the model and the influence of the ear canal and the eardrum on the earmold system is taken into account. The model parameters are easily calculated from parameters of a physical hearing aid system. Transfer function of the model is calculated and frequency response plots are obtained using the Matlab system. Results The frequency response plots of the earmold model were compared to the measurement plots of the corresponding physical earmold systems. The same changes in frequency responses caused by modification of length or diameter of a selected waveguide section, are observed in both measurement data of a real earmold system and in computed model responses. Conclusion Comparison of model responses obtained for various sets of parameters with measurement data proved that the proposed model accurately simulates the real earmold system and the developed model may be used to construct a computer system assisting the physician who performs earmold system fitting.

  12. Pathological findings and diagnostic implications of a rhesus macaque (Macacca mulatta) model of aerosol exposure to Burkholderia mallei (glanders).

    Science.gov (United States)

    Yingst, Samuel L; Facemire, Paul; Chuvala, Lara; Norwood, David; Wolcott, Mark; Huzella, Louis

    2015-06-01

    Burkholderia mallei is a Gram-negative bacillus that causes a pneumonic disease known as glanders in equids and humans, and a lymphatic infection known as farcy, primarily in equids. With the potential to infect humans by the respiratory route, aerosol exposure can result in severe, occasionally fatal, pneumonia. Today, glanders infections in humans are rare, likely due to less frequent contact with infected equids than in the past. Acutely ill humans often have non-specific clinical signs and in order to diagnose cases, especially in scenarios of multiple cases in an unexpected setting, rapid diagnostics for B. mallei may be critical. The pathogenesis of acute glanders in the rhesus macaque (Macaca mulatta) was studied as an initial effort to improve diagnostic methods. In the study described here, the diagnostic techniques of PCR, culture and histopathology were compared. The results indicated that PCR may provide rapid, non-invasive diagnosis of glanders in some cases. As expected, PCR results were positive in lung tissue in 11/12 acutely infected rhesus macaques, but more importantly in terms of diagnostic algorithm development, PCR results were frequently positive in non-invasive samples such as broncho-alveolar lavage or nasal swabs (7/12) and occasionally in blood (3/12). However, conventional bacterial culture failed to recover bacteria in many of these samples. The study showed that the clinical presentation of aerosol-exposed rhesus macaques is similar to descriptions of human glanders and that PCR has potential for rapid diagnosis of outbreaks, if not individual cases.

  13. Gene targeting in adult rhesus macaque fibroblasts

    Directory of Open Access Journals (Sweden)

    Wolf Don P

    2008-03-01

    Full Text Available Abstract Background Gene targeting in nonhuman primates has the potential to produce critical animal models for translational studies related to human diseases. Successful gene targeting in fibroblasts followed by somatic cell nuclear transfer (SCNT has been achieved in several species of large mammals but not yet in primates. Our goal was to establish the protocols necessary to achieve gene targeting in primary culture of adult rhesus macaque fibroblasts as a first step in creating nonhuman primate models of genetic disease using nuclear transfer technology. Results A primary culture of adult male fibroblasts was transfected with hTERT to overcome senescence and allow long term in vitro manipulations. Successful gene targeting of the HPRT locus in rhesus macaques was achieved by electroporating S-phase synchronized cells with a construct containing a SV40 enhancer. Conclusion The cell lines reported here could be used for the production of null mutant rhesus macaque models of human genetic disease using SCNT technology. In addition, given the close evolutionary relationship and biological similarity between rhesus macaques and humans, the protocols described here may prove useful in the genetic engineering of human somatic cells.

  14. Computer-Aided Template for Model Reuse, Development and Maintenance

    DEFF Research Database (Denmark)

    Fedorova, Marina; Sin, Gürkan; Gani, Rafiqul

    2014-01-01

    A template-based approach for model development is presented in this work. Based on a model decomposition technique, the computer-aided template concept has been developed. This concept is implemented as a software tool , which provides a user-friendly interface for following the workflow steps, ...

  15. Tenofovir disoproxil fumarate intravaginal ring protects high-dose depot medroxyprogesterone acetate-treated macaques from multiple SHIV exposures.

    Science.gov (United States)

    Smith, James M; Srinivasan, Priya; Teller, Ryan S; Lo, Yungtai; Dinh, Chuong T; Kiser, Patrick F; Herold, Betsy C

    2015-01-01

    Preclinical HIV prevention models use either a single high-dose viral challenge in depot medroxyprogesterone acetate-treated macaques or repeated viral challenges in cycling macaques. We tested the efficacy of an intravaginal tenofovir disoproxil fumarate (TDF) ring in a model combining repeated 30-mg injections of depot medroxyprogesterone acetate every 6 weeks with vaginal viral challenges weekly for 12 weeks. Twelve macaques were randomized to TDF or placebo rings. All placebo macaques became infected after a median of 2 exposures, whereas only 1 TDF macaque became infected at the eighth exposure (P = 0.0012). The TDF ring provides durable protection in a stringent challenge model.

  16. Mathematical modelling in the computer-aided process planning

    Science.gov (United States)

    Mitin, S.; Bochkarev, P.

    2016-04-01

    This paper presents new approaches to organization of manufacturing preparation and mathematical models related to development of the computer-aided multi product process planning (CAMPP) system. CAMPP system has some peculiarities compared to the existing computer-aided process planning (CAPP) systems: fully formalized developing of the machining operations; a capacity to create and to formalize the interrelationships among design, process planning and process implementation; procedures for consideration of the real manufacturing conditions. The paper describes the structure of the CAMPP system and shows the mathematical models and methods to formalize the design procedures.

  17. TRIMe7-CypA, an alternative splicing isoform of TRIMCyp in rhesus macaque, negatively modulates TRIM5α activity

    Energy Technology Data Exchange (ETDEWEB)

    Na, Lei [Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Tang, Yan-Dong [Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Biotechnology Institute of Southern Medical University, Guangzhou 510515 (China); Liu, Jian-Dong; Yu, Chang-Qing; Sun, Liu-Ke; Lin, Yue-Zhi; Wang, Xue-Feng [Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Wang, Xiaojun, E-mail: xjw@hvri.ac.cn [Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Zhou, Jian-Hua, E-mail: jianhua_uc@126.com [Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Harbin Pharmaceutical Group Biovaccine Company, Harbin 150069 (China)

    2014-04-04

    Highlights: • TRIMe7-CypA expresses in rhesus and pig-tailed, but not long-tailed macaques. • TRIMe7-CypA does not show the restriction to a HIV-GFP report virus in vitro. • It acts as a negative modulator to TRIM5α likely by competitive inhibition. - Abstract: The existence of innate, host-specific restriction factors is a major obstacle to the development of nonhuman primate models for AIDS studies, and TRIM5α is one of the most important of these restriction factors. In recent years, a TRIM5 chimeric gene that was retrotransposed by a cyclophilin A (CypA) cDNA was identified in certain macaque species. The TRIM5α-CypA fusion protein, TRIMCyp, which was expressed in these monkeys, had lost its restriction ability toward HIV-1. We previously found that TRIMe7-CypA, an alternative splicing isoform of the TRIMCyp transcripts, was expressed in pig-tailed and rhesus macaques but absent in long-tailed macaques. In this study, the anti-HIV-1 activity of TRIMe7-CypA in the rhesus macaque (RhTRIMe7-CypA) was investigated. The over-expression of RhTRIMe7-CypA in CrFK, HeLa and HEK293T cells did not restrict the infection or replication of an HIV-1-GFP reporter virus in these cells. As a positive control, rhesus (rh)TRIM5α strongly inhibited the reporter virus. Intriguingly, the anti-HIV-1 activity of RhTRIM5α was significantly reduced in a dose-dependent manner by the co-repression of RhTRIMe7-CypA. Our data indicate that although the RhTRIMe7-CypA isoform does not appear to restrict HIV-1, it may act as a negative modulator of TRIM family proteins, presumably by competitive inhibition.

  18. Extended cleavage specificity of the mast cell chymase from the crab-eating macaque (Macaca fascicularis): an interesting animal model for the analysis of the function of the human mast cell chymase.

    Science.gov (United States)

    Thorpe, Michael; Yu, Jing; Boinapally, Vamsi; Ahooghalandari, Parvin; Kervinen, Jukka; Garavilla, Lawrence de; Hellman, Lars

    2012-12-01

    Serine proteases are the major protein constituents within mast cell secretory granules. These proteases are subdivided into chymases and tryptases depending on their primary cleavage specificity. Here, we present the extended cleavage specificity of the macaque mast cell chymase and compare the specificity with human chymase (HC) and dog chymase (DC) that were produced in the same insect cell expression host. The macaque chymase (MC) shows almost identical characteristics as the HC, including both primary and extended cleavage specificities as well as sensitivity to protease inhibitors, whereas the DC differs in several of these characteristics. Although previous studies have shown that mouse mast cell protease-4 (mMCP-4) is similar in its hydrolytic specificity to the HC, mouse mast cells contain several related enzymes. Thus mice may not be the most appropriate model organism for studying HC activity and inhibition. Importantly, macaques express only one chymase and, as primates, are closely related to human general physiology. In addition, the human and macaque enzymes both cleave angiotensin I (Ang I) in the same way, generating primarily angiotensin II (Ang II) and they do not further degrade the peptide like most rodent enzymes do. Both enzymes also cleave two additional potential in vivo substrates, fibronectin and secretory leukocyte protease inhibitor (SLPI) in a similar way. Given the fact that both HC and MC are encoded by a single gene with high sequence homology and that many physiological processes are similar between these species, the macaque may be a very interesting model to study the physiological role of the chymase and to determine the potency and potential side-effects of various chymase inhibitors designed for therapeutic human use.

  19. The Actuarial Society of South Africa AIDS model.

    Science.gov (United States)

    1997-01-01

    The AIDS Committee of the Actuarial Society of South Africa has developed a demographic model to allow researchers to project the impact of HIV and AIDS in South Africa. The model is available for use as a projection tool rather than to endorse a given projected scenario as being representative. It is very flexible and can be adapted to suit different purposes by anyone with a working knowledge of Microsoft Excel. The need for a model, calibration of the model, the lack of allowance in the model for racial and cultural heterogeneity in the underlying population, and default scenario projections are discussed. The model is available free of charge via E-mail and on the worldwide web at the following respective addresses: awhitelo@oldmutual.com and http://www.und.ac.za/und/eco/eru/eru.htm.

  20. Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia

    Science.gov (United States)

    Shingai, Masashi; Nishimura, Yoshiaki; Klein, Florian; Mouquet, Hugo; Donau, Olivia K.; Plishka, Ronald; Buckler-White, Alicia; Seaman, Michael; Piatak, Michael; Lifson, Jeffrey D.; Dimitrov, Dimiter; Nussenzweig, Michel C.; Martin, Malcolm A.

    2013-11-01

    Neutralizing antibodies can confer immunity to primate lentiviruses by blocking infection in macaque models of AIDS. However, earlier studies of anti-human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies administered to infected individuals or humanized mice reported poor control of virus replication and the rapid emergence of resistant variants. A new generation of anti-HIV-1 monoclonal antibodies, possessing extraordinary potency and breadth of neutralizing activity, has recently been isolated from infected individuals. These neutralizing antibodies target different regions of the HIV-1 envelope glycoprotein including the CD4-binding site, glycans located in the V1/V2, V3 and V4 regions, and the membrane proximal external region of gp41 (refs 9, 10, 11, 12, 13, 14). Here we have examined two of the new antibodies, directed to the CD4-binding site and the V3 region (3BNC117 and 10-1074, respectively), for their ability to block infection and suppress viraemia in macaques infected with the R5 tropic simian-human immunodeficiency virus (SHIV)-AD8, which emulates many of the pathogenic and immunogenic properties of HIV-1 during infections of rhesus macaques. Either antibody alone can potently block virus acquisition. When administered individually to recently infected macaques, the 10-1074 antibody caused a rapid decline in virus load to undetectable levels for 4-7days, followed by virus rebound during which neutralization-resistant variants became detectable. When administered together, a single treatment rapidly suppressed plasma viraemia for 3-5weeks in some long-term chronically SHIV-infected animals with low CD4+ T-cell levels. A second cycle of anti-HIV-1 monoclonal antibody therapy, administered to two previously treated animals, successfully controlled virus rebound. These results indicate that immunotherapy or a combination of immunotherapy plus conventional antiretroviral drugs might be useful as a treatment for chronically HIV-1-infected

  1. Systematic Methods and Tools for Computer Aided Modelling

    DEFF Research Database (Denmark)

    Fedorova, Marina

    -friendly system, which will make the model development process easier and faster and provide the way for unified and consistent model documentation. The modeller can use the template for their specific problem or to extend and/or adopt a model. This is based on the idea of model reuse, which emphasizes the use...... and processes can be faster, cheaper and very efficient. The developed modelling framework involves five main elements: 1) a modelling tool, that includes algorithms for model generation; 2) a template library, which provides building blocks for the templates (generic models previously developed); 3) computer...... aided methods and tools, that include procedures to perform model translation, model analysis, model verification/validation, model solution and model documentation; 4) model transfer – export/import to/from other application for further extension and application – several types of formats, such as XML...

  2. Molecular ABO phenotyping in cynomolgus macaques using real-time quantitative PCR.

    Science.gov (United States)

    Premasuthan, A; Ng, J; Kanthaswamy, S; Trask, J S; Houghton, P; Farkas, T; Sestak, K; Smith, D G

    2012-10-01

    Macaques are commonly used in biomedical research as animal models of human disease. The ABO phenotype of donors and recipients plays an important role in the success of transplantation and stem cell research of both human and macaque tissue. Traditional serological methods for ABO phenotyping can be time consuming, provide ambiguous results and/or require tissue that is unavailable or unsuitable. We developed a novel method to detect the A, B, and AB phenotypes of macaques using real-time quantitative polymerase chain reaction. This method enables the simple and rapid screening of these phenotypes in macaques without the need for fresh blood or saliva. This study reports the distribution of the A, B, and AB phenotypes of captive cynomolgus macaques that, while regionally variable, closely resembles that of rhesus macaques. Blood group B, as in rhesus macaques, predominates in cynomolgus macaques and its frequency distribution leads to a probability of major incompatibility of 41%. No silencing mutations have been identified in exon 6 or 7 in macaques that could be responsible for the O phenotype, that, although rare, have been reported. The excess homozygosity of rhesus and cynomolgus macaque genotypes in this study, that assumes the absence of the O allele, suggests the possibility of some mechanism preventing the expression of the A and B transferases.

  3. Global Stability for a HIV/AIDS Model

    OpenAIRE

    Silva, Cristiana J.; Torres, Delfim F. M.

    2017-01-01

    We investigate global stability properties of a HIV/AIDS population model with constant recruitment rate, mass action incidence, and variable population size. Existence and uniqueness results for disease-free and endemic equilibrium points are proved. Global stability of the equilibria is obtained through Lyapunov's direct method and LaSalle's invariance principle.

  4. Modelling the Spread of HIV/AIDS Epidemic

    Institute of Scientific and Technical Information of China (English)

    Huang Qing-dao

    2013-01-01

    In this paper, a deterministic mathematical model for the spread of HIV/AIDS in a variable size population through horizontal transmission is considered. The existence of a threshold parameter, the basic reproduction number, is established, and the stability of both the disease-free equilibrium and the endemic equilibrium is discussed in terms of R0.

  5. Assessment and improvement of Indian-origin rhesus macaque and Mauritian-origin cynomolgus macaque genome annotations using deep transcriptome sequencing data

    Science.gov (United States)

    Peng, Xinxia; Pipes, Lenore; Xiong, Hao; Green, Richard R.; Jones, Daniel C.; Ruzzo, Walter L.; Schroth, Gary P.; Mason, Christopher E.; Palermo, Robert E.; Katze, Michael G.

    2014-01-01

    Background The genome annotations of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques, two of the most common nonhuman primate animal models, are limited. Methods We analyzed large-scale macaque RNA-based next-generation sequencing (RNAseq) data to identify un-annotated macaque transcripts. Results For both macaque species, we uncovered thousands of novel isoforms for annotated genes and thousands of un-annotated intergenic transcripts enriched with non-coding RNAs. We also identified thousands of transcript sequences which are partially or completely ‘missing’ from current macaque genome assemblies. We showed that many newly identified transcripts were differentially expressed during SIV infection of rhesus macaques or during Ebola virus infection of cynomolgus macaques. Conclusions For two important macaque species, we uncovered thousands of novel isoforms and un-annotated intergenic transcripts including coding and non-coding RNAs, polyadenylated and non-polyadenylated transcripts. This resource will greatly improve future macaque studies, as demonstrated by their applications in infectious disease studies. PMID:24810475

  6. Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model

    Directory of Open Access Journals (Sweden)

    Page Mark

    2012-07-01

    Full Text Available Abstract Background Current data suggest that an efficacious human immunodeficiency virus type 1 (HIV-1 vaccine should elicit both adaptive humoral and cell mediated immune responses. Such a vaccine will also need to protect against infection from a range of heterologous viral variants. Here we have developed a simian-human immunodeficiency virus (SHIV based model in cynomolgus macaques to investigate the breadth of protection conferred by HIV-1W61D recombinant gp120 vaccination against SHIVsbg and SHIVSF33 challenge, and to identify correlates of protection. Results High titres of anti-envelope antibodies were detected in all vaccinees. The antibodies reacted with both the homologous HIV-1W61D and heterologous HIV-1IIIB envelope rgp120 which has an identical sequence to the SHIVsbg challenge virus. Significant titres of virus neutralising antibodies were detected against SHIVW61D expressing an envelope homologous with the vaccine, but only limited cross neutralisation against SHIVsbg, SHIV-4 and SHIVSF33 was observed. Protection against SHIVsbg infection was observed in vaccinated animals but none was observed against SHIVSF33 challenge. Transfer of immune sera from vaccinated macaques to naive recipients did not confer protection against SHIVsbg challenge. In a follow-up study, T cell proliferative responses detected after immunisation with the same vaccine against a single peptide present in the second conserved region 2 of HIV-1 W61D and HIV-1 IIIB gp120, but not SF33 gp120. Conclusions Following extended vaccination with a HIV-1 rgp120 vaccine, protection was observed against heterologous virus challenge with SHIVsbg, but not SHIVSF33. Protection did not correlate with serological responses generated by vaccination, but might be associated with T cell proliferative responses against an epitope in the second constant region of HIV-1 gp120. Broader protection may be obtained with recombinant HIV-1 envelope based vaccines formulated with

  7. A model for HIV/AIDS pandemic with optimal control

    Science.gov (United States)

    Sule, Amiru; Abdullah, Farah Aini

    2015-05-01

    Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is pandemic. It has affected nearly 60 million people since the detection of the disease in 1981 to date. In this paper basic deterministic HIV/AIDS model with mass action incidence function are developed. Stability analysis is carried out. And the disease free equilibrium of the basic model was found to be locally asymptotically stable whenever the threshold parameter (RO) value is less than one, and unstable otherwise. The model is extended by introducing two optimal control strategies namely, CD4 counts and treatment for the infective using optimal control theory. Numerical simulation was carried out in order to illustrate the analytic results.

  8. MaqFACS (Macaque Facial Action Coding System) can be used to document facial movements in Barbary macaques (Macaca sylvanus).

    Science.gov (United States)

    Julle-Danière, Églantine; Micheletta, Jérôme; Whitehouse, Jamie; Joly, Marine; Gass, Carolin; Burrows, Anne M; Waller, Bridget M

    2015-01-01

    Human and non-human primates exhibit facial movements or displays to communicate with one another. The evolution of form and function of those displays could be better understood through multispecies comparisons. Anatomically based coding systems (Facial Action Coding Systems: FACS) are developed to enable such comparisons because they are standardized and systematic and aid identification of homologous expressions underpinned by similar muscle contractions. To date, FACS has been developed for humans, and subsequently modified for chimpanzees, rhesus macaques, orangutans, hylobatids, dogs, and cats. Here, we wanted to test whether the MaqFACS system developed in rhesus macaques (Macaca mulatta) could be used to code facial movements in Barbary macaques (M. sylvanus), a species phylogenetically close to the rhesus macaques. The findings show that the facial movement capacity of Barbary macaques can be reliably coded using the MaqFACS. We found differences in use and form of some movements, most likely due to specializations in the communicative repertoire of each species, rather than morphological differences.

  9. Efficient Use of Preisach Hysteresis Model in Computer Aided Design

    Directory of Open Access Journals (Sweden)

    IONITA, V.

    2013-05-01

    Full Text Available The paper presents a practical detailed analysis regarding the use of the classical Preisach hysteresis model, covering all the steps, from measuring the necessary data for the model identification to the implementation in a software code for Computer Aided Design (CAD in Electrical Engineering. An efficient numerical method is proposed and the hysteresis modeling accuracy is tested on magnetic recording materials. The procedure includes the correction of the experimental data, which are used for the hysteresis model identification, taking into account the demagnetizing effect for the sample that is measured in an open-circuit device (a vibrating sample magnetometer.

  10. A mathematical model of the spread of the AIDS virus

    Energy Technology Data Exchange (ETDEWEB)

    Hyman, J.M.; Stanley, E.A.

    1987-01-01

    A mathematical computer model of the spread of the AIDS epidemic in the US is being developed at Los Alamos National Laboratory. This model predicts the spreading of the HIV infection, and subsequent development of clinical AIDS in various population groups. These groups are chosen according to age, frequency and type of sexual contact, population density, and region of the country. Type of sexual contact includes not only the heterosexual, homosexual differentiation but also repeated contacts with such primary partners as spouses. In conjunction with the computer model, we are developing a database containing relevant information on the natural history of the viral infection, the prevalence of the infection and of clinical AIDS in the population, the distribution of people into sexual behavior groups as a function of age and information on interregional contacts. The effects of variable infectiousness and sexual activity during the long period from infection to disease are found to have a major impact on the predictions of the model. 24 refs., 5 figs.

  11. Computer-Aided Modeling of Lipid Processing Technology

    DEFF Research Database (Denmark)

    Diaz Tovar, Carlos Axel

    2011-01-01

    are widely used for design, analysis, and optimization of processes in the chemical and petrochemical industries. These computer-aided tools have helped the chemical industry to evolve beyond commodities toward specialty chemicals and ‘consumer oriented chemicals based products’. Unfortunately...... this is not the case for the edible oil and biodiesel industries. The oleochemical industry lags behind the chemical industry in terms of thermophysical property modeling and development of computational tools suitable for the design/analysis, and optimization of lipid-related processes. The aim of this work has been...... increase along with growing interest in biofuels, the oleochemical industry faces in the upcoming years major challenges in terms of design and development of better products and more sustainable processes to make them. Computer-aided methods and tools for process synthesis, modeling and simulation...

  12. Color vision test for dichromatic and trichromatic macaque monkeys.

    Science.gov (United States)

    Koida, Kowa; Yokoi, Isao; Okazawa, Gouki; Mikami, Akichika; Widayati, Kanthi Arum; Miyachi, Shigehiro; Komatsu, Hidehiko

    2013-11-01

    Dichromacy is a color vision defect in which one of the three cone photoreceptors is absent. Individuals with dichromacy are called dichromats (or sometimes "color-blind"), and their color discrimination performance has contributed significantly to our understanding of color vision. Macaque monkeys, which normally have trichromatic color vision that is nearly identical to humans, have been used extensively in neurophysiological studies of color vision. In the present study we employed two tests, a pseudoisochromatic color discrimination test and a monochromatic light detection test, to compare the color vision of genetically identified dichromatic macaques (Macaca fascicularis) with that of normal trichromatic macaques. In the color discrimination test, dichromats could not discriminate colors along the protanopic confusion line, though trichromats could. In the light detection test, the relative thresholds for longer wavelength light were higher in the dichromats than the trichromats, indicating dichromats to be less sensitive to longer wavelength light. Because the dichromatic macaque is very rare, the present study provides valuable new information on the color vision behavior of dichromatic macaques, which may be a useful animal model of human dichromacy. The behavioral tests used in the present study have been previously used to characterize the color behaviors of trichromatic as well as dichromatic new world monkeys. The present results show that comparative studies of color vision employing similar tests may be feasible to examine the difference in color behaviors between trichromatic and dichromatic individuals, although the genetic mechanisms of trichromacy/dichromacy is quite different between new world monkeys and macaques.

  13. Computer-Aided Multiscale Modelling for Chemical Process Engineering

    DEFF Research Database (Denmark)

    Morales Rodriguez, Ricardo; Gani, Rafiqul

    2007-01-01

    T) for model translation, analysis and solution. The integration of ModDev, MoT and ICAS or any other external software or process simulator (using COM-Objects) permits the generation of different models and/or process configurations for purposes of simulation, design and analysis. Consequently, it is possible......Chemical processes are generally modeled through monoscale approaches, which, while not adequate, satisfy a useful role in product-process design. In this case, use of a multi-dimensional and multi-scale model-based approach has importance in product-process development. A computer-aided framework...... for model generation, analysis, solution and implementation is necessary for the development and application of the desired model-based approach for product-centric process design/analysis. This goal is achieved through the combination of a system for model development (ModDev), and a modelling tool (Mo...

  14. 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

  15. Macaques with Rapid Disease Progression and Simian Immunodeficiency Virus Encephalitis Have a Unique Cytokine Profile in Peripheral Lymphoid Tissues

    OpenAIRE

    2001-01-01

    The influence of host cytokine response on viral load, disease progression, and neurologic lesions was investigated in the simian immunodeficiency virus (SIV)-infected macaque model of AIDS. Cytokine gene expression (interleukin-1β [IL-1β], IL-2, IL-6, IL-10, gamma interferon [IFN-γ], and tumor necrosis factor alpha [TNF-α]) and viral loads were evaluated by semiquantitative reverse transcription-PCR in lymph nodes of 5 control animals and 28 animals infected with SIVmac251 at the terminal st...

  16. Towards Cognizant Hearing Aids: Modeling of Content, Affect and Attention

    DEFF Research Database (Denmark)

    Karadogan, Seliz

    Hearing aids improved significantly after the integration of advanced digital signal processing applications. This improvement will continue and evolve through obtaining intelligent, individualized hearing aids integrating top-down (knowledge-based) and bottom-up (signal-based) approaches by making....... Initially, a novel method for automatic speech recognition using binary features from binary masks, is discussed. The performance of binary features in terms of robustness to noise is compared with the ASR state of the art features, mel frequency cepstral coefficients. Secondly, human top-down auditory...... attention is studied. A computational top-down attention model is presented and behavioral experiments are carried out to investigate the role of top-down task driven attention in the cocktail party problem. Finally, automatic emotion recognition from speech is studied using a dimensional approach...

  17. Cynomolgus macaque (Macaca fascicularis) immunoglobulin heavy chain locus description.

    Science.gov (United States)

    Yu, Guo-Yun; Mate, Suzanne; Garcia, Karla; Ward, Michael D; Brueggemann, Ernst; Hall, Matthew; Kenny, Tara; Sanchez-Lockhart, Mariano; Lefranc, Marie-Paule; Palacios, Gustavo

    2016-07-01

    Cynomolgus macaques (Macaca fascicularis) have become an important animal model for biomedical research. In particular, it is the animal model of choice for the development of vaccine candidates associated with emerging dangerous pathogens. Despite their increasing importance as animal models, the cynomolgus macaque genome is not fully characterized, hindering molecular studies for this model. More importantly, the lack of knowledge about the immunoglobulin (IG) locus organization directly impacts the analysis of the humoral response in cynomolgus macaques. Recent advances in next generation sequencing (NGS) technologies to analyze IG repertoires open the opportunity to deeply characterize the humoral immune response. However, the IG locus organization for the animal is required to completely dissect IG repertoires. Here, we describe the localization and organization of the rearranging IG heavy (IGH) genes on chromosome 7 of the cynomolgus macaque draft genome. Our annotation comprises 108 functional genes which include 63 variable (IGHV), 38 diversity (IGHD), and 7 joining (IGHJ) genes. For validation, we provide RNA transcript data for most of the IGHV genes and all of the annotated IGHJ genes, as well as proteomic data to validate IGH constant genes. The description and annotation of the rearranging IGH genes for the cynomolgus macaques will significantly facilitate scientific research. This is particularly relevant to dissect the immune response during vaccination or infection with dangerous pathogens such as Ebola, Marburg and other emerging pathogens where non-human primate models play a significant role for countermeasure development.

  18. Inhalational Monkeypox Virus Infection in Cynomolgus Macaques

    Directory of Open Access Journals (Sweden)

    Roy eBarnewall

    2012-09-01

    Full Text Available An inhalation exposure system was characterized to deliver aerosolized monkeypox virus (MPXV, and a nonhuman primate (NHP inhalation monkeypox model was developed in cynomologus macaques. A head-only aerosol exposure system was characterized, and two sampling methods were evaluated: liquid impingement via an impinger and impaction via a gelatin filter. The aerosol concentrations obtained with the gelatin filter and impinger were virtually identical, indicating that either method is acceptable for sampling aerosols containing MPXV. The mass median aerodynamic diameter (MMAD was for individual aerosol tests in the aerosol system characterization and the NHP study ranged from 1.08 to 1.15 µm, indicating that the aerosol particles were of a sufficient size to reach the alveoli. Six cynomolgus macaques (four male and two female were used on study. The animals were aerosol exposed with MPXV and received doses between 2.51 x 104 to 9.28 x 105 plaque forming units (pfu inhaled. Four of the six animals died or were euthanized due to their moribund conditions. Both animals that received the lowest exposure doses survived to the end of the observation period. The inhalation LD50 was determined to be approximately 7.8 x 104 pfu inhaled. These data demonstrate that an inhalation MPXV infection model has been developed in the cynomolgus macaque with disease course and lethal dose similar to previously published data.

  19. Consumption of a Western-style diet during pregnancy impairs offspring islet vascularization in a Japanese macaque model.

    Science.gov (United States)

    Pound, Lynley D; Comstock, Sarah M; Grove, Kevin L

    2014-07-01

    Children exposed to a maternal Western-style diet in utero have an increased risk of developing type 2 diabetes. Understanding the mechanisms and an investigation of possible interventions are critical to reversing this phenomenon. We examined the impact of maternal Western-style diet consumption on the development of islet vascularization and innervation, both of which are critical to normal islet function, in fetal and juvenile offspring. Furthermore, we assessed whether improved dietary intake or resveratrol supplementation could ameliorate the harmful consequences of Western-style diet consumption during pregnancy. Adult female Japanese macaques were maintained on a control or Western-style diet for 4-7 yr. One cohort of dams was switched back onto a control diet, whereas another cohort received resveratrol supplementation throughout gestation. Pregnancies were terminated in the early third trimester by C-section, or offspring were born naturally and sent to necropsy at 1 yr of age. Western-style diet consumption resulted in impaired fetal islet capillary density and sympathetic islet innervation. Furthermore, this reduction in vascularization persisted in the juvenile offspring. This effect is independent of changes in the expression of key angiogenic markers. Diet reversal normalized islet vascularization to control offspring levels, whereas resveratrol supplementation caused a significant increase in capillary density above controls. These data provide a novel mechanism by which maternal Western-style diet consumption leads to increased susceptibility to type 2 diabetes in the offspring. Importantly, an improved maternal diet may mitigate these harmful effects. However, until the long-term consequences of increased vascularization can be determined, resveratrol use during pregnancy is not advised. Copyright © 2014 the American Physiological Society.

  20. Directed shift of vaginal microbiota induced by vaginal application of sucrose gel in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Kai-tao Hu

    2015-04-01

    Conclusions: Rhesus macaques can be used as animal models of bacterial vaginosis to develop drugs and test treatment efficacy. Furthermore, the topical application of sucrose gel induced the shifting of vaginal flora of rhesus macaques from a BV kind of flora to a lactobacilli-dominating flora.

  1. Using a Shape Model in the Design of Hearing Aids

    DEFF Research Database (Denmark)

    Paulsen, Rasmus Reinhold; Nielsen, Claus; Laugesen, Søren

    2004-01-01

    Today the design of custom completely-in-the-canal hearing aids is a manual process and therefore there is a variation in the quality of the finished hearing aids. Especially the placement of the so-called faceplate on the hearing aid strongly influences the size and shape of the hearing aid. Since...

  2. Permeability of blood-brain barrier in macaque model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson disease.

    Science.gov (United States)

    Thiollier, Thibaud; Wu, Caisheng; Contamin, Hugues; Li, Qin; Zhang, Jinlan; Bezard, Erwan

    2016-06-01

    Brain bioavailability of drugs developed to address central nervous system diseases is classically documented through cerebrospinal fluid collected in normal animals, i.e., through an approximation as there are fundamental differences between cerebrospinal fluid and tissue contents. The fact that disease might affect brain availability of drugs is almost never considered at this stage although several conditions are associated with blood-brain barrier damage. Building upon our expertise in Parkinson's disease translational research, the present study addressed this gap comparing plasma and cerebrospinal fluid bioavailability of l-3,4-dihydroxyphenylalanine, carbamazepine, quinidine, lovastatin, and simvastatin, in healthy and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated macaques, the gold standard model of Parkinson's disease. The drugs were selected based upon their differential transport across the blood-brain barrier. Interestingly, brain bioavailability of quinidine was decreased while others were unaffected. Pharmacokinetics and pharmacodynamics experiments of drugs addressing Parkinson's disease might thus be performed in healthy animals unless the drugs are known to interact with the organic cation transporter.

  3. Using a reflection model for modeling the dynamic feedback path of digital hearing aids

    DEFF Research Database (Denmark)

    Ma, Guilin; Gran, Fredrik; Jacobsen, Finn;

    2010-01-01

    Feedback whistling is one of the severe problems with hearing aids, especially in dynamic situations when the users hug, pick up a telephone, etc. This paper investigates the properties of the dynamic feedback paths of digital hearing aids and proposes a model based on a reflection assumption...... gain. The method is also extended to dual-microphone hearing aids to assess the possibility of relating the two dynamic feedback paths through the reflection model. However, it is found that in a complicated acoustic environment, the relation between the two feedback paths can be very intricate...

  4. Macroeconomic Issues in Foreign Aid

    DEFF Research Database (Denmark)

    Hjertholm, Peter; Laursen, Jytte; White, Howard

    foreign aid, macroeconomics of aid, gap models, aid fungibility, fiscal response models, foreign debt,......foreign aid, macroeconomics of aid, gap models, aid fungibility, fiscal response models, foreign debt,...

  5. Intermediate-term emotional bookkeeping is necessary for long-term reciprocal grooming partner preferences in an agent-based model of macaque groups

    Directory of Open Access Journals (Sweden)

    Ellen Evers

    2016-01-01

    Full Text Available Whether and how primates are able to maintain long-term affiliative relationships is still under debate. Emotional bookkeeping (EB, the partner-specific accumulation of emotional responses to earlier interactions, is a candidate mechanism that does not require high cognitive abilities. EB is difficult to study in real animals, due to the complexity of primate social life. Therefore, we developed an agent-based model based on macaque behavior, the EMO-model, that implements arousal and two emotional dimensions, anxiety-FEAR and satisfaction-LIKE, which regulate social behavior. To implement EB, model individuals assign dynamic LIKE attitudes towards their group members, integrating partner-specific emotional responses to earlier received grooming episodes. Two key parameters in the model were varied to explore their effects on long-term affiliative relationships: (1 the timeframe over which earlier affiliation is accumulated into the LIKE attitudes; and (2 the degree of partner selectivity. EB over short and long timeframes gave rise to low variation in LIKE attitudes, and grooming partner preferences were only maintained over one to two months. Only EB over intermediate-term timeframes resulted in enough variation in LIKE attitudes, which, in combination with high partner selectivity, enables individuals to differentiate between regular and incidental grooming partners. These specific settings resulted in a strong feedback between differentiated LIKE attitudes and the distribution of grooming, giving rise to strongly reciprocated partner preferences that could be maintained for longer periods, occasionally up to one or two years. Moreover, at these settings the individual’s internal, socio-emotional memory of earlier affiliative episodes (LIKE attitudes corresponded best to observable behavior (grooming partner preferences. In sum, our model suggests that intermediate-term LIKE dynamics and high partner selectivity seem most plausible for

  6. Policy Capturing with Local Models: The Application of the AID technique in Modeling Judgment

    Science.gov (United States)

    1972-12-01

    or coding phases have upon the derived policy modelo . Particularly important aspects of these subtasks include: 1) Initial identification and coding of...Applying AID4UT/AIDTRE in Policy Capturing: The experience gained thus far in applying AID4UT/AIDTREl to Policy Capturing is extensive in the sense ...that numerous models have been attempted and produced, but limited in the sense that these models were all for a particular decision process, except for

  7. Expression of the memory marker CD45RO on helper T cells in macaques.

    Directory of Open Access Journals (Sweden)

    Michael Valentine

    Full Text Available BACKGROUND: In humans it has been reported that a major site of the latent reservoir of HIV is within CD4+ T cells expressing the memory marker CD45RO, defined by the mAb UCHL1. There are conflicting reports regarding the expression of this antigen in macaques, the most relevant animal species for studying HIV pathogenesis and testing new therapies. There is now a major effort to eradicate HIV reservoirs and cure the infection. One approach is to eliminate subsets of cells housing the latent reservoir, using UCHL1 to target these cells. So that such studies may be performed in macaques, it is essential to determine expression of CD45RO. METHODS: We have used immunofluorescence and flow cytometry to study cell surface expression of CD45RO on lymphocytes from PBMC, lymphoid, and GI organs of rhesus, pigtailed, and cynomolgus macaques. Both direct and indirect immunofluorescence experiments were performed. FINDINGS: CD45RO is expressed on a subset of CD4+ lymphocytes of all pigtailed, a fraction of rhesus, and neither of the cynomolgus macaques studied. The binding of UCHL1 to macaque cells was of lower avidity than to human cells. This could be overcome by forming UCHL1 multimers. Directly conjugating fluors to UCHL1 can inhibit UCHL1 binding to macaque cells. Patterns of UCHL1 expression differ somewhat in macaques and humans, and from that of other memory markers often used in macaques. CONCLUSIONS: CD45RO, defined with mAb UCHL1, is well expressed on CD4+ cells in pigtailed macaques. Using tissues recovered from latently infected pigtailed macaques we are determining whether UCHL1, or other memory markers, can define the cellular locus of the reservoir. The low avidity of this interaction could limit the utility of UCHL1, in its conventional form, to eliminate cells in vivo and test this approach in macaque models of HIV infection.

  8. Evolution of Geometric Sensitivity Derivatives from Computer Aided Design Models

    Science.gov (United States)

    Jones, William T.; Lazzara, David; Haimes, Robert

    2010-01-01

    The generation of design parameter sensitivity derivatives is required for gradient-based optimization. Such sensitivity derivatives are elusive at best when working with geometry defined within the solid modeling context of Computer-Aided Design (CAD) systems. Solid modeling CAD systems are often proprietary and always complex, thereby necessitating ad hoc procedures to infer parameter sensitivity. A new perspective is presented that makes direct use of the hierarchical associativity of CAD features to trace their evolution and thereby track design parameter sensitivity. In contrast to ad hoc methods, this method provides a more concise procedure following the model design intent and determining the sensitivity of CAD geometry directly to its respective defining parameters.

  9. The Computer-Aided Analytic Process Model. Operations Handbook for the Analytic Process Model Demonstration Package

    Science.gov (United States)

    1986-01-01

    Research Note 86-06 THE COMPUTER-AIDED ANALYTIC PROCESS MODEL : OPERATIONS HANDBOOK FOR THE ANALYTIC PROCESS MODEL DE ONSTRATION PACKAGE Ronald G...ic Process Model ; Operations Handbook; Tutorial; Apple; Systems Taxonomy Mod--l; Training System; Bradl1ey infantry Fighting * Vehicle; BIFV...8217. . . . . . . .. . . . . . . . . . . . . . . . * - ~ . - - * m- .. . . . . . . item 20. Abstract -continued companion volume-- "The Analytic Process Model for

  10. Mathematical models of the AIDS epidemic: An historical perspective

    Energy Technology Data Exchange (ETDEWEB)

    Stanley, E.A.

    1988-01-01

    Researchers developing mathematical models of the spreading of HIV, the Human Immunodeficiency Virus that causes AIDS, hope to achieve a number of goals. These goals may be classified rather broadly into three categories: understanding, prediction, and control. Understanding which are the key biological and sociological processes spreading this epidemic and leading to the deaths of those infected will allow AIDS researchers to collect better data and to identify ways of slowing the epidemic. Predicting the groups at risk and future numbers of ill people will allow an appropriate allocation of health-care resources. Analysis and comparison of proposed control methods will point out unexpected consequences and allow a better design of these programs. The processes which lead to the spread of HIV are biologically and sociologically complex. Mathematical models allow us to organize our knowledge into a coherent picture and examine the logical consequences, therefore they have the potential to be extremely useful in the search to control this disease. 24 refs., 3 figs.

  11. Computer-aided modeling framework for efficient model development, analysis and identification

    DEFF Research Database (Denmark)

    Heitzig, Martina; Sin, Gürkan; Sales Cruz, Mauricio;

    2011-01-01

    branches; the first branch deals with single-scale model development while the second branch introduces features for multiscale model development to the methodology. In this paper, the emphasis is on single-scale model development and application part. The modeling framework and the supported stepwise......Model-based computer aided product-process engineering has attained increased importance in a number of industries, including pharmaceuticals, petrochemicals, fine chemicals, polymers, biotechnology, food, energy, and water. This trend is set to continue due to the substantial benefits computer......-aided methods introduce. The key prerequisite of computer-aided product-process engineering is however the availability of models of different types, forms, and application modes. The development of the models required for the systems under investigation tends to be a challenging and time-consuming task...

  12. Performance modeling of a feature-aided tracker

    Science.gov (United States)

    Goley, G. Steven; Nolan, Adam R.

    2012-06-01

    In order to provide actionable intelligence in a layered sensing paradigm, exploitation algorithms should produce a confidence estimate in addition to the inference variable. This article presents a methodology and results of one such algorithm for feature-aided tracking of vehicles in wide area motion imagery. To perform experiments a synthetic environment was developed, which provided explicit knowledge of ground truth, tracker prediction accuracy, and control of operating conditions. This synthetic environment leveraged physics-based modeling simulations to re-create both traffic flow, reflectance of vehicles, obscuration and shadowing. With the ability to control operating conditions as well as the availability of ground truth, several experiments were conducted to test both the tracker and expected performance. The results show that the performance model produces a meaningful estimate of the tracker performance over the subset of operating conditions.

  13. High Infection Rates for Adult Macaques after Intravaginal or Intrarectal Inoculation with Zika Virus

    Science.gov (United States)

    Nalca, Aysegul; Rossi, Franco D.; Miller, Lynn J.; Wiley, Michael R.; Perez-Sautu, Unai; Washington, Samuel C.; Norris, Sarah L.; Wollen-Roberts, Suzanne E.; Shamblin, Joshua D.; Kimmel, Adrienne E.; Bloomfield, Holly A.; Valdez, Stephanie M.; Sprague, Thomas R.; Principe, Lucia M.; Bellanca, Stephanie A.; Cinkovich, Stephanie S.; Lugo-Roman, Luis; Cazares, Lisa H.; Pratt, William D.; Palacios, Gustavo F.; Bavari, Sina; Pitt, M. Louise; Nasar, Farooq

    2017-01-01

    Unprotected sexual intercourse between persons residing in or traveling from regions with Zika virus transmission is a risk factor for infection. To model risk for infection after sexual intercourse, we inoculated rhesus and cynomolgus macaques with Zika virus by intravaginal or intrarectal routes. In macaques inoculated intravaginally, we detected viremia and virus RNA in 50% of macaques, followed by seroconversion. In macaques inoculated intrarectally, we detected viremia, virus RNA, or both, in 100% of both species, followed by seroconversion. The magnitude and duration of infectious virus in the blood of macaques suggest humans infected with Zika virus through sexual transmission will likely generate viremias sufficient to infect competent mosquito vectors. Our results indicate that transmission of Zika virus by sexual intercourse might serve as a virus maintenance mechanism in the absence of mosquito-to-human transmission and could increase the probability of establishment and spread of Zika virus in regions where this virus is not present. PMID:28548637

  14. AIDS policy modeling for the 21st century: an overview of key issues.

    Science.gov (United States)

    Rauner, M S; Brandeau, M L

    2001-09-01

    Decisions about HIV prevention and treatment programs are based on factors such as program costs and health benefits, social and ethical issues, and political considerations. AIDS policy models--that is, models that evaluate the monetary and non-monetary consequences of decisions about HIV/AIDS interventions--can play a role in helping policy makers make better decisions. This paper provides an overview of the key issues related to developing useful AIDS policy models. We highlight issues of importance for researchers in the field of AIDS policy modeling as well as for policy makers. These include geographic area, setting, target groups, interventions, affordability and effectiveness of interventions, type and time horizon of policy model, and type of economic analysis. This paper is not intended to be an exhaustive review of the AIDS policy modeling literature, although many papers from the literature are discussed as examples; rather, we aim to convey the composition, achievements, and challenges of AIDS policy modeling.

  15. Rhesus macaques (Macaca mulatta are natural hosts of specific Staphylococcus aureus lineages.

    Directory of Open Access Journals (Sweden)

    Sanne van den Berg

    Full Text Available Currently, there is no animal model known that mimics natural nasal colonization by Staphylococcus aureus in humans. We investigated whether rhesus macaques are natural nasal carriers of S. aureus. Nasal swabs were taken from 731 macaques. S. aureus isolates were typed by pulsed-field gel electrophoresis (PFGE, spa repeat sequencing and multi-locus sequence typing (MLST, and compared with human strains. Furthermore, the isolates were characterized by several PCRs. Thirty-nine percent of 731 macaques were positive for S. aureus. In general, the macaque S. aureus isolates differed from human strains as they formed separate PFGE clusters, 50% of the isolates were untypeable by agr genotyping, 17 new spa types were identified, which all belonged to new sequence types (STs. Furthermore, 66% of macaque isolates were negative for all superantigen genes. To determine S. aureus nasal colonization, three nasal swabs from 48 duo-housed macaques were taken during a 5 month period. In addition, sera were analyzed for immunoglobulin G and A levels directed against 40 staphylococcal proteins using a bead-based flow cytometry technique. Nineteen percent of the animals were negative for S. aureus, and 17% were three times positive. S. aureus strains were easily exchanged between macaques. The antibody response was less pronounced in macaques compared to humans, and nasal carrier status was not associated with differences in serum anti-staphylococcal antibody levels. In conclusion, rhesus macaques are natural hosts of S. aureus, carrying host-specific lineages. Our data indicate that rhesus macaques are useful as an autologous model for studying S. aureus nasal colonization and infection prevention.

  16. Computer-Aided Modeling of Lipid Processing Technology

    DEFF Research Database (Denmark)

    Diaz Tovar, Carlos Axel

    2011-01-01

    the analysis, in terms of their design variables and their impact in the process behavior, of three lipid-related processes has been performed: the solvent recovery section of the extraction of crude soybean oil, the deodorization of palm oil, and the deacidification of soybean oil.......Vegetable oils and fats have an important role in human nutrition and in the chemical industry since they are a source of energy, fat-soluble vitamins, and now also in the production of renewable sources of energy. Nowadays as the consumer preferences for natural products and healthier foods...... increase along with growing interest in biofuels, the oleochemical industry faces in the upcoming years major challenges in terms of design and development of better products and more sustainable processes to make them. Computer-aided methods and tools for process synthesis, modeling and simulation...

  17. In vivo safety and persistence of endoribonuclease gene-transduced CD4+ T cells in cynomolgus macaques for HIV-1 gene therapy model.

    Directory of Open Access Journals (Sweden)

    Hideto Chono

    Full Text Available BACKGROUND: MazF is an endoribonuclease encoded by Escherichia coli that specifically cleaves the ACA sequence of mRNA. In our previous report, conditional expression of MazF in the HIV-1 LTR rendered CD4+ T lymphocytes resistant to HIV-1 replication. In this study, we examined the in vivo safety and persistence of MazF-transduced cynomolgus macaque CD4+ T cells infused into autologous monkeys. METHODOLOGY/PRINCIPAL FINDINGS: The in vivo persistence of the gene-modified CD4+ T cells in the peripheral blood was monitored for more than half a year using quantitative real-time PCR and flow cytometry, followed by experimental autopsy in order to examine the safety and distribution pattern of the infused cells in several organs. Although the levels of the MazF-transduced CD4+ T cells gradually decreased in the peripheral blood, they were clearly detected throughout the experimental period. Moreover, the infused cells were detected in the distal lymphoid tissues, such as several lymph nodes and the spleen. Histopathological analyses of tissues revealed that there were no lesions related to the infused gene modified cells. Antibodies against MazF were not detected. These data suggest the safety and the low immunogenicity of MazF-transduced CD4+ T cells. Finally, gene modified cells harvested from the monkey more than half a year post-infusion suppressed the replication of SHIV 89.6P. CONCLUSIONS/SIGNIFICANCE: The long-term persistence, safety and continuous HIV replication resistance of the mazF gene-modified CD4+ T cells in the non-human primate model suggests that autologous transplantation of mazF gene-modified cells is an attractive strategy for HIV gene therapy.

  18. Electric mine motor thermal models aiding design and setting thermal protections

    National Research Council Canada - National Science Library

    R Krok

    2012-01-01

      Electric mine motor thermal models aiding design and setting thermal protections The paper presents original modified thermal networks for calculations of the temperature field in induction mine...

  19. Computer-Aided Construction of Chemical Kinetic Models

    Energy Technology Data Exchange (ETDEWEB)

    Green, William H. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

    2014-12-31

    The combustion chemistry of even simple fuels can be extremely complex, involving hundreds or thousands of kinetically significant species. The most reasonable way to deal with this complexity is to use a computer not only to numerically solve the kinetic model, but also to construct the kinetic model in the first place. Because these large models contain so many numerical parameters (e.g. rate coefficients, thermochemistry) one never has sufficient data to uniquely determine them all experimentally. Instead one must work in “predictive” mode, using theoretical rather than experimental values for many of the numbers in the model, and as appropriate refining the most sensitive numbers through experiments. Predictive chemical kinetics is exactly what is needed for computer-aided design of combustion systems based on proposed alternative fuels, particularly for early assessment of the value and viability of proposed new fuels before those fuels are commercially available. This project was aimed at making accurate predictive chemical kinetics practical; this is a challenging goal which requires a range of science advances. The project spanned a wide range from quantum chemical calculations on individual molecules and elementary-step reactions, through the development of improved rate/thermo calculation procedures, the creation of algorithms and software for constructing and solving kinetic simulations, the invention of methods for model-reduction while maintaining error control, and finally comparisons with experiment. Many of the parameters in the models were derived from quantum chemistry calculations, and the models were compared with experimental data measured in our lab or in collaboration with others.

  20. Computer aided polymer design using multi-scale modelling

    Directory of Open Access Journals (Sweden)

    K. C. Satyanarayana

    2010-09-01

    Full Text Available The ability to predict the key physical and chemical properties of polymeric materials from their repeat-unit structure and chain-length architecture prior to synthesis is of great value for the design of polymer-based chemical products, with new functionalities and improved performance. Computer aided molecular design (CAMD methods can expedite the design process by establishing input-output relations between the type and number of functional groups in a polymer repeat unit and the desired macroscopic properties. A multi-scale model-based approach that combines a CAMD technique based on group contribution plus models for predicting polymer repeat unit properties with atomistic simulations for providing first-principles arrangements of the repeat units and for predictions of physical properties of the chosen candidate polymer structures, has been developed and tested for design of polymers with desired properties. A case study is used to highlight the main features of this multi-scale model-based approach for the design of a polymer-based product.

  1. Identification of an Enterocytozoon bieneusi-like microsporidian parasite in simian-immunodeficiency-virus-inoculated macaques with hepatobiliary disease.

    Science.gov (United States)

    Mansfield, K G; Carville, A; Shvetz, D; MacKey, J; Tzipori, S; Lackner, A A

    1997-04-01

    Enterocytozoon bieneusi is a common opportunistic pathogen of human patients with acquired immune deficiency syndrome (AIDS) causing significant morbidity and mortality. In a retrospective analysis utilizing conventional histochemical techniques, in situ hybridization, polymerase chain reaction, and ultrastructural examination, we identified 18 simian-immunodeficiency-virus-infected macaques (16 Macaca mulatta, 1 M. nemestrina, and 1 M. cyclopis) with Enterocytozoon infection of the hepatobiliary system and small intestine. The organisms were readily identified in the bile ducts and gall bladder by special stains and by in situ hybridization using a probe directed against the small subunit ribosomal RNA of human origin E. bieneusi. Infection of the biliary system was associated with a nonsuppurative and proliferative cholecystitis and choledochitis. Hepatic involvement was characterized by bridging portal fibrosis and nodular hepatocellular regeneration accompanied by marked bile ductular and septal duct hyperplasia. Ultrastructurally, all developmental stages of the organism were found in direct contact with the host cell cytoplasm; spores and sporoblasts contained a double layer of polar tubes. Sequencing of a 607-bp segment of the small subunit ribosomal RNA revealed 97 and 100% identity to two clones of small subunit ribosomal RNA derived from E. bieneusi of human origin. Extensive morphological and genetic similarities between the simian and human enterocytozoons suggest that experimentally infected macaques may serve as a useful model of microsporidial infection in AIDS.

  2. Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques.

    Directory of Open Access Journals (Sweden)

    Matthew T Aliota

    2016-12-01

    Full Text Available Zika virus (ZIKV; Flaviviridae, Flavivirus was declared a public health emergency of international concern by the World Health Organization (WHO in February 2016, because of the evidence linking infection with ZIKV to neurological complications, such as Guillain-Barre Syndrome in adults and congenital birth defects including microcephaly in the developing fetus. Because development of a ZIKV vaccine is a top research priority and because the genetic and antigenic variability of many RNA viruses limits the effectiveness of vaccines, assessing whether immunity elicited against one ZIKV strain is sufficient to confer broad protection against all ZIKV strains is critical. Recently, in vitro studies demonstrated that ZIKV likely circulates as a single serotype. Here, we demonstrate that immunity elicited by African lineage ZIKV protects rhesus macaques against subsequent infection with Asian lineage ZIKV.Using our recently developed rhesus macaque model of ZIKV infection, we report that the prototypical ZIKV strain MR766 productively infects macaques, and that immunity elicited by MR766 protects macaques against heterologous Asian ZIKV. Furthermore, using next generation deep sequencing, we found in vivo restoration of a putative N-linked glycosylation site upon replication in macaques that is absent in numerous MR766 strains that are widely being used by the research community. This reversion highlights the importance of carefully examining the sequence composition of all viral stocks as well as understanding how passage history may alter a virus from its original form.An effective ZIKV vaccine is needed to prevent infection-associated fetal abnormalities. Macaques whose immune responses were primed by infection with East African ZIKV were completely protected from detectable viremia when subsequently rechallenged with heterologous Asian ZIKV. Therefore, these data suggest that immunogen selection is unlikely to adversely affect the breadth of

  3. Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques

    Science.gov (United States)

    Newman, Christina M.; Mohr, Emma L.; Gellerup, Dane D.; Breitbach, Meghan E.; Buechler, Connor R.; Rasheed, Mustafa N.; Mohns, Mariel S.; Weiler, Andrea M.; Barry, Gabrielle L.; Weisgrau, Kim L.; Eudailey, Josh A.; Rakasz, Eva G.; Vosler, Logan J.; Post, Jennifer; Capuano, Saverio; Golos, Thaddeus G.; Permar, Sallie R.; Osorio, Jorge E.; Friedrich, Thomas C.; O’Connor, Shelby L.; O’Connor, David H.

    2016-01-01

    Background Zika virus (ZIKV; Flaviviridae, Flavivirus) was declared a public health emergency of international concern by the World Health Organization (WHO) in February 2016, because of the evidence linking infection with ZIKV to neurological complications, such as Guillain-Barre Syndrome in adults and congenital birth defects including microcephaly in the developing fetus. Because development of a ZIKV vaccine is a top research priority and because the genetic and antigenic variability of many RNA viruses limits the effectiveness of vaccines, assessing whether immunity elicited against one ZIKV strain is sufficient to confer broad protection against all ZIKV strains is critical. Recently, in vitro studies demonstrated that ZIKV likely circulates as a single serotype. Here, we demonstrate that immunity elicited by African lineage ZIKV protects rhesus macaques against subsequent infection with Asian lineage ZIKV. Methodology/Principal Findings Using our recently developed rhesus macaque model of ZIKV infection, we report that the prototypical ZIKV strain MR766 productively infects macaques, and that immunity elicited by MR766 protects macaques against heterologous Asian ZIKV. Furthermore, using next generation deep sequencing, we found in vivo restoration of a putative N-linked glycosylation site upon replication in macaques that is absent in numerous MR766 strains that are widely being used by the research community. This reversion highlights the importance of carefully examining the sequence composition of all viral stocks as well as understanding how passage history may alter a virus from its original form. Conclusions/Significance An effective ZIKV vaccine is needed to prevent infection-associated fetal abnormalities. Macaques whose immune responses were primed by infection with East African ZIKV were completely protected from detectable viremia when subsequently rechallenged with heterologous Asian ZIKV. Therefore, these data suggest that immunogen selection

  4. Target Impact Detection Algorithm Using Computer-aided Design (CAD) Model Geometry

    Science.gov (United States)

    2014-09-01

    UNCLASSIFIED AD-E403 558 Technical Report ARMET-TR-13024 TARGET IMPACT DETECTION ALGORITHM USING COMPUTER-AIDED DESIGN ( CAD ...DETECTION ALGORITHM USING COMPUTER-AIDED DESIGN ( CAD ) MODEL GEOMETRY 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...This report documents a method and algorithm to export geometry from a three-dimensional, computer-aided design ( CAD ) model in a format that can be

  5. A Financial Aid Competency Model for Professional Development

    Science.gov (United States)

    Woolf, Neil; Martinez, Mario

    2013-01-01

    This research explores the competencies that financial aid officers need to be successful in their jobs. A survey of 30 competencies was distributed to 508 financial aid officers in the Western United States. Respondents were asked to rate 30 job competencies for their relative importance and frequency of use. Using exploratory factor analysis,…

  6. Description and manual for the use of DRIVER - an interactive modelling aid

    CSIR Research Space (South Africa)

    Furniss, PR

    1977-09-01

    Full Text Available The modelling aid DRIVER is described. It permits the interactive manipulation of the parameters and variables of difference models which are implemented as FORTRAN subroutines. Relationships in the model can be expressed as arbitrary functions. A...

  7. Mimetic Muscles in a Despotic Macaque (Macaca mulatta) Differ from Those in a Closely Related Tolerant Macaque (M. nigra).

    Science.gov (United States)

    Burrows, Anne M; Waller, Bridget M; Micheletta, Jérôme

    2016-10-01

    Facial displays (or expressions) are a primary means of visual communication among conspecifics in many mammalian orders. Macaques are an ideal model among primates for investigating the co-evolution of facial musculature, facial displays, and social group size/behavior under the umbrella of "ecomorphology". While all macaque species share some social behaviors, dietary, and ecological parameters, they display a range of social dominance styles from despotic to tolerant. A previous study found a larger repertoire of facial displays in tolerant macaque species relative to despotic species. The present study was designed to further explore this finding by comparing the gross morphological features of mimetic muscles between the Sulawesi macaque (Macaca nigra), a tolerant species, and the rhesus macaque (M. mulatta), a despotic species. Five adult M. nigra heads were dissected and mimetic musculature was compared to those from M. mulatta. Results showed that there was general similarity in muscle presence/absence between the species as well as muscle form except for musculature around the external ear. M. mulatta had more musculature around the external ear than M. nigra. In addition, M. nigra lacked a zygomaticus minor while M. mulatta is reported to have one. These morphological differences match behavioral observations documenting a limited range of ear movements used by M. nigra during facial displays. Future studies focusing on a wider phylogenetic range of macaques with varying dominance styles may further elucidate the roles of phylogeny, ecology, and social variables in the evolution of mimetic muscles within Macaca Anat Rec, 299:1317-1324, 2016. © 2016 Wiley Periodicals, Inc.

  8. D Geological Framework Models as a Teaching Aid for Geoscience

    Science.gov (United States)

    Kessler, H.; Ward, E.; Geological ModelsTeaching Project Team

    2010-12-01

    3D geological models have great potential as a resource for universities when teaching foundation geological concepts as it allows the student to visualise and interrogate UK geology. They are especially useful when dealing with the conversion of 2D field, map and GIS outputs into three dimensional geological units, which is a common problem for all students of geology. Today’s earth science students use a variety of skills and processes during their learning experience including the application of schema’s, spatial thinking, image construction, detecting patterns, memorising figures, mental manipulation and interpretation, making predictions and deducing the orientation of themselves and the rocks. 3D geological models can reinforce spatial thinking strategies and encourage students to think about processes and properties, in turn helping the student to recognise pre-learnt geological principles in the field and to convert what they see at the surface into a picture of what is going on at depth. Learning issues faced by students may also be encountered by experts, policy managers, and stakeholders when dealing with environmental problems. Therefore educational research of student learning in earth science may also improve environmental decision making. 3D geological framework models enhance the learning of Geosciences because they: ● enable a student to observe, manipulate and interpret geology; in particular the models instantly convert two-dimensional geology (maps, boreholes and cross-sections) into three dimensions which is a notoriously difficult geospatial skill to acquire. ● can be orientated to whatever the user finds comfortable and most aids recognition and interpretation. ● can be used either to teach geosciences to complete beginners or add to experienced students body of knowledge (whatever point that may be at). Models could therefore be packaged as a complete educational journey or students and tutor can select certain areas of the model

  9. A Multi-Component Model for HIV/AIDS Prevention Education on the College Campus.

    Science.gov (United States)

    Sankaran, Gopal; And Others

    1993-01-01

    Describes an approach to building a multidimensional HIV/AIDS prevention education model for college campuses based on surveys of students' and faculty members' knowledge and attitudes about HIV/AIDS. The model emphasizes education, campus health services, campus environment, counseling and support services, and campus community coalitions. (SM)

  10. Turnover rates of B cells, T cells, and NK cells in simian immunodeficiency virus-infected and uninfected rhesus macaques

    NARCIS (Netherlands)

    Boer, R.J. de; Mohri, H.; Ho, D.D.; Perelson, A.S.

    2003-01-01

    We determined average cellular turnover rates by fitting mathematical models to 5-bromo-2'-deoxyuridine measurements in SIV-infected and uninfected rhesus macaques. The daily turnover rates of CD4(+) T cells, CD4(-) T cells, CD20(+) B cells, and CD16(+) NK cells in normal uninfected rhesus macaques

  11. Illegal trade in Barbary macaques

    NARCIS (Netherlands)

    van Uhm, Daan

    2014-01-01

    While Morocco is well known as the main port between Africa and the EU for the illegal drugs trade and migration, the illegal trade in wildlife is flourishing as well. Next to the illegal large-scale trafficking of tortoises and birds, it is estimated that as few as 5,000 Barbary macaques remain in

  12. Conserved host response to highly pathogenic avian influenza virus infection in human cell culture, mouse and macaque model systems

    Directory of Open Access Journals (Sweden)

    McDermott Jason E

    2011-11-01

    Full Text Available Abstract Background Understanding host response to influenza virus infection will facilitate development of better diagnoses and therapeutic interventions. Several different experimental models have been used as a proxy for human infection, including cell cultures derived from human cells, mice, and non-human primates. Each of these systems has been studied extensively in isolation, but little effort has been directed toward systematically characterizing the conservation of host response on a global level beyond known immune signaling cascades. Results In the present study, we employed a multivariate modeling approach to characterize and compare the transcriptional regulatory networks between these three model systems after infection with a highly pathogenic avian influenza virus of the H5N1 subtype. Using this approach we identified functions and pathways that display similar behavior and/or regulation including the well-studied impact on the interferon response and the inflammasome. Our results also suggest a primary response role for airway epithelial cells in initiating hypercytokinemia, which is thought to contribute to the pathogenesis of H5N1 viruses. We further demonstrate that we can use a transcriptional regulatory model from the human cell culture data to make highly accurate predictions about the behavior of important components of the innate immune system in tissues from whole organisms. Conclusions This is the first demonstration of a global regulatory network modeling conserved host response between in vitro and in vivo models.

  13. Transplantation of adult monkey neural stem cells into a contusion spinal cord injury model in rhesus macaque monkeys

    DEFF Research Database (Denmark)

    Nemati, Shiva Nemati; Jabbari, Reza; Hajinasrollah, Mostafa

    2014-01-01

    OBJECTIVE: Currently, cellular transplantation for spinal cord injuries (SCI) is the subject of numerous preclinical studies. Among the many cell types in the adult brain, there is a unique subpopulation of neural stem cells (NSC) that can self-renew and differentiate into neurons. The study aims......, therefore, to explore the efficacy of adult monkey NSC (mNSC) in a primate SCI model. MATERIALS AND METHODS: In this experimental study, isolated mNSCs were analyzed by flow cytometry, immunocytochemistry, and RT-PCR. Next, BrdU-labeled cells were transplanted into a SCI model. The SCI animal model...... was confirmed by magnetic resonance imaging (MRI) and histological analysis. Animals were clinically observed for 6 months. RESULTS: Analysis confirmed homing of mNSCs into the injury site. Transplanted cells expressed neuronal markers (TubIII). Hind limb performance improved in trans- planted animals based...

  14. Computer-aided pulmonary image analysis in small animal models

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Ziyue; Mansoor, Awais; Mollura, Daniel J. [Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health (NIH), Bethesda, Maryland 32892 (United States); Bagci, Ulas, E-mail: ulasbagci@gmail.com [Center for Research in Computer Vision (CRCV), University of Central Florida (UCF), Orlando, Florida 32816 (United States); Kramer-Marek, Gabriela [The Institute of Cancer Research, London SW7 3RP (United Kingdom); Luna, Brian [Microfluidic Laboratory Automation, University of California-Irvine, Irvine, California 92697-2715 (United States); Kubler, Andre [Department of Medicine, Imperial College London, London SW7 2AZ (United Kingdom); Dey, Bappaditya; Jain, Sanjay [Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 (United States); Foster, Brent [Department of Biomedical Engineering, University of California-Davis, Davis, California 95817 (United States); Papadakis, Georgios Z. [Radiology and Imaging Sciences, National Institutes of Health (NIH), Bethesda, Maryland 32892 (United States); Camp, Jeremy V. [Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky 40202 (United States); Jonsson, Colleen B. [National Institute for Mathematical and Biological Synthesis, University of Tennessee, Knoxville, Tennessee 37996 (United States); Bishai, William R. [Howard Hughes Medical Institute, Chevy Chase, Maryland 20815 and Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 (United States); Udupa, Jayaram K. [Medical Image Processing Group, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States)

    2015-07-15

    Purpose: To develop an automated pulmonary image analysis framework for infectious lung diseases in small animal models. Methods: The authors describe a novel pathological lung and airway segmentation method for small animals. The proposed framework includes identification of abnormal imaging patterns pertaining to infectious lung diseases. First, the authors’ system estimates an expected lung volume by utilizing a regression function between total lung capacity and approximated rib cage volume. A significant difference between the expected lung volume and the initial lung segmentation indicates the presence of severe pathology, and invokes a machine learning based abnormal imaging pattern detection system next. The final stage of the proposed framework is the automatic extraction of airway tree for which new affinity relationships within the fuzzy connectedness image segmentation framework are proposed by combining Hessian and gray-scale morphological reconstruction filters. Results: 133 CT scans were collected from four different studies encompassing a wide spectrum of pulmonary abnormalities pertaining to two commonly used small animal models (ferret and rabbit). Sensitivity and specificity were greater than 90% for pathological lung segmentation (average dice similarity coefficient > 0.9). While qualitative visual assessments of airway tree extraction were performed by the participating expert radiologists, for quantitative evaluation the authors validated the proposed airway extraction method by using publicly available EXACT’09 data set. Conclusions: The authors developed a comprehensive computer-aided pulmonary image analysis framework for preclinical research applications. The proposed framework consists of automatic pathological lung segmentation and accurate airway tree extraction. The framework has high sensitivity and specificity; therefore, it can contribute advances in preclinical research in pulmonary diseases.

  15. Genotyping of TRIM5 locus in northern pig-tailed macaques (Macaca leonina, a primate species susceptible to Human Immunodeficiency Virus type 1 infection

    Directory of Open Access Journals (Sweden)

    Jiang Xue-Long

    2009-06-01

    Full Text Available Abstract Background The pig-tailed macaques are the only Old World monkeys known to be susceptible to human immunodeficiency virus type 1 (HIV-1 infection. We have previously reported that the TRIM5-Cyclophilin A (TRIMCyp fusion in pig-tailed macaques (Macaca nemestrina is dysfunctional in restricting HIV-1, which may explain why pig-tailed macaques are susceptible to HIV-1 infection. Similar results have also been reported by other groups. However, according to the current primate taxonomy, the previously reported M. nemestrina are further classified into three species, which all belong to the Macaca spp. This calls for the need to look into the previous studies in more details. Results The local species Northern pig-tailed macaque (M. leonina was analyzed for the correlation of TRIM5 structure and HIV-1 infection. Eleven M. leonina animals were analyzed, and all of them were found to possess TRIM5-CypA fusion at the TRIM5 locus. The transcripts encoding the dysfunctional TRIM5-CypA should result from the G-to-T mutation in the 3'-splicing site of intron 6. Polymorphism in the putative TRIMCyp recognition domain was observed. The peripheral blood mononuclear cells (PBMCs of M. leonina were susceptible to HIV-1 infection. Consistent with the previous results, expression of the M. leonina TRIMCyp in HeLa-T4 cells rendered the cells resistant to HIV-2ROD but not to SIVmac239 infection. Conclusion The susceptibility of M. leonina to HIV-1 infection is due to the dysfunctional TRIM5-CypA fusion in the TRIM5 locus. This finding should broaden our perspective in developing better HIV/AIDS non-human primate animal models.

  16. Surgical technique for allogeneic uterus transplantation in macaques

    Science.gov (United States)

    Obara, Hideaki; Kisu, Iori; Kato, Yojiro; Yamada, Yohei; Matsubara, Kentaro; Emoto, Katsura; Adachi, Masataka; Matoba, Yusuke; Umene, Kiyoko; Nogami, Yuya; Banno, Kouji; Tsuchiya, Hideaki; Itagaki, Iori; Kawamoto, Ikuo; Nakagawa, Takahiro; Ishigaki, Hirohito; Itoh, Yasushi; Ogasawara, Kazumasa; Saiki, Yoko; Sato, Shin-ichi; Nakagawa, Kenshi; Shiina, Takashi; Aoki, Daisuke; Kitagawa, Yuko

    2016-01-01

    No study has reported an animal model of uterus transplantation (UTx) using cynomolgus macaques. We aimed to establish a surgical technique of allogeneic UTx assuming the recovery of a uterus from a deceased donor in cynomolgus macaques. Four allogeneic UTxs were performed in female cynomolgus macaques. Donor surgeries comprised en bloc recovery of organs with iliac vessels on both sides, and/or abdominal aorta/vena cava after sufficient perfusion from one femoral artery or external iliac artery. Before perfusion, 150 mL of whole blood was obtained from the donor for subsequent blood transfusion to the recipient. Four uterine grafts were orthotopically transplanted to recipients. End-to-side anastomosis was performed to the iliac vessels on one side in case 1 and iliac vessels on both sides in case 2; aorto-aorto/cavo-caval anastomosis was performed in cases 3 and 4. Arterial blood flow of the uterine grafts was determined by intraoperative indocyanine green (ICG) angiography. ICG angiography results showed sufficient blood flow to all uterine grafts, and anaemia did not progress. Under appropriate immune suppression, all recipients survived for more than 90 days post-transplantation, without any surgical complications. We describe a surgical technique for allogeneic UTx in cynomolgus macaques. PMID:27786258

  17. Characterization of SIV in the Oral Cavity and in Vitro Inhibition of SIV by Rhesus Macaque Saliva

    Science.gov (United States)

    Thomas, Jessica S.; Lacour, Nedra; Kozlowski, Pamela A.; Nelson, Steve; Bagby, Gregory J.

    2010-01-01

    Abstract Human immunodeficiency virus (HIV) infections are rarely acquired via an oral route in adults. Previous studies have shown that human whole saliva inhibits HIV infection in vitro, and multiple factors present in human saliva have been shown to contribute to this antiviral activity. Despite the widespread use of simian immunodeficiency virus (SIV)-infected rhesus macaques as models for HIV pathogenesis and transmission, few studies have monitored SIV in the oral cavity of infected rhesus macaques and evaluated the viral inhibitory capacity of macaque saliva. Utilizing a cohort of rhesus macaques infected with SIVMac251, we monitored virus levels and genotypic diversity in the saliva throughout the course of the disease; findings were similar to previous observations in HIV-infected humans. An in vitro infectivity assay was utilized to measure inhibition of HIV/SIV infection by normal human and rhesus macaque whole saliva. Both human and macaque saliva were capable of inhibiting HIV and SIV infection. The inhibitory capacity of saliva samples collected from a cohort of animals postinfection with SIV increased over the course of disease, coincident with the development of SIV-specific antibodies in the saliva. These findings suggest that both innate and adaptive factors contribute to inhibition of SIV by whole macaque saliva. This work also demonstrates that SIV-infected rhesus macaques provide a relevant model to examine the innate and adaptive immune responses that inhibit HIV/SIV in the oral cavity. PMID:20672998

  18. Using System Dynamics to model the HIV/AIDS epidemic in Botswana and Uganda

    NARCIS (Netherlands)

    Howell, R.; Wesselink, O.; Pruyt, E.

    2013-01-01

    Uganda and Botswana present two interesting and contrasting cases in the AIDS epidemic. System dynamics models of the AIDS epidemic in Botswana and Uganda were created to examine the future development of the virus in both countries and evaluate existing and future policy measures. The effect of exi

  19. Diverse Host Responses and Outcomes following Simian Immunodeficiency Virus SIVmac239 Infection in Sooty Mangabeys and Rhesus Macaques

    Science.gov (United States)

    Kaur, Amitinder; Grant, Robert M.; Means, Robert E.; McClure, Harold; Feinberg, Mark; Johnson, R. Paul

    1998-01-01

    Sooty mangabeys naturally infected with simian immunodeficiency virus (SIV) do not develop immunodeficiency despite the presence of viral loads of 105 to 107 RNA copies/ml. To investigate the basis of apathogenic SIV infection in sooty mangabeys, three sooty mangabeys and three rhesus macaques were inoculated intravenously with SIVmac239 and evaluated longitudinally for 1 year. SIVmac239 infection of sooty mangabeys resulted in 2- to 4-log-lower viral loads than in macaques and did not reproduce the high viral loads observed in natural SIVsmm infection. During acute SIV infection, polyclonal cytotoxic T-lymphocyte (CTL) activity coincident with decline in peak plasma viremia was observed in both macaques and mangabeys; 8 to 20 weeks later, CTL activity declined in the macaques but was sustained and broadly directed in the mangabeys. Neutralizing antibodies to SIVmac239 were detected in the macaques but not the mangabeys. Differences in expression of CD38 on CD8+ T lymphocytes or in the percentage of naive phenotype T cells expressing CD45RA and CD62L-selection did not correlate with development of AIDS in rhesus macaques. In macaques, the proportion of CD4+ T lymphocytes expressing CD25 declined during SIV infection, while in mangabeys, CD25-expressing CD4+ T lymphocytes increased. Longitudinal evaluation of cytokine secretion by flow cytometric analysis of unstimulated lymphocytes revealed elevation of interleukin-2 and gamma interferon in a macaque and only interleukin-10 in a concurrently infected mangabey during acute SIV infection. Differences in host responses following experimental SIVmac239 infection may be associated with the divergent outcome in sooty mangabeys and rhesus macaques. PMID:9811693

  20. The Computer-Aided Analytic Process Model. Operations Handbook for the APM (Analytic Process Model) Demonstration Package. Appendix

    Science.gov (United States)

    1986-01-01

    The Analytic Process Model for System Design and Measurement: A Computer-Aided Tool for Analyzing Training Systems and Other Human-Machine Systems. A...separate companion volume--The Computer-Aided Analytic Process Model : Operations Handbook for the APM Demonstration Package is also available under

  1. Pharmacokinetics of Cefovecin in Cynomolgus Macaques (Macaca fascicularis), Olive Baboons (Papio anubis), and Rhesus Macaques (Macaca mulatto)

    Energy Technology Data Exchange (ETDEWEB)

    Raabe, Brigitte M.; Lovaglio, Jamie A.; Grover, GScott; Brown, Scott A.; Boucher, Joseph F.; Yuan, Yang; Civil, Jacqueline R.; Gillhouse, Kimberly A.; Stubbs, Makeida N.; Hoggatt, Amber F.; Halliday, Lisa C.; Fortman, Jeffrey D.

    2011-05-01

    Cefovecin sodium is a long-acting, third-generation, cephalosporin antibiotic approved for the treatment of skin infections in dogs and cats. The pharmacokinetic properties of cefovecin were evaluated in cynomolgus macaques (Macaca fascicularis), olive baboons (Papio anubis), and rhesus macaques (Macaca mulatto) by using a single-dose (8 mg/kg SC) dosing regimen. Plasma cefovecin concentrations were determined by using ultra-performance liquid chromatography with tandem mass spectrometry, and a noncompartmental model was used to determine pharmacokinetic parameters. The half-life of cefovecin was 4.95 {+-} 1.47 h in cynomolgus macaques, 9.17 {+-} 1.84 h in olive baboons, and 8.40 {+-} 2.53 h in rhesus macaques. These values are considerably lower than the half-lives previously published for dogs (133 h) and cats (166 h). The extended half-life of cefovecin in dogs and cats is speculated to be due to active reabsorption of drug in the kidney tubules because plasma clearance is well below the normal glomerular filtration rate. In nonhuman primates, renal clearance rates approximated plasma clearance rates, suggesting that active renal reabsorption of cefovecin does not occur in these species. The pharmacokinetic properties of cefovecin in nonhuman primates are vastly different from the pharmacokinetic properties in dogs and cats, precluding its use as a long-acting antibiotic in nonhuman primates. This study highlights the importance of performing pharmacokinetic studies prior to extralabel drug usage.

  2. Computer-aided modeling framework – a generic modeling template for catalytic membrane fixed bed reactors

    DEFF Research Database (Denmark)

    Fedorova, Marina; Sin, Gürkan; Gani, Rafiqul

    2013-01-01

    This work focuses on development of computer-aided modeling framework. The framework is a knowledge-based system that is built on a generic modeling language and structured based on workflows for different general modeling tasks. The overall objective of this work is to support the model developers...... and users to generate and test models systematically, efficiently and reliably. In this way, development of products and processes can be faster, cheaper and very efficient. In this contribution, as part of the framework a generic modeling template for the systematic derivation of problem specific catalytic...... membrane fixed bed models is developed. The application of the modeling template is highlighted with a case study related to the modeling of a catalytic membrane reactor coupling dehydrogenation of ethylbenzene with hydrogenation of nitrobenzene....

  3. Computer-Aided Transformation of PDE Models: Languages, Representations, and a Calculus of Operations

    Science.gov (United States)

    2016-01-05

    Computer-aided transformation of PDE models: languages, representations, and a calculus of operations A domain-specific embedded language called...languages, representations, and a calculus of operations Report Title A domain-specific embedded language called ibvp was developed to model initial...Computer-aided transformation of PDE models: languages, representations, and a calculus of operations 1 Vision and background Physical and engineered systems

  4. Computer-aided modelling template: Concept and application

    DEFF Research Database (Denmark)

    Fedorova, Marina; Sin, Gürkan; Gani, Rafiqul

    2015-01-01

    decomposition technique which identifies generic steps and workflow involved, the computer-aided template concept has been developed. This concept is implemented as a software tool, which provides a user-friendly interface for following the workflow steps and guidance through the steps providing additional...

  5. Aiding human reliance decision making using computational models of trust

    NARCIS (Netherlands)

    Maanen, P.P. van; Klos, T.; Dongen, C.J. van

    2007-01-01

    This paper involves a human-agent system in which there is an operator charged with a pattern recognition task, using an automated decision aid. The objective is to make this human-agent system operate as effectively as possible. Effectiveness is gained by an increase of appropriate reliance on the

  6. Characterization of killer immunoglobulin-like receptor genetics and comprehensive genotyping by pyrosequencing in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Parham Peter

    2011-06-01

    Full Text Available Abstract Background Human killer immunoglobulin-like receptors (KIRs play a critical role in governing the immune response to neoplastic and infectious disease. Rhesus macaques serve as important animal models for many human diseases in which KIRs are implicated; however, the study of KIR activity in this model is hindered by incomplete characterization of KIR genetics. Results Here we present a characterization of KIR genetics in rhesus macaques (Macaca mulatta. We conducted a survey of KIRs in this species, identifying 47 novel full-length KIR sequences. Using this expanded sequence library to build upon previous work, we present evidence supporting the existence of 22 Mamu-KIR genes, providing a framework within which to describe macaque KIRs. We also developed a novel pyrosequencing-based technique for KIR genotyping. This method provides both comprehensive KIR genotype and frequency estimates of transcript level, with implications for the study of KIRs in all species. Conclusions The results of this study significantly improve our understanding of macaque KIR genetic organization and diversity, with implications for the study of many human diseases that use macaques as a model. The ability to obtain comprehensive KIR genotypes is of basic importance for the study of KIRs, and can easily be adapted to other species. Together these findings both advance the field of macaque KIRs and facilitate future research into the role of KIRs in human disease.

  7. Stability of an HIV/AIDS Treatment Model with Different Stages

    Directory of Open Access Journals (Sweden)

    Hai-Feng Huo

    2015-01-01

    Full Text Available An HIV/AIDS treatment model with different stages is proposed in this paper. The stage of the HIV infection is divided into two stages, that is, HIV-positive in the asymptomatic stage of HIV infection and HIV-positive individuals in the pre-AIDS stage. The fact that some individuals with HIV-positive individuals after the treatment can be transformed into the compartment of HIV-positive individuals in the asymptomatic stage of HIV infection, the compartment of HIV-positive individuals in the pre-AIDS stage, or the compartment of individuals with full-blown AIDS is also considered. Mathematical analyses establish the idea that the global dynamics of the HIV/AIDS model are determined by the basic reproduction number R0. The disease-free equilibrium is globally asymptotically stable if R01 for a special case. Numerical simulations are also conducted to support the analytic results.

  8. Experimental inoculation of juvenile rhesus macaques with primate enteric caliciviruses.

    Directory of Open Access Journals (Sweden)

    Karol Sestak

    Full Text Available BACKGROUND: Tissue culture-adapted Tulane virus (TV, a GI.1 rhesus enteric calicivirus (ReCV, and a mixture of GII.2 and GII.4 human norovirus (NoV-containing stool sample were used to intrastomacheally inoculate juvenile rhesus macaques (Macaca mulatta in order to evaluate infection caused by these viruses. METHODOLOGY & FINDINGS: Two of the three TV-inoculated macaques developed diarrhea, fever, virus-shedding in stools, inflammation of duodenum and 16-fold increase of TV-neutralizing (VN serum antibodies but no vomiting or viremia. No VN-antibody responses could be detected against a GI.2 ReCV strain FT285, suggesting that TV and FT285 represent different ReCV serotypes. Both NoV-inoculated macaques remained asymptomatic but with demonstrable virus shedding in one animal. Examination of duodenum biopsies of the TV-inoculated macaques showed lymphocytic infiltration of the lamina propria and villous blunting. TV antigen-positive (TV+ cells were detected in the lamina propria. In most of the TV+ cells TV co-localized perinuclearly with calnexin--an endoplasmic reticulum protein. A few CD20+TV+ double-positive B cells were also identified in duodenum. To corroborate the authenticity of CD20+TV+ B cells, in vitro cultures of peripheral blood mononuclear cells (PBMCs from healthy macaques were inoculated with TV. Multicolor flow cytometry confirmed the presence of TV antigen-containing B cells of predominantly CD20+HLA-DR+ phenotype. A 2-log increase of viral RNA by 6 days post inoculation (p<0.05 suggested active TV replication in cultured lymphocytes. CONCLUSIONS/SIGNIFICANCE: Taken together, our results show that ReCVs represent an alternative cell culture and animal model to study enteric calicivirus replication, pathogenesis and immunity.

  9. A simple multiplex polymerase chain reaction to determine ABO blood types of rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Premasuthan, A; Kanthaswamy, S; Satkoski, J; Smith, D G

    2011-06-01

    Rhesus macaques are the most common nonhuman primate model organism used in biomedical research. Their increasingly frequent use as subjects in studies involving transplantation requires that blood and other tissue antigens of donors and recipients be compatible. We report here an easy and rapid multiplex polymerase chain reaction (PCR) to determine the ABO blood group phenotypes of rhesus macaques that can be performed with only small amounts of DNA. We phenotyped 78 individuals and found this species to exhibit the A, B and AB phenotypes in frequencies that vary by geographic region. The probability of randomly pairing rhesus macaque donors and recipients that exhibit major ABO phenotype incompatibility is approximately 0.35 and 0.45 for Indian and Chinese rhesus macaques, respectively.

  10. Aid Effectiveness

    DEFF Research Database (Denmark)

    Arndt, Channing; Jones, Edward Samuel; Tarp, Finn

    Controversy over the aggregate impact of foreign aid has focused on reduced form estimates of the aid-growth link. The causal chain, through which aid affects developmental outcomes including growth, has received much less attention. We address this gap by: (i) specifying a structural model of th...

  11. Modeling strategic behavior in human-automation interaction - Why an 'aid' can (and should) go unused

    Science.gov (United States)

    Kirlik, Alex

    1993-01-01

    Task-offload aids (e.g., an autopilot, an 'intelligent' assistant) can be selectively engaged by the human operator to dynamically delegate tasks to automation. Introducing such aids eliminates some task demands but creates new ones associated with programming, engaging, and disengaging the aiding device via an interface. The burdens associated with managing automation can sometimes outweigh the potential benefits of automation to improved system performance. Aid design parameters and features of the overall multitask context combine to determine whether or not a task-offload aid will effectively support the operator. A modeling and sensitivity analysis approach is presented that identifies effective strategies for human-automation interaction as a function of three task-context parameters and three aid design parameters. The analysis and modeling approaches provide resources for predicting how a well-adapted operator will use a given task-offload aid, and for specifying aid design features that ensure that automation will provide effective operator support in a multitask environment.

  12. An epidemic model for the transmission dynamics of HIV/AIDS with different clinical stages

    Directory of Open Access Journals (Sweden)

    Sandip Omar

    2010-06-01

    Full Text Available In this paper, a five–dimensional mathematical model is proposed for the transmission dynamics of HIV/AIDS within a population of varying size. In writing the model, we have divided the population under consideration into five sub classes of susceptible, infective, pre-AIDS, AIDS related complex and that of AIDS patients. The model has two non- negative equilibria namely, a disease free and the endemic equilibrium. The model has been studied using stability theory. It is shown that the positive non-trivial equilibrium is always locally stable but it may become globally stable under certain condition showing that the disease becomes endemic due to constant migration of the population into the habitat. The effect of various parameters on the spread of the disease has also been discussed.

  13. An Integrated Model for Optimization Oriented Decision Aiding and Rule Based Decision Making in Fuzzy Environment

    Directory of Open Access Journals (Sweden)

    A. Yousefli

    2014-01-01

    Full Text Available In this paper a fuzzy decision aid system is developed base on new concepts that presented in the field of fuzzy decision making in fuzzy environment (FDMFE. This framework aids decision makers to understand different circumstances of an uncertain problem that may occur in the future. Also, to keep decision maker from the optimization problem complexities, a decision support system, which can be replaced by optimization problem, is presented to make optimum or near optimum decisions without solving optimization problem directly. An application of the developed decision aid model and the decision support system is presented in the field of inventory models.

  14. Assessing Automatic Aid as an Emergency Response Model

    Science.gov (United States)

    2013-12-01

    often include the idea of mutual and automatic aid. Clovis noted in his paper “Thinking about National Preparedness” that resources, being a...Attributes of Collaboration.” National Public Management Research Conference. October 2009. 39 Samuel Clovis , “Thinking About National Preparedness...to Fail. Boston, MA: Perseus Books Group. Kindle Edition Clovis , Samuel. “Thinking About National Preparedness: The National Planning Scenarios and

  15. Application of computer-aided multi-scale modelling framework – Aerosol case study

    DEFF Research Database (Denmark)

    Heitzig, Martina; Sin, Gürkan; Glarborg, Peter

    -aided methods provide. The key prerequisite of computer-aided product-process engineering is however the availability of models of different types, forms and application modes. The development of the models required for the systems under investigation tends to be a challenging and time-consuming task involving...... numerous steps, expert skills and different modelling tools. This motivates the development of a computer-aided modelling framework that supports the user during model development, documentation, analysis, identification, application and re-use with the goal to increase the efficiency of the modelling...... generation, optimal equation ordering, eigenvalue analysis. Once the models have been constructed and analysed the modelling framework incorporates 3 application work-flows for: identification, simulation and design. For these application work-flows different solvers that can solve a large range of different...

  16. Application of computer-aided multi-scale modelling framework – Aerosol case study

    DEFF Research Database (Denmark)

    Heitzig, Martina; Sin, Gürkan; Glarborg, Peter

    Model-based computer aided product-process engineering has attained increased importance in a number of industries, including pharmaceuticals, petrochemicals, fine chemicals, polymers, biotechnology, food, energy and water. This trend is set to continue due to the substantial benefits computer...... development part supports the modeller in model documentation, construction and analysis.Different models for properties, phenomena, unit operations, processes can be developed and analysed here or retrieved from model libraries.The model equations are introduced in a simple text format and are translated......-aided methods provide. The key prerequisite of computer-aided product-process engineering is however the availability of models of different types, forms and application modes. The development of the models required for the systems under investigation tends to be a challenging and time-consuming task involving...

  17. Application of computer-aided multi-scale modelling framework - Aerosol case study

    DEFF Research Database (Denmark)

    Heitzig, Martina; Gregson, Christopher; Sin, Gürkan;

    2011-01-01

    A computer-aided modelling tool for efficient multi-scale modelling has been developed and is applied to solve a multi-scale modelling problem related to design and evaluation of fragrance aerosol products. The developed modelling scenario spans three length scales and describes how droplets...

  18. A double hit model for the distribution of time to AIDS onset

    Science.gov (United States)

    Chillale, Nagaraja Rao

    2013-09-01

    Incubation time is a key epidemiologic descriptor of an infectious disease. In the case of HIV infection this is a random variable and is probably the longest one. The probability distribution of incubation time is the major determinant of the relation between the incidences of HIV infection and its manifestation to Aids. This is also one of the key factors used for accurate estimation of AIDS incidence in a region. The present article i) briefly reviews the work done, points out uncertainties in estimation of AIDS onset time and stresses the need for its precise estimation, ii) highlights some of the modelling features of onset distribution including immune failure mechanism, and iii) proposes a 'Double Hit' model for the distribution of time to AIDS onset in the cases of (a) independent and (b) dependent time variables of the two markers and examined the applicability of a few standard probability models.

  19. Prevalence of antibodies to 3 retroviruses in a captive colony of macaque monkeys.

    Science.gov (United States)

    Daniel, M D; Letvin, N L; Sehgal, P K; Schmidt, D K; Silva, D P; Solomon, K R; Hodi, F S; Ringler, D J; Hunt, R D; King, N W

    1988-04-15

    The prevalence of antibodies to 3 retroviruses in the macaque colony of the New England Regional Primate Research Center (NERPRC) was determined using enzyme-linked immunosorbent assay procedures as well as radioimmunoprecipitation-SDS polyacrylamide gel electrophoresis and indirect immunofluorescence tests. Out of 848 macaques, 3 (0.35%) had antibodies to simian immunodeficiency virus (SIV), 27 (3.2%) had antibodies to simian T-lymphotropic virus type I (STLV-1) and approximately 285 (34%) had antibodies to type D retrovirus. Of 3 macaques infected with SIV, 2 were rhesus monkeys (Macaca mulatta) and I was a cynomolgus monkey (Macaca fascicularis). STLV-1 and D retrovirus infection occurred in all 4 macaque species examined. SIV, STLV-1 and D retroviruses were isolated from sero-positive macaques. The low prevalence of SIV infection suggests that SIV is not being readily transmitted among macaques at NERPRC; this contrasts markedly with the high SIV prevalence in some captive mangabey colonies. In contrast to African green monkeys from eastern Africa, 160 Caribbean green monkeys examined showed no sign of SIV infection. These results provide a framework for monitoring spontaneous disease associated with infection by these 3 retroviruses and will help in further definition of STLV-1 and SIV infection of non-human primates as animal models for human disease.

  20. Decision aid reliance: modeling the effects of decision aid reliability and pressures to perform on reliance behavior

    NARCIS (Netherlands)

    Gomaa, M.I.; Hunton, J.E.; Vaassen, E.H.J.; Carree, M.A.

    2011-01-01

    We investigate the effects of decision aid reliability and pressure to perform on decision aid reliance. A total of 403 students took part in a four (pressures to perform: one through four) by five (decision aid reliability: 50%, 60%, 70%, 80% and 90%) between-participants experiment. We test two

  1. Decision aid reliance: modeling the effects of decision aid reliability and pressures to perform on reliance behavior

    NARCIS (Netherlands)

    M.I. Gomaa; J.E. Hunton; E.H.J. Vaassen; M.A. Carree

    2011-01-01

    We investigate the effects of decision aid reliability and pressure to perform on decision aid reliance. A total of 403 students took part in a four (pressures to perform: one through four) by five (decision aid reliability: 50%, 60%, 70%, 80% and 90%) between-participants experiment. We test two co

  2. Gluten-sensitive enteropathy coincides with decreased capability of intestinal T cells to secrete IL-17 and IL-22 in a macaque model for celiac disease.

    Science.gov (United States)

    Xu, Huanbin; Feely, Stephanie L; Wang, Xiaolei; Liu, David X; Borda, Juan T; Dufour, Jason; Li, Weiwei; Aye, Pyone P; Doxiadis, Gaby G; Khosla, Chaitan; Veazey, Ronald S; Sestak, Karol

    2013-04-01

    Celiac disease (CD) is an autoimmune disorder caused by intolerance to dietary gluten. The interleukin (IL)-17 and IL-22 function as innate regulators of mucosal integrity. Impaired but not well-understood kinetics of the IL-17/22 secretion was described in celiac patients. Here, the IL-17 and IL-22-producing intestinal cells were studied upon their in vitro stimulation with mitogens in class II major histocompatibility complex-defined, gluten-sensitive rhesus macaques. Pediatric biopsies were collected from distal duodenum during the stages of disease remission and relapse. Regardless of dietary gluten content, IL-17 and IL-22-producing cells consisted of CD4+ and CD8+ T lymphocytes as well as of lineage-negative (Lin-) cells. Upon introduction of dietary gluten, capability of intestinal T cells to secrete IL-17/22 started to decline (pgluten-sensitive primates.

  3. Modeling HIV transmission and AIDS in the united states

    CERN Document Server

    Hethcote, Herbert W

    1992-01-01

    The disease that came to be called acquired immunodeficiency syndrome (AIDS) was first identified in the summer of 1981. By that time, nearly 100,000 persons in the United States may have been infected with human immunodeficiency virus (HIV). By the time the routes of transmission were clearly identified and HIV was established as the cause of AIDS in 1983, over 300,000 people may have been infected. That number has continued to increase, with approximately 1,000,000 Americans believed to be infected in 1991. The epidemic is of great public health concern because HlV is infectious, causes severe morbidity and death in most if not all of those infected, and often occurs in relatively young persons. In addition, the cost of medical care for a person with HIV disease is high, and the medical care needs of HIV-infected persons place a severe burden on the medical care systems in many areas. Understanding and controlling the HIV epidemic is a particularly difficult challenge. The long and variable period between H...

  4. Color-detection thresholds in rhesus macaque monkeys and humans

    OpenAIRE

    Gagin, Galina; Bohon, Kaitlin S.; Butensky, Adam; Gates, Monica A.; Hu, Jiun-Yiing; Lafer-Sousa, Rosa; Pulumo, Reitumetse L.; Qu, Jane; Stoughton, Cleo M.; Swanbeck, Sonja N.; Conway, Bevil R.

    2014-01-01

    Macaque monkeys are a model of human color vision. To facilitate linking physiology in monkeys with psychophysics in humans, we directly compared color-detection thresholds in humans and rhesus monkeys. Colors were defined by an equiluminant plane of cone-opponent color space. All subjects were tested on an identical apparatus with a four-alternative forced-choice task. Targets were 2° square, centered 2° from fixation, embedded in luminance noise. Across all subjects, the change in detection...

  5. DecAID: a decaying wood advisory model for Oregon and Washington.

    Science.gov (United States)

    Kim Mellen; Bruce G. Marcot; Janet L. Ohmann; Karen L. Waddell; Elizabeth A. Willhite; Bruce B. Hostetler; Susan A. Livingston; Cay. Ogden

    2002-01-01

    DecAID is a knowledge-based advisory model that provides guidance to managers in determining the size, amount, and distribution of dead and decaying wood (dead and partially dead trees and down wood) necessary to maintain wildlife habitat and ecosystem functions. The intent of the model is to update and replace existing snag-wildlife models in Washington and Oregon....

  6. New Animal Model Could Boost Research on AIDS Drugs and Vaccines | Poster

    Science.gov (United States)

    By Frank Blanchard, Staff Writer, and Jeff Lifson, Guest Writer In a research milestone reported in the June 20 issue of the journal Science, scientists have developed a minimally modified version of HIV-1, the virus that causes AIDS in infected humans, that is capable of causing progressive infection and AIDS in monkeys. The advance should help create more authentic animal models of the disease and provide a potentially invaluable approach for faster and better preclinical evaluation of new drugs and vaccines.

  7. Lessons in Nonhuman Primate Models for AIDS Vaccine Research: From Minefields to Milestones

    OpenAIRE

    Jeffrey D Lifson; Nancy L Haigwood

    2012-01-01

    Nonhuman primate (NHP) disease models for AIDS have made important contributions to the search for effective vaccines for AIDS. Viral diversity, persistence, capacity for immune evasion, and safety considerations have limited development of conventional approaches using killed or attenuated vaccines, necessitating the development of novel approaches. Here we highlight the knowledge gained and lessons learned in testing vaccine concepts in different virus/NHP host combinations.

  8. Computer-aided modeling for efficient and innovative product-process engineering

    DEFF Research Database (Denmark)

    Heitzig, Martina

    Model-based computer aided product-process engineering has attained increased importance in a number of industries, including pharmaceuticals, petrochemicals, fine chemicals, polymers, biotechnology, food, energy and water. This trend is set to continue due to the substantial benefits computer...... in chemical and biochemical engineering have been solved to illustrate the application of the generic modelling methodology, the computeraided modelling framework and the developed software tool.......-aided methods provide. The key prerequisite of computer-aided productprocess engineering is however the availability of models of different types, forms and application modes. The development of the models required for the systems under investigation tends to be a challenging, time-consuming and therefore cost...

  9. Aids to determining fuel models for estimating fire behavior

    Science.gov (United States)

    Hal E. Anderson

    1982-01-01

    Presents photographs of wildland vegetation appropriate for the 13 fuel models used in mathematical models of fire behavior. Fuel model descriptions include fire behavior associated with each fuel and its physical characteristics. A similarity chart cross-references the 13 fire behavior fuel models to the 20 fuel models used in the National Fire Danger Rating System....

  10. Models as an Aid to Courses in Crystallography and Mineralogy.

    Science.gov (United States)

    Brady, K. T.

    1983-01-01

    Three models used in teaching crystallography/mineralogy at the University of Technology (Papua, New Guinea) are described. These include stereographic projection model, optical indicatrix models for Istropic/Anisotropic minerals, and model showing effect of anisotropic minerals under crossed polars. Photographs of the models are also included.…

  11. Otoacoustic Estimates of Cochlear Tuning: Testing Predictions in Macaque

    Science.gov (United States)

    Shera, Christopher A.; Bergevin, Christopher; Kalluri, Radha; Laughlin, Myles Mc; Michelet, Pascal; van der Heijden, Marcel; Joris, Philip X.

    2013-01-01

    Otoacoustic estimates of cochlear frequency selectivity suggest substantially sharper tuning in humans. However, the logic and methodology underlying these estimates remain untested by direct measurements in primates. We report measurements of frequency tuning in macaque monkeys, Old-World primates phylogenetically closer to humans than the small laboratory animals often taken as models of human hearing (e.g., cats, guinea pigs, and chinchillas). We find that measurements of tuning obtained directly from individual nerve fibers and indirectly using otoacoustic emissions both indicate that peripheral frequency selectivity in macaques is significantly sharper than in small laboratory animals, matching that inferred for humans at high frequencies. Our results validate the use of otoacoustic emissions for noninvasive measurement of cochlear tuning and corroborate the finding of sharper tuning in humans. PMID:24701000

  12. Evolutionary and biomedical insights from the rhesus macaque genome.

    Science.gov (United States)

    Gibbs, Richard A; Rogers, Jeffrey; Katze, Michael G; Bumgarner, Roger; Weinstock, George M; Mardis, Elaine R; Remington, Karin A; Strausberg, Robert L; Venter, J Craig; Wilson, Richard K; Batzer, Mark A; Bustamante, Carlos D; Eichler, Evan E; Hahn, Matthew W; Hardison, Ross C; Makova, Kateryna D; Miller, Webb; Milosavljevic, Aleksandar; Palermo, Robert E; Siepel, Adam; Sikela, James M; Attaway, Tony; Bell, Stephanie; Bernard, Kelly E; Buhay, Christian J; Chandrabose, Mimi N; Dao, Marvin; Davis, Clay; Delehaunty, Kimberly D; Ding, Yan; Dinh, Huyen H; Dugan-Rocha, Shannon; Fulton, Lucinda A; Gabisi, Ramatu Ayiesha; Garner, Toni T; Godfrey, Jennifer; Hawes, Alicia C; Hernandez, Judith; Hines, Sandra; Holder, Michael; Hume, Jennifer; Jhangiani, Shalini N; Joshi, Vandita; Khan, Ziad Mohid; Kirkness, Ewen F; Cree, Andrew; Fowler, R Gerald; Lee, Sandra; Lewis, Lora R; Li, Zhangwan; Liu, Yih-Shin; Moore, Stephanie M; Muzny, Donna; Nazareth, Lynne V; Ngo, Dinh Ngoc; Okwuonu, Geoffrey O; Pai, Grace; Parker, David; Paul, Heidie A; Pfannkoch, Cynthia; Pohl, Craig S; Rogers, Yu-Hui; Ruiz, San Juana; Sabo, Aniko; Santibanez, Jireh; Schneider, Brian W; Smith, Scott M; Sodergren, Erica; Svatek, Amanda F; Utterback, Teresa R; Vattathil, Selina; Warren, Wesley; White, Courtney Sherell; Chinwalla, Asif T; Feng, Yucheng; Halpern, Aaron L; Hillier, Ladeana W; Huang, Xiaoqiu; Minx, Pat; Nelson, Joanne O; Pepin, Kymberlie H; Qin, Xiang; Sutton, Granger G; Venter, Eli; Walenz, Brian P; Wallis, John W; Worley, Kim C; Yang, Shiaw-Pyng; Jones, Steven M; Marra, Marco A; Rocchi, Mariano; Schein, Jacqueline E; Baertsch, Robert; Clarke, Laura; Csürös, Miklós; Glasscock, Jarret; Harris, R Alan; Havlak, Paul; Jackson, Andrew R; Jiang, Huaiyang; Liu, Yue; Messina, David N; Shen, Yufeng; Song, Henry Xing-Zhi; Wylie, Todd; Zhang, Lan; Birney, Ewan; Han, Kyudong; Konkel, Miriam K; Lee, Jungnam; Smit, Arian F A; Ullmer, Brygg; Wang, Hui; Xing, Jinchuan; Burhans, Richard; Cheng, Ze; Karro, John E; Ma, Jian; Raney, Brian; She, Xinwei; Cox, Michael J; Demuth, Jeffery P; Dumas, Laura J; Han, Sang-Gook; Hopkins, Janet; Karimpour-Fard, Anis; Kim, Young H; Pollack, Jonathan R; Vinar, Tomas; Addo-Quaye, Charles; Degenhardt, Jeremiah; Denby, Alexandra; Hubisz, Melissa J; Indap, Amit; Kosiol, Carolin; Lahn, Bruce T; Lawson, Heather A; Marklein, Alison; Nielsen, Rasmus; Vallender, Eric J; Clark, Andrew G; Ferguson, Betsy; Hernandez, Ryan D; Hirani, Kashif; Kehrer-Sawatzki, Hildegard; Kolb, Jessica; Patil, Shobha; Pu, Ling-Ling; Ren, Yanru; Smith, David Glenn; Wheeler, David A; Schenck, Ian; Ball, Edward V; Chen, Rui; Cooper, David N; Giardine, Belinda; Hsu, Fan; Kent, W James; Lesk, Arthur; Nelson, David L; O'brien, William E; Prüfer, Kay; Stenson, Peter D; Wallace, James C; Ke, Hui; Liu, Xiao-Ming; Wang, Peng; Xiang, Andy Peng; Yang, Fan; Barber, Galt P; Haussler, David; Karolchik, Donna; Kern, Andy D; Kuhn, Robert M; Smith, Kayla E; Zwieg, Ann S

    2007-04-13

    The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.

  13. New GPS-Aided SINU System Modeling using an Autoregressive Model

    Directory of Open Access Journals (Sweden)

    Chot Hun Lim

    2015-09-01

    Full Text Available Stochastic error in the Micro-Electro-Mechanical-System (MEMS Strapdown Inertial Navigation Unit (SINU is the primary issue causing sensors to be unable to operate as a standalone device. Conventional implementation of MEMS SINU fuses measurement with a global positioning system (GPS through a Kalman filter in order to achieve long-term accuracy. Such integration is known as a GPS-aided SINU system, and its estimation accuracy relies on how precise the stochastic error prediction is in Kalman filtering operation. In this paper, a comprehensive study on stochastic error modeling and analysis through a Gauss-Markov (GM model and autoregressive (AR model are presented. A wavelet denoising technique is introduced prior to error modeling to remove the MEMS SINU's high frequency noise. Without a wavelet denoising technique, neither the GM model nor AR model can be utilized to represent the stochastic error of SINU. Next, details of the Kalman filter implementation to accommodate the AR model are presented. The modeling outcomes are implemented on an unmanned aerial vehicle (UAV for on-board motion sensing. The experimental results show that AR model implementation, compared to a conventional GM model, significantly reduced the estimated errors while preserving the position, velocity and orientation measurements.

  14. Auditory artificial grammar learning in macaque and marmoset monkeys.

    Science.gov (United States)

    Wilson, Benjamin; Slater, Heather; Kikuchi, Yukiko; Milne, Alice E; Marslen-Wilson, William D; Smith, Kenny; Petkov, Christopher I

    2013-11-27

    Artificial grammars (AG) are designed to emulate aspects of the structure of language, and AG learning (AGL) paradigms can be used to study the extent of nonhuman animals' structure-learning capabilities. However, different AG structures have been used with nonhuman animals and are difficult to compare across studies and species. We developed a simple quantitative parameter space, which we used to summarize previous nonhuman animal AGL results. This was used to highlight an under-studied AG with a forward-branching structure, designed to model certain aspects of the nondeterministic nature of word transitions in natural language and animal song. We tested whether two monkey species could learn aspects of this auditory AG. After habituating the monkeys to the AG, analysis of video recordings showed that common marmosets (New World monkeys) differentiated between well formed, correct testing sequences and those violating the AG structure based primarily on simple learning strategies. By comparison, Rhesus macaques (Old World monkeys) showed evidence for deeper levels of AGL. A novel eye-tracking approach confirmed this result in the macaques and demonstrated evidence for more complex AGL. This study provides evidence for a previously unknown level of AGL complexity in Old World monkeys that seems less evident in New World monkeys, which are more distant evolutionary relatives to humans. The findings allow for the development of both marmosets and macaques as neurobiological model systems to study different aspects of AGL at the neuronal level.

  15. Local Stability of AIDS Epidemic Model Through Treatment and Vertical Transmission with Time Delay

    Science.gov (United States)

    Novi W, Cascarilla; Lestari, Dwi

    2016-02-01

    This study aims to explain stability of the spread of AIDS through treatment and vertical transmission model. Human with HIV need a time to positively suffer AIDS. The existence of a time, human with HIV until positively suffer AIDS can be delayed for a time so that the model acquired is the model with time delay. The model form is a nonlinear differential equation with time delay, SIPTA (susceptible-infected-pre AIDS-treatment-AIDS). Based on SIPTA model analysis results the disease free equilibrium point and the endemic equilibrium point. The disease free equilibrium point with and without time delay are local asymptotically stable if the basic reproduction number is less than one. The endemic equilibrium point will be local asymptotically stable if the time delay is less than the critical value of delay, unstable if the time delay is more than the critical value of delay, and bifurcation occurs if the time delay is equal to the critical value of delay.

  16. Ormiaochracea as a Model Organism in Sound Localization Experiments and in Inventing Hearing Aids.

    Directory of Open Access Journals (Sweden)

    - -

    1998-09-01

    Full Text Available Hearing aid prescription for patients suffering hearing loss has always been one of the main concerns of the audiologists. Thanks to technology that has provided Hearing aids with digital and computerized systems which has improved the quality of sound heard by hearing aids. Though we can learn from nature in inventing such instruments as in the current article that has been channeled to a kind of fruit fly. Ormiaochracea is a small yellow nocturnal fly, a parasitoid of crickets. It is notable because of its exceptionally acute directional hearing. In the current article we will discuss how it has become a model organism in sound localization experiments and in inventing hearing aids.

  17. Computer-Aided Model Based Analysis for Design and Operation of a Copolymerization Process

    DEFF Research Database (Denmark)

    Lopez-Arenas, Maria Teresa; Sales-Cruz, Alfonso Mauricio; Gani, Rafiqul

    2006-01-01

    The advances in computer science and computational algorithms for process modelling, process simulation, numerical methods and design/synthesis algorithms, makes it advantageous and helpful to employ computer-aided modelling systems and tools for integrated process analysis. This is illustrated....... This will allow analysis of the process behaviour, contribute to a better understanding of the polymerization process, help to avoid unsafe conditions of operation, and to develop operational and optimizing control strategies. In this work, through a computer-aided modeling system ICAS-MoT, two first......, the process design and conditions of operation on the polymer grade and the production rate....

  18. A first course in computer-aided physiological modeling.

    Science.gov (United States)

    Rideout, V C

    1991-01-01

    Early experiences at Wisconsin with analog and analog-hybrid modeling of physiological systems (particularly cardiovascular systems) were successful in arousing student interest and led to later applications of modeling in research work by these students. Beginning in the early '80s, all-digital modeling was used in the senior-grad course ECE 620, using the ACSL language, and applications were included in compartment modeling of pharmacokinetics, modeling of cardiovascular and respiratory pressure-flow and transport, thermoregulation, and prosthetic systems. In this course initial model programs of some complexity (up to 30 differential equations, some of them nonlinear) were provided to the students so that they could easily begin to work with models of meaningful size. The use of module and "multiple model" schemes appear to make this approach successful, and extension to more advanced models is possible.

  19. [AIDS prevention in Germany - a successful model in crisis].

    Science.gov (United States)

    Rosenbrock, R

    2007-04-01

    The rising number of new HIV infections in Germany, particularly among men who have sex with men, raises the question whether the previously successful prevention strategy should be revised. This strategy has been based on a New Public Health approach which arose from the specific historical context in Europe at the start of the epidemic. The hallmarks of this approach are: the active involvement of the target groups; the central role of non-governmental organizations; the combination of population level and targeted, context specific interventions; and an emphasis on social integration and voluntary participation in the work with target group members. Current challenges include: changes in risk perception (at least in part due to the availability of more effective treatments); a diversification of prevention behavioral strategies among target group members; the formation of new sexual subcultures and target groups; as well as changes in hard-to-reach populations such as immigrants and people of lower socioeconomic status. In order to meet these challenges the following measures are necessary: an increased investment in prevention research (with a particular focus on interventions specific to social contexts in which risk behavior is increasing); further development of the institutional infrastructure for prevention, including the full implementation of UNAIDS guidelines for national prevention strategies; and improving the prevention work of local AIDS service organizations and public health authorities through an increase in funding and the implementation of quality assurance measures based on participatory action research.

  20. Computer-Aided Design of a Respirator Facepiece Model

    Science.gov (United States)

    1984-12-01

    anthropometric data by a sculptor or artist (an analog concept); a gas mask form is again sculpted from clay or plasticine over this form (again an...model-making and sculpting . ,•~- 15 - The ,iature of model-making and its application to such problems in "three-dimensional geometry as models for gas...the process of model-making - "- " the plasticine - headform - sculpture combination - is completely analog in its nature. Headforms are sculpted from

  1. Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac Disease.

    Science.gov (United States)

    Mohan, Mahesh; Chow, Cheryl-Emiliane T; Ryan, Caitlin N; Chan, Luisa S; Dufour, Jason; Aye, Pyone P; Blanchard, James; Moehs, Charles P; Sestak, Karol

    2016-10-28

    The composition of the gut microbiome reflects the overall health status of the host. In this study, stool samples representing the gut microbiomes from 6 gluten-sensitive (GS) captive juvenile rhesus macaques were compared with those from 6 healthy, age- and diet-matched peers. A total of 48 samples representing both groups were studied using V4 16S rRNA gene DNA analysis. Samples from GS macaques were further characterized based on type of diet administered: conventional monkey chow, i.e., wheat gluten-containing diet (GD), gluten-free diet (GFD), barley gluten-derived diet (BOMI) and reduced gluten barley-derived diet (RGB). It was hypothesized that the GD diet would lower the gut microbial diversity in GS macaques. This is the first report illustrating the reduction of gut microbial alpha-diversity (p gluten in GS macaques. Selected bacterial families (e.g., Streptococcaceae and Lactobacillaceae) were enriched in GS macaques while Coriobacteriaceae was enriched in healthy animals. Within several weeks after the replacement of the GD by the GFD diet, the composition (beta-diversity) of gut microbiome in GS macaques started to change (p = 0.011) towards that of a normal macaque. Significance for alpha-diversity however, was not reached by the day 70 when the feeding experiment ended. Several inflammation-associated microRNAs (miR-203, -204, -23a, -23b and -29b) were upregulated (p < 0.05) in jejunum of 4 biopsied GS macaques fed GD with predicted binding sites on 16S ribosomal RNA of Lactobacillus reuteri (accession number: NR_025911), Prevotella stercorea (NR_041364) and Streptococcus luteciae (AJ297218) that were overrepresented in feces. Additionally, claudin-1, a validated tight junction protein target of miR-29b was significantly downregulated in jejunal epithelium of GS macaques. Taken together, we predict that with the introduction of effective treatments in future studies the diversity of gut microbiomes in GS macaques will approach those of healthy

  2. Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac Disease

    Science.gov (United States)

    Mohan, Mahesh; Chow, Cheryl-Emiliane T.; Ryan, Caitlin N.; Chan, Luisa S.; Dufour, Jason; Aye, Pyone P.; Blanchard, James; Moehs, Charles P.; Sestak, Karol

    2016-01-01

    The composition of the gut microbiome reflects the overall health status of the host. In this study, stool samples representing the gut microbiomes from 6 gluten-sensitive (GS) captive juvenile rhesus macaques were compared with those from 6 healthy, age- and diet-matched peers. A total of 48 samples representing both groups were studied using V4 16S rRNA gene DNA analysis. Samples from GS macaques were further characterized based on type of diet administered: conventional monkey chow, i.e., wheat gluten-containing diet (GD), gluten-free diet (GFD), barley gluten-derived diet (BOMI) and reduced gluten barley-derived diet (RGB). It was hypothesized that the GD diet would lower the gut microbial diversity in GS macaques. This is the first report illustrating the reduction of gut microbial alpha-diversity (p < 0.05) following the consumption of dietary gluten in GS macaques. Selected bacterial families (e.g., Streptococcaceae and Lactobacillaceae) were enriched in GS macaques while Coriobacteriaceae was enriched in healthy animals. Within several weeks after the replacement of the GD by the GFD diet, the composition (beta-diversity) of gut microbiome in GS macaques started to change (p = 0.011) towards that of a normal macaque. Significance for alpha-diversity however, was not reached by the day 70 when the feeding experiment ended. Several inflammation-associated microRNAs (miR-203, -204, -23a, -23b and -29b) were upregulated (p < 0.05) in jejunum of 4 biopsied GS macaques fed GD with predicted binding sites on 16S ribosomal RNA of Lactobacillus reuteri (accession number: NR_025911), Prevotella stercorea (NR_041364) and Streptococcus luteciae (AJ297218) that were overrepresented in feces. Additionally, claudin-1, a validated tight junction protein target of miR-29b was significantly downregulated in jejunal epithelium of GS macaques. Taken together, we predict that with the introduction of effective treatments in future studies the diversity of gut microbiomes in GS

  3. Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac Disease

    Directory of Open Access Journals (Sweden)

    Mahesh Mohan

    2016-10-01

    Full Text Available The composition of the gut microbiome reflects the overall health status of the host. In this study, stool samples representing the gut microbiomes from 6 gluten-sensitive (GS captive juvenile rhesus macaques were compared with those from 6 healthy, age- and diet-matched peers. A total of 48 samples representing both groups were studied using V4 16S rRNA gene DNA analysis. Samples from GS macaques were further characterized based on type of diet administered: conventional monkey chow, i.e., wheat gluten-containing diet (GD, gluten-free diet (GFD, barley gluten-derived diet (BOMI and reduced gluten barley-derived diet (RGB. It was hypothesized that the GD diet would lower the gut microbial diversity in GS macaques. This is the first report illustrating the reduction of gut microbial alpha-diversity (p < 0.05 following the consumption of dietary gluten in GS macaques. Selected bacterial families (e.g., Streptococcaceae and Lactobacillaceae were enriched in GS macaques while Coriobacteriaceae was enriched in healthy animals. Within several weeks after the replacement of the GD by the GFD diet, the composition (beta-diversity of gut microbiome in GS macaques started to change (p = 0.011 towards that of a normal macaque. Significance for alpha-diversity however, was not reached by the day 70 when the feeding experiment ended. Several inflammation-associated microRNAs (miR-203, -204, -23a, -23b and -29b were upregulated (p < 0.05 in jejunum of 4 biopsied GS macaques fed GD with predicted binding sites on 16S ribosomal RNA of Lactobacillus reuteri (accession number: NR_025911, Prevotella stercorea (NR_041364 and Streptococcus luteciae (AJ297218 that were overrepresented in feces. Additionally, claudin-1, a validated tight junction protein target of miR-29b was significantly downregulated in jejunal epithelium of GS macaques. Taken together, we predict that with the introduction of effective treatments in future studies the diversity of gut microbiomes

  4. Examining the impacts of precipitation isotope input (δ18Oppt on distributed, tracer-aided hydrological modelling

    Directory of Open Access Journals (Sweden)

    C. J. Delavau

    2017-05-01

    δ18Oppt observations, and the value such models have in defining modelling uncertainty. In this study, application of a tracer-aided model is able to identify simulations with improved internal process representation, reinforcing the fact that tracer-aided modelling approaches assist with resolving hydrograph component contributions and work towards diagnosing equifinality.

  5. Computer-aided biokinetic modelling combined with in vitro data

    NARCIS (Netherlands)

    Ommen, B. van; Jongh, J. de; Sandt, J. van de; Blaauboer, B.; Hissink, E.; Bogaards, J.; Bladeren, P. van

    1995-01-01

    Within the framework of in vitro alternatives for in vivo safety assessment, the kinetic behaviour of a compound can be described by biokinetic models. These models, with emphasis on the physiologically based pharmacokinetic models, need a variety of biological, physicochemical and biochemical param

  6. The Conceptualization of the Mathematical Modelling Process in Technology-Aided Environment

    Science.gov (United States)

    Hidiroglu, Çaglar Naci; Güzel, Esra Bukova

    2017-01-01

    The aim of the study is to conceptualize the technology-aided mathematical modelling process in the frame of cognitive modelling perspective. The grounded theory approach was adopted in the study. The research was conducted with seven groups consisting of nineteen prospective mathematics teachers. The data were collected from the video records of…

  7. A user-friendly model for spray drying to aid pharmaceutical product development

    NARCIS (Netherlands)

    Grasmeijer, Niels; de Waard, Hans; Hinrichs, Wouter L J; Frijlink, Henderik W

    2013-01-01

    The aim of this study was to develop a user-friendly model for spray drying that can aid in the development of a pharmaceutical product, by shifting from a trial-and-error towards a quality-by-design approach. To achieve this, a spray dryer model was developed in commercial and open source spreadshe

  8. Intersegmental Coordination in the Kinematics of Prehension Movements of Macaques

    Science.gov (United States)

    Sartori, Luisa; Camperio-Ciani, Andrea; Bulgheroni, Maria; Castiello, Umberto

    2015-01-01

    The most popular model to explain how prehensile movements are organized assumes that they comprise two “components”, the reaching component encoding information regarding the object’s spatial location and the grasping component encoding information on the object’s intrinsic properties such as size and shape. Comparative kinematic studies on grasping behavior in the humans and in macaques have been carried out to investigate the similarities and differences existing across the two species. Although these studies seem to favor the hypothesis that macaques and humans share a number of kinematic features it remains unclear how the reaching and grasping components are coordinated during prehension movements in free-ranging macaque monkeys. Twelve hours of video footage was filmed of the monkeys as they snatched food items from one another (i.e., snatching) or collect them in the absence of competitors (i.e., unconstrained). The video samples were analyzed frame-by-frame using digitization techniques developed to perform two-dimensional post-hoc kinematic analyses of the two types of actions. The results indicate that only for the snatching condition when the reaching variability increased there was an increase in the amplitude of maximum grip aperture. Besides, the start of a break-point along the deceleration phase of the velocity profile correlated with the time at which maximum grip aperture occurred. These findings suggest that macaques can spatially and temporally couple the reaching and the grasping components when there is pressure to act quickly. They offer a substantial contribution to the debate about the nature of how prehensile actions are programmed. PMID:26176232

  9. Computer-Aided Structural Engineering (CASE) Project. User’s Guide: Computer-Aided Structural Modeling (CASM). Version 5.00

    Science.gov (United States)

    1994-04-01

    w transferred to the laeral resistance localions by tributary wee or continuous bean model . For rigid diaphragms, lateral loads we translerred to the...floors aid roof planes, a Flexible Diaphragm dialog window wil appea Didnu.•e Leeuds aewd On- 0 Siml I.. Model 0 Ceiwmus Bean Model a. Select Simple

  10. An Interrogative Model of Computer-Aided Adaptive Testing: Some Experimental Evidence

    Science.gov (United States)

    1988-09-01

    aquired knowledge. This thesis proposes and validates a computer-aided testing model called the Interrogative Diagnostic Model (IDM). The model is...PROGRAM DESIGN The design of a program to implement the model vas quite straight forvard. dB&8B III Plus vas the language selected for Implementation...true/false. Due to the inability of the dBASE III Plus in processing natural language essay type questions vere excluded. The content of the questions

  11. Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir.

    Directory of Open Access Journals (Sweden)

    J Gerardo García-Lerma

    2008-02-01

    Full Text Available BACKGROUND: In the absence of an effective vaccine, HIV continues to spread globally, emphasizing the need for novel strategies to limit its transmission. Pre-exposure prophylaxis (PrEP with antiretroviral drugs could prove to be an effective intervention strategy if highly efficacious and cost-effective PrEP modalities are identified. We evaluated daily and intermittent PrEP regimens of increasing antiviral activity in a macaque model that closely resembles human transmission. METHODS AND FINDINGS: We used a repeat-exposure macaque model with 14 weekly rectal virus challenges. Three drug treatments were given once daily, each to a different group of six rhesus macaques. Group 1 was treated subcutaneously with a human-equivalent dose of emtricitabine (FTC, group 2 received orally the human-equivalent dosing of both FTC and tenofovir-disoproxil fumarate (TDF, and group 3 received subcutaneously a similar dosing of FTC and a higher dose of tenofovir. A fourth group of six rhesus macaques (group 4 received intermittently a PrEP regimen similar to group 3 only 2 h before and 24 h after each weekly virus challenge. Results were compared to 18 control macaques that did not receive any drug treatment. The risk of infection in macaques treated in groups 1 and 2 was 3.8- and 7.8-fold lower than in untreated macaques (p = 0.02 and p = 0.008, respectively. All six macaques in group 3 were protected. Breakthrough infections had blunted acute viremias; drug resistance was seen in two of six animals. All six animals in group 4 that received intermittent PrEP were protected. CONCLUSIONS: This model suggests that single drugs for daily PrEP can be protective but a combination of antiretroviral drugs may be required to increase the level of protection. Short but potent intermittent PrEP can provide protection comparable to that of daily PrEP in this SHIV/macaque model. These findings support PrEP trials for HIV prevention in humans and identify promising Pr

  12. A Mathematical Model of Complacency in HIV/AIDS Scenario: Sex-Structure Approach

    Directory of Open Access Journals (Sweden)

    Gbolahan BOLARIN

    2012-12-01

    Full Text Available In this study we use sex-structure approach to examine the effect of complacent sexual behaviour (risky sexual activities on the rate of infection of HIV/AIDS in a population. We partitioned the population into two classes (male and female represented by to express our model equation as a set of differential equations. We were able to express the number of AIDS cases (male and female as linear functions that depend on the number of AIDS patient present in the population. We were also able to determine the equilibra states of the model. We found that the Basic Reproduction Number (R0, which is the number of secondary infections due to introduction of infective into the population of both female and male partitions of the population is given as R0=sqrt(R0fRom.

  13. COMPUTER- AIDED MODELING AND IMPROVING OF RISOGRAPH PRINTING

    Directory of Open Access Journals (Sweden)

    P. E. Sulim

    2014-01-01

    Full Text Available The considered improvement of qualit y of the risofraph print based on a mathematical model in the environment Matlab by using the specialized algorithms and digital filter of the Image Processing Toolbox. Use the model of screen printing in Matlab environment for risograph provide an opportunit y to improve the qualit y of prints by adjusting profile risograph to a specific view and the t ype of digital image. The use of the proposed technology will reduce the flow of the film and the paint by eliminating printing test prints and reducing the time spent printing.

  14. Modeling Soil Erosion with the Aid of GIS

    Institute of Scientific and Technical Information of China (English)

    WU Ping-li

    2005-01-01

    Soil erosion caused by water is an increasing global problem. In order to relieve this problem, several erosion models have been developed to measure the rate of erosion for soil conservation planning. This study takes Lee County, South Carolina, USA as an example to map soil erosion within ArcGIS environment by using the RUSLE with erosion indexes retrieved from DEM. This study proves that the integration of soil erosion models with GIS is a very simple but efficient tool for soil conservation.

  15. Toward Developing Genetic Algorithms to Aid in Critical Infrastructure Modeling

    Energy Technology Data Exchange (ETDEWEB)

    2007-05-01

    Today’s society relies upon an array of complex national and international infrastructure networks such as transportation, telecommunication, financial and energy. Understanding these interdependencies is necessary in order to protect our critical infrastructure. The Critical Infrastructure Modeling System, CIMS©, examines the interrelationships between infrastructure networks. CIMS© development is sponsored by the National Security Division at the Idaho National Laboratory (INL) in its ongoing mission for providing critical infrastructure protection and preparedness. A genetic algorithm (GA) is an optimization technique based on Darwin’s theory of evolution. A GA can be coupled with CIMS© to search for optimum ways to protect infrastructure assets. This includes identifying optimum assets to enforce or protect, testing the addition of or change to infrastructure before implementation, or finding the optimum response to an emergency for response planning. This paper describes the addition of a GA to infrastructure modeling for infrastructure planning. It first introduces the CIMS© infrastructure modeling software used as the modeling engine to support the GA. Next, the GA techniques and parameters are defined. Then a test scenario illustrates the integration with CIMS© and the preliminary results.

  16. Inversion aided systems for stratigraphic models; Systemes d'aide a l'inversion des modeles stratigraphiques

    Energy Technology Data Exchange (ETDEWEB)

    Dobranszky, G.

    2005-12-15

    Stratigraphic modeling aims at rebuilding the history of the sedimentary basins by simulating the processes of erosion, transport and deposit of sediments using physical models. The objective is to determine the location of the bed-rocks likely to contain the organic matter, the location of the porous rocks that could trap the hydrocarbons during their migration and the location of the impermeable rocks likely to seal the reservoir. The model considered within this thesis is based on a multi-lithological diffusive transport model and applies to large scales of time and space. Due to the complexity of the phenomena and scales considered, none of the model parameters is directly measurable. Therefore it is essential to inverse them. The standard approach, which consists in inverting all the parameters by minimizing a cost function using a gradient method, proved very sensitive to the choice of the parameterization, to the weights given to the various terms of the cost function (hearing on data of very diverse nature) and to the numerical noise. These observations led us to give up this method and to carry out the in-version step by step by decoupling the parameters. This decoupling is not obtained by fixing the parameters but by making several assumptions on the model resulting in a range of reduced but relevant models. In this thesis, we show how these models enable us to inverse all the parameters in a robust and interactive way. (author)

  17. Operator function modeling: Cognitive task analysis, modeling and intelligent aiding in supervisory control systems

    Science.gov (United States)

    Mitchell, Christine M.

    1990-01-01

    The design, implementation, and empirical evaluation of task-analytic models and intelligent aids for operators in the control of complex dynamic systems, specifically aerospace systems, are studied. Three related activities are included: (1) the models of operator decision making in complex and predominantly automated space systems were used and developed; (2) the Operator Function Model (OFM) was used to represent operator activities; and (3) Operator Function Model Expert System (OFMspert), a stand-alone knowledge-based system was developed, that interacts with a human operator in a manner similar to a human assistant in the control of aerospace systems. OFMspert is an architecture for an operator's assistant that uses the OFM as its system and operator knowledge base and a blackboard paradigm of problem solving to dynamically generate expectations about upcoming operator activities and interpreting actual operator actions. An experiment validated the OFMspert's intent inferencing capability and showed that it inferred the intentions of operators in ways comparable to both a human expert and operators themselves. OFMspert was also augmented with control capabilities. An interface allowed the operator to interact with OFMspert, delegating as much or as little control responsibility as the operator chose. With its design based on the OFM, OFMspert's control capabilities were available at multiple levels of abstraction and allowed the operator a great deal of discretion over the amount and level of delegated control. An experiment showed that overall system performance was comparable for teams consisting of two human operators versus a human operator and OFMspert team.

  18. Markov chain modelling analysis of HIV/AIDS progression: A race-based forecast in the United States

    Directory of Open Access Journals (Sweden)

    S Lee

    2014-01-01

    Full Text Available HIV/AIDS has reached a pandemic level across the world with more than 33 million people who are living with HIV. In the United States, more than half a million people have been victims of AIDS. This study investigates the most vulnerable racial minority population (the African Americans in the United States and the second least affected (the Caucasians in order to predict the trends of the epidemic. A Markov chain analysis was used to model the progression of the disease among vulnerable people, infective people and AIDS cases for the two races separately, based on the 2009 Centers of Disease Control and Prevention HIV/AIDS Surveillance Report. Based on the Markov model, our study predicts that the number of African American people living with AIDS diagnosis and HIV infection and dead due to HIV/AIDS will be 662.2, 1225.3 and 62.9 in 2015 and 794.9, 1566.5 and 79.2 in 2030, respectively. The number of Caucasian people living with AIDS diagnosis and HIV infection and dead due to HIV/AIDS will be 96.4, 160 and 6.5 in 2015 and 118.6, 206.9 and 8.3 in 2030, respectively. The numbers of deaths due to HIV/AIDS are quite stable over the years in both the races. There is an increasing trend in the number of people living with HIV infection and AIDS diagnosis in Caucasians compared with African Americans. The absolute number of Caucasians living with AIDS diagnosis and HIV infection is quite smaller compared with African Americans. The results reveal discrepancy in HIV infection, AIDS diagnosis and deaths due to HIV/AIDS among the African Americans and the Caucasians races. There is a need for interventions focusing on HIV/AIDS prevention and management, optimum resource allocation and development of antiAIDS campaigns to reduce the infection rate.

  19. Markov Chain Modelling Analysis of HIV/AIDS Progression: A Race-based Forecast in the United States.

    Science.gov (United States)

    Lee, S; Ko, J; Tan, Xi; Patel, Isha; Balkrishnan, R; Chang, J

    2014-03-01

    HIV/AIDS has reached a pandemic level across the world with more than 33 million people who are living with HIV. In the United States, more than half a million people have been victims of AIDS. This study investigates the most vulnerable racial minority population (the African Americans) in the United States and the second least affected (the Caucasians) in order to predict the trends of the epidemic. A Markov chain analysis was used to model the progression of the disease among vulnerable people, infective people and AIDS cases for the two races separately, based on the 2009 Centers of Disease Control and Prevention HIV/AIDS Surveillance Report. Based on the Markov model, our study predicts that the number of African American people living with AIDS diagnosis and HIV infection and dead due to HIV/AIDS will be 662.2, 1225.3 and 62.9 in 2015 and 794.9, 1566.5 and 79.2 in 2030, respectively. The number of Caucasian people living with AIDS diagnosis and HIV infection and dead due to HIV/AIDS will be 96.4, 160 and 6.5 in 2015 and 118.6, 206.9 and 8.3 in 2030, respectively. The numbers of deaths due to HIV/AIDS are quite stable over the years in both the races. There is an increasing trend in the number of people living with HIV infection and AIDS diagnosis in Caucasians compared with African Americans. The absolute number of Caucasians living with AIDS diagnosis and HIV infection is quite smaller compared with African Americans. The results reveal discrepancy in HIV infection, AIDS diagnosis and deaths due to HIV/AIDS among the African Americans and the Caucasians races. There is a need for interventions focusing on HIV/AIDS prevention and management, optimum resource allocation and development of antiAIDS campaigns to reduce the infection rate.

  20. A web service for service composition to aid geospatial modelers

    Science.gov (United States)

    Bigagli, L.; Santoro, M.; Roncella, R.; Mazzetti, P.

    2012-04-01

    The identification of appropriate mechanisms for process reuse, chaining and composition is considered a key enabler for the effective uptake of a global Earth Observation infrastructure, currently pursued by the international geospatial research community. In the Earth and Space Sciences, such a facility could primarily enable integrated and interoperable modeling, for what several approaches have been proposed and developed, over the last years. In fact, GEOSS is specifically tasked with the development of the so-called "Model Web". At increasing levels of abstraction and generalization, the initial stove-pipe software tools have evolved to community-wide modeling frameworks, to Component-Based Architecture solution, and, more recently, started to embrace Service-Oriented Architectures technologies, such as the OGC WPS specification and the WS-* stack of W3C standards for service composition. However, so far, the level of abstraction seems too low for implementing the Model Web vision, and far too complex technological aspects must still be addressed by both providers and users, resulting in limited usability and, eventually, difficult uptake. As by the recent ICT trend of resource virtualization, it has been suggested that users in need of a particular processing capability, required by a given modeling workflow, may benefit from outsourcing the composition activities into an external first-class service, according to the Composition as a Service (CaaS) approach. A CaaS system provides the necessary interoperability service framework for adaptation, reuse and complementation of existing processing resources (including models and geospatial services in general) in the form of executable workflows. This work introduces the architecture of a CaaS system, as a distributed information system for creating, validating, editing, storing, publishing, and executing geospatial workflows. This way, the users can be freed from the need of a composition infrastructure and

  1. Stigma, sexual risks, and the war on drugs: Examining drug policy and HIV/AIDS inequities among African Americans using the Drug War HIV/AIDS Inequities Model.

    Science.gov (United States)

    Kerr, Jelani; Jackson, Trinidad

    2016-11-01

    The relationship between drug policy and HIV vulnerability is well documented. However, little research examines the links between racial/ethnic HIV disparities via the Drug War, sexual risk, and stigma. The Drug War HIV/AIDS Inequities Model has been developed to address this dearth. This model contends that inequitable policing and sentencing promotes sexual risks, resource deprivation, and ultimately greater HIV risk for African-Americans. The Drug War also socially marginalizes African Americans and compounds stigma for incarcerated and formerly incarcerated persons living with HIV/AIDS. This marginalization has implications for sexual risk-taking, access to health-promoting resources, and continuum of care participation. The Drug War HIV/AIDS Inequities Model may help illuminate mechanisms that promote increased HIV vulnerability as well as inform structural intervention development and targeting to address racial/ethnic disparities. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. A Patient Monitoring Tool For An HIV/AIDS Integral Care Model

    Science.gov (United States)

    2007-11-02

    AIDS INTEGRAL CARE MODEL C. Cáceres, E.J. Gómez, F. Del Pozo Grupo de Bioingeniería y Telemedicina , Universidad Politécnica de Madrid, Madrid...Performing Organization Name(s) and Address(es) Grupo de Bioingenieria y Telemedicina Universidad Politecnica de Madrid Madrid, Spain Performing

  3. Which Cooperative Ownership Model Performs Better? A Financial-Decision Aid Approach

    NARCIS (Netherlands)

    Kalogeras, N.; Pennings, J.M.E.; Benos, T.; Doumpos, M.

    2013-01-01

    In this article the financial/ownership structures of agribusiness cooperatives are analyzed to examine whether new cooperative models perform better than the more traditional ones. The assessment procedure introduces a new financial decision-aid approach, which is based on data-analysis techniques

  4. Capacity expansion modelling to aid water supply investment decisions

    OpenAIRE

    Padula, S

    2015-01-01

    Increasing population, economic development, and environmental changes imply that maintaining the water supply-demand balance will remain a top priority. Water resource systems may need to be expanded in order to respond to demand growth. Capacity expansion studies can be used to answer the question of what the optimal expansion size, timing and location of new infrastructure should be. This thesis develops and applies capacity expansion optimisation modelling approaches. We begin with the 'E...

  5. Computer-Aided Process Model For Carbon/Phenolic Materials

    Science.gov (United States)

    Letson, Mischell A.; Bunker, Robert C.

    1996-01-01

    Computer program implements thermochemical model of processing of carbon-fiber/phenolic-matrix composite materials into molded parts of various sizes and shapes. Directed toward improving fabrication of rocket-engine-nozzle parts, also used to optimize fabrication of other structural components, and material-property parameters changed to apply to other materials. Reduces costs by reducing amount of laboratory trial and error needed to optimize curing processes and to predict properties of cured parts.

  6. Minor contributions of the maxillary sinus to the air-conditioning performance in macaque monkeys.

    Science.gov (United States)

    Mori, Futoshi; Hanida, Sho; Kumahata, Kiyoshi; Miyabe-Nishiwaki, Takako; Suzuki, Juri; Matsuzawa, Teruo; Nishimura, Takeshi D

    2015-08-01

    The nasal passages mainly adjust the temperature and humidity of inhaled air to reach the alveolar condition required in the lungs. By contrast to most other non-human primates, macaque monkeys are distributed widely among tropical, temperate and subarctic regions, and thus some species need to condition the inhaled air in cool and dry ambient atmospheric areas. The internal nasal anatomy is believed to have undergone adaptive modifications to improve the air-conditioning performance. Furthermore, the maxillary sinus (MS), an accessory hollow communicating with the nasal cavity, is found in macaques, whereas it is absent in most other extant Old World monkeys, including savanna monkeys. In this study, we used computational fluid dynamics simulations to simulate the airflow and heat and water exchange over the mucosal surface in the nasal passage. Using the topology models of the nasal cavity with and without the MS, we demonstrated that the MS makes little contribution to the airflow pattern and the air-conditioning performance within the nasal cavity in macaques. Instead, the inhaled air is conditioned well in the anterior portion of the nasal cavity before reaching the MS in both macaques and savanna monkeys. These findings suggest that the evolutionary modifications and coetaneous variations in the nasal anatomy are rather independent of transitions and variations in the climate and atmospheric environment found in the habitats of macaques. © 2015. Published by The Company of Biologists Ltd.

  7. Variation in intergroup encounters among two provisioned free-ranging populations of Japanese macaques Macaca fuscata

    Institute of Scientific and Technical Information of China (English)

    Peng ZHANG; Kunio WATANABE

    2012-01-01

    Typically,Japanese macaques are thought to avoid encountering other groups wherever possible.Intergroup relations between macaques on Shodoshima Island,however,appear exceptional.We show that neighboring groups of Shodoshima monkeys spent 32.8% of their active time in proximity to (<100 m) and even foraged simultaneously at the same provisioning site with another group.The average duration and rate of intergroup encounters at Shodoshima (59.8 min,0.33 times/hour,n=269)were approximately ten times longer and 16.5 times more frequent than those at Jigokudani (6.1 min,0.02 times/hour,n=14).Since both populations have similar provisioning and ecological conditions,such variation cannot be explained by the socioecology model alone.Compared with other populations of Japanese macaques,intergroup relations of Shodoshima monkeys are also characterized by more frequent neutral encounters,less frequent agonistic encounters,more frequent unsuccessful displacement,a lower intensity of aggression,and more frequent counter-aggression between groups.These characteristics suggest that intergroup relationships on Shodoshima Island are more tolerant than those in other Japanese macaque populations.This study reveals considerable differences in intergroup encounters within local populations of Japanese macaques living in similar environments,and emphasizes the role of social factors in such intra-specific variation.

  8. Model-aided Navigation with Sea Current Estimation for an Autonomous Underwater Vehicle

    Directory of Open Access Journals (Sweden)

    Alain Martinez

    2015-07-01

    Full Text Available This paper presents a strategy to improve the navigation solution of the HRC-AUV by deploying a model-aided inertial navigation system (MA-INS. Based on a simpler three-DOF linear dynamic model (DM of the vehicle, and implemented through a Kalman filter (KF, the performance of the proposed MA-INS is compared to state-of-the-art solutions based on non-linear models. The model allows the online estimation of the sea current parameters before and during the navigation mission. Qualitative and quantitative evaluations as well as a statistical significance test are performed using both simulated and real data, demonstrating the usefulness of the proposed model-aided navigation.

  9. Model-Aided Navigation with Sea Current Estimation for an Autonomous Underwater Vehicle

    Directory of Open Access Journals (Sweden)

    Alain Martinez

    2015-07-01

    Full Text Available This paper presents a strategy to improve the navigation solution of the HRC-AUV by deploying a model-aided inertial navigation system (MA-INS. Based on a simpler three-DOF linear dynamic model (DM of the vehicle, and implemented through a Kalman filter (KF, the performance of the proposed MA-INS is compared to state-of-the-art solutions based on non-linear models. The model allows the online estimation of the sea current parameters before and during the navigation mission. Qualitative and quantitative evaluations as well as a statistical significance test are performed using both simulated and real data, demonstrating the usefulness of the proposed model-aided navigation.

  10. Model-based computer-aided design for controlled release of pesticides

    DEFF Research Database (Denmark)

    Muro Sunè, Nuria; Gani, Rafiqul; Bell, G.;

    2005-01-01

    In the field of controlled release technology for pesticides or active ingredients (AI), models that can predict its delivery during application are important for purposes of design and marketing of the pesticide product. Appropriate models for the controlled release of pesticides, if available, ...... extended models have been developed and implemented into a computer-aided system. The total model consisting of the property models embedded into the release models are then employed to study the release of different combinations of AIs and polymer-based microcapsules....

  11. Serologic host response to Helicobacter pylori and Campylobacter jejuni in socially housed Rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Kienesberger, Sabine; Perez-Perez, Guillermo I; Rivera-Correa, Juan L; Tosado-Acevedo, Rafael; Li, Huilin; Dubois, Andre; Gonzalez-Martinez, Janis A; Dominguez-Bello, Maria Gloria; Blaser, Martin J

    2012-08-24

    Helicobacter pylori are successful colonizers of the human gastric mucosa. Colonization increases the risk of peptic ulcer disease and adenocarcinoma. However, potential benefits of H. pylori colonization include protection against early-onset asthma and against gastrointestinal infections. Campylobacter jejuni are a leading cause of bacterial diarrhea and complications include Guillain-Barré syndrome. Here, we describe the development of reliable serological assays to detect antibodies against those two bacteria in Rhesus macaques and investigated their distribution within a social group of monkeys. Two cohorts of monkeys were analyzed. The first cohort consisted of 30 monkeys and was used to establish an enzyme-linked immunosorbent assay (ELISA) for H. pylori antibodies detection. To evaluate colonization of those macaques, stomach biopsies were collected and analyzed for the presence of H. pylori by histology and culture. C. jejuni ELISAs were established using human serum with known C. jejuni antibody status. Next, plasma samples of the 89 macaques (Cohort 2) were assayed for antibodies and then statistically analyzed. An H. pylori IgG ELISA, which was 100% specific and 93% sensitive, was established. In contrast, the IgA ELISA was only 82% specific and 61% sensitive. The CagA IgG assay was 100% sensitive and 61% of the macaques were positive. In cohort 2, 62% macaques were H. pylori sero-positive and 52% were CagA positive. The prevalence of H. pylori IgG and CagA IgG increased with monkey age as described for humans. Of the 89 macaques 52% showed IgG against C. jejuni but in contrast to H. pylori, the sero-prevalence was not associated with increasing age. However, there was a drop in the IgG (but not in IgA) mean values between infant and juvenile macaques, similar to trends described in humans. Rhesus macaques have widespread exposure to H. pylori and C. jejuni, reflecting their social conditions and implying that Rhesus macaques might provide a model to

  12. Serologic host response to Helicobacter pylori and Campylobacter jejuni in socially housed Rhesus macaques (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Kienesberger Sabine

    2012-08-01

    conditions and implying that Rhesus macaques might provide a model to study effects of these two important human mucosal bacteria on a population.

  13. Immunoglobulin VH gene diversity and somatic hypermutation during SIV infection of rhesus macaques.

    Science.gov (United States)

    Guo, Kejun; Halemano, Kalani; Schmitt, Kimberly; Katuwal, Miki; Wang, Yaqiong; Harper, Michael S; Heilman, Karl J; Kuwata, Takeo; Stephens, Edward B; Santiago, Mario L

    2015-07-01

    B cell functional defects are associated with delayed neutralizing antibody development in pathogenic lentivirus infections. However, the timeframe for alterations in the antibody repertoire and somatic hypermutation (SHM) remains unclear. Here, we utilized the SIV/rhesus macaque (RM) model to investigate the dynamics of immunoglobulin V(H) gene diversity and SHM following infection. Three RMs were infected with SIVmac239, and V(H)1, V(H)3, and V(H)4 genes were amplified from peripheral blood at 0, 2, 6, 24, and 36 weeks postinfection for next-generation sequencing. Analysis of over 3.8 million sequences against currently available RM germline V(H) genes revealed a highly biased V(H) gene repertoire in outbred RMs. SIV infection did not significantly perturb the predominant IgG1 response, but overall immunoglobulin SHM declined during the course of SIV infection. Moreover, SHM at the AID deamination hotspot, WRC, rapidly decreased and was suppressed throughout SIV infection. In contrast, a transient increase in mutations at the APOBEC3G deamination hotspot, CCC, coincided with a spike in APOBEC3G expression during acute SIV infection. The results outline a timetable for altered V(H) gene repertoire and IgG SHM in the SIV/RM model and suggest a burst of APOBEC3G-mediated antibody SHM during acute SIV infection.

  14. Unique pattern of enzootic primate viruses in Gibraltar macaques.

    Science.gov (United States)

    Engel, Gregory A; Pizarro, Mark; Shaw, Eric; Cortes, John; Fuentes, Agustin; Barry, Peter; Lerche, Nicholas; Grant, Richard; Cohn, Douglas; Jones-Engel, Lisa

    2008-07-01

    Because Gibraltar's macaques (Macaca sylvanus) have frequent contact with humans, we assayed 79 macaques for antibodies to enzootic primate viruses. All macaques were seronegative for herpesvirus B, simian T-cell lymphotropic virus, simian retrovirus, simian immunodeficiency virus, and rhesus cytomegalovirus. Seroprevalence of simian foamy virus reached 88% among adult animals.

  15. Craniodental variation among Macaques (Macaca, nonhuman primates

    Directory of Open Access Journals (Sweden)

    Pan Ruliang

    2002-05-01

    Full Text Available Abstract Background In terms of structure and function, the skull is one of the most complicated organs in the body. It is also one of the most important parts in terms of developmental and evolutionary origins. This complexity makes it difficult to obtain evolutionary assessments if, as is usually the case with fossils, only part of the skull is available. For this reason this study involves a set of comparisons whereby the smallest functional units are studied first, and these built up, through a triple-nested hierarchical design, into more complex anatomical regions and eventually into the skull-as-a-whole. This design has been applied to macaques (Macaca in order to reveal patterns of variation at the different levels. The profiles of such variation have been obtained both within and between species. This has lead to a search for the skull parts that have undergone similar selection pressures during evolution and comparable development patterns in both ontogeny and phylogeny. Results Morphometric analysis (Principal Components was used to obtain these profiles of species and sex separations based on 77 cranial variables from 11 species of macaques. The results showed that 7 functional units could be aggregated into three functionally reasonable anatomical regions on the basis of similarities in profiles. These were: the masticatory apparatus containing mandible, lower teeth and upper teeth, the face as a whole combining maxilla (actually lower face and upper face, and the cranium as a whole involving cranium and calvaria. Twenty-six variables were finally selected for analyzing the morphology of the whole skull. This last showed an overall profile similar to that revealed in the masticatory apparatus but also contained additional information pertaining to individual species and species-groups separations. Conclusions The study provides a model for carrying out analysis of species separations and sex variation simultaneously. Through this

  16. Laboratory rhesus macaque social housing and social changes: Implications for research.

    Science.gov (United States)

    Hannibal, Darcy L; Bliss-Moreau, Eliza; Vandeleest, Jessica; McCowan, Brenda; Capitanio, John

    2017-01-01

    Macaque species, specifically rhesus (Macaca mulatta), are the most common nonhuman primates (NHPs) used in biomedical research due to their suitability as a model of high priority diseases (e.g., HIV, obesity, cognitive aging), cost effective breeding and housing compared to most other NHPs, and close evolutionary relationship to humans. With this close evolutionary relationship, however, is a shared adaptation for a socially stimulating environment, without which both their welfare and suitability as a research model are compromised. While outdoor social group housing provides the best approximation of a social environment that matches the macaque behavioral biology in the wild, this is not always possible at all facilities, where animals may be housed indoors in small groups, in pairs, or alone. Further, animals may experience many housing changes in their lifetime depending on project needs, changes in social status, management needs, or health concerns. Here, we review the evidence for the physiological and health effects of social housing changes and the potential impacts on research outcomes for studies using macaques, particularly rhesus. We situate our review in the context of increasing regulatory pressure for research facilities to both house NHPs socially and mitigate trauma from social aggression. To meet these regulatory requirements and further refine the macaque model for research, significant advances must be made in our understanding and management of rhesus macaque social housing, particularly pair-housing since it is the most common social housing configuration for macaques while on research projects. Because most NHPs are adapted for sociality, a social context is likely important for improving repeatability, reproducibility, and external validity of primate biomedical research. Am. J. Primatol. 79:e22528, 2017. © 2016 Wiley Periodicals, Inc.

  17. Modelling and Evaluation of Spectra in Beam Aided Spectroscopy

    Science.gov (United States)

    von Hellermann, M. G.; Delabie, E.; Jaspers, R.; Lotte, P.; Summers, H. P.

    2008-10-01

    The evaluation of active beam induced spectra requires advanced modelling of both active and passive features. Three types of line shapes are addressed in this paper: Thermal spectra representing Maxwellian distribution functions described by Gaussian-like line shapes, secondly broad-band fast ion spectra with energies well above local ion temperatures, and, finally, the narrow lines shapes of the equi-spaced Motion Stark multiplet (MSE) of excited neutral beam particles travelling through the magnetic field confining the plasma. In each case additional line shape broadening caused by Gaussian-like instrument functions is taken into account. Further broadening effects are induced by collision velocity dependent effective atomic rates where the observed spectral shape is the result of a convolution of emission rate function and velocity distribution function projected into the direction of observation. In the case of Beam Emission Spectroscopy which encompasses the Motional Stark features, line broadening is also caused by the finite angular spread of injected neutrals and secondly by a ripple in the acceleration voltage associated with high energy neutral beams.

  18. Stereolithographic modelling as an aid to orbital brachytherapy.

    Science.gov (United States)

    Poulsen, M; Lindsay, C; Sullivan, T; D'Urso, P

    1999-06-01

    This paper describes the technique of stereolithographic biomodelling and its application to a patient who was treated using orbital brachytherapy. The process uses a moving laser beam, directed by a computer, to draw cross-sections of the model onto the surface of photo-curable liquid plastic. Using a stereolithographic apparatus (SLA), solid or surface data is sliced by software into very thin cross-sections. A helium cadmium (HeCd) laser then generates a small intense spot of ultraviolet (UV) light that is moved across the top of a vat of liquid photo monomer by a computerised optical scanning system. The laser polymerises the liquid into a solid where it touches, precisely printing each cross-section. A vertical elevator lowers the newly formed layer, and a recoating and levelling system establishes the next layer's thickness. Successive cross-sections (0.25 mm thick), each one adhering to the one below, are built one on top of the other, to form the part from the bottom up. The biomodel allowed the implant to be planned in detail prior to the surgery. The accurate placement of brachytherapy catheters was assured, and the dosimetry could be determined and optimised prior to the definitive procedure. Stereolithography is a useful technique in the area of orbital brachytherapy. It allows the implant to to be carried out with greater accuracy and confidence. For the patient, it minimises the risk to the eye and provides them with a greater understanding of the procedure.

  19. OCT-aided anastomosis platform study in the rodent model

    Science.gov (United States)

    Huang, Yong; Tong, Dedi; Zhu, Shan; Wu, Lehao; Ibrahim, Zuhaib; Lee, WP Andrew; Brandacher, Gerald; Kang, Jin U.

    2014-02-01

    Anastomosis is one of the most commonly performed procedure in the clinical environment that involves tubular structures, such as blood vessel, lymphatic vessel, seminal duct and ureter. Suture based anastomosis is still the foundation for most basic surgical training and clinical operation, although alternate techniques have been developed and under development. For those tubular-structure-anastomosis, immediate real-time post-operative evaluation of the surgical outcome is critical to the success of surgery. Previously evaluation is mostly based on surgeons' experience. Fourier-domain optical coherence tomography is high-speed, high-resolution noninvasive 3D imaging modality that has been widely used in the biomedical research and clinical study. In this study we used Fourier-domain optical coherence tomography as an evaluation tool for anastomosis of lymphatic vessels, ureter and seminal duct in rodent model. Immediate post-operative and long term surgical site data were collected and analyzed. Critical clinical parameters such as lumen patency, anastomosed site narrowing and suture error detection are provided to surgeons.

  20. Characterization of the Cag pathogenicity island in Helicobacter pylori from naturally infected rhesus macaques.

    Science.gov (United States)

    Skoog, Emma C; Deck, Samuel L; Entwistle, Hasan D; Hansen, Lori M; Solnick, Jay V

    2016-12-01

    Helicobacter pylori commonly infects the epithelial layer of the human stomach and in some individuals causes peptic ulcers, gastric adenocarcinoma or gastric lymphoma. Helicobacter pylori is a genetically diverse species, and the most important bacterial virulence factor that increases the risk of developing disease, versus asymptomatic colonization, is the cytotoxin associated gene pathogenicity island (cagPAI). Socially housed rhesus macaques are often naturally infected with H. pylori similar to that which colonizes humans, but little is known about the cagPAI. Here we show that H. pylori strains isolated from naturally infected rhesus macaques have a cagPAI very similar to that found in human clinical isolates, and like human isolates, it encodes a functional type IV secretion system. These results provide further support for the relevance of rhesus macaques as a valid experimental model for H. pylori infection in humans.

  1. Comparative analysis of the macroscale structural connectivity in the macaque and human brain.

    Directory of Open Access Journals (Sweden)

    Alexandros Goulas

    2014-03-01

    Full Text Available The macaque brain serves as a model for the human brain, but its suitability is challenged by unique human features, including connectivity reconfigurations, which emerged during primate evolution. We perform a quantitative comparative analysis of the whole brain macroscale structural connectivity of the two species. Our findings suggest that the human and macaque brain as a whole are similarly wired. A region-wise analysis reveals many interspecies similarities of connectivity patterns, but also lack thereof, primarily involving cingulate regions. We unravel a common structural backbone in both species involving a highly overlapping set of regions. This structural backbone, important for mediating information across the brain, seems to constitute a feature of the primate brain persevering evolution. Our findings illustrate novel evolutionary aspects at the macroscale connectivity level and offer a quantitative translational bridge between macaque and human research.

  2. Research on Computer Aided Innovation Model of Weapon Equipment Requirement Demonstration

    Science.gov (United States)

    Li, Yong; Guo, Qisheng; Wang, Rui; Li, Liang

    Firstly, in order to overcome the shortcoming of using only AD or TRIZ solely, and solve the problems currently existed in weapon equipment requirement demonstration, the paper construct the method system of weapon equipment requirement demonstration combining QFD, AD, TRIZ, FA. Then, we construct a CAI model frame of weapon equipment requirement demonstration, which include requirement decomposed model, requirement mapping model and requirement plan optimization model. Finally, we construct the computer aided innovation model of weapon equipment requirement demonstration, and developed CAI software of equipment requirement demonstration.

  3. Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets

    KAUST Repository

    Najera, Julia A.

    2016-04-23

    Background Methamphetamine (Meth) abuse is a major health problem linked to the aggravation of HIV- associated complications, especially within the Central Nervous System (CNS). Within the CNS, Meth has the ability to modify the activity/function of innate immune cells and increase brain viral loads. Here, we examined changes in the gene expression profile of neuron-free microglial cell preparations isolated from the brain of macaques infected with the Simian Immunodeficiency Virus (SIV), a model of neuroAIDS, and exposed to Meth. We aimed to identify molecular patterns triggered by Meth that could explain the detection of higher brain viral loads and the development of a pro-inflammatory CNS environment in the brain of infected drug abusers. Results We found that Meth alone has a strong effect on the transcription of genes associated with immune pathways, particularly inflammation and chemotaxis. Systems analysis led to a strong correlation between Meth exposure and enhancement of molecules associated with chemokines and chemokine receptors, especially CXCR4 and CCR5, which function as co-receptors for viral entry. The increase in CCR5 expression was confirmed in the brain in correlation with increased brain viral load. Conclusions Meth enhances the availability of CCR5-expressing cells for SIV in the brain, in correlation with increased viral load. This suggests that Meth is an important factor in the susceptibility to the infection and to the aggravated CNS inflammatory pathology associated with SIV in macaques and HIV in humans.

  4. Supplementary Material for: Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets

    KAUST Repository

    Najera, Julia

    2016-01-01

    Abstract Background Methamphetamine (Meth) abuse is a major health problem linked to the aggravation of HIV- associated complications, especially within the Central Nervous System (CNS). Within the CNS, Meth has the ability to modify the activity/function of innate immune cells and increase brain viral loads. Here, we examined changes in the gene expression profile of neuron-free microglial cell preparations isolated from the brain of macaques infected with the Simian Immunodeficiency Virus (SIV), a model of neuroAIDS, and exposed to Meth. We aimed to identify molecular patterns triggered by Meth that could explain the detection of higher brain viral loads and the development of a pro-inflammatory CNS environment in the brain of infected drug abusers. Results We found that Meth alone has a strong effect on the transcription of genes associated with immune pathways, particularly inflammation and chemotaxis. Systems analysis led to a strong correlation between Meth exposure and enhancement of molecules associated with chemokines and chemokine receptors, especially CXCR4 and CCR5, which function as co-receptors for viral entry. The increase in CCR5 expression was confirmed in the brain in correlation with increased brain viral load. Conclusions Meth enhances the availability of CCR5-expressing cells for SIV in the brain, in correlation with increased viral load. This suggests that Meth is an important factor in the susceptibility to the infection and to the aggravated CNS inflammatory pathology associated with SIV in macaques and HIV in humans.

  5. A novel modeling method for manufacturing hearing aid using 3D medical images

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyeong Gyun [Dept of Radiological Science, Far East University, Eumseong (Korea, Republic of)

    2016-06-15

    This study aimed to suggest a novel method of modeling a hearing aid ear shell based on Digital Imaging and Communication in Medicine (DICOM) in the hearing aid ear shell manufacturing method using a 3D printer. In the experiment, a 3D external auditory meatus was extracted by using the critical values in the DICOM volume images, a nd t he modeling surface structures were compared in standard type STL (STereoLithography) files which could be recognized by a 3D printer. In this 3D modeling method, a conventional ear model was prepared, and the gaps between adjacent isograms produced by a 3D scanner were filled with 3D surface fragments to express the modeling structure. In this study, the same type of triangular surface structures were prepared by using the DICOM images. The result showed that the modeling surface structure based on the DICOM images provide the same environment that the conventional 3D printers may recognize, eventually enabling to print out the hearing aid ear shell shape.

  6. Electre Tri-C, a multiple criteria decision aiding sorting model applied to assisted reproduction.

    Science.gov (United States)

    Figueira, J R; Almeida-Dias, J; Matias, S; Roy, B; Carvalho, M J; Plancha, C E

    2011-04-01

    The aim of this paper is to apply an informatics tool for dealing with a medical decision aiding problem to help infertile couples to become parents, when using assisted reproduction. A multiple criteria decision aiding method for sorting or ordinal classification problems, called Electre Tri-C, was chosen in order to assign each couple to an embryo-transfer category. The set of categories puts in evidence a way for increasing the single pregnancy rate, while minimizing multiple pregnancies. The decision aiding sorting model was co-constructed through an interaction process between the decision aiding analysts and the medical experts. According to the sample used in this study, the Electre Tri-C method provides a unique category in 86% of the cases and it achieves a sorting accuracy of 61%. Retrospectively, the medical experts do agree that some of their judgments concerning the number of embryos to transfer back to the uterus of the woman could be different according to these results. The current ART methodology achieves a single pregnancy rate of 47% and a twin pregnancy rate of 14%. Thus, this informatics tools may play an important role for supporting ART medical decisions, aiming to increase the single pregnancy rate, while minimizing multiple pregnancies. Building the set of criteria comprises a part of arbitrariness and imperfect knowledge, which require time and expertise to be refined. Among them, three criteria are modeled by means of a holistic classification procedure by the medical experts. 2010 Elsevier Ireland Ltd. All rights reserved.

  7. The DREAM model's effectiveness in health promotion of AIDS patients in Africa.

    Science.gov (United States)

    Magnano San Lio, M; Mancinelli, S; Palombi, L; Buonomo, E; Altan, A Doro; Germano, P; Magid, N A; Pesaresi, A; Renzi, E; Scarcella, P; Zimba, I; Marazzi, M C

    2009-03-01

    This study evaluates the effectiveness of a holistic model for treating people living with AIDS in Africa; the model aims to improve knowledge about AIDS prevention and care, increase trust in the health centre, impact behaviour, and promote a high level of adherence to HAART. The study took place in the context of the DREAM (Drug Resource Enhancement against AIDS and Malnutrition) programme in Mozambique, designed by the Community of Sant'Egidio to treat HIV patients in Africa. It provides patients with free anti-retroviral drugs, laboratory tests (including viral load), home care and nutritional support. This is a prospective study involving 531 patients over a 12-month period. The patients, predominantly poor and with a low level of education, demonstrated a good level of knowledge about AIDS (more than 90% know how it is transmitted) and trust in the treatment, with a relatively small percentage turning to traditional healers. Overall the patients had a low level of engaging in risky sexual behaviour and a very good level of adherence to HAART (69.5% of the 531 subjects had a pill count higher than 95%). The positive results of the programme's educational initiatives were confirmed with the patients' good clinical results.

  8. Effective spatial scales for evaluating environmental determinants of population density in Yakushima macaques.

    Science.gov (United States)

    Agetsuma, Naoki; Koda, Ryosuke; Tsujino, Riyou; Agetsuma-Yanagihara, Yoshimi

    2015-02-01

    Population densities of wildlife species tend to be correlated with resource productivity of habitats. However, wildlife density has been greatly modified by increasing human influences. For effective conservation, we must first identify the significant factors that affect wildlife density, and then determine the extent of the areas in which the factors should be managed. Here, we propose a protocol that accomplishes these two tasks. The main threats to wildlife are thought to be habitat alteration and hunting, with increases in alien carnivores being a concern that has arisen recently. Here, we examined the effect of these anthropogenic disturbances, as well as natural factors, on the local density of Yakushima macaques (Macaca fuscata yakui). We surveyed macaque densities at 30 sites across their habitat using data from 403 automatic cameras. We quantified the effect of natural vegetation (broad-leaved forest, mixed coniferous/broad-leaved forest, etc.), altered vegetation (forestry area and agricultural land), hunting pressure, and density of feral domestic dogs (Canis familiaris). The effect of each vegetation type was analyzed at numerous spatial scales (between 150 and 3,600-m radii from the camera locations) to determine the best scale for explaining macaque density (effective spatial scale). A model-selection procedure (generalized linear mixed model) was used to detect significant factors affecting macaque density. We detected that the most effective spatial scale was 400 m in radius, a scale that corresponded to group range size of the macaques. At this scale, the amount of broad-leaved forest was selected as a positive factor, whereas mixed forest and forestry area were selected as negative factors for macaque density. This study demonstrated the importance of the simultaneous evaluation of all possible factors of wildlife population density at the appropriate spatial scale.

  9. Evolutionary interrogation of human biology in well-annotated genomic framework of rhesus macaque.

    Science.gov (United States)

    Zhang, Shi-Jian; Liu, Chu-Jun; Yu, Peng; Zhong, Xiaoming; Chen, Jia-Yu; Yang, Xinzhuang; Peng, Jiguang; Yan, Shouyu; Wang, Chenqu; Zhu, Xiaotong; Xiong, Jingwei; Zhang, Yong E; Tan, Bertrand Chin-Ming; Li, Chuan-Yun

    2014-05-01

    With genome sequence and composition highly analogous to human, rhesus macaque represents a unique reference for evolutionary studies of human biology. Here, we developed a comprehensive genomic framework of rhesus macaque, the RhesusBase2, for evolutionary interrogation of human genes and the associated regulations. A total of 1,667 next-generation sequencing (NGS) data sets were processed, integrated, and evaluated, generating 51.2 million new functional annotation records. With extensive NGS annotations, RhesusBase2 refined the fine-scale structures in 30% of the macaque Ensembl transcripts, reporting an accurate, up-to-date set of macaque gene models. On the basis of these annotations and accurate macaque gene models, we further developed an NGS-oriented Molecular Evolution Gateway to access and visualize macaque annotations in reference to human orthologous genes and associated regulations (www.rhesusbase.org/molEvo). We highlighted the application of this well-annotated genomic framework in generating hypothetical link of human-biased regulations to human-specific traits, by using mechanistic characterization of the DIEXF gene as an example that provides novel clues to the understanding of digestive system reduction in human evolution. On a global scale, we also identified a catalog of 9,295 human-biased regulatory events, which may represent novel elements that have a substantial impact on shaping human transcriptome and possibly underpin recent human phenotypic evolution. Taken together, we provide an NGS data-driven, information-rich framework that will broadly benefit genomics research in general and serves as an important resource for in-depth evolutionary studies of human biology.

  10. A Link Loss Model for the On-body Propagation Channel for Binaural Hearing Aids

    CERN Document Server

    Chandra, Rohit

    2013-01-01

    Binaural hearing aids communicate with each other through a wireless link for synchronization. A propagation model is needed to estimate the ear-to-ear link loss for such binaural hearing aids. The link loss is a critical parameter in a link budget to decide the sensitivity of the transceiver. In this paper, we have presented a model for the deterministic component of the ear-to-ear link loss. The model takes into account the dominant paths having most of the power of the creeping wave from the transceiver in one ear to the transceiver in other ear and the effect of the protruding part of the outer ear called pinna. Simulations are done to validate the model using in-the-ear (ITE) placement of antennas at 2.45 GHz on two heterogeneous phantoms of different age-group and body size. The model agrees with the simulations. The ear-to-ear link loss between the antennas for the binaural hearing aids in the homogeneous SAM phantom is compared with a heterogeneous phantom. It is found that the absence of the pinna an...

  11. A Link Loss Model for the On-Body Propagation Channel for Binaural Hearing Aids

    Science.gov (United States)

    Chandra, Rohit; Johansson, Anders J.

    2013-12-01

    Binaural hearing aids communicate with each other through a wireless link for synchronization. A propagation model is needed to estimate the ear-to-ear link loss for such binaural hearing aids. The link loss is a critical parameter in a link budget to decide the sensitivity of the transceiver. In this paper, we have presented a model for the deterministic component of the ear-to-ear link loss. The model takes into account the dominant paths having most of the power of the creeping wave from the transceiver in one ear to the transceiver in other ear and the effect of the protruding part of the outer ear called pinna. Simulations are done to validate the model using in-the-ear (ITE) placement of antennas at 2.45 GHz on two heterogeneous phantoms of different age-group and body size. The model agrees with the simulations. The ear-to-ear link loss between the antennas for the binaural hearing aids in the homogeneous SAM phantom is compared with a heterogeneous phantom. It is found that the absence of the pinna and the lossless shell in the SAM phantom underestimate the link loss. This is verified by the measurements on a phantom where we have included the pinnas fabricated by 3D-printing.

  12. Analysis of copy number variation in the rhesus macaque genome identifies candidate loci for evolutionary and human disease studies.

    Science.gov (United States)

    Lee, Arthur S; Gutiérrez-Arcelus, María; Perry, George H; Vallender, Eric J; Johnson, Welkin E; Miller, Gregory M; Korbel, Jan O; Lee, Charles

    2008-04-15

    Copy number variants (CNVs) are heritable gains and losses of genomic DNA in normal individuals. While copy number variation is widely studied in humans, our knowledge of CNVs in other mammalian species is more limited. We have designed a custom array-based comparative genomic hybridization (aCGH) platform with 385 000 oligonucleotide probes based on the reference genome sequence of the rhesus macaque (Macaca mulatta), the most widely studied non-human primate in biomedical research. We used this platform to identify 123 CNVs among 10 unrelated macaque individuals, with 24% of the CNVs observed in multiple individuals. We found that segmental duplications were significantly enriched at macaque CNV loci. We also observed significant overlap between rhesus macaque and human CNVs, suggesting that certain genomic regions are prone to recurrent CNV formation and instability, even across a total of approximately 50 million years of primate evolution ( approximately 25 million years in each lineage). Furthermore, for eight of the CNVs that were observed in both humans and macaques, previous human studies have reported a relationship between copy number and gene expression or disease susceptibility. Therefore, the rhesus macaque offers an intriguing, non-human primate outbred model organism with which hypotheses concerning the specific functions of phenotypically relevant human CNVs can be tested.

  13. Application of Radial Basis Network Model for HIV/AIDs Regimen Specifications

    CERN Document Server

    Balasubramanie, P

    2009-01-01

    HIV/AIDs Regimen specification one of many problems for which bioinformaticians have implemented and trained machine learning methods such as neural networks. Predicting HIV resistance would be much easier, but unfortunately we rarely have enough structural information available to train a neural network. To network model designed to predict how long the HIV patient can prolong his/her life time with certain regimen specification. To learn this model 300 patient's details have taken as a training set to train the network and 100 patients medical history has taken to test this model. This network model is trained using MAT lab implementation.

  14. Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac Disease

    OpenAIRE

    2016-01-01

    The composition of the gut microbiome reflects the overall health status of the host. In this study, stool samples representing the gut microbiomes from 6 gluten-sensitive (GS) captive juvenile rhesus macaques were compared with those from 6 healthy, age- and diet-matched peers. A total of 48 samples representing both groups were studied using V4 16S rRNA gene DNA analysis. Samples from GS macaques were further characterized based on type of diet administered: conventional monkey chow, i.e., ...

  15. Modeling the effects of spirituality/religion on patients' perceptions of living with HIV/AIDS.

    Science.gov (United States)

    Szaflarski, Magdalena; Ritchey, P Neal; Leonard, Anthony C; Mrus, Joseph M; Peterman, Amy H; Ellison, Christopher G; McCullough, Michael E; Tsevat, Joel

    2006-12-01

    Spirituality/religion is an important factor in health and illness, but more work is needed to determine its link to quality of life in patients with HIV/AIDS. To estimate the direct and indirect effects of spirituality/religion on patients' perceptions of living with HIV/AIDS. In 2002 and 2003, as part of a multicenter longitudinal study of patients with HIV/AIDS, we collected extensive demographic, clinical, and behavioral data from chart review and patient interviews. We used logistic regression and path analysis combining logistic and ordinary least squares regression. Four hundred and fifty outpatients with HIV/AIDS from 4 sites in 3 cities. The dependent variable was whether patients felt that life had improved since being diagnosed with HIV/AIDS. Spirituality/religion was assessed by using the Duke Religion Index, Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being-Expanded, and Brief RCOPE measures. Mediating factors included social support, self-esteem, healthy beliefs, and health status/health concerns. Approximately one-third of the patients felt that their life was better now than it was before being diagnosed with HIV/AIDS. A 1-SD increase in spirituality/religion was associated with a 68.50% increase in odds of feeling that life has improved--29.97% due to a direct effect, and 38.54% due to indirect effects through healthy beliefs (29.15%) and health status/health concerns (9.39%). Healthy beliefs had the largest effect on feeling that life had improved; a 1-SD increase in healthy beliefs resulted in a 109.75% improvement in feeling that life changed. In patients with HIV/AIDS, the level of spirituality/religion is associated, both directly and indirectly, with feeling that life is better now than previously. Future research should validate our new conceptual model using other samples and longitudinal studies. Clinical education interventions should focus on raising awareness among clinicians about the importance of spirituality

  16. Macaque monkeys experience visual crowding.

    Science.gov (United States)

    Crowder, Erin A; Olson, Carl R

    2015-01-01

    In peripheral vision, objects that are easily discriminated on their own become less discriminable in the presence of surrounding clutter. This phenomenon is known as crowding.The neural mechanisms underlying crowding are not well understood. Better insight might come from single-neuron recording in nonhuman primates, provided they exhibit crowding; however, previous demonstrations of crowding have been confined to humans. In the present study, we set out to determine whether crowding occurs in rhesus macaque monkeys. We found that animals trained to identify a target letter among flankers displayed three hallmarks of crowding as established in humans. First, at a given eccentricity, increasing the spacing between the target and the flankers improved recognition accuracy. Second, the critical spacing, defined as the minimal spacing at which target discrimination was reliable, was proportional to eccentricity. Third, the critical spacing was largely unaffected by object size. We conclude that monkeys, like humans, experience crowding. These findings open the door to studies of crowding at the neuronal level in the monkey visual system.

  17. Ambiguity aversion in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Benjamin eHayden

    2010-09-01

    Full Text Available People generally prefer risky options, which have fully specified outcome probabilities, to ambiguous options, which have unspecified probabilities. This preference, formalized in economics, is strong enough that people will reliably prefer a risky option to an ambiguous option with a greater expected value. Explanations for ambiguity aversion often invoke uniquely human faculties like language, self-justification, or a desire to avoid public embarrassment. Challenging these ideas, here we demonstrate that a preference for unambiguous options is shared with rhesus macaques. We trained four monkeys to choose between pairs of options that both offered explicitly cued probabilities of large and small juice outcomes. We then introduced occasional trials where one of the options was obscured and examined their resulting preferences; we ran humans in a parallel experiment on a nearly identical task. We found that monkeys reliably preferred risky options to ambiguous ones, even when this bias was costly, closely matching the behavior of humans in the analogous task. Notably, ambiguity aversion varied parametrically with the extent of ambiguity. As expected, ambiguity aversion gradually declined as monkeys learned the underlying probability distribution of rewards. These data indicate that ambiguity aversion reflects fundamental cognitive biases shared with other animals rather than uniquely human factors guiding decisions.

  18. Comparative Pathobiology of Macaque Lymphocryptoviruses

    Science.gov (United States)

    Carville, Angela; Mansfield, Keith G

    2008-01-01

    Lymphocryptoviruses (LCVs) have been identified as naturally occurring infections of both Old and New World nonhuman primates. These viruses are closely related to Epstein–Barr virus (EBV, Human herpesvirus 4) and share similar genomic organization and biological properties. Nonhuman primate LCVs have the ability to immortalize host cells and express a similar complement of viral lytic and latent genes as those found in EBV. Recent evidence indicates that nonhuman primate LCVs can immortalize B cells from genetically related species, suggesting a close evolutionary relationship between these viruses and their respective hosts. Early work with EBV in tamarins and owl monkeys revealed that cross species transmission of lymphocryptoviruses from the natural to inadvertent host may be associated with oncogenesis and the development of malignant lymphoma. Moreover, simian LCVs have the ability to induce malignant lymphomas in immunodeficient hosts and have been associated with posttransplantation lymphoproliferative disease in cynomolgus macaques undergoing solid organ transplantation. This review will focus on the comparative pathobiology of lymphocryptoviral infection and discuss the derivation of specific pathogen-free animals. PMID:19793458

  19. Mathematical and Numerical Analysis of Model Equations on Interactions of the HIV/AIDS Virus and the Immune System

    Science.gov (United States)

    Parumasur, N.; Willie, R.

    2008-09-01

    We consider a simple HIV/AIDs finite dimensional mathematical model on interactions of the blood cells, the HIV/AIDs virus and the immune system for consistence of the equations to the real biomedical situation that they model. A better understanding to a cure solution to the illness modeled by the finite dimensional equations is given. This is accomplished through rigorous mathematical analysis and is reinforced by numerical analysis of models developed for real life cases.

  20. Application of the Consumer Decision-Making Model to Hearing Aid Adoption in First-Time Users.

    Science.gov (United States)

    Amlani, Amyn M

    2016-05-01

    Since 1980, hearing aid adoption rates have remained essentially the same, increasing at a rate equal to the organic growth of the population. Researchers have used theoretical models from psychology and sociology to determine those factors or constructs that lead to the adoption of hearing aids by first-time impaired listeners entering the market. In this article, a theoretical model, the Consumer Decision-Making Model (CDM), premised on the neobehavioral approach that considers an individual's psychological and cognitive emphasis toward a product or service, is described. Three theoretical models (i.e., transtheoretical, social model of disability, Health Belief Model), and their relevant findings to the hearing aid market, are initially described. The CDM is then presented, along with supporting evidence of the model's various factors from the hearing aid literature. Future applications of the CDM to hearing health care also are discussed.

  1. The rhesus macaque is three times as diverse but more closely equivalent in damaging coding variation as compared to the human

    Directory of Open Access Journals (Sweden)

    Yuan Qiaoping

    2012-06-01

    Full Text Available Abstract Background As a model organism in biomedicine, the rhesus macaque (Macaca mulatta is the most widely used nonhuman primate. Although a draft genome sequence was completed in 2007, there has been no systematic genome-wide comparison of genetic variation of this species to humans. Comparative analysis of functional and nonfunctional diversity in this highly abundant and adaptable non-human primate could inform its use as a model for human biology, and could reveal how variation in population history and size alters patterns and levels of sequence variation in primates. Results We sequenced the mRNA transcriptome and H3K4me3-marked DNA regions in hippocampus from 14 humans and 14 rhesus macaques. Using equivalent methodology and sampling spaces, we identified 462,802 macaque SNPs, most of which were novel and disproportionately located in the functionally important genomic regions we had targeted in the sequencing. At least one SNP was identified in each of 16,797 annotated macaque genes. Accuracy of macaque SNP identification was conservatively estimated to be >90%. Comparative analyses using SNPs equivalently identified in the two species revealed that rhesus macaque has approximately three times higher SNP density and average nucleotide diversity as compared to the human. Based on this level of diversity, the effective population size of the rhesus macaque is approximately 80,000 which contrasts with an effective population size of less than 10,000 for humans. Across five categories of genomic regions, intergenic regions had the highest SNP density and average nucleotide diversity and CDS (coding sequences the lowest, in both humans and macaques. Although there are more coding SNPs (cSNPs per individual in macaques than in humans, the ratio of dN/dS is significantly lower in the macaque. Furthermore, the number of damaging nonsynonymous cSNPs (have damaging effects on protein functions from PolyPhen-2 prediction in the macaque is more

  2. Estimation Of Demand System In An Aids Model:The Opportunity For Exporting Thai Agricultural Products

    Directory of Open Access Journals (Sweden)

    Waripas Jiumpanyarach

    2012-06-01

    Full Text Available This paper reports the results of the estimation of Almost Ideal Demand System(AIDS model is developed to estimate quantity respond based on price. Five major export agricultural products data from the office of Agricultural Economics, Thailand and Biofuel policy from the office of the National Economic and Social Development Broad were used. The AIDS model estimatesdemand of palm, cassava, and sugar are highly response to changed price. Rubber and rice has less response to the changed price. All of major agricultural products are affect expenditure of Thailand export. This result suggest that the opportunity for increasing supply of energy plants, which benefits to Thai farmer communities for expanding market share in energy plants in domestic and global market.

  3. A user-friendly model for spray drying to aid pharmaceutical product development.

    Science.gov (United States)

    Grasmeijer, Niels; de Waard, Hans; Hinrichs, Wouter L J; Frijlink, Henderik W

    2013-01-01

    The aim of this study was to develop a user-friendly model for spray drying that can aid in the development of a pharmaceutical product, by shifting from a trial-and-error towards a quality-by-design approach. To achieve this, a spray dryer model was developed in commercial and open source spreadsheet software. The output of the model was first fitted to the experimental output of a Büchi B-290 spray dryer and subsequently validated. The predicted outlet temperatures of the spray dryer model matched the experimental values very well over the entire range of spray dryer settings that were tested. Finally, the model was applied to produce glassy sugars by spray drying, an often used excipient in formulations of biopharmaceuticals. For the production of glassy sugars, the model was extended to predict the relative humidity at the outlet, which is not measured in the spray dryer by default. This extended model was then successfully used to predict whether specific settings were suitable for producing glassy trehalose and inulin by spray drying. In conclusion, a spray dryer model was developed that is able to predict the output parameters of the spray drying process. The model can aid the development of spray dried pharmaceutical products by shifting from a trial-and-error towards a quality-by-design approach.

  4. Co-operative models for HIV/AIDS sheltered housing in South Africa

    DEFF Research Database (Denmark)

    Eskemose Andersen, Jørgen; Meltzer, Graham; Mullins, Michael

    2001-01-01

    The prevailing delivery model for public housing in South Africa consists of small single-family dwellings on subdivided stands. These suburbs of individual dwellings undermine extended families, which are the cultral norm in South Africa, particularly in rural areas. They will moreover be inadeq...... be inadequate, wasteful and unsustainable in the face of the imminent consequences of HIV/AIDS. A wider perspective of urban dwelling forms must be recognized in which communal facilities and shared responsibilities may be accommodated....

  5. Children affected by HIV/AIDS: SAFE, a model for promoting their security, health, and development.

    Science.gov (United States)

    Betancourt, Theresa S; Fawzi, Mary K S; Bruderlein, Claude; Desmond, Chris; Kim, Jim Y

    2010-05-01

    A human security framework posits that individuals are the focus of strategies that protect the safety and integrity of people by proactively promoting children's well being, placing particular emphasis on prevention efforts and health promotion. This article applies this framework to a rights-based approach in order to examine the health and human rights of children affected by HIV/AIDS. The SAFE model describes sources of insecurity faced by children across four fundamental dimensions of child well-being and the survival strategies that children and families may employ in response. The SAFE model includes: Safety/protection; Access to health care and basic physiological needs; Family/connection to others; and Education/livelihoods. We argue that it is critical to examine the situation of children through an integrated lens that effectively looks at human security and children's rights through a holistic approach to treatment and care rather than artificially limiting our scope of work to survival-oriented interventions for children affected by HIV/AIDS. Interventions targeted narrowly at children, in isolation of their social and communal environment as outlined in the SAFE model, may in fact undermine protective resources in operation in families and communities and present additional threats to children's basic security. An integrated approach to the basic security and care of children has implications for the prospects of millions of children directly infected or indirectly affected by HIV/AIDS around the world. The survival strategies that young people and their families engage in must be recognized as a roadmap for improving their protection and promoting healthy development. Although applied to children affected by HIV/AIDS in the present analysis, the SAFE model has implications for guiding the care and protection of children and families facing adversity due to an array of circumstances from armed conflict and displacement to situations of extreme poverty.

  6. A Mulditisiciplinary Model of Family Therapy with people living with HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Ismael Fernando Díaz Oropeza

    2003-01-01

    Full Text Available The multidisciplinary model includes Family Therapy with persons living with HIV/AIDS and their families. Its theoretical basis is based in Medical Family Therapy, biopsychosocial and systemic perspectives. Collaborative and narrative therapies, solution building and reflecting team‘s ideas are combined in clinical practice. As results, families have normalized illness’ impact, they have co generated possibilities such as strengthening of abilities for coping problems related to illness though agency, communion, empowerment, normalizing, reframing and mobilizing family resources.

  7. A Mulditisiciplinary Model of Family Therapy with people living with HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Ismael Fernando Díaz Oropeza

    2003-01-01

    Full Text Available The multidisciplinary model includes Family Therapy with persons living with HIV/AIDS and their families. Its theoretical basis is based in Medical Family Therapy, biopsychosocial and systemic perspectives. Collaborative and narrative therapies, solution building and reflecting team‘s ideas are combined in clinical practice. As results, families have normalized illness’ impact, they have co generated possibilities such as strengthening of abilities for coping problems related to illness though agency, communion, empowerment, normalizing, reframing and mobilizing family resources.

  8. Severe Encephalitis in Cynomolgus Macaques Exposed to Aerosolized Eastern Equine Encephalitis Virus

    Science.gov (United States)

    2007-08-01

    report here that cynomolgus macaques are also suitable as a model for aerosol exposure to EEE viruses. MATERIALS AND METHODS Animals. Healthy, adult... trocar , the arterial catheter was routed through the subcuta- neous space to the inguinal incision. With an 18-gauge needle, the arterial catheter was

  9. Macaques with Rapid Disease Progression and Simian Immunodeficiency Virus Encephalitis Have a Unique Cytokine Profile in Peripheral Lymphoid Tissues

    Science.gov (United States)

    Orandle, Marlene S.; Williams, Kenneth C.; MacLean, Andrew G.; Westmoreland, Susan V.; Lackner, Andrew A.

    2001-01-01

    The influence of host cytokine response on viral load, disease progression, and neurologic lesions was investigated in the simian immunodeficiency virus (SIV)-infected macaque model of AIDS. Cytokine gene expression (interleukin-1β [IL-1β], IL-2, IL-6, IL-10, gamma interferon [IFN-γ], and tumor necrosis factor alpha [TNF-α]) and viral loads were evaluated by semiquantitative reverse transcription-PCR in lymph nodes of 5 control animals and 28 animals infected with SIVmac251 at the terminal stages of AIDS. Infected animals showed higher expression of IFN-γ, IL-6, and IL-10 mRNAs compared with controls. Levels of all cytokines were comparable between animals with rapid (survival, 200 days) disease progression. However, among rapid progressors, the eight animals with SIV encephalitis had a unique cytokine profile (increased IL-2, IL-6, and IFN-γ) that was associated with higher viral loads. These observations provide evidence that host cytokine responses may influence SIV neuropathogenesis independent of disease progression. PMID:11287599

  10. Response of a simian immunodeficiency virus (SIVmac251 to raltegravir: a basis for a new treatment for simian AIDS and an animal model for studying lentiviral persistence during antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Greenhouse Jack

    2010-03-01

    Full Text Available Abstract Background In this study we successfully created a new approach to ART in SIVmac251 infected nonhuman primates. This drug regimen is entirely based on drugs affecting the pre-integration stages of replication and consists of only two nucleotidic/nucleosidic reverse transcriptase inhibitors (Nt/NRTIs and raltegravir, a promising new drug belonging to the integrase strand transfer inhibitor (INSTI class. Results In acutely infected human lymphoid CD4+ T-cell lines MT-4 and CEMx174, SIVmac251 replication was efficiently inhibited by raltegravir, which showed an EC90 in the low nanomolar range. This result was confirmed in primary macaque PBMCs and enriched CD4+ T cell fractions. In vivo monotherapy with raltegravir for only ten days resulted in reproducible decreases in viral load in two different groups of animals. When emtricitabine (FTC and tenofovir (PMPA were added to treatment, undetectable viral load was reached in two weeks, and a parallel increase in CD4 counts was observed. In contrast, the levels of proviral DNA did not change significantly during the treatment period, thus showing persistence of this lentiviral reservoir during therapy. Conclusions In line with the high conservation of the three main amino acids Y143, Q148 and N155 (responsible for raltegravir binding and molecular docking simulations showing similar binding modes of raltegravir at the SIVmac251 and HIV-1 IN active sites, raltegravir is capable of inhibiting SIVmac251 replication both in tissue culture and in vivo. This finding may help to develop effective ART regimens for the simian AIDS model entirely based on drugs adopted for treatment in humans. This ART-treated AIDS nonhuman primate model could be employed to find possible strategies for virus eradication from the body.

  11. Epidemic model of HIV infection and AIDS in Argentina. Status in 1990 and predictive estimates.

    Science.gov (United States)

    Raggi, R; Blanco, G A

    1992-01-01

    The purpose of this paper was to evaluate the prevalence of HIV infection and AIDS in Argentina, to study the dynamics of the spread of HIV and to predict the future course by means of an epidemic model. The model was constructed using differential equations to describe the interactions between members of the various groups at risk. The functional form of the solutions was used in a back calculation procedure using data from cohort studies which were done in other countries (U.S.A. and France) together with data of AIDS cases reported to the National AIDS Program, to determine the time evolution of HIV-infection in each of the groups at risk defined. Results show that HIV was introduced in Argentina during the early 80's and affected persons of the homosexual/bisexual group in a first stage. In April 1990 it was estimated that there were a total of 34,131 HIV-infected persons. Intravenous drug users (IVDU) represented 39.5%, homosexual/bisexual men 47.6% and heterosexual adults 11%. It is estimated that in December 1992 there will be 107,946 HIV-infected persons where heterosexuals contribute with more than 20% of that value. AIDS cases predicted for the same period are 4130, with 1958 among homosexual/bisexual, 1483 among IVDU, 449 in heterosexual adults, 153 in children under 4 years old and 87 among hemophiliacs or patients with blood coagulation disorders. By the end of 1994 the model predicts more than 200,000 HIV infected persons with an important proportion of heterosexual adults and more than 12,000 AIDS cases. The values of this period must be considered as a future possible scenario if the present spread conditions are preserved. Infection among heterosexual adults is at the present time in a first and exponential phase of spread and dominated by transmission from IVDU group and bisexual men. It is concluded that the future course of AIDS epidemic in Argentina may be particularly influenced by changes in the heterosexual behavior particularly in those

  12. Intrasulcal electrocorticography in macaque monkeys with minimally invasive neurosurgical protocols

    Directory of Open Access Journals (Sweden)

    Takeshi eMatsuo

    2011-05-01

    Full Text Available Electrocorticography (ECoG, multichannel brain-surface recording and stimulation with probe electrode arrays, has become a potent methodology not only for clinical neurosurgery but also for basic neuroscience using animal models. The highly evolved primate’s brain has deep cerebral sulci, and both gyral and intrasulcal cortical regions have been implicated in important functional processes. However, direct experimental access is typically limited to gyral regions, since placing probes into sulci is difficult without damaging the surrounding tissues. Here we describe a novel methodology for intrasulcal ECoG in macaque monkeys. We designed and fabricated ultra-thin flexible probes for macaques with micro-electro-mechanical systems (MEMS technology. We developed minimally invasive operative protocols to implant the probes by introducing cutting edge devices for human neurosurgery. To evaluate the feasibility of intrasulcal ECoG, we conducted electrophysiological recording and stimulation experiments. First, we inserted parts of the Parylene-C-based probe into the superior temporal sulcus to compare visually evoked ECoG responses from the ventral bank of the sulcus with those from the surface of the inferior temporal cortex. Analyses of power spectral density and signal-to-noise ratio revealed that the quality of the ECoG signal was comparable inside and outside of the sulcus. Histological examination revealed no obvious physical damage in the implanted areas. Second, we placed a modified silicone ECoG probe into the central sulcus and also on the surface of the precentral gyrus for stimulation. Thresholds for muscle twitching were significantly lower during intrasulcal stimulation compared to gyral stimulation. These results demonstrate the feasibility of intrasulcal ECoG in macaques. The novel methodology proposed here opens up a new frontier in neuroscience research, enabling the direct measurement and manipulation of electrical activity in the

  13. Intrasulcal electrocorticography in macaque monkeys with minimally invasive neurosurgical protocols.

    Science.gov (United States)

    Matsuo, Takeshi; Kawasaki, Keisuke; Osada, Takahiro; Sawahata, Hirohito; Suzuki, Takafumi; Shibata, Masahiro; Miyakawa, Naohisa; Nakahara, Kiyoshi; Iijima, Atsuhiko; Sato, Noboru; Kawai, Kensuke; Saito, Nobuhito; Hasegawa, Isao

    2011-01-01

    Electrocorticography (ECoG), multichannel brain-surface recording and stimulation with probe electrode arrays, has become a potent methodology not only for clinical neurosurgery but also for basic neuroscience using animal models. The highly evolved primate's brain has deep cerebral sulci, and both gyral and intrasulcal cortical regions have been implicated in important functional processes. However, direct experimental access is typically limited to gyral regions, since placing probes into sulci is difficult without damaging the surrounding tissues. Here we describe a novel methodology for intrasulcal ECoG in macaque monkeys. We designed and fabricated ultra-thin flexible probes for macaques with micro-electro-mechanical systems technology. We developed minimally invasive operative protocols to implant the probes by introducing cutting-edge devices for human neurosurgery. To evaluate the feasibility of intrasulcal ECoG, we conducted electrophysiological recording and stimulation experiments. First, we inserted parts of the Parylene-C-based probe into the superior temporal sulcus to compare visually evoked ECoG responses from the ventral bank of the sulcus with those from the surface of the inferior temporal cortex. Analyses of power spectral density and signal-to-noise ratio revealed that the quality of the ECoG signal was comparable inside and outside of the sulcus. Histological examination revealed no obvious physical damage in the implanted areas. Second, we placed a modified silicone ECoG probe into the central sulcus and also on the surface of the precentral gyrus for stimulation. Thresholds for muscle twitching were significantly lower during intrasulcal stimulation compared to gyral stimulation. These results demonstrate the feasibility of intrasulcal ECoG in macaques. The novel methodology proposed here opens up a new frontier in neuroscience research, enabling the direct measurement and manipulation of electrical activity in the whole brain.

  14. SIV Infection Facilitates Mycobacterium tuberculosis Infection of Rhesus Macaques

    Science.gov (United States)

    Guo, Ming; Xian, Qiao-Yang; Rao, Yan; Zhang, Jing; Wang, Yong; Huang, Zhi-Xiang; Wang, Xin; Bao, Rong; Zhou, Li; Liu, Jin-Biao; Tang, Zhi-Jiao; Guo, De-yin; Qin, Chuan; Li, Jie-Liang; Ho, Wen-Zhe

    2017-01-01

    Tuberculosis (TB) is a common opportunistic infection and the leading cause of death for human immunodeficiency virus (HIV)-infected patients. Thus, it is necessary to understand the pathogenetic interactions between M.tb and HIV infection. In this study, we examined M.tb and/or simian immunodeficiency virus (SIV) infection of Chinese rhesus macaques. While there was little evidence that M.tb enhanced SIV infection of macaques, SIV could facilitate M.tb infection as demonstrated by X-rays, pathological and microbiological findings. Chest X-rays showed that co-infected animals had disseminated lesions in both left and right lungs, while M.tb mono-infected animals displayed the lesions only in right lungs. Necropsy of co-infected animals revealed a disseminated M.tb infection not only in the lungs but also in the extrapulmonary organs including spleen, pancreas, liver, kidney, and heart. The bacterial counts in the lungs, the bronchial lymph nodes, and the extrapulmonary organs of co-infected animals were significantly higher than those of M.tb mono-infected animals. The mechanistic studies demonstrated that two of three co-infected animals had lower levels of M.tb specific IFN-γ and IL-22 in PBMCs than M.tb mono-infected animals. These findings suggest that Chinese rhesus macaque is a suitable and alternative non-human primate model for SIV/M.tb coinfection studies. The impairment of the specific anti-TB immunity is likely to be a contributor of SIV-mediated enhancement M.tb infection. PMID:28133458

  15. Cross-Species Rhesus Cytomegalovirus Infection of Cynomolgus Macaques

    Science.gov (United States)

    Bimber, Benjamin N.; Reed, Jason S.; Uebelhoer, Luke S.; Bhusari, Amruta; Hammond, Katherine B.; Klug, Alex; Legasse, Alfred W.; Axthelm, Michael K.; Nelson, Jay A.; Streblow, Daniel N.; Picker, Louis J.; Früh, Klaus; Sacha, Jonah B.

    2016-01-01

    Cytomegaloviruses (CMV) are highly species-specific due to millennia of co-evolution and adaptation to their host, with no successful experimental cross-species infection in primates reported to date. Accordingly, full genome phylogenetic analysis of multiple new CMV field isolates derived from two closely related nonhuman primate species, Indian-origin rhesus macaques (RM) and Mauritian-origin cynomolgus macaques (MCM), revealed distinct and tight lineage clustering according to the species of origin, with MCM CMV isolates mirroring the limited genetic diversity of their primate host that underwent a population bottleneck 400 years ago. Despite the ability of Rhesus CMV (RhCMV) laboratory strain 68–1 to replicate efficiently in MCM fibroblasts and potently inhibit antigen presentation to MCM T cells in vitro, RhCMV 68–1 failed to productively infect MCM in vivo, even in the absence of host CD8+ T and NK cells. In contrast, RhCMV clone 68–1.2, genetically repaired to express the homologues of the HCMV anti-apoptosis gene UL36 and epithelial cell tropism genes UL128 and UL130 absent in 68–1, efficiently infected MCM as evidenced by the induction of transgene-specific T cells and virus shedding. Recombinant variants of RhCMV 68–1 and 68–1.2 revealed that expression of either UL36 or UL128 together with UL130 enabled productive MCM infection, indicating that multiple layers of cross-species restriction operate even between closely related hosts. Cumulatively, these results implicate cell tropism and evasion of apoptosis as critical determinants of CMV transmission across primate species barriers, and extend the macaque model of human CMV infection and immunology to MCM, a nonhuman primate species with uniquely simplified host immunogenetics. PMID:27829026

  16. SIV Infection Facilitates Mycobacterium tuberculosis Infection of Rhesus Macaques.

    Science.gov (United States)

    Guo, Ming; Xian, Qiao-Yang; Rao, Yan; Zhang, Jing; Wang, Yong; Huang, Zhi-Xiang; Wang, Xin; Bao, Rong; Zhou, Li; Liu, Jin-Biao; Tang, Zhi-Jiao; Guo, De-Yin; Qin, Chuan; Li, Jie-Liang; Ho, Wen-Zhe

    2016-01-01

    Tuberculosis (TB) is a common opportunistic infection and the leading cause of death for human immunodeficiency virus (HIV)-infected patients. Thus, it is necessary to understand the pathogenetic interactions between M.tb and HIV infection. In this study, we examined M.tb and/or simian immunodeficiency virus (SIV) infection of Chinese rhesus macaques. While there was little evidence that M.tb enhanced SIV infection of macaques, SIV could facilitate M.tb infection as demonstrated by X-rays, pathological and microbiological findings. Chest X-rays showed that co-infected animals had disseminated lesions in both left and right lungs, while M.tb mono-infected animals displayed the lesions only in right lungs. Necropsy of co-infected animals revealed a disseminated M.tb infection not only in the lungs but also in the extrapulmonary organs including spleen, pancreas, liver, kidney, and heart. The bacterial counts in the lungs, the bronchial lymph nodes, and the extrapulmonary organs of co-infected animals were significantly higher than those of M.tb mono-infected animals. The mechanistic studies demonstrated that two of three co-infected animals had lower levels of M.tb specific IFN-γ and IL-22 in PBMCs than M.tb mono-infected animals. These findings suggest that Chinese rhesus macaque is a suitable and alternative non-human primate model for SIV/M.tb coinfection studies. The impairment of the specific anti-TB immunity is likely to be a contributor of SIV-mediated enhancement M.tb infection.

  17. Improved xenobiotic metabolism and reduced susceptibility to cancer in gluten-sensitive macaques upon introduction of a gluten-free diet

    National Research Council Canada - National Science Library

    Sestak, Karol; Conroy, Lauren; Aye, Pyone P; Mehra, Smriti; Doxiadis, Gaby G; Kaushal, Deepak

    2011-01-01

    A non-human primate (NHP) model of gluten sensitivity was employed to study the gene perturbations associated with dietary gluten changes in small intestinal tissues from gluten-sensitive rhesus macaques (Macaca mulatta...

  18. Accelerated Failure Time Shared Frailty Models: Application to HIV/AIDS Patients on Anti-Retroviral Therapy in Delhi, India

    Directory of Open Access Journals (Sweden)

    Prafulla Kumar SWAIN

    2016-04-01

    Full Text Available Objective: The present paper demonstrates the applications of Accelerated Failure Time (AFT model with gamma and inverse Gaussian frailty distributions to estimate the effect of prognostic factors on the survival of HIV/AIDS patients undergoing Antiretroviral Therapy (ART in Delhi, India. Material and Methods: The results of both these models have been compared to without frailty model. Akaike Information Criterion (AIC and Bayesian Information criterion (BIC have been used to select best model for HIV/AIDS data. Results: The prognostic factors sex, mode of transmission, baseline hemoglobin and weight are found to be statistically significant (P-value <0.05 for HIV/AIDS patients on ART. Gamma shared frailty model with lognormal as baseline distribution is found to be the best model for HIV/AIDS patients. The model also reflected there is strong evidence of high degree of heterogeneity in the HIV/AIDS patients. Conclusion: Therefore shared frailty model is an appropriate approach for analyzing the HIV/AIDS data than without frailty model.

  19. Computer-aided Nonlinear Control System Design Using Describing Function Models

    CERN Document Server

    Nassirharand, Amir

    2012-01-01

    A systematic computer-aided approach provides a versatile setting for the control engineer to overcome the complications of controller design for highly nonlinear systems. Computer-aided Nonlinear Control System Design provides such an approach based on the use of describing functions. The text deals with a large class of nonlinear systems without restrictions on the system order, the number of inputs and/or outputs or the number, type or arrangement of nonlinear terms. The strongly software-oriented methods detailed facilitate fulfillment of tight performance requirements and help the designer to think in purely nonlinear terms, avoiding the expedient of linearization which can impose substantial and unrealistic model limitations and drive up the cost of the final product. Design procedures are presented in a step-by-step algorithmic format each step being a functional unit with outputs that drive the other steps. This procedure may be easily implemented on a digital computer with example problems from mecha...

  20. Risk factors for dystocia in pigtailed macaques (Macaca nemestrina).

    Science.gov (United States)

    Stockinger, Diane E; Torrence, Anne E; Hukkanen, Renee R; Vogel, Keith W; Hotchkiss, Charlotte E; Ha, James C

    2011-04-01

    Dystocia (difficult labor) is an important component of the management of nonhuman primates and results in significant fetal and maternal morbidity and increased use of veterinary resources. Dystocias can arise from abnormalities of the maternal pelvis or fetus or uncoordinated uterine activity. Although risk factors for stillbirths have been established in nonhuman primates, risk factors for dystocias have not. The objective of this study was to determine maternal and fetal risk factors for dystocia in macaques. Retrospective data were collected from 83 pigtailed macaques (Macaca nemestrina) diagnosed with dystocia. The diagnosis of dystocia was made based on clinical or pathologic evidence. Maternal records of age, reproductive history, experimental history, clinical records, and fetal birth weight and any applicable fetal necropsy reports were reviewed. The gestational age of the fetus, the infant's birth weight, total previous births by the dam, and the proportions of both viable delivery (inverse effect) and surgical pregnancy interventions (direct effect) in the dam's history generated a model that maximized the experimental variance for predicting dystocia in the current pregnancy and explained 24% of the dystocia deliveries. The number of total previous births and proportion of previous cesarean sections accounted for the greatest effect. This model can identify individual dams within a colony that are at risk for dystocias and allow for changes in breeding colony management, more intense monitoring of dams at risk, or allocation of additional resources.

  1. Tracking Epidermal Nerve Fiber Changes in Asian Macaques: Tools and Techniques for Quantitative Assessment.

    Science.gov (United States)

    Mangus, Lisa M; Dorsey, Jamie L; Weinberg, Rachel L; Ebenezer, Gigi J; Hauer, Peter; Laast, Victoria A; Mankowski, Joseph L

    2016-08-01

    Quantitative assessment of epidermal nerve fibers (ENFs) has become a widely used clinical tool for the diagnosis of small fiber neuropathies such as diabetic neuropathy and human immunodeficiency virus-associated sensory neuropathy (HIV-SN). To model and investigate the pathogenesis of HIV-SN using simian immunodeficiency virus (SIV)-infected Asian macaques, we adapted the skin biopsy and immunostaining techniques currently employed in human patients and then developed two unbiased image analysis techniques for quantifying ENF in macaque footpad skin. This report provides detailed descriptions of these tools and techniques for ENF assessment in macaques and outlines important experimental considerations that we have identified in the course of our long-term studies. Although initially developed for studies of HIV-SN in the SIV-infected macaque model, these methods could be readily translated to a range of studies involving peripheral nerve degeneration and neurotoxicity in nonhuman primates as well as preclinical investigations of agents aimed at neuroprotection and regeneration.

  2. An AIDS model with distributed incubation and variable infectiousness: applications to i.v. drug users in Latium, Italy.

    Science.gov (United States)

    Iannelli, M; Loro, R; Milner, F; Pugliese, A; Rabbiolo, G

    1992-07-01

    An AIDS model with distributed incubation and variable infectiousness is considered and simulated via a second-order numerical method. The method is applied to the HIV epidemic among IV drug users in the Latium region of Italy, using available data on the length of the incubation period before the onset of AIDS, on the infectivity of infected individuals during that period, and on the demography of drug users. The contact rate is adjusted to match the actual number of AIDS cases. The sensitivity of the model to uncertainties in the parameters is finally investigated, by performing several simulations.

  3. Stability analysis of an HIV/AIDS epidemic model with treatment

    Science.gov (United States)

    Cai, Liming; Li, Xuezhi; Ghosh, Mini; Guo, Baozhu

    2009-07-01

    An HIV/AIDS epidemic model with treatment is investigated. The model allows for some infected individuals to move from the symptomatic phase to the asymptomatic phase by all sorts of treatment methods. We first establish the ODE treatment model with two infective stages. Mathematical analyses establish that the global dynamics of the spread of the HIV infectious disease are completely determined by the basic reproduction number [real]0. If [real]01. Then, we introduce a discrete time delay to the model to describe the time from the start of treatment in the symptomatic stage until treatment effects become visible. The effect of the time delay on the stability of the endemically infected equilibrium is investigated. Moreover, the delay model exhibits Hopf bifurcations by using the delay as a bifurcation parameter. Finally, numerical simulations are presented to illustrate the results.

  4. Design model of computerized personal decision aid for youth: An expert review

    Science.gov (United States)

    Sarif, Siti Mahfuzah; Ibrahim, Norfiza; Shiratuddin, Norshuhada

    2016-08-01

    This paper provides a structured review of a design model of a computerized personal decision aid that is intended for youth, named as YouthPDA Design Model. The proposed design model was examined by experts in related areas to ensure the appropriateness of the proposed components and elements, relevancy of the terminologies used, logic of the flow, usability, and practicality of the design model towards development of YouthPDA application. Seven experts from related areas were involved in the evaluation. Discussions on the findings obtained from the expert review are included in this paper. Finally, a revised design model of YouthPDA is proposed as main guidance to develop YouthPDA application.

  5. Quality of life of men with AIDS and the model of social determinants of health1

    Science.gov (United States)

    da Cunha, Gilmara Holanda; Fiuza, Maria Luciana Teles; Gir, Elucir; Aquino, Priscila de Souza; Pinheiro, Ana Karina Bezerra; Galvão, Marli Teresinha Gimeniz

    2015-01-01

    OBJECTIVE: to analyze the quality of life (QoL) of men with AIDS from the perspective of the model of social determinants of health (MSDH). METHOD: cross-sectional study conducted in an outpatient infectious diseases clinic from a Brazilian university hospital over the course of one year with a sample of 138 patients. A form based on the MSDH was used to collect sociodemographic data addressing individual, proximal, intermediate determinants and the influence of social networks together with an instrument used to assess the QoL of people with HIV/AIDS. The project was approved by the Institutional Review Board (Protocol No. 040.06.12). RESULTS: according to MSDH, most men with AIDS were between 30 and 49 years old (68.1%), mixed race (59.4%), heterosexual (46.4%), single (64.5%), Catholic (68.8%), had a bachelor's degree (39.2%), had no children (61.6%), and had a formal job (71.0%). The perception of QoL in the physical, level of independence, environment, and spirituality domains was intermediate, while QoL was perceived to be superior in the domains of psychological and social relationship. A perception of lower QoL was presented by homosexual (p=0.037) and married men (p=0.077), and those with income below one times the minimum wage (p=0.042). A perception of greater QoL was presented by those without a religion (p=0.005), living with a partner (p=0.049), and those who had a formal job (p=0.045). CONCLUSION: social determinants influence the QoL of men with AIDS. PMID:26039287

  6. Quality of life of men with AIDS and the model of social determinants of health

    Directory of Open Access Journals (Sweden)

    Gilmara Holanda da Cunha

    2015-04-01

    Full Text Available OBJECTIVE: to analyze the quality of life (QoL of men with AIDS from the perspective of the model of social determinants of health (MSDH. METHOD: cross-sectional study conducted in an outpatient infectious diseases clinic from a Brazilian university hospital over the course of one year with a sample of 138 patients. A form based on the MSDH was used to collect sociodemographic data addressing individual, proximal, intermediate determinants and the influence of social networks together with an instrument used to assess the QoL of people with HIV/AIDS. The project was approved by the Institutional Review Board (Protocol No. 040.06.12. RESULTS: according to MSDH, most men with AIDS were between 30 and 49 years old (68.1%, mixed race (59.4%, heterosexual (46.4%, single (64.5%, Catholic (68.8%, had a bachelor's degree (39.2%, had no children (61.6%, and had a formal job (71.0%. The perception of QoL in the physical, level of independence, environment, and spirituality domains was intermediate, while QoL was perceived to be superior in the domains of psychological and social relationship. A perception of lower QoL was presented by homosexual (p=0.037 and married men (p=0.077, and those with income below one times the minimum wage (p=0.042. A perception of greater QoL was presented by those without a religion (p=0.005, living with a partner (p=0.049, and those who had a formal job (p=0.045. CONCLUSION: social determinants influence the QoL of men with AIDS.

  7. Characterization of single-nucleotide variation in Indian-origin rhesus macaques (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Wheeler David A

    2011-06-01

    Full Text Available Abstract Background Rhesus macaques are the most widely utilized nonhuman primate model in biomedical research. Previous efforts have validated fewer than 900 single nucleotide polymorphisms (SNPs in this species, which limits opportunities for genetic studies related to health and disease. Extensive information about SNPs and other genetic variation in rhesus macaques would facilitate valuable genetic analyses, as well as provide markers for genome-wide linkage analysis and the genetic management of captive breeding colonies. Results We used the available rhesus macaque draft genome sequence, new sequence data from unrelated individuals and existing published sequence data to create a genome-wide SNP resource for Indian-origin rhesus monkeys. The original reference animal and two additional Indian-origin individuals were resequenced to low coverage using SOLiD™ sequencing. We then used three strategies to validate SNPs: comparison of potential SNPs found in the same individual using two different sequencing chemistries, and comparison of potential SNPs in different individuals identified with either the same or different sequencing chemistries. Our approach validated approximately 3 million SNPs distributed across the genome. Preliminary analysis of SNP annotations suggests that a substantial number of these macaque SNPs may have functional effects. More than 700 non-synonymous SNPs were scored by Polyphen-2 as either possibly or probably damaging to protein function and these variants now constitute potential models for studying functional genetic variation relevant to human physiology and disease. Conclusions Resequencing of a small number of animals identified greater than 3 million SNPs. This provides a significant new information resource for rhesus macaques, an important research animal. The data also suggests that overall genetic variation is high in this species. We identified many potentially damaging non-synonymous coding SNPs

  8. Peptide-binding motifs associated with MHC molecules common in Chinese rhesus macaques are analogous to those of human HLA supertypes and include HLA-B27-like alleles

    DEFF Research Database (Denmark)

    Mothé, Bianca R.; Southwood, Scott; Sidney, John

    2013-01-01

    and deciphering outcomes of infection and vaccine efficacy. In this study, we have provided detailed characterization of six prevalent Chinese rhesus macaque MHC class I alleles, yielding a combined phenotypic frequency of 29 %. The peptide-binding specificity of two of these alleles, Mamu-A2*01:02 and Mamu-B*010...... in humans. All six alleles characterized in the present study were found to have specificities analogous to HLA supertype alleles. These data contribute to the concept that Chinese rhesus macaque MHC immunogenetics is more similar to HLA than their Indian rhesus macaque counterparts and thereby warrants......Chinese rhesus macaques are of particular interest in simian immunodeficiency virus/human immunodeficiency virus (SIV/HIV) research as these animals have prolonged kinetics of disease progression to acquired immunodeficiency syndrome (AIDS), compared to their Indian counterparts, suggesting...

  9. Challenges to achieving sustainable community health development within a donor aid business model.

    Science.gov (United States)

    Ashwell, Helen; Barclay, Lesley

    2010-06-01

    This paper explores the paradox of donor aid being delivered through a business model through a case study in Papua New Guinea. A retrospective review of project implementation and an outcome evaluation provided an opportunity to examine the long-term results and sustainability of a large project. Analysis was informed by data collected from 175 interviews (national, provincial, district and village), 93 community discussions and observations across 10 provinces. Problems with the business model of delivering aid were evident from implementation data and in an evaluation conducted two years after project completion (2006). Compounding the business model effect were challenges of over-ambitious project goals with limited flexibility to adapt to changing circumstances, a donor payment system requiring short-term productivity and excessive reporting requirements. An overly ambitious project design, donor dominance within the business model and limited local counterpart capacity created problems in the community initiatives component of the project. Contractual pressures can negatively influence long-term outcomes that require development of local leadership and capacity. Future planning for donor project designs needs to be flexible, smaller in scope and have a longer timeframe of seven to 10 years. Donor-funded projects need to be sufficiently flexible to apply proven principles of community development, build local ownership and allow adequate time to build counterpart knowledge and skills.

  10. Computer aided segmentation of kidneys using locally shape constrained deformable models on CT images

    Science.gov (United States)

    Erdt, Marius; Sakas, Georgios

    2010-03-01

    This work presents a novel approach for model based segmentation of the kidney in images acquired by Computed Tomography (CT). The developed computer aided segmentation system is expected to support computer aided diagnosis and operation planning. We have developed a deformable model based approach based on local shape constraints that prevents the model from deforming into neighboring structures while allowing the global shape to adapt freely to the data. Those local constraints are derived from the anatomical structure of the kidney and the presence and appearance of neighboring organs. The adaptation process is guided by a rule-based deformation logic in order to improve the robustness of the segmentation in areas of diffuse organ boundaries. Our work flow consists of two steps: 1.) a user guided positioning and 2.) an automatic model adaptation using affine and free form deformation in order to robustly extract the kidney. In cases which show pronounced pathologies, the system also offers real time mesh editing tools for a quick refinement of the segmentation result. Evaluation results based on 30 clinical cases using CT data sets show an average dice correlation coefficient of 93% compared to the ground truth. The results are therefore in most cases comparable to manual delineation. Computation times of the automatic adaptation step are lower than 6 seconds which makes the proposed system suitable for an application in clinical practice.

  11. Human Exposure to Herpesvirus B–Seropositive Macaques, Bali, Indonesia

    Science.gov (United States)

    Engel, Gregory A.; Schillaci, Michael A.; Suaryana, Komang Gde; Putra, Artha; Fuentes, Agustin; Henkel, Richard

    2002-01-01

    Herpesvirus B (Cercopithecine herpesvirus 1) has been implicated as the cause of approximately 40 cases of meningoencephalitis affecting persons in direct or indirect contact with laboratory macaques. However, the threat of herpesvirus B in nonlaboratory settings worldwide remains to be addressed. We investigated the potential for exposure to herpesvirus B in workers at a “monkey forest” (a temple that has become a tourist attraction because of its monkeys) in Bali, Indonesia. In July 2000, 105 workers at the Sangeh Monkey Forest in Central Bali were surveyed about contact with macaques (Macaca fascicularis). Nearly half of those interviewed had either been bitten or scratched by a macaque. Prevalence of injury was higher in those who fed macaques. Serum from 31 of 38 Sangeh macaques contained antibodies to herpesvirus B. We conclude that workers coming into contact with macaques at the Sangeh Monkey Forest are at risk for exposure to herpesvirus B. PMID:12141963

  12. Human exposure to herpesvirus B-seropositive macaques, Bali, Indonesia.

    Science.gov (United States)

    Engel, Gregory A; Jones-Engel, Lisa; Schillaci, Michael A; Suaryana, Komang Gde; Putra, Artha; Fuentes, Agustin; Henkel, Richard

    2002-08-01

    Herpesvirus B (Cercopithecine herpesvirus 1) has been implicated as the cause of approximately 40 cases of meningoencephalitis affecting persons in direct or indirect contact with laboratory macaques. However, the threat of herpesvirus B in nonlaboratory settings worldwide remains to be addressed. We investigated the potential for exposure to herpesvirus B in workers at a "monkey forest" (a temple that has become a tourist attraction because of its monkeys) in Bali, Indonesia. In July 2000, 105 workers at the Sangeh Monkey Forest in Central Bali were surveyed about contact with macaques (Macaca fascicularis). Nearly half of those interviewed had either been bitten or scratched by a macaque. Prevalence of injury was higher in those who fed macaques. Serum from 31 of 38 Sangeh macaques contained antibodies to herpesvirus B. We conclude that workers coming into contact with macaques at the Sangeh Monkey Forest are at risk for exposure to herpesvirus B.

  13. A 22-channel receive array with Helmholtz transmit coil for anesthetized macaque MRI at 3 T.

    Science.gov (United States)

    Janssens, Thomas; Keil, Boris; Serano, Peter; Mareyam, Azma; McNab, Jennifer A; Wald, Lawrence L; Vanduffel, Wim

    2013-11-01

    The macaque monkey is an important model for cognitive and sensory neuroscience that has been used extensively in behavioral, electrophysiological, molecular and, more recently, neuroimaging studies. However, macaque MRI has unique technical differences relative to human MRI, such as the geometry of highly parallel receive arrays, which must be addressed to optimize imaging performance. A 22-channel receive coil array was constructed specifically for rapid high-resolution anesthetized macaque monkey MRI at 3 T. A local Helmholtz transmit coil was used for excitation. Signal-to-noise ratios (SNRs) and noise amplification for parallel imaging were compared with those of single- and four-channel receive coils routinely used for macaque MRI. The 22-channel coil yielded significant improvements in SNR throughout the brain. Using this coil, the SNR in peripheral brain was 2.4 and 1.7 times greater than that obtained with single- or four-channel coils, respectively. In the central brain, the SNR gain was 1.5 times that of both the single- and four-channel coils. Finally, the performance of the array for functional, anatomical and diffusion-weighted imaging was evaluated. For all three modalities, the use of the 22-channel array allowed for high-resolution and accelerated image acquisition.

  14. Suicide prevention by online support groups: an action theory-based model of emotional first aid.

    Science.gov (United States)

    Gilat, Itzhak; Shahar, Golan

    2009-01-01

    In the last two decades, online support groups have become a valuable source of help for individuals in suicidal crisis. Their attractiveness is attributed to features that enhance help-seeking and self-disclosure such as availability, anonymity, and use of written communication. However, online support groups also suffer from limitations and potential risks as agents of suicide prevention. The Israeli Association for Emotional First Aid (ERAN) has developed a practical model that seeks to maximize the benefits and minimize the risks of online suicide prevention. The model applies the Action Theory concepts whereby individuals shape their own environment. The present paper presents the model, which is based on an online support group combined with personal chat and a telephonic help line. The online support group is moderated by paraprofessionals who function as both process regulators and support providers. The principles and practice of the model are described, the theoretical rationale is presented, and directions for future research are suggested.

  15. En route to a multi-model scheme for clinker comminution with chemical grinding aids

    CERN Document Server

    Mishra, R K; Carmona, H A; Wittel, F K; Sawley, M L; Weibel, M; Gallucci, E; Herrmann, H J; Heinz, H; Flatt, R J

    2015-01-01

    We present a multi-model simulation approach, targeted at understanding the behavior of comminution and the effect of grinding aids (GAs) in industrial cement mills. On the atomistic scale we use Molecular Dynamics (MD) simulations with validated force field models to quantify elastic and structural properties, cleavage energies as well as the organic interactions with mineral surfaces. Simulations based on the Discrete Element Method (DEM) are used to integrate the information gained from MD simulations into the clinker particle behavior at larger scales. Computed impact energy distributions from DEM mill simulations can serve as a link between large-scale industrial and laboratory sized mills. They also provide the required input for particle impact fragmentation models. Such a multi-scale, multi-model methodology paves the way for a structured approach to the design of chemical additives aimed at improving mill performance.

  16. Policy Analysis Implications of a Model to Improve the Delivery of Financial Aid to Disadvantaged Students. AIR 1983 Annual Forum Paper.

    Science.gov (United States)

    Fenske, Robert H.; Porter, John D.

    The role of institutional research in policy analysis regarding the operation of a computer model for delivery of financial aid to disadvantaged students is considered. A student financial aid model at Arizona State University is designed to develop a profile of late appliers for aid funds and also those who file inaccurate or incomplete…

  17. Stability Analysis of an HIV/AIDS Dynamics Model with Drug Resistance

    Directory of Open Access Journals (Sweden)

    Qianqian Li

    2012-01-01

    Full Text Available A mathematical model of HIV/AIDS transmission incorporating treatment and drug resistance was built in this study. We firstly calculated the threshold value of the basic reproductive number (R0 by the next generation matrix and then analyzed stability of two equilibriums by constructing Lyapunov function. When R0<1, the system was globally asymptotically stable and converged to the disease-free equilibrium. Otherwise, the system had a unique endemic equilibrium which was also globally asymptotically stable. While an antiretroviral drug tried to reduce the infection rate and prolong the patients’ survival, drug resistance was neutralizing the effects of treatment in fact.

  18. On the Consumption Structure of Rural Residents in Xi’an City Based on AIDS Model

    Institute of Scientific and Technical Information of China (English)

    Shuanghong; TANG; Xianli; XIA

    2015-01-01

    Under the background of the financial crisis,expanding domestic demand for stimulating economic role is self-evident. As China has a large rural population,increasing rural residents’ income and expanding their consumer demand is becoming the pinnacle of expanding domestic demand. The urban residents have good conditions than more countryside dwellers. Since few articles are dedicated to the research of this group,this article selects rural residents of Xi’an as object,uses AIDS model to analyze the consumption structure of rural residents,and draw the conclusion that increasing cultural recreation,medical and health spending is the main way to increase their incomes.

  19. Prevention of vaginal SHIV transmission in macaques by a coitally-dependent Truvada regimen.

    Directory of Open Access Journals (Sweden)

    Jessica Radzio

    Full Text Available BACKGROUND: Daily pre-exposure prophylaxis (PrEP with Truvada (a combination of emtricitabine (FTC and tenofovir (TFV disoproxil fumarate (TDF is a novel HIV prevention strategy recently found to prevent HIV transmission in men who have sex with men and heterosexual couples. We previously showed that a coitally-dependent Truvada regimen protected macaques against rectal SHIV transmission. Here we examined FTC and tenofovir TFV exposure in vaginal tissues after oral dosing and assessed if peri-coital Truvada also protects macaques against vaginal SHIV infection. METHODS: The pharmacokinetic profile of emtricitabine (FTC and tenofovir (TFV was evaluated at first dose. FTC and TFV levels were measured in blood plasma, rectal, and vaginal secretions. Intracellular concentrations of FTC-triphosphate (FTC-TP and TFV-diphosphate (TFV-DP were measured in PBMCs, rectal tissues, and vaginal tissues. Efficacy of Truvada in preventing vaginal SHIV infection was assessed using a repeat-exposure vaginal SHIV transmission model consisting of weekly exposures to low doses of SHIV162p3. Six pigtail macaques with normal menstrual cycles received Truvada 24 h before and 2 h after each weekly virus exposure and six received placebo. Infection was monitored by serology and PCR amplification of SHIV RNA and DNA. RESULTS: As in humans, the concentration of FTC was higher than the concentration of TFV in vaginal secretions. Also as in humans, TFV levels in vaginal secretions were lower than in rectal secretions. Intracellular TFV-DP concentrations were also lower in vaginal tissues than in rectal tissues. Despite the low vaginal TFV exposure, all six treated macaques were protected from infection after 18 exposures or 4 full menstrual cycles. In contrast, all 6 control animals were infected. CONCLUSIONS: We modeled a peri-coital regimen with two doses of Truvada and showed that it fully protected macaques from repeated SHIV exposures. Our results open the possibility

  20. Systemic model for the aid for operating of the reactor Siloe; Modelisation systeme pour l`aide a l`exploitation du reacteur de recherche Siloe

    Energy Technology Data Exchange (ETDEWEB)

    Royer, J.C.; Moulin, V.; Monge, F. [CEA Centre d`Etudes de Grenoble, 38 (France). Direction des Reacteurs Nucleaires; Baradel, C. [ITMI APTOR, 38 - Meylan (France)

    1995-12-31

    The Service of the Reactor Siloe (CEA/DRN/DRE/SRS), fully aware of the abilities and knowledge of his teams in the field of research reactor operating, has undertaken a project of knowledge engineering in this domain. The following aims have been defined: knowledge capitalization for the installation in order to insure its perenniality and valorization, elaboration of a project for the aid of the reactor operators. This article deals with the different actions by the SRS to reach the aims: realization of a technical model for the operation of the Siloe reactor, development of a knowledge-based system for the aid for operating. These actions based on a knowledge engineering methodology, SAGACE, and using industrial tools will lead to an amelioration of the security and the operating of the Siloe reactor. (authors). 13 refs., 7 figs.

  1. Computer aided modeling and simulation of hydroforming on tubular engineering products

    Directory of Open Access Journals (Sweden)

    Jeremy (Zheng Li

    2013-01-01

    Full Text Available Hydroforming processes have been widely applied in many different industrial fields including aerospace, automotive, and modern plastics for weight-reduction and strength enhancement. Hydroforming on tubular products is better than the process of welding tubular assemblies from stampings including increased strength, reduction of work applied to the unit weight, decreased processing and tool costs, improved structural stability, less secondary operation, enhanced stiffness, and more uniform in product thickness. Although the hydroforming becomes popular manufacturing methodology, few researches have been done to study the hydroforming mechanism through computational modeling and simulation. This paper focuses on the study of hydroforming process and mechanism based on computer-aided modeling (FEA and prototype testing to determine the material behaviors in hydroforming process. The objective of this research is to verify the effects of major manufacturing parameters on hydroforming processes. The computational analysis and prototype testing indicate that some factors including applied internal pressure path and compressive axial loading play important roles in hydroforming deformation. Both computer-aided modeling and prototyping experiment show close results which verifies the credibility of this research and analytic methodology.

  2. Introduction to n-adaptive fuzzy models to analyze public opinion on AIDS

    CERN Document Server

    Kandasamy, D W B V; Kandasamy, Dr.W.B.Vasantha; Smarandache, Dr.Florentin

    2006-01-01

    There are many fuzzy models like Fuzzy matrices, Fuzzy Cognitive Maps, Fuzzy relational Maps, Fuzzy Associative Memories, Bidirectional Associative memories and so on. But almost all these models can give only one sided solution like hidden pattern or a resultant output vector dependent on the input vector depending in the problem at hand. So for the first time we have defined a n-adaptive fuzzy model which can view or analyze the problem in n ways (n >=2) Though we have defined these n- adaptive fuzzy models theorectically we are not in a position to get a n-adaptive fuzzy model for n > 2 for practical real world problems. The highlight of this model is its capacity to analyze the same problem in different ways thereby arriving at various solutions that mirror multiple perspectives. We have used the 2-adaptive fuzzy model having the two fuzzy models, fuzzy matrices model and BAMs viz. model to analyze the views of public about HIV/ AIDS disease, patient and the awareness program. This book has five chapters ...

  3. Development of Computer Aided Modelling Templates for Model Re-use in Chemical and Biochemical Process and Product Design: Importand export of models

    DEFF Research Database (Denmark)

    2015-01-01

    been established, in order to provide a wider range of modelling capabilities. Through this link, developed models can be exported/imported to/from other modelling-simulation software environments to allow model reusability in chemical and biochemical product and process design. The use of this link......This paper focuses on the challenges in model development related to model reuse and compatibility and integration of different tools that are used in modelling. A link between two modelling tools, the computer-aided modelling framework of the ICAS system and the modelling environment, MOSAIC, has...

  4. A model of mechanical contacts in hearing aids for uncertainty analysis

    DEFF Research Database (Denmark)

    Creixell Mediante, Ester; Brunskog, Jonas; Jensen, Jakob Søndergaard;

    2015-01-01

    Modelling the contact between assembled parts is a key point in the design of complex structures. Uncertainties at the joint parameters arise as a result of randomness in physical properties such as contact surface, load distribution or geometric details. This is a challenge of concern in the hea......Modelling the contact between assembled parts is a key point in the design of complex structures. Uncertainties at the joint parameters arise as a result of randomness in physical properties such as contact surface, load distribution or geometric details. This is a challenge of concern...... in the hearing aid field, where the small lightweight structures present vibration modes at frequencies within the hearing range. To approach this issue, a model of contacts based on lumped elements is suggested. The joint parameters are the stiffness of a series of spring elements placed along the contact...

  5. Model-based Computer Aided Framework for Design of Process Monitoring and Analysis Systems

    DEFF Research Database (Denmark)

    Singh, Ravendra; Gernaey, Krist; Gani, Rafiqul

    2009-01-01

    -aided framework including the methods and tools through which the design of monitoring and analysis systems for product quality control can be generated, analyzed and/or validated, has been developed. Two important supporting tools developed as part of the framework are a knowledge base and a model library...... subject to the maintenance constraints of the desired product quality. The application of the model-based framework is highlighted through a case study involving the operation of a fermentation process.......In the manufacturing industry, for example, the pharmaceutical industry, a thorough understanding of the process is necessary in addition to a properly designed monitoring and analysis system (PAT system) to consistently obtain the desired end-product properties. A model-based computer...

  6. Depot-medroxyprogesterone acetate does not reduce the prophylactic efficacy of emtricitabine and tenofovir disoproxil fumarate in macaques.

    Science.gov (United States)

    Radzio, Jessica; Hanley, Krisztina; Mitchell, James; Ellis, Shanon; Deyounks, Frank; Jenkins, Leecresia; Heneine, Walid; García-Lerma, J Gerardo

    2014-12-01

    Concerns that the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) may increase the risk of HIV acquisition in women led to questions on whether DMPA could reduce efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention. We used a macaque model to investigate the impact of prolonged DMPA exposure on PrEP with emtricitabine/tenofovir disoproxil fumarate. Twelve pigtail macaques treated with DMPA were exposed vaginally to simian HIV once a week for up to 5 months and received either placebo (n = 6) or emtricitabine/tenofovir disoproxil fumarate (n = 6). All control macaques were infected, whereas the PrEP-treated animals remained protected (P = 0.0007). This model suggests that women using DMPA will fully benefit from PrEP.

  7. Directed shift of vaginal microbiota induced by vaginal application of sucrose gel in rhesus macaques.

    Science.gov (United States)

    Hu, Kai-tao; Zheng, Jin-xin; Yu, Zhi-jian; Chen, Zhong; Cheng, Hang; Pan, Wei-guang; Yang, Wei-zhi; Wang, Hong-yan; Deng, Qi-wen; Zeng, Zhong-ming

    2015-04-01

    Sucrose gel was used to treat bacterial vaginosis in a phase III clinical trial. However, the changes of vaginal flora after treatment were only examined by Nugent score in that clinical trial, While the vaginal microbiota of rhesus macaques is characterized by anaerobic, Gram-negative bacteria, few lactobacilli, and pH levels above 4.6, similar to the microbiota of patients with bacterial vaginosis. This study is aimed to investigate the change of the vaginal microbiota of rehsus macaques after topical use of sucrose gel to reveal more precisely the bacterial population shift after the topical application of sucrose gel. Sixteen rhesus macaques were treated with 0.5 g sucrose gel vaginally and three with 0.5 g of placebo gel. Vaginal swabs were collected daily following treatment. Vaginal pH levels and Nugent scores were recorded. The composition of the vaginal micotbiota was tested by V3∼V4 16S rDNA metagenomic sequencing. Dynamic changes in the Lactobacillus genus were analyzed by qPCR. The vaginal microbiota of rhesus macaques are dominated by anaerobic Gram-negative bacteria, with few lactobacilli and high pH levels above 4.6. After five days' treatment with topical sucrose gel, the component percentage of Lactobacillus in vaginal microbiota increased from 1.31% to 81.59%, while the component percentage of Porphyromonas decreased from 18.60% to 0.43%, Sneathia decreased from 15.09% to 0.89%, Mobiluncus decreased from 8.23% to 0.12%, etc.. The average vaginal pH values of 16 rhesus macaques of the sucrose gel group decreased from 5.4 to 3.89. There were no significant changes in microbiota and vaginal pH observed in the placebo group. Rhesus macaques can be used as animal models of bacterial vaginosis to develop drugs and test treatment efficacy. Furthermore, the topical application of sucrose gel induced the shifting of vaginal flora of rhesus macaques from a BV kind of flora to a lactobacilli-dominating flora. Copyright © 2015 The Authors. Published by

  8. Assessing the trend of HIV/AIDS mortality rate in Asia and North Africa: an application of latent growth models.

    Science.gov (United States)

    Zayeri, F; Talebi Ghane, E; Borumandnia, N

    2016-02-01

    Over the last 30 years, HIV/AIDS has emerged as a major global health challenge. This study evaluates the change of HIV/AIDS mortality rates in Asian and North African countries from 1990 to 2010 using the Global Burden of Disease (GBD) study. HIV/AIDS mortality rates were derived from the GBD database from 1990 to 2010, for 52 countries in Asia and North Africa. First, a Latent Growth Model was employed to assess the change in AIDS mortality rate over time in six different regions of Asia, and also the change in AIDS mortality rate over time for males and females in Asia and North Africa. Finally, Latent Growth Mixture Models (LGMMs) were applied to identify distinct groups in which countries within each group have similar trends over time. Our results showed that increase in mortality rate over time for males is about three times greater than for females. The highest and lowest trend of AIDS mortality rates were observed in South-East Asia and high-income Asia-Pacific regions, respectively. The LGMM allocated most countries in the South and South-East region into two classes with the highest trend of AIDS mortality rates. Although the HIV/AIDS mortality rates are decreasing in some countries and clusters, the general trend in the Asian continent is upwards. Therefore, it is necessary to provide programmes to achieve the goal of access to HIV prevention measures, treatment, care, and support for high-risk groups, especially in countries with a higher trend of AIDS mortality rates.

  9. AIDS awareness and VCT behaviour: An application of the integrated model of behaviour prediction

    Directory of Open Access Journals (Sweden)

    Hilde Diteweg

    2013-05-01

    Full Text Available In order to limit the expansion of the HIV and AIDS epidemic in South Africa, it is important to develop targeted prevention strategies. The voluntary HIV counselling and testing (VCT programme appears to be effective for preventing the spread of the HI virus. This study adapted guidelines of the integrated model of behaviour prediction (IMBP into a questionnaire and examined the extent to which it predicts behaviour. A sample of 92 sports team members from Limpopo ranging from 14 to 30 years of age completed the questionnaire. Results suggested that beliefs about the outcomes of behaviour and beliefs about the expectations of others had a direct influence on the intention to undergo HIV counselling and testing. Efficacy beliefs, namely beliefs that there are factors that can facilitate behaviour, can lead to actual testing behaviour if accompanied by self-efficacy. Knowledge, intention and stigma are not related to VCT behaviour. Findings show that some constructs influence intention and test behaviour, but in ways not predicted by the model. Thus, the adequacy of the IMBP to determine HIV and AIDS-preventative behavioural intentions is questioned.

  10. The application of computer aided product development techniques in medical modelling topic: rehabilitation and prostheses.

    Science.gov (United States)

    Bibb, R; Brown, R

    2000-01-01

    When considering reconstructive surgery it is often difficult to ascertain the exact nature of affected internal anatomy. Although advances in Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) have enabled the generation of 3D reconstructions of internal anatomy, they are often only available as fixed 2D images. These may obscure important details or prove ambiguous depending upon the angle of view. Another problem is maintaining accuracy of reconstruction that may involve osteotomy, tissue grafts or implants. In such circumstances the ability to plan and rehearse complex procedures can prove invaluable, greatly improving surgical results whilst helping to eliminate potential errors and reducing theatre time. In this context 3D scan data can be treated as the equivalent of Computer Aided Design (CAD) data and can be applied to the production of accurate physical models. The approach undertaken by the DERC is based on close collaboration with surgical departments and enables the rapid and economic production of medical models based on CT/MRI data. This paper illustrates the transfer of product design technologies into a clinical context. Specifically, the use of 3D surface scanning and rapid prototyping technologies as an aid to post operative reconstruction is described. An evaluation of the application of product development tools within a clinical context is presented. The paper concludes with an assessment of likely future application in this area.

  11. Vicarious Reinforcement In Rhesus Macaques (Macaca mulatta)

    OpenAIRE

    Chang, Steve W. C.; Amy A. Winecoff; Platt, Michael L.

    2011-01-01

    What happens to others profoundly influences our own behavior. Such other-regarding outcomes can drive observational learning, as well as motivate cooperation, charity, empathy, and even spite. Vicarious reinforcement may serve as one of the critical mechanisms mediating the influence of other-regarding outcomes on behavior and decision-making in groups. Here we show that rhesus macaques spontaneously derive vicarious reinforcement from observing rewards given to another monkey, and that t...

  12. Vicarious Reinforcement in Rhesus Macaques (Macaca Mulatta)

    OpenAIRE

    Chang, Steve W. C.; Amy A. Winecoff; Platt, Michael L.

    2011-01-01

    What happens to others profoundly influences our own behavior. Such other-regarding outcomes can drive observational learning, as well as motivate cooperation, charity, empathy, and even spite. Vicarious reinforcement may serve as one of the critical mechanisms mediating the influence of other-regarding outcomes on behavior and decision-making in groups. Here we show that rhesus macaques spontaneously derive vicarious reinforcement from observing rewards given to another monkey, and that this...

  13. Gravity orientation tuning in macaque anterior thalamus.

    Science.gov (United States)

    Laurens, Jean; Kim, Byounghoon; Dickman, J David; Angelaki, Dora E

    2016-12-01

    Gravity may provide a ubiquitous allocentric reference to the brain's spatial orientation circuits. Here we describe neurons in the macaque anterior thalamus tuned to pitch and roll orientation relative to gravity, independently of visual landmarks. We show that individual cells exhibit two-dimensional tuning curves, with peak firing rates at a preferred vertical orientation. These results identify a thalamic pathway for gravity cues to influence perception, action and spatial cognition.

  14. Progression of pathogenic events in cynomolgus macaques infected with variola virus.

    Directory of Open Access Journals (Sweden)

    Victoria Wahl-Jensen

    Full Text Available Smallpox, caused by variola virus (VARV, is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections - an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions.

  15. Mapping the hierarchical layout of the structural network of the macaque prefrontal cortex.

    Science.gov (United States)

    Goulas, Alexandros; Uylings, Harry B M; Stiers, Peter

    2014-05-01

    A consensus on the prefrontal cortex (PFC) holds that it is pivotal for flexible behavior and the integration of the cognitive, affective, and motivational domains. Certain models have been put forth and a dominant model postulates a hierarchical anterior-posterior gradient. The structural connectivity principles of this model dictate that increasingly anterior PFC regions exhibit more efferent connections toward posterior ones than vice versa. Such hierarchical asymmetry principles are thought to pertain to the macaque PFC. Additionally, the laminar patterns of the connectivity of PFC regions can be used for defining hierarchies. In the current study, we formally tested the asymmetry-based hierarchical principles of the anterior-posterior model by employing an exhaustive dataset on macaque PFC connectivity and tools from network science. On the one hand, the asymmetry-based principles and predictions of the hierarchical anterior-posterior model were not confirmed. The wiring of the macaque PFC does not fully correspond to the principles of the model, and its asymmetry-based hierarchical layout does not follow a strict anterior-posterior gradient. On the other hand, our results suggest that the laminar-based hierarchy seems a more tenable working hypothesis for models advocating an anterior-posterior gradient. Our results can inform models of the human PFC.

  16. A holistic model for matching high-tech hearing aid features to elderly patients.

    Science.gov (United States)

    Johnson, C E; Danhauer, J L; Krishnamurti, S

    2000-12-01

    Successful hearing aid fittings using high-technology features for elderly patients require consideration of factors beyond results obtained from routine audiologic evaluations. A holistic hearing aid selection, fitting, and evaluation approach that considers patient characteristics from communication, physical, psychological, and social assessment domains is presented here along with a checklist and flowcharts for matching high-tech hearing aid features to older persons who are hearing aid candidates.

  17. The Children's Aid Society community schools: a full-service partnership model.

    Science.gov (United States)

    Quinn, Jane

    2005-01-01

    In 1989, the Children's Aid Society (CAS) created an unprecedented partnership with the New York City Board of Education by developing a comprehensive response to the pressing needs of children and families in the northern Manhattan neighborhood of Washington Heights. After three years of careful planning, CAS and the New York City public schools opened the first community school at Intermediate School 218, offering a full array of supports, services, and learning opportunities. Adding, on average, one partnership school per year and remaining very flexible in adapting its model to the individual needs of each community, CAS now has thirteen community schools around New York City. The model's flexibility is seen also in the success of its national and international adaptation-an intentional part of CAS's work.

  18. Computer-aided design model for anaerobic-phased-solids digester system

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Z.; Zhang, R. [University of California, Davis, CA (United States); Tiangco, V. [California Energy Commission, Sacramento, CA (United States)

    1999-07-01

    The anaerobic-phased-solids (APS) digester system is a newly developed anaerobic digestion system for converting solid wastes, such as crop residues and food wastes, into biogas for power and heat generation. A computer-aided engineering design model has been developed to design the APS-digester system and study the heat transfer from the reactors and energy production of the system. Simulation results of a case study are presented by using the model to predict the heating energy requirement and biogas energy production for anaerobic digestion of garlic waste. The important factors, such as environmental conditions, insulation properties, and characteristics of the wastes, on net energy production are also investigated. (author)

  19. Depressive-like behavioural profiles in captive-bred single- and socially-housed rhesus and cynomolgus macaques: a species comparison

    Directory of Open Access Journals (Sweden)

    Sandrine MJ Camus

    2014-02-01

    Full Text Available Background: To unravel the causes of major depressive disorder (MDD, the third leading cause of disease burden around the world, ethological animal models have recently been proposed. Our previous studies highlighted a depressive-like profile among single- and socially-housed farm-bred cynomolgus macaques. Although phylogenetically close, cynomolgus and rhesus macaques, the two most commonly used macaque species in biomedical research, differ on several levels such as patterns of aggression, reconciliation, temperament or dominance styles. The question of whether one captive macaque species was more vulnerable than another in the development of a pathological profile reminiscent of MDD symptoms was explored.Methods: Behavioural data (including body postures, orientations, gaze directions, inter-individual distances and locations in the cage were collected in farming conditions. Using an unbiased validated ethological scan-sampling method, followed by multiple correspondence and hierarchical clustering analyses, 40 single- and 35 socially-housed rhesus macaques were assessed. Independently, for each housing condition, inter-species comparisons were made with previously acquired data on farm-bred cynomolgus monkeys.Results: Consistent with our previous studies, we found depressive-like characteristics (e.g. inactivity, low level of investigation and maintenance, long time spent inactive while facing the wall among single- and socially-housed rhesus macaques. Species-specificities were reported in non-depressive time budgets and in the prevalence of the pathological profiles.Conclusions: Our results suggest that rhesus may be more vulnerable to developing a despair-like state than cynomolgus macaques, both in single- and in social-housing conditions. Therefore, rhesus macaques are more suitable for use as a spontaneous model of depressive disorders.

  20. Depressive-like behavioral profiles in captive-bred single- and socially-housed rhesus and cynomolgus macaques: a species comparison

    Science.gov (United States)

    Camus, Sandrine M. J.; Rochais, Céline; Blois-Heulin, Catherine; Li, Qin; Hausberger, Martine; Bezard, Erwan

    2014-01-01

    Background: To unravel the causes of major depressive disorder (MDD), the third leading cause of disease burden around the world, ethological animal models have recently been proposed. Our previous studies highlighted a depressive-like profile among single- and socially-housed farm-bred cynomolgus macaques. Although phylogenetically close, cynomolgus and rhesus macaques, the two most commonly used macaque species in biomedical research, differ on several levels such as patterns of aggression, reconciliation, temperament, or dominance styles. The question of whether one captive macaque species was more vulnerable than another in the development of a pathological profile reminiscent of MDD symptoms was explored. Methods: Behavioral data (including body postures, orientations, gaze directions, inter-individual distances, and locations in the cage) were collected in farming conditions. Using an unbiased validated ethological scan-sampling method, followed by multiple correspondence and hierarchical clustering analyses, 40 single- and 35 socially-housed rhesus macaques were assessed. Independently, for each housing condition, inter-species comparisons were made with previously acquired data on farm-bred cynomolgus monkeys. Results: Consistent with our previous studies, we found depressive-like characteristics (e.g., inactivity, low level of investigation and maintenance, long time spent inactive while facing the wall) among single- and socially-housed rhesus macaques. Species-specificities were reported in non-depressive time budgets and in the prevalence of the pathological profiles. Conclusions: Our results suggest that rhesus may be more vulnerable to developing a despair-like state than cynomolgus macaques, both in single- and in social-housing conditions. Therefore, rhesus macaques are more suitable for use as a “spontaneous” model of depressive disorders. PMID:24600363

  1. A stochastic model for the analysis of bivariate longitudinal AIDS data.

    Science.gov (United States)

    Sy, J P; Taylor, J M; Cumberland, W G

    1997-06-01

    We present a model for multivariate repeated measures that incorporates random effects, correlated stochastic processes, and measurement errors. The model is a multivariate generalization of the model for univariate longitudinal data given by Taylor, Cumberland, and Sy (1994, Journal of the American Statistical Association 89, 727-736). The stochastic process used in this paper is the multivariate integrated Ornstein-Uhlenbeck (OU) process, which includes Brownian motion and a random effects model as special limiting cases. This process is an underlying continuous-time autoregressive order [AR(1)] process for the derivatives of the multivariate observations. The model allows unequally spaced observations and missing values for some of the variables. We analyze CD4 T-cell and beta-2-microglobulin measurements of the seroconverters at multiple time points from the Los Angeles section of the Multicenter AIDS Cohort Study. The model allows us to investigate the relationship between CD4 and beta-2-microglobulin through the correlations between their random effects and their serial correlation. The data suggest that CD4 and beta-2-microglobulin follow a bivariate Brownian motion process. The fit of the model implies that an increase in beta-2-microglobulin is associated with a decrease in future CD4 but not vice versa, agreeing with immunologic postulates about the relationship between these two variables.

  2. Visualization of transepithelial passage of the immunogenic 33-residue peptide from alpha-2 gliadin in gluten-sensitive macaques.

    Directory of Open Access Journals (Sweden)

    Kaushiki Mazumdar

    Full Text Available BACKGROUND: Based on clinical, histopathological and serological similarities to human celiac disease (CD, we recently established the rhesus macaque model of gluten sensitivity. In this study, we further characterized this condition based on presence of anti-tissue transglutaminase 2 (TG2 antibodies, increased intestinal permeability and transepithelial transport of a proteolytically resistant, immunotoxic, 33-residue peptide from alpha(2-gliadin in the distal duodenum of gluten-sensitive macaques. METHODOLOGY/PRINCIPAL FINDINGS: Six rhesus macaques were selected for study from a pool of 500, including two healthy controls and four gluten-sensitive animals with elevated anti-gliadin or anti-TG2 antibodies as well as history of non-infectious chronic diarrhea. Pediatric endoscope-guided pinch biopsies were collected from each animal's distal duodenum following administration of a gluten-containing diet (GD and again after remission by gluten-free diet (GFD. Control biopsies always showed normal villous architecture, whereas gluten-sensitive animals on GD exhibited histopathology ranging from mild lymphocytic infiltration to villous atrophy, typical of human CD. Immunofluorescent microscopic analysis of biopsies revealed IgG+ and IgA+ plasma-like cells producing antibodies that colocalized with TG2 in gluten-sensitive macaques only. Following instillation in vivo, the Cy-3-labeled 33-residue gluten peptide colocalized with the brush border protein villin in all animals. In a substantially enteropathic macaque with "leaky" duodenum, the peptide penetrated beneath the epithelium into the lamina propria. CONCLUSIONS/SIGNIFICANCE: The rhesus macaque model of gluten sensitivity not only resembles the histopathology of CD but it also may provide a model for studying intestinal permeability in states of epithelial integrity and disrepair.

  3. A method of computer aided design with self-generative models in NX Siemens environment

    Science.gov (United States)

    Grabowik, C.; Kalinowski, K.; Kempa, W.; Paprocka, I.

    2015-11-01

    Currently in CAD/CAE/CAM systems it is possible to create 3D design virtual models which are able to capture certain amount of knowledge. These models are especially useful in an automation of routine design tasks. These models are known as self-generative or auto generative and they can behave in an intelligent way. The main difference between the auto generative and fully parametric models consists in the auto generative models ability to self-organizing. In this case design model self-organizing means that aside from the possibility of making of automatic changes of model quantitative features these models possess knowledge how these changes should be made. Moreover they are able to change quality features according to specific knowledge. In spite of undoubted good points of self-generative models they are not so often used in design constructional process which is mainly caused by usually great complexity of these models. This complexity makes the process of self-generative time and labour consuming. It also needs a quite great investment outlays. The creation process of self-generative model consists of the three stages it is knowledge and information acquisition, model type selection and model implementation. In this paper methods of the computer aided design with self-generative models in NX Siemens CAD/CAE/CAM software are presented. There are the five methods of self-generative models preparation in NX with: parametric relations model, part families, GRIP language application, knowledge fusion and OPEN API mechanism. In the paper examples of each type of the self-generative model are presented. These methods make the constructional design process much faster. It is suggested to prepare this kind of self-generative models when there is a need of design variants creation. The conducted research on assessing the usefulness of elaborated models showed that they are highly recommended in case of routine tasks automation. But it is still difficult to distinguish

  4. Differences in compact bone tissue microscopic structure between adult humans (Homo sapiens) and Assam macaques (Macaca assamensis).

    Science.gov (United States)

    Nganvongpanit, Korakot; Phatsara, Manussabhorn; Settakorn, Jongkolnee; Mahakkanukrauh, Pasuk

    2015-09-01

    This study investigated the osteon structure of adult humans and Assam macaques, which served as a nonhuman primate model, to find an adequate key for species identification. Samples of compact bone from humans (n=5) and Assam macaques (n=5) - including humerus (n=20), radius (n=20), ulna (n=20), femur (n=20), tibia (n=20) and fibula (n=20) - were processed using conventional histological techniques. 100 secondary osteons from each sample were evaluated under light microscopy. Parameter measurements included: diameter, perimeter and area of Haversian canal and osteon; distance between centers of Haversian canals; and ratio between diameter of Haversian canal and osteon. Four parameters, including diameters and areas of Haversian canal and osteon, demonstrated significantly higher (P<0.05) values in humans than in Assam macaques. Therefore, compact bone microstructure could thus be used as a potential tool to differentiate human and nonhuman primates.

  5. Earth Science Data and Models for Improved Targeting of Humanitarian Aid

    Science.gov (United States)

    Brown, Molly E.

    2011-01-01

    Humanitarian assistance to developing countries has long focused on countries that have political, economic and strategic interest to the United States. Recent changes in global security concerns have heightened the perception that humanitarian action is becoming increasingly politicized. This is seen to be largely driven by the 'global war on terror' along with a push by donors and the United Nations for closer integration between humanitarian action and diplomatic, military and other spheres of engagement in conflict and crisis-affected states (HPG 2010). As we enter an era of rising commodity prices and increasing uncertainty in global food production due to a changing climate, scientific data and analysis will be increasingly important to improve the targeting of humanitarian assistance. Earth science data enables appropriate humanitarian response to complex food emergencies that arise in regions outside the areas of current strategic and security focus. As the climate changes, new places will become vulnerable to food insecurity and will need emergency assistance. Earth science data and multidisciplinary models will enable an information-based comparison of need that goes beyond strategic and political considerations to identify new hotspots of food insecurity as they emerge. These analyses will improve aid targeting and timeliness while reducing strategic risk by highlighting new regions at risk of crisis in a rapidly changing world. Improved targeting with respect to timing and location could reduce cost while increasing the likelihood that those who need aid get it.

  6. The relationship between Chinese construction workers' HIV/AIDS-related knowledge, attitudes and behaviour: a structural equation model.

    Science.gov (United States)

    Qu, B; Guo, H Q; Liu, J; Zuo, T M; Zhang, Y; Sun, G

    2009-01-01

    This study explored the relationship between human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS)-related knowledge, attitudes and behaviour in migrant urban construction workers using structural equation modelling (SEM). A cross-sectional study was conducted among 428 male subjects on three building sites in Shenyang City. The SEM model of HIV/AIDS-related knowledge, attitudes and behaviour was built using LISREL version 8.5 and it fitted the data well, as shown by an adjusted goodness of fit index of 0.82 and a root mean square error of approximation of 0.094. Knowledge of HIV/AIDS was closely correlated with attitudes and behaviour. Age was an important factor affecting HIV/AIDS-related knowledge, attitudes and behaviour. These findings suggest that increasing HIV/AIDS-related knowledge could improve the attitude and behaviour of migrant urban construction workers, enabling them to avoid high-risk behaviour that increases the spread of HIV/AIDS. Any intervention used will need to take the important factor of age into consideration.

  7. Fructosamine reference ranges in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Williams-Fritze, Misty J; Smith, Peter C; Zelterman, Daniel; Scholz, Jodi A Carlson

    2011-07-01

    Naturally occurring diabetes mellitus (DM) is common in several species of Old and New World nonhuman primates. Fructosamine values provide important information about recent glycemic control and can be useful in the diagnosis and management of DM. However, despite an abundance of reports in the literature describing spontaneous and induced DM in monkeys, few reference ranges are available for fructosamine. Reference ranges have been published for woolly monkeys (Lagothrix lagotricha), cynomolgus macaques (Macaca fascicularis), and stumptail macaques (Macaca arctoides) but currently are not available for rhesus macaques. At our institution, DM is a common diagnosis in aging rhesus macaques. Here we report a reference range for fructosamine in rhesus macaques. The overall range was 157 to 230 μmol/L, with male rhesus and macaques 10 y or older having significantly higher values than do female rhesus and macaques younger than 10 y, respectively. This range provides clinical veterinarians with an additional tool for evaluating glycemic control in rhesus macaques. Copyright 2011 by the American Association for Laboratory Animal Science

  8. Ab initio identification of transcription start sites in the Rhesus macaque genome by histone modification and RNA-Seq

    OpenAIRE

    2011-01-01

    Rhesus macaque is a widely used primate model organism. Its genome annotations are however still largely comparative computational predictions derived mainly from human genes, which precludes studies on the macaque-specific genes, gene isoforms or their regulations. Here we took advantage of histone H3 lysine 4 trimethylation (H3K4me3)’s ability to mark transcription start sites (TSSs) and the recently developed ChIP-Seq and RNA-Seq technology to survey the transcript structures. We generated...

  9. Development and Psychometrics of Health Belief Model Instrument about HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Mohammad Masod Vakili

    2012-09-01

    Full Text Available Background: With no effective vaccine for prevention or a definite cure for treatment, health education is considered the most effective intervention against HIV. Using a valid tool to evaluate the effect of health education interventions is an inevitable necessity. The aim of this study was to design a tool and to assess its validity and reliability based on native culture characterization in order to evaluate the health belief model constructs about AIDS. Materials and Methods: 480 women covered by health bases of the city of Zanjan, in the age group of 20-30 years, married, and with at least first middle school education participated in this cross-sectional study. After reviewing the literature, the tool was designed and its validity and reliability was approved based on psychometric processes and feedback from the target group and a panel of experts through calculating the content validity ratio, content validity index, exploratory factor analysis, and determining internal consistency.Results: The validity of 37 items were assessed and selected through calculating the index score of the item effect above 1.5, content validity index ratio greater than 0.49, and content validity index higher than 0.79 and by using exploratory factor analysis with a special value greater than 1; seven factors and 34 items were kept and classified into five categories based on literature review and content items. The reliability of the research tool was calculated with Cronbach’s alpha equal to 0.82.Conclusion: The results of this study provide appropriate evidence about the strength of structural factors and the reliability of the assessment tool for structures of health belief models about AIDS, and the creation of accessibility to a reliable tool for assessing the structures of health belief model.

  10. Effects of tourists on Barbary macaques at Gibraltar.

    Science.gov (United States)

    O'Leary, H; Fa, J E

    1993-01-01

    Interactions between tourists and Barbary macaques (Macaca sylvanus) at Queen's Gate, Gibraltar, are described. Interaction rates are high, with 99.6 interactions/h at peak times. Macaques spend 13.2% of their day interacting with tourists and 41.9% inactive. An overall ratio of 3.2:1 between human-initiated and macaque-initiated interactions was found. Of interactions involving humans, 85% concerned tourists. Diurnal activity patterns of the macaques were adapted to tourist visitation patterns. Old animals initiated more food-related interactions than younger ones. Infants/juveniles were the commonest class in contacts with humans and vehicles. Interactions involving more than one macaque were rare. High interaction rates were recorded for mothers and babies.

  11. Health Belief Model and HIV/AIDS among high school female students in Yazd, Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Baghianimoghadam

    2010-01-01

    ="font-family: "Times New Roman","serif";"> containing HIV. (1-4   It is such a strange and frightening disease that sometimes people stopped thinking about it as a disease and start to wrap it in different layers of mystery.(5 According to the latest figures published in the UNAIDS/WHO 2006 AIDS Epidemic Update, an estimated 39.5 million people are living with HIV. (6 An important factor in the spread of HIV/AIDS is believed to be poor knowledge about how it is spread and can be prevented. The utility of the Health Belief Model continues to be suggested in identifying preventive behaviors. This study is a cross- sectional study that 180 female students from three high schools in Yazd, Iran, completed a specially designed questionnaire, based on Health Belief Model in spring 2009. Our data showed that the mean score of perceived susceptibility was 21.19 (out of 32 and perceived severity was 12.47 (out of 24. Also the mean score of perceived benefits and barriers were 9.05 and 9.45 (out of 12 and out of 16 respectively. The respondents acquired 46.61% of total knowledge score, 66.21% of perceived susceptibility, 51.95% of perceived severity, 75.41% of perceived benefits and 59.06% of perceived barriers. A positive association found

  12. Mathematical models as aids for design and development of experiments: the case of transgenic mosquitoes.

    Science.gov (United States)

    Robert, Michael A; Legros, Mathieu; Facchinelli, Luca; Valerio, Laura; Ramsey, Janine M; Scott, Thomas W; Gould, Fred; Lloyd, Alun L

    2012-11-01

    We demonstrate the utility of models as aids in the design and development of experiments aimed at measuring the effects of proposed vector population control strategies. We describe the exploration of a stochastic, age-structured model that simulates field cage experiments that test the ability of a female-killing strain of the mosquito Aedes aegypti (L.) to suppress a wild-type population. Model output predicts that choices of release ratio and population size can impact mean extinction time and variability in extinction time among experiments. We find that unless fitness costs are >80% they will not be detectable in experiments with high release ratios. At lower release ratios, the predicted length of the experiment increases significantly for fitness costs >20%. Experiments with small populations may more accurately reflect field conditions, but extinction can occur even in the absence of a functional female-killing construct because of stochastic effects. We illustrate how the model can be used to explore experimental designs that aim to study the impact of density dependence and immigration; predictions indicate that cage population eradication may not always be obtainable in an operationally realistic time frame. We propose a method to predict the extinction time of a cage population based on the rate of population reduction with the goal of shortening the duration of the experiment. We discuss the model as a tool for exploring and assessing the utility of a wider range of scenarios than would be feasible to test experimentally because of financial and temporal restraints.

  13. An Intelligent Master Model of Computer Aided Process Planning for Large Complicated Stampings

    Institute of Scientific and Technical Information of China (English)

    Zheng Jinqiao; Wang Yilin; Li Zhigang

    2005-01-01

    Process planning for large complicated stampings is more complicated, illegible and multiform than that for common stampings.In this paper, an intelligent master model of computer aided process planning (CAPP) for large complicated stampings has been developed based on knowledge based engineering (KBE) and feature technology. This innovative model consists of knowledge base ( KB), process control structure (PCS), process information model (PIM), multidisciplinary design optimization (MDO), model link environment (MLE) and simulation engine (SE), to realize process planning, optimization, simulation and management integrated to complete intelligent CAPP system. In this model, KBE provides knowledge base, open architecture and knowledge reuse ability to deal with the multi-domain and multi-expression of process knowledge, and forms an integrated environment. With PIM,all the knowledge consisting of objects, constraints, experience and decision-makings is carried by object-oriented method dynamically for knowledge-reasoning. PCS makes dynamical knowledge modified and updated timely and accordingly. MLE provides sev eral methods to make CAPP system associated and integrated. SE provides a programmable mechanism to interpret simulation course and result. Meanwhile, collaborative optimization, one method of MDO, is imported to deal with the optimization distributed for multiple purposes. All these make CAPP system integrated and open to other systems, such as die design and manufacturing system.

  14. Studies on Pumice Lightweight Aggregate Concrete with Quarry Dust Using Mathematical Modeling Aid of ACO Techniques

    Directory of Open Access Journals (Sweden)

    J. Rex

    2016-01-01

    Full Text Available The lightweight aggregate is an aggregate that weighs less than the usual rock aggregate and the quarry dust is a rock particle used in the concrete for the experimentation. The significant intention of the proposed technique is to frame a mathematical modeling with the aid of the optimization techniques. The mathematical modeling is done by minimizing the cost and time consumed in the case of extension of the real time experiment. The proposed mathematical modeling is utilized to predict four output parameters such as compressive strength (Mpa, split tensile strength (Mpa, flexural strength (Mpa, and deflection (in mm. Here, the modeling is carried out with three different optimization techniques like genetic algorithm (GA, particle swarm optimization (PSO, and ant colony optimization (ACO with 80% of data from experiment utilized for the training and the remaining 20% for the validation. Finally, while testing, the error value is minimized and the performance obtained in the ACO for the parameters such as compressive strength, split tensile strength, flexural strength, and deflection is 91%, 98%, 87%, and 94% of predicted values, respectively, in the mathematical modeling.

  15. Optogenetic Activation of Normalization in Alert Macaque Visual Cortex.

    Science.gov (United States)

    Nassi, Jonathan J; Avery, Michael C; Cetin, Ali H; Roe, Anna W; Reynolds, John H

    2015-06-17

    Normalization has been proposed as a canonical computation that accounts for a variety of nonlinear neuronal response properties associated with sensory processing and higher cognitive functions. A key premise of normalization is that the excitability of a neuron is inversely proportional to the overall activity level of the network. We tested this by optogenetically activating excitatory neurons in alert macaque primary visual cortex and measuring changes in neuronal activity as a function of stimulation intensity, with or without variable-contrast visual stimulation. Optogenetic depolarization of excitatory neurons either facilitated or suppressed baseline activity, consistent with indirect recruitment of inhibitory networks. As predicted by the normalization model, neurons exhibited sub-additive responses to optogenetic and visual stimulation, which depended lawfully on stimulation intensity and luminance contrast. We conclude that the normalization computation persists even under the artificial conditions of optogenetic stimulation, underscoring the canonical nature of this form of neural computation.

  16. Comparative Pathology of Smallpox and Monkeypox in Man and Macaques

    Science.gov (United States)

    Cann, J. A.; Jahrling, P. B.; Hensley, L. E.; Wahl-Jensen, V.

    2012-01-01

    Summary In the three decades since the eradication of smallpox and cessation of routine vaccination, the collective memory of the devastating epidemics caused by this orthopoxvirus has waned, and the human population has become increasingly susceptible to a disease that remains high on the list of possible bioterrorism agents. Research using surrogate orthopoxviruses in their natural hosts, as well as limited variola virus research in animal models, continues worldwide; however, interpretation of findings is often limited by our relative lack of knowledge about the naturally occurring disease. For modern comparative pathologists, many of whom have no first-hand knowledge of naturally occurring smallpox, this work provides a contemporary review of this historical disease, as well as discussion of how it compares with human monkeypox and the corresponding diseases in macaques. PMID:22884034

  17. Fitness-related patterns of genetic variation in rhesus macaques.

    Science.gov (United States)

    Blomquist, Gregory E

    2009-03-01

    The patterning of quantitative genetic descriptions of genetic and residual variation for 15 skeletal and six life history traits was explored in a semi-free-ranging group of rhesus macaques (Macaca mulatta Zimmerman 1780). I tested theoretical predictions that explain the magnitude of genetic and residual variation as a result of 1. strength of a trait's association with evolutionary fitness, or 2. developmental and physiological relationships among traits. I found skeletal traits had higher heritabilities and lower coefficients of residual variation than more developmentally and physiologically dependent life history traits. Total lifetime fertility had a modest heritability (0.336) in this population, and traits with stronger correlations to fitness had larger amounts of residual variance. Censoring records of poorly-performing individuals on lifetime fertility and lifespan substantially reduced their heritabilities. These results support models for the fitness-related patterning of genetic variation based on developmental and physiological relationships among traits rather than the action of selection eroding variation.

  18. X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Youjun [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); Graduate School, Chinese Academy of Sciences, Beijing (China); Qi, Jianxun [Graduate School, Chinese Academy of Sciences, Beijing (China); Institute of Physics, Chinese Academy of Sciences, Beijing 100080 (China); Zhang, Huimin; Wang, Jinzi [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); Liu, Jinhua [College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China); Jiang, Fan [Institute of Physics, Chinese Academy of Sciences, Beijing 100080 (China); Gao, Feng, E-mail: gaofeng@im.ac.cn [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China)

    2006-01-01

    X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide. Simian immunodeficiency virus (SIV) in the rhesus macaque is regarded as a classic animal model, playing a crucial role in HIV vaccine strategies and therapeutics by characterizing various cytotoxic T-lymphocyte (CTL) responses in macaque monkeys. However, the availability of well documented structural reports focusing on rhesus macaque major histocompatibility complex class I (MHC I) molecules remains extremely limited. Here, a complex of the rhesus macaque MHC I molecule (Mamu-A*02) with human β{sub 2}m and an immunodominant SIV-Gag nonapeptide, GESNLKSLY (GY9), has been crystallized. The crystal diffracts X-rays to 2.7 Å resolution and belongs to space group C2, with unit-cell parameters a = 124.11, b = 110.45, c = 100.06 Å, and contains two molecules in the asymmetric unit. The availability of the structure, which is being solved by molecular replacement, will provide new insights into rhesus macaque MHC I (Mamu-A*02) presenting pathogenic SIV peptides.

  19. Natural host genetic resistance to lentiviral CNS disease: a neuroprotective MHC class I allele in SIV-infected macaques.

    Directory of Open Access Journals (Sweden)

    Joseph L Mankowski

    Full Text Available Human immunodeficiency virus (HIV infection frequently causes neurologic disease even with anti-retroviral treatment. Although associations between MHC class I alleles and acquired immunodeficiency syndrome (AIDS have been reported, the role MHC class I alleles play in restricting development of HIV-induced organ-specific diseases, including neurologic disease, has not been characterized. This study examined the relationship between expression of the MHC class I allele Mane-A*10 and development of lentiviral-induced central nervous system (CNS disease using a well-characterized simian immunodeficiency (SIV/pigtailed macaque model. The risk of developing CNS disease (SIV encephalitis was 2.5 times higher for animals that did not express the MHC class I allele Mane-A*10 (P = 0.002; RR = 2.5. Animals expressing the Mane-A*10 allele had significantly lower amounts of activated macrophages, SIV RNA, and neuronal dysfunction in the CNS than Mane-A*10 negative animals (P<0.001. Mane-A*10 positive animals with the highest CNS viral burdens contained SIV gag escape mutants at the Mane-A*10-restricted KP9 epitope in the CNS whereas wild type KP9 sequences dominated in the brain of Mane-A*10 negative animals with comparable CNS viral burdens. These concordant findings demonstrate that particular MHC class I alleles play major neuroprotective roles in lentiviral-induced CNS disease.

  20. White-cheeked macaque (Macaca leucogenys): A new macaque species from Medog, southeastern Tibet.

    Science.gov (United States)

    Li, Cheng; Zhao, Chao; Fan, Peng-Fei

    2015-07-01

    We describe a newly discovered Macaca species from the Medog, in southeastern Tibet, China, Macaca leucogenys sp. nov or the "white-cheeked macaque". Based on 738 photos taken during direct observations and captured by camera traps this new species appears to be distinct from the Macaca sinica species group. Moreover, the species is distinguished from all potential sympatric macaque species (M. mulatta, M. thibetana, M. assamensis, and M. munzala) in exhibiting a suite of pelage characteristics including relatively uniform dorsal hair pattern, hairy ventral pelage, relative hairless short tail, prominent pale to white side- and chin-whiskers creating a white cheek and round facial appearance, dark facial skin on the muzzle, long and thick hairs on its neck, and a round rather than arrow-shaped male genitalia. This new macaque species was found to exploit a diverse set of habitat types from tropical forest at 1395 m, to primary and secondary evergreen broad-leaved forest at 2000 m, as well as mixed broadleaf-conifer forest at 2700 m. Its range may extend to neighboring counties in Tibet and the part of southeastern Tibet controlled by India. The white-cheeked macaque is threatened by illegal hunting and the construction of hydropower stations. Discovery of this new primate species further highlights the high value for biodiversity conservation of southeastern Tibet and calls for more intensive surveys, studies, and environmental protection in this area.

  1. Underwater Digital Terrain Model with GPS-aided High-resolution Profile-scan Sonar Images

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yong-jun; KOU Xin-jian

    2008-01-01

    The whole procedures of underwater digital terrain model (DTM) were presented by building with the global positioning system (GPS) aided high-resolution profile-scan sonar images. The algorithm regards the digital image scanned in a cycle as the raw data. First the label rings are detected with the improved Hough transform (HT) method and followed by curve-fitting for accurate location; then the most probable window for each ping is detected with weighted neighborhood gray-level co-occurrence matrix; and finally the DTM is built by integrating the GPS data with sonar data for 3D visualization. The case of an underwater trench for immersed tube road tunnel is illustrated.

  2. A Computer-aided Application for Modeling and Monitoring Operational and Maintenance Information in Mining Trucks

    Science.gov (United States)

    Nikulin, Christopher; Ulloa, Andres; Carmona, Carlos; Creixell, Werner

    2016-09-01

    The combination of maintenance planning and key performance indicators are relevant to create a more holistic scenario of the mining activities. On the one hand, reliability and maintainability are system characteristics suitable for planning maintenance strategies. On the other hand, key performance indicators are suitable to analyze cost and resource consumption information about mining equipment. Nevertheless in practice, both approaches are modeled separately and frequently by different team-works of a mining company. With this in mind, a computer-aided application was conceived to drive with better efficacy the operational and maintenance strategy in a complex process where the equipment is in continuous movement such as the transportation process in an open-mine pit.

  3. Establishment of AIDS Animal Model with SIVmac239 Infected Chinese Rhesus Monkey

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In the present research, two Chinese rhesus monkeys were inoculated intravenously with 5000 TCID50 of SIVmac239. The changes in the numbers of CD4+T lymphocyte in peripheral blood,plasma viral loads, proviral DNA and humoral antibodies against virus were periodically monitored during 121 days. At the early stage of infection, proviral DNA had been detected in PBMCs, and infectious SIVmac239 virus had been isolated from PBMCs. At the same period, the numbers of CD4+T lymphocytes were significantly decreased, and maintained at low level during the 121-day period of infection. Plasma viral loads reached the peak at week 2 post-inoculation and kept at a steady state subsequently. Moreover, antibodies against viral proteins were detected from plasma. All the results showed that the two Chinese rhesus monkeys had been infected with SIVmac239 successfully. This animal model can be applied for further AIDS researches.

  4. Computer-aided geometric modeling of the human eye and orbit.

    Science.gov (United States)

    Parshall, R F

    1991-01-01

    The author advocates, as a long-term development agenda for the profession, a shift in the working methods of medical illustrators from a two-dimensional image processing mode to a computer-aided design and drafting (CADD) mode. Existing CADD technology, which can make short work of the complex graphic construction problems of anatomical visualization, performs virtually all of its manipulations through systematic exercise of graphic geometry which illustrators tend to reduce to an intuitive, almost vestigial supplement to 2D image processing methods. The primary barrier to the immediate use of CADD is a lack of geometric database materials on anatomical component systems of the body. An on-going experimental project in modeling the human eye and orbit, utilizing a Silicon Graphics Iris workstation and Control Data Corporation's Integrated Computerized Engineering and Manufacturing (ICEM) software, exemplifies the preparatory work needed to create such database materials.

  5. Auditory Rehabilitation in Rhesus Macaque Monkeys (Macaca mulatta) with Auditory Brainstem Implants

    Institute of Scientific and Technical Information of China (English)

    Zhen-Min Wang; Zhi-Jun Yang; Fu Zhao; Bo Wang; Xing-Chao Wang; Pei-Ran Qu; Pi-Nan Liu

    2015-01-01

    Background:The auditory brainstem implants (ABIs) have been used to treat deafness for patients with neurofibromatosis Type 2 and nontumor patients.The lack of an appropriate animal model has limited the study of improving hearing rehabilitation by the device.This study aimed to establish an animal model of ABI in adult rhesus macaque monkey (Macaca mulatta).Methods:Six adult rhesus macaque monkeys (M.mulatta) were included.Under general anesthesia,a multichannel ABI was implanted into the lateral recess of the fourth ventricle through the modified suboccipital-retrosigmoid (RS) approach.The electrical auditory brainstem response (EABR) waves were tested to ensure the optimal implant site.After the operation,the EABR and computed tomography (CT) were used to test and verify the effectiveness via electrophysiology and anatomy,respectively.The subjects underwent behavioral observation for 6 months,and the postoperative EABR was tested every two weeks from the 1st month after implant surgery.Result:The implant surgery lasted an average of 5.2 h,and no monkey died or sacrificed.The averaged latencies of peaks Ⅰ,Ⅱ and Ⅳ were 1.27,2.34 and 3.98 ms,respectively in the ABR.One-peak EABR wave was elicited in the operation,and one-or two-peak waves were elicited during the postoperative period.The EABR wave latencies appeared to be constant under different stimulus intensities;however,the amplitudes increased as the stimulus increased within a certain scope.Conclusions:It is feasible and safe to implant ABIs in rhesus macaque monkeys (M.mulatta) through a modified suboccipital RS approach,and EABR and CT are valid tools for animal model establishment.In addition,this model should be an appropriate animal model for the electrophysiological and behavioral study of rhesus macaque monkey with ABI.

  6. IgG Binding Characteristics of Rhesus Macaque FcγR.

    Science.gov (United States)

    Chan, Ying N; Boesch, Austin W; Osei-Owusu, Nana Y; Emileh, Ali; Crowley, Andrew R; Cocklin, Sarah L; Finstad, Samantha L; Linde, Caitlyn H; Howell, Rebecca A; Zentner, Isaac; Cocklin, Simon; Miles, Adam R; Eckman, Joshua W; Alter, Galit; Schmitz, Joern E; Ackerman, Margaret E

    2016-10-01

    Indian rhesus macaques (Macaca mulatta) are routinely used in preclinical studies to evaluate therapeutic Abs and candidate vaccines. The efficacy of these interventions in many cases is known to rely heavily on the ability of Abs to interact with a set of Ab FcγR expressed on innate immune cells. Yet, despite their presumed functional importance, M. mulatta Ab receptors are largely uncharacterized, posing a fundamental limit to ensuring accurate interpretation and translation of results from studies in this model. In this article, we describe the binding characteristics of the most prevalent allotypic variants of M. mulatta FcγR for binding to both human and M. mulatta IgG of varying subclasses. The resulting determination of the affinity, specificity, and glycan sensitivity of these receptors promises to be useful in designing and evaluating studies of candidate vaccines and therapeutic Abs in this key animal model and exposes significant evolutionary divergence between humans and macaques.

  7. Modelling, Simulation and Testing of a Reconfigurable Cable-Based Parallel Manipulator as Motion Aiding System

    Directory of Open Access Journals (Sweden)

    Gianni Castelli

    2010-01-01

    Full Text Available This paper presents results on the modelling, simulation and experimental tests of a cable-based parallel manipulator to be used as an aiding or guiding system for people with motion disabilities. There is a high level of motivation for people with a motion disability or the elderly to perform basic daily-living activities independently. Therefore, it is of great interest to design and implement safe and reliable motion assisting and guiding devices that are able to help end-users. In general, a robot for a medical application should be able to interact with a patient in safety conditions, i.e. it must not damage people or surroundings; it must be designed to guarantee high accuracy and low acceleration during the operation. Furthermore, it should not be too bulky and it should exert limited wrenches after close interaction with people. It can be advisable to have a portable system which can be easily brought into and assembled in a hospital or a domestic environment. Cable-based robotic structures can fulfil those requirements because of their main characteristics that make them light and intrinsically safe. In this paper, a reconfigurable four-cable-based parallel manipulator has been proposed as a motion assisting and guiding device to help people to accomplish a number of tasks, such as an aiding or guiding system to move the upper and lower limbs or the whole body. Modelling and simulation are presented in the ADAMS environment. Moreover, experimental tests are reported as based on an available laboratory prototype.

  8. A novel trivalent HPV 16/18/58 vaccine with anti-HPV 16 and 18 neutralizing antibody responses comparable to those induced by the Gardasil quadrivalent vaccine in rhesus macaque model.

    Science.gov (United States)

    Yin, Fei; Wang, Yajun; Chen, Na; Jiang, Dunquan; Qiu, Yefeng; Wang, Yan; Yan, Mei; Chen, Jianping; Zhang, Haijiang; Liu, Yongjiang

    2017-06-01

    Persistent infection with human papillomavirus (HPV) is a key factor in the development of precancerous lesions and invasive cervical cancer. Prophylactic vaccines to immunize against HPV are an effective approach to reducing HPV related disease burden. In this study, we investigated the immunogenicity and dosage effect of a trivalent HPV 16/18/58 vaccine (3vHPV) produced in Escherichia coli (E.coli), with Gardasil quadrivalent vaccine (4vHPV, Merck & Co.) as a positive control. Sera collected from rhesus macaques vaccinated with three dosage formulations of 3vHPV (termed low-, mid-, and high-dosage formulations, respectively), and the 4vHPV vaccine were analyzed by both Pseudovirus-Based Neutralization Assay (PBNA) and Enzyme-Linked Immunosorbent Assay (ELISA). Strong immune responses against HPV 16/18/58 were successfully elicited, and dosage-dependence was observed, with likely occurrence of immune interference between different L1-VLP antigens. HPV 16/18 specific neutralizing antibody (nAb) and total immunoglobulin G (IgG) antibody responses in rhesus macaques receiving 3vHPV at the three dosages tested were generally non-inferior to those observed in rhesus macaques receiving 4vHPV throughout the study period. Particularly, HPV 18 nAb titers induced by the mid-dosage formulation that contained the same amounts of HPV 16/18 L1-VLPs as Gardasil 4vHPV were between 7.3 to 12.7-fold higher compared to the positive control arm from weeks 24-64. The durability of antibody responses specific to HPV 16/18 elicited by 3vHPV vaccines was also shown to be non-inferior to that associated with Gardasil 4vHPV. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Transepithelial transport and enzymatic detoxification of gluten in gluten-sensitive rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Michael T Bethune

    Full Text Available BACKGROUND AND AIMS: In a previous report, we characterized a condition of gluten sensitivity in juvenile rhesus macaques that is similar in many respects to the human condition of gluten sensitivity, celiac disease. This animal model of gluten sensitivity may therefore be useful toward studying both the pathogenesis and the treatment of celiac disease. Here, we perform two pilot experiments to demonstrate the potential utility of this model for studying intestinal permeability toward an immunotoxic gluten peptide and pharmacological detoxification of gluten in vivo by an oral enzyme drug candidate. METHODS: Intestinal permeability was investigated in age-matched gluten-sensitive and control macaques by using mass spectrometry to detect and quantify an orally dosed, isotope labeled 33-mer gluten peptide delivered across the intestinal epithelium to the plasma. The protective effect of a therapeutically promising oral protease, EP-B2, was evaluated in a gluten-sensitive macaque by administering a daily gluten challenge with or without EP-B2 supplementation. ELISA-based antibody assays and blinded clinical evaluations of this macaque and of an age-matched control were conducted to assess responses to gluten. RESULTS: Labeled 33-mer peptide was detected in the plasma of a gluten-sensitive macaque, both in remission and during active disease, but not in the plasma of healthy controls. Administration of EP-B2, but not vehicle, prevented clinical relapse in response to a dietary gluten challenge. Unexpectedly, a marked increase in anti-gliadin (IgG and IgA and anti-transglutaminase (IgG antibodies was observed during the EP-B2 treatment phase. CONCLUSIONS: Gluten-sensitive rhesus macaques may be an attractive resource for investigating important aspects of celiac disease, including enhanced intestinal permeability and pharmacology of oral enzyme drug candidates. Orally dosed EP-B2 exerts a protective effect against ingested gluten. Limited data

  10. SHIV-162P3 infection of rhesus macaques given maraviroc gel vaginally does not involve resistant viruses.

    Directory of Open Access Journals (Sweden)

    Athe M N Tsibris

    Full Text Available Maraviroc (MVC gels are effective at protecting rhesus macaques from vaginal SHIV transmission, but breakthrough infections can occur. To determine the effects of a vaginal MVC gel on infecting SHIV populations in a macaque model, we analyzed plasma samples from three rhesus macaques that received a MVC vaginal gel (day 0 but became infected after high-dose SHIV-162P3 vaginal challenge. Two infected macaques that received a placebo gel served as controls. The infecting SHIV-162P3 stock had an overall mean genetic distance of 0.294±0.027%; limited entropy changes were noted across the envelope (gp160. No envelope mutations were observed consistently in viruses isolated from infected macaques at days 14-21, the time of first detectable viremia, nor selected at later time points, days 42-70. No statistically significant differences in MVC susceptibilities were observed between the SHIV inoculum (50% inhibitory concentration [IC(50] 1.87 nM and virus isolated from the three MVC-treated macaques (MVC IC(50 1.18 nM, 1.69 nM, and 1.53 nM, respectively. Highlighter plot analyses suggested that infection was established in each MVC-treated animal by one founder virus genotype. The expected Poisson distribution of pairwise Hamming Distance frequency counts was observed and a phylogenetic analysis did not identify infections with distinct lineages from the challenge stock. These data suggest that breakthrough infections most likely result from incomplete viral inhibition and not the selection of MVC-resistant variants.

  11. A prototype computer-aided modelling tool for life-support system models

    Science.gov (United States)

    Preisig, H. A.; Lee, Tae-Yeong; Little, Frank

    1990-01-01

    Based on the canonical decomposition of physical-chemical-biological systems, a prototype kernel has been developed to efficiently model alternative life-support systems. It supports (1) the work in an interdisciplinary group through an easy-to-use mostly graphical interface, (2) modularized object-oriented model representation, (3) reuse of models, (4) inheritance of structures from model object to model object, and (5) model data base. The kernel is implemented in Modula-II and presently operates on an IBM PC.

  12. An Ontological Model of Evaluation: A Dynamic Model for Aiding Organizational Development.

    Science.gov (United States)

    Peper, John B.

    Evaluation models imply or assume theories of organization, behavior, and decision-making. Seldom does an evaluation model specify these assumptions. As a result, program evaluators often choose mechanistic models and their resultant information is either inadequate or inappropriate for most of the client's purposes. The Ontological Evaluation…

  13. Electric mine motor thermal models aiding design and setting thermal protections

    National Research Council Canada - National Science Library

    Krok, R

    2012-01-01

    The paper presents original modified thermal networks for calculations of the temperature field in induction mine motors under steady and transient conditions aiding design and setting thermal protections...

  14. Depletion of CD8+ cells does not affect the lifespan of productively infected cells during pathogenic sivmac239 infection of rhesus macaques

    Energy Technology Data Exchange (ETDEWEB)

    Shudo, Emi [Los Alamos National Laboratory; Ribeiro, Ruy M [Los Alamos National Laboratory; Perelson, Alan S [Los Alamos National Laboratory

    2008-01-01

    While CD8+ T cell responses are clearly important in anti-viral immunity during HIV/SIV infection, the mechanisms by which CD8+ T cells induce this effect remain poorly understood, as emphasized by the failure of the Merck adenovirus-based, cytotoxic T lymphocyte (CTL)-inducing AIDS vaccine in a large phase IIb clinical trial. In this study, we measured the in vivo effect of CD8+ lymphocytes on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques by treating two groups of animals (i.e., CD8+ lymphocyte-depleted or controls) with antiretroviral therapy (PMPA and FTC). The lifespan of productively infected cells was calculated based on the slope of the decline of SIV plasma viremia using a well-accepted mathematical model. We found that, in both early (i.e., day 57 post-inoculation) and late (i.e., day 177 post-inoculation) chronic SIV infection, depletion of CD8+ lymphocytes did not result in an increased lifespan of productively infected cells in vivo. This result indicates that direct killing of cells producing virus is unlikely to be a major mechanism underlying the anti-viral effect of CD8+ T cells during SIV infection. These results have profound implications for the development of AIDS vaccines.

  15. Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques

    Science.gov (United States)

    Gonzalez, Denise F.; Kieu, Hung T.; Castillo, Luis D.; Messaoudi, Ilhem; Shen, Xiaoying; Tomaras, Georgia D.; Shacklett, Barbara L.; Barry, Peter A.; Sparger, Ellen E.

    2017-01-01

    Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP) model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to characterize circulating rhesus B cell subsets. Significant differences between human and macaque B cells included the proportions of cells within IgD+ and switched memory populations and a prominent CD21-CD27+ unswitched memory population detected only in macaques. We then utilized the expanded panel to analyze B cell alterations associated with aging and acute simian immunodeficiency virus (SIV) infection in the NHP model. In the aging study, distinct patterns of B cell subset frequencies were observed for macaques aged one to five years compared to those between ages 5 and 30 years. In the SIV infection study, B cell frequencies and absolute number were dramatically reduced following acute infection, but recovered within four weeks of infection. Thereafter, the frequencies of activated memory B cells progressively increased; these were significantly correlated with the magnitude of SIV-specific IgG responses, and coincided with impaired maturation of anti-SIV antibody avidity, as previously reported for HIV-1 infection. These observations further validate the NHP model for investigation of mechanisms responsible for B cells alterations associated with immunosenescence and infectious disease. PMID:28095513

  16. A Context-Recognition-Aided PDR Localization Method Based on the Hidden Markov Model

    Directory of Open Access Journals (Sweden)

    Yi Lu

    2016-11-01

    Full Text Available Indoor positioning has recently become an important field of interest because global navigation satellite systems (GNSS are usually unavailable in indoor environments. Pedestrian dead reckoning (PDR is a promising localization technique for indoor environments since it can be implemented on widely used smartphones equipped with low cost inertial sensors. However, the PDR localization severely suffers from the accumulation of positioning errors, and other external calibration sources should be used. In this paper, a context-recognition-aided PDR localization model is proposed to calibrate PDR. The context is detected by employing particular human actions or characteristic objects and it is matched to the context pre-stored offline in the database to get the pedestrian’s location. The Hidden Markov Model (HMM and Recursive Viterbi Algorithm are used to do the matching, which reduces the time complexity and saves the storage. In addition, the authors design the turn detection algorithm and take the context of corner as an example to illustrate and verify the proposed model. The experimental results show that the proposed localization method can fix the pedestrian’s starting point quickly and improves the positioning accuracy of PDR by 40.56% at most with perfect stability and robustness at the same time.

  17. Computer-Aided Modeling and Analysis of Power Processing Systems (CAMAPPS), phase 1

    Science.gov (United States)

    Kim, S.; Lee, J.; Cho, B. H.; Lee, F. C.

    1986-01-01

    The large-signal behaviors of a regulator depend largely on the type of power circuit topology and control. Thus, for maximum flexibility, it is best to develop models for each functional block a independent modules. A regulator can then be configured by collecting appropriate pre-defined modules for each functional block. In order to complete the component model generation for a comprehensive spacecraft power system, the following modules were developed: solar array switching unit and control; shunt regulators; and battery discharger. The capability of each module is demonstrated using a simplified Direct Energy Transfer (DET) system. Large-signal behaviors of solar array power systems were analyzed. Stability of the solar array system operating points with a nonlinear load is analyzed. The state-plane analysis illustrates trajectories of the system operating point under various conditions. Stability and transient responses of the system operating near the solar array's maximum power point are also analyzed. The solar array system mode of operation is described using the DET spacecraft power system. The DET system is simulated for various operating conditions. Transfer of the software program CAMAPPS (Computer Aided Modeling and Analysis of Power Processing Systems) to NASA/GSFC (Goddard Space Flight Center) was accomplished.

  18. A Context-Recognition-Aided PDR Localization Method Based on the Hidden Markov Model.

    Science.gov (United States)

    Lu, Yi; Wei, Dongyan; Lai, Qifeng; Li, Wen; Yuan, Hong

    2016-11-30

    Indoor positioning has recently become an important field of interest because global navigation satellite systems (GNSS) are usually unavailable in indoor environments. Pedestrian dead reckoning (PDR) is a promising localization technique for indoor environments since it can be implemented on widely used smartphones equipped with low cost inertial sensors. However, the PDR localization severely suffers from the accumulation of positioning errors, and other external calibration sources should be used. In this paper, a context-recognition-aided PDR localization model is proposed to calibrate PDR. The context is detected by employing particular human actions or characteristic objects and it is matched to the context pre-stored offline in the database to get the pedestrian's location. The Hidden Markov Model (HMM) and Recursive Viterbi Algorithm are used to do the matching, which reduces the time complexity and saves the storage. In addition, the authors design the turn detection algorithm and take the context of corner as an example to illustrate and verify the proposed model. The experimental results show that the proposed localization method can fix the pedestrian's starting point quickly and improves the positioning accuracy of PDR by 40.56% at most with perfect stability and robustness at the same time.

  19. A Mathematical Model for the Dynamics of HIV/AIDS with Gradual Behaviour Change

    Directory of Open Access Journals (Sweden)

    F. Baryarama

    2006-01-01

    Full Text Available An HIV/AIDS model that incorporates gradual behaviour change is formulated with a variable force of infection for the adult population. The variability is modelled using a general function of time since introduction of the initial infective and exemplified for three specific functions. Expressions for the time taken for the reproductive number to reduce to unity and expressions for the time taken to attain a stationary steady state are deduced and discussed. Model projections for urban, peri-urban and rural Uganda are compared with corresponding antenatal clinic sites prevalence trends. The analysis shows that the dramatic decline in HIV prevalence in Uganda in the early 1990s was only possible through drastic declines in the force of infection. Since prevalence was high and reductions in frequency of sexual acts was minimal, the huge reduction could be attributed to reductions in probability of transmission per sexual act probably due to increased selective condom use among high risk sexual partnerships since overall condom use was low.

  20. Small-world network model of propagation of the AIDS epidemic

    Science.gov (United States)

    Shi, Pengliang; Small, Michael

    2004-03-01

    Sexual contact and intravenus drug-use are the most common modes of transmission of HIV-AIDS. In this paper, homogenerous and heterogeneous models are proposed to model the dynamics in a system contains Small-World clusters. Four high risk groups: intravenus drug-users (D); homosexuals (H); individuals with multiple-sexual partners (M) and prostitutes (P), are classified using two models. Both networks are embedded among a background (low-risk) population using rich-get-richer preferential attachment. When a network is established, an epidemic is simulated in it by seeding randomly. We compare the two epidemic networks in detail and consider the effect of different levels of control policies in both. This study highlights two main conclusions: (i) set high protection coefficient for a massive-linkage-vertex (i.e. protect the highly connected individuals); and, (ii) a quick removal for the infected massive-linkage-veterx from the network is essential (rapidly quarantine infected individuals). While these conclusions may be intuitive, they indicate a necessary change of public policy toward prostitution in some developing countries such as China and India. An active effort to prevent possible infection from super-spreader is recommended.

  1. Ulcerative cheilitis in a rhesus macaque.

    Science.gov (United States)

    Bailey, C C; Miller, A D

    2012-03-01

    A 2-year-old, female, simian immunodeficiency virus E543-infected rhesus macaque (Macaca mulatta) was presented for necropsy following euthanasia due to a history of diarrhea, weight loss, and a small, round ulcer along the left labial commissure. Histopathologic examination of the ulcer revealed infiltration by large numbers of degenerate and nondegenerate neutrophils and macrophages admixed with syncytial epithelial cells. Rare epithelial cells contained herpetic inclusion bodies. These cells stained positive for Human herpesvirus 1 via immunohistochemistry, and DNA sequencing confirmed the presence of closely related Macacine herpesvirus 1 (B virus).

  2. Pengembangan Model Pembelajaran Project Based Learning pada Mata Kuliah Computer Aided Design

    Directory of Open Access Journals (Sweden)

    Satoto Endar Nayono

    2013-09-01

    Full Text Available One of the key competencies of graduates majoring in Civil Engineering and Planning Education, Faculty of Engineering, Yogyakarta State University (YSU is able to plan buildings. CAD courses aim to train students to be able to pour the planning concepts into the picture. One of the obstacles faced in the course are concepts and pictures that created by the students often do not correspond to the standards used in the field. This study aims to develop a model of project-based learning so that the students’ pictures are more in line with the actual conditions in the field. This study was carried out through the stages as follows: (1 Pre test, (2 Planning of learning, (3 Implementation of the learning model of project-based learning, (4 monitoring and evaluation (5 Reflection and revision, (6 Implementation of learning in the next cycle, and (7 Evaluation of the learning outcomes. This study was conducted for four months in 2012 in the Department of Civil Engineering and Planning Education, Faculty of Engineering, YSU. The subjects of this study are the students who took the course of Computer Aided Design. The analysis of the data used descriptive qualitative and descriptive statistics. The results of this study were: (1 The implementation of project based learning model was proven to increase the learning process and the learning outcomes of students in the subject of CAD through the provision of buildings planning pictures tasks of school buildings based on the real conditions in the field. The task was delivered in every meeting and improved based on the feedback from their lecturers, (2 the learning model of project based learning will be easier to be implemented if it is accompanied by the model of peer tutoring and the learning model of PAIKEM.

  3. Computer Simulation Modeling: A Method for Predicting the Utilities of Alternative Computer-Aided Treat Evaluation Algorithms

    Science.gov (United States)

    1990-09-01

    0 Technical Report 911 D~i. FiLE COPY Computer Simulation Modeling : A Method for Predicting the Utilities of Alternative Computer-Aided Threat...63007A 793 1202 HI 11. TITLE (Include Security Classification) Computer Simulation Modeling : A Method for Predicting the Utilities of Alternative...SECURITY CLASSIFICATION OF THIS PAGE("wn Data Entered) ii Technical Report 911 Computer Simulation Modeling : A Method for Predicting the Utilities of

  4. Physiological, Behavioral, and Scientific Impact of Different Fluid Control Protocols in the Rhesus Macaque (Macaca mulatta)

    Science.gov (United States)

    Bertrand, Henri; Mindus, Claire; Flecknell, Paul

    2016-01-01

    Abstract Rhesus macaques are an important model in behavioral neuroscience due to their advanced cognitive abilities. To motivate animals to engage in complex tasks, fluid rewards, in conjunction with fluid control protocols, are often used. The impact of these protocols on animal welfare is controversial. We compared two fluid control protocols against a protocol providing free access to water and evaluated the impacts on physiological states of hydration, behavioral measures of welfare, and scientific output. Blood physiology did not significantly differ between any of the protocols, and urine measures were indicative of well functioning, healthy kidneys. Changes in behaviors were limited, the main one being an increase in motivation to drink on the stricter fluid control protocol, and improved task performance early in the week. Overall, fluid control protocols had little measurable impact on the welfare of rhesus macaques while ensuring that scientific data of high quality could be obtained. PMID:27679812

  5. Fear reactions to snakes in naïve mouse lemurs and pig-tailed macaques.

    Science.gov (United States)

    Weiss, Lucie; Brandl, Pavel; Frynta, Daniel

    2015-07-01

    Primates have been predated on by snakes throughout their evolution and as a result, antipredator responses accompanied by signs of fear are often witnessed in the wild. In captivity, however, the fear of snakes is less clear, as experiments with naïve nonhuman primates have given inconsistent results. In this study, we present evidence that naïve mouse lemurs (Microcebus murinus) and putatively naïve pig-tailed macaques (Macaca nemestrina) do exhibit fear of snakes, even though the apparent reactions are mild. In an experiment with control- or snake-odoured boxes, mouse lemurs clearly avoided feeding in the latter. When the latency of touching rubber models was measured, pig-tailed macaques took longer to touch a toy snake compared with a toy lizard. Our findings that fear of snakes is shown by naïve individuals support the hypothesis that it is innate in primates.

  6. An effort to use human-based exome capture methods to analyze chimpanzee and macaque exomes

    DEFF Research Database (Denmark)

    Jin, Xin; He, Mingze; Ferguson, Betsy;

    2012-01-01

    Non-human primates have emerged as an important resource for the study of human disease and evolution. The characterization of genomic variation between and within non-human primate species could advance the development of genetically defined non-human primate disease models. However, non-human...... primate specific reagents that would expedite such research, such as exon-capture tools, are lacking. We evaluated the efficiency of using a human exome capture design for the selective enrichment of exonic regions of non-human primates. We compared the exon sequence recovery in nine chimpanzees, two crab......-eating macaques and eight Japanese macaques. Over 91% of the target regions were captured in the non-human primate samples, although the specificity of the capture decreased as evolutionary divergence from humans increased. Both intra-specific and inter-specific DNA variants were identified; Sanger...

  7. Zika Virus Tissue and Blood Compartmentalization in Acute Infection of Rhesus Macaques

    Science.gov (United States)

    Coffey, Lark L.; Pesavento, Patricia A.; Keesler, Rebekah I.; Singapuri, Anil; Watanabe, Jennifer; Watanabe, Rie; Yee, JoAnn; Bliss-Moreau, Eliza; Cruzen, Christina; Christe, Kari L.; Reader, J. Rachel; von Morgenland, Wilhelm; Gibbons, Anne M.; Allen, A. Mark; Linnen, Jeff; Gao, Kui; Delwart, Eric; Simmons, Graham; Stone, Mars; Lanteri, Marion; Bakkour, Sonia; Busch, Michael; Morrison, John

    2017-01-01

    Animal models of Zika virus (ZIKV) are needed to better understand tropism and pathogenesis and to test candidate vaccines and therapies to curtail the pandemic. Humans and rhesus macaques possess similar fetal development and placental biology that is not shared between humans and rodents. We inoculated 2 non-pregnant rhesus macaques with a 2015 Brazilian ZIKV strain. Consistent with most human infections, the animals experienced no clinical disease but developed short-lived plasma viremias that cleared as neutralizing antibody developed. In 1 animal, viral RNA (vRNA) could be detected longer in whole blood than in plasma. Despite no major histopathologic changes, many adult tissues contained vRNA 14 days post-infection with highest levels in hemolymphatic tissues. These observations warrant further studies to investigate ZIKV persistence and its potential clinical implications for transmission via blood products or tissue and organ transplants. PMID:28141843

  8. Attention and normalization circuits in macaque V1.

    Science.gov (United States)

    Sanayei, M; Herrero, J L; Distler, C; Thiele, A

    2015-04-01

    Attention affects neuronal processing and improves behavioural performance. In extrastriate visual cortex these effects have been explained by normalization models, which assume that attention influences the circuit that mediates surround suppression. While normalization models have been able to explain attentional effects, their validity has rarely been tested against alternative models. Here we investigate how attention and surround/mask stimuli affect neuronal firing rates and orientation tuning in macaque V1. Surround/mask stimuli provide an estimate to what extent V1 neurons are affected by normalization, which was compared against effects of spatial top down attention. For some attention/surround effect comparisons, the strength of attentional modulation was correlated with the strength of surround modulation, suggesting that attention and surround/mask stimulation (i.e. normalization) might use a common mechanism. To explore this in detail, we fitted multiplicative and additive models of attention to our data. In one class of models, attention contributed to normalization mechanisms, whereas in a different class of models it did not. Model selection based on Akaike's and on Bayesian information criteria demonstrated that in most cells the effects of attention were best described by models where attention did not contribute to normalization mechanisms. This demonstrates that attentional influences on neuronal responses in primary visual cortex often bypass normalization mechanisms.

  9. Attention and normalization circuits in macaque V1

    Science.gov (United States)

    Sanayei, M; Herrero, J L; Distler, C; Thiele, A

    2015-01-01

    Attention affects neuronal processing and improves behavioural performance. In extrastriate visual cortex these effects have been explained by normalization models, which assume that attention influences the circuit that mediates surround suppression. While normalization models have been able to explain attentional effects, their validity has rarely been tested against alternative models. Here we investigate how attention and surround/mask stimuli affect neuronal firing rates and orientation tuning in macaque V1. Surround/mask stimuli provide an estimate to what extent V1 neurons are affected by normalization, which was compared against effects of spatial top down attention. For some attention/surround effect comparisons, the strength of attentional modulation was correlated with the strength of surround modulation, suggesting that attention and surround/mask stimulation (i.e. normalization) might use a common mechanism. To explore this in detail, we fitted multiplicative and additive models of attention to our data. In one class of models, attention contributed to normalization mechanisms, whereas in a different class of models it did not. Model selection based on Akaike's and on Bayesian information criteria demonstrated that in most cells the effects of attention were best described by models where attention did not contribute to normalization mechanisms. This demonstrates that attentional influences on neuronal responses in primary visual cortex often bypass normalization mechanisms. PMID:25757941

  10. A recently isolated Lassa virus from Mali demonstrates atypical clinical disease manifestations and decreased virulence in cynomolgus macaques.

    Science.gov (United States)

    Safronetz, David; Strong, James E; Feldmann, Friederike; Haddock, Elaine; Sogoba, Nafomon; Brining, Douglas; Geisbert, Thomas W; Scott, Dana P; Feldmann, Heinz

    2013-04-15

    The virulence of Soromba-R, a Lassa virus strain recently isolated from southern Mali, was assessed in 2 animal models of Lassa fever: inbred strain 13 guinea pigs and cynomolgus macaques. In both models, the Malian isolate demonstrated tissue tropism and viral titers similar to those of historical Lassa virus isolates from Sierra Leone (Josiah) and Liberia (Z-132); however, the Soromba-R isolate was found to be less pathogenic, as determined by decreased mortality and prolonged time to euthanasia in macaques. Interestingly, in addition to the classic indicators of Lassa fever, Soromba-R infection presented with moderate to severe pulmonary manifestations in the macaque model. Analysis of host responses demonstrated increased immune activation in Soromba-R-infected macaques, particularly in neutrophil-activating or -potentiating proinflammatory cytokines or growth factors, including tumor necrosis factor α, macrophage inflammatory protein 1α, interleukin 1β, and granulocyte colony-stimulating factor, as well as interleukin 5, which may be responsible for the decreased lethality and uncharacteristic clinical presentation. These results suggest that the strain of Lassa virus circulating in Mali might be less pathogenic than strains circulating in the historical region of endemicity and may result in an atypical presentation for Lassa fever, which could complicate clinical diagnosis.

  11. Implementation of a tolerance model in a computer aided design and inspection system

    Directory of Open Access Journals (Sweden)

    R. Hunter

    2006-04-01

    Full Text Available Purpose: Purpose of this paper is present a detailed framework to integrate the Computer Aided Design (CAD and Inspection (CAI systems through the integration of the Geometric Dimensioning and Tolerancing (GD&T with the inspection process in coordinate measuring machines (CMMs.Design/methodology/approach: The approach used to develop a prototype of a Knowledge Based System (KBS applied to inspection process establishes a new methodology for integrate the geometric dimensioning and tolerancing (GD&T. The integration is achieved through the definition of the knowledge units for functional properties of GD&T, inspection resources and inspection operations in a common knowledge model. The manufacturing and processing applications are the main topics approach of this paper.Findings: The findings are focused in modeling the features and interactions between knowledge units associated to topology, geometry and tolerances with the inspection process activities. The implementation of the product knowledge model is presented in a computer platform that extracts and represents the GD&T information in a CAI system.Research limitations/implications: The implications are focused on the automation of the inspection process in a KBS application. The future research is focused on the use of artificial intelligent technique, such as genetic algorithms and neural networks, to optimize the time to execute the inspection process.Practical implications: The main outcomes and implication of the KBS prototype application are focused on the reduction of the time spend to develop the inspection process. This KBS application provides the needed information to elaborate this process without the human interface.Originality/value: The original value of this paper is the integration of the design and inspection specification in a unique prototype application. The knowledge model has been defined in a common modeling language (UML and can be implemented in different

  12. An Optimization Model for the Allocation of University Based Merit Aid

    Science.gov (United States)

    Sugrue, Paul K.

    2010-01-01

    The allocation of merit-based financial aid during the college admissions process presents postsecondary institutions with complex and financially expensive decisions. This article describes the application of linear programming as a decision tool in merit based financial aid decisions at a medium size private university. The objective defined for…

  13. Teaching children who use augmentative and alternative communication to ask inverted yes/no questions using aided modeling.

    Science.gov (United States)

    Kent-Walsh, Jennifer; Binger, Cathy; Buchanan, Carolyn

    2015-05-01

    This study investigated the effects of a direct intervention program involving aided modeling and the presentation of contrastive targets on the aided production of inverted yes/no questions and possible generalization to other sentence types by children using augmentative and alternative communication (AAC). A single-case, multiple-probe, experimental design across participants was used to evaluate the effects of the instructional program with 3 children who had motor speech disorders and used AAC (ages 4;10 [years;months], 6;2, and 4;9). The treatment involved aided modeling of treatment and contrastive targets through concentrated modeling and interactive play activities. Direct treatment outcomes were examined by measuring the accuracy of producing inverted yes/no questions and to be declaratives through probes. All 3 participants showed a direct treatment effect, producing a greater number of inverted yes/no questions and to be declaratives within the probes following treatment compared with before treatment. All 3 participants evidenced some generalization to novel sentences. Results provide initial evidence that instruction involving aided modeling with contrastive targets holds promise in targeting specific linguistic rules with children using AAC. Patterns of generalization may depend on participants' specific language deficits and acquisition patterns during intervention.

  14. Individual and social learning processes involved in the acquisition and generalization of tool use in macaques

    Science.gov (United States)

    Macellini, S.; Maranesi, M.; Bonini, L.; Simone, L.; Rozzi, S.; Ferrari, P. F.; Fogassi, L.

    2012-01-01

    Macaques can efficiently use several tools, but their capacity to discriminate the relevant physical features of a tool and the social factors contributing to their acquisition are still poorly explored. In a series of studies, we investigated macaques' ability to generalize the use of a stick as a tool to new objects having different physical features (study 1), or to new contexts, requiring them to adapt the previously learned motor strategy (study 2). We then assessed whether the observation of a skilled model might facilitate tool-use learning by naive observer monkeys (study 3). Results of study 1 and study 2 showed that monkeys trained to use a tool generalize this ability to tools of different shape and length, and learn to adapt their motor strategy to a new task. Study 3 demonstrated that observing a skilled model increases the observers' manipulations of a stick, thus facilitating the individual discovery of the relevant properties of this object as a tool. These findings support the view that in macaques, the motor system can be modified through tool use and that it has a limited capacity to adjust the learnt motor skills to a new context. Social factors, although important to facilitate the interaction with tools, are not crucial for tool-use learning. PMID:22106424

  15. On the solution of mixed-integer nonlinear programming models for computer aided molecular design.

    Science.gov (United States)

    Ostrovsky, Guennadi M; Achenie, Luke E K; Sinha, Manish

    2002-11-01

    This paper addresses the efficient solution of computer aided molecular design (CAMD) problems, which have been posed as mixed-integer nonlinear programming models. The models of interest are those in which the number of linear constraints far exceeds the number of nonlinear constraints, and with most variables participating in the nonconvex terms. As a result global optimization methods are needed. A branch-and-bound algorithm (BB) is proposed that is specifically tailored to solving such problems. In a conventional BB algorithm, branching is performed on all the search variables that appear in the nonlinear terms. This translates to a large number of node traversals. To overcome this problem, we have proposed a new strategy for branching on a set of linear branchingfunctions, which depend linearly on the search variables. This leads to a significant reduction in the dimensionality of the search space. The construction of linear underestimators for a class of functions is also presented. The CAMD problem that is considered is the design of optimal solvents to be used as cleaning agents in lithographic printing.

  16. A QFD-based decision making model for computer-aided design software selection

    Directory of Open Access Journals (Sweden)

    Kanika Prasad

    2016-03-01

    Full Text Available With the progress in technology and innovation in product development, the contribution of computer- aided design (CAD software in the design and manufacture of parts/products is growing on significantly. Selection of an appropriate CAD software is not a trifling task as it involves analyzing the appositeness of the available software packages to the unique requirements of the organization. Existence of a large number of CAD software vendors, presence of discordance among different hardware and software systems, and dearth of technical knowledge and experience of the decision makers further complicate the selection procedure. Moreover, there are very few published research papers related to CAD software selection, and majority of them have either employed criteria weights computed utilizing subjective judgements of the end users or floundered to incorporate the voice of customers in the decision making process. Quality function deployment (QFD is a well-known technique for determining the relative importance of customers’ defined criteria for selection of any product or service. Therefore, this paper deals with design and development of a QFD-based decision making model in Visual BASIC 6.0 for selection of CAD software for manufacturing organizations. In order to demonstrate the applicability and potentiality of the developed model in the form of a software prototype, two illustrative examples are also provided.

  17. Variations in the Biological Functions of HIV-1 Clade C Envelope in a SHIV-Infected Rhesus Macaque during Disease Progression.

    Directory of Open Access Journals (Sweden)

    For Yue Tso

    Full Text Available A better understanding of how the biological functions of the HIV-1 envelope (Env changes during disease progression may aid the design of an efficacious anti-HIV-1 vaccine. Although studies from patient had provided some insights on this issue, the differences in the study cohorts and methodology had make it difficult to reach a consensus of the variations in the HIV-1 Env functions during disease progression. To this end, an animal model that can be infected under controlled environment and reflect the disease course of HIV-1 infection in human will be beneficial. Such an animal model was previously demonstrated by the infection of macaque with SHIV, expressing HIV-1 clade C Env V1-V5 region. By using this model, we examined the changes in biological functions of Env in the infected animal over the entire disease course. Our data showed an increase in the neutralization resistance phenotype over time and coincided with the decrease in the net charges of the V1-V5 region. Infection of PBMC with provirus expressing various Env clones, isolated from the infected animal over time, showed a surprisingly better replicative fitness for viruses expressing the Env from early time point. Biotinylation and ELISA data also indicated a decrease of cell-surface-associated Env and virion-associated gp120 content with disease progression. This decrease did not affect the CD4-binding capability of Env, but were positively correlated with the decrease of Env fusion ability. Interestingly, some of these changes in biological functions reverted to the pre-AIDS level during advance AIDS. These data suggested a dynamic relationship between the Env V1-V5 region with the host immune pressure. The observed changes of biological functions in this setting might reflect and predict those occurring during natural disease progression in human.

  18. Serum Cobalamin (Vitamin B12) Concentrations in Rhesus Macaques (Macaca mulatta) and Pigtailed Macaques (Macaca nemestrina) with Chronic Idiopathic Diarrhea.

    Science.gov (United States)

    Izzi, Jessica M; Beck, Sarah E; Adams, Robert J; Metcalf Pate, Kelly A; Hutchinson, Eric K

    2016-01-01

    Chronic diarrhea poses a significant threat to the health of NHP research colonies, and its primary etiology remains unclear. In macaques, the clinical presentation of intractable diarrhea and weight loss that are accompanied by inflammatory infiltrates within the gastrointestinal tract closely resembles inflammatory bowel disease of humans, dogs, and cats, in which low serum and tissue cobalamin (vitamin B12) levels are due to intestinal malabsorption. We therefore hypothesized that macaques with chronic idiopathic diarrhea (CID) have lower serum cobalamin concentrations than do healthy macaques. Here we measured serum cobalamin concentrations in both rhesus and pigtailed macaques with CID and compared them with those of healthy controls. Serum cobalamin levels were 2.5-fold lower in pigtailed macaques with CID than control animals but did not differ between rhesus macaques with CID and their controls. This finding supports the use of serum cobalamin concentration as an adjunct diagnostic tool in pigtailed macaques that present with clinical symptoms of chronic gastrointestinal disease. This use of serum vitamin B12 levels has implications for the future use of parenteral cobalamin supplementation to improve clinical outcomes in this species.

  19. Grooming reciprocity in male Tibetan macaques.

    Science.gov (United States)

    Xia, Dong-Po; Li, Jin-Hua; Garber, Paul A; Matheson, Megan D; Sun, Bing-Hua; Zhu, Yong

    2013-10-01

    In several primate species, adult males are reported to compete for access to reproductive partners as well as forming affiliative and cohesive social bonds based on the exchange of goods or services. We hypothesized that among a broad set of fitness-maximizing strategies, grooming can be used by individual adult males to enhance social relationships through reciprocity and/or through the interchange of grooming for a different but equivalent good or service. We used focal animal sampling and continuously recorded dyadic grooming and agonistic interactions to test a series of predictions regarding male social interactions in a free-ranging group of Tibetan macaques (Macaca thibetana) at Huangshan, China. During the non-mating season or between males of similar rank throughout the year, grooming effort given was matched by grooming effort received. However, lower ranking males groomed higher ranking males at a greater rate and/or for a longer duration during both the mating and non-mating periods. We found that higher ranking males directed less aggression towards males with whom they formed a frequent grooming partnership, indicating that grooming received was interchanged for increased social tolerance. These data suggest that individual male Tibetan macaques employ alternative social strategies associated with grooming reciprocity or interchange depending on dominance rank and rates of aggression, and highlight the importance of both biological markets and grooming reciprocity as behavioral mechanisms used by resident adult males to form and maintain affiliative social bonds.

  20. Developing Snow Model Forcing Data From WRF Model Output to Aid in Water Resource Forecasting

    Science.gov (United States)

    Havens, S.; Marks, D. G.; Watson, K. A.; Masarik, M.; Flores, A. N.; Kormos, P.; Hedrick, A. R.

    2015-12-01

    Traditional operational modeling tools used by water managers in the west are challenged by more frequently occurring uncharacteristic stream flow patterns caused by climate change. Water managers are now turning to new models based on the physical processes within a watershed to combat the increasing number of events that do not follow the historical patterns. The USDA-ARS has provided near real time snow water equivalent (SWE) maps using iSnobal since WY2012 for the Boise River Basin in southwest Idaho and since WY2013 for the Tuolumne Basin in California that feeds the Hetch Hetchy reservoir. The goal of these projects is to not only provide current snowpack estimates but to use the Weather Research and Forecasting (WRF) model to drive iSnobal in order to produce a forecasted stream flow when coupled to a hydrology model. The first step is to develop methods on how to create snow model forcing data from WRF outputs. Using a reanalysis 1km WRF dataset from WY2009 over the Boise River Basin, WRF model results like surface air temperature, relative humidity, wind, precipitation, cloud cover, and incoming long wave radiation must be downscaled for use in iSnobal. iSnobal results forced with WRF output are validated at point locations throughout the basin, as well as compared with iSnobal results forced with traditional weather station data. The presentation will explore the differences in forcing data derived from WRF outputs and weather stations and how this affects the snowpack distribution.

  1. Modeling AIDS survival after initiation of antiretroviral treatment by Weibull models with changepoints

    Directory of Open Access Journals (Sweden)

    Yiannoutsos Constantin T

    2009-06-01

    Full Text Available Abstract Background Mortality of HIV-infected patients initiating antiretroviral therapy in the developing world is very high immediately after the start of ART therapy and drops sharply thereafter. It is necessary to use models of survival time that reflect this change. Methods In this endeavor, parametric models with changepoints such as Weibull models can be useful in order to explicitly model the underlying failure process, even in the case where abrupt changes in the mortality rate are present. Estimation of the temporal location of possible mortality changepoints has important implications on the effective management of these patients. We briefly describe these models and apply them to the case of estimating survival among HIV-infected patients who are initiating antiretroviral therapy in a care and treatment programme in sub-Saharan Africa. Results As a first reported data-driven estimate of the existence and location of early mortality changepoints after antiretroviral therapy initiation, we show that there is an early change in risk of death at three months, followed by an intermediate risk period lasting up to 10 months after therapy. Conclusion By explicitly modelling the underlying abrupt changes in mortality risk after initiation of antiretroviral therapy we are able to estimate their number and location in a rigorous, data-driven manner. The existence of a high early risk of death after initiation of antiretroviral therapy and the determination of its duration has direct implications for the optimal management of patients initiating therapy in this setting.

  2. Modeling of Women's 100-m Dash World Record: Wind-Aided or Not?

    Science.gov (United States)

    Hazelrigg, Conner; Waibel, Bryson; Baker, Blane

    2015-11-01

    On July 16, 1988, Florence Griffith Joyner (FGJ) shattered the women's 100-m dash world record (WR) with a time of 10.49 s, breaking the previous mark by an astonishing 0.27 s. By all accounts FGJ dominated the race that day, securing her place as the premiere female sprinter of that era, and possibly all time. In the aftermath of such an extraordinary performance, track officials immediately assumed that her posted time was wind aided—that is, attained under tailwind conditions beyond the legal limit of 2.0 m/s for world records. However, wind-measuring devices at the track site showed zero wind conditions during her WR performance. Before and during FGJ's race, other wind-measuring devices indicated speeds exceeding 4.0 m/s at the site of the triple jump runway, located on the same field as the running track. Video clips of flags placed near the starting line of FGJ's race also revealed tailwind conditions. Using available data from that era, the study here incorporates modeling techniques to compute velocity and position as functions of time for no wind and tailwind conditions. Modeling under no wind conditions produces a 100-m time of 10.70 s, a performance clearly attainable by FGJ during this stage of her sprinting career. Incorporating tailwinds of 4.0 m/s into the computations reduces this time by approximately 0.20 s, in close agreement with FGJ's record-breaking performance. These results strongly suggest that tailwinds of order 4 m/s were present during FGJ's world record race even though wind-measuring devices at the track site did not register these speeds. In spite of such strong evidence to support a wind-aided race on July 16, 1988, FGJ remains one of the top female sprinters in history and would likely hold the WR even today, given that she attained a non-wind-aided 100-m time of 10.61 s on the day following her WR performance.

  3. Ab initio identification of transcription start sites in the Rhesus macaque genome by histone modification and RNA-Seq.

    Science.gov (United States)

    Liu, Yi; Han, Dali; Han, Yixing; Yan, Zheng; Xie, Bin; Li, Jing; Qiao, Nan; Hu, Haiyang; Khaitovich, Philipp; Gao, Yuan; Han, Jing-Dong J

    2011-03-01

    Rhesus macaque is a widely used primate model organism. Its genome annotations are however still largely comparative computational predictions derived mainly from human genes, which precludes studies on the macaque-specific genes, gene isoforms or their regulations. Here we took advantage of histone H3 lysine 4 trimethylation (H3K4me3)'s ability to mark transcription start sites (TSSs) and the recently developed ChIP-Seq and RNA-Seq technology to survey the transcript structures. We generated 14,013,757 sequence tags by H3K4me3 ChIP-Seq and obtained 17,322,358 paired end reads for mRNA, and 10,698,419 short reads for sRNA from the macaque brain. By integrating these data with genomic sequence features and extending and improving a state-of-the-art TSS prediction algorithm, we ab initio predicted and verified 17,933 of previously electronically annotated TSSs at 500-bp resolution. We also predicted approximately 10,000 novel TSSs. These provide an important rich resource for close examination of the species-specific transcript structures and transcription regulations in the Rhesus macaque genome. Our approach exemplifies a relatively inexpensive way to generate a reasonably reliable TSS map for a large genome. It may serve as a guiding example for similar genome annotation efforts targeted at other model organisms.

  4. Tactile Aids

    Directory of Open Access Journals (Sweden)

    Mohtaramossadat Homayuni

    1996-04-01

    Full Text Available Tactile aids, which translate sound waves into vibrations that can be felt by the skin, have been used for decades by people with severe/profound hearing loss to enhance speech/language development and improve speechreading.The development of tactile aids dates from the efforts of Goults and his co-workers in the 1920s; Although The power supply was too voluminous and it was difficult to carry specially by children, it was too huge and heavy to be carried outside the laboratories and its application was restricted to the experimental usage. Nowadays great advances have been performed in producing this instrument and its numerous models is available in markets around the world.

  5. Conditional Aid Effectiveness

    DEFF Research Database (Denmark)

    Doucouliagos, Hristos; Paldam, Martin

    The AEL (aid effectiveness literature) studies the effect of development aid using econometrics on macro data. It contains about 100 papers of which a third analyzes conditional models where aid effectiveness depends upon z, so that aid only works for a certain range of the variable. The key term...... in this family of AEL models is thus an interaction term of z times aid. The leading candidates for z are a good policy index and aid itself. In this paper, meta-analysis techniques are used (i) to determine whether the AEL has established the said interaction terms, and (ii) to identify some of the determinants...... of the differences in results between studies. Taking all available studies in consideration, we find no support for conditionality with respect to policy, while conditionality regarding aid itself is dubious. However, the results differ depending on the authors’ institutional affiliation....

  6. Genetic diversity and population structure of long-tailed macaque (Macaca fascicularis) populations in Peninsular Malaysia.

    Science.gov (United States)

    Nikzad, Sonia; Tan, Soon Guan; Yong Seok Yien, Christina; Ng, Jillian; Alitheen, Noorjahan Banu; Khan, Razib; Rovie-Ryan, Jeffrine J; Valdiani, Alireza; Khajeaian, Parastoo; Kanthaswamy, Sree

    2014-12-01

    The genetic diversity and structure of long-tailed macaques (Macaca fascicularis) in Peninsular Malaysia, a widely used non-human primate species in biomedical research, have not been thoroughly characterized. Thirteen sites of wild populations of long-tailed macaques representing six states were sampled and analyzed with 18 STR markers. The Sunggala and Penang Island populations showed the highest genetic diversity estimates, while the Jerejak Island population was the most genetically discrete due to isolation from the mainland shelf. Concordant with pairwise F(st) estimates, STRUCTURE analyses of the seven PCA-correlated clusters revealed low to moderate differentiation among the sampling sites. No association between geographic and genetic distances exists, suggesting that the study sites, including island study sites, are genetically if not geographically contiguous. The status of the genetic structure and composition of long-tailed macaque populations require further scrutiny to develop this species as an important animal model in biomedical research. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Attenuated Disease in SIV-Infected Macaques Treated with a Monoclonal Antibody against FasL

    Directory of Open Access Journals (Sweden)

    Maria S. Salvato

    2007-01-01

    Full Text Available Acute SIVmac infection in macaques is accompanied by high levels of plasma viremia that decline with the appearance of viral immunity and is a model for acute HIV disease in man. Despite specific immune responses, the virus establishes a chronic, persistent infection. The destruction of CD4+ and CD4- lymphocyte subsets in macaques contributes to viral persistence and suggests the importance of mechanisms for depleting both infected and uninfected (bystander cells. Bystander cell killing can occur when FasL binds the Fas receptor on activated lymphocytes, which include T and B cell subpopulations that are responding to the infection. Destruction of specific immune cells could be an important mechanism for blunting viral immunity and establishing persistent infection with chronic disease. We inhibited the Fas pathway in vivo with a monoclonal antibody against FasL (RNOK203. Here we show that treatment with anti-FasL reduced cell death in circulating T and B cells, increased CTL and antibody responses to viral proteins, and lowered the setpoint viremia. By blocking FasL during only the first few weeks after infection, we attenuated SIVmac disease and increased the life span for infected and treated macaques.

  8. Postexposure protection of macaques from vaginal SHIV infection by topical integrase inhibitors.

    Science.gov (United States)

    Dobard, Charles; Sharma, Sunita; Parikh, Urvi M; West, Rolieria; Taylor, Andrew; Martin, Amy; Pau, Chou-Pong; Hanson, Debra L; Lipscomb, Jonathan; Smith, James; Novembre, Francis; Hazuda, Daria; Garcia-Lerma, J Gerardo; Heneine, Walid

    2014-03-12

    Coitally delivered microbicide gels containing antiretroviral drugs are important for HIV prevention. However, to date, microbicides have contained entry or reverse transcriptase inhibitors that block early steps in virus infection and thus need to be given as a preexposure dose that interferes with sexual practices and may limit compliance. Integrase inhibitors block late steps after virus infection and therefore are more suitable for post-coital dosing. We first determined the kinetics of strand transfer in vitro and confirmed that integration begins about 6 hours after infection. We then used a repeat-challenge macaque model to assess efficacy of vaginal gels containing integrase strand transfer inhibitors when applied before or after simian/human immunodeficiency virus (SHIV) challenge. We showed that gel containing the strand transfer inhibitor L-870812 protected two of three macaques when applied 30 min before SHIV challenge. We next evaluated the efficacy of 1% raltegravir gel and demonstrated its ability to protect macaques when applied 3 hours after SHIV exposure (five of six protected; P test). Breakthrough infections showed no evidence of drug resistance in plasma or vaginal secretions despite continued gel dosing after infection. We documented rapid vaginal absorption reflecting a short pharmacological lag time and noted that vaginal, but not plasma, virus load was substantially reduced in the breakthrough infection after raltegravir gel treatment. We provide a proof of concept that topically applied integrase inhibitors protect against vaginal SHIV infection when administered shortly before or 3 hours after virus exposure.

  9. Computer-Aided Design, Modeling and Simulation of a New Solar Still Design

    Directory of Open Access Journals (Sweden)

    Jeremy (Zheng Li

    2011-01-01

    Full Text Available The clean and pure drinking water is important in today's life but current water sources are usually brackish with bacteria that cannot be used for drinking. About 78% of water available in the sea is salty, 21% of water is brackish, and only 1% of water is fresh. Distillation is one of the feasible processes applied to water purification, and it requires the energy inputs, such as solar radiation. Water is evaporated in this distillation process and water vapor can be separated and condensed to pure water. Now, with the change from conventional fuels to renewable and environment friendly fuels sources, the modern technology allows to use the abundant energy from the sun. It is better to use solar energy to process the water desalination since it is more economical than the use of conventional energies. The main focus of this paper is applying computer-aided modeling and simulation to design a less complex solar water distillation system. The prototype of this solar still system is also built to verify its feasibility, functionality, and reliability. The computational simulation and prototype testing show the reliability and proper functionality of this solar water distillation system.

  10. Towards the Significance of Decision Aid in Building Information Modeling (BIM Software Selection Process

    Directory of Open Access Journals (Sweden)

    Omar Mohd Faizal

    2014-01-01

    Full Text Available Building Information Modeling (BIM has been considered as a solution in construction industry to numerous problems such as delays, increased lead in times and increased costs. This is due to the concept and characteristic of BIM that will reshaped the way construction project teams work together to increase productivity and improve the final project outcomes (cost, time, quality, safety, functionality, maintainability, etc.. As a result, the construction industry has witnesses numerous of BIM software available in market. Each of this software has offers different function, features. Furthermore, the adoption of BIM required high investment on software, hardware and also training expenses. Thus, there is indentified that there is a need of decision aid for appropriated BIM software selection that fulfill the project needs. However, research indicates that there is limited study attempt to guide decision in BIM software selection problem. Thus, this paper highlight the importance of decision making and support for BIM software selection as it is vital to increase productivity, construction project throughout building lifecycle.

  11. Condylomatous genital lesions in cynomolgus macaques from Mauritius.

    Science.gov (United States)

    Harari, Ariana; Wood, Charles E; Van Doorslaer, Koenraad; Chen, Zigui; Domaingue, Marie Claire; Elmore, David; Koenig, Patricia; Wagner, Janice D; Jennings, Ryan N; Burk, Robert D

    2013-08-01

    Genital condyloma-like lesions were observed on male and female cynomolgus macaque monkeys (Macaca fascicularis) originating from the island of Mauritius. Cytobrush and/or biopsy samples were obtained from lesions of 57 affected macaques. Primary histologic features included eosinophilic, neutrophilic, and lymphoplasmacytic penile and vulvar inflammation, epidermal hyperplasia with acanthosis, and increased collagenous stroma. Polymerase chain reaction-based assays to amplify viral DNA revealed the presence of macaque lymphocryptovirus (LCV) DNA but not papillomavirus or poxvirus DNA. Subsequent DNA analyses of 3 genomic regions of LCV identified isolates associated with lesions in 19/25 (76%) biopsies and 19/57 (33%) cytology samples. Variable immunolabeling for proteins related to the human LCV Epstein Barr Virus was observed within intralesional plasma cells, stromal cells, and epithelial cells. Further work is needed to characterize the epidemiologic features of these lesions and their association with LCV infection in Mauritian-origin macaques.

  12. Using the Continuum of Design Modelling Techniques to Aid the Development of CAD Modeling Skills in First Year Industrial Design Students

    Science.gov (United States)

    Storer, I. J.; Campbell, R. I.

    2012-01-01

    Industrial Designers need to understand and command a number of modelling techniques to communicate their ideas to themselves and others. Verbal explanations, sketches, engineering drawings, computer aided design (CAD) models and physical prototypes are the most commonly used communication techniques. Within design, unlike some disciplines,…

  13. Using the Continuum of Design Modelling Techniques to Aid the Development of CAD Modeling Skills in First Year Industrial Design Students

    Science.gov (United States)

    Storer, I. J.; Campbell, R. I.

    2012-01-01

    Industrial Designers need to understand and command a number of modelling techniques to communicate their ideas to themselves and others. Verbal explanations, sketches, engineering drawings, computer aided design (CAD) models and physical prototypes are the most commonly used communication techniques. Within design, unlike some disciplines,…

  14. An Integrated Model for Optimization Oriented Decision Aiding and Rule Based Decision Making in Fuzzy Environment

    OpenAIRE

    A. Yousefli; M. Ghazanfari; M. B. Abiri

    2014-01-01

    In this paper a fuzzy decision aid system is developed base on new concepts that presented in the field of fuzzy decision making in fuzzy environment (FDMFE). This framework aids decision makers to understand different circumstances of an uncertain problem that may occur in the future. Also, to keep decision maker from the optimization problem complexities, a decision support system, which can be replaced by optimization problem, is presented to make optimum or near optimum decisions without ...

  15. Complete Taiwanese Macaque (Macaca cyclopis) Mitochondrial Genome: Reference-Assisted de novo Assembly with Multiple k-mer Strategy.

    Science.gov (United States)

    Huang, Yu-Feng; Midha, Mohit; Chen, Tzu-Han; Wang, Yu-Tai; Smith, David Glenn; Pei, Kurtis Jai-Chyi; Chiu, Kuo Ping

    2015-01-01

    The Taiwanese (Formosan) macaque (Macaca cyclopis) is the only nonhuman primate endemic to Taiwan. This primate species is valuable for evolutionary studies and as subjects in medical research. However, only partial fragments of the mitochondrial genome (mitogenome) of this primate species have been sequenced, not mentioning its nuclear genome. We employed next-generation sequencing to generate 2 x 90 bp paired-end reads, followed by reference-assisted de novo assembly with multiple k-mer strategy to characterize the M. cyclopis mitogenome. We compared the assembled mitogenome with that of other macaque species for phylogenetic analysis. Our results show that, the M. cyclopis mitogenome consists of 16,563 nucleotides encoding for 13 protein-coding genes, 2 ribosomal RNAs and 22 transfer RNAs. Phylogenetic analysis indicates that M. cyclopis is most closely related to M. mulatta lasiota (Chinese rhesus macaque), supporting the notion of Asia-continental origin of M. cyclopis proposed in previous studies based on partial mitochondrial sequences. Our work presents a novel approach for assembling a mitogenome that utilizes the capabilities of de novo genome assembly with assistance of a reference genome. The availability of the complete Taiwanese macaque mitogenome will facilitate the study of primate evolution and the characterization of genetic variations for the potential usage of this species as a non-human primate model for medical research.

  16. The Characteristics of Herpes Simplex Virus Type 1 Infection in Rhesus Macaques and the Associated Pathological Features

    Science.gov (United States)

    Fan, Shengtao; Cai, Hongzhi; Xu, Xingli; Feng, Min; Wang, Lichun; Liao, Yun; Zhang, Ying; He, Zhanlong; Yang, Fengmei; Yu, Wenhai; Wang, Jingjing; Zhou, Jumin; Li, Qihan

    2017-01-01

    As one of the major pathogens for human herpetic diseases, herpes simplex virus type 1 (HSV1) causes herpes labialis, genital herpes and herpetic encephalitis. Our aim here was to investigate the infectious process of HSV1 in rhesus macaques and the pathological features induced during this infection. Clinical symptoms that manifested in the rhesus macaque during HSV1 infection included vesicular lesions and their pathological features. Viral distribution in the nervous tissues and associated pathologic changes indicated the typical systematic pathological processes associated with viral distribution of HSV1. Interestingly, vesicular lesions recurred in oral skin or in mucosa associated with virus shedding in macaques within four to five months post-infection, and viral latency-associated transcript (LAT) mRNA was found in the trigeminal ganglia (TG) on day 365 post-infection. Neutralization testing and enzyme-linked immunospot (ELISpot) detection of specific T cell responses confirmed the specific immunity induced by HSV1 infection. Thus, rhesus macaques could serve as an infectious model for HSV1 due to their typical clinical symptoms and the pathological recurrence associated with viral latency in nervous tissues. PMID:28146109

  17. Regional climate modeling and development of climate adaptation decision aids for energy use in the Southwestern US

    Science.gov (United States)

    Higgins, G.; Darmenova, K.; Apling, D.; Kiley, H.

    2010-12-01

    There is currently a gap between the relatively coarse resolution science data that Global Climate Models (GCMs) produce and the high resolution tailored products that planners need to develop climate adaptation and mitigation strategies. Planners need to make decisions on infrastructure, budgets, policy, and programs related to their energy use and consumption and the impacts on the rest of the energy sector. We apply the Weather Research and Forecasting (WRF) model to conduct regional dynamical downscaling in the Southwestern US. The European Center/Hamburg Model (ECHAM5) GCM is used to provide initial and boundary conditions. Our methodology involves development of climatological indices of extreme weather and a variety of climate adaptation decision aids. We have further developed energy decision aids to translate the output from the WRF Regional Climate Model (RCM) into future electricity and natural gas demand for several sites in Colorado. These energy decision aids are developed using available energy consumption records from these sites over an historical period. These data are correlated with Heating Degree Days (HDD) and Cooling Degree Days (CCD) data from the RCM to develop models of energy use as a function of HDD/CDD. RCM estimates of HDD/CDD are presented for a current and future period along with projections of energy use. Additionally, derived statistical confidence bounds for these products are provided.

  18. Co-transplantation of macaque autologous Schwann cells and human embryonic nerve stem cells in treatment of macaque Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Ying Xia; Chengchuan Jiang; Zuowei Cao; Keshan Shi; Yang Wang

    2012-01-01

    Objective:To investigate the therapeutic effects of co-transplantation with Schwann cells (SCs) and human embryonic nerve stem cells (NSCs) on macaque Parkinson's disease (PD). Methods:Macaque autologous SCs and human embryonic NSCs were adopted for the treatment of macaque PD. Results: Six months after transplantation, positron emission computerized tomography showed that 18F-FP-β-CIT was significantly concentrated in the injured striatum in the co-transplanted group. Immunohistochemical staining of transplanted area tissue showed migration of tyroxine hydroxylase positive cells from the transplant area to the surrounding area was significantly increased in the co-transplanted group. Conclusions: Co-transplantation of SCs and NSCs could effectively cure PD in macaques. SCs harvested from the autologous peripheral nerves can avoid rejection and the ethics problems, so it is expected to be applied clinically.

  19. Clinical monitoring and correlates of nephropathy in SIV-infected macaques during high-dose antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Hebblewaite Diane

    2011-01-01

    Full Text Available Abstract Background In many preclinical AIDS research studies, antiretroviral therapy (ART is administered to experimentally simian immunodeficiency (SIV-infected rhesus macaques for reduction of viral load to undetectable levels. Prolonged treatment of macaques with a high dose of PMPA (9-[2-(r-(phosphonomethoxy propyl] adenine or tenofovir; 30 mg/kg of body weight subcutaneously once daily can result in proximal renal tubular dysfunction, a Fanconi-like syndrome characterized by glucosuria, aminoaciduria, hypophosphatemia, and bone pathology. In contrast, chronic administration of a low dose of PMPA (10 mg/kg subcutaneously once daily starting at birth does not seem to be associated with any adverse health effects within 3 years of treatment. In contrast to PMPA, limited information on systemic toxicity in rhesus monkeys is available for FTC (5-fluoro-1-(2R,5S-[2-(hydroxymethyl-1,3-oxathiolan-5-yl]cytosine; emtricitabine and stavudine (d4T. Results In this study, the clinical and biochemical correlates of tubular nephrosis in SIV-infected rhesus macaques associated with systemic administration of high-dose ART consisting of the three nucleoside analog inhibitors PMPA, FTC, and d4T were investigated. It was found that acute renal failure was uncommon (7.1% of treated animals and that morphologic evidence of nephropathy, which persisted for more than 300 days following discontinuation of the drug cocktail, was more frequent (52.4% of treated animals. While parameters from single time points lacked predictive value, biochemical alterations in Blood Urea Nitrogen (BUN and phosphorus were frequently identified longitudinally in the blood of ART-treated animals that developed evidence of nephropathy, and these longitudinal changes correlated with disease severity. Conclusions Recommendations are proposed to limit the impact of drug-induced renal disease in future SIV macaque studies.

  20. Similar protective immunity induced by an inactivated enterovirus 71 (EV71) vaccine in neonatal rhesus macaques and children.

    Science.gov (United States)

    Zhang, Ying; Wang, Lichun; Liao, Yun; Liu, Longding; Ma, Kaili; Yang, Erxia; Wang, Jingjing; Che, Yanchun; Jiang, Li; Pu, Jing; Guo, Lei; Feng, Min; Liang, Yan; Cui, Wei; Yang, Huai; Li, Qihan

    2015-11-17

    During the development of enterovirus 71 (EV71) inactivated vaccine for preventing human hand, foot and mouth diseases (HFMD) by EV71 infection, an effective animal model is presumed to be significant and necessary. Our previous study demonstrated that the vesicles in oral regions and limbs potentially associated with viremia, which are the typical manifestations of HFMD, and remarkable pathologic changes were identified in various tissues of neonatal rhesus macaque during EV71 infection. Although an immune response in terms of neutralizing antibody and T cell memory was observed in animals infected by the virus or stimulated by viral antigen, whether such a response could be considered as an indicator to justify the immune response in individuals vaccinated or infected in a pandemic needs to be investigated. Here, a comparative analysis of the neutralizing antibody response and IFN-γ-specific T cell response in vaccinated neonatal rhesus macaques and a human clinical trial with an EV71 inactivated vaccine was performed, and the results showed the identical tendency and increased level of neutralizing antibody and the IFN-γ-specific T cell response stimulated by the EV71 antigen peptide. Importantly, the clinical protective efficacy against virus infection by the elicited immune response in the immunized population compared with the placebo control and the up-modulated gene profile associated with immune activation were similar to those in infected macaques. Further safety verification of this vaccine in neonatal rhesus macaques and children confirmed the potential use of the macaque as a reliable model for the evaluation of an EV71 candidate vaccine.

  1. Keep children away from macaque monkeys!

    Science.gov (United States)

    Bréhin, Camille; Debuisson, Cécile; Mansuy, Jean-Michel; Niphuis, Henk; Buitendijk, Hester; Mengelle, Catherine; Grouteau, Erick; Claudet, Isabelle

    2016-03-01

    To warn physicians and parents about the risk of macaque bites, we present two pediatric cases (a 4-year-old boy and a 10-year-old girl) of bites sustained while on holiday. The young boy developed febrile dermohypodermitis and was hospitalized for IV antibiotic treatment. He received an initial antirabies vaccine while still in the holiday destination. Except for local wound disinfection and antibiotic ointment, the girl did not receive any specific treatment while abroad. Both were negative for simian herpes PCR. When travelling in countries or cities with endemic simian herpes virus, parents should keep children away from monkeys. Travel agencies, pediatricians and family physicians should better inform families about the zoonotic risk.

  2. Vicarious reinforcement in rhesus macaques (macaca mulatta).

    Science.gov (United States)

    Chang, Steve W C; Winecoff, Amy A; Platt, Michael L

    2011-01-01

    What happens to others profoundly influences our own behavior. Such other-regarding outcomes can drive observational learning, as well as motivate cooperation, charity, empathy, and even spite. Vicarious reinforcement may serve as one of the critical mechanisms mediating the influence of other-regarding outcomes on behavior and decision-making in groups. Here we show that rhesus macaques spontaneously derive vicarious reinforcement from observing rewards given to another monkey, and that this reinforcement can motivate them to subsequently deliver or withhold rewards from the other animal. We exploited Pavlovian and instrumental conditioning to associate rewards to self (M1) and/or rewards to another monkey (M2) with visual cues. M1s made more errors in the instrumental trials when cues predicted reward to M2 compared to when cues predicted reward to M1, but made even more errors when cues predicted reward to no one. In subsequent preference tests between pairs of conditioned cues, M1s preferred cues paired with reward to M2 over cues paired with reward to no one. By contrast, M1s preferred cues paired with reward to self over cues paired with reward to both monkeys simultaneously. Rates of attention to M2 strongly predicted the strength and valence of vicarious reinforcement. These patterns of behavior, which were absent in non-social control trials, are consistent with vicarious reinforcement based upon sensitivity to observed, or counterfactual, outcomes with respect to another individual. Vicarious reward may play a critical role in shaping cooperation and competition, as well as motivating observational learning and group coordination in rhesus macaques, much as it does in humans. We propose that vicarious reinforcement signals mediate these behaviors via homologous neural circuits involved in reinforcement learning and decision-making.

  3. Vicarious Reinforcement In Rhesus Macaques (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Steve W. C. Chang

    2011-03-01

    Full Text Available What happens to others profoundly influences our own behavior. Such other-regarding outcomes can drive observational learning, as well as motivate cooperation, charity, empathy, and even spite. Vicarious reinforcement may serve as one of the critical mechanisms mediating the influence of other-regarding outcomes on behavior and decision-making in groups. Here we show that rhesus macaques spontaneously derive vicarious reinforcement from observing rewards given to another monkey, and that this reinforcement can motivate them to subsequently deliver or withhold rewards from the other animal. We exploited Pavlovian and instrumental conditioning to associate rewards to self (M1 and/or rewards to another monkey (M2 with visual cues. M1s made more errors in the instrumental trials when cues predicted reward to M2 compared to when cues predicted reward to M1, but made even more errors when cues predicted reward to no one. In subsequent preference tests between pairs of conditioned cues, M1s preferred cues paired with reward to M2 over cues paired with reward to no one. By contrast, M1s preferred cues paired with reward to self over cues paired with reward to both monkeys simultaneously. Rates of attention to M2 strongly predicted the strength and valence of vicarious reinforcement. These patterns of behavior, which were absent in nonsocial control trials, are consistent with vicarious reinforcement based upon sensitivity to observed, or counterfactual, outcomes with respect to another individual. Vicarious reward may play a critical role in shaping cooperation and competition, as well as motivating observational learning and group coordination in rhesus macaques, much as it does in humans. We propose that vicarious reinforcement signals mediate these behaviors via homologous neural circuits involved in reinforcement learning and decision-making.

  4. Modeling uncertainty in classification design of a computer-aided detection system

    Science.gov (United States)

    Hosseini, Rahil; Dehmeshki, Jamshid; Barman, Sarah; Mazinani, Mahdi; Qanadli, Salah

    2010-03-01

    A computerized image analysis technology suffers from imperfection, imprecision and vagueness of the input data and its propagation in all individual components of the technology including image enhancement, segmentation and pattern recognition. Furthermore, a Computerized Medical Image Analysis System (CMIAS) such as computer aided detection (CAD) technology deals with another source of uncertainty that is inherent in image-based practice of medicine. While there are several technology-oriented studies reported in developing CAD applications, no attempt has been made to address, model and integrate these types of uncertainty in the design of the system components, even though uncertainty issues directly affect the performance and its accuracy. In this paper, the main uncertainty paradigms associated with CAD technologies are addressed. The influence of the vagueness and imprecision in the classification of the CAD, as a second reader, on the validity of ROC analysis results is defined. In order to tackle the problem of uncertainty in the classification design of the CAD, two fuzzy methods are applied and evaluated for a lung nodule CAD application. Type-1 fuzzy logic system (T1FLS) and an extension of it, interval type-2 fuzzy logic system (IT2FLS) are employed as methods with high potential for managing uncertainty issues. The novelty of the proposed classification methods is to address and handle all sources of uncertainty associated with a CAD system. The results reveal that IT2FLS is superior to T1FLS for tackling all sources of uncertainty and significantly, the problem of inter and intra operator observer variability.

  5. Tenofovir treatment augments anti-viral immunity against drug-resistant SIV challenge in chronically infected rhesus macaques

    Directory of Open Access Journals (Sweden)

    Marx Preston

    2006-12-01

    Full Text Available Abstract Background Emergence of drug-resistant strains of human immunodeficiency virus type 1 (HIV-1 is a major obstacle to successful antiretroviral therapy (ART in HIV-infected patients. Whether antiviral immunity can augment ART by suppressing replication of drug-resistant HIV-1 in humans is not well understood, but can be explored in non-human primates infected with simian immunodeficiency virus (SIV. Rhesus macaques infected with live, attenuated SIV develop robust SIV-specific immune responses but remain viremic, often at low levels, for periods of months to years, thus providing a model in which to evaluate the contribution of antiviral immunity to drug efficacy. To investigate the extent to which SIV-specific immune responses augment suppression of drug-resistant SIV, rhesus macaques infected with live, attenuated SIVmac239Δnef were treated with the reverse transcriptase (RT inhibitor tenofovir, and then challenged with pathogenic SIVmac055, which has a five-fold reduced sensitivity to tenofovir. Results Replication of SIVmac055 was detected in untreated macaques infected with SIVmac239Δnef, and in tenofovir-treated, naïve control macaques. The majority of macaques infected with SIVmac055 experienced high levels of plasma viremia, rapid CD4+ T cell loss and clinical disease progression. By comparison, macaques infected with SIVmac239Δnef and treated with tenofovir showed no evidence of replicating SIVmac055 in plasma using allele-specific real-time PCR assays with a limit of sensitivity of 50 SIV RNA copies/ml plasma. These animals remained clinically healthy with stable CD4+ T cell counts during three years of follow-up. Both the tenofovir-treated and untreated macaques infected with SIVmac239Δnef had antibody responses to SIV gp130 and p27 antigens and SIV-specific CD8+ T cell responses prior to SIVmac055 challenge, but only those animals receiving concurrent treatment with tenofovir resisted infection with SIVmac055. Conclusion

  6. [The fight against HIV/AIDS as a model of disease management in Sub-Saharan Africa?

    Science.gov (United States)

    Gbocho, Yapo Antoine

    2017-04-27

    The inefficacy of health systems in Sub-Saharan Africa has now been clearly established. Analysis of the relative success of the management of HIV/AIDS can constitute an example of efficacy that could be extended to other fields. Based on a social and community approach, the example of HIV/AIDS can be used as a model of disease management, as it is distinguished by a fairly extensive management dimension, especially integrating socio-economic support. It is also characterized by the large place attributed to the patient and the family, and the community, as the main stakeholders. Without claiming to propose a miracle solution, this model, based on local sociocultural values and realities, constitutes a promising approach to health promotion in Sub-Saharan Africa.

  7. A mathematical model for surface roughness of fluidic channels produced by grinding aided electrochemical discharge machining (G-ECDM)

    OpenAIRE

    Ladeesh V. G.; Manu R

    2017-01-01

    Grinding aided electrochemical discharge machining is a hybrid technique, which combines the grinding action of an abrasive tool and thermal effects of electrochemical discharges to remove material from the workpiece for producing complex contours. The present study focuses on developing fluidic channels on borosilicate glass using G-ECDM and attempts to develop a mathematical model for surface roughness of the machined channel. Preliminary experiments are conducted to study the effect of mac...

  8. Constructing Hope: a Multi-Agency Programme model for Young Sex Offenders living with HIV/AIDS in South Africa

    OpenAIRE

    Douglas P. Boer; Dario Dosio

    2007-01-01

    Many young sex offenders in South Africa have HIV/AIDS. This fact both complicates and underlines the importance of delivering effective multi-agency sex offender programmes to these individuals. Reducing reoffending rates is of obvious importance, as stopping these young offenders from offending also means limiting the spread of HIV to new victims. We are proposing an integrative programme that incorporates proven models of sex offender treatment in combination with medical, educational and ...

  9. Heterogeneity in rhesus macaque complement factor H binding to meningococcal factor H binding protein (FHbp) informs selection of primates to assess immunogenicity of FHbp-based vaccines.

    Science.gov (United States)

    Beernink, Peter T; Shaughnessy, Jutamas; Stefek, Heather; Ram, Sanjay; Granoff, Dan M

    2014-11-01

    Neisseria meningitidis causes disease only in humans. An important mechanism underlying this host specificity is the ability of the organism to resist complement by recruiting the complement downregulator factor H (FH) to the bacterial surface. In previous studies, binding of FH to one of the major meningococcal FH ligands, factor H binding protein (FHbp), was reported to be specific for human FH. Here we report that sera from 23 of 73 rhesus macaques (32%) tested had high FH binding to FHbp. Similar to human FH, binding of macaque FH to the meningococcal cell surface inhibited the complement alternative pathway by decreasing deposition of C3b. FH contains 20 domains (or short consensus repeats), with domains 6 and 7 being responsible for binding of human FH to FHbp. DNA sequence analyses of FH domains 6 and 7 from macaques with high or low FH binding showed a polymorphism at residue 352 in domain 6, with Tyr being associated with high binding and His with low binding. A recombinant macaque FH 6,7/Fc fragment with Tyr352 showed higher binding to FHbp than the corresponding fragment with His352. In previous studies in human FH transgenic mice, binding of FH to FHbp vaccines decreased protective antibody responses, and mutant FHbp vaccines with decreased FH binding elicited serum antibodies with greater protective activity. Thus, macaques with high FH binding to FHbp represent an attractive nonhuman primate model to investigate further the effects of FH binding on the immunogenicity of FHbp vaccines.

  10. Circulating natural killer and γδ T cells decrease soon after infection of rhesus macaques with lymphocytic choriomeningitis virus

    Directory of Open Access Journals (Sweden)

    Juan D Rodas

    2009-07-01

    Full Text Available Rhesus macaques infected with the WE strain of lymphocytic choriomeningitis virus (LCMV-WE serve as a model for human infection with Lassa fever virus. To identify the earliest events of acute infection, rhesus macaques were monitored immediately after lethal infection for changes in peripheral blood mononuclear cells (PBMCs. Changes in CD3, CD4, CD8 and CD20 subsets did not vary outside the normal fluctuations of these blood cell populations; however, natural killer (NK and γδ T cells increased slightly on day 1 and then decreased significantly after two days. The NK subsets responsible for the decrease were primarily CD3-CD8+ or CD3-CD16+ and not the NKT (primarily CD3+CD56+ subset. Macaques infected with a non-virulent arenavirus, LCMV-Armstrong, showed a similar drop in circulating NK and γδ T cells, indicating that this is not a pathogenic event. V³9 T cells, representing the majority of circulating γδ T cells in rhesus macaques, displayed significant apoptosis when incubated with LCMV in cell culture; however, the low amount of cell death for virus-co-cultured NK cells was insufficient to account for the observed disappearance of this subset. Our observations in primates are similar to those seen in LCMV-infected mice, where decreased circulating NK cells were attributed to margination and cell death. Thus, the disappearance of these cells during acute hemorrhagic fever in rhesus macaques may be a cytokine-induced lymphopenia common to many virus infections.

  11. Bovine spongiform encephalopathy infection alters endogenous retrovirus expression in distinct brain regions of cynomolgus macaques (Macaca fascicularis

    Directory of Open Access Journals (Sweden)

    Montag Judith

    2011-06-01

    Full Text Available Abstract Background Prion diseases such as bovine spongiform encephalopathies (BSE are transmissible neurodegenerative diseases which are presumably caused by an infectious conformational isoform of the cellular prion protein. Previous work has provided evidence that in murine prion disease the endogenous retrovirus (ERV expression is altered in the brain. To determine if prion-induced changes in ERV expression are a general phenomenon we used a non-human primate model for prion disease. Results Cynomolgus macaques (Macaca fasicularis were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the basis pontis and vermis cerebelli of the six animals and the same regions from four healthy controls were subjected to ERV expression profiling using a retrovirus-specific microarray and quantitative real-time PCR. We could show that Class I gammaretroviruses HERV-E4-1, ERV-9, and MacERV-4 increase expression in BSE-infected macaques. In a second approach, we analysed ERV-K-(HML-2 RNA and protein expression in extracts from the same cynomolgus macaques. Here we found a significant downregulation of both, the macaque ERV-K-(HML-2 Gag protein and RNA in the frontal/parietal cortex of BSE-infected macaques. Conclusions We provide evidence that dysregulation of ERVs in response to BSE-infection can be detected on both, the RNA and the protein level. To our knowledge, this is the first report on the differential expression of ERV-derived structural proteins in prion disorders. Our findings suggest that endogenous retroviruses may induce or exacerbate the pathological consequences of prion-associated neurodegeneration.

  12. Mixed convection aiding flow in a vertical porous annulus-two temperature model

    Science.gov (United States)

    Salman Ahmed, N. J.; AAAl-Rashed, Abdullah A.; Kamangar, Sarfaraz; Khaleed, H. M. T.; YunusKhan, T. M.; Athani, Abdulgaphur

    2016-09-01

    The effect of convective heat transfer on mixed convection flow in a vertical porous annulus embedded with fluid saturated porous medium for aiding flow is studied. The inner surface of the annular cylinder is heated with constant temperature whereas the outer surface remains at ambient temperature. The governing partial differential equations are solved using Finite Element Method (FEM). It is assumed that the Darcy law is applicable and thermal nonequilibrium TNE exists between solid and fluid phases of porous medium. The aiding flow behavior of heat transfer with respect to Radius ratioRr, Aspect ratio ArandRadiation parameter Rd for different values of Peclet number Peare investigated.

  13. Seed dispersal by rhesus macaques Macaca mulatta in Northern India.

    Science.gov (United States)

    Sengupta, Asmita; McConkey, Kim R; Radhakrishna, Sindhu

    2014-12-01

    Frugivorous primates are important seed dispersers and their absence from forest patches is predicted to be detrimental to tropical forest regeneration and recruitment. With the reduction of primate populations globally, ecologically resilient primate species, characterized by dietary flexibility and the ability to thrive in a variety of habitats, assume new importance as seed dispersers. The most widely distributed non-human primate, the rhesus macaque Macaca mulatta has been intensively studied but little is known about its role in maintaining ecosystem structure and functions. Due to their frugivorous diet, large group sizes, large home ranges and tolerance to disturbance, rhesus macaques may be effective seed dispersers. We studied seed dispersal by rhesus macaques at the Buxa Tiger Reserve, India, through a combination of behavioural observations and germination experiments. Rhesus macaques dispersed 84% of the 49 species they fed on either through spitting or defecation. Nearly 96% of the handled seeds were undamaged and 61% of the species for which germination tests were performed had enhanced germination. Almost 50% of the monitored seeds among those deposited in situ germinated and 22% established seedlings, suggesting that rhesus macaques are important seed dispersers in tropical forests. Due to their widespread distribution and large populations, rhesus macaques are perceived as common and are categorized as Least Concern on the IUCN Red List, effectively excluding them from any conservation plans. Based on the results of our study, we argue that rhesus macaques fulfill critical ecological functions in their habitat and that this parameter must be taken into consideration when they are reviewed for conservation priorities.

  14. Characterization of an in vitro Rhesus Macaque Blood-Brain Barrier

    OpenAIRE

    2002-01-01

    The blood-brain barrier has been modeled in vitro in a number of species, including rat, cow and human. Coculture of multiple cell types is required for the correct expression of tight junction proteins by microvascular brain endothelial cells (MBEC). Markers of inflammation, especially MHC-II, and cell adhesion molecules, such as VCAM-1, are not expressed on the luminal surface of the barrier under resting conditions. The rhesus macaque model has been used to study early events of HIV-neurop...

  15. 带有发病年龄的HIV/AIDS传播的数学建模及分析%Modeling with the AIDS-age on HIV/AIDS Transmission and Its Analysis

    Institute of Scientific and Technical Information of China (English)

    徐英

    2012-01-01

    In this paper, I formulate a dynamic HIV/AIDS model with vertical transmission, AIDS-age, and the different capacity of treatment. I assume that there is an imperfect vaccine with therapeutic effect, which induces reversal from the AIDS stage to asymptomatic stage. From this HIV/AIDS model described by coupled equations of partial differential equations and ordinary differential equations, I can get that the total population decreases when the death rate caused by AIDS is not equal to zero. By using method of functional analysis, especially the semigroup theory of linear operators on Banach space, I prove well-posed-ness of the model and existence of the positive solution.%所建的模型是用含有常微分方程和偏微分方程的方程组来描述的,考虑了垂直感染,发病年龄,AIDS病人有希望恢复到潜伏期以及不同患者接受治疗的能力不同等诸多因素.利用导出的方程,直接推出:当AIDS引起死亡率增加时,社会总人口衰减.利用泛函分析方法和有界线性算子半群理论分析了系统的适定性,并证明了系统方程存在正解.

  16. Extracting the invariant model from the feedback paths of digital hearing aids

    DEFF Research Database (Denmark)

    Ma, Guilin; Gran, Fredrik; Jacobsen, Finn;

    2011-01-01

    Feedback whistling is a severe problem with hearing aids. A typical acoustical feedback path represents a wave propagation path from the receiver to the microphone and includes many complicated effects among which some are invariant or nearly invariant for all users and in all acoustical environm...

  17. Binaural Model-Based Speech Intelligibility Enhancement and Assessment in Hearing Aids

    NARCIS (Netherlands)

    Schlesinger, A.

    2012-01-01

    The enhancement of speech intelligibility in noise is still the main subject in hearing aid research. Based on the advanced results obtained with the hearing glasses, in the present research the speech intelligibility is even further improved by the application of binaural post-filters. The function

  18. Computer aided molecular design with combined molecular modeling and group contribution

    DEFF Research Database (Denmark)

    Harper, Peter Mathias; Gani, Rafiqul; Kolar, Petr

    1999-01-01

    Computer-aided molecular design (CAMD) provides a means for determining molecules or mixtures of molecules (CAMMD) having a desirable set of physicochemical properties. The application range of CAMD is restricted due to limitations on the complexity of the generated molecular structures and on th...

  19. A Characterization of Aerosolized Sudan Virus Infection in African Green Monkeys, Cynomolgus Macaques, and Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Donald K. Nichols

    2012-10-01

    Full Text Available Filoviruses are members of the genera Ebolavirus, Marburgvirus, and “Cuevavirus”. Because they cause human disease with high lethality and could potentially be used as a bioweapon, these viruses are classified as CDC Category A Bioterrorism Agents. Filoviruses are relatively stable in aerosols, retain virulence after lyophilization, and can be present on contaminated surfaces for extended periods of time. This study explores the characteristics of aerosolized Sudan virus (SUDV Boniface in non-human primates (NHP belonging to three different species. Groups of cynomolgus macaques (cyno, rhesus macaques (rhesus, and African green monkeys (AGM were challenged with target doses of 50 or 500 plaque-forming units (pfu of aerosolized SUDV. Exposure to either viral dose resulted in increased body temperatures in all three NHP species beginning on days 4–5 post-exposure. Other clinical findings for all three NHP species included leukocytosis, thrombocytopenia, anorexia, dehydration, and lymphadenopathy. Disease in all of the NHPs was severe beginning on day 6 post-exposure, and all animals except one surviving rhesus macaque were euthanized by day 14. Serum alanine transaminase (ALT and aspartate transaminase (AST concentrations were elevated during the course of disease in all three species; however, AGMs had significantly higher ALT and AST concentrations than cynos and rhesus. While all three species had detectable viral load by days 3-4 post exposure, Rhesus had lower average peak viral load than cynos or AGMs. Overall, the results indicate that the disease course after exposure to aerosolized SUDV is similar for all three species of NHP.

  20. Hearing Aids

    Science.gov (United States)

    ... more in both quiet and noisy situations. Hearing aids help people who have hearing loss from damage ... your doctor. There are different kinds of hearing aids. They differ by size, their placement on or ...

  1. AIDS (image)

    Science.gov (United States)

    AIDS (acquired immune deficiency syndrome) is caused by HIV (human immunodeficiency virus), and is a syndrome that ... life-threatening illnesses. There is no cure for AIDS, but treatment with antiviral medicine can suppress symptoms. ...

  2. Examining the species-specificity of rhesus macaque cytomegalovirus (RhCMV in cynomolgus macaques.

    Directory of Open Access Journals (Sweden)

    Angie K Marsh

    Full Text Available Cytomegalovirus (CMV is a highly species-specific virus that has co-evolved with its host over millions of years and thus restricting cross-species infection. To examine the extent to which host restriction may prevent cross-species research between closely related non-human primates, we evaluated experimental infection of cynomolgus macaques with a recombinant rhesus macaque-derived CMV (RhCMV-eGFP. Twelve cynomolgus macaques were randomly allocated to three groups: one experimental group (RhCMV-eGFP and two control groups (UV-inactivated RhCMV-eGFP or media alone. The animals were given two subcutaneous inoculations at week 0 and week 8, and a subset of animals received an intravenous inoculation at week 23. No overt clinical or haematological changes were observed and PBMCs isolated from RhCMV-eGFP inoculated animals had comparable eGFP- and IE-1-specific cellular responses to the control animals. Following inoculation with RhCMV-eGFP, we were unable to detect evidence of infection in any blood or tissue samples up to 4 years post-inoculation, using sensitive viral co-culture, qPCR, and Western blot assays. Co-culture of urine and saliva samples demonstrated the presence of endogenous cynomolgus CMV (CyCMV cytopathic effect, however no concomitant eGFP expression was observed. The absence of detectable RhCMV-eGFP suggests that the CyCMV-seropositive cynomolgus macaques were not productively infected with RhCMV-eGFP under these inoculation conditions. In a continued effort to develop CMV as a viral vector for an HIV/SIV vaccine, these studies demonstrate that CMV is highly restricted to its host species and can be highly affected by laboratory cell culture. Consideration of the differences between lab-adapted and primary viruses with respect to species range and cell tropism should be a priority in evaluating CMV as vaccine vector for HIV or other pathogens at the preclinical development stage.

  3. Case Report: Severe and Complicated Cynomolgi Malaria in a Rhesus Macaque Resulted in Similar Histopathological Changes as Those Seen in Human Malaria.

    Science.gov (United States)

    J Joyner, Chester; Consortium, The MaHPIC; Wood, Jennifer S; Moreno, Alberto; Garcia, Anapatricia; Galinski, Mary R

    2017-08-01

    Histopathological data collected from patients with severe malaria have been instrumental for studying malaria pathogenesis. Animal models of malaria are critical to complement such studies. Here, the histopathological changes observed in a rhesus macaque with severe and complicated Plasmodium cynomolgi malaria are reported. The animal presented with thrombocytopenia, severe anemia, and hyperparasitemia during the acute infection. The macaque was given subcurative antimalarial treatment, fluid support, and a blood transfusion to treat the clinical complications, but at the time of transfusion, kidney function was compromised. These interventions did not restore kidney function, and the animal was euthanized due to irreversible renal failure. Gross pathological and histological examinations revealed that the lungs, kidneys, liver, spleen, and bone marrow exhibited abnormalities similar to those described in patients with malaria. Overall, this case report illustrates the similarities in the pathophysiological complications that can occur in human malaria and cynomolgi malaria in rhesus macaques.

  4. Aid and Growth

    DEFF Research Database (Denmark)

    Arndt, Channing; Jones, Edward Samuel; Tarp, Finn

    2009-01-01

    The micro-macro paradox has been revived. Despite broadly positive evaluations at the micro and meso-levels, recent literature has turned decidedly pessimistic with respect to the ability of foreign aid to foster economic growth. Policy implications, such as the complete cessation of aid to Africa......, are being drawn on the basis of fragile evidence. This paper first assesses the aid-growth literature with a focus on recent contributions. The aid-growth literature is then framed, for the first time, in terms of the Rubin Causal Model, applied at the macroeconomic level. Our results show that aid has...... a positive and statistically significant causal effect on growth over the long run with point estimates at levels suggested by growth theory. We conclude that aid remains an important tool for enhancing the development prospects of poor nations....

  5. Aid and Growth

    DEFF Research Database (Denmark)

    Arndt, Channing; Jones, Edward Samuel; Tarp, Finn

    The micro-macro paradox has been revived. Despite broadly positive evaluations at the micro and meso-levels, recent literature has turned decidedly pessimistic with respect to the ability of foreign aid to foster economic growth. Policy implications, such as the complete cessation of aid to Africa......, are being drawn on the basis of fragile evidence. This paper first assesses the aid-growth literature with a focus on recent contributions. The aid-growth literature is then framed, for the first time, in terms of the Rubin Causal Model, applied at the macroeconomic level. Our results show that aid has...... a positive and statistically significant causal effect on growth over the long run with point estimates at levels suggested by growth theory. We conclude that aid remains an important tool for enhancing the development prospects of poor nations....

  6. Economic choices reveal probability distortion in macaque monkeys.

    Science.gov (United States)

    Stauffer, William R; Lak, Armin; Bossaerts, Peter; Schultz, Wolfram

    2015-02-18

    Economic choices are largely determined by two principal elements, reward value (utility) and probability. Although nonlinear utility functions have been acknowledged for centuries, nonlinear probability weighting (probability distortion) was only recently recognized as a ubiquitous aspect of real-world choice behavior. Even when outcome probabilities are known and acknowledged, human decision makers often overweight low probability outcomes and underweight high probability outcomes. Whereas recent studies measured utility functions and their corresponding neural correlates in monkeys, it is not known whether monkeys distort probability in a manner similar to humans. Therefore, we investigated economic choices in macaque monkeys for evidence of probability distortion. We trained two monkeys to predict reward from probabilistic gambles with constant outcome values (0.5 ml or nothing). The probability of winning was conveyed using explicit visual cues (sector stimuli). Choices between the gambles revealed that the monkeys used the explicit probability information to make meaningful decisions. Using these cues, we measured probability distortion from choices between the gambles and safe rewards. Parametric modeling of the choices revealed classic probability weighting functions with inverted-S shape. Therefore, the animals overweighted low probability rewards and underweighted high probability rewards. Empirical investigation of the behavior verified that the choices were best explained by a combination of nonlinear value and nonlinear probability distortion. Together, these results suggest that probability distortion may reflect evolutionarily preserved neuronal processing. Copyright © 2015 Stauffer et al.

  7. Serial memory strategies in macaque monkeys: behavioral and theoretical aspects.

    Science.gov (United States)

    Orlov, Tanya; Yakovlev, Volodya; Amit, Daniel; Hochstein, Shaul; Zohary, Ehud

    2002-03-01

    Serial memory is the ability to encode and retrieve a list of items in their correct temporal order. To study nonverbal strategies involved in serial memory, we trained four macaque monkeys on a novel delayed sequence-recall task and analysed the mechanisms underlying their performance in terms of a neural network model. Thirty fractal images, divided into 10 triplets, were presented repeatedly in fixed temporal order. On each trial the monkeys viewed three sequentially presented sample images, followed by a test stimulus consisting of the same triplet of images and a distractor image (chosen randomly from the remaining 27). The task was to touch the three images in their original order, avoiding the distractor. The monkeys' most common error was touching the distractor when it had the same ordinal position (in its own triplet) as the correct image. This finding suggests that monkeys naturally categorize images by their ordinal number. Additional, secondary strategies were eventually used to avoid distractor images. These include memory of the sample images (working memory) and associations between triplet members. Further direct evidence for ordinal number categorization was provided by a transfer of learning to untrained images of the same ordinal category, following reassignment of image categories within each triplet. We propose a generic three-tier neuronal framework that can explain the components and complex set of characteristics of the observed behavior. This framework, with its intermediate level representing ordinal categories, can also explain the transfer of learning following category reassignment.

  8. Maternal effects on offspring mortality in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Blomquist, Gregory E

    2013-03-01

    The genetics of primate life histories are poorly understood, but quantitative genetic patterns in other mammals suggest phenotypic differences among individuals early in life can be strongly affected by interactions with mothers or other caretakers. I used generalized linear mixed model extensions of complex pedigree quantitative genetic techniques to explore regression coefficients and variance components for infant and juvenile mortality rates across prereproductive age classes in the semifree ranging Cayo Santiago rhesus macaques. Using a large set of records (maximum n = 977 mothers, 6,240 offspring), strong maternal effects can be identified early in development but they rapidly "burn off" as offspring age and mothers become less consistent buffers from increasingly prominent environmental variation. The different ways behavioral ecologists and animal breeders have defined and studied maternal effects can be subsumed, and even blended, within the quantitative genetic framework. Regression coefficients identify loss of the mother, maternal age, and offspring age within their birth cohort as having significant maternal effects on offspring mortality, while variance components for maternal identity record significant maternal influence in the first month of life.

  9. Color-detection thresholds in rhesus macaque monkeys and humans.

    Science.gov (United States)

    Gagin, Galina; Bohon, Kaitlin S; Butensky, Adam; Gates, Monica A; Hu, Jiun-Yiing; Lafer-Sousa, Rosa; Pulumo, Reitumetse L; Qu, Jane; Stoughton, Cleo M; Swanbeck, Sonja N; Conway, Bevil R

    2014-07-15

    Macaque monkeys are a model of human color vision. To facilitate linking physiology in monkeys with psychophysics in humans, we directly compared color-detection thresholds in humans and rhesus monkeys. Colors were defined by an equiluminant plane of cone-opponent color space. All subjects were tested on an identical apparatus with a four-alternative forced-choice task. Targets were 2° square, centered 2° from fixation, embedded in luminance noise. Across all subjects, the change in detection thresholds from initial testing to plateau performance (“learning”) was similar for +L − M (red) colors and +M − L (bluish-green) colors. But the extent of learning was higher for +S (lavender) than for −S (yellow-lime); moreover, at plateau performance, the cone contrast at the detection threshold was higher for +S than for −S. These asymmetries may reflect differences in retinal circuitry for S-ON and S-OFF. At plateau performance, the two species also had similar detection thresholds for all colors, although monkeys had shorter reaction times than humans and slightly lower thresholds for colors that modulated L/M cones. We discuss whether these observations, together with previous work showing that monkeys have lower spatial acuity than humans, could be accounted for by selective pressures driving higher chromatic sensitivity at the cost of spatial acuity amongst monkeys, specifically for the more recently evolved L − M mechanism.

  10. Aid and Income

    DEFF Research Database (Denmark)

    Lof, Matthijs; Mekasha, Tseday Jemaneh; Tarp, Finn

    2015-01-01

    to nonrandom omission of a large proportion of observations. Furthermore, we show that NDHKM’s use of co-integrated regressions is not a suitable empirical strategy for estimating the causal effect of aid on income. Evidence from a Panel VAR model estimated on the dataset of NDHKM, suggests a positive...... and statistically significant long-run effect of aid on income....

  11. Kinetics of liver macrophages (Kupffer cells) in SIV-infected macaques

    Energy Technology Data Exchange (ETDEWEB)

    Ahsan, Muhammad H.; Gill, Amy F.; Alvarez, Xavier; Lackner, Andrew A.; Veazey, Ronald S., E-mail: rveazey@tulane.edu

    2013-11-15

    Since the liver drains antigens from the intestinal tract, and since the intestinal tract is a major site of viral replication, we examined the dynamics of liver macrophages (Kupffer cells) throughout SIV infection. Absolute numbers of Kupffer cells increased in the livers in acute infection, and in animals with AIDS. Significantly higher percentages of proliferating (BrdU+) Kupffer cells were detected in acute infection and in AIDS with similar trends in blood monocytes. Significantly higher percentages of apoptotic (AC3+) Kupffer cells were also found in acute and AIDS stages. However, productively infected cells were not detected in liver of 41/42 animals examined, despite abundant infected cells in gut and lymph nodes of all animals. Increased rates of Kupffer cell proliferation resulting in an increase in Kupffer cells without productive infection indicate SIV infection affects Kupffer cells, but the liver does not appear to be a major site of productive viral replication. - Highlights: • Kupffer cells increase in the liver of SIV-infected macaques. • Increased proliferation and apoptosis of Kupffer cells occurs in SIV infection. • Productively infected cells are rarely detected in the liver. • The liver is not a major site for SIV replication.

  12. Protection of Macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies.

    Science.gov (United States)

    Mascola, J R; Lewis, M G; Stiegler, G; Harris, D; VanCott, T C; Hayes, D; Louder, M K; Brown, C R; Sapan, C V; Frankel, S S; Lu, Y; Robb, M L; Katinger, H; Birx, D L

    1999-05-01

    The role of antibody in protection against human immunodeficiency virus (HIV-1) has been difficult to study in animal models because most primary HIV-1 strains do not infect nonhuman primates. Using a chimeric simian/human immunodeficiency virus (SHIV) based on the envelope of a primary isolate (HIV-89.6), we performed passive-transfer experiments in rhesus macaques to study the role of anti-envelope antibodies in protection. Based on prior in vitro data showing neutralization synergy by antibody combinations, we evaluated HIV immune globulin (HIVIG), and human monoclonal antibodies (MAbs) 2F5 and 2G12 given alone, compared with the double combination 2F5/2G12 and the triple combination HIVIG/2F5/2G12. Antibodies were administered 24 h prior to intravenous challenge with the pathogenic SHIV-89.6PD. Six control monkeys displayed high plasma viremia, rapid CD4(+)-cell decline, and clinical AIDS within 14 weeks. Of six animals given HIVIG/2F5/2G12, three were completely protected; the remaining three animals became SHIV infected but displayed reduced plasma viremia and near normal CD4(+)-cell counts. One of three monkeys given 2F5/2G12 exhibited only transient evidence of infection; the other two had marked reductions in viral load. All monkeys that received HIVIG, 2F5, or 2G12 alone became infected and developed high-level plasma viremia. However, compared to controls, monkeys that received HIVIG or MAb 2G12 displayed a less profound drop in CD4(+) T cells and a more benign clinical course. These data indicate a general correlation between in vitro neutralization and protection and suggest that a vaccine that elicits neutralizing antibody should have a protective effect against HIV-1 infection or disease.

  13. Integrating aerodynamic surface modeling for computational fluid dynamics with computer aided structural analysis, design, and manufacturing

    Science.gov (United States)

    Thorp, Scott A.

    1992-01-01

    This presentation will discuss the development of a NASA Geometry Exchange Specification for transferring aerodynamic surface geometry between LeRC systems and grid generation software used for computational fluid dynamics research. The proposed specification is based on a subset of the Initial Graphics Exchange Specification (IGES). The presentation will include discussion of how the NASA-IGES standard will accommodate improved computer aided design inspection methods and reverse engineering techniques currently being developed. The presentation is in viewgraph format.

  14. A potential aphrodisiac for female macaques.

    Science.gov (United States)

    Pertovaara, Antti; Linnankoski, Ilkka; Artchakov, Denis; Rämä, Pia; Carlson, Synnöve

    2004-09-01

    Earlier studies suggest that alpha2-adrenoceptor antagonists and dopamine receptor agonists may enhance sexual activity in human and nonhuman male primates. It is not known whether these compounds influence the sexual behavior of female primates. We determined whether the administration of a selective alpha2-adrenoceptor antagonist (atipamezole), a dopamine receptor agonist (apomorphine), or their combination to female Macaca arctoides (stumptail macaque) monkeys produces changes in sexual behavior of the female with a male. Following the administration of drugs to the female, the behavior of the female with a male stumptail was observed for 30 min. Atipamezole dose dependently (0.03-0.3 mg/kg im) increased short-time mounting behavior of the male and the total number of copulations. Apomorphine alone (0.125-0.25 mg/kg) or in combination with atipamezole had no significant effects on sexual behavior. The result indicates that a selective alpha2-adrenoceptor antagonist administered in the female stumptail increases sexual behavior of the male with the female. A plausible explanation for this finding is that a selective alpha2-adrenoceptor antagonist increases sexual arousal in female stumptails and this, possibly due to a change in psychosocial behavior of the female, triggers increased sexual activity in males.

  15. Retinotopy versus face selectivity in macaque visual cortex.

    Science.gov (United States)

    Rajimehr, Reza; Bilenko, Natalia Y; Vanduffel, Wim; Tootell, Roger B H

    2014-12-01

    Retinotopic organization is a ubiquitous property of lower-tier visual cortical areas in human and nonhuman primates. In macaque visual cortex, the retinotopic maps extend to higher-order areas in the ventral visual pathway, including area TEO in the inferior temporal (IT) cortex. Distinct regions within IT cortex are also selective to specific object categories such as faces. Here we tested the topographic relationship between retinotopic maps and face-selective patches in macaque visual cortex using high-resolution fMRI and retinotopic face stimuli. Distinct subregions within face-selective patches showed either (1) a coarse retinotopic map of eccentricity and polar angle, (2) a retinotopic bias to a specific location of visual field, or (3) nonretinotopic selectivity. In general, regions along the lateral convexity of IT cortex showed more overlap between retinotopic maps and face selectivity, compared with regions within the STS. Thus, face patches in macaques can be subdivided into smaller patches with distinguishable retinotopic properties.

  16. Investigation on a perforated model by seismic modeling - as an aid to facilitate physical modeling associated with the complicated overburden structure of oil deposits

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Yul; Kim, Yoo Sung; Hyun, Hye Ja [Korea Institute of Geology Mining and Materials, Taejon (Korea, Republic of)

    1996-12-01

    Results of model studies on a perforated model are described. The highly efficient machine(CNC-machine) developed in the past years of this project made it possible to construct a perforated model by properly drilling work, which allows to reduce the velocity of the given model plate. After that, two component-measurements (vertical and horizontal) have been perforated on each discrete spatial grid of the whole model plate. The abundant amount of data thereby gathered have been studied by Hodogram analysis and by snapshot presentation as well. Furthermore, a numerical approach computed by FEM(Finite Element Method) technique has aided in the understanding and the interpretation of wave propagation observed on the perforated model. It was shown that the velocity of the perforated medium should be nearly homogeneous and that its boundary might be approximated by a discontinuity of first order. There results will help extend the applicability of physical modeling and hence dedicate to activating various physical modeling for complicated overburden structures of oil deposits. (author). 6 refs., 14 figs.

  17. Changes of inflammation-associated cytokine expressions during early phase of experimental endotoxic shock in macaques

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hui Ji; Ke-Yi Sun; Yan-Hong Feng; Guo-Qing Yin

    2004-01-01

    AIM: To study changes of inflammation-associated cytokine expressions during early phase of endotoxic shock in macague.METHODS: Experiments were performed in Macaque mulatta treated with LPS 2.8 mg/kg in shock model group or with normal saline in control group. Blood samples were collected before, or 60 min, or 120 min after LPS injection,respectively. Liver and spleen tissues were obtained at 120 min after LPS injection. The plasma levels of TNF-α,IL-1 β, IL-10 and IL-12P40 were determined by doubleantibody sandwich ELISA with antibodies against human cytokines. The mRNA levels of TNF-α, IL-1 β, and IL-18 in peripheral blood mononuclear cells (PBMCs), liver and spleen were examined by real-time fluorescence semi-quantitative RT-PCR with the primers based on human genes.RESULTS: Mean systemic arterial pressure (MAP), systemic vascular resistance index (SVRI) and left ventricular work index (LVWI) of macaques were significant declined in shock model group on average 60 min after LPS injection. The plasma levels of TNF-α and IL-10 were significantly increased 60 min after LPS injection and then decreased.The plasma levels of IL-1 β and IL-12P40 were significantly increased at 120 min after LPS injection. The mRNA levels of TNF-α and IL-1 β were significantly increased 60 min after LPS stimulation in PBMCs and 120 min after LPS stimulation in livers. The mRNA level of IL-18 was significantly increased 120 min after LPS stimulation in PBMCs and livers. But in spleen, only TNF-α mRNA level in LPS group was significantly higher 120 min after LPS stimulation, compared with that in control group.CONCLUSION: An endotoxic shock model of Macaque mulatta was successfully established. Both antibodies for ELISA and PCR primers based on human cytokine assays were successfully applied to detect macaque cytokines. In the model, inflammatory cytokines, such as TNF-α, IL-1 β,IL-12 and IL-18 as well as anti-inflammation cytokine IL-10,were released at very early phase of

  18. Sex-specific heritability of spontaneous lipid levels in an extended pedigree of Indian-origin rhesus macaques (Macaca mulatta.

    Directory of Open Access Journals (Sweden)

    Amanda Vinson

    Full Text Available The rhesus macaque is an important model for human atherosclerosis but genetic determinants of relevant phenotypes have not yet been investigated in this species. Because lipid levels are well-established and heritable risk factors for human atherosclerosis, our goal was to assess the heritability of lipoprotein cholesterol and triglyceride levels in a single, extended pedigree of 1,289 Indian-origin rhesus macaques. Additionally, because increasing evidence supports sex differences in the genetic architecture of lipid levels and lipid metabolism in humans and macaques, we also explored sex-specific heritability for all lipid measures investigated in this study. Using standard methods, we measured lipoprotein cholesterol and triglyceride levels from fasted plasma in a sample of 193 pedigreed rhesus macaques selected for membership in large, paternal half-sib cohorts, and maintained on a low-fat, low cholesterol chow diet. Employing a variance components approach, we found moderate heritability for total cholesterol (h²=0.257, P=0.032, LDL cholesterol (h²=0.252, P=0.030, and triglyceride levels (h²=0.197, P=0.034 in the full sample. However, stratification by sex (N=68 males, N=125 females revealed substantial sex-specific heritability for total cholesterol (0.644, P=0.004, females only, HDL cholesterol (0.843, P=0.0008, females only, VLDL cholesterol (0.482, P=0.018, males only, and triglyceride levels (0.705, P=0.001, males only that was obscured or absent when sexes were combined in the full sample. We conclude that genes contribute to spontaneous variation in circulating lipid levels in the Indian-origin rhesus macaque in a sex-specific manner, and that the rhesus macaque is likely to be a valuable model for sex-specific genetic effects on lipid risk factors for human atherosclerosis. These findings are a first-ever report of heritability for cholesterol levels in this species, and support the need for expanded analysis of these traits in

  19. Human-wildlife conflict: proximate predictors of aggression between humans and rhesus macaques in India.

    Science.gov (United States)

    Beisner, Brianne A; Heagerty, Allison; Seil, Shannon K; Balasubramaniam, Krishna N; Atwill, Edward R; Gupta, Brij K; Tyagi, Praveen C; Chauhan, Netrapal P S; Bonal, B S; Sinha, P R; McCowan, Brenda

    2015-02-01

    Macaques live in close contact with humans across South and Southeast Asia, and direct interaction is frequent. Aggressive contact is a concern in many locations, particularly among populations of rhesus and longtail macaques that co-inhabit urbanized cities and towns with humans. We investigated the proximate factors influencing the occurrence of macaque aggression toward humans as well as human aggression toward macaques to determine the extent to which human behavior elicits macaque aggression and vice versa. We conducted a 3-month study of four free-ranging populations of rhesus macaques in Dehradun, India from October-December 2012, using event sampling to record all instances of human-macaque interaction (N = 3120). Our results show that while human aggression was predicted by the potential for economic losses or damage, macaque aggression was influenced by aggressive or intimidating behavior by humans as well as recent rates of conspecific aggression. Further, adult female macaques participated in aggression more frequently than expected, whereas adult and subadult males participated as frequently as expected. Our analyses demonstrate that neither human nor macaque aggression is unprovoked. Rather, both humans and macaques are responding to one another's behavior. Mitigation of human-primate conflict, and indeed other types of human-wildlife conflict in such coupled systems, will require a holistic investigation of the ways in which each participant is responding to, and consequently altering, the behavior of the other.

  20. Computer aided reliability, availability, and safety modeling for fault-tolerant computer systems with commentary on the HARP program

    Science.gov (United States)

    Shooman, Martin L.

    1991-01-01

    Many of the most challenging reliability problems of our present decade involve complex distributed systems such as interconnected telephone switching computers, air traffic control centers, aircraft and space vehicles, and local area and wide area computer networks. In addition to the challenge of complexity, modern fault-tolerant computer systems require very high levels of reliability, e.g., avionic computers with MTTF goals of one billion hours. Most analysts find that it is too difficult to model such complex systems without computer aided design programs. In response to this need, NASA has developed a suite of computer aided reliability modeling programs beginning with CARE 3 and including a group of new programs such as: HARP, HARP-PC, Reliability Analysts Workbench (Combination of model solvers SURE, STEM, PAWS, and common front-end model ASSIST), and the Fault Tree Compiler. The HARP program is studied and how well the user can model systems using this program is investigated. One of the important objectives will be to study how user friendly this program is, e.g., how easy it is to model the system, provide the input information, and interpret the results. The experiences of the author and his graduate students who used HARP in two graduate courses are described. Some brief comparisons were made with the ARIES program which the students also used. Theoretical studies of the modeling techniques used in HARP are also included. Of course no answer can be any more accurate than the fidelity of the model, thus an Appendix is included which discusses modeling accuracy. A broad viewpoint is taken and all problems which occurred in the use of HARP are discussed. Such problems include: computer system problems, installation manual problems, user manual problems, program inconsistencies, program limitations, confusing notation, long run times, accuracy problems, etc.

  1. Effect of habitat quality on diet flexibility in Barbary macaques.

    Science.gov (United States)

    Ménard, Nelly; Motsch, Peggy; Delahaye, Alexia; Saintvanne, Alice; Le Flohic, Guillaume; Dupé, Sandrine; Vallet, Dominique; Qarro, Mohamed; Tattou, Mohamed Ibn; Pierre, Jean-Sébastien

    2014-07-01

    Barbary macaques live in extreme temperate environments characterized by strongly seasonal resource availability. They are mainly terrestrial while foraging, harvesting food from the herbaceous layer. These monkeys are threatened mainly because of anthropogenic habitat degradation. We studied the adaptive capacities of wild groups of Barbary macaques that lived in different cedar forests undergoing varying extents of grazing pressure from domestic livestock. In all three sites, diet varied seasonally. Heavy grazing led to a significant decrease in herbaceous production and species richness. As a consequence, the monkeys' diet in this poor habitat showed a decreased plant species richness. Moreover, it incorporated fewer above-ground herbaceous resources, and a greater proportion of subterranean resources (especially hypogeous fungi and subterranean invertebrates such as earthworms, eggs and adults of earwigs, and ant's larvae) than the diet of monkeys inhabiting ungrazed forest. Cedar bark, cedar strobiles, earthworms, and earwigs were part of the monkeys' diet only in grazed forest. Monkeys in heavily grazed forest compensated for a lack of herbaceous foods by eating subterranean foods preferentially to tree and shrub products. The foods they consumed take longer to harvest and process than the seeds or leaves consumed by Barbary macaques in less heavily grazed forest habitats. Our results suggest that monkeys do differ in their diets according to the degree of habitat change induced by human activities. They also highlight the dietary flexibility of Barbary macaques as a key element that allows them to cope with degraded habitats. We later compare the dietary adjustments of Barbary macaques facing environmental change to dietary strategies of other macaques and temperate-zone primates. © 2014 Wiley Periodicals, Inc.

  2. Social relevance drives viewing behavior independent of low-level salience in rhesus macaques

    Directory of Open Access Journals (Sweden)

    James Andrew Solyst

    2014-11-01

    Full Text Available Quantifying attention to social stimuli during the viewing of complex social scenes with eye tracking has proven to be a sensitive method in the diagnosis of autism spectrum disorders years before average clinical diagnosis. Rhesus macaques provide an ideal model for understanding the mechanisms underlying social viewing behavior, but to date no comparable behavioral task has been developed for use in monkeys. Using a novel scene-viewing task, we monitored the gaze of three rhesus macaques while they freely viewed well-controlled composed social scenes and analyzed the time spent viewing objects and monkeys. In each of six behavioral sessions, monkeys viewed a set of 90 images (540 unique scenes with each image presented twice. In two-thirds of the repeated scenes, either a monkey or an object was replaced with a novel item (manipulated scenes. When viewing a repeated scene, monkeys made longer fixations and shorter saccades, shifting from a rapid orienting to global scene contents to a more local analysis of fewer items. In addition to this repetition effect, in manipulated scenes, monkeys demonstrated robust memory by spending more time viewing the replaced items. By analyzing attention to specific scene content, we found that monkeys strongly preferred to view conspecifics and that this was not related to their salience in terms of low-level image features. A model-free analysis of viewing statistics found that monkeys that were viewed earlier and longer had direct gaze and redder sex skin around their face and rump, two important visual social cues. These data provide a quantification of viewing strategy, memory and social preferences in rhesus macaques viewing complex social scenes, and they provide an important baseline with which to compare to the effects of therapeutics aimed at enhancing social cognition.

  3. The UNC-Wisconsin Rhesus Macaque Neurodevelopment Database: A Structural MRI and DTI Database of Early Postnatal Development

    Science.gov (United States)

    Young, Jeffrey T.; Shi, Yundi; Niethammer, Marc; Grauer, Michael; Coe, Christopher L.; Lubach, Gabriele R.; Davis, Bradley; Budin, Francois; Knickmeyer, Rebecca C.; Alexander, Andrew L.; Styner, Martin A.

    2017-01-01

    Rhesus macaques are commonly used as a translational animal model in neuroimaging and neurodevelopmental research. In this report, we present longitudinal data from both structural and diffusion MRI images generated on a cohort of 34 typically developing monkeys from 2 weeks to 36 months of age. All images have been manually skull stripped and are being made freely available via an online repository for use by the research community. PMID:28210206

  4. A mathematical model for surface roughness of fluidic channels produced by grinding aided electrochemical discharge machining (G-ECDM

    Directory of Open Access Journals (Sweden)

    Ladeesh V. G.

    2017-01-01

    Full Text Available Grinding aided electrochemical discharge machining is a hybrid technique, which combines the grinding action of an abrasive tool and thermal effects of electrochemical discharges to remove material from the workpiece for producing complex contours. The present study focuses on developing fluidic channels on borosilicate glass using G-ECDM and attempts to develop a mathematical model for surface roughness of the machined channel. Preliminary experiments are conducted to study the effect of machining parameters on surface roughness. Voltage, duty factor, frequency and tool feed rate are identified as the significant factors for controlling surface roughness of the channels produced by G-ECDM. A mathematical model was developed for surface roughness by considering the grinding action and thermal effects of electrochemical discharges in material removal. Experiments are conducted to validate the model and the results obtained are in good agreement with that predicted by the model.

  5. Effect of sildenafil citrate on penile erection of rhesus macaques

    Institute of Scientific and Technical Information of China (English)

    Xun-BinHuang; Cheng-LiangXiong; Cheng-GaoYu; Jie-LingZhou; Ji-YunShen

    2004-01-01

    Aim: To examine the effect of sildenafil citrate on penile erection of male rhesus macaque. Methods:Twenty Macaca mulatta were divided into the sildenafil treated and the control groups of l0 animals each. The penile size, the corpus cavernosal electromyogram (EMG) and the intra-corpus cavernosal pressure (ICP) were determined. Results: The diameter of penis and the ICP were significantly increased and the corpus cavernosal EMG significantly reduced in the sildenafil group. Conclusion: Sildenafil citrate increases the penile size and ICP and reduces the corpus cavernosal EMG in male rhesus macaque. (Asian J Androl 2004 Sep; 6: 233-235)

  6. SIV Infection Facilitates Mycobacterium tuberculosis Infection of Rhesus Macaques

    OpenAIRE

    Guo, Ming; Xian, Qiao-Yang; Rao, Yan; Zhang, Jing; Wang,Yong; Huang, Zhi-Xiang; Wang, Xin; Bao, Rong; Zhou, Li; Liu, Jin-Biao; Tang, Zhi-Jiao; Guo, De-Yin; Qin, Chuan; Li, Jie-Liang; Ho, Wen-Zhe

    2017-01-01

    Tuberculosis (TB) is a common opportunistic infection and the leading cause of death for human immunodeficiency virus (HIV)-infected patients. Thus, it is necessary to understand the pathogenetic interactions between M.tb and HIV infection. In this study, we examined M.tb and/or simian immunodeficiency virus (SIV) infection of Chinese rhesus macaques. While there was little evidence that M.tb enhanced SIV infection of macaques, SIV could facilitate M.tb infection as demonstrated by X-rays, pa...

  7. Modeling and development of INS-aided PLLs in a GNSS/INS deeply-coupled hardware prototype for dynamic applications.

    Science.gov (United States)

    Zhang, Tisheng; Niu, Xiaoji; Ban, Yalong; Zhang, Hongping; Shi, Chuang; Liu, Jingnan

    2015-01-05

    A GNSS/INS deeply-coupled system can improve the satellite signals tracking performance by INS aiding tracking loops under dynamics. However, there was no literature available on the complete modeling of the INS branch in the INS-aided tracking loop, which caused the lack of a theoretical tool to guide the selections of inertial sensors, parameter optimization and quantitative analysis of INS-aided PLLs. This paper makes an effort on the INS branch in modeling and parameter optimization of phase-locked loops (PLLs) based on the scalar-based GNSS/INS deeply-coupled system. It establishes the transfer function between all known error sources and the PLL tracking error, which can be used to quantitatively evaluate the candidate inertial measurement unit (IMU) affecting the carrier phase tracking error. Based on that, a steady-state error model is proposed to design INS-aided PLLs and to analyze their tracking performance. Based on the modeling and error analysis, an integrated deeply-coupled hardware prototype is developed, with the optimization of the aiding information. Finally, the performance of the INS-aided PLLs designed based on the proposed steady-state error model is evaluated through the simulation and road tests of the hardware prototype.

  8. Diversity Research on Income Difference and Consumption Behavior of Rural Residents in China - Empirical Analysis Based on AIDS Model

    Institute of Scientific and Technical Information of China (English)

    JinFan

    2004-01-01

    By building up an AIDS model of Chinese rural residents, classified into fivegroups by income, concluding six commodities (services), analyses the diversity of consumption behavior out of income difference. We draw the following conclusions: Firstly, there exists some difference between different income groups in commodities (services) consumption.Secondly, increase of farmers' income will be favorable to the enhancement of consumption level and upgrading of consumption structure. Thirdly, the medium income group, as one special mass, features a transitional main body of consumption structure. Finally, the policymakers should support the farmers with lower income in compulsory education, such as more and necessary transfer payments.

  9. Acute traumatic spinal cord injury induces glial activation in the cynomolgus macaque (Macaca fascicularis).

    Science.gov (United States)

    Miller, A D; Westmoreland, S V; Evangelous, N R; Graham, A; Sledge, J; Nesathurai, S

    2012-06-01

    Traumatic spinal cord injury leads to direct myelin and axonal damage and leads to the recruitment of inflammatory cells to site of injury. Although rodent models have provided the greatest insight into the genesis of traumatic spinal cord injury (TSCI), recent studies have attempted to develop an appropriate non-human primate model. We explored TSCI in a cynomolgus macaque model using a balloon catheter to mimic external trauma to further evaluate the underlying mechanisms of acute TSCI. Following 1hour of spinal cord trauma, there were focal areas of hemorrhage and necrosis at the site of trauma. Additionally, there was a marked increased expression of macrophage-related protein 8, MMP9, IBA-1, and inducible nitric oxide synthase in macrophages and microglia at the site of injury. This data indicate that acute TSCI in the cynomolgus macaque is an appropriate model and that the earliest immunohistochemical changes noted are within macrophage and microglia populations. © 2012 John Wiley & Sons A/S.

  10. Protective immunity in macaques vaccinated with a modified vaccinia virus Ankara-based measles virus vaccine in the presence of passively acquired antibodies

    NARCIS (Netherlands)

    K.J. Stittelaar (Koert); L.S. Wyatt (Linda); R.L. de Swart (Rik); H.W. Vos (Helma); J. Groen (Jan); G. van Amerongen (Geert); R.S. van Binnendijk (Rob); S. Rozenblatt (Shmuel); B. Moss (Bernard); A.D.M.E. Osterhaus (Albert)

    2000-01-01

    textabstractRecombinant modified vaccinia virus Ankara (MVA), encoding the measles virus (MV) fusion (F) and hemagglutinin (H) (MVA-FH) glycoproteins, was evaluated in an MV vaccination-challenge model with macaques. Animals were vaccinated twice in the absence or presence of passively transferred M

  11. Protective immunity in macaques vaccinated with a modified vaccinia virus Ankara-based measles virus vaccine in the presence of passively acquired antibodies

    NARCIS (Netherlands)

    K.J. Stittelaar (Koert); L.S. Wyatt (Linda); R.L. de Swart (Rik); H.W. Vos (Helma); J. Groen (Jan); R.S. van Binnendijk (Rob); S. Rozenblatt (Shmuel); B. Moss (Bernard); G. van Amerongen (Geert); A.D.M.E. Osterhaus (Albert)

    2000-01-01

    textabstractRecombinant modified vaccinia virus Ankara (MVA), encoding the measles virus (MV) fusion (F) and hemagglutinin (H) (MVA-FH) glycoproteins, was evaluated in an MV vaccination-challenge model with macaques. Animals were vaccinated twice in the absence or presence of passi

  12. The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys

    DEFF Research Database (Denmark)

    Dorph-Petersen, Karl-Anton; Pierri, Joseph N; Perel, James M

    2005-01-01

    It is unclear to what degree antipsychotic therapy confounds longitudinal imaging studies and post-mortem studies of subjects with schizophrenia. To investigate this problem, we developed a non-human primate model of chronic antipsychotic exposure. Three groups of six macaque monkeys each were...

  13. Laboratory Fire Modeling. 1. Wind-Aided Flame Spread. 2. Wet Coagulation of Smoke.

    Science.gov (United States)

    1986-11-21

    K. L.; Carrier, G. F.; Fendell , F. E.; Gat, N.; Hsu, C. T.; 110 Kwoh. D. S. W.: Lake, B. M.: Wagner, R. M.; Wolff. M. F. 13a. TYPE OF REPORT 13b...Richard Wagner. Theoretical work associated with both tasks was carried out by George Carrier, Francis Fendell , Michael Kezerian, and Lawrence...34,,.’,.’ %. , ,,’, ..’, . ,- .. ’,.. -.% ,,.’.’. .<. .,’ e .,. .t,’%,. Fleeter, R., Fendell , F., Cohen, L. M., Gat, N., and Witte, A. B. 1984 Laboratory facility for wind-aided firespread along a

  14. Comparative analysis of genotypic diversity in Entamoeba nuttalli isolates from Tibetan macaques and rhesus macaques in China.

    Science.gov (United States)

    Guan, Yue; Feng, Meng; Cai, Junlong; Min, Xiangyang; Zhou, Xingyu; Xu, Qing; Tan, Ning; Cheng, Xunjia; Tachibana, Hiroshi

    2016-03-01

    We have recently demonstrated the potentially virulent species Entamoeba nuttalli as one of the highly prevalent parasites in rhesus macaques (Macaca mulatta) in Mount Long-hu and Gui-yang in China. Tibetan macaque (Macaca thibetana) is a unique species living in China. To evaluate the prevalence of Entamoeba species in wild Tibetan macaques, we obtained 89 stool samples in Mount E-mei of Si-chuan Province in China. PCR analysis detected E. nuttalli, Entamoeba coli, and Entamoeba polecki ST2 in 17%, 42%, and 66% of the samples, respectively, whereas Entamoeba histolytica and Entamoeba dispar were undetected. This study is the first to report on the detection of E. nuttalli from Tibetan macaques. Six E. nuttalli isolates were obtained, 18S rRNA gene and six tRNA-linked short tandem repeat (STR) loci of the isolates were sequenced. The Mantel test results gave an r value of 0.97 of relationships between geographical distance and genetic diversity of Chinese E. nuttalli populations, indicating a significant isolation-by-distance effect in Chinese E. nuttalli according to the tRNA-STR loci sequences. Structural analysis of E. nuttalli isolates based on tRNA-linked STR loci demonstrated three Chinese E. nuttalli populations with their respective features, but the Gui-yang population was located in the middle. In the distance-based NJ tree, E. nuttalli isolates were divided into five different branches, and E-mei isolates were attributed to an independent branch to distinguish them from Gui-yang and Long-hu isolates. Genetic analysis in this study provided clues of the genetic differences between E. nuttalli isolates from Tibetan macaques and rhesus macaques in China.

  15. Phenotypic and Functional Characterization of Monoclonal Antibodies with Specificity for Rhesus Macaque CD200, CD200R and Mincle.

    Directory of Open Access Journals (Sweden)

    Siddappa N Byrareddy

    Full Text Available Lectin-like molecules and their receptors are cell surface molecules that have been shown to play a role in either facilitating infection or serving as transporters of HIV/SIV in vivo. The role of these lectin-like molecules in the pathogenesis of HIV/SIV infection continues to be defined. In efforts to gain further insight on the potential role of these lectin-like molecules, our laboratory generated monoclonal antibodies (mAb against the human analogs of rhesus macaque CD200, CD200R and Mincle, since the rhesus macaques are accepted as the most reliable animal model to study human HIV infection. The characterization of the cell lineages from the blood and various tissues of rhesus macaques that express these lectin-like molecules are described herein. Among the mononuclear cells, the cells of the myeloid lineage of rhesus macaques are the predominant cell lineages that express readily detectable levels of CD200, CD200R and Mincle that is similar to the expression of Siglec-1 and Siglec-3 reported by our laboratory earlier. Subset analysis revealed that a higher frequency of the CD14+/CD16- subset from normal rhesus macaques express CD200, CD200R and Mincle. Differences in the frequencies and density of expression of these molecules by the gated population of CD14+ cells from various tissues are noted with PBMC and bone marrow expressing the highest and the mononuclear cells isolated from the colon and ileum expressing the lowest levels. While a significant frequency of pDCs and mDCs express Siglec-1/Siglec-3, a much lower frequency expresses CD200, CD200R and Mincle in PBMCs from rhesus macaques. The mAb against CD200 and CD200R but not Mincle appear to inhibit the infection of macrophage tropic SIV/SHIV in vitro. We conclude that these mAbs may have potential to be used as adjunctive therapeutic agents to control/inhibit SIV/HIV infection.

  16. Endozoochorous seed dispersal by Japanese macaques (Macaca fuscata): Effects of temporal variation in ranging and seed characteristics on seed shadows.

    Science.gov (United States)

    Tsuji, Yamato; Morimoto, Mayumi

    2016-02-01

    Variation in seed shadows generated by frugivores is caused by daily, seasonal, and inter-annual variation in ranging, as well as inter-specific variability in gut passage times according to seed characteristics. We studied the extent to which seed weight, specific gravity, and daily (morning, afternoon, and evening) and inter-annual (2004 vs. 2005) variation in ranging affected seed shadows generated by wild Japanese macaques (Macaca fuscata) in northern Japan. The macaques ingested fleshy fruits of 11 species during the two year study period; Viburnum dilatatum (Caprifoliaceae: heavier seeds with higher specific gravity) and Rosa multiflora (Rosaceae: lighter seeds with lower specific gravity) were eaten frequently in both years. The travel distances of macaques after feeding on V. dilatatum and R. multiflora fruits were estimated by combining feeding locations and ranging patterns measured in the field with gut passage times of model seeds in captive animals. Median travel distances after fruit feeding were 431 (quantile range: 277-654) and 478 m (265-646), respectively, with a maximum of 1,261 m. Neither year nor time of day affected travel distances. The gut passage time of model V. dilatatum seeds was longer than that of model R. multiflora seed, but this did not affect dispersal distances. Seed shadows for both species over 2 years showed unimodal distribution (peak: 101-500 m) and more than 90%, 20%, and 3% of ingested seeds were estimated to be dispersed >100, >500, and >1000 m, respectively, the longest known distances among macaque species. R. multiflora seeds tended to be dispersed further in 2004 than 2005, but V. dilatatum seeds were not, implying that inter-annual variations in ranging pattern due to the distribution and abundance of nut fruiting could affect dispersal distance.

  17. Psychological model of ART adherence behaviors in persons living with HIV/AIDS in Mexico: a structural equation analysis

    Science.gov (United States)

    Sagarduy, José Luis Ybarra; López, Julio Alfonso Piña; Ramírez, Mónica Teresa González; Dávila, Luis Enrique Fierros

    2017-01-01

    ABSTRACT OBJECTIVE The objective of this study has been to test the ability of variables of a psychological model to predict antiretroviral therapy medication adherence behavior. METHODS We have conducted a cross-sectional study among 172 persons living with HIV/AIDS (PLWHA), who completed four self-administered assessments: 1) the Psychological Variables and Adherence Behaviors Questionnaire, 2) the Stress-Related Situation Scale to assess the variable of Personality, 3) The Zung Depression Scale, and 4) the Duke-UNC Functional Social Support Questionnaire. Structural equation modeling was used to construct a model to predict medication adherence behaviors. RESULTS Out of all the participants, 141 (82%) have been considered 100% adherent to antiretroviral therapy. Structural equation modeling has confirmed the direct effect that personality (decision-making and tolerance of frustration) has on motives to behave, or act accordingly, which was in turn directly related to medication adherence behaviors. In addition, these behaviors have had a direct and significant effect on viral load, as well as an indirect effect on CD4 cell count. The final model demonstrates the congruence between theory and data (x 2/df. = 1.480, goodness of fit index = 0.97, adjusted goodness of fit index = 0.94, comparative fit index = 0.98, root mean square error of approximation = 0.05), accounting for 55.7% of the variance. CONCLUSIONS The results of this study support our theoretical model as a conceptual framework for the prediction of medication adherence behaviors in persons living with HIV/AIDS. Implications for designing, implementing, and evaluating intervention programs based on the model are to be discussed. PMID:28876412

  18. Foreign aid

    DEFF Research Database (Denmark)

    Tarp, Finn

    2008-01-01

    Foreign aid has evolved significantly since the Second World War in response to a dramatically changing global political and economic context. This article (a) reviews this process and associated trends in the volume and distribution of foreign aid; (b) reviews the goals, principles and instituti......Foreign aid has evolved significantly since the Second World War in response to a dramatically changing global political and economic context. This article (a) reviews this process and associated trends in the volume and distribution of foreign aid; (b) reviews the goals, principles...

  19. Model and experiences of initiating collaboration with traditional healers in validation of ethnomedicines for HIV/AIDS in Namibia

    Directory of Open Access Journals (Sweden)

    Chinsembu Kazhila C

    2009-10-01

    Full Text Available Abstract Many people with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS in Namibia have access to antiretroviral drugs but some still use traditional medicines to treat opportunistic infections and offset side-effects from antiretroviral medication. Namibia has a rich biodiversity of indigenous plants that could contain novel anti-HIV agents. However, such medicinal plants have not been identified and properly documented. Various ethnomedicines used to treat HIV/AIDS opportunistic infections have not been scientifically validated for safety and efficacy. These limitations are mostly attributable to the lack of collaboration between biomedical scientists and traditional healers. This paper presents a five-step contextual model for initiating collaboration with Namibian traditional healers in order that candidate plants that may contain novel anti-HIV agents are identified, and traditional medicines used to treat HIV/AIDS opportunistic infections are subjected to scientific validation. The model includes key structures and processes used to initiate collaboration with traditional healers in Namibia; namely, the National Biosciences Forum, a steering committee with the University of Namibia (UNAM as the focal point, a study tour to Zambia and South Africa where other collaborative frameworks were examined, commemorations of the African Traditional Medicine Day (ATMD, and consultations with stakeholders in north-eastern Namibia. Experiences from these structures and processes are discussed. All traditional healers in north-eastern Namibia were willing to collaborate with UNAM in order that their traditional medicines could be subjected to scientific validation. The current study provides a framework for future collaboration with traditional healers and the selection of candidate anti-HIV medicinal plants and ethnomedicines for scientific testing in Namibia.

  20. Model and experiences of initiating collaboration with traditional healers in validation of ethnomedicines for HIV/AIDS in Namibia.

    Science.gov (United States)

    Chinsembu, Kazhila C

    2009-10-23

    Many people with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) in Namibia have access to antiretroviral drugs but some still use traditional medicines to treat opportunistic infections and offset side-effects from antiretroviral medication. Namibia has a rich biodiversity of indigenous plants that could contain novel anti-HIV agents. However, such medicinal plants have not been identified and properly documented. Various ethnomedicines used to treat HIV/AIDS opportunistic infections have not been scientifically validated for safety and efficacy. These limitations are mostly attributable to the lack of collaboration between biomedical scientists and traditional healers. This paper presents a five-step contextual model for initiating collaboration with Namibian traditional healers in order that candidate plants that may contain novel anti-HIV agents are identified, and traditional medicines used to treat HIV/AIDS opportunistic infections are subjected to scientific validation. The model includes key structures and processes used to initiate collaboration with traditional healers in Namibia; namely, the National Biosciences Forum, a steering committee with the University of Namibia (UNAM) as the focal point, a study tour to Zambia and South Africa where other collaborative frameworks were examined, commemorations of the African Traditional Medicine Day (ATMD), and consultations with stakeholders in north-eastern Namibia. Experiences from these structures and processes are discussed. All traditional healers in north-eastern Namibia were willing to collaborate with UNAM in order that their traditional medicines could be subjected to scientific validation. The current study provides a framework for future collaboration with traditional healers and the selection of candidate anti-HIV medicinal plants and ethnomedicines for scientific testing in Namibia.

  1. Murine AIDS: a model for the human disease or a distinct entity?

    Science.gov (United States)

    Cunnigham, R K; Thacore, H R; Zhou, P; Terzian, R; Nakeeb, S; Zaleski, M B

    1994-01-01

    The LP-BM5 mixture of murine retroviruses elicits a disease in mice referred to as murine immunodeficiency syndrome (MAIDS) that is considered by some to be an animal homologue of human AIDS. In this article, we present and discuss some recent findings on the pathogenesis of the murine disease and their implications for the proposed homology between murine and human syndromes. The murine disease seems to display as many similarities to as it does differences from human AIDS. Among the latter are: definitive and exclusive viral etiology, a strong genetic effect on susceptibility to infection, expansion of the CD4+ cell population in spleen and peripheral blood, consistent transmissibility by a single transfusion of the minute amounts of blood or plasma from infected donors, and striking similarity between virus-induced alteration of the in vitro spleen cell proliferation and those caused by treatment with a protein kinase inhibitor K252a. With this in mind, the use of the noncommittal term retrovirus-induced murine lymphoproliferative disease instead of MAIDS appears to be more appropriate at this time.

  2. Functional NPY variation as a factor in stress resilience and alcohol consumption in rhesus macaques.

    Science.gov (United States)

    Lindell, Stephen G; Schwandt, Melanie L; Sun, Hui; Sparenborg, Jeffrey D; Björk, Karl; Kasckow, John W; Sommer, Wolfgang H; Goldman, David; Higley, J Dee; Suomi, Stephen J; Heilig, Markus; Barr, Christina S

    2010-04-01

    Neuropeptide Y (NPY) counters stress and is involved in neuroadaptations that drive escalated alcohol drinking in rodents. In humans, low NPY expression predicts amygdala response and emotional reactivity. Genetic variation that affects the NPY system could moderate stress resilience and susceptibility to alcohol dependence. To determine whether functional NPY variation influences behavioral adaptation to stress and alcohol consumption in a nonhuman primate model of early adversity (peer rearing). We sequenced the rhesus macaque NPY locus (rhNPY) and performed in silico analysis to identify functional variants. We performed gel shift assays using nuclear extract from testes, brain, and hypothalamus. Levels of NPY in cerebrospinal fluid were measured by radioimmunoassay, and messenger RNA levels were assessed in the amygdala using real-time polymerase chain reaction. Animals were exposed to repeated social separation stress and tested for individual differences in alcohol consumption. Animals were genotyped for -1002 T > G, and the data were analyzed using analysis of variance. National Institutes of Health Animal Center. Subjects Ninety-six rhesus macaques. Main Outcome Measure Behavior arousal during social separation stress and ethanol consumption. The G allele altered binding of regulatory proteins in all nuclear extracts tested, and -1002 T > G resulted in lower levels of NPY expression in the amygdala. Macaques exposed to adversity had lower cerebrospinal fluid NPY levels and exhibited higher levels of arousal during stress, but only as a function of the G allele. We also found that stress-exposed G allele carriers consumed more alcohol and exhibited an escalation in intake over cycles of alcohol availability and deprivation. Our results suggest a role for NPY promoter variation in the susceptibility to alcohol use disorders and point to NPY as a candidate for examining gene x environment interactions in humans.

  3. Characterization and phylogenetic epitope mapping of CD38 ADPR cyclase in the cynomolgus macaque

    Directory of Open Access Journals (Sweden)

    Titti Fausto

    2004-09-01

    Full Text Available Abstract Background The CD38 transmembrane glycoprotein is an ADP-ribosyl cyclase that moonlights as a receptor in cells of the immune system. Both functions are independently implicated in numerous areas related to human health. This study originated from an inherent interest in studying CD38 in the cynomolgus monkey (Macaca fascicularis, a species closely related to humans that also represents a cogent animal model for the biomedical analysis of CD38. Results A cDNA was isolated from cynomolgus macaque peripheral blood leukocytes and is predicted to encode a type II membrane protein of 301 amino acids with 92% identity to human CD38. Both RT-PCR-mediated cDNA cloning and genomic DNA PCR surveying were possible with heterologous human CD38 primers, demonstrating the striking conservation of CD38 in these primates. Transfection of the cDNA coincided with: (i surface expression of cynomolgus macaque CD38 by immunofluorescence; (ii detection of ~42 and 84 kDa proteins by Western blot and (iii the appearance of ecto-enzymatic activity. Monoclonal antibodies were raised against the cynomolgus CD38 ectodomain and were either species-specific or cross-reactive with human CD38, in which case they were directed against a common disulfide-requiring conformational epitope that was mapped to the C-terminal disulfide loop. Conclusion This multi-faceted characterization of CD38 from cynomolgus macaque demonstrates its high genetic and biochemical similarities with human CD38 while the immunological comparison adds new insights into the dominant epitopes of the primate CD38 ectodomain. These results open new prospects for the biomedical and pharmacological investigations of this receptor-enzyme.

  4. Lack of prophylactic efficacy of oral maraviroc in macaques despite high drug concentrations in rectal tissues.

    Science.gov (United States)

    Massud, Ivana; Aung, Wutyi; Martin, Amy; Bachman, Shanon; Mitchell, James; Aubert, Rachael; Solomon Tsegaye, Theodros; Kersh, Ellen; Pau, Chou-Pong; Heneine, Walid; García-Lerma, J Gerardo

    2013-08-01

    Maraviroc (MVC) is a potent CCR5 coreceptor antagonist that is in clinical testing for daily oral pre-exposure prophylaxis (PrEP) for HIV prevention. We used a macaque model consisting of weekly SHIV162p3 exposures to evaluate the efficacy of oral MVC in preventing rectal SHIV transmission. MVC dosing was informed by the pharmacokinetic profile seen in blood and rectal tissues and consisted of a human-equivalent dose given 24 h before virus exposure, followed by a booster postexposure dose. In rectal secretions, MVC peaked at 24 h (10,242 ng/ml) with concentrations at 48 h that were about 40 times those required to block SHIV infection of peripheral blood mononuclear cells (PBMCs) in vitro. Median MVC concentrations in rectal tissues at 24 h (1,404 ng/g) were 30 and 10 times those achieved in vaginal or lymphoid tissues, respectively. MVC significantly reduced macrophage inflammatory protein 1β-induced CCR5 internalization in rectal mononuclear cells, an indication of efficient binding to CCR5 in rectal lymphocytes. The half-life of CCR5-bound MVC in PBMCs was 2.6 days. Despite this favorable profile, 5/6 treated macaques were infected during five rectal SHIV exposures as were 3/4 controls. MVC treatment was associated with a significant increase in the percentage of CD3(+)/CCR5(+) cells in blood. We show that high and durable MVC concentrations in rectal tissues are not sufficient to prevent SHIV infection in macaques. The increases in CD3(+)/CCR5(+) cells seen during MVC treatment point to unique immunological effects of CCR5 inhibition by MVC. The implications of these immunological effects on PrEP with MVC require further evaluation.

  5. Histopathological observation of immunized rhesus macaques with plague vaccines after subcutaneous infection of Yersinia pestis.

    Directory of Open Access Journals (Sweden)

    Guang Tian

    Full Text Available In our previous study, complete protection was observed in Chinese-origin rhesus macaques immunized with SV1 (20 µg F1 and 10 µg rV270 and SV2 (200 µg F1 and 100 µg rV270 subunit vaccines and with EV76 live attenuated vaccine against subcutaneous challenge with 6×10(6 CFU of Y. pestis. In the present study, we investigated whether the vaccines can effectively protect immunized animals from any pathologic changes using histological and immunohistochemical techniques. In addition, the glomerular basement membranes (GBMs of the immunized animals and control animals were checked by electron microscopy. The results show no signs of histopathological lesions in the lungs, livers, kidneys, lymph nodes, spleens and hearts of the immunized animals at Day 14 after the challenge, whereas pathological alterations were seen in the corresponding tissues of the control animals. Giemsa staining, ultrastructural examination, and immunohistochemical staining revealed bacteria in some of the organs of the control animals, whereas no bacterium was observed among the immunized animals. Ultrastructural observation revealed that no glomerular immune deposits on the GBM. These observations suggest that the vaccines can effectively protect animals from any pathologic changes and eliminate Y. pestis from the immunized animals. The control animals died from multi-organ lesions specifically caused by the Y. pestis infection. We also found that subcutaneous infection of animals with Y. pestis results in bubonic plague, followed by pneumonic and septicemic plagues. The histopathologic features of plague in rhesus macaques closely resemble those of rodent and human plagues. Thus, Chinese-origin rhesus macaques serve as useful models in studying Y. pestis pathogenesis, host response and the efficacy of new medical countermeasures against plague.

  6. Cholinergic control of visual categorisation in macaques

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    Nikolaos C. Aggelopoulos

    2011-11-01

    Full Text Available Acetylcholine (ACh is a neurotransmitter acting via muscarinic and nicotinic receptors that is implicated in several cognitive functions and impairments, such as Alzheimer’s disease. It is believed to especially affect the acquisition of new information, which is particularly important when behaviour needs to be adapted to new situations and to novel sensory events. Categorisation, the process of assigning stimuli to a category, is a cognitive function that also involves information acquisition. The role of ACh on categorisation has not been previously studied. We have examined the effects of scopolamine, an antagonist of muscarinic ACh receptors, on visual categorisation in macaque monkeys using familiar and novel stimuli. When the peripheral effects of scopolamine on the parasympathetic nervous system were controlled for, categorisation performance was disrupted following systemic injections of scopolamine. This impairment was observed only when the stimuli that needed to be categorised had not been seen before. In other words, the monkeys were not impaired by the central action of scopolamine in categorising a set of familiar stimuli (stimuli which they had categorised successfully in previous sessions. Categorisation performance also deteriorated as the stimulus became less salient by an increase in the level of visual noise. However, scopolamine did not cause additional performance disruptions for difficult categorisation judgements at lower coherence levels. Scopolamine, therefore, specifically affects the assignment of new exemplars to established cognitive categories, presumably by impairing the processing of novel information. Since we did not find an effect of scopolamine in the categorisation of familiar stimuli, scopolamine had no significant central action on other cognitive functions such as perception, attention, memory or executive control within the context of our categorisation task.

  7. Tracer-aided modelling to explore non-linearities in flow paths, hydrological connectivity and faecal contamination risk

    Science.gov (United States)

    Neill, A. J.; Tetzlaff, D.; Strachan, N.; Soulsby, C.

    2016-12-01

    The non-linearities of runoff generation processes are strongly influenced by the connectivity of hillslopes and channel networks, particularly where overland flow is an important runoff mechanism. Despite major advances in understanding hydrological connectivity and runoff generation, the role of connectivity in the contamination of potable water supplies by faecal pathogens from grazing animals remains unclear. This is a water quality issue with serious implications for public health. Here, we sought to understand the dynamics of hydrological connectivity, flow paths and linked faecal pathogen transport in a montane catchment in Scotland with high deer populations. We firstly calibrated, within an uncertainty framework, a parsimonious tracer-aided hydrological model to daily discharge and stream isotope data. The model, developed on the basis of past empirical and tracer studies, conceptualises the catchment as three interacting hydrological source areas (dynamic saturation zone, dynamic hillslope, and groundwater) for which water fluxes, water ages and storage-based connectivity can be simulated. We next coupled several faecal indicator organism (FIO; a common indicator of faecal pathogen contamination) behaviour and transport schemes to the robust hydrological models. A further calibration was then undertaken based on the ability of each coupled model to simulate daily FIO concentrations. This gave us a final set of coupled behavioural models from which we explored how in-stream FIO dynamics could be related to the changing connectivity between the three hydrological source areas, flow paths, water ages and consequent dominant runoff generation processes. We found that high levels of FIOs were transient and episodic, and strongly correlated with periods of high connectivity through overland flow. This non-linearity in connectivity and FIO flux was successfully captured within our dynamic, tracer-aided hydrological model.

  8. Asynchronous onset of clinical disease in BSE-infected macaques.

    Science.gov (United States)

    Montag, Judith; Schulz-Schaeffer, Walter; Schrod, Annette; Hunsmann, Gerhard; Motzkus, Dirk

    2013-07-01

    To estimate the effect of the variability of prion disease onset on primary bovine spongiform encephalopathy transmission to humans, we studied 6 cynomolgus macaques. The preclinical incubation period was significantly prolonged in 2 animals, implying that onset of variant Creutzfeldt-Jacob disease in humans could be more diverse than previously expected.

  9. Testosterone Correlates with Venezuelan Equine Encephalitis Virus in Macaques

    Science.gov (United States)

    2006-03-29

    19], and azoosper- mia has been associated with SIV infection in young male rhesus macaques [20]. Depressed androgen levels during physiological...Cytokine Networks in Tissue Immunity Edited by: Meltzer MS, Mantovani A. New York:Wiley-Liss; 1991:77-82. 11. Muehlenbein MP, Bribiescas RG

  10. Spatial Relational Memory in 9-Month-Old Macaque Monkeys

    Science.gov (United States)

    Lavenex, Pierre; Lavenex, Pamela Banta

    2006-01-01

    This experiment assesses spatial and nonspatial relational memory in freely moving 9-mo-old and adult (11-13-yr-old) macaque monkeys ("Macaca mulatta"). We tested the use of proximal landmarks, two different objects placed at the center of an open-field arena, as conditional cues allowing monkeys to predict the location of food rewards hidden in…

  11. Evolutionary and biomedical insights from the rhesus macaque genome

    DEFF Research Database (Denmark)

    Gibbs, Richard A; Rogers, Jeffrey; Katze, Michael G

    2007-01-01

    The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedi...

  12. Foreign aid

    DEFF Research Database (Denmark)

    Tarp, Finn

    2008-01-01

    Foreign aid has evolved significantly since the Second World War in response to a dramatically changing global political and economic context. This article (a) reviews this process and associated trends in the volume and distribution of foreign aid; (b) reviews the goals, principles...

  13. Brand Aid

    DEFF Research Database (Denmark)

    Richey, Lisa Ann; Ponte, Stefano

    A critical account of the rise of celebrity-driven “compassionate consumption” Cofounded by the rock star Bono in 2006, Product RED exemplifies a new trend in celebrity-driven international aid and development, one explicitly linked to commerce, not philanthropy. Brand Aid offers a deeply informed...

  14. The impact of Helicobacter pylori infection on the gastric microbiota of the rhesus macaque.

    Directory of Open Access Journals (Sweden)

    Miriam E Martin

    Full Text Available Helicobacter pylori colonization is highly prevalent among humans and causes significant gastric disease in a subset of those infected. When present, this bacterium dominates the gastric microbiota of humans and induces antimicrobial responses in the host. Since the microbial context of H. pylori colonization influences the disease outcome in a mouse model, we sought to assess the impact of H. pylori challenge upon the pre-existing gastric microbial community members in the rhesus macaque model. Deep sequencing of the bacterial 16S rRNA gene identified a community profile of 221 phylotypes that was distinct from that of the rhesus macaque distal gut and mouth, although there were taxa in common. High proportions of both H. pylori and H. suis were observed in the post-challenge libraries, but at a given time, only one Helicobacter species was dominant. However, the relative abundance of non-Helicobacter taxa was not significantly different before and after challenge with H. pylori. These results suggest that while different gastric species may show competitive exclusion in the gastric niche, the rhesus gastric microbial community is largely stable despite immune and physiological changes due to H. pylori infection.

  15. Alcohol Response and Consumption in Adolescent Rhesus Macaques: Life History and Genetic Influences

    Science.gov (United States)

    Schwandt, Melanie L.; Lindell, Stephen G.; Chen, Scott; Higley, J. Dee; Suomi, Stephen J.; Heilig, Markus; Barr, Christina S.

    2009-01-01

    The use of alcohol by adolescents is a growing problem and has become an important research topic in the etiology of the alcohol use disorders. A key component of this research has been the development of animal models of adolescent alcohol consumption and alcohol response. Due to their extended period of adolescence, rhesus macaques are especially well-suited for modeling alcohol-related phenotypes that contribute to the adolescent propensity for alcohol consumption. In this review, we discuss studies from our laboratory that have investigated both the initial response to acute alcohol administration and the consumption of alcohol in voluntary self-administration paradigms in adolescent rhesus macaques. These studies confirm that adolescence is a time of dynamic change both behaviorally and physiologically, and that alcohol response and alcohol consumption are influenced by life history variables such as age, sex, and adverse early experience in the form of peer-rearing. Furthermore, genetic variants that alter functioning of the serotonin, endogenous opioid, and corticotropin releasing hormone systems are shown to influence both physiological and behavioral outcomes, in some cases interacting with early experience to indicate gene by environment interactions. These findings highlight several of the pathways involved in alcohol response and consumption, namely reward, behavioral dyscontrol, and vulnerability to stress, and demonstrate a role for these pathways during the early stages of alcohol exposure in adolescence. PMID:20113875

  16. Lower respiratory tract infection in cynomolgus macaques (Macaca fascicularis) infected with group A Streptococcus.

    Science.gov (United States)

    Olsen, Randall J; Ashraf, Madiha; Gonulal, Vedia E; Ayeras, Ara A; Cantu, Concepcion; Shea, Patrick R; Carroll, Ronan K; Humbird, Tammy; Greaver, Jamieson L; Swain, Jody L; Chang, Ellen; Ragasa, Willie; Jenkins, Leslie; Lally, Kevin P; Blasdel, Terry; Cagle, Philip; Musser, James M

    2010-12-01

    Group A Streptococcus (GAS), a human-specific pathogen, is best known for causing pharyngitis ("strep-throat") and necrotizing fasciitis ("flesh-eating disease"). However, the organism is also an uncommon but important cause of community-acquired bronchopneumonia, an infection with an exceptionally high mortality rate. Inasmuch as little is known about the molecular pathogenesis of GAS lower respiratory tract infection, we sought to develop a relevant human infection model. Nine cynomolgus macaques were infected by intra-bronchial instillation of either sterile saline or GAS (10(5) or 10(7) CFU). Animals were continuously monitored and sacrificed at five days post-inoculation. Serial bronchial alveolar lavage specimens and tissues collected at necropsy were used for histologic and immunohistochemical examination, quantitative microbial culture, lung and blood biomarker analysis, and in vivo GAS gene expression studies. The lower respiratory tract disease observed in cynomolgus macaques mimicked the clinical and pathological features of severe GAS bronchopneumonia in humans. This new monkey model will be useful for testing hypotheses bearing on the molecular pathogenesis of GAS in the lower respiratory tract.

  17. ThE Alaska Native Tribal Health System Dental Health Aide Therapist as a dentist-centric model.

    Science.gov (United States)

    Williard, Mary

    2012-01-01

    Differences in disease patterns and living circumstances should play no role in the quality of oral health care or in dentists' role in directing this care. Such differences, however, very likely suggest that the delivery model that works in many circumstances may not be best in all. The Alaska Tribal Health System Dental Health Aide Therapist (DHAT) model is one alternative whose potential is being evaluated. These teams are managed by dentists and have several features in common with general practice residency training programs. Alaska dentists supervising DHATs customize their practice protocols based on the skills of the therapists and the needs of the communities served. The emphasis of therapists is on prevention and basic oral health services, leaving the dentists to focus on higher level treatment that better uses the skills for which they have been trained. The characteristics of effective dentist team managers and the economic and social realities of this program are discussed.

  18. Computer-aided process planning in prismatic shape die components based on Standard for the Exchange of Product model data

    Directory of Open Access Journals (Sweden)

    Awais Ahmad Khan

    2015-11-01

    Full Text Available Insufficient technologies made good integration between the die components in design, process planning, and manufacturing impossible in the past few years. Nowadays, the advanced technologies based on Standard for the Exchange of Product model data are making it possible. This article discusses the three main steps for achieving the complete process planning for prismatic parts of the die components. These three steps are data extraction, feature recognition, and process planning. The proposed computer-aided process planning system works as part of an integrated system to cover the process planning of any prismatic part die component. The system is built using Visual Basic with EWDraw system for visualizing the Standard for the Exchange of Product model data file. The system works successfully and can cover any type of sheet metal die components. The case study discussed in this article is taken from a large design of progressive die.

  19. Social rank and cortisol among female rhesus macaques (Macaca mulatta)

    Institute of Scientific and Technical Information of China (English)

    Dong-Dong QIN; Joshua Dominic Rizak; Xiao-Li FENG; Xun-Xun CHU; Shang-Chuan YANG; Chun-Lu LI; Long-Bao LV; Yuan-Ye MA; Xin-Tian HU

    2013-01-01

    In animal societies,some stressful events can lead to higher levels of physiological stress.Such stressors,like social rank,also predict an increased vulnerability to an array of diseases.However,the physiological relationship between social rank and stress varies between different species,as well as within groups of a single species.For example,dominant individuals are more socially stressed at times,while at other times it is the subordinate ones who experience this stress.Together,these variations make it difficult to assess disease vulnerability as connected to social interactions.In order to leam more about how physiological rank relationships vary between groups of a single species,cortisol measurements from hair samples were used to evaluate the effects of dominance rank on long-term stress levels in despotic and less stringent female rhesus macaque hierarchal groups.In despotic groups,cortisol levels were found not to be correlated with social rank,but a negative correlation was found between social rank and cortisol levels in less stringent hierarchies.Low ranking monkeys in less stringent groups secreted elevated levels of cortisol compared to higher ranking animals.These data suggest that variations in the strictness of the dominance hierarchy are determining factors in rank related stress physiology.The further consideration of nonhuman primate social system diversity and the linear degree of their hierarchies may allow for the development of valid rank-related stress models that will help increase our understanding and guide the development of new therapeutics for diseases related to human socioeconomic status.

  20. 基因修饰中国猕猴技术的研究进展%Advances in Genetically Modified Chinese Macaques

    Institute of Scientific and Technical Information of China (English)

    马云瀚; 杨世华

    2014-01-01

    实验动物是人类疾病研究的终身伴侣.由于在遗传进化、生理生化及病理方面与人类接近,猕猴成为不可或缺的实验动物.基因修饰猕猴(或称基因工程猕猴)是从基因和基因调控角度在机体整体发育水平上认识人类生理和病理分子机制的重要实验材料和高等模型动物.目前,高效的猕猴辅助生殖技术(assisted reproductive technologies,ARTs)和精确的基因编辑技术成为研制基因修饰猕猴的唯一途径.在中国猕猴(或恒河猴)的ARTs方面,已经完成了精液采集与冷冻保存、超数排卯、体外受精和胚胎培养、胚胎移植和妊娠管理,高效完成了“试管猴”.在基因编辑技术方面,最近创建了ZFN (zinc-finger nucleases)、TALEN (transcription activator-like effector nucleases)、CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/Cas9)载体,为制作基因修饰猕猴创造了条件.我国已经成功研制了转基因和基因敲除的中国猕猴.随着基因编辑技术的突破和发展,结合我国现有丰富的实验猕猴资源,研究避免猕猴的生殖生理障碍,我国有望成为国际化的、重要的基因修饰猕猴研发和生产基地.%Experimental animals and human disease research are a symbiotic relationship in life science field.Due to the proximity with humans in the aspects of genetic evolution,physiology,biochemistry and pathology,macaque monkeys become indispensable experimental animals in biomedicine research.Genetically modified macaques (also known as genetic engineering macaques) could be important experimental materials and advanced animal models for understanding molecular mechanisms of human physiology and pathology under observation of expression and being regulation of the targeted gene modified in the whole life of animals.Currently,combination of high-efficient assisted reproductive technologies (ARTs) in macaques with precise gene editing technologies is the only way of

  1. Metabolic changes in the visual cortex of binocular blindness macaque monkeys: a proton magnetic resonance spectroscopy study.

    Directory of Open Access Journals (Sweden)

    Lingjie Wu

    Full Text Available PURPOSE: To evaluate proton magnetic resonance spectroscopy ((1H-MRS in a study of cross-modal plasticity in the visual cortex of binocular blindness macaque monkeys. MATERIALS AND METHODS: Four healthy neonatal macaque monkeys were randomly divided into 2 groups, with 2 in each group. Optic nerve transection was performed in both monkeys in the experimental group (group B to obtain binocular blindness. Two healthy macaque monkeys served as a control group (group A. After sixteen months post-procedure, (1H-MRS was performed in the visual cortex of all monkeys. We compared the peak areas of NAA, Cr, Cho, Glx and Ins and the ratios of NAA/Cr, Cho/Cr, Glx/Cr and Ins/Cr of each monkey in group B with group A. RESULTS: The peak area of NAA and the NAA/Cr ratio in the visual cortex of monkey 4 in group B were found to be dramatically decreased, the peak area of NAA slightly decreased and the NAA/Cr ratio clearly decreased in visual cortex of monkey 3 in group B than those in group A. The peak area of Ins and the Ins/Cr ratio in the visual cortex of monkey 4 in group B slightly increased. The peak area of Cho and the Cho/Cr ratio in the visual cortex of all monkeys in group B dramatically increased compared with group A. The peak area of Glx in the visual cortex of all monkeys in group B slightly increased compared with group A. CONCLUSIONS: (1H-MRS could detect biochemical and metabolic changes in the visual cortex and therefore this technique can be used to provide valuable information for investigating the mechanisms of cross-modal plasticity of binocular blindness in a macaque monkey model.

  2. Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques.

    Science.gov (United States)

    Falzarano, Darryl; de Wit, Emmie; Rasmussen, Angela L; Feldmann, Friederike; Okumura, Atsushi; Scott, Dana P; Brining, Doug; Bushmaker, Trenton; Martellaro, Cynthia; Baseler, Laura; Benecke, Arndt G; Katze, Michael G; Munster, Vincent J; Feldmann, Heinz

    2013-10-01

    The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) is of global concern: the virus has caused severe respiratory illness, with 111 confirmed cases and 52 deaths at the time of this article's publication. Therapeutic interventions have not been evaluated in vivo; thus, patient management relies exclusively on supportive care, which, given the high case-fatality rate, is not highly effective. The rhesus macaque is the only known model organism for MERS-CoV infection, developing an acute localized to widespread pneumonia with transient clinical disease that recapitulates mild to moderate human MERS-CoV cases. The combination of interferon-α2b and ribavirin was effective in reducing MERS-CoV replication in vitro; therefore, we initiated this treatment 8 h after inoculation of rhesus macaques. In contrast to untreated, infected macaques, treated animals did not develop breathing abnormalities and showed no or very mild radiographic evidence of pneumonia. Moreover, treated animals showed lower levels of systemic (serum) and local (lung) proinflammatory markers, in addition to fewer viral genome copies, distinct gene expression and less severe histopathological changes in the lungs. Taken together, these data suggest that treatment of MERS-CoV infected rhesus macaques with IFN-α2b and ribavirin reduces virus replication, moderates the host response and improves clinical outcome. As these two drugs are already used in combination in the clinic for other infections, IFN-α2b and ribavirin should be considered for the management of MERS-CoV cases.

  3. Reciprocation and interchange of grooming, agonistic support, feeding tolerance, and aggression in semi-free-ranging Barbary macaques.

    Science.gov (United States)

    Carne, Charlotte; Wiper, Sue; Semple, Stuart

    2011-11-01

    Evidence from a range of primate species indicates that grooming can be exchanged either for itself or for other rank-related "commodities," such as agonistic support, feeding tolerance, or reduced aggression. Patterns of exchange behavior have been found to vary considerably between species, and understanding the causes of this variation is central to the study of the evolution of primate social systems. It is, therefore, essential that exchange behavior is examined in a wide range of species and settings. This article is the first to explore the reciprocation and interchange of grooming in the Barbary macaque (Macaca sylvanus). We collected focal data on semi-free-ranging adult female Barbary macaques at Trentham Monkey Forest, England, and analyzed dyadic data using Generalized Linear Mixed Models. We found evidence for the reciprocal exchange of grooming and for the interchange of grooming for agonistic support and tolerance while feeding. There was no evidence that grooming was traded for a reduction in aggression; indeed, we found a positive relationship between aggression given and grooming received. This may reflect the "extortion" of grooming from subordinates by dominant animals. These results will facilitate comparative analyses of exchange behavior by adding to the current database a new species, characterized by a different social style from those macaque species previously investigated.

  4. Analysis of immunoglobulin, complements and CRP levels in serum of captive northern pig-tailed macaques (Macaca leonina).

    Science.gov (United States)

    Zhang, Xiao-Liang; Pang, Wei; Deng, De-Yao; Lv, Long-Bao; Feng, Yue; Zheng, Yong-Tang

    2014-05-01

    The northern pig-tailed macaque (NPM,Macaca leonina) has become a widely used animal model in biomedical research. In this study, we measured serum immunoglobulin IgG, IgM, IgA, complement C3, C4 and CRP levels in 3-11 year old captive northern pig-tailed macaques using HITACHI 7600-20 automated chemistry analyzer in order to determine the influences of age and gender on these items. The results showed that serum IgA, IgM, C3 and C4 levels were not correlated with age (P>0.05), while serum IgG levels increased progressively with age (r=0.202;P=0.045). Serum IgG, IgA, IgM and C3 levels were higher in females than in males (P<0.05). Moreover, serum C3 concentration was both positively and strongly correlated with that of C4 (r=0.700; P<0.0001). This study provides basic serum immunoglobulin and complement data of captive northern pig-tailed macaques, which may prove useful for future breeding efforts and biomedical research.

  5. Reasoning about geological space: Coupling 3D GeoModels and topological queries as an aid to spatial data selection

    Science.gov (United States)

    Pouliot, Jacynthe; Bédard, Karine; Kirkwood, Donna; Lachance, Bernard

    2008-05-01

    Topological relationships between geological objects are of great interest for mining and petroleum exploration. Indeed, adjacency, inclusion and intersection are common relationships between geological objects such as faults, geological units, fractures, mineralized zones and reservoirs. However, in the context of 3D modeling, actual geometric data models used to store those objects are not designed to manage explicit topological relationships. For example, with Gocad© software, topological analyses are possible but they require a series of successive manipulations and are time consuming. This paper presents the development of a 3D topological query prototype, TQuery, compatible with Gocad© modeling platform. It allows the user to export Gocad© objects to a data storage model that regularizes the topological relationships between objects. The development of TQuery was oriented towards the use of volumetric objects that are composed of tetrahedrons. Exported data are then retrieved and used for 3D topological and spatial queries. One of the advantages of TQuery is that different types of objects can be queried at the same time without restricting the operations to voxel regions. TQuery allows the user to analyze data more quickly and efficiently and does not require a 3D modeling specialist to use it, which is particularly attractive in the context of a decision-making aid. The prototype was tested on a 3D GeoModel of a continental red-bed copper deposit in the Silurian Robitaille Formation (Transfiguration property, Québec, Canada).

  6. Computer Aided Design in Digital Human Modeling for Human Computer Interaction in Ergonomic Assessment: A Review

    Directory of Open Access Journals (Sweden)

    Suman Mukhopadhyay , Sanjib Kumar Das and Tania Chakraborty

    2012-12-01

    Full Text Available Research in Human-Computer Interaction (HCI hasbeen enormously successful in the area of computeraidedergonomics or human-centric designs. Perfectfit for people has always been a target for productdesign. Designers traditionally used anthropometricdimensions for 3D product design which created a lotof fitting problems when dealing with thecomplexities of the human body shapes. Computeraided design (CAD, also known as Computer aideddesign and drafting (CADD is the computertechnology used for the design processing and designdocumentation. CAD has now been used extensivelyin many applications such as automotive,shipbuilding, aerospace industries, architectural andindustrial designs, prosthetics, computer animationfor special effects in movies, advertising andtechnical manuals. As a technology, digital humanmodeling (DHM has rapidly emerged as atechnology that creates, manipulates and controlhuman representations and human-machine systemsscenes on computers for interactive ergonomic designproblem solving. DHM promises to profoundlychange how products or systems are designed, howergonomics analysis is performed, how disorders andimpairments are assessed and how therapies andsurgeries are conducted. The imperative andemerging need for the DHM appears to be consistentwith the fact that the past decade has witnessedsignificant growth in both the software systemsoffering DHM capabilities as well as the corporateadapting the technology.The authors shall dwell atlength and deliberate on how research in DHM hasfinally brought about an enhanced HCI, in thecontext of computer-aided ergonomics or humancentricdesign and discuss about future trends in thiscontext.

  7. Modeling HIV/AIDS drug price determinants in Brazil: is generic competition a myth?

    Science.gov (United States)

    Meiners, Constance; Sagaon-Teyssier, Luis; Hasenclever, Lia; Moatti, Jean-Paul

    2011-01-01

    Brazil became the first developing country to guarantee free and universal access to HIV/AIDS treatment, with antiretroviral drugs (ARVs) being delivered to nearly 190,000 patients. The analysis of ARV price evolution and market dynamics in Brazil can help anticipate issues soon to afflict other developing countries, as the 2010 revision of the World Health Organization guidelines shifts demand towards more expensive treatments, and, at the same time, current evolution of international legislation and trade agreements on intellectual property rights may reduce availability of generic drugs for HIV care. Our analyses are based on effective prices paid for ARV procurement in Brazil between 1996 and 2009. Data panel structure was exploited to gather ex-ante and ex-post information and address various sources of statistical bias. In-difference estimation offered in-depth information on ARV market characteristics which significantly influence prices. Although overall ARV prices follow a declining trend, changing characteristics in the generic segment help explain recent increase in generic ARV prices. Our results show that generic suppliers are more likely to respond to factors influencing demand size and market competition, while originator suppliers tend to set prices strategically to offset compulsory licensing threats and generic competition. In order to guarantee the long term sustainability of access to antiretroviral treatment, our findings highlight the importance of preserving and stimulating generic market dynamics to sustain developing countries' bargaining power in price negotiations undertaken with originator companies.

  8. Modeling HIV/AIDS drug price determinants in Brazil: is generic competition a myth?

    Directory of Open Access Journals (Sweden)

    Constance Meiners

    Full Text Available BACKGROUND: Brazil became the first developing country to guarantee free and universal access to HIV/AIDS treatment, with antiretroviral drugs (ARVs being delivered to nearly 190,000 patients. The analysis of ARV price evolution and market dynamics in Brazil can help anticipate issues soon to afflict other developing countries, as the 2010 revision of the World Health Organization guidelines shifts demand towards more expensive treatments, and, at the same time, current evolution of international legislation and trade agreements on intellectual property rights may reduce availability of generic drugs for HIV care. METHODS AND FINDINGS: Our analyses are based on effective prices paid for ARV procurement in Brazil between 1996 and 2009. Data panel structure was exploited to gather ex-ante and ex-post information and address various sources of statistical bias. In-difference estimation offered in-depth information on ARV market characteristics which significantly influence prices. Although overall ARV prices follow a declining trend, changing characteristics in the generic segment help explain recent increase in generic ARV prices. Our results show that generic suppliers are more likely to respond to factors influencing demand size and market competition, while originator suppliers tend to set prices strategically to offset compulsory licensing threats and generic competition. SIGNIFICANCE: In order to guarantee the long term sustainability of access to antiretroviral treatment, our findings highlight the importance of preserving and stimulating generic market dynamics to sustain developing countries' bargaining power in price negotiations undertaken with originator companies.

  9. Macaques in farms and folklore: exploring the human-nonhuman primate interface in Sulawesi, Indonesia.

    Science.gov (United States)

    Riley, Erin P; Priston, Nancy E C

    2010-09-01

    The island of Sulawesi is an ecologically diverse and anthropogenically complex region in the Indonesian archipelago; it is home to multiple macaque species and a key locus of human-nonhuman primate interconnections. Here, we review the ethnoprimatology of Sulawesi by exploring two primary domains of the human-macaque interface: overlapping resource use and cultural perceptions of macaques. Crop raiding is the primary form of overlapping resource use. While the raiding of cacao plantations predominates in Central and South Sulawesi, subsistence crops (e.g., sweet potato and maize) are most vulnerable on Buton, Southeast Sulawesi. Despite this overlap levels of conflict are generally low, with farmers showing considerable tolerance. This tolerance can be explained by positive perceptions of the macaques despite their crop raiding behavior, and the finding that in some areas macaques figure prominently in local folklore, hence affording them protection. These findings provide some hope for the future management and conservation of these endemic macaques.

  10. A comparative approach to computer aided design model of a dog femur.

    Science.gov (United States)

    Turamanlar, O; Verim, O; Karabulut, A

    2016-01-01

    Computer assisted technologies offer new opportunities in medical imaging and rapid prototyping in biomechanical engineering. Three dimensional (3D) modelling of soft tissues and bones are becoming more important. The accuracy of the analysis in modelling processes depends on the outline of the tissues derived from medical images. The aim of this study is the evaluation of the accuracy of 3D models of a dog femur derived from computed tomography data by using point cloud method and boundary line method on several modelling software. Solidworks, Rapidform and 3DSMax software were used to create 3D models and outcomes were evaluated statistically. The most accurate 3D prototype of the dog femur was created with stereolithography method using rapid prototype device. Furthermore, the linearity of the volumes of models was investigated between software and the constructed models. The difference between the software and real models manifests the sensitivity of the software and the devices used in this manner.

  11. Computational Modeling aided Near Net Shape Manufacturing for Aluminum Alloys Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This program will focus on developing and validating computational models for near-net shape processing of aluminum alloys. Computational models will be developed...