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Sample records for macaque aids model

  1. Stepping toward a Macaque Model of HIV-1 Induced AIDS

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    Jason T. Kimata

    2014-09-01

    Full Text Available HIV-1 exhibits a narrow host range, hindering the development of a robust animal model of pathogenesis. Past studies have demonstrated that the restricted host range of HIV-1 may be largely due to the inability of the virus to antagonize and evade effector molecules of the interferon response in other species. They have also guided the engineering of HIV-1 clones that can replicate in CD4 T-cells of Asian macaque species. However, while replication of these viruses in macaque hosts is persistent, it has been limited and without progression to AIDS. In a new study, Hatziioannou et al., demonstrate for the first time that adapted macaque-tropic HIV-1 can persistently replicate at high levels in pigtailed macaques (Macaca nemestrina, but only if CD8 T-cells are depleted at the time of inoculation. The infection causes rapid disease and recapitulates several aspects of AIDS in humans. Additionally, the virus undergoes genetic changes to further escape innate immunity in association with disease progression. Here, the importance of these findings is discussed, as they relate to pathogenesis and model development.

  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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    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.

  3. Insights into the Impact of CD8+ Immune Modulation on Human Immunodeficiency Virus Evolutionary Dynamics in Distinct Anatomical Compartments by Using Simian Immunodeficiency Virus-Infected Macaque Models of AIDS Progression.

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    Rife Magalis, Brittany; Nolan, David J; Autissier, Patrick; Burdo, Tricia H; Williams, Kenneth C; Salemi, Marco

    2017-12-01

    A thorough understanding of the role of human immunodeficiency virus (HIV) intrahost evolution in AIDS pathogenesis has been limited by the need for longitudinally sampled viral sequences from the vast target space within the host, which are often difficult to obtain from human subjects. CD8 + lymphocyte-depleted macaques infected with simian immunodeficiency virus (SIV) provide an increasingly utilized model of pathogenesis due to clinical manifestations similar to those for HIV-1 infection and AIDS progression, as well as a characteristic rapid disease onset. Comparison of this model with SIV-infected non-CD8 + lymphocyte-depleted macaques also provides a unique opportunity to investigate the role of CD8 + cells in viral evolution and population dynamics throughout the duration of infection. Using several different phylogenetic methods, we analyzed viral gp120 sequences obtained from extensive longitudinal sampling of multiple tissues and enriched leukocyte populations from SIVmac251-infected macaques with or without CD8 + lymphocyte depletion. SIV evolutionary and selection patterns in non-CD8 + lymphocyte-depleted animals were characterized by sequential population turnover and continual viral adaptation, a scenario readily comparable to intrahost evolutionary patterns during human HIV infection in the absence of antiretroviral therapy. Alternatively, animals that were depleted of CD8 + lymphocytes exhibited greater variation in population dynamics among tissues and cell populations over the course of infection. Our findings highlight the major role for CD8 + lymphocytes in prolonging disease progression through continual control of SIV subpopulations from various anatomical compartments and the potential for greater independent viral evolutionary behavior among these compartments in response to immune modulation. IMPORTANCE Although developments in combined antiretroviral therapy (cART) strategies have successfully prolonged the time to AIDS onset in HIV-1

  4. 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

    2009-09-01

    Full Text Available 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.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.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.

  5. 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.

  6. Identification of SIV Nef CD8(+) T cell epitopes restricted by a MHC class I haplotype associated with lower viral loads in a macaque AIDS model.

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    Nomura, Takushi; Yamamoto, Hiroyuki; Takahashi, Naofumi; Naruse, Taeko K; Kimura, Akinori; Matano, Tetsuro

    2014-07-25

    Virus-specific CD8(+) T-cell responses are crucial for the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication. Multiple studies on HIV-infected individuals and SIV-infected macaques have indicated association of several major histocompatibility complex class I (MHC-I) genotypes with lower viral loads and delayed AIDS progression. Understanding of the viral control mechanism associated with these MHC-I genotypes would contribute to the development of intervention strategy for HIV control. We have previously reported a rhesus MHC-I haplotype, 90-120-Ia, associated with lower viral loads after SIVmac239 infection. Gag206-216 and Gag241-249 epitope-specific CD8(+) T-cell responses have been shown to play a central role in the reduction of viral loads, whereas the effect of Nef-specific CD8(+) T-cell responses induced in all the 90-120-Ia(+) macaques on SIV replication remains unknown. Here, we identified three CD8(+) T-cell epitopes, Nef9-19, Nef89-97, and Nef193-203, associated with 90-120-Ia. Nef9-19 and Nef193-203 epitope-specific CD8(+) T-cell responses frequently selected for mutations resulting in viral escape from recognition by these CD8(+) T cells, indicating that these CD8(+) T cells exert strong suppressive pressure on SIV replication. Results would be useful for elucidation of the viral control mechanism associated with 90-120-Ia. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. 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

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

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    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...

  9. 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].

  10. 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.

  11. Function and Innervation of the Locus Ceruleus in a Macaque Model of Functional Hypothalamic Amenorrhea

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

    2012-01-01

    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. Afte...

  12. 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.

  13. An SIV/macaque model targeted to study HIV-associated neurocognitive disorders.

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    Beck, Sarah E; Queen, Suzanne E; Metcalf Pate, Kelly A; Mangus, Lisa M; Abreu, Celina M; Gama, Lucio; Witwer, Kenneth W; Adams, Robert J; Zink, M Christine; Clements, Janice E; Mankowski, Joseph L

    2018-04-01

    Simian immunodeficiency virus (SIV) infection of pigtailed macaques is a highly representative and well-characterized animal model for HIV neuropathogenesis studies that provides an excellent opportunity to study and develop prognostic markers of HIV-associated neurocognitive disorders (HAND) for HIV-infected individuals. SIV studies can be performed in a controlled setting that enhances reproducibility and offers high-translational value. Similar to observations in HIV-infected patients receiving antiretroviral therapy (ART), ongoing neurodegeneration and inflammation are present in SIV-infected pigtailed macaques treated with suppressive ART. By developing quantitative viral outgrowth assays that measure both CD4+ T cells and macrophages harboring replication competent SIV as well as a highly sensitive mouse-based viral outgrowth assay, we have positioned the SIV/pigtailed macaque model to advance our understanding of latent cellular reservoirs, including potential CNS reservoirs, to promote HIV cure. In addition to contributing to our understanding of the pathogenesis of HAND, the SIV/pigtailed macaque model also provides an excellent opportunity to test innovative approaches to eliminate the latent HIV reservoir in the brain.

  14. Strabismus and the Oculomotor System: Insights from Macaque Models

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    Das, Vallabh E.

    2017-01-01

    Disrupting binocular vision in infancy leads to strabismus and oftentimes to a variety of associated visual sensory deficits and oculomotor abnormalities. Investigation of this disorder has been aided by the development of various animal models, each of which has advantages and disadvantages. In comparison to studies of binocular visual responses in cortical structures, investigations of neural oculomotor structures that mediate the misalignment and abnormalities of eye movements have been more recent, and these studies have shown that different brain areas are intimately involved in driving several aspects of the strabismic condition, including horizontal misalignment, dissociated deviations, A and V patterns of strabismus, disconjugate eye movements, nystagmus, and fixation switch. The responses of cells in visual and oculomotor areas that potentially drive the sensory deficits and also eye alignment and eye movement abnormalities follow a general theme of disrupted calibration, lower sensitivity, and poorer specificity compared with the normally developed visual oculomotor system. PMID:28532347

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

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    Elisabetta Monfardini

    Full Text Available 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.

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

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    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

  17. Computer-Aided Modeling Framework

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    Fedorova, Marina; Sin, Gürkan; Gani, Rafiqul

    Models are playing important roles in design and analysis of chemicals based products and the processes that manufacture them. Computer-aided methods and tools have the potential to reduce the number of experiments, which can be expensive and time consuming, and there is a benefit of working...... 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...

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

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    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.

  19. Modeling vocalization with ECoG cortical activity recorded during vocal production in the macaque monkey.

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    Fukushima, Makoto; Saunders, Richard C; Fujii, Naotaka; Averbeck, Bruno B; Mishkin, Mortimer

    2014-01-01

    Vocal production is an example of controlled motor behavior with high temporal precision. Previous studies have decoded auditory evoked cortical activity while monkeys listened to vocalization sounds. On the other hand, there have been few attempts at decoding motor cortical activity during vocal production. Here we recorded cortical activity during vocal production in the macaque with a chronically implanted electrocorticographic (ECoG) electrode array. The array detected robust activity in motor cortex during vocal production. We used a nonlinear dynamical model of the vocal organ to reduce the dimensionality of `Coo' calls produced by the monkey. We then used linear regression to evaluate the information in motor cortical activity for this reduced representation of calls. This simple linear model accounted for circa 65% of the variance in the reduced sound representations, supporting the feasibility of using the dynamical model of the vocal organ for decoding motor cortical activity during vocal production.

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

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    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.

  1. Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques.

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    Borggren, Marie; Vinner, Lasse; Andresen, Betina Skovgaard; Grevstad, Berit; Repits, Johanna; Melchers, Mark; Elvang, Tara Laura; Sanders, Rogier W; Martinon, Frédéric; Dereuddre-Bosquet, Nathalie; Bowles, Emma Joanne; Stewart-Jones, Guillaume; Biswas, Priscilla; Scarlatti, Gabriella; Jansson, Marianne; Heyndrickx, Leo; Grand, Roger Le; Fomsgaard, Anders

    2013-07-19

    HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

  2. Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques

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    Roger Le Grand

    2013-07-01

    Full Text Available HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb. We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

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

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    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.

  4. The Cynomolgus Macaque Natural History Model of Pneumonic Tularemia for Predicting Clinical Efficacy Under the Animal Rule

    Science.gov (United States)

    Guina, Tina; Lanning, Lynda L.; Omland, Kristian S.; Williams, Mark S.; Wolfraim, Larry A.; Heyse, Stephen P.; Houchens, Christopher R.; Sanz, Patrick; Hewitt, Judith A.

    2018-01-01

    Francisella tularensis is a highly infectious Gram-negative bacterium that is the etiologic agent of tularemia in animals and humans and a Tier 1 select agent. The natural incidence of pneumonic tularemia worldwide is very low; therefore, it is not feasible to conduct clinical efficacy testing of tularemia medical countermeasures (MCM) in human populations. Development and licensure of tularemia therapeutics and vaccines need to occur under the Food and Drug Administration's (FDA's) Animal Rule under which efficacy studies are conducted in well-characterized animal models that reflect the pathophysiology of human disease. The Tularemia Animal Model Qualification (AMQ) Working Group is seeking qualification of the cynomolgus macaque (Macaca fascicularis) model of pneumonic tularemia under Drug Development Tools Qualification Programs with the FDA based upon the results of studies described in this manuscript. Analysis of data on survival, average time to death, average time to fever onset, average interval between fever and death, and bacteremia; together with summaries of clinical signs, necropsy findings, and histopathology from the animals exposed to aerosolized F. tularensis Schu S4 in five natural history studies and one antibiotic efficacy study form the basis for the proposed cynomolgus macaque model. Results support the conclusion that signs of pneumonic tularemia in cynomolgus macaques exposed to 300–3,000 colony forming units (cfu) aerosolized F. tularensis Schu S4, under the conditions described herein, and human pneumonic tularemia cases are highly similar. Animal age, weight, and sex of animals challenged with 300–3,000 cfu Schu S4 did not impact fever onset in studies described herein. This study summarizes critical parameters and endpoints of a well-characterized cynomolgus macaque model of pneumonic tularemia and demonstrates this model is appropriate for qualification, and for testing efficacy of tularemia therapeutics under Animal Rule. PMID

  5. Development of a Lethal Intranasal Exposure Model of Ebola Virus in the Cynomolgus Macaque

    Directory of Open Access Journals (Sweden)

    Kendra J. Alfson

    2017-10-01

    Full Text Available Ebola virus (EBOV is a filovirus that can cause Ebola virus disease (EVD. No approved vaccines or therapies exist for filovirus infections, despite an urgent need. The development and testing of effective countermeasures against EBOV requires use of animal models and a thorough understanding of how the model aligns with EVD in humans. The majority of published studies report outcomes of parenteral exposures for emulating needle stick transmission. However, based on data from EVD outbreaks, close contact exposures to infected bodily fluid seems to be one of the primary routes of EBOV transmission. Thus, further work is needed to develop models that represent mucosal exposure. To characterize the outcome of mucosal exposure to EBOV, cynomolgus macaques were exposed to EBOV via intranasal (IN route using the LMA® mucosal atomization device (LMA® MAD. For comparison, four non-human primates (NHPs were exposed to EBOV via intramuscular (IM route. This IN exposure model was uniformly lethal and correlated with a statistically significant delay in time to death when compared to exposure via the IM route. This more closely reflects the timeframes observed in human infections. An IN model of exposure offers an attractive alternative to other models as it can offer insight into the consequences of exposure via a mucosal surface and allows for screening countermeasures via a different exposure route.

  6. 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

  7. In vivo bone strain and finite element modeling of a rhesus macaque mandible during mastication.

    Science.gov (United States)

    Panagiotopoulou, Olga; Iriarte-Diaz, José; Wilshin, Simon; Dechow, Paul C; Taylor, Andrea B; Mehari Abraha, Hyab; Aljunid, Sharifah F; Ross, Callum F

    2017-10-01

    Finite element analysis (FEA) is a commonly used tool in musculoskeletal biomechanics and vertebrate paleontology. The accuracy and precision of finite element models (FEMs) are reliant on accurate data on bone geometry, muscle forces, boundary conditions and tissue material properties. Simplified modeling assumptions, due to lack of in vivo experimental data on material properties and muscle activation patterns, may introduce analytical errors in analyses where quantitative accuracy is critical for obtaining rigorous results. A subject-specific FEM of a rhesus macaque mandible was constructed, loaded and validated using in vivo data from the same animal. In developing the model, we assessed the impact on model behavior of variation in (i) material properties of the mandibular trabecular bone tissue and teeth; (ii) constraints at the temporomandibular joint and bite point; and (iii) the timing of the muscle activity used to estimate the external forces acting on the model. The best match between the FEA simulation and the in vivo experimental data resulted from modeling the trabecular tissue with an isotropic and homogeneous Young's modulus and Poisson's value of 10GPa and 0.3, respectively; constraining translations along X,Y, Z axes in the chewing (left) side temporomandibular joint, the premolars and the m 1 ; constraining the balancing (right) side temporomandibular joint in the anterior-posterior and superior-inferior axes, and using the muscle force estimated at time of maximum strain magnitude in the lower lateral gauge. The relative strain magnitudes in this model were similar to those recorded in vivo for all strain locations. More detailed analyses of mandibular strain patterns during the power stroke at different times in the chewing cycle are needed. Copyright © 2017. Published by Elsevier GmbH.

  8. 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

    , 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...... on Tarlov's scale and our established behavioral tests for monkeys. CONCLUSION: Our findings have indicated that mNSCs can facilitate recovery in contusion SCI models in rhesus macaque monkeys. Additional studies are necessary to determine the im- provement mechanisms after cell transplantation....

  9. 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.

  10. Altered regional homogeneity of brain spontaneous signals in SIV infected rhesus macaque model.

    Science.gov (United States)

    Zhao, Jing; Jing, Bin; Chen, Feng; Liu, Jiaojiao; Wang, Yuanyuan; Li, Hongjun

    2017-04-01

    Regional homogeneity (ReHo), a measurement from resting-state functional magnetic imaging (rs-fMRI) to reflect local synchronization of brain activities, has been widely explored in previous studies of neurological diseases. SIV infected model for detecting the neurological changes with progression was studied. In the study, six rhesus macaques infected by simian immunodeficiency virus (SIV) were scanned by resting-state fMRI at the following time points: before SIV inoculation (baseline), 12weeks and 24weeks post inoculation (12wpi, 24wpi). Meanwhile, the immunological parameters including serum percentage of CD4+ T cell, CD4/CD8 ratio and absolute CD4+ T cell number were measured and analyzed. In comparison of baseline, significant decreased ReHo was found in the left superior frontal gyrus, left superior temporal gyrus, left hippocampus, right precuneus, left angular gyrus, and bilateral occipital gyrus; in contrast increased ReHo in putamen at 12wpi. Moreover, at the time of 24wpi, decreased ReHo was observed in the right postcentral gyrus, left precentral gyrus, posterior cingulated gyrus and thalamus, while ReHo was increased in the left putamen, hippocampus, left anterior cingulated cortex and precentral cortex. The correlation analysis revealed that ReHo in the superior frontal gyrus showed negative association with CD4/CD8 ratio and positive with absolute CD4+ T cell number. The correlation analysis showed that percentage of CD4+ was correlated with the ReHo values in right middle frontal gyrus, bilateral thalamus and amygdala positively; negative relationship with left putamen, left superior frontal gyrus, left superior and middle temporal gyrus. The study first indicates that hippocampus, putamen, frontal and occipital lobe were impaired by using rs-fMRI and correlated with immunological parameters. Thus, ReHo value can be utilized as a noninvasive biomarker of spontaneous brain activity changes caused by the progression of neurological impairments

  11. 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...

  12. 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...... populations. In this study, we have characterized two additional alleles expressed with high frequency in Chinese rhesus macaques, Mamu-A1*02601 and Mamu-B*08301. Upon the development of MHC–peptide-binding assays and definition of their associated motifs, we reveal that these Mamu alleles share peptide...

  13. Development of a rectal sexually transmitted infection (STI) Model in Rhesus macaques using Chlamydia trachomatis serovars E and L2.

    Science.gov (United States)

    Henning, Tara R; Morris, Monica; Ellis, Shanon; Kelley, Kristen; Phillips, Christi; Ritter, Jana; Jones, Tara; Nachamkin, Eli; Chen, Cheng Y; Hong, Jaeyoung; Kang, Joseph; Patton, Dorothy; McNicholl, Janet; Papp, John; Kersh, Ellen N

    2017-10-01

    Rectal STI coinfection models enhance the understanding of rectal HIV transmission risk factors. Rhesus macaques (n=9) were exposed to one of three rectal Chlamydia trachomatis (CT) challenges: C. trachomatis L 2 (CT-L 2 ); C. trachomatis serovar E (CT-E), followed by CT-L 2 ; or CT-E, treatment/clearance, then CT-L 2 . Infections were monitored by PCR. Weekly blood and rectal secretion/lavage samples were collected for cytokine analyzes and/or epithelial sloughing, occult, and overt blood determinations. Chlamydial infections were successfully established in each animal, with varying degrees of persistence. Mucosal IL-1beta was upregulated in animals consecutively infected with CT-E then CT-L 2 (P=.05). Epithelial sloughing was also significantly increased post-infection in this group (P=.0003). This study demonstrates successful rectal infection of rhesus macaques with CT-E and CT-L 2 and describes measures of assessing rectal inflammation and pathology. Different infection strategies yield varying inflammatory and pathologic outcomes, providing well-described models for future SIV/SHIV susceptibility studies. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. 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 the m...

  15. Aiding pest control management of long-tailed macaques (Macaca fascicularis fascicularis) in Malaysia by using molecular markers of mitochondrial DNA

    Science.gov (United States)

    Abdul-Latiff, M. A. B.; Abdul-Patah, P.; Yaakop, S.; Md-Zain, B. M.

    2017-10-01

    The long-tailed macaques (Macaca fascicularis fascicularis) has been the center of human wildlife conflict in Malaysia since 1970s. This well-adapted and opportunistic primates have been dominating wide range of habitat in Malaysia such as primary and secondary forest, mangrove, as well as human settlements. The conventional practices of translocation by the authorities are threatening the uniqueness of gene pool for this species and ironically contradicting with the ultimate purpose of genetic conservation of this species. The objectives of this study is to determine the level of genetic separation between populations of long-tailed macaques, primarily focusing on populations distributed in northern Peninsular Malaysia. A total of 954 base pairs of control regions mtDNA was sequenced and analyzed from 27 samples of M. fascicularis. The results exhibited a highly homogenous state of populations for long-tailed macaques genetically and this ultimately indicate unsuitable management and planning in terms of pest control management of the species. Authorities are suggested to translocate the species at least within the state boundaries to avoid homogeneity of gene pools for the particular species.

  16. A single gp120 residue can affect HIV-1 tropism in macaques.

    Directory of Open Access Journals (Sweden)

    Gregory Q Del Prete

    2017-09-01

    Full Text Available Species-dependent variation in proteins that aid or limit virus replication determines the ability of lentiviruses to jump between host species. Identifying and overcoming these differences facilitates the development of animal models for HIV-1, including models based on chimeric SIVs that express HIV-1 envelope (Env glycoproteins, (SHIVs and simian-tropic HIV-1 (stHIV strains. Here, we demonstrate that the inherently poor ability of most HIV-1 Env proteins to use macaque CD4 as a receptor is improved during adaptation by virus passage in macaques. We identify a single amino acid, A281, in HIV-1 Env that consistently changes during adaptation in macaques and affects the ability of HIV-1 Env to use macaque CD4. Importantly, mutations at A281 do not markedly affect HIV-1 Env neutralization properties. Our findings should facilitate the design of HIV-1 Env proteins for use in non-human primate models and thus expedite the development of clinically relevant reagents for testing interventions against HIV-1.

  17. Clinical and parasitological protection in a Leishmania infantum-macaque model vaccinated with adenovirus and the recombinant A2 antigen.

    Science.gov (United States)

    Grimaldi, Gabriel; Teva, Antonio; Porrozzi, Renato; Pinto, Marcelo A; Marchevsky, Renato S; Rocha, Maria Gabrielle L; Dutra, Miriam S; Bruña-Romero, Oscar; Fernandes, Ana-Paula; Gazzinelli, Ricardo T

    2014-06-01

    Visceral leishmaniasis (VL) is a severe vector-born disease of humans and dogs caused by Leishmania donovani complex parasites. Approximately 0.2 to 0.4 million new human VL cases occur annually worldwide. In the new world, these alarming numbers are primarily due to the impracticality of current control methods based on vector reduction and dog euthanasia. Thus, a prophylactic vaccine appears to be essential for VL control. The current efforts to develop an efficacious vaccine include the use of animal models that are as close to human VL. We have previously reported a L. infantum-macaque infection model that is reliable to determine which vaccine candidates are most worthy for further development. Among the few amastigote antigens tested so far, one of specific interest is the recombinant A2 (rA2) protein that protects against experimental L. infantum infections in mice and dogs. Primates were vaccinated using three rA2-based prime-boost immunization regimes: three doses of rA2 plus recombinant human interleukin-12 (rhIL-12) adsorbed in alum (rA2/rhIL-12/alum); two doses of non-replicative adenovirus recombinant vector encoding A2 (Ad5-A2) followed by two boosts with rA2/rhIL-12/alum (Ad5-A2+rA2/rhIL12/alum); and plasmid DNA encoding A2 gene (DNA-A2) boosted with two doses of Ad5-A2 (DNA-A2+Ad5-A2). Primates received a subsequent infectious challenge with L. infantum. Vaccines, apart from being safe, were immunogenic as animals responded with increased pre-challenge production of anti-A2-specific IgG antibodies, though with some variability in the response, depending on the vaccine formulation/protocol. The relative parasite load in the liver was significantly lower in immunized macaques as compared to controls. Protection correlated with hepatic granuloma resolution, and reduction of clinical symptoms, particularly when primates were vaccinated with the Ad5-A2+rA2/rhIL12/alum protocol. The remarkable clinical protection induced by A2 in an animal model that is

  18. Clinical and parasitological protection in a Leishmania infantum-macaque model vaccinated with adenovirus and the recombinant A2 antigen.

    Directory of Open Access Journals (Sweden)

    Gabriel Grimaldi

    2014-06-01

    Full Text Available BACKGROUND: Visceral leishmaniasis (VL is a severe vector-born disease of humans and dogs caused by Leishmania donovani complex parasites. Approximately 0.2 to 0.4 million new human VL cases occur annually worldwide. In the new world, these alarming numbers are primarily due to the impracticality of current control methods based on vector reduction and dog euthanasia. Thus, a prophylactic vaccine appears to be essential for VL control. The current efforts to develop an efficacious vaccine include the use of animal models that are as close to human VL. We have previously reported a L. infantum-macaque infection model that is reliable to determine which vaccine candidates are most worthy for further development. Among the few amastigote antigens tested so far, one of specific interest is the recombinant A2 (rA2 protein that protects against experimental L. infantum infections in mice and dogs. METHODOLOGY/PRINCIPAL FINDINGS: Primates were vaccinated using three rA2-based prime-boost immunization regimes: three doses of rA2 plus recombinant human interleukin-12 (rhIL-12 adsorbed in alum (rA2/rhIL-12/alum; two doses of non-replicative adenovirus recombinant vector encoding A2 (Ad5-A2 followed by two boosts with rA2/rhIL-12/alum (Ad5-A2+rA2/rhIL12/alum; and plasmid DNA encoding A2 gene (DNA-A2 boosted with two doses of Ad5-A2 (DNA-A2+Ad5-A2. Primates received a subsequent infectious challenge with L. infantum. Vaccines, apart from being safe, were immunogenic as animals responded with increased pre-challenge production of anti-A2-specific IgG antibodies, though with some variability in the response, depending on the vaccine formulation/protocol. The relative parasite load in the liver was significantly lower in immunized macaques as compared to controls. Protection correlated with hepatic granuloma resolution, and reduction of clinical symptoms, particularly when primates were vaccinated with the Ad5-A2+rA2/rhIL12/alum protocol. CONCLUSIONS

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

    Science.gov (United States)

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

    2017-09-01

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

  20. 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.

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

    International Nuclear Information System (INIS)

    Vamathevan, Jessica J.; Hall, Matthew D.; Hasan, Samiul; Woollard, Peter M.; Xu, Meng; Yang, Yulan; Li, Xin; Wang, Xiaoli; Kenny, Steve; Brown, James R.; Huxley-Jones, Julie; Lyon, Jon; Haselden, John; Min, Jiumeng; Sanseau, Philippe

    2013-01-01

    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. 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.

  3. Monyet Ekor Panjang (Macaca fascicularis sebagai Model Diabetes Melitus: Pengaruh Hiperglikemia pada Lipid Darah, Serum Oksida Nitrik, dan Tingkah Laku Klinis (THE LONG TAILED MACAQUE (MACACA FASCICULARIS AS A MODEL OF DIABETES MELITUS : EFFECT OF HYPE

    Directory of Open Access Journals (Sweden)

    Sri Kayati Widyastuti

    2016-08-01

    Full Text Available Monyet Ekor Panjang (Macaca fascicularis sebagai Model Diabetes Melitus: Pengaruh Hiperglikemia pada Lipid Darah, Serum Oksida Nitrik, dan Tingkah Laku Klinis   (THE LONG TAILED MACAQUE (MACACA FASCICULARIS AS A MODEL OF DIABETES MELITUS : EFFECT OF HYPERGLICEMIA ON BLOOD LIPID, SERUM NITRIC OXIDE, AND CLINICAL BEHAVIOUR

  4. The Effect of Short Moderate Stress on the Midbrain CRF System in a Macaque Model of Functional Hypothalamic Amenorrhea

    Science.gov (United States)

    Bethea, Cynthia L; Phu, Kenny; Reddy, Arubala P; Cameron, Judy L

    2014-01-01

    Objective To study the effect of moderate stress on CRF components in the serotonergic midbrain region in a monkey model of FHA. Design After characterization of stress sensitivity, monkeys were moved to a novel room and given 20% less chow for 5 days prior to euthanasia. Setting University of Pittsburgh nonhuman primate facility. Animals Female cynomolgus macaques (Macaca fascicularis) characterized as highly stress resilient (HSR, n=5), medium stress resilient (MSR, N=4) or stress sensitive (SS, n=4). Intervention 5 days of diet in a novel room with unfamiliar conspecifics. Main Outcome Measures Density of CRF axons in the serotonergic dorsal raphe nucleus; the number of UCN1 cells; the density of UCN1 axons; the expression of CRF-R1 and CRF-R2 in the dorsal raphe nucleus. Results CRF innervation was higher in HSR than SS animals; UCN1 cell number was higher in HSR than SS animals and UCN1 axon bouton density was not different, all opposite of non-stressed animals. CRF-R1 was not different between the sensitivity groups, but CRF-R2 was higher in HSR than SS animals. The relative expression of CRF-R1 and R2 was similar to non-stressed animals. Conclusions HSR animals respond to stress with an increase in CRF delivery to serotonin neurons. With stress, UCN1 transport decreases in HSR animals. CRF receptor expression was similar with or without stress. These changes may contribute to resilience in HSR animals. PMID:23849846

  5. 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

  6. 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

    Of the two rhesus macaque subspecies used for AIDS studies, the Simian immunodeficiency virus-infected Indian rhesus macaque (Macaca mulatta) is the most established model of HIV infection, providing both insight into pathogenesis and a system for testing novel vaccines. Despite the Chinese rhesus.......3%) of the sequences identified were novel. From all MHC alleles detected, we prioritized Mamu-A1*02201 for functional characterization based on its higher frequency of expression. Upon the development of MHC/peptide binding assays and definition of its associated motif, we revealed that this allele shares peptide...

  7. 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.

  8. Mitochondrial DNA analyses and ecological niche modeling reveal post-LGM expansion of the Assam macaque (Macaca assamensis) in the foothills of Nepal Himalaya.

    Science.gov (United States)

    Khanal, Laxman; Chalise, Mukesh K; He, Kai; Acharya, Bipin K; Kawamoto, Yoshi; Jiang, Xuelong

    2018-03-01

    Genetic diversity of a species is influenced by multiple factors, including the Quaternary glacial-interglacial cycles and geophysical barriers. Such factors are not yet well documented for fauna from the southern border of the Himalayan region. This study used mitochondrial DNA (mtDNA) sequences and ecological niche modeling (ENM) to explore how the late Pleistocene climatic fluctuations and complex geography of the Himalayan region have shaped genetic diversity, population genetic structure, and demographic history of the Nepalese population of Assam macaques (Macaca assamensis) in the Himalayan foothills. A total of 277 fecal samples were collected from 39 wild troops over almost the entire distribution of the species in Nepal. The mtDNA fragment encompassing the complete control region (1121 bp) was recovered from 208 samples, thus defining 54 haplotypes. Results showed low nucleotide diversity (0.0075 ± SD 0.0001) but high haplotype diversity (0.965 ± SD 0.004). The mtDNA sequences revealed a shallow population genetic structure with a moderate but statistically significant effect of isolation by distance. Demographic history analyses using mtDNA sequences suggested a post-pleistocene population expansion. Paleodistribution reconstruction projected that the potential habitat of the Assam macaque was confined to the lower elevations of central Nepal during the Last Glacial Maximum. With the onset of the Holocene climatic optimum, the glacial refugia population experienced eastward range expansion to higher elevations. We conclude that the low genetic diversity and shallow population genetic structure of the Assam macaque population in the Nepal Himalaya region are the consequence of recent demographic and spatial expansion. © 2018 Wiley Periodicals, Inc.

  9. 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.

  10. 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 ...

  11. Geometric modeling for computer aided design

    Science.gov (United States)

    Schwing, James L.; Olariu, Stephen

    1995-01-01

    The primary goal of this grant has been the design and implementation of software to be used in the conceptual design of aerospace vehicles particularly focused on the elements of geometric design, graphical user interfaces, and the interaction of the multitude of software typically used in this engineering environment. This has resulted in the development of several analysis packages and design studies. These include two major software systems currently used in the conceptual level design of aerospace vehicles. These tools are SMART, the Solid Modeling Aerospace Research Tool, and EASIE, the Environment for Software Integration and Execution. Additional software tools were designed and implemented to address the needs of the engineer working in the conceptual design environment. SMART provides conceptual designers with a rapid prototyping capability and several engineering analysis capabilities. In addition, SMART has a carefully engineered user interface that makes it easy to learn and use. Finally, a number of specialty characteristics have been built into SMART which allow it to be used efficiently as a front end geometry processor for other analysis packages. EASIE provides a set of interactive utilities that simplify the task of building and executing computer aided design systems consisting of diverse, stand-alone, analysis codes. Resulting in a streamlining of the exchange of data between programs reducing errors and improving the efficiency. EASIE provides both a methodology and a collection of software tools to ease the task of coordinating engineering design and analysis codes.

  12. 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

    2010-05-01

    Full Text Available 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.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.In conclusion, oral minocycline alleviates neuronal damage induced by the AIDS virus.

  13. Macaque monkeys can learn token values from human models through vicarious reward.

    Science.gov (United States)

    Bevacqua, Sara; Cerasti, Erika; Falcone, Rossella; Cervelloni, Milena; Brunamonti, Emiliano; Ferraina, Stefano; Genovesio, Aldo

    2013-01-01

    Monkeys can learn the symbolic meaning of tokens, and exchange them to get a reward. Monkeys can also learn the symbolic value of a token by observing conspecifics but it is not clear if they can learn passively by observing other actors, e.g., humans. To answer this question, we tested two monkeys in a token exchange paradigm in three experiments. Monkeys learned token values through observation of human models exchanging them. We used, after a phase of object familiarization, different sets of tokens. One token of each set was rewarded with a bit of apple. Other tokens had zero value (neutral tokens). Each token was presented only in one set. During the observation phase, monkeys watched the human model exchange tokens and watched them consume rewards (vicarious rewards). In the test phase, the monkeys were asked to exchange one of the tokens for food reward. Sets of three tokens were used in the first experiment and sets of two tokens were used in the second and third experiments. The valuable token was presented with different probabilities in the observation phase during the first and second experiments in which the monkeys exchanged the valuable token more frequently than any of the neutral tokens. The third experiments examined the effect of unequal probabilities. Our results support the view that monkeys can learn from non-conspecific actors through vicarious reward, even a symbolic task like the token-exchange task.

  14. Characterization of the rhesus macaque (Macaca mulatta) scrub typhus model: Susceptibility to intradermal challenge with the human pathogen Orientia tsutsugamushi Karp

    Science.gov (United States)

    Sunyakumthorn, Piyanate; Somponpun, Suwit J.; Im-erbsin, Rawiwan; Anantatat, Tippawan; Jenjaroen, Kemajittra; Dunachie, Susanna J.; Lombardini, Eric D.; Burke, Robin L.; Blacksell, Stuart D.; Jones, James W.; Mason, Carl J.; Richards, Allen L.; Day, Nicholas P. J.

    2018-01-01

    Background Scrub typhus is an important endemic disease in tropical Asia caused by Orientia tsutsugamushi for which no effective broadly protective vaccine is available. The successful evaluation of vaccine candidates requires well-characterized animal models and a better understanding of the immune response against O. tsutsugamushi. While many animal species have been used to study host immunity and vaccine responses in scrub typhus, only limited data exists in non-human primate (NHP) models. Methodology/Principle findings In this study we evaluated a NHP scrub typhus disease model based on intradermal inoculation of O. tsutsugamushi Karp strain in rhesus macaques (n = 7). After an intradermal inoculation with 106 murine LD50 of O. tsutsugamushi at the anterior thigh (n = 4) or mock inoculum (n = 3), a series of time course investigations involving hematological, biochemical, molecular and immunological assays were performed, until day 28, when tissues were collected for pathology and immunohistochemistry. In all NHPs with O. tsutsugamushi inoculation, but not with mock inoculation, the development of a classic eschar with central necrosis, regional lymphadenopathy, and elevation of body temperature was observed on days 7–21 post inoculation (pi); bacteremia was detected by qPCR on days 6–18 pi; and alteration of liver enzyme function and increase of white blood cells on day 14 pi. Immune assays demonstrated raised serum levels of soluble cell adhesion molecules, anti-O. tsutsugamushi-specific antibody responses (IgM and IgG) and pathogen-specific cell-mediated immune responses in inoculated macaques. The qPCR assays detected O. tsutsugamushi in eschar, spleen, draining and non-draining lymph nodes, and immuno-double staining demonstrated intracellular O. tsutsugamushi in antigen presenting cells of eschars and lymph nodes. Conclusions/Significance These data show the potential of using rhesus macaques as a scrub typhus model, for evaluation of correlates of

  15. 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.

  16. 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

    OpenAIRE

    Mothé, Bianca R.; Southwood, Scott; Sidney, John; English, A. Michelle; Wriston, Amanda; Hoof, Ilka; Shabanowitz, Jeffrey; Hunt, Donald F.; Sette, Alessandro

    2013-01-01

    Chinese rhesus macaques are of particular interest in SIV/HIV research as these animals have prolonged kinetics of disease progression to AIDS, compared to their Indian counterparts, suggesting that they may be a better model for HIV. Nevertheless, the specific mechanism(s) accounting for these kinetics remains unclear. The study of Major Histocompatibility Complex (MHC) molecules, including their MHC:peptide binding motifs, provides valuable information for measuring cellular immune response...

  17. Modeling Determinants of Discriminatory Attitude towards HIV/AIDS ...

    African Journals Online (AJOL)

    PROF. OLIVER OSUAGWA

    Department of Statistics, University of Ibadan, Nigeria and Department of Statistics, University of ... Keywords: Bayesian inference, binomial, generalized additive mixed model, HIV/AIDS, ... probability sample design was used for selection.

  18. 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.

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

    International Nuclear Information System (INIS)

    Na, Lei; Tang, Yan-Dong; Liu, Jian-Dong; Yu, Chang-Qing; Sun, Liu-Ke; Lin, Yue-Zhi; Wang, Xue-Feng; Wang, Xiaojun; Zhou, Jian-Hua

    2014-01-01

    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

  20. 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

  1. Novel full-length major histocompatibility complex class I allele discovery and haplotype definition in pig-tailed macaques.

    Science.gov (United States)

    Semler, Matthew R; Wiseman, Roger W; Karl, Julie A; Graham, Michael E; Gieger, Samantha M; O'Connor, David H

    2017-11-13

    Pig-tailed macaques (Macaca nemestrina, Mane) are important models for human immunodeficiency virus (HIV) studies. Their infectability with minimally modified HIV makes them a uniquely valuable animal model to mimic human infection with HIV and progression to acquired immunodeficiency syndrome (AIDS). However, variation in the pig-tailed macaque major histocompatibility complex (MHC) and the impact of individual transcripts on the pathogenesis of HIV and other infectious diseases is understudied compared to that of rhesus and cynomolgus macaques. In this study, we used Pacific Biosciences single-molecule real-time circular consensus sequencing to describe full-length MHC class I (MHC-I) transcripts for 194 pig-tailed macaques from three breeding centers. We then used the full-length sequences to infer Mane-A and Mane-B haplotypes containing groups of MHC-I transcripts that co-segregate due to physical linkage. In total, we characterized full-length open reading frames (ORFs) for 313 Mane-A, Mane-B, and Mane-I sequences that defined 86 Mane-A and 106 Mane-B MHC-I haplotypes. Pacific Biosciences technology allows us to resolve these Mane-A and Mane-B haplotypes to the level of synonymous allelic variants. The newly defined haplotypes and transcript sequences containing full-length ORFs provide an important resource for infectious disease researchers as certain MHC haplotypes have been shown to provide exceptional control of simian immunodeficiency virus (SIV) replication and prevention of AIDS-like disease in nonhuman primates. The increased allelic resolution provided by Pacific Biosciences sequencing also benefits transplant research by allowing researchers to more specifically match haplotypes between donors and recipients to the level of nonsynonymous allelic variation, thus reducing the risk of graft-versus-host disease.

  2. A situation-response model for intelligent pilot aiding

    Science.gov (United States)

    Schudy, Robert; Corker, Kevin

    1987-01-01

    An intelligent pilot aiding system needs models of the pilot information processing to provide the computational basis for successful cooperation between the pilot and the aiding system. By combining artificial intelligence concepts with the human information processing model of Rasmussen, an abstraction hierarchy of states of knowledge, processing functions, and shortcuts are developed, which is useful for characterizing the information processing both of the pilot and of the aiding system. This approach is used in the conceptual design of a real time intelligent aiding system for flight crews of transport aircraft. One promising result was the tentative identification of a particular class of information processing shortcuts, from situation characterizations to appropriate responses, as the most important reliable pathway for dealing with complex time critical situations.

  3. 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.

  4. Ancestry, Plasmodium cynomolgi prevalence and rhesus macaque admixture in cynomolgus macaques (Macaca fascicularis) bred for export in Chinese breeding farms.

    Science.gov (United States)

    Zhang, Xinjun; Meng, Yuhuan; Houghton, Paul; Liu, Mingyu; Kanthaswamy, Sreetharan; Oldt, Robert; Ng, Jillian; Trask, Jessica Satkoski; Huang, Ren; Singh, Balbir; Du, Hongli; Smith, David Glenn

    2017-04-01

    Most cynomolgus macaques (Macaca fascicularis) used in the United States as animal models are imported from Chinese breeding farms without documented ancestry. Cynomolgus macaques with varying rhesus macaque ancestry proportions may exhibit differences, such as susceptibility to malaria, that affect their suitability as a research model. DNA of 400 cynomolgus macaques from 10 Chinese breeding farms was genotyped to characterize their regional origin and rhesus ancestry proportion. A nested PCR assay was used to detect Plasmodium cynomolgi infection in sampled individuals. All populations exhibited high levels of genetic heterogeneity and low levels of inbreeding and genetic subdivision. Almost all individuals exhibited an Indochinese origin and a rhesus ancestry proportion of 5%-48%. The incidence of P. cynomolgi infection in cynomolgus macaques is strongly associated with proportion of rhesus ancestry. The varying amount of rhesus ancestry in cynomolgus macaques underscores the importance of monitoring their genetic similarity in malaria research. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Genetic characterization of rhesus macaques (Macaca mulatta) in Nepal.

    Science.gov (United States)

    Kyes, Randall C; Jones-Engel, Lisa; Chalise, Mukesh K; Engel, Gregory; Heidrich, John; Grant, Richard; Bajimaya, Shyam S; McDonough, John; Smith, David Glenn; Ferguson, Betsy

    2006-05-01

    Indian-origin rhesus macaques (Macaca mulatta) have long served as an animal model for the study of human disease and behavior. Given the current shortage of Indian-origin rhesus, many researchers have turned to rhesus macaques from China as a substitute. However, a number of studies have identified marked genetic differences between the Chinese and Indian animals. We investigated the genetic characteristics of a third rhesus population, the rhesus macaques of Nepal. Twenty-one rhesus macaques at the Swoyambhu Temple in Kathmandu, Nepal, were compared with more than 300 Indian- and Chinese-origin rhesus macaques. The sequence analyses of two mitochondrial DNA (mtDNA) loci, from the HVS I and 12 S rRNA regions, showed that the Nepali animals were more similar to Indian-origin than to Chinese-origin animals. The distribution of alleles at 24 short tandem repeat (STR) loci distributed across 17 chromosomes also showed greater similarity between the Nepali and Indian-origin animals. Finally, an analysis of seven major histocompatibility complex (MHC) alleles showed that the Nepali animals expressed Class I alleles that are common to Indian-origin animals, including Mamu-A*01. All of these analyses also revealed a low level of genetic diversity within this Nepali rhesus sample. We conclude that the rhesus macaques of Nepal more closely resemble rhesus macaques of Indian origin than those of Chinese origin. As such, the Nepali rhesus may offer an additional resource option for researchers who wish to maintain research protocols with animals that possess key genetic features characteristic of Indian-origin rhesus macaques. 2005 Wiley-Liss, Inc.

  6. Characterization of 47 MHC class I sequences in Filipino cynomolgus macaques

    Science.gov (United States)

    Campbell, Kevin J.; Detmer, Ann M.; Karl, Julie A.; Wiseman, Roger W.; Blasky, Alex J.; Hughes, Austin L.; Bimber, Benjamin N.; O’Connor, Shelby L.; O’Connor, David H.

    2009-01-01

    Cynomolgus macaques (Macaca fascicularis) provide increasingly common models for infectious disease research. Several geographically distinct populations of these macaques from Southeast Asia and the Indian Ocean island of Mauritius are available for pathogenesis studies. Though host genetics may profoundly impact results of such studies, similarities and differences between populations are often overlooked. In this study we identified 47 full-length MHC class I nucleotide sequences in 16 cynomolgus macaques of Filipino origin. The majority of MHC class I sequences characterized (39 of 47) were unique to this regional population. However, we discovered eight sequences with perfect identity and six sequences with close similarity to previously defined MHC class I sequences from other macaque populations. We identified two ancestral MHC haplotypes that appear to be shared between Filipino and Mauritian cynomolgus macaques, notably a Mafa-B haplotype that has previously been shown to protect Mauritian cynomolgus macaques against challenge with a simian/human immunodeficiency virus, SHIV89.6P. We also identified a Filipino cynomolgus macaque MHC class I sequence for which the predicted protein sequence differs from Mamu-B*17 by a single amino acid. This is important because Mamu-B*17 is strongly associated with protection against simian immunodeficiency virus (SIV) challenge in Indian rhesus macaques. These findings have implications for the evolutionary history of Filipino cynomolgus macaques as well as for the use of this model in SIV/SHIV research protocols. PMID:19107381

  7. Manual lateralization in macaques: handedness, target laterality and task complexity.

    Science.gov (United States)

    Regaiolli, Barbara; Spiezio, Caterina; Vallortigara, Giorgio

    2016-01-01

    Non-human primates represent models to understand the evolution of handedness in humans. Despite several researches have been investigating non-human primates handedness, few studies examined the relationship between target position, hand preference and task complexity. This study aimed at investigating macaque handedness in relation to target laterality and tastiness, as well as task complexity. Seven pig-tailed macaques (Macaca nemestrina) were involved in three different "two alternative choice" tests: one low-level task and two high-level tasks (HLTs). During the first and the third tests macaques could select a preferred food and a non-preferred food, whereas by modifying the design of the second test, macaques were presented with no-difference alternative per trial. Furthermore, a simple-reaching test was administered to assess hand preference in a social context. Macaques showed hand preference at individual level both in simple and complex tasks, but not in the simple-reaching test. Moreover, target position seemed to affect hand preference in retrieving an object in the low-level task, but not in the HLT. Additionally, individual hand preference seemed to be affected from the tastiness of the item to be retrieved. The results suggest that both target laterality and individual motivation might influence hand preference of macaques, especially in simple tasks.

  8. Computer-Aided Multiscale Modelling for Chemical Process Engineering

    DEFF Research Database (Denmark)

    Morales Rodriguez, Ricardo; Gani, Rafiqul

    2007-01-01

    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...

  9. 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...

  10. A Single Amino Acid Change in the Marburg Virus Glycoprotein Arises during Serial Cell Culture Passages and Attenuates the Virus in a Macaque Model of Disease.

    Science.gov (United States)

    Alfson, Kendra J; Avena, Laura E; Delgado, Jenny; Beadles, Michael W; Patterson, Jean L; Carrion, Ricardo; Griffiths, Anthony

    2018-01-01

    Marburg virus (MARV) causes disease with high case fatality rates, and there are no approved vaccines or therapies. Licensing of MARV countermeasures will likely require approval via the FDA's Animal Efficacy Rule, which requires well-characterized animal models that recapitulate human disease. This includes selection of the virus used for exposure and ensuring that it retains the properties of the original isolate. The consequences of amplification of MARV for challenge studies are unknown. Here, we serially passaged and characterized MARV through 13 passes from the original isolate. Surprisingly, the viral genome was very stable, except for a single nucleotide change that resulted in an amino acid substitution in the hydrophobic region of the signal peptide of the glycoprotein (GP). The particle/PFU ratio also decreased following passages, suggesting a role for the amino acid in viral infectivity. To determine if amplification introduces a phenotype in an animal model, cynomolgus macaques were exposed to either 100 or 0.01 PFU of low- and high-passage-number MARV. All animals succumbed when exposed to 100 PFU of either passage 3 or 13 viruses, although animals exposed to the high-passage-number virus survived longer. However, none of the passage 13 MARV-exposed animals succumbed to 0.01-PFU exposure compared to 75% of passage 3-exposed animals. This is consistent with other filovirus studies that show some particles that are unable to yield a plaque in cell culture can cause lethal disease in vivo . These results have important consequences for the design of experiments that investigate MARV pathogenesis and that test the efficacy of MARV countermeasures. IMPORTANCE Marburg virus (MARV) causes disease with a high case fatality rate, and there are no approved vaccines or therapies. Serial amplification of viruses in cell culture often results in accumulation of mutations, but the effect of such cell culture passage on MARV is unclear. Serial passages of MARV

  11. Budget model can aid group practice planning.

    Science.gov (United States)

    Bender, A D

    1991-12-01

    A medical practice can enhance its planning by developing a budgetary model to test effects of planning assumptions on its profitability and cash requirements. A model focusing on patient visits, payment mix, patient mix, and fee and payment schedules can help assess effects of proposed decisions. A planning model is not a substitute for planning but should complement a plan that includes mission, goals, values, strategic issues, and different outcomes.

  12. Models of Human Information Requirements: "When Reasonable Aiding Systems Disagree"

    Science.gov (United States)

    Corker, Kevin; Pisanich, Gregory; Shafto, Michael (Technical Monitor)

    1994-01-01

    Aircraft flight management and Air Traffic Control (ATC) automation are under development to maximize the economy of flight and to increase the capacity of the terminal area airspace while maintaining levels of flight safety equal to or better than current system performance. These goals are being realized by the introduction of flight management automation aiding and operations support systems on the flight deck and by new developments of ATC aiding systems that seek to optimize scheduling of aircraft while potentially reducing required separation and accounting for weather and wake vortex turbulence. Aiding systems on both the flight deck and the ground operate through algorithmic functions on models of the aircraft and of the airspace. These models may differ from each other as a result of variations in their models of the immediate environment. The resultant flight operations or ATC commands may differ in their response requirements (e.g. different preferred descent speeds or descent initiation points). The human operators in the system must then interact with the automation to reconcile differences and resolve conflicts. We have developed a model of human performance including cognitive functions (decision-making, rule-based reasoning, procedural interruption recovery and forgetting) that supports analysis of the information requirements for resolution of flight aiding and ATC conflicts. The model represents multiple individuals in the flight crew and in ATC. The model is supported in simulation on a Silicon Graphics' workstation using Allegro Lisp. Design guidelines for aviation automation aiding systems have been developed using the model's specification of information and team procedural requirements. Empirical data on flight deck operations from full-mission flight simulation are provided to support the model's predictions. The paper describes the model, its development and implementation, the simulation test of the model predictions, and the empirical

  13. 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...

  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. Computer-Aided Modeling of Lipid Processing Technology

    DEFF Research Database (Denmark)

    Diaz Tovar, Carlos Axel

    2011-01-01

    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...... 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...... to develop systematic computer-aided methods (property models) and tools (database) related to the prediction of the necessary physical properties suitable for design and analysis of processes employing lipid technologies. The methods and tools include: the development of a lipid-database (CAPEC...

  16. Computer Aided Multi-Data Fusion Dismount Modeling

    Science.gov (United States)

    2012-03-22

    dependent on a particular environmental condition. They are costly, cumbersome, and involve dedicated software practices and particular knowledge to operate...allow manipulation of 2D matrices, like Microsoft Excel or Libre Office. The second alternative is to modify an already created model (MEM). The model... software . Therefore, with the described computer aided multi-data dismount model the researcher will be able to attach signatures to any desired

  17. 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.

  18. Pharmacokinetics and Preliminary Safety of Pod-Intravaginal Rings Delivering the Monoclonal Antibody VRC01-N for HIV Prophylaxis in a Macaque Model.

    Science.gov (United States)

    Zhao, Chunxia; Gunawardana, Manjula; Villinger, Francois; Baum, Marc M; Remedios-Chan, Mariana; Moench, Thomas R; Zeitlin, Larry; Whaley, Kevin J; Bohorov, Ognian; Smith, Thomas J; Anderson, Deborah J; Moss, John A

    2017-07-01

    The broadly neutralizing antibody (bNAb) VRC01, capable of neutralizing 91% of known human immunodeficiency virus type 1 (HIV-1) isolates in vitro , is a promising candidate microbicide for preventing sexual HIV infection when administered topically to the vagina; however, accessibility to antibody-based prophylactic treatment by target populations in sub-Saharan Africa and other underdeveloped regions may be limited by the high cost of conventionally produced antibodies and the limited capacity to manufacture such antibodies. Intravaginal rings of the pod design (pod-IVRs) delivering Nicotiana -manufactured VRC01 (VRC01-N) over a range of release rates have been developed. The pharmacokinetics and preliminary safety of VRC01-N pod-IVRs were evaluated in a rhesus macaque model. The devices sustained VRC01-N release for up to 21 days at controlled rates, with mean steady-state VRC01-N levels in vaginal fluids in the range of 10 2 to 10 3 μg g -1 being correlated with in vitro release rates. No adverse safety indications were observed. These findings indicate that pod-IVRs are promising devices for the delivery of the candidate topical microbicide VRC01-N against HIV-1 infection and merit further preclinical evaluation. Copyright © 2017 American Society for Microbiology.

  19. The role of the sutures in biomechanical dynamic simulation of a macaque cranial finite element model: Implications for the evolution of craniofacial form

    Science.gov (United States)

    Wang, Qian; Wood, Sarah A.; Grosse, Ian R.; Ross, Callum F.; Zapata, Uriel; Byron, Craig D.; Wright, Barth W.; Strait, David S.

    2012-01-01

    The global biomechanical impact of cranial sutures on the face and cranium during dynamic conditions is not well understood. It is hypothesized that sutures act as energy absorbers protecting skulls subjected to dynamic loads. This hypothesis predicts that sutures have a significant impact on global patterns of strain and cranial structural stiffness when analyzed using dynamic simulations; and that this global impact is influenced by suture material properties. In a finite element model developed from a juvenile Rhesus macaque cranium, five different sets of suture material properties for the zygomaticotemporal sutures were tested. The static and dynamic analyses produced similar results in terms of strain patterns and reaction forces, indicating that the zygomaticotemporal sutures have limited impact on global skull mechanics regardless of loading design. Contrary to the functional hypothesis tested here, the zygomaticotemporal sutures did not absorb significant amounts of energy during dynamic simulations regardless of loading speed. It is alternatively hypothesized that sutures are mechanically significant only insofar as they are weak points on the cranium that must be shielded from unduly high stresses so as not to disrupt vitally important growth processes. Thus, sutural and overall cranial form in some vertebrates may be optimized to minimize or otherwise modulate sutural stress and strain. PMID:22190334

  20. Same-sex attraction: a model to aid nurses' understanding.

    Science.gov (United States)

    Richardson, Brian

    2009-12-01

    Young people attracted to people of their own sex are at risk of bullying and discrimination. It is often difficult for them to find support. Either emotionally or in relation to their health needs. This article explores a model to aid nurses in understanding the process individuals go through before coming to terms with their sexuality. The model also outlines the steps that nurses can take to enhance the care they provide for this vulnerable group of patients and clients.

  1. 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

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

    Science.gov (United States)

    Evers, Ellen; de Vries, Han; Spruijt, Berry M; Sterck, Elisabeth H M

    2016-01-01

    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 primates relying on

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

    Science.gov (United States)

    Evers, Ellen; de Vries, Han; Spruijt, Berry M.

    2016-01-01

    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 primates relying on

  4. 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.

  5. 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.

  6. 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.

  7. Correction of refractive errors in rhesus macaques (Macaca mulatta) involved in visual research.

    Science.gov (United States)

    Mitchell, Jude F; Boisvert, Chantal J; Reuter, Jon D; Reynolds, John H; Leblanc, Mathias

    2014-08-01

    Macaques are the most common animal model for studies in vision research, and due to their high value as research subjects, often continue to participate in studies well into old age. As is true in humans, visual acuity in macaques is susceptible to refractive errors. Here we report a case study in which an aged macaque demonstrated clear impairment in visual acuity according to performance on a demanding behavioral task. Refraction demonstrated bilateral myopia that significantly affected behavioral and visual tasks. Using corrective lenses, we were able to restore visual acuity. After correction of myopia, the macaque's performance on behavioral tasks was comparable to that of a healthy control. We screened 20 other male macaques to assess the incidence of refractive errors and ocular pathologies in a larger population. Hyperopia was the most frequent ametropia but was mild in all cases. A second macaque had mild myopia and astigmatism in one eye. There were no other pathologies observed on ocular examination. We developed a simple behavioral task that visual research laboratories could use to test visual acuity in macaques. The test was reliable and easily learned by the animals in 1 d. This case study stresses the importance of screening macaques involved in visual science for refractive errors and ocular pathologies to ensure the quality of research; we also provide simple methodology for screening visual acuity in these animals.

  8. A multi-criteria optimization model for humanitarian aid distribution

    OpenAIRE

    Vitoriano, Begoña; Ortuño, M. Teresa; Tirado, Gregorio; Montero, Javier

    2011-01-01

    Natural disasters are phenomenons which strike countries all around the world. Sometimes, either by the intensity of the phenomenon or the vulnerability of the country, help is requested from the rest of the world and relief organizations respond by delivering basic aid to those in need. Humanitarian logistics is a critical factor in managing relief operations and, in general, there is a lack of attention on the development of mathematical models and solution algorithms for strategic and tact...

  9. Modeling electric fields in two dimensions using computer aided design

    International Nuclear Information System (INIS)

    Gilmore, D.W.; Giovanetti, D.

    1992-01-01

    The authors describe a method for analyzing static electric fields in two dimensions using AutoCAD. The algorithm is coded in LISP and is modeled after Coloumb's Law. The software platform allows for facile graphical manipulations of field renderings and supports a wide range of hardcopy-output and data-storage formats. More generally, this application is representative of the ability to analyze data that is the solution to known mathematical functions with computer aided design (CAD)

  10. 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

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

    Science.gov (United States)

    Haddow, Andrew D; 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

    2017-08-01

    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.

  12. 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......Modelling is an important enabling technology in modern chemical engineering applications. A template-based approach is presented in this work to facilitate the construction and documentation of the models and enable their maintenance for reuse in a wider application range. Based on a model...

  13. 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.

  14. 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...... use of research done within cognitive science that is the interdisciplinary study of mind and intelligence bringing together various disciplines including Artificial Intelligence, Cognitive Psychology, and Neuroscience. This thesis focuses on three subjects within cognitive science related to hearing...... 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...

  15. The effect of short moderate stress on the midbrain corticotropin-releasing factor system in a macaque model of functional hypothalamic amenorrhea.

    Science.gov (United States)

    Bethea, Cynthia L; Phu, Kenny; Reddy, Arubala P; Cameron, Judy L

    2013-10-01

    To study the effect of moderate stress on corticotropin-releasing factor (CRF) components in the serotonergic midbrain region in a monkey model of functional hypothalamic amenorrhea. After characterization of stress sensitivity, monkeys were moved to a novel room and given 20% less chow for 5 days before euthanasia. Primate research center. Female cynomolgus macaques (Macaca fascicularis) characterized as highly stress resilient (HSR, n = 5), medium stress resilient (n = 4), or stress sensitive (SS, n = 4). Five days of diet in a novel room with unfamiliar conspecifics. Density of CRF axons in the serotonergic dorsal raphe nucleus; the number of urocortin 1 (UCN1) cells; the density of UCN1 axons; the expression of CRF receptor 1 (CRF-R1) and CRF-R2 in the dorsal raphe nucleus. The CRF innervation was higher in HSR than in SS animals; UCN1 cell number was higher in HSR than in SS animals and UCN1 axon bouton density was not different; all opposite of nonstressed animals. The CRF-R1 was not different between the sensitivity groups, but CRF-R2 was higher in HSR than in SS animals. The relative expression of CRF-R1 and CRF-R2 was similar to nonstressed animals. The HSR animals respond to stress with an increase in CRF delivery to serotonin neurons. With stress, UCN1 transport decreases in HSR animals. The CRF receptor expression was similar with or without stress. These changes may contribute to resilience in HSR animals. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  16. 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

    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....... The methodology has been implemented into a computer-aided modeling framework, which combines expert skills, tools, and database connections that are required for the different steps of the model development work-flow with the goal to increase the efficiency of the modeling process. The framework has two main...

  17. 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

  18. 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...

  19. Geometric and computer-aided spline hob modeling

    Science.gov (United States)

    Brailov, I. G.; Myasoedova, T. M.; Panchuk, K. L.; Krysova, I. V.; Rogoza, YU A.

    2018-03-01

    The paper considers acquiring the spline hob geometric model. The objective of the research is the development of a mathematical model of spline hob for spline shaft machining. The structure of the spline hob is described taking into consideration the motion in parameters of the machine tool system of cutting edge positioning and orientation. Computer-aided study is performed with the use of CAD and on the basis of 3D modeling methods. Vector representation of cutting edge geometry is accepted as the principal method of spline hob mathematical model development. The paper defines the correlations described by parametric vector functions representing helical cutting edges designed for spline shaft machining with consideration for helical movement in two dimensions. An application for acquiring the 3D model of spline hob is developed on the basis of AutoLISP for AutoCAD environment. The application presents the opportunity for the use of the acquired model for milling process imitation. An example of evaluation, analytical representation and computer modeling of the proposed geometrical model is reviewed. In the mentioned example, a calculation of key spline hob parameters assuring the capability of hobbing a spline shaft of standard design is performed. The polygonal and solid spline hob 3D models are acquired by the use of imitational computer modeling.

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

    DEFF Research Database (Denmark)

    Fedorova, Marina; Sin, Gürkan; Gani, Rafiqul

    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...

  1. 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. © 2016 Wiley Periodicals, Inc.

  2. Illegal trade in Barbary macaques

    NARCIS (Netherlands)

    van Uhm, Daan|info:eu-repo/dai/nl/380477025

    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

  3. 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.

  4. 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

  5. [Evaluation of national prevention campaigns against AIDS: analysis model].

    Science.gov (United States)

    Hausser, D; Lehmann, P; Dubois, F; Gutzwiller, F

    1987-01-01

    The evaluation of the "Stop-Aids" campaign is based upon a model of behaviour modification (McAlister) which includes the communication theory of McGuire and the social learning theory of Bandura. Using this model, it is possible to define key variables that are used to measure the impact of the campaign. Process evaluation allows identification of multipliers that reinforce and confirm the initial message of prevention (source) thereby encouraging behaviour modifications that are likely to reduce the transmission of HIV (condom use, no sharing of injection material, monogamous relationship, etc.). Twelve studies performed by seven teams in the three linguistic areas contribute to the project. A synthesis of these results will be performed by the IUMSP.

  6. 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,...

  7. Modeling Determinants of Discriminatory Attitude towards HIV/AIDS ...

    African Journals Online (AJOL)

    The Binomial distribution was used to handle the dichotomous nature of the three dependent variables considered. The dependent variables are stigmatization towards relative sick with HIV/AIDS, teacher who has HIV/AIDS but is not sick and a food vendor who has HIV/AIDS. We found that the people who seem to be ...

  8. Occipital White Matter Tracts in Human and Macaque.

    Science.gov (United States)

    Takemura, Hiromasa; Pestilli, Franco; Weiner, Kevin S; Keliris, Georgios A; Landi, Sofia M; Sliwa, Julia; Ye, Frank Q; Barnett, Michael A; Leopold, David A; Freiwald, Winrich A; Logothetis, Nikos K; Wandell, Brian A

    2017-06-01

    We compare several major white-matter tracts in human and macaque occipital lobe using diffusion magnetic resonance imaging. The comparison suggests similarities but also significant differences in the tracts. There are several apparently homologous tracts in the 2 species, including the vertical occipital fasciculus (VOF), optic radiation, forceps major, and inferior longitudinal fasciculus (ILF). There is one large human tract, the inferior fronto-occipital fasciculus, with no corresponding fasciculus in macaque. We could identify the macaque VOF (mVOF), which has been little studied. Its position is consistent with classical invasive anatomical studies by Wernicke. VOF homology is supported by similarity of the endpoints in V3A and ventral V4 across species. The mVOF fibers intertwine with the dorsal segment of the ILF, but the human VOF appears to be lateral to the ILF. These similarities and differences between the occipital lobe tracts will be useful in establishing which circuitry in the macaque can serve as an accurate model for human visual cortex. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. 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.

  10. 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.

  11. 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.

  12. Molecular and functional aspects of menstruation in the macaque.

    Science.gov (United States)

    Brenner, Robert M; Slayden, Ov D

    2012-12-01

    Much of our understanding of the molecular control of menstruation arises from laboratory models that experimentally recapitulate some, but not all, aspects of uterine bleeding observed in women. These models include: in vitro culture of endometrial explants or isolated endometrial cells, transplantation of human endometrial tissue into immunodeficient mice and the induction of endometrial breakdown in appropriately pretreated mice. Each of these models has contributed to our understanding of molecular and cellular mechanisms of menstruation, but nonhuman primates, especially macaques, are the animal model of choice for evaluating therapies for menstrual disorders. In this chapter we review some basic aspects of menstruation, with special emphasis on the macaque model and its relevance to the clinical issues of irregular and heavy menstrual bleeding (HMB).

  13. 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...

  14. 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

  15. 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.

  16. 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.

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

    DEFF Research Database (Denmark)

    Heitzig, Martina; Sin, Gürkan; Glarborg, Peter

    2011-01-01

    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 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...

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  19. Nursing research on a first aid model of double personnel for major burn patients.

    Science.gov (United States)

    Wu, Weiwei; Shi, Kai; Jin, Zhenghua; Liu, Shuang; Cai, Duo; Zhao, Jingchun; Chi, Cheng; Yu, Jiaao

    2015-03-01

    This study explored the effect of a first aid model employing two nurses on the efficient rescue operation time and the efficient resuscitation time for major burn patients. A two-nurse model of first aid was designed for major burn patients. The model includes a division of labor between the first aid nurses and the re-organization of emergency carts. The clinical effectiveness of the process was examined in a retrospective chart review of 156 cases of major burn patients, experiencing shock and low blood volume, who were admitted to the intensive care unit of the department of burn surgery between November 2009 and June 2013. Of the 156 major burn cases, 87 patients who received first aid using the double personnel model were assigned to the test group and the 69 patients who received first aid using the standard first aid model were assigned to the control group. The efficient rescue operation time and the efficient resuscitation time for the patients were compared between the two groups. Student's t tests were used to the compare the mean difference between the groups. Statistically significant differences between the two groups were found on both measures (P's first aid model based on scientifically validated procedures and a reasonable division of labor can shorten the efficient rescue operation time and the efficient resuscitation time for major burn patients. Given these findings, the model appears to be worthy of clinical application.

  20. 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

  1. Ex-vivo α-galactosylceramide activation of NKT cells in humans and macaques.

    Science.gov (United States)

    Fernandez, Caroline S; Cameron, Garth; Godfrey, Dale I; Kent, Stephen J

    2012-08-31

    NKT cells are key mediators of antiviral and anticancer immunity. Experiments in mice have demonstrated that activation of NKT cells in vivo induces the expression of multiple effector molecules critical to successful immunity. Human clinical trials have shown similar responses, although in vivo activation of NKT cells in humans or primate models are far more limited in number and scope. Measuring ex vivo activation of NKT cells by the CD1d-restricted glycolipid ligand α-Galactosylceramide (α-GalCer) through cytokine expression profiles is a useful marker of NKT cell function, but for reasons that are unclear, this approach does not appear to work as well in humans and non-human primate macaque models in comparison to mice. We performed a series of experiments on human and macaque (Macaca nemestrina) fresh whole blood samples to define optimal conditions to detect NKT cell cytokine (TNF, IFNγ, IL-2) and degranulation marker (CD107a) expression by flow cytometry. We found that conditions previously described for mouse splenocyte NKT cell activation were suboptimal on human or macaque blood NKT cells. In contrast, a 6h incubation with brefeldin A added for the last 4h, in a 96-well plate based assay, and using an α-GalCer concentration of 1 μg/ml were optimal methods to stimulate NKT cells in fresh blood from both humans and macaques. Unexpectedly, we noted that blood NKT cells from macaques infected with SIV were more readily activated by α-GalCer than NKT cells from uninfected macaques, suggesting that SIV infection may have primed the NKT cells. In conclusion, we describe optimized methods for the ex vivo antigen-specific activation of human and macaque blood NKT cells. These assays should be useful in monitoring NKT cells in disease and in immunotherapy studies. Copyright © 2012 Elsevier B.V. All rights reserved.

  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

    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

  3. EIA models and capacity building in Viet Nam: an analysis of development aid programs

    International Nuclear Information System (INIS)

    Doberstein, Brent

    2004-01-01

    There has been a decided lack of empirical research examining development aid agencies as 'agents of change' in environmental impact assessment (EIA) systems in developing countries, particularly research examining the model of environmental planning practice promoted by aid agencies as part of capacity building. This paper briefly traces a conceptual framework of EIA, then introduces the concept of 'EIA capacity building'. Using Viet Nam as a case study, the paper then outlines the empirical results of the research, focusing on the extent to which aid agency capacity-building programs promoted a Technical vs. Planning Model of EIA and on the coherence of capacity-building efforts across all aid programs. A discussion follows, where research results are interpreted within the Vietnamese context, and implications of research results are identified for three main groups of actors. The paper concludes by calling for development aid agencies to reconceptualise EIA capacity building as an opportunity to transform developing countries' development planning processes

  4. Population-averaged macaque brain atlas with high-resolution ex vivo DTI integrated into in vivo space.

    Science.gov (United States)

    Feng, Lei; Jeon, Tina; Yu, Qiaowen; Ouyang, Minhui; Peng, Qinmu; Mishra, Virendra; Pletikos, Mihovil; Sestan, Nenad; Miller, Michael I; Mori, Susumu; Hsiao, Steven; Liu, Shuwei; Huang, Hao

    2017-12-01

    Animal models of the rhesus macaque (Macaca mulatta), the most widely used nonhuman primate, have been irreplaceable in neurobiological studies. However, a population-averaged macaque brain diffusion tensor imaging (DTI) atlas, including comprehensive gray and white matter labeling as well as bony and facial landmarks guiding invasive experimental procedures, is not available. The macaque white matter tract pathways and microstructures have been rarely recorded. Here, we established a population-averaged macaque brain atlas with high-resolution ex vivo DTI integrated into in vivo space incorporating bony and facial landmarks, and delineated microstructures and three-dimensional pathways of major white matter tracts in vivo MRI/DTI and ex vivo (postmortem) DTI of ten rhesus macaque brains were acquired. Single-subject macaque brain DTI template was obtained by transforming the postmortem high-resolution DTI data into in vivo space. Ex vivo DTI of ten macaque brains was then averaged in the in vivo single-subject template space to generate population-averaged macaque brain DTI atlas. The white matter tracts were traced with DTI-based tractography. One hundred and eighteen neural structures including all cortical gyri, white matter tracts and subcortical nuclei, were labeled manually on population-averaged DTI-derived maps. The in vivo microstructural metrics of fractional anisotropy, axial, radial and mean diffusivity of the traced white matter tracts were measured. Population-averaged digital atlas integrated into in vivo space can be used to label the experimental macaque brain automatically. Bony and facial landmarks will be available for guiding invasive procedures. The DTI metric measurements offer unique insights into heterogeneous microstructural profiles of different white matter tracts.

  5. A long-acting integrase inhibitor protects female macaques from repeated high-dose intravaginal SHIV challenge.

    Science.gov (United States)

    Andrews, Chasity D; Yueh, Yun Lan; Spreen, William R; St Bernard, Leslie; Boente-Carrera, Mar; Rodriguez, Kristina; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Ford, Susan; Mohri, Hiroshi; Cheng-Mayer, Cecilia; Hong, Zhi; Ho, David D; Markowitz, Martin

    2015-01-14

    Long-acting GSK1265744 (GSK744 LA) is a strand transfer inhibitor of the HIV/SIV (simian immunodeficiency virus) integrase and was shown to be an effective preexposure prophylaxis (PrEP) agent in a low-dose intrarectal SHIV (simian-human immunodeficiency virus) rhesus macaque challenge model. We examined the pharmacokinetics and efficacy of GSK744 LA as PrEP against repeat high-dose intravaginal SHIV challenge in female rhesus macaques treated with Depo-Provera (depot medroxyprogesterone acetate), which promotes viral transmission vaginally. When Depo-Provera-treated female rhesus macaques were dosed with GSK744 LA (50 mg/kg) monthly, systemic and tissue drug concentrations were lower than previously observed in male rhesus macaques. GSK744 concentrations were fivefold lower on average in cervical tissues than in rectal tissues. Eight female rhesus macaques were treated with GSK744 LA at week 0, and four female rhesus macaques served as controls. All animals received a high-dose challenge of SHIV162P3 at week 1. No infection was detected in GSK744 LA-treated rhesus macaques, whereas viremia was detected 1 to 2 weeks after SHIV challenge in all control animals. The GSK744 LA-treated rhesus macaques were given a second administration of drug at week 4 and further challenged at weeks 5 and 7. GSK744 LA treatment protected six of eight female rhesus macaques against three high-dose SHIV challenges, whereas all control animals became infected after the first challenge (P = 0.0003, log-rank test). These results support further clinical development of GSK744 LA for PrEP. Copyright © 2015, American Association for the Advancement of Science.

  6. Using multiple decrement models to estimate risk and morbidity from specific AIDS illnesses. Multicenter AIDS Cohort Study (MACS).

    Science.gov (United States)

    Hoover, D R; Peng, Y; Saah, A J; Detels, R R; Day, R S; Phair, J P

    A simple non-parametric approach is developed to simultaneously estimate net incidence and morbidity time from specific AIDS illnesses in populations at high risk for death from these illnesses and other causes. The disease-death process has four-stages that can be recast as two sandwiching three-state multiple decrement processes. Non-parametric estimation of net incidence and morbidity time with error bounds are achieved from these sandwiching models through modification of methods from Aalen and Greenwood, and bootstrapping. An application to immunosuppressed HIV-1 infected homosexual men reveals that cytomegalovirus disease, Kaposi's sarcoma and Pneumocystis pneumonia are likely to occur and cause significant morbidity time.

  7. 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 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.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.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 PrEP modalities.

  8. Aid Effectiveness

    DEFF Research Database (Denmark)

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

    of the main relationships; (ii) estimating the impact of aid on a range of final and intermediate outcomes; and (iii) quantifying a simplied representation of the full structural form, where aid impacts on growth through key intermediate outcomes. A coherent picture emerges: aid stimulates growth and reduces......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...... poverty through physical capital investment and improvements in health....

  9. Modelling a traditional game as an agent in HIV/AIDS behaviour ...

    African Journals Online (AJOL)

    Modelling a traditional game as an agent in HIV/AIDS behaviour-change education and communication. ... such as traditional games as a means of health communication and agent of behaviour change. ... AJOL African Journals Online.

  10. Towards a Non-Human Primate Model of Alpha-Synucleinopathy for Development of Therapeutics for Parkinson's Disease: Optimization of AAV1/2 Delivery Parameters to Drive Sustained Expression of Alpha Synuclein and Dopaminergic Degeneration in Macaque.

    Directory of Open Access Journals (Sweden)

    James B Koprich

    Full Text Available Recent failures in clinical trials for disease modification in Parkinson's disease have highlighted the need for a non-human primate model of the synucleinopathy underpinning dopaminergic neuron degeneration. The present study was defined to begin the development of such a model in cynomolgus macaque. We have validated surgical and vector parameters to define a means to provide a robust over-expression of alpha-synuclein which is associated with Lewy-like pathology and robust degeneration of the nigrostriatal pathway. Thus, an AAV1/2 vector incorporating strong transcription and transduction regulatory elements was used to deliver the gene for the human A53T mutation of alpha-synuclein. When injected into 4 sites within each substantia nigra (7 μl per site, 1.7 x 1012 gp/ml, this vector provided expression lasting at least 4 months, and a 50% loss of nigral dopaminergic neurons and a 60% reduction in striatal dopamine. Further studies will be required to develop this methodology into a validated model of value as a drug development platform.

  11. A computer-aided framework for development, identification andmanagement of physiologically-based pharmacokinetic models

    DEFF Research Database (Denmark)

    Heitzig, Martina; Linninger, Andreas; Sin, Gürkan

    2014-01-01

    The objective of this work is the development of a generic computer-aided modelling framework to support the development of physiologically-based pharmacokinetic models thereby increasing the efficiency and quality of the modelling process. In particular, the framework systematizes the modelling...

  12. 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.

  13. 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...

  14. Perturbations de l'homéostasie lymphocytaire T chez le macaque rhésus chinois en phase aiguë d'infection par le SIVmac251

    OpenAIRE

    Ponte, Rosalie

    2014-01-01

    As a model to study type 1 human immunodeficiency virus (HIV-1) pathogenesis, rhesus macaques infected with the simian immunodeficiency virus (SIV) are under extensive investigation. Two subspecies of rhesus macaques have been defined, based on a different geographic origin. Indian rhesus macaques exhibit a rapid disease progression and acute infection is characterized by a massive CD4 T-cell loss in the intestinal mucosa. This was associated to the translocation of bacterial products through...

  15. 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....

  16. Monkey business : the illegal trade in Barbary macaques

    NARCIS (Netherlands)

    van Uhm, D.P.|info:eu-repo/dai/nl/380477025

    2016-01-01

    This article focuses on the organization, modus operandi and trade route of the illegal trade in Barbary macaques. The Barbary macaque is the most seized CITES mammal in the EU, accounting for almost 25% of live mammalrelated seizures. It is estimated that as few as 5,000-6,000 Barbary macaques

  17. 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....

  18. Feline immunodeficiency virus model for designing HIV/AIDS vaccines.

    Science.gov (United States)

    Yamamoto, Janet K; Sanou, Missa P; Abbott, Jeffrey R; Coleman, James K

    2010-01-01

    Feline immunodeficiency virus (FIV) discovered in 1986 is a lentivirus that causes AIDS in domestic cats. FIV is classified into five subtypes (A-E), and all subtypes and circulating intersubtype recombinants have been identified throughout the world. A commercial FIV vaccine, consisting of inactivated subtype-A and -D viruses (Fel-O-Vax FIV, Fort Dodge Animal Health), was released in the United States in 2002. The United States Department of Agriculture approved the commercial release of Fel-O-Vax FIV based on two efficacy trials using 105 laboratory cats and a major safety trial performed on 689 pet cats. The prototype and commercial FIV vaccines had broad prophylactic efficacy against global FIV subtypes and circulating intersubtype recombinants. The mechanisms of cross-subtype efficacy are attributed to FIV-specific T-cell immunity. Findings from these studies are being used to define the prophylactic epitopes needed for an HIV-1 vaccine for humans.

  19. 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...

  20. 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. © 2016 Wiley Periodicals, Inc.

  1. Novel multipurpose pod-intravaginal ring for the prevention of HIV, HSV, and unintended pregnancy: Pharmacokinetic evaluation in a macaque model.

    Science.gov (United States)

    Smith, James M; Moss, John A; Srinivasan, Priya; Butkyavichene, Irina; Gunawardana, Manjula; Fanter, Rob; Miller, Christine S; Sanchez, Debbie; Yang, Flora; Ellis, Shanon; Zhang, Jining; Marzinke, Mark A; Hendrix, Craig W; Kapoor, Amita; Baum, Marc M

    2017-01-01

    Globally, women bear an uneven burden for sexual HIV acquisition. Results from two clinical trials evaluating intravaginal rings (IVRs) delivering the antiretroviral agent dapivirine have shown that protection from HIV infection can be achieved with this modality, but high adherence is essential. Multipurpose prevention technologies (MPTs) can potentially increase product adherence by offering protection against multiple vaginally transmitted infections and unintended pregnancy. Here we describe a coitally independent, long-acting pod-IVR MPT that could potentially prevent HIV and HSV infection as well as unintended pregnancy. The pharmacokinetics of MPT pod-IVRs delivering tenofovir alafenamide hemifumarate (TAF2) to prevent HIV, acyclovir (ACV) to prevent HSV, and etonogestrel (ENG) in combination with ethinyl estradiol (EE), FDA-approved hormonal contraceptives, were evaluated in pigtailed macaques (N = 6) over 35 days. Pod IVRs were exchanged at 14 days with the only modification being lower ENG release rates in the second IVR. Plasma progesterone was monitored weekly to determine the effect of ENG/EE on menstrual cycle. The mean in vivo release rates (mg d-1) for the two formulations over 30 days ranged as follows: TAF2 0.35-0.40; ACV 0.56-0.70; EE 0.03-0.08; ENG (high releasing) 0.63; and ENG (low releasing) 0.05. Mean peak progesterone levels were 4.4 ± 1.8 ng mL-1 prior to IVR insertion and 0.075 ± 0.064 ng mL-1 for 5 weeks after insertion, suggesting that systemic EE/ENG levels were sufficient to suppress menstruation. The TAF2 and ACV release rates and resulting vaginal tissue drug concentrations (medians: TFV, 2.4 ng mg-1; ACV, 0.2 ng mg-1) may be sufficient to protect against HIV and HSV infection, respectively. This proof of principle study demonstrates that MPT-pod IVRs could serve as a potent biomedical prevention tool to protect women's sexual and reproductive health and may increase adherence to HIV PrEP even among younger high-risk populations.

  2. Novel multipurpose pod-intravaginal ring for the prevention of HIV, HSV, and unintended pregnancy: Pharmacokinetic evaluation in a macaque model.

    Directory of Open Access Journals (Sweden)

    James M Smith

    Full Text Available Globally, women bear an uneven burden for sexual HIV acquisition. Results from two clinical trials evaluating intravaginal rings (IVRs delivering the antiretroviral agent dapivirine have shown that protection from HIV infection can be achieved with this modality, but high adherence is essential. Multipurpose prevention technologies (MPTs can potentially increase product adherence by offering protection against multiple vaginally transmitted infections and unintended pregnancy. Here we describe a coitally independent, long-acting pod-IVR MPT that could potentially prevent HIV and HSV infection as well as unintended pregnancy. The pharmacokinetics of MPT pod-IVRs delivering tenofovir alafenamide hemifumarate (TAF2 to prevent HIV, acyclovir (ACV to prevent HSV, and etonogestrel (ENG in combination with ethinyl estradiol (EE, FDA-approved hormonal contraceptives, were evaluated in pigtailed macaques (N = 6 over 35 days. Pod IVRs were exchanged at 14 days with the only modification being lower ENG release rates in the second IVR. Plasma progesterone was monitored weekly to determine the effect of ENG/EE on menstrual cycle. The mean in vivo release rates (mg d-1 for the two formulations over 30 days ranged as follows: TAF2 0.35-0.40; ACV 0.56-0.70; EE 0.03-0.08; ENG (high releasing 0.63; and ENG (low releasing 0.05. Mean peak progesterone levels were 4.4 ± 1.8 ng mL-1 prior to IVR insertion and 0.075 ± 0.064 ng mL-1 for 5 weeks after insertion, suggesting that systemic EE/ENG levels were sufficient to suppress menstruation. The TAF2 and ACV release rates and resulting vaginal tissue drug concentrations (medians: TFV, 2.4 ng mg-1; ACV, 0.2 ng mg-1 may be sufficient to protect against HIV and HSV infection, respectively. This proof of principle study demonstrates that MPT-pod IVRs could serve as a potent biomedical prevention tool to protect women's sexual and reproductive health and may increase adherence to HIV PrEP even among younger high

  3. Systematic Methods and Tools for Computer Aided Modelling

    DEFF Research Database (Denmark)

    Fedorova, Marina

    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......-format and COM-objects, are incorporated to allow the export and import of mathematical models; 5) a user interface that provides the work-flow and data-flow to guide the user through the different modelling tasks....

  4. 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.

  5. A comparative study of two communication models in HIV/AIDS coverage in selected Nigerian newspapers.

    Science.gov (United States)

    Okidu, Onjefu

    2013-01-30

    The current overriding thought in HIV/AIDS communication in developing countries is the need for a shift from the cognitive model, which emphasises the decision-making of the individual, to the activity model, which emphasises the context of the individual. In spite of the acknowledged media shift from the cognitive to the activity model in some developing countries, some HIV/AIDS communication scholars have felt otherwise. It was against this background that this study examined the content of some selected Nigerian newspapers to ascertain the attention paid to HIV/AIDS cognitive and activity information. Generally, the study found that Nigerian newspapers had shifted from the cognitive to the activity model of communication in their coverage of HIV/AIDS issues. The findings of the study seem inconsistent with the theoretical argument of some scholars that insufficient attention has been paid by mass media in developing countries to the activity model of HIV/AIDS communication. It is suggested that future research replicate the study for Nigerian and other developing countries' mass media.

  6. 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.

  7. 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.

  8. ROCK-CAD - computer aided geological modelling system

    International Nuclear Information System (INIS)

    Saksa, P.

    1995-12-01

    The study discusses surface and solid modelling methods, their use and interfacing with geodata. Application software named ROCK-CAD suitable for geological bedrock modelling has been developed with support from Teollisuuden Voima Oy (TVO). It has been utilized in the Finnish site characterization programme for spent nuclear fuel waste disposal during the 1980s and 1990s. The system is based on the solid modelling technique. It comprises also rich functionality for the particular geological modelling scheme. The ROCK-CAD system provides, among other things, varying graphical vertical and horizontal intersections and perspective illustrations. The specially developed features are the application of the boundary representation modelling method, parametric object generation language and the discipline approach. The ROCK-CAD system has been utilized in modelling spatial distribution of rock types and fracturing structures in TVO's site characterization. The Olkiluoto site at Eurajoki serves as an example case. The study comprises the description of the modelling process, models and illustration examples. The utilization of bedrock models in site characterization, in tentative repository siting as well as in groundwater flow simulation is depicted. The application software has improved the assessment of the sites studied, given a new basis for the documentation of interpretation and modelling work, substituted hand-drawing and enabled digital transfer to numerical analysis. Finally, aspects of presentation graphics in geological modelling are considered. (84 refs., 30 figs., 11 tabs.)

  9. 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.

  10. 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.

  11. Seroconversion to HCoV-NL63 in Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Lia van der Hoek

    2009-10-01

    Full Text Available HCoV-NL63 is a recently identified respiratory virus. Its pathogenesis has not been fully unraveled because an animal model is currently lacking. Here we examined whether rhesus macaques encounter HCoV-NL63 infections during life, by examining the levels of antibodies to HCoV-NL63 in time. The animals were followed for 7 up till 19 years, and in three animals we observed a steep rise in antibodies during follow up, indicative of a natural infection with HCoV-NL63.

  12. 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…

  13. Model-aided optimization of delta-endotoxin-formation in continuous culture systems

    Energy Technology Data Exchange (ETDEWEB)

    Schulz, V; Schorcht, R; Ignatenko, Yu N; Sakharova, Z V; Khovrychev, M P

    1985-01-01

    A mathematical model of growth, sporulation and delta-endotoxin-formation of bac. thuringiensis is given. The results of model-aided optimization of steady-state continuous culture systems indicate that the productivity in the one-stage system is 1.9% higher and in the two-stage system is 18.5% higher than in the batch process.

  14. 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

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

    DEFF Research Database (Denmark)

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

    2004-01-01

    shapes by a skilled operator. These faceplate planes are aligned to the average shape from the shape model and an average faceplate plane is calculated. Given a surface representation of a new ear canal, the shape model is fitted using a combination of the iterative closest point algorithm and the active...... shape model approach. The average faceplate from the training set can now be placed on the new ear canal using the position of the fitted shape model. A leave-one-out study shows that the algorithm is able to produce results comparable to a human operator....

  16. Phylogeny and History of the Lost SIV from Crab-Eating Macaques: SIVmfa.

    Science.gov (United States)

    McCarthy, Kevin R; Johnson, Welkin E; Kirmaier, Andrea

    2016-01-01

    In the 20th century, thirteen distinct human immunodeficiency viruses emerged following independent cross-species transmission events involving simian immunodeficiency viruses (SIV) from African primates. In the late 1900s, pathogenic SIV strains also emerged in the United Sates among captive Asian macaque species following their unintentional infection with SIV from African sooty mangabeys (SIVsmm). Since their discovery in the 1980s, SIVs from rhesus macaques (SIVmac) and pig-tailed macaques (SIVmne) have become invaluable models for studying HIV pathogenesis, vaccine design and the emergence of viruses. SIV isolates from captive crab-eating macaques (SIVmfa) were initially described but lost prior to any detailed molecular and genetic characterization. In order to infer the origins of the lost SIVmfa lineage, we located archived material and colony records, recovered its genomic sequence by PCR, and assessed its phylogenetic relationship to other SIV strains. We conclude that SIVmfa is the product of two cross-species transmission events. The first was the established transmission of SIVsmm to rhesus macaques, which occurred at the California National Primate Research Center in the late 1960s and the virus later emerged as SIVmac. In a second event, SIVmac was transmitted to crab-eating macaques, likely at the Laboratory for Experimental Medicine and Surgery in Primates in the early 1970s, and it was later spread to the New England Primate Research Center colony in 1973 and eventually isolated in 1986. Our analysis suggests that SIVmac had already emerged by the early 1970s and had begun to diverge into distinct lineages. Furthermore, our findings suggest that pathogenic SIV strains may have been more widely distributed than previously appreciated, raising the possibility that additional isolates may await discovery.

  17. Phylogeny and History of the Lost SIV from Crab-Eating Macaques: SIVmfa.

    Directory of Open Access Journals (Sweden)

    Kevin R McCarthy

    Full Text Available In the 20th century, thirteen distinct human immunodeficiency viruses emerged following independent cross-species transmission events involving simian immunodeficiency viruses (SIV from African primates. In the late 1900s, pathogenic SIV strains also emerged in the United Sates among captive Asian macaque species following their unintentional infection with SIV from African sooty mangabeys (SIVsmm. Since their discovery in the 1980s, SIVs from rhesus macaques (SIVmac and pig-tailed macaques (SIVmne have become invaluable models for studying HIV pathogenesis, vaccine design and the emergence of viruses. SIV isolates from captive crab-eating macaques (SIVmfa were initially described but lost prior to any detailed molecular and genetic characterization. In order to infer the origins of the lost SIVmfa lineage, we located archived material and colony records, recovered its genomic sequence by PCR, and assessed its phylogenetic relationship to other SIV strains. We conclude that SIVmfa is the product of two cross-species transmission events. The first was the established transmission of SIVsmm to rhesus macaques, which occurred at the California National Primate Research Center in the late 1960s and the virus later emerged as SIVmac. In a second event, SIVmac was transmitted to crab-eating macaques, likely at the Laboratory for Experimental Medicine and Surgery in Primates in the early 1970s, and it was later spread to the New England Primate Research Center colony in 1973 and eventually isolated in 1986. Our analysis suggests that SIVmac had already emerged by the early 1970s and had begun to diverge into distinct lineages. Furthermore, our findings suggest that pathogenic SIV strains may have been more widely distributed than previously appreciated, raising the possibility that additional isolates may await discovery.

  18. Modelling physics detectors in a computer aided design system for simulation purposes

    International Nuclear Information System (INIS)

    Ahvenainen, J.; Oksakivi, T.; Vuoskoski, J.

    1995-01-01

    The possibility of transferring physics detector models from computer aided design systems into physics simulation packages like GEANT is receiving increasing attention. The problem of exporting detector models constructed in CAD systems into GEANT is well known. We discuss the problem and describe an application, called DDT, which allows one to design detector models in a CAD system and then transfer the models into GEANT for simulation purposes. (orig.)

  19. 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

  20. Mathematical modeling of ultradeep sequencing data reveals that acute CD8+ T-lymphocyte responses exert strong selective pressure in simian immunodeficiency virus-infected macaques but still fail to clear founder epitope sequences.

    Science.gov (United States)

    Love, Tanzy M T; Thurston, Sally W; Keefer, Michael C; Dewhurst, Stephen; Lee, Ha Youn

    2010-06-01

    The prominent role of antiviral cytotoxic CD8(+) T-lymphocytes (CD8-TL) in containing the acute viremia of human and simian immunodeficiency viruses (HIV-1 and SIV) has rationalized the development of T-cell-based vaccines. However, the presence of escape mutations in the acute stage of infection has raised a concern that accelerated escape from vaccine-induced CD8-TL responses might undermine vaccine efficacy. We reanalyzed previously published data of 101,822 viral genomes of three CD8-TL epitopes, Nef(103-111)RM9 (RM9), Tat(28-35)SL8 (SL8), and Gag(181-189)CM9 (CM9), sampled by ultradeep pyrosequencing from eight macaques. Multiple epitope variants appeared during the resolution of acute viremia, followed by the predominance of a single mutant epitope. By fitting a mathematical model, we estimated the first acute escape rate as 0.36 day(-1) within escape-prone epitopes, RM9 and SL8, and the chronic escape rate as 0.014 day(-1) within the CM9 epitope. Our estimate of SIV acute escape rates was found to be comparable to very early HIV-1 escape rates. The timing of the first escape was more highly correlated with the timing of the peak CD8-TL response than with the magnitude of the CD8-TL response. The transmitted epitope decayed more than 400 times faster during the acute viral decline stage than predicted by a neutral evolution model. However, the founder epitope persisted as a minor population even at the viral set point; in contrast, the majority of acute escape epitopes were completely cleared. Our results suggest that a reservoir of SIV infection is preferentially formed by virus with the transmitted epitope.

  1. A critical period of progesterone withdrawal precedes menstruation in macaques

    Science.gov (United States)

    Slayden, Ov D; Brenner, Robert M

    2006-01-01

    Macaques are menstruating nonhuman primates that provide important animal models for studies of hormonal regulation in the uterus. In women and macaques the decline of progesterone (P) at the end of the cycle triggers endometrial expression of a variety of matrix metalloproteinase (MMP) enzymes that participate in tissue breakdown and menstrual sloughing. To determine the minimal duration of P withdrawal required to induce menses, we assessed the effects of adding P back at various time points after P withdrawal on both frank bleeding patterns and endometrial MMP expression. Artificial menstrual cycles were induced by treating the animals sequentially with implants releasing estradiol (E2) and progesterone (P). To assess bleeding patterns, P implants were removed at the end of a cycle and then added back at 12, 24, 30, 36, 40, 48, 60, or 72 hours (h) after the initial P withdrawal. Observational analysis of frank bleeding patterns showed that P replacement at 12 and 24 h blocked menses, replacement at 36 h reduced menses but replacement after 36 h failed to block menses. These data indicate that in macaques, a critical period of P withdrawal exists and lasts approximately 36 h. In other similarly cycled animals, we withdrew P and then added P back either during (12–24 h) or after (48 h) the critical period, removed the uterus 24 h after P add back and evaluated endometrial MMP expression. Immunocytochemistry showed that replacement of P during the critical period suppressed MMP-1, -2 and -3 expression along with menses, but replacement of P at 48 h, which failed to suppress mense, suppressed MMP-1 and MMP-3 but did not block MMP-2. We concluded that upregulation of MMPs is essential to menses induction, but that after the critical period, menses will occur even if some MMPs are experimentally blocked. PMID:17118170

  2. 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.

  3. Genetic Divergence of the Rhesus Macaque Major Histocompatibility Complex

    Science.gov (United States)

    Daza-Vamenta, Riza; Glusman, Gustavo; Rowen, Lee; Guthrie, Brandon; Geraghty, Daniel E.

    2004-01-01

    The major histocompatibility complex (MHC) is comprised of the class I, class II, and class III regions, including the MHC class I and class II genes that play a primary role in the immune response and serve as an important model in studies of primate evolution. Although nonhuman primates contribute significantly to comparative human studies, relatively little is known about the genetic diversity and genomics underlying nonhuman primate immunity. To address this issue, we sequenced a complete rhesus macaque MHC spanning over 5.3 Mb, and obtained an additional 2.3 Mb from a second haplotype, including class II and portions of class I and class III. A major expansion of from six class I genes in humans to as many as 22 active MHC class I genes in rhesus and levels of sequence divergence some 10-fold higher than a similar human comparison were found, averaging from 2% to 6% throughout extended portions of class I and class II. These data pose new interpretations of the evolutionary constraints operating between MHC diversity and T-cell selection by contrasting with models predicting an optimal number of antigen presenting genes. For the clinical model, these data and derivative genetic tools can be implemented in ongoing genetic and disease studies that involve the rhesus macaque. PMID:15289473

  4. 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)

  5. 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

    . 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 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......-principles models have been investigated with respect to design and operational issues for solution copolymerization reactors in general, and for the methyl methacrylate/vinyl acetate system in particular. The Model 1 is taken from literature and is commonly used for low conversion region, while the Model 2 has...

  6. 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

  7. Personality structure and social style in macaques.

    Science.gov (United States)

    Adams, Mark James; Majolo, Bonaventura; Ostner, Julia; Schülke, Oliver; De Marco, Arianna; Thierry, Bernard; Engelhardt, Antje; Widdig, Anja; Gerald, Melissa S; Weiss, Alexander

    2015-08-01

    Why regularities in personality can be described with particular dimensions is a basic question in differential psychology. Nonhuman primates can also be characterized in terms of personality structure. Comparative approaches can help reveal phylogenetic constraints and social and ecological patterns associated with the presence or absence of specific personality dimensions. We sought to determine how different personality structures are related to interspecific variation in social style. Specifically, we examined this question in 6 different species of macaques, because macaque social style is well characterized and can be categorized on a spectrum of despotic (Grade 1) versus tolerant (Grade 4) social styles. We derived personality structures from adjectival ratings of Japanese (Macaca fuscata; Grade 1), Assamese (M. assamensis; Grade 2), Barbary (M. sylvanus; Grade 3), Tonkean (M. tonkeana; Grade 4), and crested (M. nigra; Grade 4) macaques and compared these species with rhesus macaques (M. mulatta; Grade 1) whose personality was previously characterized. Using a nonparametric method, fuzzy set analysis, to identify commonalities in personality dimensions across species, we found that all but 1 species exhibited consistently defined Friendliness and Openness dimensions, but that similarities in personality dimensions capturing aggression and social competence reflect similarities in social styles. These findings suggest that social and phylogenetic relationships contribute to the origin, maintenance, and diversification of personality. (c) 2015 APA, all rights reserved.

  8. Project Lifescape - The Macaques of India

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 6; Issue 9. Project Lifescape - The Macaques of India. Anindya Sinha. Classroom Volume 6 Issue 9 September 2001 pp 94-105. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/006/09/0094-0105 ...

  9. Computer-aided-engineering system for modeling and analysis of ECLSS integration testing

    Science.gov (United States)

    Sepahban, Sonbol

    1987-01-01

    The accurate modeling and analysis of two-phase fluid networks found in environmental control and life support systems is presently undertaken by computer-aided engineering (CAE) techniques whose generalized fluid dynamics package can solve arbitrary flow networks. The CAE system for integrated test bed modeling and analysis will also furnish interfaces and subsystem/test-article mathematical models. Three-dimensional diagrams of the test bed are generated by the system after performing the requisite simulation and analysis.

  10. Human performance models for computer-aided engineering

    Science.gov (United States)

    Elkind, Jerome I. (Editor); Card, Stuart K. (Editor); Hochberg, Julian (Editor); Huey, Beverly Messick (Editor)

    1989-01-01

    This report discusses a topic important to the field of computational human factors: models of human performance and their use in computer-based engineering facilities for the design of complex systems. It focuses on a particular human factors design problem -- the design of cockpit systems for advanced helicopters -- and on a particular aspect of human performance -- vision and related cognitive functions. By focusing in this way, the authors were able to address the selected topics in some depth and develop findings and recommendations that they believe have application to many other aspects of human performance and to other design domains.

  11. Modelling and Control of HIV/AIDS Propagation - A Case Study of ...

    African Journals Online (AJOL)

    Modelling and Control of HIV/AIDS Propagation - A Case Study of the Ashanti Region of Ghana. ... Open Access DOWNLOAD FULL TEXT ... in the Ashanti Region of Ghana for the period 1982 to 2001 with a view to assessing the level and impact of the pandemic as well as the effectiveness of the existing control measures.

  12. 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

  13. From humanitarianism to good governance? Reflections on a Danish-Ethiopian aid model

    DEFF Research Database (Denmark)

    Wilson, Fiona

    The report reflects on what people engaged in development research and practice mean by 'aid models'. Illustrating the argument is the history of an NGO alliance between Ethiopia and Denmark over the last 10 years. The report argues that 'northern' NGOs are often guilty of imposing new concepts a...

  14. AIDS: An ICT Model for Integrating Teaching, Learning and Research in Technical University Education in Ghana

    Science.gov (United States)

    Asabere, Nana; Togo, Gilbert; Acakpovi, Amevi; Torby, Wisdom; Ampadu, Kwame

    2017-01-01

    Information and Communication Technologies (ICT) has changed the way we communicate and carry out certain daily activities. Globally, ICT has become an essential means for disseminating information. Using Accra Technical University in Ghana as a case study, this paper proposes an ICT model called Awareness Incentives Demand and Support (AIDS). Our…

  15. ATHENA AIDE

    International Nuclear Information System (INIS)

    Fink, R.K.; Callow, R.A.; Larson, T.K.; Ransom, V.H.

    1987-01-01

    An expert system called the ATHENA AIDE that assists in the preparation of input models for the ATHENA thermal-hydraulics code has been developed by researchers at the Idaho National Engineering Laboratory. The ATHENA AIDE uses a menu driven graphics interface and rule-based and object-oriented programming techniques to assist users of the ATHENA code in performing the tasks involved in preparing the card image input files required to run ATHENA calculations. The ATENA AIDE was developed and currently runs on single-user Xerox artificial intelligence workstations. Experience has shown that the intelligent modeling environment provided by the ATHENA AIDE expert system helps ease the modeling task by relieving the analyst of many mundane, repetitive, and error prone procedures involved in the construction of an input model. This reduces errors in the resulting models, helps promote standardized modeling practices, and allows models to be constructed more quickly than was previously possible

  16. Conceptualization of Approaches and Thought Processes Emerging in Validating of Model in Mathematical Modeling in Technology Aided Environment

    Science.gov (United States)

    Hidiroglu, Çaglar Naci; Bukova Güzel, Esra

    2013-01-01

    The aim of the present study is to conceptualize the approaches displayed for validation of model and thought processes provided in mathematical modeling process performed in technology-aided learning environment. The participants of this grounded theory study were nineteen secondary school mathematics student teachers. The data gathered from the…

  17. Model checking as an aid to procedure design

    International Nuclear Information System (INIS)

    Zhang, Wenhu

    2001-01-01

    The OECD Halden Reactor Project has been actively working on computer assisted operating procedures for many years. The objective of the research has been to provide computerised assistance for procedure design, verification and validation, implementation and maintenance. For the verification purpose, the application of formal methods has been considered in several reports. The recent formal verification activity conducted at the Halden Project is based on using model checking to the verification of procedures. This report presents verification approaches based on different model checking techniques and tools for the formalization and verification of operating procedures. Possible problems and relative merits of the different approaches are discussed. A case study of one of the approaches is presented to show the practical application of formal verification. Application of formal verification in the traditional procedure design process can reduce the human resources involved in reviews and simulations, and hence reduce the cost of verification and validation. A discussion of the integration of the formal verification with the traditional procedure design process is given at the end of this report. (Author)

  18. 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

    2011-01-01

    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. PMID:21535929

  19. Skew-t partially linear mixed-effects models for AIDS clinical studies.

    Science.gov (United States)

    Lu, Tao

    2016-01-01

    We propose partially linear mixed-effects models with asymmetry and missingness to investigate the relationship between two biomarkers in clinical studies. The proposed models take into account irregular time effects commonly observed in clinical studies under a semiparametric model framework. In addition, commonly assumed symmetric distributions for model errors are substituted by asymmetric distribution to account for skewness. Further, informative missing data mechanism is accounted for. A Bayesian approach is developed to perform parameter estimation simultaneously. The proposed model and method are applied to an AIDS dataset and comparisons with alternative models are performed.

  20. A critical assessment of theories/models used in health communication for HIV/AIDS.

    Science.gov (United States)

    Airhihenbuwa, C O; Obregon, R

    2000-01-01

    Most theories and models used to develop human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) communication are based on social psychology that emphasizes individualism. Researchers including communication and health scholars are now questioning the presumed global relevance of these models and thus the need to develop innovative theories and models that take into account regional contexts. In this paper, we discuss the commonly used theories and models in HIV/AIDS communication. Furthermore, we argue that the flaws in the application of the commonly used "classical" models in health communication are because of contextual differences in locations where these models are applied. That is to say that these theories and models are being applied in contexts for which they were not designed. For example, the differences in health behaviors are often the function of culture. Therefore, culture should be viewed for its strength and not always as a barrier. The metaphorical coupling of "culture" and "barrier" needs to be exposed, deconstructed, and reconstructed so that new, positive, cultural linkages can be forged. The HIV/AIDS pandemic has served as a flashpoint to either highlight the importance or deny the relevance of theories and models while at the same time addressing the importance of culture in the development and implementation of communication programs.

  1. 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.

  2. 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

    environments given a specific type of hearing aids. Based on this observation, a feedback path model that consists of an invariant model and a variant model is proposed. A common-acoustical-pole and zero model-based approach and an iterative least-square search-based approach are used to extract the invariant...... model from a set of impulse responses of the feedback paths. A hybrid approach combining the two methods is also proposed. The general properties of the three methods are studied using artificial datasets, and the methods are cross-validated using the measured feedback paths. The results show...

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

    Science.gov (United States)

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

    2017-03-27

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

  4. 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.

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

    International Nuclear Information System (INIS)

    Kim, Hyeong Gyun

    2016-01-01

    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. Young macaques (Macaca fascicularis) preferentially bias attention towards closer, older, and better tool users.

    Science.gov (United States)

    Tan, Amanda W Y; Hemelrijk, Charlotte K; Malaivijitnond, Suchinda; Gumert, Michael D

    2018-05-12

    Examining how animals direct social learning during skill acquisition under natural conditions, generates data for examining hypotheses regarding how transmission biases influence cultural change in animal populations. We studied a population of macaques on Koram Island, Thailand, and examined model-based biases during interactions by unskilled individuals with tool-using group members. We first compared the prevalence of interactions (watching, obtaining food, object exploration) and proximity to tool users during interactions, in developing individuals (infants, juveniles) versus mature non-learners (adolescents, adults), to provide evidence that developing individuals are actively seeking information about tool use from social partners. All infants and juveniles, but only 49% of mature individuals carried out interacted with tool users. Macaques predominantly obtained food by scrounging or stealing, suggesting maximizing scrounging opportunities motivates interactions with tool users. However, while interactions by adults was limited to obtaining food, young macaques and particularly infants also watched tool users and explored objects, indicating additional interest in tool use itself. We then ran matrix correlations to identify interaction biases, and what attributes of tool users influenced these. Biases correlated with social affiliation, but macaques also preferentially targeted tool users that potentially increase scrounging and learning opportunities. Results suggest that social structure may constrain social learning, but the motivation to bias interactions towards tool users to maximize feeding opportunities may also socially modulate learning by facilitating close proximity to better tool users, and further interest in tool-use actions and materials, especially during development.

  7. Design of a physical model of the PBMR with the aid of Flownet

    International Nuclear Information System (INIS)

    Greyvenstein, G.P.; Rousseau, P.G.

    2002-01-01

    The design of a physical model of the PBMR with the aid of the code Flownet is discussed in this paper. The purpose of the physical model is to test the control strategies and operating procedures of the PBMR and also to demonstrate the accuracy of Flownet. Flownet is first used to do component matching and to determine the detail steady-state performance of the system. It is then demonstrated how the code was used to simulate the start-up procedure as well as a load following and a load rejection scenario. The study demonstrates how a micro model of the PBMR can be designed with the aid of a powerful simulation tool in a relatively short period of time and at low cost using commercially available turbochargers. (author)

  8. Expression, purification, crystallization and preliminary X-ray diffraction analysis of rhesus macaque CD8αα homodimer

    International Nuclear Information System (INIS)

    Zong, Lili; Chen, Yong; Yan, Jinghua; Zhang, Jianhua

    2010-01-01

    CD8α exodomain protein, a crucial immune-system factor in rhesus macaque (M. mulatta), one of the best animal models for vaccine design, was assembled and crystallized. The full structure data will contribute to future studies of immune responses in rhesus macaques. As a T-cell co-receptor, CD8 binds to MHC class I molecules and plays a pivotal role in the activation of cytotoxic T lymphocytes. To date, structures of CD8 have been solved for two different mammals: human and mouse. The infection of rhesus macaques (Macaca mulatta) by simian immunodeficiency virus (SIV) is the best animal model for studying HIV. In this study, the rhesus macaque CD8 (rCD8) αα homodimer was obtained and rCD8α exodomain protein crystals were successfully obtained for further structural analysis. Diffraction data were collected to a resolution of 2.4 Å. The crystal belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 46.52, b = 56.28, c = 82.40 Å. These data will facilitate further studies on the structural differences between these CD8 structures and the cellular immune responses of rhesus macaque

  9. 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

  10. Beneficial effect of hot spring bathing on stress levels in Japanese macaques.

    Science.gov (United States)

    Takeshita, Rafaela S C; Bercovitch, Fred B; Kinoshita, Kodzue; Huffman, Michael A

    2018-05-01

    The ability of animals to survive dramatic climates depends on their physiology, morphology and behaviour, but is often influenced by the configuration of their habitat. Along with autonomic responses, thermoregulatory behaviours, including postural adjustments, social aggregation, and use of trees for shelter, help individuals maintain homeostasis across climate variations. Japanese macaques (Macaca fuscata) are the world's most northerly species of nonhuman primates and have adapted to extremely cold environments. Given that thermoregulatory stress can increase glucocorticoid concentrations in primates, we hypothesized that by using an available hot spring, Japanese macaques could gain protection against weather-induced cold stress during winter. We studied 12 adult female Japanese macaques living in Jigokudani Monkey Park, Japan, during the spring birth season (April to June) and winter mating season (October to December). We collected faecal samples for determination of faecal glucocorticoid (fGC) metabolite concentrations by enzyme immunoassay, as well as behavioural data to determine time spent in the hot springs, dominance rank, aggression rates, and affiliative behaviours. We used nonparametric statistics to examine seasonal changes in hot spring bathing, and the relationship between rank and air temperature on hot spring bathing. We used general linear mixed-effect models to examine factors impacting hormone concentrations. We found that Japanese macaques use hot spring bathing for thermoregulation during the winter. In the studied troop, the single hot spring is a restricted resource favoured by dominant females. High social rank had both costs and benefits: dominant females sustained high fGC levels, which were associated with high aggression rates in winter, but benefited by priority of access to the hot spring, which was associated with low fGC concentrations and therefore might help reduce energy expenditure and subsequent body heat loss. This unique

  11. Efficient generation of monoclonal antibodies from single rhesus macaque antibody secreting cells.

    Science.gov (United States)

    Meng, Weixu; Li, Leike; Xiong, Wei; Fan, Xuejun; Deng, Hui; Bett, Andrew J; Chen, Zhifeng; Tang, Aimin; Cox, Kara S; Joyce, Joseph G; Freed, Daniel C; Thoryk, Elizabeth; Fu, Tong-Ming; Casimiro, Danilo R; Zhang, Ningyan; A Vora, Kalpit; An, Zhiqiang

    2015-01-01

    Nonhuman primates (NHPs) are used as a preclinical model for vaccine development, and the antibody profiles to experimental vaccines in NHPs can provide critical information for both vaccine design and translation to clinical efficacy. However, an efficient protocol for generating monoclonal antibodies from single antibody secreting cells of NHPs is currently lacking. In this study we established a robust protocol for cloning immunoglobulin (IG) variable domain genes from single rhesus macaque (Macaca mulatta) antibody secreting cells. A sorting strategy was developed using a panel of molecular markers (CD3, CD19, CD20, surface IgG, intracellular IgG, CD27, Ki67 and CD38) to identify the kinetics of B cell response after vaccination. Specific primers for the rhesus macaque IG genes were designed and validated using cDNA isolated from macaque peripheral blood mononuclear cells. Cloning efficiency was averaged at 90% for variable heavy (VH) and light (VL) domains, and 78.5% of the clones (n = 335) were matched VH and VL pairs. Sequence analysis revealed that diverse IGHV subgroups (for VH) and IGKV and IGLV subgroups (for VL) were represented in the cloned antibodies. The protocol was tested in a study using an experimental dengue vaccine candidate. About 26.6% of the monoclonal antibodies cloned from the vaccinated rhesus macaques react with the dengue vaccine antigens. These results validate the protocol for cloning monoclonal antibodies in response to vaccination from single macaque antibody secreting cells, which have general applicability for determining monoclonal antibody profiles in response to other immunogens or vaccine studies of interest in NHPs.

  12. Cabotegravir long acting injection protects macaques against intravenous challenge with SIVmac251.

    Science.gov (United States)

    Andrews, Chasity D; Bernard, Leslie St; Poon, Amanda Yee; Mohri, Hiroshi; Gettie, Natanya; Spreen, William R; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Hong, Zhi; Ho, David D; Markowitz, Martin

    2017-02-20

    We evaluated the effectiveness of cabotegravir (CAB; GSK1265744 or GSK744) long acting as preexposure prophylaxis (PrEP) against intravenous simian immunodeficiency virus (SIV) challenge in a model that mimics blood transfusions based on the per-act probability of infection. CAB long acting is an integrase strand transfer inhibitor formulated as a 200 mg/ml injectable nanoparticle suspension that is an effective PrEP agent against rectal and vaginal simian/human immunodeficiency virus transmission in macaques. Three groups of rhesus macaques (n = 8 per group) were injected intramuscularly with CAB long acting and challenged intravenously with 17 animal infectious dose 50% SIVmac251 on week 2. Group 1 was injected with 50 mg/kg on week 0 and 4 to evaluate the protective efficacy of the CAB long-acting dose used in macaque studies mimicking sexual transmission. Group 2 was injected with 50 mg/kg on week 0 to evaluate the necessity of the second injection of CAB long acting for protection against intravenous challenge. Group 3 was injected with 25 mg/kg on week 0 and 50 mg/kg on week 4 to correlate CAB plasma concentrations at the time of challenge with protection. Five additional macaques remained untreated as controls. CAB long acting was highly protective with 21 of the 24 CAB long-acting-treated macaques remaining aviremic, resulting in 88% protection. The plasma CAB concentration at the time of virus challenge appeared to be more important for protection than sustaining therapeutic plasma concentrations with the second CAB long acting injection. These results support the clinical investigation of CAB long acting as PrEP in people who inject drugs.

  13. 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.

  14. 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.

  15. 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.......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...

  16. 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 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....

  17. 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.

  18. 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.

  19. Sensitivity analysis of the parameters of an HIV/AIDS model with condom campaign and antiretroviral therapy

    Science.gov (United States)

    Marsudi, Hidayat, Noor; Wibowo, Ratno Bagus Edy

    2017-12-01

    In this article, we present a deterministic model for the transmission dynamics of HIV/AIDS in which condom campaign and antiretroviral therapy are both important for the disease management. We calculate the effective reproduction number using the next generation matrix method and investigate the local and global stability of the disease-free equilibrium of the model. Sensitivity analysis of the effective reproduction number with respect to the model parameters were carried out. Our result shows that efficacy rate of condom campaign, transmission rate for contact with the asymptomatic infective, progression rate from the asymptomatic infective to the pre-AIDS infective, transmission rate for contact with the pre-AIDS infective, ARV therapy rate, proportion of the susceptible receiving condom campaign and proportion of the pre-AIDS receiving ARV therapy are highly sensitive parameters that effect the transmission dynamics of HIV/AIDS infection.

  20. Scaling up depot medroxyprogesterone acetate (DMPA): a systematic literature review illustrating the AIDED model.

    Science.gov (United States)

    Curry, Leslie; Taylor, Lauren; Pallas, Sarah Wood; Cherlin, Emily; Pérez-Escamilla, Rafael; Bradley, Elizabeth H

    2013-08-02

    Use of depot medroxyprogesterone acetate (DMPA), often known by the brand name Depo-Provera, has increased globally, particularly in multiple low- and middle-income countries (LMICs). As a reproductive health technology that has scaled up in diverse contexts, DMPA is an exemplar product innovation with which to illustrate the utility of the AIDED model for scaling up family health innovations. We conducted a systematic review of the enabling factors and barriers to scaling up DMPA use in LMICs. We searched 11 electronic databases for academic literature published through January 2013 (n = 284 articles), and grey literature from major health organizations. We applied exclusion criteria to identify relevant articles from peer-reviewed (n = 10) and grey literature (n = 9), extracting data on scale up of DMPA in 13 countries. We then mapped the resulting factors to the five AIDED model components: ASSESS, INNOVATE, DEVELOP, ENGAGE, and DEVOLVE. The final sample of sources included studies representing variation in geographies and methodologies. We identified 15 enabling factors and 10 barriers to dissemination, diffusion, scale up, and/or sustainability of DMPA use. The greatest number of factors were mapped to the ASSESS, DEVELOP, and ENGAGE components. Findings offer early empirical support for the AIDED model, and provide insights into scale up of DMPA that may be relevant for other family planning product innovations.

  1. Comparison of Peer and Self-Video Modeling in Teaching First Aid Skills to Children with Intellectual Disability

    Science.gov (United States)

    Ozkan, Serife Yucesoy

    2013-01-01

    The purposes of this study were to (1) compare peer and self-video modeling in terms of effectiveness and efficiency in teaching first aid skills to children with intellectual disability and (2) analyze the error patterns made in probe sessions to determine whether the children who took the role of sufferers during the first aid skill sessions…

  2. Directed coupling in local field potentials of macaque V4 during visual short-term memory revealed by multivariate autoregressive models

    Directory of Open Access Journals (Sweden)

    Gregor M Hoerzer

    2010-05-01

    Full Text Available Processing and storage of sensory information is based on the interaction between different neural populations rather than the isolated activity of single neurons. In order to characterize the dynamic interaction and transient cooperation of sub-circuits within a neural network, multivariate autoregressive (MVAR models have proven to be an important analysis tool. In this study, we apply directed functional coupling based on MVAR models and describe the temporal and spatial changes of functional coupling between simultaneously recorded local field potentials (LFP in extrastriate area V4 during visual memory. Specifically, we compare the strength and directional relations of coupling based on Generalized Partial Directed Coherence (GDPC measures while two rhesus monkeys perform a visual short-term memory task. In both monkeys we find increases in theta power during the memory period that are accompanied by changes in directed coupling. These interactions are most prominent in the low frequency range encompassing the theta band (3-12~Hz and, more importantly, are asymmetric between pairs of recording sites. Furthermore, we find that the degree of interaction decreases as a function of distance between electrode positions, suggesting that these interactions are a predominantly local phenomenon. Taken together, our results show that directed coupling measures based on MVAR models are able to provide important insights into the spatial and temporal formation of local functionally coupled ensembles during visual memory in V4. Moreover, our findings suggest that visual memory is accompanied not only by a temporary increase of oscillatory activity in the theta band, but by a direction-dependent change in theta coupling, which ultimately represents a change in functional connectivity within the neural circuit.

  3. Computer-aided and predictive models for design of controlled release of pesticides

    DEFF Research Database (Denmark)

    Suné, Nuria Muro; Gani, Rafiqul

    2004-01-01

    In the field of pesticide controlled release technology, a computer based model that can predict the delivery of the Active Ingredient (AI) from fabricated units is important for purposes of product design and marketing. A model for the release of an M from a microcapsule device is presented...... in this paper, together with a specific case study application to highlight its scope and significance. The paper also addresses the need for predictive models and proposes a computer aided modelling framework for achieving it through the development and introduction of reliable and predictive constitutive...... models. A group-contribution based model for one of the constitutive variables (AI solubility in polymers) is presented together with examples of application and validation....

  4. Systemic model for the aid for operating of the reactor Siloe

    International Nuclear Information System (INIS)

    Royer, J.C.; Moulin, V.; Monge, F.

    1995-01-01

    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

  5. 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...

  6. Bayesian conditional-independence modeling of the AIDS epidemic in England and Wales

    Science.gov (United States)

    Gilks, Walter R.; De Angelis, Daniela; Day, Nicholas E.

    We describe the use of conditional-independence modeling, Bayesian inference and Markov chain Monte Carlo, to model and project the HIV-AIDS epidemic in homosexual/bisexual males in England and Wales. Complexity in this analysis arises through selectively missing data, indirectly observed underlying processes, and measurement error. Our emphasis is on presentation and discussion of the concepts, not on the technicalities of this analysis, which can be found elsewhere [D. De Angelis, W.R. Gilks, N.E. Day, Bayesian projection of the the acquired immune deficiency syndrome epidemic (with discussion), Applied Statistics, in press].

  7. Isolation of a monoclonal antibody from a phage display library binding the rhesus macaque MHC class I allomorph Mamu-A1*001.

    Directory of Open Access Journals (Sweden)

    Nathan Holman

    Full Text Available Monoclonal antibodies that bind to human leukocyte antigen (HLA are useful tools for HLA-typing, tracking donor-recipient chimerisms after bone marrow transplants, and characterizing specific major histocompatibility complexes (MHC on cell surfaces. Unfortunately, equivalent reagents are not available for rhesus macaques, which are commonly used animal as models in organ transplant and infectious disease research. To address this deficiency, we isolated an antibody that recognizes the common Indian rhesus macaque MHC class I molecule, Mamu-A1*001. We induced Mamu-A1*001-binding antibodies by alloimmunizing a female Mamu-A1*001-negative rhesus macaque with peripheral blood mononuclear cells (PBMC from a male Mamu-A1*001-positive donor. A Fab phage display library was constructed with PBMC from the alloimmunized macaque and panned to isolate an antibody that binds to Mamu-A1*001 but not to other common rhesus macaque MHC class I molecules. The isolated antibody distinguishes PBMC from Mamu-A1*001-positive and -negative macaques. Additionally, the Mamu-A1*001-specific antibody binds the cynomolgus macaque MHC class I ortholog Mafa-A1*001:01 but not variants Mafa-A1*001:02/03, indicating a high degree of binding specificity. The Mamu-A1*001-specific antibody will be useful for identifying Mamu-A1*001-positive rhesus macaques, for detecting Mamu-A1*001-positive cells in populations of Mamu-A1*001-negative cells, and for examining disease processes that alter expression of Mamu-A1*001 on cell surfaces. Moreover, the alloimmunization process we describe will be useful for isolating additional MHC allomorph-specific monoclonal antibodies or antibodies against other polymorphic host proteins which are difficult to isolate with traditional technologies.

  8. 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

  9. Computer-aided-design-model-assisted absolute three-dimensional shape measurement.

    Science.gov (United States)

    Li, Beiwen; Bell, Tyler; Zhang, Song

    2017-08-20

    Conventional three-dimensional (3D) shape measurement methods are typically generic to all types of objects. Yet, for many measurement conditions, such a level of generality is inessential when having the preknowledge of the object geometry. This paper introduces a novel adaptive algorithm for absolute 3D shape measurement with the assistance of the object computer-aided-design (CAD) model. The proposed algorithm includes the following major steps: (1) export the 3D point cloud data from the CAD model; (2) transform the CAD model into the camera perspective; (3) obtain a wrapped phase map from three phase-shifted fringe images; and (4) retrieve absolute phase and 3D geometry assisted by the CAD model. We demonstrate that if object CAD models are available, such an algorithm is efficient in recovering absolute 3D geometries of both simple and complex objects with only three phase-shifted fringe images.

  10. 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.

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

    International Nuclear Information System (INIS)

    Feng, Youjun; Qi, Jianxun; Zhang, Huimin; Wang, Jinzi; Liu, Jinhua; Jiang, Fan; Gao, Feng

    2005-01-01

    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 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

  12. 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.

  13. Discovery of a secular trend in Cayo Santiago macaque reproduction.

    Science.gov (United States)

    Hernández-Pacheco, Raisa; Rawlins, Richard G; Kessler, Matthew J; Delgado, Diana L; Ruiz-Lambides, Angelina V; Sabat, Alberto M

    2016-02-01

    Reproductive synchrony and the consequent clustering of births are hypothesized to be regulated by seasonal changes in rainfall and food availability. Such climate-related seasonality is, however, questionable in tropical populations occupying temporally invariant habitats year round. Using the long-term data of the Cayo Santiago rhesus macaques from 1973 to 2013, this study distinguishes synchrony (a greater than chance clustering of births) from seasonality (a cluster of births during a period of the year when abiotic conditions are favorable) and shows that females are highly synchronized (>72% of births in a 3-month period) but the effects of environmental zeitgebers on reproduction are overridden by biological factors. Specifically, biotic and abiotic factors including (i) loss of immature offspring; (ii) population density; (iii) age at delivery; (iv) rainfall; and (v) changes in colony management were modeled in relation to the annual onset of births and the median birth date. Females experiencing loss of immature offspring had an interbirth interval of trend in both the onset of births and the median date of birth is documented and the model predicts that the median birth date will advance across all calendar-based seasons by 2050. The secular trend in reproduction appears to be triggered by changes in the age at delivery of females, the absence of physiological constraints from maternal investment due to offspring loss, shorter interbirth interval, and a higher degree of coordination due to increasing population density. This study challenges the reproductive phenology previously described for rhesus macaques highlighting the importance of long-term studies in addressing the ultimate causes of reproductive synchrony. © 2015 Wiley Periodicals, Inc.

  14. 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

    Directory of Open Access Journals (Sweden)

    Fei Yin

    2017-06-01

    Full Text Available 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. Keywords: Human papillomavirus, HPV 16/18/58, GMTs, Trivalent, Immunogenicity

  15. Teaching Basic First-Aid Skills against Home Accidents to Children with Autism through Video Modeling

    Science.gov (United States)

    Ergenekon, Yasemin

    2012-01-01

    It is known that children with DD can learn first-aid skills and use whenever needed. Applying first-aid skills was taught to three inclusion students with autism through "first-aid skills training package". In the study multiple probe design with probe trials across behaviors was used. The findings indicated that first-aid skills…

  16. Altered response hierarchy and increased T-cell breadth upon HIV-1 conserved element DNA vaccination in macaques.

    Directory of Open Access Journals (Sweden)

    Viraj Kulkarni

    Full Text Available HIV sequence diversity and potential decoy epitopes are hurdles in the development of an effective AIDS vaccine. A DNA vaccine candidate comprising of highly conserved p24(gag elements (CE induced robust immunity in all 10 vaccinated macaques, whereas full-length gag DNA vaccination elicited responses to these conserved elements in only 5 of 11 animals, targeting fewer CE per animal. Importantly, boosting CE-primed macaques with DNA expressing full-length p55(gag increased both magnitude of CE responses and breadth of Gag immunity, demonstrating alteration of the hierarchy of epitope recognition in the presence of pre-existing CE-specific responses. Inclusion of a conserved element immunogen provides a novel and effective strategy to broaden responses against highly diverse pathogens by avoiding decoy epitopes, while focusing responses to critical viral elements for which few escape pathways exist.

  17. Computed tomography or necropsy diagnosis of multiple bullae and the treatment of pneumothorax in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Kim, Jong-Min; Han, Sungyoung; Shin, Jun-Seop; Min, Byoung-Hoon; Jeong, Won Young; Lee, Ga Eul; Kim, Min Sun; Kim, Ju Eun; Chung, Hyunwoo; Park, Chung-Gyu

    2017-10-01

    Pulmonary bullae and pneumothorax have various etiologies in veterinary medicine. We diagnosed multiple pulmonary bullae combined with or without pneumothorax by computed tomography (CT) or necropsy in seven rhesus macaques (Macaca mulatta) imported from China. Two of seven rhesus macaques accompanied by pneumothorax were cured by fixation of ruptured lung through left or right 3rd intercostal thoracotomy. Pneumonyssus simicola, one of the etiologies of pulmonary bullae, was not detected from tracheobronchiolar lavage. To the best of our knowledge, this is the first case report on the CT-aided diagnosis of pulmonary bullae and the successful treatment of combined pneumothorax by thoracotomy in non-human primates (NHPs). © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Assessment of RANS and LES Turbulence Modeling for Buoyancy-Aided/Opposed Forced and Mixed Convection

    Science.gov (United States)

    Clifford, Corey; Kimber, Mark

    2017-11-01

    Over the last 30 years, an industry-wide shift within the nuclear community has led to increased utilization of computational fluid dynamics (CFD) to supplement nuclear reactor safety analyses. One such area that is of particular interest to the nuclear community, specifically to those performing loss-of-flow accident (LOFA) analyses for next-generation very-high temperature reactors (VHTR), is the capacity of current computational models to predict heat transfer across a wide range of buoyancy conditions. In the present investigation, a critical evaluation of Reynolds-averaged Navier-Stokes (RANS) and large-eddy simulation (LES) turbulence modeling techniques is conducted based on CFD validation data collected from the Rotatable Buoyancy Tunnel (RoBuT) at Utah State University. Four different experimental flow conditions are investigated: (1) buoyancy-aided forced convection; (2) buoyancy-opposed forced convection; (3) buoyancy-aided mixed convection; (4) buoyancy-opposed mixed convection. Overall, good agreement is found for both forced convection-dominated scenarios, but an overly-diffusive prediction of the normal Reynolds stress is observed for the RANS-based turbulence models. Low-Reynolds number RANS models perform adequately for mixed convection, while higher-order RANS approaches underestimate the influence of buoyancy on the production of turbulence.

  19. 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.

  20. Prior Exposure to Zika Virus Significantly Enhances Peak Dengue-2 Viremia in Rhesus Macaques

    OpenAIRE

    George, Jeffy; Valiant, William G.; Mattapallil, Mary J.; Walker, Michelle; Huang, Yan-Jang S.; Vanlandingham, Dana L.; Misamore, John; Greenhouse, Jack; Weiss, Deborah E.; Verthelyi, Daniela; Higgs, Stephen; Andersen, Hanne; Lewis, Mark G.; Mattapallil, Joseph J.

    2017-01-01

    Structural and functional homologies between the Zika and Dengue viruses? envelope proteins raise the possibility that cross-reactive antibodies induced following Zika virus infection might enhance subsequent Dengue infection. Using the rhesus macaque model we show that prior infection with Zika virus leads to a significant enhancement of Dengue-2 viremia that is accompanied by neutropenia, lympocytosis, hyperglycemia, and higher reticulocyte counts, along with the activation of pro-inflammat...

  1. 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.

  2. Predictors of insubordinate aggression among captive female rhesus macaques.

    Science.gov (United States)

    Seil, Shannon K; Hannibal, Darcy L; Beisner, Brianne A; McCowan, Brenda

    2017-11-01

    Cercopithicine primates tend to have nepotistic hierarchies characterized by predictable, kinship-based dominance. Although aggression is typically directed down the hierarchy, insubordinate aggression does occur. Insubordination is important to understand because it can precipitate social upheaval and undermine group stability; however, the factors underlying it are not well understood. We test whether key social and demographic variables predict insubordination among captive female rhesus macaques. To identify factors influencing insubordination, multivariate analyses of 10,821 dyadic conflicts among rhesus macaque females were conducted, using data from six captive groups. A segmented regression analysis was used to identify dyads with insubordination. Negative binomial regression analyses and an information theoretic approach were used to assess predictors of insubordination among dyads. In the best models, weight difference (w = 1.0; IRR = 0.930), age (dominant: w = 1.0, IRR = 0.681; subordinate: w = 1.0, IRR = 1.069), the subordinate's total number of allies (w = 0.727, IRR = 1.060) or non-kin allies (w = 0.273, IRR = 1.165), the interaction of the dominant's kin allies and weight difference (w = 0.938, IRR = 1.046), violation of youngest ascendancy (w = 1.0; IRR = 2.727), and the subordinate's maternal support (w = 1.0; IRR = 2.928), are important predictors of insubordination. These results show that both intrinsic and social factors influence insubordinate behavior. This adds to evidence of the importance of intrinsic factors and flexibility in a social structure thought to be rigid and predetermined by external factors. Further, because insubordination can precipitate social overthrow, determining predictors of insubordination will shed light on mechanisms underlying stability in nepotistic societies. © 2017 Wiley Periodicals, Inc.

  3. Influence of Mobility Models in Precision Spray Aided by Wireless Sensor Networks

    International Nuclear Information System (INIS)

    Gonçalves, L B L; Neves, L A; Zafalon, G F D; Costa, F G; Ueyama, J; Montez, C; Pinto, A S R

    2015-01-01

    Precision Spray is a technique to increase performance of Precision Agriculture. This spray technique may be aided by a Wireless Sensor Network, however, for such approach, the communication between the agricultural input applicator vehicle and network is critical due to its proper functioning. Thus, this work analyzes how the number of nodes in a wireless sensor network, its type of distribution and different areas of scenario affects the performance of communication. We performed simulations to observe system's behavior changing to find the most fitted non-controlled mobility model to the system

  4. 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.

  5. Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques.

    Science.gov (United States)

    Chang, W L William; 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.

  6. Quantitative Proteomic Analysis of Hepatic Tissue of T2DM Rhesus Macaque

    Directory of Open Access Journals (Sweden)

    Tingfu Du

    2017-01-01

    Full Text Available Type 2 diabetes mellitus (T2DM is a metabolic disorder that severely affects human health, but the pathogenesis of the disease remains unknown. The high-fat/high-sucrose diets combined with streptozotocin- (STZ- induced nonhuman primate animal model of diabetes are a valuable research source of T2DM. Here, we present a study of a STZ rhesus macaque model of T2DM that utilizes quantitative iTRAQ-based proteomic method. We compared the protein profiles in the liver of STZ-treated macaques as well as age-matched healthy controls. We identified 171 proteins differentially expressed in the STZ-treated groups, about 70 of which were documented as diabetes-related gene in previous studies. Pathway analyses indicated that the biological functions of differentially expressed proteins were related to glycolysis/gluconeogenesis, fatty acid metabolism, complements, and coagulation cascades. Expression change in tryptophan metabolism pathway was also found in this study which may be associations with diabetes. This study is the first to explore genome-wide protein expression in hepatic tissue of diabetes macaque model using HPLC-Q-TOF/MS technology. In addition to providing potential T2DM biomarkers, this quantitative proteomic study may also shed insights regarding the molecular pathogenesis of T2DM.

  7. 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…

  8. 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 ...

  9. 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.

  10. 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; Van Rompay, Koen K A

    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.

  11. Zika Virus Tissue and Blood Compartmentalization in Acute Infection of Rhesus Macaques.

    Directory of Open Access Journals (Sweden)

    Lark L Coffey

    Full Text Available 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.

  12. Psychological first aid: a consensus-derived, empirically supported, competency-based training model.

    Science.gov (United States)

    McCabe, O Lee; Everly, George S; Brown, Lisa M; Wendelboe, Aaron M; Abd Hamid, Nor Hashidah; Tallchief, Vicki L; Links, Jonathan M

    2014-04-01

    Surges in demand for professional mental health services occasioned by disasters represent a major public health challenge. To build response capacity, numerous psychological first aid (PFA) training models for professional and lay audiences have been developed that, although often concurring on broad intervention aims, have not systematically addressed pedagogical elements necessary for optimal learning or teaching. We describe a competency-based model of PFA training developed under the auspices of the Centers for Disease Control and Prevention and the Association of Schools of Public Health. We explain the approach used for developing and refining the competency set and summarize the observable knowledge, skills, and attitudes underlying the 6 core competency domains. We discuss the strategies for model dissemination, validation, and adoption in professional and lay communities.

  13. Computer-aided polymer design using group contribution plus property models

    DEFF Research Database (Denmark)

    Satyanarayana, Kavitha Chelakara; Abildskov, Jens; Gani, Rafiqul

    2009-01-01

    . Polymer repeat unit property prediction models are required to calculate the properties of the generated repeat units. A systematic framework incorporating recently developed group contribution plus (GC(+)) models and an extended CAMD technique to include design of polymer repeat units is highlighted...... in this paper. The advantage of a GC(+) model in CAMD applications is that a very large number of polymer structures can be considered even though some of the group parameters may not be available. A number of case studies involving different polymer design problems have been solved through the developed......The preliminary step for polymer product design is to identify the basic repeat unit structure of the polymer that matches the target properties. Computer-aided molecular design (CAMD) approaches can be applied for generating the polymer repeat unit structures that match the required constraints...

  14. 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...

  15. 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

    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....... The knowledge base provides the necessary information/data during the design of the PAT system while the model library generates additional or missing data needed for design and analysis. Optimization of the PAT system design is achieved in terms of product data analysis time and/or cost of monitoring equipment......-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...

  16. Analysis of an HIV/AIDS treatment model with a nonlinear incidence

    International Nuclear Information System (INIS)

    Cai Liming; Wu Jingang

    2009-01-01

    An HIV/AIDS treatment model with a nonlinear incidence is formulated. The infectious period is partitioned into the asymptotic and the symptomatic phases according to clinical stages. The constant recruitment rate, disease-induced death, drug therapies, as well as a nonlinear incidence, are incorporated into the model. The basic reproduction number R 0 of the model is determined by the method of next generation matrix. Mathematical analysis establishes that the global dynamics of the spread of the HIV infectious disease are completely determined by the basic reproduction number R 0 . If R 0 ≤1, the disease always dies out and the disease-free equilibrium is globally stable. If R 0 >1, the disease persists and the unique endemic equilibrium is globally asymptotically stable in the interior of the feasible region.

  17. 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

  18. 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. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  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. © 2013 Wiley Periodicals, Inc.

  20. Comparison of the vaginal environment in rhesus and cynomolgus macaques pre- and post-lactobacillus colonization.

    Science.gov (United States)

    Daggett, Gregory J; Zhao, Chunxia; Connor-Stroud, Fawn; Oviedo-Moreno, Patricia; Moon, Hojin; Cho, Michael W; Moench, Thomas; Anderson, Deborah J; Villinger, Francois

    2017-10-01

    Rhesus and cynomologus macaques are valuable animal models for the study of human immunodeficiency virus (HIV) prevention strategies. However, for such studies focused on the vaginal route of infection, differences in vaginal environment may have deterministic impact on the outcome of such prevention, providing the rationale for this study. We tested the vaginal environment of rhesus and cynomolgus macaques longitudinally to characterize the normal microflora based on Nugent scores and pH. This evaluation was extended after colonization of the vaginal space with Lactobacilli in an effort to recreate NHP models representing the healthy human vaginal environment. Nugent scores and pH differed significantly between species, although data from both species were suggestive of stable bacterial vaginosis. Colonization with Lactobacilli was successful in both species leading to lower Nugent score and pH, although rhesus macaques appeared better able to sustain Lactobacillus spp over time. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. 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

  2. Hierarchical ordering with partial pairwise hierarchical relationships on the macaque brain data sets.

    Directory of Open Access Journals (Sweden)

    Woosang Lim

    Full Text Available Hierarchical organizations of information processing in the brain networks have been known to exist and widely studied. To find proper hierarchical structures in the macaque brain, the traditional methods need the entire pairwise hierarchical relationships between cortical areas. In this paper, we present a new method that discovers hierarchical structures of macaque brain networks by using partial information of pairwise hierarchical relationships. Our method uses a graph-based manifold learning to exploit inherent relationship, and computes pseudo distances of hierarchical levels for every pair of cortical areas. Then, we compute hierarchy levels of all cortical areas by minimizing the sum of squared hierarchical distance errors with the hierarchical information of few cortical areas. We evaluate our method on the macaque brain data sets whose true hierarchical levels are known as the FV91 model. The experimental results show that hierarchy levels computed by our method are similar to the FV91 model, and its errors are much smaller than the errors of hierarchical clustering approaches.

  3. The Johns Hopkins model of psychological first aid (RAPID-PFA): curriculum development and content validation.

    Science.gov (United States)

    Everly, George S; Barnett, Daniel J; Links, Jonathan M

    2012-01-01

    There appears to be virtual universal endorsement of the need for and value of acute "psychological first aid" (PFA) in the wake of trauma and disasters. In this paper, we describe the development of the curriculum for The Johns Hopkins RAPID-PFA model of psychological first aid. We employed an adaptation of the basic framework for the development of a clinical science as recommended by Millon which entailed: historical review, theoretical development, and content validation. The process of content validation of the RAPID-PFA curriculum entailed the assessment of attitudes (confidence in the application of PFA interventions, preparedness in the application of PFA); knowledge related to the application of immediate mental health interventions; and behavior (the ability to recognize clinical markers in the field as assessed via a videotape recognition exercise). Results of the content validation phase suggest the six-hour RAPID-PFA curriculum, initially based upon structural modeling analysis, can improve confidence in the application of PFA interventions, preparedness in the application of PFA, knowledge related to the application of immediate mental health interventions, and the ability to recognize clinical markers in the field as assessed via a videotape recognition exercise.

  4. [Computer aided diagnosis model for lung tumor based on ensemble convolutional neural network].

    Science.gov (United States)

    Wang, Yuanyuan; Zhou, Tao; Lu, Huiling; Wu, Cuiying; Yang, Pengfei

    2017-08-01

    The convolutional neural network (CNN) could be used on computer-aided diagnosis of lung tumor with positron emission tomography (PET)/computed tomography (CT), which can provide accurate quantitative analysis to compensate for visual inertia and defects in gray-scale sensitivity, and help doctors diagnose accurately. Firstly, parameter migration method is used to build three CNNs (CT-CNN, PET-CNN, and PET/CT-CNN) for lung tumor recognition in CT, PET, and PET/CT image, respectively. Then, we aimed at CT-CNN to obtain the appropriate model parameters for CNN training through analysis the influence of model parameters such as epochs, batchsize and image scale on recognition rate and training time. Finally, three single CNNs are used to construct ensemble CNN, and then lung tumor PET/CT recognition was completed through relative majority vote method and the performance between ensemble CNN and single CNN was compared. The experiment results show that the ensemble CNN is better than single CNN on computer-aided diagnosis of lung tumor.

  5. Assessing the seasonality and uncertainty in evapotranspiration partitioning using a tracer-aided model

    Science.gov (United States)

    Smith, A. A.; Welch, C.; Stadnyk, T. A.

    2018-05-01

    Evapotranspiration (ET) partitioning is a growing field of research in hydrology due to the significant fraction of watershed water loss it represents. The use of tracer-aided models has improved understanding of watershed processes, and has significant potential for identifying time-variable partitioning of evaporation (E) from ET. A tracer-aided model was used to establish a time-series of E/ET using differences in riverine δ18O and δ2H in four northern Canadian watersheds (lower Nelson River, Manitoba, Canada). On average E/ET follows a parabolic trend ranging from 0.7 in the spring and autumn to 0.15 (three watersheds) and 0.5 (fourth watershed) during the summer growing season. In the fourth watershed wetlands and shrubs dominate land cover. During the summer, E/ET ratios are highest in wetlands for three watersheds (10% higher than unsaturated soil storage), while lowest for the fourth watershed (20% lower than unsaturated soil storage). Uncertainty of the ET partition parameters is strongly influenced by storage volumes, with large storage volumes increasing partition uncertainty. In addition, higher simulated soil moisture increases estimated E/ET. Although unsaturated soil storage accounts for larger surface areas in these watersheds than wetlands, riverine isotopic composition is more strongly affected by E from wetlands. Comparisons of E/ET to measurement-intensive studies in similar ecoregions indicate that the methodology proposed here adequately partitions ET.

  6. Do pre-trained deep learning models improve computer-aided classification of digital mammograms?

    Science.gov (United States)

    Aboutalib, Sarah S.; Mohamed, Aly A.; Zuley, Margarita L.; Berg, Wendie A.; Luo, Yahong; Wu, Shandong

    2018-02-01

    Digital mammography screening is an important exam for the early detection of breast cancer and reduction in mortality. False positives leading to high recall rates, however, results in unnecessary negative consequences to patients and health care systems. In order to better aid radiologists, computer-aided tools can be utilized to improve distinction between image classifications and thus potentially reduce false recalls. The emergence of deep learning has shown promising results in the area of biomedical imaging data analysis. This study aimed to investigate deep learning and transfer learning methods that can improve digital mammography classification performance. In particular, we evaluated the effect of pre-training deep learning models with other imaging datasets in order to boost classification performance on a digital mammography dataset. Two types of datasets were used for pre-training: (1) a digitized film mammography dataset, and (2) a very large non-medical imaging dataset. By using either of these datasets to pre-train the network initially, and then fine-tuning with the digital mammography dataset, we found an increase in overall classification performance in comparison to a model without pre-training, with the very large non-medical dataset performing the best in improving the classification accuracy.

  7. Individualized computer-aided education in mammography based on user modeling: concept and preliminary experiments.

    Science.gov (United States)

    Mazurowski, Maciej A; Baker, Jay A; Barnhart, Huiman X; Tourassi, Georgia D

    2010-03-01

    The authors propose the framework for an individualized adaptive computer-aided educational system in mammography that is based on user modeling. The underlying hypothesis is that user models can be developed to capture the individual error making patterns of radiologists-in-training. In this pilot study, the authors test the above hypothesis for the task of breast cancer diagnosis in mammograms. The concept of a user model was formalized as the function that relates image features to the likelihood/extent of the diagnostic error made by a radiologist-in-training and therefore to the level of difficulty that a case will pose to the radiologist-in-training (or "user"). Then, machine learning algorithms were implemented to build such user models. Specifically, the authors explored k-nearest neighbor, artificial neural networks, and multiple regression for the task of building the model using observer data collected from ten Radiology residents at Duke University Medical Center for the problem of breast mass diagnosis in mammograms. For each resident, a user-specific model was constructed that predicts the user's expected level of difficulty for each presented case based on two BI-RADS image features. In the experiments, leave-one-out data handling scheme was applied to assign each case to a low-predicted-difficulty or a high-predicted-difficulty group for each resident based on each of the three user models. To evaluate whether the user model is useful in predicting difficulty, the authors performed statistical tests using the generalized estimating equations approach to determine whether the mean actual error is the same or not between the low-predicted-difficulty group and the high-predicted-difficulty group. When the results for all observers were pulled together, the actual errors made by residents were statistically significantly higher for cases in the high-predicted-difficulty group than for cases in the low-predicted-difficulty group for all modeling

  8. 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)

  9. Cognitive models and computer aids for nuclear plant control room operators

    International Nuclear Information System (INIS)

    Sheridan, T.B.

    1982-01-01

    This paper reviews what is usually meant by a cognitive model of a control room operator in a nuclear power plant. It emphasizes the idea of internal (that is, mental) representation of external events and the use of such representation for the cognitive steps of attending, recognizing or learning, assessing and deciding. As computers play an increasingly important role in nuclear power plants, especially as cognitive aids to human supervisors of highly automated control systems, it is important that the software and computer interface characteristics be compatible with the operator's internal model. Specific examples discussed in this paper are in the monitoring and prediction of the plant state and in the detection and diagnosis of failures. Current trends in SPDS (safety parameter display system) and failure detection/location systems will be discussed in this regard

  10. Phase aided 3D imaging and modeling: dedicated systems and case studies

    Science.gov (United States)

    Yin, Yongkai; He, Dong; Liu, Zeyi; Liu, Xiaoli; Peng, Xiang

    2014-05-01

    Dedicated prototype systems for 3D imaging and modeling (3DIM) are presented. The 3D imaging systems are based on the principle of phase-aided active stereo, which have been developed in our laboratory over the past few years. The reported 3D imaging prototypes range from single 3D sensor to a kind of optical measurement network composed of multiple node 3D-sensors. To enable these 3D imaging systems, we briefly discuss the corresponding calibration techniques for both single sensor and multi-sensor optical measurement network, allowing good performance of the 3DIM prototype systems in terms of measurement accuracy and repeatability. Furthermore, two case studies including the generation of high quality color model of movable cultural heritage and photo booth from body scanning are presented to demonstrate our approach.

  11. 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

  12. Distribution of glutamatergic, GABAergic, and glycinergic neurons in the auditory pathways of macaque monkeys.

    Science.gov (United States)

    Ito, T; Inoue, K; Takada, M

    2015-12-03

    Macaque monkeys use complex communication calls and are regarded as a model for studying the coding and decoding of complex sound in the auditory system. However, little is known about the distribution of excitatory and inhibitory neurons in the auditory system of macaque monkeys. In this study, we examined the overall distribution of cell bodies that expressed mRNAs for VGLUT1, and VGLUT2 (markers for glutamatergic neurons), GAD67 (a marker for GABAergic neurons), and GLYT2 (a marker for glycinergic neurons) in the auditory system of the Japanese macaque. In addition, we performed immunohistochemistry for VGLUT1, VGLUT2, and GAD67 in order to compare the distribution of proteins and mRNAs. We found that most of the excitatory neurons in the auditory brainstem expressed VGLUT2. In contrast, the expression of VGLUT1 mRNA was restricted to the auditory cortex (AC), periolivary nuclei, and cochlear nuclei (CN). The co-expression of GAD67 and GLYT2 mRNAs was common in the ventral nucleus of the lateral lemniscus (VNLL), CN, and superior olivary complex except for the medial nucleus of the trapezoid body, which expressed GLYT2 alone. In contrast, the dorsal nucleus of the lateral lemniscus, inferior colliculus, thalamus, and AC expressed GAD67 alone. The absence of co-expression of VGLUT1 and VGLUT2 in the medial geniculate, medial superior olive, and VNLL suggests that synaptic responses in the target neurons of these nuclei may be different between rodents and macaque monkeys. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Dynamic Interaction of Enterovirus 71 and Dendritic Cells in Infected Neonatal Rhesus Macaques.

    Science.gov (United States)

    Zhao, Ting; Zhang, Zhixiao; Zhang, Ying; Feng, Min; Fan, Shengtao; Wang, Lichun; Liu, Longding; Wang, Xi; Wang, Qinglin; Zhang, Xiaolong; Wang, Jingjing; Liao, Yun; He, Zhanlong; Lu, Shuaiyao; Yang, Huai; Li, Qihan

    2017-01-01

    Enterovirus 71 (EV71) is one of the main pathogens responsible for hand, foot, and mouth disease (HFMD). Infection with EV71 can lead to severe clinical disease via extensive infections of either the respiratory or alimentary tracts in children. Based on the previous pathological study of EV71 infections in neonatal rhesus macaques, our work using this animal model and an EV71 chimera that expresses enhanced green fluorescent protein (EGFP-EV71) primarily explored where EV71 localizes and proliferates, and the subsequent initiation of the pathological process. The chimeric EGFP-EV71 we constructed was similar to the wild-type EV71 (WT-EV71) virus in its biological characteristics. Similar clinical manifestations and histo-pathologic features were equally displayed in neonatal rhesus macaques infected with either WT-EV71 or EGFP-EV71 via the respiratory route. Fluorescent signal tracing in tissues from the animals infected with EGFP-EV71 showed that EV71 proliferated primarily in the respiratory tract epithelium and the associated lymphoid tissues. Immunofluorescence and flow cytometry analyses revealed that EV71 was able to enter a pre-conventional dendritic cell (DC) population at the infection sites. The viremia identified in the macaques infected by WT-EV71 or EGFP-EV71 was present even in the artificial presence of a specific antibody against the virus. Our results suggest that EV71 primarily proliferates in the respiratory tract epithelium followed by subsequent entry into a pre-cDC population of DCs. These cells are then hijacked by the virus and they can potentially transmit the virus from local sites to other organs through the blood circulation during the infection process. Our results suggest that the EV71 infection process in this DC population does not interfere with the induction of an independent immune response against the EV71 infection in the neonatal macaques.

  14. 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.

  15. 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 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.

  16. Natural and cross-inducible anti-SIV antibodies in Mauritian cynomolgus macaques.

    Directory of Open Access Journals (Sweden)

    Hongzhao Li

    Full Text Available Cynomolgus macaques are an increasingly important nonhuman primate model for HIV vaccine research. SIV-free animals without pre-existing anti-SIV immune responses are generally needed to evaluate the effect of vaccine-induced immune responses against the vaccine epitopes. Here, in order to select such animals for vaccine studies, we screened 108 naïve female Mauritian cynomolgus macaques for natural (baseline antibodies to SIV antigens using a Bio-Plex multiplex system. The antigens included twelve 20mer peptides overlapping the twelve SIV protease cleavage sites (-10/+10, respectively (PCS peptides, and three non-PCS Gag or Env peptides. Natural antibodies to SIV antigens were detected in subsets of monkeys. The antibody reactivity to SIV was further confirmed by Western blot using purified recombinant SIV Gag and Env proteins. As expected, the immunization of monkeys with PCS antigens elicited anti-PCS antibodies. However, unexpectedly, antibodies to non-PCS peptides were also induced, as shown by both Bio-Plex and Western blot analyses, while the non-PCS peptides do not share sequence homology with PCS peptides. The presence of natural and vaccine cross-inducible SIV antibodies in Mauritian cynomolgus macaques should be considered in animal selection, experimental design and result interpretation, for their best use in HIV vaccine research.

  17. Test-and-treat approach to HIV/AIDS: a primer for mathematical modeling.

    Science.gov (United States)

    Nah, Kyeongah; Nishiura, Hiroshi; Tsuchiya, Naho; Sun, Xiaodan; Asai, Yusuke; Imamura, Akifumi

    2017-09-05

    The public benefit of test-and-treat has induced a need to justify goodness for the public, and mathematical modeling studies have played a key role in designing and evaluating the test-and-treat strategy for controlling HIV/AIDS. Here we briefly and comprehensively review the essence of contemporary understanding of the test-and-treat policy through mathematical modeling approaches and identify key pitfalls that have been identified to date. While the decrease in HIV incidence is achieved with certain coverages of diagnosis, care and continued treatment, HIV prevalence is not necessarily decreased and sometimes the test-and-treat is accompanied by increased long-term cost of antiretroviral therapy (ART). To confront with the complexity of assessment on this policy, the elimination threshold or the effective reproduction number has been proposed for its use in determining the overall success to anticipate the eventual elimination. Since the publication of original model in 2009, key issues of test-and-treat modeling studies have been identified, including theoretical problems surrounding the sexual partnership network, heterogeneities in the transmission dynamics, and realistic issues of achieving and maintaining high treatment coverage in the most hard-to-reach populations. To explicitly design country-specific control policy, quantitative modeling approaches to each single setting with differing epidemiological context would require multi-disciplinary collaborations among clinicians, public health practitioners, laboratory technologists, epidemiologists and mathematical modelers.

  18. 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.

  19. Adaptive parametric model order reduction technique for optimization of vibro-acoustic models: Application to hearing aid design

    DEFF Research Database (Denmark)

    Creixell Mediante, Ester; Jensen, Jakob Søndergaard; Naets, Frank

    2018-01-01

    Finite Element (FE) models of complex structural-acoustic coupled systems can require a large number of degrees of freedom in order to capture their physical behaviour. This is the case in the hearing aid field, where acoustic-mechanical feedback paths are a key factor in the overall system...... by projecting the full system into a reduced space. A drawback of most of the existing techniques is that the vector basis of the reduced space is built at an offline phase where the full system must be solved for a large sample of parameter values, which can also become highly time consuming. In this work, we...

  20. 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.

  1. 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.

  2. Use of photogrammetry as a means to assess hybrids of rhesus (Macaca mulatta) and long-tailed (M. fascicularis) macaques.

    Science.gov (United States)

    Jadejaroen, Janya; Hamada, Yuzuru; Kawamoto, Yoshi; Malaivijitnond, Suchinda

    2015-01-01

    Rhesus (Macaca mulatta) and long-tailed (M. fascicularis) macaques are the most commonly used non-human primate models for biomedical research, but it is difficult to identify these two species in the hybrid zone (15-20°N). In this work, we used morphological values obtained via photogrammetry to assess hybrids of rhesus and long-tailed macaques at Khao Khieow Open Zoo (KKZ; 13°21'N, 101°06'E), eastern Thailand. Long-tailed and rhesus macaques have species-specific tail lengths and contrasts of their yellowish pelages. The accuracy and precision of the relative tail length (%RTL) and the contrast of the yellow hue (Cb*) of the pelage, as obtained from photographs, were compared with the corresponding direct measurements (morphometrics). The photogrammetric and morphometric measurements of %RTL and Cb* were highly significantly correlated (r = 0.989 and 0.980, p photogrammetry can be utilized to identify macaque species or hybrids when species identification relies mainly on tail length and pelage color.

  3. A genetic-algorithm-aided stochastic optimization model for regional air quality management under uncertainty.

    Science.gov (United States)

    Qin, Xiaosheng; Huang, Guohe; Liu, Lei

    2010-01-01

    A genetic-algorithm-aided stochastic optimization (GASO) model was developed in this study for supporting regional air quality management under uncertainty. The model incorporated genetic algorithm (GA) and Monte Carlo simulation techniques into a general stochastic chance-constrained programming (CCP) framework and allowed uncertainties in simulation and optimization model parameters to be considered explicitly in the design of least-cost strategies. GA was used to seek the optimal solution of the management model by progressively evaluating the performances of individual solutions. Monte Carlo simulation was used to check the feasibility of each solution. A management problem in terms of regional air pollution control was studied to demonstrate the applicability of the proposed method. Results of the case study indicated the proposed model could effectively communicate uncertainties into the optimization process and generate solutions that contained a spectrum of potential air pollutant treatment options with risk and cost information. Decision alternatives could be obtained by analyzing tradeoffs between the overall pollutant treatment cost and the system-failure risk due to inherent uncertainties.

  4. Creating computer aided 3D model of spleen and kidney based based on Visible Human Project

    International Nuclear Information System (INIS)

    Aldur, Muhammad M.

    2005-01-01

    To investigate the efficacy of computer aided 3-dimensional (3D) reconstruction technique on visualization and modeling of gross anatomical structures with an affordable methodology applied on the spleen and kidney. From The Visible Human Project Dataset cryosection images, developed by the National Library of Medicine, the spleen and kidney sections were preferred to be used due to their highly distinct contours. The software used for the reconstruction were Surf Driver 3.5.3 for Mac and Cinema 4D X L version 7.1 for Mac OS X. This study was carried out in May 2004 at the Department of Anatomy, Hacettepe University, Ankara, Turkey. As a result of this study, it is determined that these 2 programs could be effectively used both for 3D modeling of the mentioned organs and volumetric analyses on these models. It is also seen that it is possible to hold the physical models of these gross anatomical digital ones with stereolithography technique by means of the data exchange file format provided by the program and present such images as anaglyph. Surf Driver 3.5.3 for Mac OS and Cinema 4 DXL version 7.1 for Mac OS X can be used effectively for reconstruction of gross anatomical structures from serial parallel sections with distinct contours such as spleen and kidney and the animation of models. These software constitute a highly effective way of getting volumetric calculations, spatial relations and morphometrical measurements of reconstructed structures. (author)

  5. 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

    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....

  6. 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.

  7. 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.

  8. Adaptive parametric model order reduction technique for optimization of vibro-acoustic models: Application to hearing aid design

    Science.gov (United States)

    Creixell-Mediante, Ester; Jensen, Jakob S.; Naets, Frank; Brunskog, Jonas; Larsen, Martin

    2018-06-01

    Finite Element (FE) models of complex structural-acoustic coupled systems can require a large number of degrees of freedom in order to capture their physical behaviour. This is the case in the hearing aid field, where acoustic-mechanical feedback paths are a key factor in the overall system performance and modelling them accurately requires a precise description of the strong interaction between the light-weight parts and the internal and surrounding air over a wide frequency range. Parametric optimization of the FE model can be used to reduce the vibroacoustic feedback in a device during the design phase; however, it requires solving the model iteratively for multiple frequencies at different parameter values, which becomes highly time consuming when the system is large. Parametric Model Order Reduction (pMOR) techniques aim at reducing the computational cost associated with each analysis by projecting the full system into a reduced space. A drawback of most of the existing techniques is that the vector basis of the reduced space is built at an offline phase where the full system must be solved for a large sample of parameter values, which can also become highly time consuming. In this work, we present an adaptive pMOR technique where the construction of the projection basis is embedded in the optimization process and requires fewer full system analyses, while the accuracy of the reduced system is monitored by a cheap error indicator. The performance of the proposed method is evaluated for a 4-parameter optimization of a frequency response for a hearing aid model, evaluated at 300 frequencies, where the objective function evaluations become more than one order of magnitude faster than for the full system.

  9. A New Optimization Model for Computer-Aided Molecular Design Problems

    DEFF Research Database (Denmark)

    Zhang, Lei; Cignitti, Stefano; Gani, Rafiqul

    Computer-Aided Molecular Design (CAMD) is a method to design molecules with desired properties. That is, through CAMD, it is possible to generate molecules that match a specified set of target properties. CAMD has attracted much attention in recent years due to its ability to design novel as well...... with structure information considered due to the increased size of the mathematical problem and number of alternatives. Thus, decomposition-based approach is proposed to solve the problem. In this approach, only first-order groups are considered in the first step to obtain the building block of the designed...... molecule, then the property model is refined with second-order groups based on the results of the first step. However, this may result in the possibility of an optimal solution being excluded. Samudra and Sahinidis [4] used property relaxation method in the first step to avoid this situation...

  10. Use of logic flowgraph models in a computer aided process analysis and management system

    International Nuclear Information System (INIS)

    Guarro, S.B.; Okrent, D.

    1985-07-01

    The development of a multi-function computer-aided process analysis and management (CAPAM) system, to be implemented in nuclear power plant control rooms, is proposed and discussed. The design goals identified for such a system are early disturbance detection and diagnosis, accompanied by identification of the best possible recovery actions or alternative success paths. The CAPAM structure is articulated in three functional levels with dedicated CRT displays. Increasing amount of diagnostic or recovery information is made available to the operators at the lower display levels. Probabilistic safety margins to the loss of important safety functions may be also calculated. The proposed implementation of the CAPAM concept is based on the use of logic flowgraph networks for the more detailed system modeling. Examples of such an implementation are given. 7 refs., 3 figs., 2 tabs

  11. 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.

  12. CFD aided analysis of a scaled down model of the Brazilian Multipurpose Reactor (RMB) pool

    International Nuclear Information System (INIS)

    Schweizer, Fernando L.A.; Lima, Claubia P.B.; Costa, Antonella L.; Veloso, Maria A.F.

    2013-01-01

    Research reactors are commonly built inside deep pools that provide radiological and thermal protection and easy access to its core. Reactors with thermal power in the order of MW usually use an auxiliary thermal-hydraulic circuit at the top of its pool to create a purified hot water layer (HWL). Thermal-hydraulic analysis of the flow configuration in the pool and HWL is paramount to insure radiological protection. A useful tool for these analyses is the application of CFD (Computational Fluid Dynamics). To obtain satisfactory results using CFD it is necessary the verification and validation of the CFD numerical model. Verification is divided in code and solution verifications. In the first one establishes the correctness of the CFD code implementation and in the former estimates the numerical accuracy of a particular calculation. Validation is performed through comparison of numerical and experimental results. This paper presents a dimensional analysis of the RMB (Brazilian Multipurpose Reactor) pool to determine a scaled down experimental installation able to aid in the HWL numerical investigation. Two CFD models were created one with the same dimensions and boundary conditions of the reactor prototype and the other with 1/10 proportion size and boundary conditions set to achieve the same inertial and buoyant forces proportions represented by Froude Number between the two models. Results comparing the HWL thickness show consistence between the prototype and the scaled down model behavior. (author)

  13. Longitudinal study to assess the safety and efficacy of a live-attenuated SHIV vaccine in long term immunized rhesus macaques

    International Nuclear Information System (INIS)

    Yankee, Thomas M.; Sheffer, Darlene; Liu Zhengian; Dhillon, Sukhbir; Jia Fenglan; Chebloune, Yahia; Stephens, Edward B.; Narayan, Opendra

    2009-01-01

    Live-attenuated viruses derived from SIV and SHIV have provided the most consistent protection against challenge with pathogenic viruses, but concerns regarding their long-term safety and efficacy have hampered their clinical usefulness. We report a longitudinal study in which we evaluated the long-term safety and efficacy of ΔvpuSHIV PPC , a live virus vaccine derived from SHIV PPC . Macaques were administered two inoculations of ΔvpuSHIV PPC , three years apart, and followed for eight years. None of the five vaccinated macaques developed an AIDS-like disease from the vaccine. At eight years, macaques were challenged with pathogenic SIV and SHIV. None of the four macaques with detectable cellular-mediated immunity prior to challenge had detectable viral RNA in the plasma. This study demonstrates that multiple inoculations of a live vaccine virus can be used safely and can significantly extend the efficacy of the vaccine, as compared to a single inoculation, which is efficacious for approximately three years

  14. Determining Nurse Aide Staffing Requirements to Provide Care Based on Resident Workload: A Discrete Event Simulation Model.

    Science.gov (United States)

    Schnelle, John F; Schroyer, L Dale; Saraf, Avantika A; Simmons, Sandra F

    2016-11-01

    Nursing aides provide most of the labor-intensive activities of daily living (ADL) care to nursing home (NH) residents. Currently, most NHs do not determine nurse aide staffing requirements based on the time to provide ADL care for their unique resident population. The lack of an objective method to determine nurse aide staffing requirements suggests that many NHs could be understaffed in their capacity to provide consistent ADL care to all residents in need. Discrete event simulation (DES) mathematically models key work parameters (eg, time to provide an episode of care and available staff) to predict the ability of the work setting to provide care over time and offers an objective method to determine nurse aide staffing needs in NHs. This study had 2 primary objectives: (1) to describe the relationship between ADL workload and the level of nurse aide staffing reported by NHs; and, (2) to use a DES model to determine the relationship between ADL workload and nurse aide staffing necessary for consistent, timely ADL care. Minimum Data Set data related to the level of dependency on staff for ADL care for residents in over 13,500 NHs nationwide were converted into 7 workload categories that captured 98% of all residents. In addition, data related to the time to provide care for the ADLs within each workload category was used to calculate a workload score for each facility. The correlation between workload and reported nurse aide staffing levels was calculated to determine the association between staffing reported by NHs and workload. Simulations to project staffing requirements necessary to provide ADL care were then conducted for 65 different workload scenarios, which included 13 different nurse aide staffing levels (ranging from 1.6 to 4.0 total hours per resident day) and 5 different workload percentiles (ranging from the 5th to the 95th percentile). The purpose of the simulation model was to determine the staffing necessary to provide care within each workload

  15. Bipedal locomotion of bonnet macaques after spinal cord injury.

    Science.gov (United States)

    Babu, Rangasamy Suresh; Anand, P; Jeraud, Mathew; Periasamy, P; Namasivayam, A

    2007-10-01

    Experimental studies concerning the analysis of locomotor behavior in spinal cord injury research are widely performed in rodent models. The purpose of this study was to quantitatively evaluate the degree of functional recovery in reflex components and bipedal locomotor behavior of bonnet macaques (Macaca radiata) after spinal contusive injury. Six monkeys were tested for various reflex components (grasping, righting, hopping, extension withdrawal) and were trained preoperatively to walk in bipedal fashion on the simple and complex locomotor runways (narrow beam, grid, inclined plane, treadmill) of this investigation. The overall performance of the animals'motor behavior and the functional status of limb movements during bipedal locomotion were graded by the Combined Behavioral Score (CBS) system. Using the simple Allen weight-drop technique, a contusive injury was produced by dropping a 13-g weight from a height of 30 cm to the exposed spinal cord at the T12-L1 vertebral level of the trained monkeys. All the monkeys showed significant impairments in every reflex activity and in walking behavior during the early part of the postoperative period. In subsequent periods, the animals displayed mild alterations in certain reflex responses, such as grasping, extension withdrawal, and placing reflexes, which persisted through a 1-year follow-up. The contused animals traversed locomotor runways--narrow beam, incline plane, and grid runways--with more steps and few errors, as evaluated with the CBS system. Eventually, the behavioral performance of all spinal-contused monkeys recovered to near-preoperative level by the fifth postoperative month. The findings of this study reveal the recovery time course of various reflex components and bipedal locomotor behavior of spinal-contused macaques on runways for a postoperative period of up to 1 year. Our spinal cord research in primates is advantageous in understanding the characteristics of hind limb functions only, which possibly

  16. 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.

  17. Modelling elderly cardiac patients decision making using Cognitive Work Analysis: identifying requirements for patient decision aids.

    Science.gov (United States)

    Dhukaram, Anandhi Vivekanandan; Baber, Chris

    2015-06-01

    Patients make various healthcare decisions on a daily basis. Such day-to-day decision making can have significant consequences on their own health, treatment, care, and costs. While decision aids (DAs) provide effective support in enhancing patient's decision making, to date there have been few studies examining patient's decision making process or exploring how the understanding of such decision processes can aid in extracting requirements for the design of DAs. This paper applies Cognitive Work Analysis (CWA) to analyse patient's decision making in order to inform requirements for supporting self-care decision making. This study uses focus groups to elicit information from elderly cardiovascular disease (CVD) patients concerning a range of decision situations they face on a daily basis. Specifically, the focus groups addressed issues related to the decision making of CVD in terms of medication compliance, pain, diet and exercise. The results of these focus groups are used to develop high level views using CWA. CWA framework decomposes the complex decision making problem to inform three approaches to DA design: one design based on high level requirements; one based on a normative model of decision-making for patients; and the third based on a range of heuristics that patients seem to use. CWA helps in extracting and synthesising decision making from different perspectives: decision processes, work organisation, patient competencies and strategies used in decision making. As decision making can be influenced by human behaviour like skills, rules and knowledge, it is argued that patients require support to different types of decision making. This paper also provides insights for designers in using CWA framework for the design of effective DAs to support patients in self-management. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Computer-aided design and computer-aided modeling (CAD/CAM) generated surgical splints, cutting guides and custom-made implants: Which indications in orthognathic surgery?

    Science.gov (United States)

    Scolozzi, P

    2015-12-01

    The purpose of the present report was to describe our indications, results and complications of computer-aided design and computer-aided modeling CAD/CAM surgical splints, cutting guides and custom-made implants in orthognathic surgery. We analyzed the clinical and radiological data of ten consecutive patients with dentofacial deformities treated using a CAD/CAM technique. Four patients had surgical splints and cutting guides for correction of maxillomandibular asymmetries, three had surgical cutting guides and customized internal distractors for correction of severe maxillary deficiencies and three had custom-made implants for additional chin contouring and/or mandibular defects following bimaxillary osteotomies and sliding genioplasty. We recorded age, gender, dentofacial deformity, surgical procedure and intra- and postoperative complications. All of the patients had stable cosmetic results with a high rate of patient satisfaction at the 1-year follow-up examination. No intra- and/or postoperative complications were encountered during any of the different steps of the procedure. This study demonstrated that the application of CAD/CAM patient-specific surgical splints, cutting guides and custom-made implants in orthognathic surgery allows for a successful outcome in the ten patients presented in this series. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  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. Risk and Resilience: Early Manipulation of Macaque Social Experience and Persistent Behavioral and Neurophysiological Outcomes

    Science.gov (United States)

    Stevens, Hanna E.; Leckman, James F.; Coplan, Jeremy D.; Suomi, Stephen J.

    2009-01-01

    A literature review on macaque monkeys finds that peer rearing of young macaques and rearing of young macaques by mothers that are undergoing variable foraging conditions result in emotional and neurophysiological disturbance. Certain genotypes contribute to resilience to this disturbance. The findings have implications to child mental health and…

  1. Talking about AIDS in Hong Kong: Cultural Models in Public Health Discourse.

    Science.gov (United States)

    Jones, Rodney H.

    A study explored the issues of cultural identity and interaction in public health discourse concerning Acquired Immune Deficiency Syndrome (AIDS) in Hong Kong's multilingual, multicultural social context. Twenty public service announcements (PSAs) concerning AIDS awareness televised in both English and Cantonese in Hong Kong from 1987 to 1994 were…

  2. 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…

  3. New Animal Model Could Boost Research on AIDS Drugs and Vaccines | FNLCR

    Science.gov (United States)

    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 i

  4. 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

  5. Halting HIV/AIDS with avatars and havatars: a virtual world approach to modelling epidemics

    Directory of Open Access Journals (Sweden)

    Smith? Robert J

    2009-11-01

    Full Text Available Abstract Background A major deficit of all approaches to epidemic modelling to date has been the need to approximate or guess at human behaviour in disease-transmission-related contexts. Avatars are generally human-like figures in virtual computer worlds controlled by human individuals. Methods We introduce the concept of a "havatar", which is a (human, avatar pairing. Evidence is mounting that this pairing behaves in virtual contexts much like the human in the pairing might behave in analogous real-world contexts. Results We propose that studies of havatars, in a virtual world, may give a realistic approximation of human behaviour in real-world contexts. If the virtual world approximates the real world in relevant details (geography, transportation, etc., virtual epidemics in that world could accurately simulate real-world epidemics. Havatar modelling of epidemics therefore offers a complementary tool for tackling how best to halt epidemics, including perhaps HIV/AIDS, since sexual behaviour is a significant component of some virtual worlds, such as Second Life. Conclusion Havatars place the control parameters of an epidemic in the hands of each individual. By providing tools that everyone can understand and use, we could democratise epidemiology.

  6. Computer-Aided Modelling and Analysis of PV Systems: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Charalambos Koukouvaos

    2014-01-01

    Full Text Available Modern scientific advances have enabled remarkable efficacy for photovoltaic systems with regard to the exploitation of solar energy, boosting them into having a rapidly growing position among the systems developed for the production of renewable energy. However, in many cases the design, analysis, and control of photovoltaic systems are tasks which are quite complex and thus difficult to be carried out. In order to cope with this kind of problems, appropriate software tools have been developed either as standalone products or parts of general purpose software platforms used to model and simulate the generation, transmission, and distribution of solar energy. The utilization of this kind of software tools may be extremely helpful to the successful performance evaluation of energy systems with maximum accuracy and minimum cost in time and effort. The work presented in this paper aims on a first level at the performance analysis of various configurations of photovoltaic systems through computer-aided modelling. On a second level, it provides a comparative evaluation of the credibility of two of the most advanced graphical programming environments, namely, Simulink and LabVIEW, with regard to their application in photovoltaic systems.

  7. Potential for PET scanning as an aid to heat transfer modeling

    International Nuclear Information System (INIS)

    Samulski, T.V.; Harris, C.; Winget, J.M.; Dewhirst, M.W.

    1987-01-01

    Positron Emission Tomography (PET) using /sup 68/Ga labelled microspheres (15μ diam.) for quantitative imaging of perfusion is being investigated for its potential to aid in verification of parameter estimation techniques. Such techniques have been used in bioheat transfer modeling where direct measurement of perfusion has not been possible. Perfusion is needed, to utilize bioheat transfer to predict temperatures between measured points during hyperthermia therapy. A preliminary study showing that PET could be used for verification of parameter estimation was done by heating a melanoma in a dog in which multiple thermometry catheters were placed in a central plane. Microspheres were injected at the end of a one hour heat treatment session before power down. CT and PET images of the same plane were aligned so that relative counts/pixel in 2 cm regions of interest of the PET image were measured along several catheter tracks. In all tracks measured an inverse correlation was shown between relative perfusion and temperature along the catheter during thermal steady state. These data strongly imply that PET scans obtained in the manner described bear relevance to bioheat transfer and for verification of perfusion in heated tissues as estimated by heat transfer modeling

  8. Rotational displacement skills in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Hughes, Kelly D; Santos, Laurie R

    2012-11-01

    Rotational displacement tasks, in which participants must track an object at a hiding location within an array while the array rotates, exhibit a puzzling developmental pattern in humans. Human children take an unusually long time to master this task and tend to solve rotational problems through the use of nongeometric features or landmarks as opposed to other kinds of spatial cues. We investigated whether these developmental characteristics are unique to humans by testing rotational displacement skills in a monkey species, the rhesus macaque (Macaca mulatta), using a looking-time method. Monkeys first saw food hidden in two differently colored boxes within an array. The array was then rotated 180° and the boxes reopened to reveal the food in an expected or unexpected location. Our first two experiments explored the developmental time-course of performance on this rotational displacement task. We found that adult macaques looked longer at the unexpected event, but such performance was not mirrored in younger-aged macaques. In a third study, we systematically varied featural information and visible access to the array to investigate which strategies adult macaques used in solving rotational displacements. Our results show that adult macaques need both sets of information to solve the task. Taken together, these results suggest both similarities and differences in mechanisms by which human and nonhuman primates develop this spatial skill.

  9. Analysis of carboxylesterase 2 transcript variants in cynomolgus macaque liver.

    Science.gov (United States)

    Uno, Yasuhiro; Igawa, Yoshiyuki; Tanaka, Maori; Ohura, Kayoko; Hosokawa, Masakiyo; Imai, Teruko

    2018-04-27

    Carboxylesterase (CES) is important for the detoxification of a wide range of drugs and xenobiotics. In this study, the hepatic level of CES2 mRNA was examined in cynomolgus macaques used widely in preclinical studies for drug metabolism. Three CES2 mRNAs were present in cynomolgus macaque liver. The mRNA level was highest for cynomolgus CES2A (formerly CES2v3), much lower for cynomolgus CES2B (formerly CES2v1) and extremely low for cynomolgus CES2C (formerly CES2v2). Most various transcript variants produced from cynomolgus CES2B gene did not contain a complete coding region. Thus, CES2A is the major CES2 enzyme in cynomolgus liver. A new transcript variant of CES2A, CES2Av2, was identified. CES2Av2 contained exon 3 region different from wild-type (CES2Av1). In cynomolgus macaques expressing only CES2Av2 transcript, CES2A contained the sequence of CES2B in exon 3 and vicinity, probably due to gene conversion. On genotyping, this CES2Av2 allele was prevalent in Indochinese cynomolgus macaques, but not in Indonesian cynomolgus or rhesus macaques. CES2Av2 recombinant protein showed similar activity to CES2Av1 protein for several substrates. It is concluded that CES2A is the major cynomolgus hepatic CES2, and new transcript variant, CES2Av2, has similar functions to CES2Av1.

  10. Intermittent pair-housing, pair relationship qualities, and HPA activity in adult female rhesus macaques.

    Science.gov (United States)

    Hannibal, Darcy L; Cassidy, Lauren C; Vandeleest, Jessica; Semple, Stuart; Barnard, Allison; Chun, Katie; Winkler, Sasha; McCowan, Brenda

    2018-05-02

    Laboratory rhesus macaques are often housed in pairs and may be temporarily or permanently separated for research, health, or management reasons. While both long-term social separations and introductions can stimulate a stress response that impacts inflammation and immune function, the effects of short-term overnight separations and whether qualities of the pair relationship mediate these effects are unknown. In this study, we investigated the effects of overnight separations on the urinary cortisol concentration of 20 differentially paired adult female rhesus macaques (Macaca mulatta) at the California National Primate Research Center. These females were initially kept in either continuous (no overnight separation) or intermittent (with overnight separation) pair-housing and then switched to the alternate pair-housing condition part way through the study. Each study subject was observed for 5 weeks, during which we collected measures of affiliative, aggressive, anxious, abnormal, and activity-state behaviors in both pair-housing conditions. Additionally, up to three urine samples were collected from each subject per week and assayed for urinary free cortisol and creatinine. Lastly, the behavioral observer scored each pair on four relationship quality attributes ("Anxious," "Tense," "Well-meshed," and "Friendly") using a seven-point scale. Data were analyzed using a generalized linear model with gamma distribution and an information theoretic approach to determine the best model set. An interaction between the intermittent pairing condition and tense pair adjective rating was in the top three models of the best model set. Dominance and rates of affiliation were also important for explaining urinary cortisol variation. Our results suggest that to prevent significant changes in HPA-axis activation in rhesus macaque females, which could have unintended effects on research outcomes, pairs with "Tense" relationships and overnight separations preventing tactile contact

  11. 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.

  12. Optical coherence tomography and computer-aided diagnosis of a murine model of chronic kidney disease

    Science.gov (United States)

    Wang, Bohan; Wang, Hsing-Wen; Guo, Hengchang; Anderson, Erik; Tang, Qinggong; Wu, Tongtong; Falola, Reuben; Smith, Tikina; Andrews, Peter M.; Chen, Yu

    2017-12-01

    Chronic kidney disease (CKD) is characterized by a progressive loss of renal function over time. Histopathological analysis of the condition of glomeruli and the proximal convolutional tubules over time can provide valuable insights into the progression of CKD. Optical coherence tomography (OCT) is a technology that can analyze the microscopic structures of a kidney in a nondestructive manner. Recently, we have shown that OCT can provide real-time imaging of kidney microstructures in vivo without administering exogenous contrast agents. A murine model of CKD induced by intravenous Adriamycin (ADR) injection is evaluated by OCT. OCT images of the rat kidneys have been captured every week up to eight weeks. Tubular diameter and hypertrophic tubule population of the kidneys at multiple time points after ADR injection have been evaluated through a fully automated computer-vision system. Results revealed that mean tubular diameter and hypertrophic tubule population increase with time in post-ADR injection period. The results suggest that OCT images of the kidney contain abundant information about kidney histopathology. Fully automated computer-aided diagnosis based on OCT has the potential for clinical evaluation of CKD conditions.

  13. Experimental Comparison of Efficiency of First Aid Dressings in Burning White Phosphorus on Bacon Model

    Science.gov (United States)

    Witkowski, Wojciech; Surowiecka-Pastewka, Agnieszka; Biesaga, Magdalena; Gierczak, Tomasz

    2015-01-01

    Background The aim of this study was to determine effectiveness of first aid dressings in extinguishing burning white phosphorous (WP), eliminating WP pieces from the surface, inhibiting re-ignition on the model (fresh bacon covered with military uniform), and preventing from late re-ignition caused by persistent WP pieces. Material/Methods Burning WP was extinguished with several dressings: tactical Military Dressing (WJ10), wet gauze, 2 hydrocolloids, and 3 prototypes of hydrocolloids developed by the authors. Results All examined dressings were effective in extinguishing WP provided that the entire area of the burning substance was completely covered. Moist gauze was especially effective in extinguishing WP, and also removed and absorbed the majority of the WP mass, preventing deeper penetration of WP particles. The immediate re-ignition was observed when all the remaining examined dressings were removed from the bacon. A stream of water was dangerous, as it splashed and transferred pieces of WP around. Conclusions Moist gauze placed on burning WP for approximately 3 min was most effective in extinguishing WP and removing most of the WP pieces. We recommend moist gauze, used once or twice, as the best primary means for WP elimination and preventing tissue penetration. As a dressing used for medical evacuation (MEDEVAC), or as a second step after complete removal of visible WP, innovative hydrocolloid or hydrogel dressings should be used. PMID:26264209

  14. 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.

  15. Cultural context in the effort to improve oral health among Alaska Native people: the dental health aide therapist model.

    Science.gov (United States)

    Wetterhall, Scott; Burrus, Barri; Shugars, Daniel; Bader, James

    2011-10-01

    The Alaska Native people in rural Alaska face serious challenges in obtaining dental care. Itinerant care models have failed to meet their needs for more than 50 years. The dental health aide therapist (DHAT) model, which entails training midlevel care providers to perform limited restorative, surgical, and preventive procedures, was adopted to address some of the limitations of the itinerant model. We used quantitative and qualitative methods to assess residents' satisfaction with the model and the role of DHATs in the cultural context in which they operate. Our findings suggest that the DHAT model can provide much-needed access to urgent care and is beneficial from a comprehensive cultural perspective.

  16. Some aspects of finite element modelling of ultrasonically aided micro-EDM of CoCr alloys

    Directory of Open Access Journals (Sweden)

    Ghiculescu Daniel

    2017-01-01

    Full Text Available The paper deals with finite element modelling of micromachining CoCr alloys by ultrasonically aided electrical discharge machining. This hybrid machining process has two components: a thermal one due to EDM, and a mechanical one to ultrasonic assistance. Both components were modelled using Thermal and Structural Mechanics time dependent modules of Comsol Multiphysics. The results were compared with the experimental data obtained in our laboratories, proving a good agreement and offering some solutions for machining optimization.

  17. [Innovative Services: The Use of Parent Aides in Child Protective Services]. Module 2. Program Models--Which One is Right for You?

    Science.gov (United States)

    Anderson, Stephen C.; And Others

    Module 2 of a seven module package for child protective service workers explores various types of parent aide programs for abused and neglected children and their families. Four training activities address models of parent aide programs, organization analysis, and selection of the appropriate program model. Included are directions for using the…

  18. 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,…

  19. 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.

  20. Assessing the Effectiveness of Defensive Aid Suite Technology Using a Field Trial and Modelling and Simulation

    National Research Council Canada - National Science Library

    Fournier, Pierre

    2002-01-01

    ...) community that Defensive Aid Suite (DAS) technologies can improve the protection of LAVs. A prototype DAS system was developed by DRDC Valcartier and tested in field trials held in 1995 and 1999...

  1. Saints and sinners: training Papua New Guinean (PNG) Christian Clergy to respond to HIV and AIDS using a model of care.

    Science.gov (United States)

    Benton, Kerry William Kim

    2008-09-01

    Papua New Guinea has experienced a growing HIV/AIDS epidemic. The Christian Churches have played a vital role in responding to HIV, through community support, encouragement and social change. Strong, effective Church leadership can help create safe environments of care and support for those infected and for prevention of HIV. Method A series of trainings in capacity development for clergy were undertaken by the National AIDS Council Secretariat (NACS)/National HIV/AIDS Support Project (NHASP). Results A model "Church's Response to HIV and AIDS in a Care Continuum" was developed to assist the training. This paper discusses the model and the lessons learned.

  2. 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. © 2015 Wiley Periodicals, Inc.

  3. Bilingual Education Model in Prekmurje, and the Dictionary as a Teaching Aid

    Directory of Open Access Journals (Sweden)

    Jutka Rudaš

    2018-01-01

    Full Text Available The model of bilingual education is one of the two-way models of preserving two languages and cultures. This paper describes the successful implementation of a bilingual education process, with a short developmental span and an emphasis on the key deficiencies of the model. By getting to know two cultures and two social relationships and by understanding them, pupils develop a positive attitude to cultural diversity as well as intercultural relationships. Within the framework of school subjects, we teach professional terminology in both languages and thus educate speakers in a way that they experience linguistic and cultural diversity in the ethnically mixed area of Prekmurje. The model of the two-way preservation of the mother tongue makes sense only if the community and the society benefit from bilingualism, and if important and above-average intercultural and social competences that contribute to peaceful coexistence of different cultures are allowed access. Practice shows that so far these goals have not been fully implemented, that there is no ideal relationship between the languages of instruction and that the desired results are not implemented. We have found that there are two shortcomings in this respect: the incomplete didactic aspect and the inadequate competence of teachers in bilingual educational institutions owing to the lack of possibility of acquiring the appropriate competences, particularly in the Hungarian language. Among the most important means for the efficiency of the language structure acquisition and language use are bilingual textbooks and other teaching aids. Based on these findings, this paper presents cognitive and other skills that enable the integration of a bilingual dictionary into the teaching process. As this is a demanding and important skill, it is crucial that teachers and pupils are trained in this activity. The dictionary as a didactic tool is not merely a means of information but also a basis for the

  4. 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

  5. Long-term immunogenicity studies of formalin-inactivated enterovirus 71 whole-virion vaccine in macaques.

    Directory of Open Access Journals (Sweden)

    Chia-Chyi Liu

    Full Text Available Enterovirus 71 (EV71 has caused epidemics of hand, foot and mouth diseases in Asia during the past decades and no vaccine is available. A formalin-inactivated EV71 candidate vaccine (EV71vac based on B4 subgenotype has previously been developed and found to elicit strong neutralizing antibody responses in mice and humans. In this study, we evaluated the long-term immunogenicity and safety of this EV71vac in a non-human primate model. Juvenile macaques were immunized at 0, 3 and 6 weeks either with 10 or 5 µg doses of EV71vac formulated with AlPO4 adjuvant, or PBS as control. During the 56 weeks of studies, no fever nor local redness and swelling at sites of injections was observed in the immunized macaques. After single immunization, 100% seroconversion based on 4-fold increased in neutralization titer (Nt was detected in EV71vac immunized monkeys but not PBS controls. A dose-dependent IgG antibody response was observed in monkeys receiving EV71vac immunization. The Nt of EV71vac immunized macaques had reached the peak after 3 vaccinations, then decreased gradually; however, the GMT of neutralizing antibody in the EV71vac immunized macaques were still above 100 at the end of the study. Correspondingly, both dose- and time-dependent interferon-γ and CD4+ T cell responses were detected in monkeys receiving EV71vac. Interestingly, similar to human responses, the dominant T cell epitopes of macaques were identified mainly in VP2 and VP3 regions. In addition, strong cross-neutralizing antibodies against most EV71 subgenotypes except some C2 and C4b strains, and Coxsackievirus A16 were observed. In summary, our results indicate that EV71vac elicits dose-dependent T-cell and antibody responses in macaques that could be a good animal model for evaluating the long-term immune responses elicited by EV71 vaccines.

  6. Kinetics of liver macrophages (Kupffer cells) in SIV-infected macaques

    International Nuclear Information System (INIS)

    Ahsan, Muhammad H.; Gill, Amy F.; Alvarez, Xavier; Lackner, Andrew A.; Veazey, Ronald S.

    2013-01-01

    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

  7. 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.

  8. Model-Aided Altimeter-Based Water Level Forecasting System in Mekong River

    Science.gov (United States)

    Chang, C. H.; Lee, H.; Hossain, F.; Okeowo, M. A.; Basnayake, S. B.; Jayasinghe, S.; Saah, D. S.; Anderson, E.; Hwang, E.

    2017-12-01

    Mekong River, one of the massive river systems in the world, has drainage area of about 795,000 km2 covering six countries. People living in its drainage area highly rely on resources given by the river in terms of agriculture, fishery, and hydropower. Monitoring and forecasting the water level in a timely manner, is urgently needed over the Mekong River. Recently, using TOPEX/Poseidon (T/P) altimetry water level measurements in India, Biancamaria et al. [2011] has demonstrated the capability of an altimeter-based flood forecasting system in Bangladesh, with RMSE from 0.6 - 0.8 m for lead times up to 5 days on 10-day basis due to T/P's repeat period. Hossain et al. [2013] further established a daily water level forecasting system in Bangladesh using observations from Jason-2 in India and HEC-RAS hydraulic model, with RMSE from 0.5 - 1.5 m and an underestimating mean bias of 0.25 - 1.25 m. However, such daily forecasting system relies on a collection of Jason-2 virtual stations (VSs) to ensure frequent sampling and data availability. Since the Mekong River is a meridional river with few number of VSs, the direct application of this system to the Mekong River becomes challenging. To address this problem, we propose a model-aided altimeter-based forecasting system. The discharge output by Variable Infiltration Capacity hydrologic model is used to reconstruct a daily water level product at upstream Jason-2 VSs based on the discharge-to-level rating curve. The reconstructed daily water level is then used to perform regression analysis with downstream in-situ water level to build regression models, which are used to forecast a daily water level. In the middle reach of the Mekong River from Nakhon Phanom to Kratie, a 3-day lead time forecasting can reach RMSE about 0.7 - 1.3 m with correlation coefficient around 0.95. For the lower reach of the Mekong River, the water flow becomes more complicated due to the reversal flow between the Tonle Sap Lake and the Mekong River

  9. Neurological Complications of AIDS

    Science.gov (United States)

    ... protect against infection) in causing disease in the central nervous system of adult macaques. The focus of these projects includes gene ... protect against infection) in causing disease in the central nervous system of adult macaques. The focus of these projects includes gene ...

  10. 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.

  11. The presence of the casein kinase II phosphorylation sites of Vpu enhances the CD4+ T cell loss caused by the simian-human immunodeficiency virus SHIVKU-lbMC33 in pig-tailed macaques

    International Nuclear Information System (INIS)

    Singh, Dinesh K.; Griffin, Darcy M.; Pacyniak, Erik; Jackson, Mollie; Werle, Michael J.; Wisdom, Bo; Sun, Francis; Hout, David R.; Pinson, David M.; Gunderson, Robert S.; Powers, Michael F.; Wong, Scott W.; Stephens, Edward B.

    2003-01-01

    The simian-human immunodeficiency virus (SHIV)/ macaque model for human immunodeficiency virus type 1 has become a useful tool to assess the role of Vpu in lentivirus pathogenesis. In this report, we have mutated the two phosphorylated serine residues of the HIV-1 Vpu to glycine residues and have reconstructed a SHIV expressing this nonphosphorylated Vpu (SHIV S52,56G ). Expression studies revealed that this protein was localized to the same intracellular compartment as wild-type Vpu. To determine if this virus was pathogenic, four pig-tailed macaques were inoculated with SHIV S52,56G and virus burdens and circulating CD4 + T cells monitored up to 1 year. Our results indicate that SHIV S52,56G caused rapid loss in the circulating CD4 + T cells within 3 weeks of inoculation in one macaque (CC8X), while the other three macaques developed no or gradual numbers of CD4 + T cells and a wasting syndrome. Histological examination of tissues revealed that macaque CC8X had lesions in lymphoid tissues (spleen, lymph nodes, and thymus) that were typical for macaques inoculated with pathogenic parental SHIV KU-1bMC33 and had no lesions within the CNS. To rule out that macaque CC8X had selected for a virus in which there was reversion of the glycine residues at positions 52 and 56 to serine residues and/or compensating mutations occurred in other genes associated with CD4 down-regulation, sequence analysis was performed on amplified vpu sequences isolated from PBMC and from several lymphoid tissues at necropsy. Sequence analysis revealed a reversion of the glycine residues back to serine residues in this macaque. The other macaques maintained low virus burdens, with one macaque (P003) developing a wasting syndrome between months 9 and 11. Histological examination of tissues from this macaque revealed a thymus with severe atrophy that was similar to that of a previously reported macaque inoculated with a SHIV lacking vpu (Virology 293, 2002, 252). Sequence analysis revealed no

  12. 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.; Bustamante, Eduardo A.; Bortell, Nikki; Morsey, Brenda; Fox, Howard S.; Ravasi, Timothy; Marcondes, Maria Cecilia Garibaldi

    2016-01-01

    /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

  13. 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; Bustamante, Eduardo; Bortell, Nikki; Morsey, Brenda; Fox, Howard; Ravasi, Timothy; Marcondes, Maria

    2016-01-01

    /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

  14. 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.

  15. Detection thresholds of macaque otolith afferents.

    Science.gov (United States)

    Yu, Xiong-Jie; Dickman, J David; Angelaki, Dora E

    2012-06-13

    The vestibular system is our sixth sense and is important for spatial perception functions, yet the sensory detection and discrimination properties of vestibular neurons remain relatively unexplored. Here we have used signal detection theory to measure detection thresholds of otolith afferents using 1 Hz linear accelerations delivered along three cardinal axes. Direction detection thresholds were measured by comparing mean firing rates centered on response peak and trough (full-cycle thresholds) or by comparing peak/trough firing rates with spontaneous activity (half-cycle thresholds). Thresholds were similar for utricular and saccular afferents, as well as for lateral, fore/aft, and vertical motion directions. When computed along the preferred direction, full-cycle direction detection thresholds were 7.54 and 3.01 cm/s(2) for regular and irregular firing otolith afferents, respectively. Half-cycle thresholds were approximately double, with excitatory thresholds being half as large as inhibitory thresholds. The variability in threshold among afferents was directly related to neuronal gain and did not depend on spike count variance. The exact threshold values depended on both the time window used for spike count analysis and the filtering method used to calculate mean firing rate, although differences between regular and irregular afferent thresholds were independent of analysis parameters. The fact that minimum thresholds measured in macaque otolith afferents are of the same order of magnitude as human behavioral thresholds suggests that the vestibular periphery might determine the limit on our ability to detect or discriminate small differences in head movement, with little noise added during downstream processing.

  16. Cholinergic control of visual categorisation in macaques

    Directory of Open Access Journals (Sweden)

    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.

  17. The First Aid Training Picture.

    Science.gov (United States)

    Moore, Ian

    2000-01-01

    Discusses the history of first aid training provisions in the United Kingdom with respect to the outdoor industry, what to look for in a first aid training provider, an experiential model of first aid training, and the current National Governing Body requirements for first aid training for various types of coaches and instructors. (TD)

  18. Experimental Oral Herpes Simplex Virus-1 (HSV-1 Co-infection in Simian Immunodeficiency Virus (SIV-Infected Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Meropi Aravantinou

    2017-12-01

    Full Text Available Herpes simplex virus 1 and 2 (HSV-1/2 similarly initiate infection in mucosal epithelia and establish lifelong neuronal latency. Anogenital HSV-2 infection augments the risk for sexual human immunodeficiency virus (HIV transmission and is associated with higher HIV viral loads. However, whether oral HSV-1 infection contributes to oral HIV susceptibility, viremia, or oral complications of HIV infection is unknown. Appropriate non-human primate (NHP models would facilitate this investigation, yet there are no published studies of HSV-1/SIV co-infection in NHPs. Thus, we performed a pilot study for an oral HSV-1 infection model in SIV-infected rhesus macaques to describe the feasibility of the modeling and resultant immunological changes. Three SIV-infected, clinically healthy macaques became HSV-1-infected by inoculation with 4 × 108 pfu HSV-1 McKrae on buccal, tongue, gingiva, and tonsils after gentle abrasion. HSV-1 DNA was shed in oral swabs for up to 21 days, and shedding recurred in association with intra-oral lesions after periods of no shedding during 56 days of follow up. HSV-1 DNA was detected in explant cultures of trigeminal ganglia collected at euthanasia on day 56. In the macaque with lowest baseline SIV viremia, SIV plasma RNA increased following HSV-1 infection. One macaque exhibited an acute pro-inflammatory response, and all three animals experienced T cell activation and mobilization in blood. However, T cell and antibody responses to HSV-1 were low and atypical. Through rigorous assessesments, this study finds that the virulent HSV-1 strain McKrae resulted in a low level HSV-1 infection that elicited modest immune responses and transiently modulated SIV infection.

  19. Developing Land Use Land Cover Maps for the Lower Mekong Basin to Aid SWAT Hydrologic Modeling

    Science.gov (United States)

    Spruce, J.; Bolten, J. D.; Srinivasan, R.

    2017-12-01

    This presentation discusses research to develop Land Use Land Cover (LULC) maps for the Lower Mekong Basin (LMB). Funded by a NASA ROSES Disasters grant, the main objective was to produce updated LULC maps to aid the Mekong River Commission's (MRC's) Soil and Water Assessment Tool (SWAT) hydrologic model. In producing needed LULC maps, temporally processed MODIS monthly NDVI data for 2010 were used as the primary data source for classifying regionally prominent forest and agricultural types. The MODIS NDVI data was derived from processing MOD09 and MYD09 8-day reflectance data with the Time Series Product Tool, a custom software package. Circa 2010 Landsat multispectral data from the dry season were processed into top of atmosphere reflectance mosaics and then classified to derive certain locally common LULC types, such as urban areas and industrial forest plantations. Unsupervised ISODATA clustering was used to derive most LULC classifications. GIS techniques were used to merge MODIS and Landsat classifications into final LULC maps for Sub-Basins (SBs) 1-8 of the LMB. The final LULC maps were produced at 250-meter resolution and delivered to the MRC for use in SWAT modeling for the LMB. A map accuracy assessment was performed for the SB 7 LULC map with 14 classes. This assessment was performed by comparing random locations for sampled LULC types to geospatial reference data such as Landsat RGBs, MODIS NDVI phenologic profiles, high resolution satellite data from Google Map/Earth, and other reference data from the MRC (e.g., crop calendars). LULC accuracy assessment results for SB 7 indicated an overall agreement to reference data of 81% at full scheme specificity. However, by grouping 3 deciduous forest classes into 1 class, the overall agreement improved to 87%. The project enabled updated LULC maps, plus more specific rice types were classified compared to the previous LULC maps. The LULC maps from this project should improve the use of SWAT for modeling

  20. MLH1-rheMac hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques.

    Science.gov (United States)

    Brammer, David W; Gillespie, Patrick J; Tian, Mei; Young, Daniel; Raveendran, Muthuswamy; Williams, Lawrence E; Gagea, Mihai; Benavides, Fernando J; Perez, Carlos J; Broaddus, Russell R; Bernacky, Bruce J; Barnhart, Kirstin F; Alauddin, Mian M; Bhutani, Manoop S; Gibbs, Richard A; Sidman, Richard L; Pasqualini, Renata; Arap, Wadih; Rogers, Jeffrey; Abee, Christian R; Gelovani, Juri G

    2018-03-13

    Over the past two decades, 33 cases of colonic adenocarcinomas have been diagnosed in rhesus macaques ( Macaca mulatta ) at the nonhuman primate colony of the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center. The distinctive feature in these cases, based on PET/computed tomography (CT) imaging, was the presence of two or three tumor lesions in different locations, including proximal to the ileocecal juncture, proximal to the hepatic flexure, and/or in the sigmoid colon. These colon carcinoma lesions selectively accumulated [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) and [ 18 F]fluoroacetate ([ 18 F]FACE) at high levels, reflecting elevated carbohydrate and fatty acid metabolism in these tumors. In contrast, the accumulation of [ 18 F]fluorothymidine ([ 18 F]FLT) was less significant, reflecting slow proliferative activity in these tumors. The diagnoses of colon carcinomas were confirmed by endoscopy. The expression of MLH1, MSH2, and MSH6 proteins and the degree of microsatellite instability (MSI) was assessed in colon carcinomas. The loss of MLH1 protein expression was observed in all tumors and was associated with a deletion mutation in the MLH1 promoter region and/or multiple single-nucleotide polymorphism (SNP) mutations in the MLH1 gene. All tumors exhibited various degrees of MSI. The pedigree analysis of this rhesus macaque population revealed several clusters of affected animals related to each other over several generations, suggesting an autosomal dominant transmission of susceptibility for colon cancer. The newly discovered hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques, termed MLH1 -rheMac, may serve as a model for development of novel approaches to diagnosis and therapy of Lynch syndrome in humans. Copyright © 2018 the Author(s). Published by PNAS.

  1. Tracing the phylogeographic history of Southeast Asian long-tailed macaques through mitogenomes of museum specimens.

    Science.gov (United States)

    Yao, Lu; Li, Hongjie; Martin, Robert D; Moreau, Corrie S; Malhi, Ripan S

    2017-11-01

    The biogeographical history of Southeast Asia is complicated due to the continuous emergences and disappearances of land bridges throughout the Pleistocene. Here, we use long-tailed macaques (Macaca fascicularis), which are widely distributed throughout the mainland and islands of Southeast Asia, asa model for better understanding the biogeographical patterns of diversification in this geographically complex region. A reliable intraspecific phylogeny including individuals from localities on oceanic islands, continental islands, and the mainland is needed to trace relatedness along with the pattern and timing of colonization in this region. We used high-throughput sequencing techniques to sequence mitochondrial genomes (mitogenomes) from 95 Southeast Asian M. fascicularis specimens housed at natural history museums around the world. To achieve a comprehensive picture, we more than tripled the mitogenome sample size for M. fascicularis from previous studies, and for the first time included documented samples from the Philippines and several small Indonesian islands. Confirming the result from a previous, recent intraspecific phylogeny for M. fascicularis, the newly reconstructed phylogeny of 135 specimens divides the samples into two major clades: Clade A includes haplotypes from the mainland and some from northern Sumatra, while Clade B includes all insular haplotypes along with lineages from southern Sumatra. This study resolves a previous disparity by revealing a disjunction in the origin of Sumatran macaques, with separate lineages originating within the two major clades, suggesting that at least two major migrations to Sumatra occurred. However, our dated phylogeny reveals that the two major clades split ∼1.88Ma, which is earlier than in previously published phylogenies. Our new data reveal that most Philippine macaque lineages diverged from the Borneo stock within the last ∼0.06-0.43Ma. Finally, our study provides insight into successful sequencing of DNA

  2. 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.

  3. Naltrexone treatment reverses astrocyte atrophy and immune dysfunction in self-harming macaques.

    Science.gov (United States)

    Lee, Kim M; Chiu, Kevin B; Didier, Peter J; Baker, Kate C; MacLean, Andrew G

    2015-11-01

    The role of glia in the development and treatment of behavioral abnormalities is understudied. Recent reports have observed glial activation in several disorders, including depression, autism spectrum disorders and self-injurious behaviors (SIB). In the current study, we examined SIB in the physiologically and anatomically relevant nonhuman primate (NHP) model. At the Tulane National Primate Research Center (TNPRC), approximately 5% of singly housed macaques develop symptoms of SIB. We have previously demonstrated that naltrexone hydrochloride can be effective in reducing SIB. We have also demonstrated that the astrocytes of animals with SIB are distinctly atrophic and display heightened innate immune activation compared with control animals. We have added a third group of animals (five macaques identified with SIB and treated with oral naltrexone at a dose of 3.2mg/kg) to the previous cohort (six macaques with a history of SIB but not treated, and nine animals with no history of SIB) for this study. Gray and white matter astrocytes from frontal cortical tissue were examined following necropsy. Innate immune activation of astrocytes, which was increased in SIB animals, was markedly decreased in animals receiving naltrexone, as was atrophy of both grey and white matter astrocytes. This was concomitant with improved behavioral correlates. Preventing astrocyte activation in select areas of the brain to reduce injurious behavior is an innovative concept with implications for mental health studies. Differences in multiple areas of primate brain would help determine how self-injurious behavior develops. These studies suggest a stronger role for astrocytes in the cellular events associated with self-injurious behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Women Living with HIV in Rural Areas. Implementing a Response using the HIV and AIDS Risk Assessment and Reduction Model

    Directory of Open Access Journals (Sweden)

    Sarah Bandali

    2014-01-01

    Full Text Available The global fight against HIV is progressing; however, women living in rural areas particularly in sub-Saharan Africa (SSA continue to face the devastating consequences of HIV and AIDS. Lack of knowledge and geographical barriers to HIV services are compounded by gender norms often limiting the negotiation of safe sexual practices among women living in rural areas. This paper discusses findings from a qualitative study conducted in rural areas of Mozambique examining factors that influenced women to engage in HIV risk-reduction practices. The findings from this study led to the emergence of an HIV and AIDS risk assessment and reduction (HARAR model, which is described in detail. The model helps in understanding gender-related factors influencing men and women to engage in risk-reduction practices, which can be used as a framework in other settings to design more nuanced and contextual policies and programs.

  5. Cost-efficiency assessment of 3 different pediatric first-aid training models for caregivers and teachers in Shanghai.

    Science.gov (United States)

    Li, Feng; Jiang, Fan; Jin, Xing-Ming; Shen, Xiao-Ming

    2011-05-01

    The object of this study was to assess, in cost-effective measures, 3 different models for pediatric first-aid training among caregivers and teachers. Quasi-experimental design was used. A stratified random sampling method was used to obtain 1282 teachers working at nurseries and kindergartens in Shanghai that consists of 18 districts and 1 county. One thousand two hundred eighty-two teachers were allocated randomly to the 3 models of training: 441 to interactive training model (group A), 441 to lecture-based training model (group B), and 400 to video instruction training model (group C). The first-aid knowledge in the 3 models was evaluated before and after the training. There was a statistical significance in the results of postassessment among the 3 training models. In group A, 329 (87.3%) trainees passed the course; in group B, 294 (81.7%) passed; and in group C, 262 (79.4%) passed. The total cost of group A was ¥2361 per edition, the total cost of group B was ¥1955 per edition, and the total cost of group C was ¥1064 per edition (P training model may slightly increase the rate of trainees who passed the course, the cost-effectiveness of video instruction training model is clearly superior.

  6. Educational aids

    International Nuclear Information System (INIS)

    Lenkeit, S.

    1989-01-01

    Educational aids include printed matter, aural media, visual media, audiovisual media and objects. A distinction is made between learning aids, which include blackboards, overhead projectors, flipcharts, wallcharts and pinboards, and learning aids, which include textbooks, worksheets, documentation and experimental equipment. The various aids are described and their use explained. The aids available at the School for Nuclear Technology of the Karlsruhe Nuclear Research Centre are described

  7. Combined Transcriptomics and Metabolomics in a Rhesus Macaque Drug Administration Study

    Directory of Open Access Journals (Sweden)

    Kevin J. Lee

    2014-10-01

    Full Text Available We describe a multi-omic approach to understanding the effects that the anti-malarial drug pyrimethamine has on immune physiology in rhesus macaques (Macaca mulatta. Whole blood and bone marrow RNA-Seq and plasma metabolome profiles (each with over 15,000 features have been generated for five naïve individuals at up to seven time-points before, during and after three rounds of drug administration. Linear modelling and Bayesian network analyses are both considered, alongside investigations of the impact of statistical modeling strategies on biological inference. Individual macaques were found to be a major source of variance for both omic data types, and factoring individuals into subsequent modelling increases power to detect temporal effects. A major component of the whole blood transcriptome follows the bone marrow with a time-delay, while other components of variation are unique to each compartment. We demonstrate that pyrimethamine administration does impact both compartments throughout the experiment, but very limited perturbation of transcript or metabolite abundance following each round of drug exposure is observed. New insights into the mode of action of the drug are presented in the context of pyrimethamine’s predicted effect on suppression of cell division and metabolism in the immune system.

  8. 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......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...

  9. 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...

  10. Reconciliation and relationship quality in Assamese macaques (Macaca assamensis)

    NARCIS (Netherlands)

    Cooper, M.A.; Bernstein, I.S.; Hemelrijk, C.K.

    A consistent conclusion in reconciliation research is that animals that reconcile are likely to have strong social bonds. This has led to the hypothesis that reconciliation occurs most often between valuable social partners. We tested this hypothesis in a group of Assamese macaques (Macaca

  11. Molecular characterization and polymorphisms of butyrylcholinesterase in cynomolgus macaques.

    Science.gov (United States)

    Uno, Yasuhiro; Uehara, Shotaro; Mahadhi, Hassan M D; Ohura, Kayoko; Hosokawa, Masakiyo; Imai, Teruko

    2018-06-01

    Butyrylcholinesterase (BChE), an enzyme essential for drug metabolism, has been investigated as antidotes against organophosphorus nerve agents, and the efficacy and safety have been studied in cynomolgus macaques. BChE polymorphisms partly account for variable BChE activities among individuals in humans, but have not been investigated in cynomolgus macaques. Molecular characterization was carried out by analyzing primary sequence, gene, tissue expression, and genetic variants. In cynomolgus and human BChE, phylogenetically closely related, amino acid residues important for enzyme function were conserved, and gene and genomic structure were similar. Cynomolgus BChE mRNA was most abundantly expressed in liver among the 10 tissue types analyzed. Re-sequencing found 26 non-synonymous genetic variants in 121 cynomolgus and 23 rhesus macaques, indicating that macaque BChE is polymorphic, although none of these variants corresponded to the null or defective alleles of human BChE. These results suggest molecular similarities of cynomolgus and human BChE. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Expression of cytochrome P450 regulators in cynomolgus macaque.

    Science.gov (United States)

    Uno, Yasuhiro; Yamazaki, Hiroshi

    2017-09-11

    1. Cytochrome P450 (P450) regulators including nuclear receptors and transcription factors have not been fully investigated in cynomolgus macaques, an important species used in drug metabolism studies. In this study, we analyzed 17 P450 regulators by sequence and phylogenetic analysis, and tissue expression. 2. Gene and genome structures of 17 P450 regulators were similar to the human orthologs, and the deduced amino acid sequences showed high sequence identities (92-95%) and more closely clustered in a phylogenetic tree, with the human orthologs. 3. Many of the P450 regulator mRNAs were preferentially expressed in the liver, kidney, and/or jejunum. Among the P450 regulator mRNAs, PXR was most abundant in the liver and jejunum, and HNF4α in the kidney. In the liver, the expression of most P450 regulator mRNAs did not show significant differential expression (>2.5-fold) between cynomolgus macaques bred in Cambodia, China, and Indonesia, or rhesus macaques. 4. By correlation analysis, most of the P450 regulators were significantly (p < 0.05) correlated to other P450 regulators, and many of them were also significantly (p < 0.05) correlated with P450s. 5. These results suggest that 17 P450 regulators of cynomolgus macaques had similar molecular characteristics to the human orthologs.

  13. Mutual aid in oil spill response: The Alaskan north slope model

    International Nuclear Information System (INIS)

    McKenzie, B.; Ingram, N.

    1993-01-01

    The Alaskan Arctic Region provides one of the world's most remote and challenging environments in which to mount an oil spill response. To facilitate the timeliness and appropriateness of the response, Alaska Clean Seas (ACS) and the operators of the North Slope oil fields have implemented a mutual aid concept for spill response. The concept is based upon each operator on the North Slope maintaining its own inventory of personnel [a spill response team (SRT)] and equipment that is available on short notice to respond to a spill. If the spill exceeds the responsible operator's resources, additional resources can be obtained from other operators and/or ACS through mutual aid. Individuals from diverse organizations are brought together in a mutual aid event. To allow different organizations to function effectively in a multi-organizational environment, a common management structure was required. The structure chosen for the North Slope was the incident command system (ICS). A key concern when discussing mutual aid is the provision of indemnification from liability for responders. For the North Slope, ACS and its member companies are indemnified when responding to a spill through provisions in the ACS charter and the ACS response action contract

  14. Beyond the political model of reporting: nonspecific symptoms in media communication about AIDS.

    Science.gov (United States)

    Check, W A

    1987-01-01

    Mass media have functioned well in transmitting much of the basic information about the AIDS epidemic; however, media coverage of AIDS has been flawed. In many ways these flaws have resulted from the limitations and conventions of traditional journalism, especially the need to appeal to a large mainstream audience and a reliance on authorities as sources and validators of information. News stories typically rely on a single articulate authority, and articles that involve conspiracy or controversy or have a high entertainment value are favored. Although coverage of politics and social issues is not distorted by these journalistic conventions, coverage of science suffers. Analysis of news coverage of AIDS shows that mass media often respond to sensationalism rather than to important scientific developments. In addition, scientific disagreements are better adjudicated by evidence than by appeals to authority. As a result, media coverage often obscures the process of scientific deliberation. Public health officials need to consider setting up a special channel of communications to clarify information about AIDS.

  15. The nucleus pararaphales in the human, chimpanzee, and macaque monkey.

    Science.gov (United States)

    Baizer, Joan S; Weinstock, Nadav; Witelson, Sandra F; Sherwood, Chet C; Hof, Patrick R

    2013-03-01

    The human cerebral cortex and cerebellum are greatly expanded compared to those of other mammals, including the great apes. This expansion is reflected in differences in the size and organization of precerebellar brainstem structures, such as the inferior olive. In addition, there are cell groups unique to the human brainstem. One such group may be the nucleus pararaphales (PRa); however, there is disagreement among authors about the size and location of this nucleus in the human brainstem. The name "pararaphales" has also been used for neurons in the medulla shown to project to the flocculus in the macaque monkey. We have re-examined the existence and status of the PRa in eight humans, three chimpanzees, and four macaque monkeys using Nissl-stained sections as well as immunohistochemistry. In the human we found a cell group along the midline of the medulla in all cases; it had the form of interrupted cell columns and was variable among cases in rostrocaudal and dorsoventral extent. Cells and processes were highly immunoreactive for non-phosphorylated neurofilament protein (NPNFP); somata were immunoreactive to the synthetic enzyme for nitric oxide, nitric oxide synthase, and for calretinin. In macaque monkey, there was a much smaller oval cell group with NPNFP immunoreactivity. In the chimpanzee, we found a region of NPNFP-immunoreactive cells and fibers similar to what was observed in macaques. These results suggest that the "PRa" in the human may not be the same structure as the flocculus-projecting cell group described in the macaque. The PRa, like the arcuate nucleus, therefore may be unique to humans.

  16. Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques.

    Science.gov (United States)

    Meyer, C; Walker, J; Dewane, J; Engelmann, F; Laub, W; Pillai, S; Thomas, Charles R; Messaoudi, I

    2015-09-01

    In this study we examined the effects of non-myeloablative total body irradiation (TBI) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. Our results show that the administration of cyclosporin A or tacrolimus without radiotherapy did not result in lymphopenia. The addition of TBI to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. Dendritic cell (DC) numbers in whole blood were largely unaffected, while the monocyte population was altered by immunosuppressive treatment. Irradiation also resulted in increased levels of circulating cytokines and chemokines that correlated with T cell proliferative bursts and with the shift towards memory T cells. We also report that anti-thymocyte globulin (ATG) treatment and CD3 immunotoxin administration resulted in a selective and rapid depletion of naive CD4 and CD8 T cells and increased frequency of memory T cells. We also examined the impact of these treatments on reactivation of latent simian varicella virus (SVV) infection as a model of varicella zoster virus (VZV) infection of humans. None of the treatments resulted in overt SVV reactivation; however, select animals had transient increases in SVV-specific T cell responses following immunosuppression, suggestive of subclinical reactivation. Overall, we provide detailed observations into immune modulation by TBI and chemotherapeutic agents in rhesus macaques, an important research model of human disease. © 2015 British Society for Immunology.

  17. Complex assembly, crystallization and preliminary X-ray crystallographic studies of rhesus macaque MHC Mamu-A*01 complexed with an immunodominant SIV-Gag nonapeptide

    International Nuclear Information System (INIS)

    Chu, Fuliang; Lou, Zhiyong; Gao, Bin; Bell, John I.; Rao, Zihe; Gao, George F.

    2005-01-01

    Crystallization of the first rhesus macaque MHC class I complex. Simian immunodeficiency virus (SIV) infection in rhesus macaques has been used as the best model for the study of human immunodeficiency virus (HIV) infection in humans, especially in the cytotoxic T-lymphocyte (CTL) response. However, the structure of rhesus macaque (or any other monkey model) major histocompatibility complex class I (MHC I) presenting a specific peptide (the ligand for CTL) has not yet been elucidated. Here, using in vitro refolding, the preparation of the complex of the rhesus macaque MHC I allele (Mamu-A*01) with human β 2 m and an immunodominant peptide, CTPYDINQM (Gag-CM9), derived from SIV Gag protein is reported. The complex (45 kDa) was crystallized; the crystal belongs to space group I422, with unit-cell parameters a = b = 183.8, c = 155.2 Å. The crystal contains two molecules in the asymmetric unit and diffracts X-rays to 2.8 Å resolution. The structure is being solved by molecular replacement and this is the first attempt to determined the crystal structure of a peptide–nonhuman primate MHC complex

  18. 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.

  19. Protection of macaques with diverse MHC genotypes against a heterologous SIV by vaccination with a deglycosylated live-attenuated SIV.

    Directory of Open Access Journals (Sweden)

    Chie Sugimoto

    Full Text Available HIV vaccine development has been hampered by issues such as undefined correlates of protection and extensive diversity of HIV. We addressed these issues using a previously established SIV-macaque model in which SIV mutants with deletions of multiple gp120 N-glycans function as potent live attenuated vaccines to induce near-sterile immunity against the parental pathogenic SIVmac239. In this study, we investigated the protective efficacy of these mutants against a highly pathogenic heterologous SIVsmE543-3 delivered intravenously to rhesus macaques with diverse MHC genotypes. All 11 vaccinated macaques contained the acute-phase infection with blood viral loads below the level of detection between 4 and 10 weeks postchallenge (pc, following a transient but marginal peak of viral replication at 2 weeks in only half of the challenged animals. In the chronic phase, seven vaccinees contained viral replication for over 80 weeks pc, while four did not. Neutralizing antibodies against challenge virus were not detected. Although overall levels of SIV specific T cell responses did not correlate with containment of acute and chronic viral replication, a critical role of cellular responses in the containment of viral replication was suggested. Emergence of viruses with altered fitness due to recombination between the vaccine and challenge viruses and increased gp120 glycosylation was linked to the failure to control SIV. These results demonstrate the induction of effective protective immune responses in a significant number of animals against heterologous virus by infection with deglycosylated attenuated SIV mutants in macaques with highly diverse MHC background. These findings suggest that broad HIV cross clade protection is possible, even in hosts with diverse genetic backgrounds. In summary, results of this study indicate that deglycosylated live-attenuated vaccines may provide a platform for the elucidation of correlates of protection needed for a

  20. Predictive Value of Parkinsonian Primates in Pharmacologic Studies: A Comparison between the Macaque, Marmoset, and Squirrel Monkey.

    Science.gov (United States)

    Veyres, Nicolas; Hamadjida, Adjia; Huot, Philippe

    2018-05-01

    The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate is the gold-standard animal model of Parkinson disease (PD) and has been used to assess the effectiveness of experimental drugs on dyskinesia, parkinsonism, and psychosis. Three species have been used in most studies-the macaque, marmoset, and squirrel monkey-the last much less so than the first two species; however, the predictive value of each species at forecasting clinical efficacy, or lack thereof, is poorly documented. Here, we have reviewed all the published literature detailing pharmacologic studies that assessed the effects of experimental drugs on dyskinesia, parkinsonism, and psychosis in each of these species and have calculated their predictive value of success and failure at the clinical level. We found that, for dyskinesia, the macaque has a positive predictive value of 87.5% and a false-positive rate of 38.1%, whereas the marmoset has a positive predictive value of 76.9% and a false-positive rate of 15.6%. For parkinsonism, the macaque has a positive predictive value of 68.2% and a false-positive rate of 44.4%, whereas the marmoset has a positive predictive value of 86.9% and a false-positive rate of 41.7%. No drug that alleviates psychosis in the clinic has shown efficacy at doing so in the macaque, whereas the marmoset has 100% positive predictive value. The small number of studies conducted in the squirrel monkey precluded us from calculating its predictive efficacy. We hope our results will help in the design of pharmacologic experiments and will facilitate the drug discovery and development process in PD. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  1. Therapeutic administration of a recombinant human monoclonal antibody reduces the severity of chikungunya virus disease in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Rebecca Broeckel

    2017-06-01

    Full Text Available Chikungunya virus (CHIKV is a mosquito-borne virus that causes a febrile syndrome in humans associated with acute and chronic debilitating joint and muscle pain. Currently no licensed vaccines or therapeutics are available to prevent or treat CHIKV infections. We recently isolated a panel of potently neutralizing human monoclonal antibodies (mAbs, one (4N12 of which exhibited prophylactic and post-exposure therapeutic activity against CHIKV in immunocompromised mice. Here, we describe the development of an engineered CHIKV mAb, designated SVIR001, that has similar antigen binding and neutralization profiles to its parent, 4N12. Because therapeutic administration of SVIR001 in immunocompetent mice significantly reduced viral load in joint tissues, we evaluated its efficacy in a rhesus macaque model of CHIKV infection. Rhesus macaques that were treated after infection with SVIR001 showed rapid elimination of viremia and less severe joint infiltration and disease compared to animals treated with SVIR002, an isotype control mAb. SVIR001 reduced viral burden at the site of infection and at distant sites and also diminished the numbers of activated innate immune cells and levels of pro-inflammatory cytokines and chemokines. SVIR001 therapy; however, did not substantively reduce the induction of CHIKV-specific B or T cell responses. Collectively, these results show promising therapeutic activity of a human anti-CHIKV mAb in rhesus macaques and provide proof-of-principle for its possible use in humans to treat active CHIKV infections.

  2. An electrocorticographic electrode array for simultaneous recording from medial, lateral, and intrasulcal surface of the cortex in macaque monkeys.

    Science.gov (United States)

    Fukushima, Makoto; Saunders, Richard C; Mullarkey, Matthew; Doyle, Alexandra M; Mishkin, Mortimer; Fujii, Naotaka

    2014-08-15

    Electrocorticography (ECoG) permits recording electrical field potentials with high spatiotemporal resolution over a large part of the cerebral cortex. Application of chronically implanted ECoG arrays in animal models provides an opportunity to investigate global spatiotemporal neural patterns and functional connectivity systematically under various experimental conditions. Although ECoG is conventionally used to cover the gyral cortical surface, recent studies have shown the feasibility of intrasulcal ECoG recordings in macaque monkeys. Here we developed a new ECoG array to record neural activity simultaneously from much of the medial and lateral cortical surface of a single hemisphere, together with the supratemporal plane (STP) of the lateral sulcus in macaque monkeys. The ECoG array consisted of 256 electrodes for bipolar recording at 128 sites. We successfully implanted the ECoG array in the left hemisphere of three rhesus monkeys. The electrodes in the auditory and visual cortex detected robust event related potentials to auditory and visual stimuli, respectively. Bipolar recording from adjacent electrode pairs effectively eliminated chewing artifacts evident in monopolar recording, demonstrating the advantage of using the ECoG array under conditions that generate significant movement artifacts. Compared with bipolar ECoG arrays previously developed for macaque monkeys, this array significantly expands the number of cortical target areas in gyral and intralsulcal cortex. This new ECoG array provides an opportunity to investigate global network interactions among gyral and intrasulcal cortical areas. Published by Elsevier B.V.

  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. © 2011 Wiley Periodicals, Inc.

  4. Implementation and display of Computer Aided Design (CAD) models in Monte Carlo radiation transport and shielding applications

    International Nuclear Information System (INIS)

    Burns, T.J.

    1994-01-01

    An Xwindow application capable of importing geometric information directly from two Computer Aided Design (CAD) based formats for use in radiation transport and shielding analyses is being developed at ORNL. The application permits the user to graphically view the geometric models imported from the two formats for verification and debugging. Previous models, specifically formatted for the radiation transport and shielding codes can also be imported. Required extensions to the existing combinatorial geometry analysis routines are discussed. Examples illustrating the various options and features which will be implemented in the application are presented. The use of the application as a visualization tool for the output of the radiation transport codes is also discussed

  5. 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. ...

  6. 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...... and institutions of the aid system; and (c) discusses whether aid has been effective. While much of the original optimism about the impact of foreign aid needed modification, there is solid evidence that aid has indeed helped further growth and poverty reduction...

  7. Modeling HIV/AIDS Drug Price Determinants in Brazil: Is Generic Competition a Myth?

    OpenAIRE

    Meiners, Constance; Sagaon-Teyssier, Luis; Hasenclever, Lia; Moatti, Jean-Paul

    2011-01-01

    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 internat...

  8. 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.

  9. An effort to use human-based exome capture methods to analyze chimpanzee and macaque exomes.

    Directory of Open Access Journals (Sweden)

    Xin Jin

    Full Text Available 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-based resequencing validated 85.4% of 41 randomly selected SNPs. Among the short indels identified, a majority (54.6%-77.3% of the variants resulted in a change of 3 base pairs, consistent with expectations for a selection against frame shift mutations. Taken together, these findings indicate that use of a human design exon-capture array can provide efficient enrichment of non-human primate gene regions. Accordingly, use of the human exon-capture methods provides an attractive, cost-effective approach for the comparative analysis of non-human primate genomes, including gene-based DNA variant discovery.

  10. Plasmodium coatneyi in Rhesus Macaques Replicates the Multisystemic Dysfunction of Severe Malaria in Humans

    Science.gov (United States)

    Cabrera-Mora, Monica; Garcia, AnaPatricia; Orkin, Jack; Strobert, Elizabeth; Barnwell, John W.; Galinski, Mary R.

    2013-01-01

    Severe malaria, a leading cause of mortality among children and nonimmune adults, is a multisystemic disorder characterized by complex clinical syndromes that are mechanistically poorly understood. The interplay of various parasite and host factors is critical in the pathophysiology of severe malaria. However, knowledge regarding the pathophysiological mechanisms and pathways leading to the multisystemic disorders of severe malaria in humans is limited. Here, we systematically investigate infections with Plasmodium coatneyi, a simian malaria parasite that closely mimics the biological characteristics of P. falciparum, and develop baseline data and protocols for studying erythrocyte turnover and severe malaria in greater depth. We show that rhesus macaques (Macaca mulatta) experimentally infected with P. coatneyi develop anemia, coagulopathy, and renal and metabolic dysfunction. The clinical course of acute infections required suppressive antimalaria chemotherapy, fluid support, and whole-blood transfusion, mimicking the standard of care for the management of severe malaria cases in humans. Subsequent infections in the same animals progressed with a mild illness in comparison, suggesting that immunity played a role in reducing the severity of the disease. Our results demonstrate that P. coatneyi infection in rhesus macaques can serve as a highly relevant model to investigate the physiological pathways and molecular mechanisms of malaria pathogenesis in naïve and immune individuals. Together with high-throughput postgenomic technologies, such investigations hold promise for the identification of new clinical interventions and adjunctive therapies. PMID:23509137

  11. Limited SHIV env diversification in macaques failing oral antiretroviral pre-exposure prophylaxis.

    Science.gov (United States)

    Zheng, Qi; Ruone, Susan; Switzer, William M; Heneine, Walid; García-Lerma, J Gerardo

    2012-05-09

    Pre-exposure prophylaxis (PrEP) with daily Truvada [a combination of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF)] is a novel HIV prevention strategy recently found to prevent HIV transmission among men who have sex with men and heterosexual couples. Acute infection in adherent persons who fail PrEP will inevitably occur under concurrent antiretroviral therapy, thus raising questions regarding the potential impact of PrEP on early viral dynamics. We investigated viral evolution dynamics in a macaque model of PrEP consisting of repeated rectal exposures to SHIV162P3 in the presence of PrEP. Four macaques were infected during daily or intermittent PrEP with FTC or FTC/TDF, and five were untreated controls. SHIV env sequence evolution was monitored by single genome amplification with phylogenetic and sequence analysis. Mean nucleotide divergence from transmitted founder viruses calculated 17 weeks (range = 12-20) post peak viremia was significantly lower in PrEP failures than in control animals (7.2 × 10-3 compared to 1.6 × 10-2 nucleotide substitutions per site per year, respectively, p diversification during early infection might enhance immune control by slowing the selection of escape mutants.

  12. Propagated but Topologically Distributed Forebrain Neurons Expressing Alpha-Synuclein in Aged Macaques.

    Directory of Open Access Journals (Sweden)

    Katsuo Kimura

    Full Text Available In neurodegenerative disorders, such as Parkinson's disease (PD, alpha-synuclein (α-syn accumulates to induce cell death and/or form a cytoplasmic inclusion called Lewy body (LB. This α-syn-related pathology is termed synucleinopathy. It remains unclear how α-syn accumulation expands during the progress of synucleinopathy in the human brain. In our study, we investigated the patterns of distribution and propagation of forebrain neurons expressing α-syn in aged macaques. It was found that the occurrence of α-syn-positive neurons proceeded topologically based on the midbrain dopamine pathways arising from the substantia nigra and the ventral tegmental area where they were primarily observed. In the nigrostriatal or mesolimbic dopamine pathway, the age-dependent increase in α-syn-positive neurons was evident in the striatum or the nucleus accumbens, respectively. Concerning the nigrostriatal pathway, a mediolateral or rostrocaudal gradient was seen in the substantia nigra or the striatum, respectively, and a compensatory increase in dopamine transporter occurred in the striatum regardless of the decreased dopamine level. In the mesocortical dopamine pathway, α-syn-positive neurons appeared in the prefrontal and then motor areas of the frontal lobe. Given that neither LB formation nor clinical phenotype manifestation was detected in any of the monkeys examined in the present study, aged macaques may be useful as a potential presymptomatic model for PD and LB-related neuropsychiatric disorders.

  13. Social modulation of cognition: Lessons from rhesus macaques relevant to education.

    Science.gov (United States)

    Monfardini, Elisabetta; Reynaud, Amélie J; Prado, Jérôme; Meunier, Martine

    2017-11-01

    Any animal, human or non-human, lives in a world where there are others like itself. Individuals' behaviors are thus inevitably influenced by others, and cognition is no exception. Long acknowledged in psychology, social modulations of cognition have been neglected in cognitive neuroscience. Yet, infusing this classic topic in psychology with brain science methodologies could yield valuable educational insights. In recent studies, we used a non-human primate model, the rhesus macaque, to identify social influences representing ancient biases rooted in evolution, and neuroimaging to shed light on underlying mechanisms. The behavioral and neural data garnered in humans and macaques are summarized, with a focus on two findings relevant to human education. First, peers' mistakes stand out as exceptional professors and seem to have devoted areas and neurons in the primates' brain. Second, peers' mere presence suffices to enhance performance in well-learned tasks, possibly by boosting activity in the brain network involved in the task at hand. These findings could be translated into concrete pedagogical interventions in the classroom. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. HEALTH BELIEF MODEL DAN KAITANNYA DENGAN KETIDAKPATUHAN TERAPI ANTIRETEROVIRAL PADA ORANG DENGAN HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Abdul Kharis Sisyahid

    2017-01-01

    Full Text Available Antiretroviral (ARV therapy for people living with HIV/AIDS (PLHIV may reduce mortality and improve the quality of life among them. Non-adherence of HIV/AIDS patients in ARV therapy may lead to cease of therapy, increase risk of death, complicate evaluation of ARV services, and increase the risk of ARV resistance if they wish to start over. This study aimed to determine the factors that cause non-adherence to ARV therapy among PLHIV in Pemalang Regency. The research used qualitative method with case study approach. Data collection was conducted through in-depth interviews, observations, and documentation to 6 HIV/ AIDS patients who were listed as non-adherence patient in ARV therapy. Data analysis was done descriptively with triangulation method and data analysis. Results revealed that the factors that cause non-adherence to ARV therapy among PLHIV were lack of vulnerability perception to illness in the future, lack of illness perception among informants about the severity of illness, lack of benefit perception perceived by most informants, and barrier perception of side effects, lack of facilities to access ARV, and pudency that their HIV-positive status was known by others.

  15. Identification of Rotavirus VP6-Specific CD4+ T Cell Epitopes in a G1P[8] Human Rotavirus-Infected Rhesus Macaque

    Directory of Open Access Journals (Sweden)

    Wei Zhao

    2008-01-01

    Full Text Available A non-human primate model was used to evaluate its potential for identification of rotavirus viral protein 6 (VP6 CD4+ T cell epitopes. Four juvenile rhesus macaques were inoculated with a mixed inoculum (G1P[8] and G9P[8] of human rotaviruses. Infection accompanied by G1P[8] shedding was achieved in the two macaques that had no rotavirus immunoglobulin A (IgA in plasma. To measure the interferon gamma (IFN-γ and tumor necrosis factor (TNF anti-viral cytokines produced by peripheral CD4+ cells that recognize VP6 epitopes, whole blood cells from one infected macaque were stimulated in vitro with VP6 peptides. Stimulation with peptide pools derived from the simian rotavirus VP6 161–395 region revealed reactivity of CD4+ T cells with the VP6 281–331 domain. A VP6 301–315 region was identified as the epitope responsible for IFN-γ production while a broader VP6 293–327 domain was linked to TNF production. These results suggest that human rotavirus-infected macaques can be used for identification of additional epitopes and domains to address specific questions related to the development of pediatric vaccines.

  16. Aid and Growth

    DEFF Research Database (Denmark)

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

    , 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......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...... 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....

  17. Identification and characterization of short tandem repeats in the Tibetan macaque genome based on resequencing data.

    Science.gov (United States)

    Liu, San-Xu; Hou, Wei; Zhang, Xue-Yan; Peng, Chang-Jun; Yue, Bi-Song; Fan, Zhen-Xin; Li, Jing

    2018-07-18

    The Tibetan macaque, which is endemic to China, is currently listed as a Near Endangered primate species by the International Union for Conservation of Nature (IUCN). Short tandem repeats (STRs) refer to repetitive elements of genome sequence that range in length from 1-6 bp. They are found in many organisms and are widely applied in population genetic studies. To clarify the distribution characteristics of genome-wide STRs and understand their variation among Tibetan macaques, we conducted a genome-wide survey of STRs with next-generation sequencing of five macaque samples. A total of 1 077 790 perfect STRs were mined from our assembly, with an N50 of 4 966 bp. Mono-nucleotide repeats were the most abundant, followed by tetra- and di-nucleotide repeats. Analysis of GC content and repeats showed consistent results with other macaques. Furthermore, using STR analysis software (lobSTR), we found that the proportion of base pair deletions in the STRs was greater than that of insertions in the five Tibetan macaque individuals (Pgenome showed good amplification efficiency and could be used to study population genetics in Tibetan macaques. The neighbor-joining tree classified the five macaques into two different branches according to their geographical origin, indicating high genetic differentiation between the Huangshan and Sichuan populations. We elucidated the distribution characteristics of STRs in the Tibetan macaque genome and provided an effective method for screening polymorphic STRs. Our results also lay a foundation for future genetic variation studies of macaques.

  18. 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....

  19. 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.

  20. The use of 3D CADD (Computer Aided Design and Drafting) models in operation and maintenance cost reduction

    International Nuclear Information System (INIS)

    Didsbury, R.; Bains, N.; Cho, U.Y.

    1998-01-01

    The use of three dimensional(3D) computer-aided design and drafting(CADD) models, and the associated information technology and databases, in the engineering and construction phases of large projects is well established and yielding significant improvements in project cost, schedule and quality. The information contained in these models can also be extremely valuable to operating plants, particularly when the visual and spatial information contained in the 3D models is interfaced to other plant information databases. Indeed many plant owners and operators in the process and power industries are already using this technology to assist with such activities as plant configuration management, staff training, work planning and radiation protection. This paper will explore the application of 3D models and the associated databases in an operating plant environment and describe the resulting operational benefits and cost reduction benefits. Several industrial experience case studies will be presented along with suggestions for further future applications. (author). 4 refs., 1 tab., 8 figs

  1. Testosterone correlates with Venezuelan equine encephalitis virus infection in macaques

    Directory of Open Access Journals (Sweden)

    Koterski James

    2006-03-01

    Full Text Available Abstract Here we briefly report testosterone and cytokine responses to Venezuelan equine encephalitis virus (VEEV in macaques which were used as part of a larger study conducted by the Department of Defense to better characterize pathological responses to aerosolized VEEV in non-human primates. Serial samples were collected and analyzed for testosterone and cytokines prior to and during infection in 8 captive male macaques. Infected animals exhibited a febrile response with few significant changes in cytokine levels. Baseline testosterone levels were positively associated with viremia following exposure and were significantly higher than levels obtained during infection. Such findings suggest that disease-induced androgen suppression is a reasonable area for future study. Decreased androgen levels during physiological perturbations may function, in part, to prevent immunosuppression by high testosterone levels and to prevent the use of energetic resources for metabolically-expensive anabolic functions.

  2. Radiographic changes in rhesus macaques affected by scurvy

    International Nuclear Information System (INIS)

    Morgan, J.P.; Eisele, P.H.

    1992-01-01

    Spontaneous vitamin C deficiency, or scurvy, was recognized in juvenile rhesus monkeys maintained in a research center as a result of being fed a commercial diet for 2 to 3 months with low levels of vitamin C. Most severely affected animals (13) were radiographed repeatedly up to day 300 following detection of the disease. Early radiographic changes consisted of widened, lucent metaphyses with lateral flaring and radiopaque metaphyseal lines at the junction of the metaphyses and physes. Physeal slippage was noted commonly. Following institution of vitamin C therapy, calcification of subperiosteal hemorrhage occurred in the metaphyseal regions. Metaphyses and physes returned to normal radiographic appearance within 15 to 30 days. Initially, the subperiosteal hemorrhage progressed and a longer time was required for solution of the calcified hematomas. The macaques improved clinically and were released from the hospital when fractures were stable at 4-5 weeks after admission. Of the 13 macaques studied, all but one returned as normal members of the colony

  3. Astrocyte atrophy and immune dysfunction in self-harming macaques.

    Science.gov (United States)

    Lee, Kim M; Chiu, Kevin B; Sansing, Hope A; Inglis, Fiona M; Baker, Kate C; MacLean, Andrew G

    2013-01-01

    Self-injurious behavior (SIB) is a complex condition that exhibits a spectrum of abnormal neuropsychological and locomotor behaviors. Mechanisms for neuropathogenesis could include irregular immune activation, host soluble factors, and astrocyte dysfunction. We examined the role of astrocytes as modulators of immune function in macaques with SIB. We measured changes in astrocyte morphology and function. Paraffin sections of frontal cortices from rhesus macaques identified with SIB were stained for glial fibrillary acidic protein (GFAP) and Toll-like receptor 2 (TLR2). Morphologic features of astrocytes were determined using computer-assisted camera lucida. There was atrophy of white matter astrocyte cell bodies, decreased arbor length in both white and gray matter astrocytes, and decreased bifurcations and tips on astrocytes in animals with SIB. This was combined with a five-fold increase in the proportion of astrocytes immunopositive for TLR2. These results provide direct evidence that SIB induces immune activation of astrocytes concomitant with quantifiably different morphology.

  4. Spontaneous extracutaneous systemic mastocytosis in a cynomolgus macaque ()

    OpenAIRE

    Martina , Z. Zöller; Joachim , Kaspareit

    2010-01-01

    Abstract A uniform cell population of proliferating mast cells with poor cytoplasmic granularity and few eosinophilic infiltrates was observed in hepatic portal tracts and the cecal submucosa of an adult male cynomolgus macaque (Macaca fascicularis) that was part of a drug safety assessment toxicity study. The proliferating mast cells were positive for Giemsa and toluidine blue staining and had strong immunoreactivity for mast cell tryptase and CD68. Considering size, morphology, i...

  5. Social interactions through the eyes of macaques and humans.

    Directory of Open Access Journals (Sweden)

    Richard McFarland

    Full Text Available Group-living primates frequently interact with each other to maintain social bonds as well as to compete for valuable resources. Observing such social interactions between group members provides individuals with essential information (e.g. on the fighting ability or altruistic attitude of group companions to guide their social tactics and choice of social partners. This process requires individuals to selectively attend to the most informative content within a social scene. It is unclear how non-human primates allocate attention to social interactions in different contexts, and whether they share similar patterns of social attention to humans. Here we compared the gaze behaviour of rhesus macaques and humans when free-viewing the same set of naturalistic images. The images contained positive or negative social interactions between two conspecifics of different phylogenetic distance from the observer; i.e. affiliation or aggression exchanged by two humans, rhesus macaques, Barbary macaques, baboons or lions. Monkeys directed a variable amount of gaze at the two conspecific individuals in the images according to their roles in the interaction (i.e. giver or receiver of affiliation/aggression. Their gaze distribution to non-conspecific individuals was systematically varied according to the viewed species and the nature of interactions, suggesting a contribution of both prior experience and innate bias in guiding social attention. Furthermore, the monkeys' gaze behavior was qualitatively similar to that of humans, especially when viewing negative interactions. Detailed analysis revealed that both species directed more gaze at the face than the body region when inspecting individuals, and attended more to the body region in negative than in positive social interactions. Our study suggests that monkeys and humans share a similar pattern of role-sensitive, species- and context-dependent social attention, implying a homologous cognitive mechanism of

  6. Psychological model of ART adherence behaviors in persons living with HIV/AIDS in Mexico: a structural equation analysis

    Directory of Open Access Journals (Sweden)

    José Luis Ybarra Sagarduy

    2017-09-01

    Full Text Available 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 (x2/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.

  7. 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

    2017-09-04

    The objective of this study has been to test the ability of variables of a psychological model to predict antiretroviral therapy medication adherence behavior. 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. 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 (x2/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. 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.

  8. Development of a computer aided diagnosis model for prostate cancer classification on multi-parametric MRI

    Science.gov (United States)

    Alfano, R.; Soetemans, D.; Bauman, G. S.; Gibson, E.; Gaed, M.; Moussa, M.; Gomez, J. A.; Chin, J. L.; Pautler, S.; Ward, A. D.

    2018-02-01

    Multi-parametric MRI (mp-MRI) is becoming a standard in contemporary prostate cancer screening and diagnosis, and has shown to aid physicians in cancer detection. It offers many advantages over traditional systematic biopsy, which has shown to have very high clinical false-negative rates of up to 23% at all stages of the disease. However beneficial, mp-MRI is relatively complex to interpret and suffers from inter-observer variability in lesion localization and grading. Computer-aided diagnosis (CAD) systems have been developed as a solution as they have the power to perform deterministic quantitative image analysis. We measured the accuracy of such a system validated using accurately co-registered whole-mount digitized histology. We trained a logistic linear classifier (LOGLC), support vector machine (SVC), k-nearest neighbour (KNN) and random forest classifier (RFC) in a four part ROI based experiment against: 1) cancer vs. non-cancer, 2) high-grade (Gleason score ≥4+3) vs. low-grade cancer (Gleason score work will form the basis for a tool that enhances the radiologist's ability to detect malignancies, potentially improving biopsy guidance, treatment selection, and focal therapy for prostate cancer patients, maximizing the potential for cure and increasing quality of life.

  9. Psychological first aid training for the faith community: a model curriculum.

    Science.gov (United States)

    McCabe, O Lee; Lating, Jeffrey M; Everly, George S; Mosley, Adrian M; Teague, Paula J; Links, Jonathan M; Kaminsky, Michael J

    2007-01-01

    Traditionally faith communities have served important roles in helping survivors cope in the aftermath of public health disasters. However, the provision of optimally effective crisis intervention services for persons experiencing acute or prolonged emotional trauma following such incidents requires specialized knowledge, skills, and abilities. Supported by a federally-funded grant, several academic health centers and faith-based organizations collaborated to develop a training program in Psychological First Aid (PFA) and disaster ministry for members of the clergy serving urban minorities and Latino immigrants in Baltimore, Maryland. This article describes the one-day training curriculum composed of four content modules: Stress Reactions of Mind-Body-Spirit, Psychological First Aid and Crisis Intervention, Pastoral Care and Disaster Ministry, and Practical Resources and Self Care for the Spiritual Caregiver Detailed descriptions of each module are provided, including its purpose; rationale and background literature; learning objectives; topics and sub-topics; and educational methods, materials and resources. The strengths, weaknesses, and future applications of the training template are discussed from the vantage points of participants' subjective reactions to the training.

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

    Directory of Open Access Journals (Sweden)

    Karol Sestak

    2011-04-01

    Full Text Available 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.Stages of remission and relapse were accomplished in gluten-sensitive animals by administration of gluten-free (GFD and gluten-containing (GD diets, as described previously. Pin-head-sized biopsies, obtained non-invasively by pediatric endoscope from duodenum while on GFD or GD, were used for preparation of total RNA and gene profiling, using the commercial Rhesus Macaque Microarray (Agilent Technologies,targeting expression of over 20,000 genes.When compared with normal healthy control, gluten-sensitive macaques showed differential gene expressions induced by GD. While observed gene perturbations were classified into one of 12 overlapping categories--cancer, metabolism, digestive tract function, immune response, cell growth, signal transduction, autoimmunity, detoxification of xenobiotics, apoptosis, actin-collagen deposition, neuronal and unknown function--this study focused on cancer-related gene networks such as cytochrome P450 family (detoxification function and actin-collagen-matrix metalloproteinases (MMP genes.A loss of detoxification function paralleled with necessity to metabolize carcinogens was revealed in gluten-sensitive animals while on GD. An increase in cancer-promoting factors and a simultaneous decrease in cancer-preventing factors associated with altered expression of actin-collagen-MMP gene network were noted. In addition, gluten-sensitive macaques showed reduced number of differentially expressed genes including the cancer-associated ones upon withdrawal of dietary gluten. Taken together, these findings indicate potentially expanded utility of gluten-sensitive rhesus macaques in cancer research.

  11. Improved Xenobiotic Metabolism and Reduced Susceptibility to Cancer in Gluten-Sensitive Macaques upon Introduction of a Gluten-Free Diet

    Science.gov (United States)

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

    2011-01-01

    Background 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). Methodology Stages of remission and relapse were accomplished in gluten-sensitive animals by administration of gluten-free (GFD) and gluten-containing (GD) diets, as described previously. Pin-head-sized biopsies, obtained non-invasively by pediatric endoscope from duodenum while on GFD or GD, were used for preparation of total RNA and gene profiling, using the commercial Rhesus Macaque Microarray (Agilent Technologies),targeting expression of over 20,000 genes. Principal Findings When compared with normal healthy control, gluten-sensitive macaques showed differential gene expressions induced by GD. While observed gene perturbations were classified into one of 12 overlapping categories - cancer, metabolism, digestive tract function, immune response, cell growth, signal transduction, autoimmunity, detoxification of xenobiotics, apoptosis, actin-collagen deposition, neuronal and unknown function - this study focused on cancer-related gene networks such as cytochrome P450 family (detoxification function) and actin-collagen-matrix metalloproteinases (MMP) genes. Conclusions/Significance A loss of detoxification function paralleled with necessity to metabolize carcinogens was revealed in gluten-sensitive animals while on GD. An increase in cancer-promoting factors and a simultaneous decrease in cancer-preventing factors associated with altered expression of actin-collagen-MMP gene network were noted. In addition, gluten-sensitive macaques showed reduced number of differentially expressed genes including the cancer-associated ones upon withdrawal of dietary gluten. Taken together, these findings indicate potentially expanded utility of gluten-sensitive rhesus macaques in cancer research. PMID:21533263

  12. Distributed acoustic cues for caller identity in macaque vocalization.

    Science.gov (United States)

    Fukushima, Makoto; Doyle, Alex M; Mullarkey, Matthew P; Mishkin, Mortimer; Averbeck, Bruno B

    2015-12-01

    Individual primates can be identified by the sound of their voice. Macaques have demonstrated an ability to discern conspecific identity from a harmonically structured 'coo' call. Voice recognition presumably requires the integrated perception of multiple acoustic features. However, it is unclear how this is achieved, given considerable variability across utterances. Specifically, the extent to which information about caller identity is distributed across multiple features remains elusive. We examined these issues by recording and analysing a large sample of calls from eight macaques. Single acoustic features, including fundamental frequency, duration and Weiner entropy, were informative but unreliable for the statistical classification of caller identity. A combination of multiple features, however, allowed for highly accurate caller identification. A regularized classifier that learned to identify callers from the modulation power spectrum of calls found that specific regions of spectral-temporal modulation were informative for caller identification. These ranges are related to acoustic features such as the call's fundamental frequency and FM sweep direction. We further found that the low-frequency spectrotemporal modulation component contained an indexical cue of the caller body size. Thus, cues for caller identity are distributed across identifiable spectrotemporal components corresponding to laryngeal and supralaryngeal components of vocalizations, and the integration of those cues can enable highly reliable caller identification. Our results demonstrate a clear acoustic basis by which individual macaque vocalizations can be recognized.

  13. Acquisition and production of skilled behavior in dynamic decision-making tasks: Modeling strategic behavior in human-automation interaction: Why and aid can (and should) go unused

    Science.gov (United States)

    Kirlik, Alex

    1991-01-01

    Advances in computer and control technology offer the opportunity for task-offload aiding in human-machine systems. A task-offload aid (e.g., an autopilot, an intelligent assistant) can be selectively engaged by the human operator to dynamically delegate tasks to an automated system. Successful design and performance prediction in such systems requires knowledge of the factors influencing the strategy the operator develops and uses for managing interaction with the task-offload aid. A model is presented that shows how such strategies can be predicted as a function of three task context properties (frequency and duration of secondary tasks and costs of delaying secondary tasks) and three aid design properties (aid engagement and disengagement times, aid performance relative to human performance). Sensitivity analysis indicates how each of these contextual and design factors affect the optimal aid aid usage strategy and attainable system performance. The model is applied to understanding human-automation interaction in laboratory experiments on human supervisory control behavior. The laboratory task allowed subjects freedom to determine strategies for using an autopilot in a dynamic, multi-task environment. Modeling results suggested that many subjects may indeed have been acting appropriately by not using the autopilot in the way its designers intended. Although autopilot function was technically sound, this aid was not designed with due regard to the overall task context in which it was placed. These results demonstrate the need for additional research on how people may strategically manage their own resources, as well as those provided by automation, in an effort to keep workload and performance at acceptable levels.

  14. 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.

  15. Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure

    Science.gov (United States)

    Johnston, Sara C.; Lin, Kenny L.; Twenhafel, Nancy A.; Raymond, Jo Lynne W.; Shamblin, Joshua D.; Wollen, Suzanne E.; Wlazlowski, Carly B.; Wilkinson, Eric R.; Botto, Miriam A.; Goff, Arthur J.

    2015-01-01

    Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-exposed animals, 100 PFU was the first target dose that was not significantly different than higher target doses in terms of time to disposition, clinical pathology, and histopathology. Although a significant difference was not observed between aerosol-exposed animals in the 10 PFU and 100 PFU target dose groups, 100 PFU was determined to be the lowest target dose that could be consistently obtained and accurately titrated in aerosol studies. PMID:26413900

  16. Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure.

    Directory of Open Access Journals (Sweden)

    Sara C Johnston

    Full Text Available Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-exposed animals, 100 PFU was the first target dose that was not significantly different than higher target doses in terms of time to disposition, clinical pathology, and histopathology. Although a significant difference was not observed between aerosol-exposed animals in the 10 PFU and 100 PFU target dose groups, 100 PFU was determined to be the lowest target dose that could be consistently obtained and accurately titrated in aerosol studies.

  17. The Effects of Service-Delivery Model and Purchase Price on Hearing-Aid Outcomes in Older Adults: A Randomized Double-Blind Placebo-Controlled Clinical Trial.

    Science.gov (United States)

    Humes, Larry E; Rogers, Sara E; Quigley, Tera M; Main, Anna K; Kinney, Dana L; Herring, Christine

    2017-03-01

    The objectives of this study were to determine efficacy of hearing aids in older adults using audiology best practices, to evaluate the efficacy of an alternative over-the-counter (OTC) intervention, and to examine the influence of purchase price on outcomes for both service-delivery models. The design of this study was a single-site, prospective, double-blind placebo-controlled randomized trial with three parallel branches: (a) audiology best practices (AB), (b) consumer decides OTC model (CD), and (c) placebo devices (P). Outcome measures were obtained after a typical 6-week trial period with follow-up 4-week AB-based trial for those initially assigned to CD and P groups. Older adults from the general community were recruited via newspaper and community flyers to participate at a university research clinic. Participants were adults, ages 55-79 years, with mild-to-moderate hearing loss. There were 188 eligible participants: 163 enrolled as a volunteer sample, and 154 completed the intervention. All participants received the same high-end digital mini-behind-the-ear hearing aids fitted bilaterally. AB and P groups received best-practice services from audiologists; differing mainly in use of appropriate (AB) or placebo (P) hearing aid settings. CD participants self-selected their own pre-programmed hearing aids via an OTC model. Primary outcome measure was a 66-item self-report, Profile of Hearing Aid Benefit (Cox & Gilmore, 1990). Secondary outcome measure was the Connected Speech Test (Cox, Alexander, & Gilmore, 1987) benefit. Additional measures of hearing-aid benefit, satisfaction, and usage were also obtained. Per-protocol analyses were performed. AB service-delivery model was found to be efficacious for most of the outcome measures, with moderate or large effect sizes (Cohen's d). CD service-delivery model was efficacious, with similar effect sizes. However, CD group had a significantly (p purchase hearing aids after the trial. Hearing aids are efficacious in

  18. Viral and immunological factors associated with breast milk transmission of SIV in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Fresh Lynn

    2004-07-01

    Full Text Available Abstract Background The viral and host factors involved in transmission of HIV through breastfeeding are largely unknown, and intervention strategies are urgently needed to protect at-risk populations. To evaluate the viral and immunological factors directly related to milk transmission of virus, we have evaluated the disease course of Simian Immunodeficiency Virus (SIV in lactating rhesus macaques (Macaca mulatta as a model of natural breast milk transmission of HIV. Results Fourteen lactating macaques were infected intravenously with SIV/DeltaB670, a pathogenic isolate of SIV and were pair-housed with their suckling infants throughout the disease course. Transmission was observed in 10 mother-infant pairs over a one-year period. Two mothers transmitted virus during the period of initial viremia 14–21 days post inoculation (p.i. and were classified as early transmitters. Peak viral loads in milk and plasma of early transmitters were similar to other animals, however the early transmitters subsequently displayed a rapid progressor phenotype and failed to control virus expression as well as other animals at 56 days p.i. Eight mothers were classified as late transmitters, with infant infection detected at time points in the chronic stage of the maternal SIV disease course (81 to 360 days. Plasma viral loads, CD4+ T cell counts and SIV-specific antibody titers were similar in late transmitters and non-transmitters. Late breast milk transmission, however, was correlated with higher average milk viral loads and more persistent viral expression in milk 12 to 46 weeks p.i. as compared to non-transmitters. Four mothers failed to transmit virus, despite disease progression and continuous lactation. Conclusion These studies validate the SIV-infected rhesus macaque as a model for breast milk transmission of HIV. As observed in studies of HIV-infected women, transmission occurred at time points throughout the period of lactation. Transmission during the

  19. Longitudinal analysis reveals characteristically high proportions of bacterial vaginosis-associated bacteria and temporal variability of vaginal microbiota in northern pig-tailed macaques (Macaca leonina)

    OpenAIRE

    ZHU, Lin; LEI, Ai-Hua; ZHENG, Hong-Yi; LYU, Long-Bao; ZHANG, Zhi-Gang; ZHENG, Yong-Tang

    2015-01-01

    The complex and dynamic vaginal microbial ecosystem is critical to both health and disease of the host. Studies focusing on how vaginal microbiota influences HIV-1 infection may face limitations in selecting proper animal models. Given that northern pig-tailed macaques (Macaca leonina) are susceptible to HIV-1 infection, they may be an optimal animal model for elucidating the mechanisms by which vaginal microbiota contributes to resistance and susceptibility to HIV-1 infection. However, littl...

  20. MiniCD4 microbicide prevents HIV infection of human mucosal explants and vaginal transmission of SHIV(162P3 in cynomolgus macaques.

    Directory of Open Access Journals (Sweden)

    Nathalie Dereuddre-Bosquet

    Full Text Available In complement to an effective vaccine, development of potent anti-HIV microbicides remains an important priority. We have previously shown that the miniCD4 M48U1, a functional mimetic of sCD4 presented on a 27 amino-acid stable scaffold, inhibits a broad range of HIV-1 isolates at sub-nanomolar concentrations in cellular models. Here, we report that M48U1 inhibits efficiently HIV-1(Ba-L in human mucosal explants of cervical and colorectal tissues. In vivo efficacy of M48U1 was evaluated in nonhuman primate (NHP model of mucosal challenge with SHIV(162P3 after assessing pharmacokinetics and pharmacodynamics of a miniCD4 gel formulation in sexually matured female cynomolgus macaques. Among 12 females, half were treated with hydroxyethylcellulose-based gel (control, the other half received the same gel containing 3 mg/g of M48U1, one hour before vaginal route challenge with 10 AID(50 of SHIV(162P3. All control animals were infected with a peak plasma viral load of 10(5-10(6 viral RNA (vRNA copies per mL. In animals treated with miniCD4, 5 out of 6 were fully protected from acquisition of infection, as assessed by qRT-PCR for vRNA detection in plasma, qPCR for viral DNA detection in PBMC and lymph node cells. The only infected animal in this group had a delayed peak of viremia of one week. These results demonstrate that M48U1 miniCD4 acts in vivo as a potent entry inhibitor, which may be considered in microbicide developments.

  1. Interindividual Differences in Neonatal Imitation and the Development of Action Chains in Rhesus Macaques

    Science.gov (United States)

    Ferrari, Pier Francesco; Paukner, Annika; Ruggiero, Angela; Darcey, Lisa; Unbehagen, Sarah; Suomi, Stephen J.

    2009-01-01

    The capacity to imitate facial gestures is highly variable in rhesus macaques and this variability may be related to differences in specific neurobehavioral patterns of development. This study evaluated the differential neonatal imitative response of 41 macaques in relation to the development of sensory, motor, and cognitive skills throughout the…

  2. Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS.

    Directory of Open Access Journals (Sweden)

    Anjie Zhen

    2017-12-01

    Full Text Available Chimeric Antigen Receptor (CAR T-cells have emerged as a powerful immunotherapy for various forms of cancer and show promise in treating HIV-1 infection. However, significant limitations are persistence and whether peripheral T cell-based products can respond to malignant or infected cells that may reappear months or years after treatment remains unclear. Hematopoietic Stem/Progenitor Cells (HSPCs are capable of long-term engraftment and have the potential to overcome these limitations. Here, we report the use of a protective CD4 chimeric antigen receptor (C46CD4CAR to redirect HSPC-derived T-cells against simian/human immunodeficiency virus (SHIV infection in pigtail macaques. CAR-containing cells persisted for more than 2 years without any measurable toxicity and were capable of multilineage engraftment. Combination antiretroviral therapy (cART treatment followed by cART withdrawal resulted in lower viral rebound in CAR animals relative to controls, and demonstrated an immune memory-like response. We found CAR-expressing cells in multiple lymphoid tissues, decreased tissue-associated SHIV RNA levels, and substantially higher CD4/CD8 ratios in the gut as compared to controls. These results show that HSPC-derived CAR T-cells are capable of long-term engraftment and immune surveillance. This study demonstrates for the first time the safety and feasibility of HSPC-based CAR therapy in a large animal preclinical model.

  3. A Pilot Model for the NASA Simplified Aid for EVA Rescue (SAFER) (Single-Axis Pitch Task)

    Science.gov (United States)

    Handley, Patrick Mark

    This thesis defines, tests, and validates a descriptive pilot model for a single-axis pitch control task of the Simplified Aid for EVA Rescue (SAFER). SAFER is a small propulsive jetpack used by astronauts for self-rescue. Pilot model research supports development of improved self-rescue strategies and technologies through insights into pilot behavior.This thesis defines a multi-loop pilot model. The innermost loop controls the hand controller, the middle loop controls pitch rate, and the outer loop controls pitch angle. A human-in-the-loop simulation was conducted to gather data from a human pilot. Quantitative and qualitative metrics both indicate that the model is an acceptable fit to the human data. Fuel consumption was nearly identical; time to task completion matched very well. There is some evidence that the model responds faster to initial pitch rates than the human, artificially decreasing the model's time to task completion. This pilot model is descriptive, not predictive, of the human pilot. Insights are made into pilot behavior from this research. Symmetry implies that the human responds to positive and negative initial conditions with the same strategy. The human pilot appears indifferent to pitch angles within 0.5 deg, coasts at a constant pitch rate 1.09 deg/s, and has a reaction delay of 0.1 s.

  4. Geologic characterization of fractures as an aid to hydrologic modeling of the SCV block at the Stripa mine

    International Nuclear Information System (INIS)

    Martel, S.

    1992-04-01

    A series of hydrologic tests have been conducted at the Stripa research mine in Sweden to develop hydrologic characterization techniques for rock masses in which fractures form the primary flow paths. The structural studies reported here were conducted to aid in the hydrologic examination of a cubic block of granite with dimensions of 150 m on a side. This block (the SCV block) is located between the 310- and 460-m depth levels at the Stripa mine. This report describes and interprets the fracture system geology at Stripa as revealed in drift exposures, checks the interpretive model against borehole records and discusses the hydrologic implication of the model, and examines the likely effects of stress redistribution around a drift (the Validation drift) on inflow to the drift along a prominent fracture zone. (72 refs.) (au)

  5. 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.

  6. Construction sequence scale model: an aid to productivity and quality assurance

    International Nuclear Information System (INIS)

    Clothier, W.A. Sr.

    1978-01-01

    The natural tendencies of an engineering scale model to promote a high level of quality by error prevention during design and construction stages of a project are studied. A brief section on the basic history of engineering modeling is used to describe TVA's usage of the model. The basic design model is explored in an overview touching the highlights of that form of modeling. A detailed look at the construction sequence model, a relatively new form of model, is presented to demonstrate quality and productivity awareness

  7. 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...

  8. 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...

  9. A multimethod Global Sensitivity Analysis to aid the calibration of geomechanical models via time-lapse seismic data

    Science.gov (United States)

    Price, D. C.; Angus, D. A.; Garcia, A.; Fisher, Q. J.; Parsons, S.; Kato, J.

    2018-03-01

    Time-lapse seismic attributes are used extensively in the history matching of production simulator models. However, although proven to contain information regarding production induced stress change, it is typically only loosely (i.e. qualitatively) used to calibrate geomechanical models. In this study we conduct a multimethod Global Sensitivity Analysis (GSA) to assess the feasibility and aid the quantitative calibration of geomechanical models via near-offset time-lapse seismic data. Specifically, the calibration of mechanical properties of the overburden. Via the GSA, we analyse the near-offset overburden seismic traveltimes from over 4000 perturbations of a Finite Element (FE) geomechanical model of a typical High Pressure High Temperature (HPHT) reservoir in the North Sea. We find that, out of an initially large set of material properties, the near-offset overburden traveltimes are primarily affected by Young's modulus and the effective stress (i.e. Biot) coefficient. The unexpected significance of the Biot coefficient highlights the importance of modelling fluid flow and pore pressure outside of the reservoir. The FE model is complex and highly nonlinear. Multiple combinations of model parameters can yield equally possible model realizations. Consequently, numerical calibration via a large number of random model perturbations is unfeasible. However, the significant differences in traveltime results suggest that more sophisticated calibration methods could potentially be feasible for finding numerous suitable solutions. The results of the time-varying GSA demonstrate how acquiring multiple vintages of time-lapse seismic data can be advantageous. However, they also suggest that significant overburden near-offset seismic time-shifts, useful for model calibration, may take up to 3 yrs after the start of production to manifest. Due to the nonlinearity of the model behaviour, similar uncertainty in the reservoir mechanical properties appears to influence overburden

  10. Abordagem psicológica da AIDS através do enfoque cognitivo-comportamental Psychological approach to AIDS based on the cognitive-behavioral model

    Directory of Open Access Journals (Sweden)

    Eduardo Augusto Remor

    1999-01-01

    Full Text Available Este artigo apresenta um conjunto de conhecimentos que são fruto do trabalho clínico e de reflexões, juntamente com a revisão teórica dos principais aspectos relacionados com a Infecção pelo HIV, abordagem terapêutica e um panorama geral das possíveis alterações emocionais que podem apresentar as pessoas infectadas pelo HIV ou que já tenham desenvolvido AIDS. Pretende centrar-se nos aspectos relacionados à intervenção psicológica a partir do enfoque terapêutico cognitivo-comportamental. Demonstra-se que a problemática apresentada por pessoas infectadas pelo vírus da AIDS requer uma atenção específica. Propõe-se uma abordagem bio-psico-social de seus problemas, pois, além das necessidades de atenção da própria doença, juntam-se outros aspectos relacionados com a mesma, como o rechaço social que a doença gera, a atenção às famílias, os problemas sociais, jurídicos e laborais, assim como a necessidade de informação, assessoramento e apoio psicológico ao afetado e as suas famílias.This article presents the outcomes of clinical practice and a theoretical review of the main issues related to HIV Infection, including a general panorama of possible emotional alterations that can be present in HIV-positive persons or in those who have AIDS. The issues related to psychological intervention based on the cognitive-behavioral therapeutic approach are the central theme. It will be shown that the problems of persons infected with the AIDS virus, require specific attention if a bio-psycho-social approach to these problems is proposed. Besides the need for attention to the actual illness, there are other aspects related to the social rejection it causes, family care, social, legal, and labor problems, as well as the need for information, counseling, and psychological support for the patients and their family.

  11. Online Adaptation and Over-Trial Learning in Macaque Visuomotor Control

    Science.gov (United States)

    Braun, Daniel A.; Aertsen, Ad; Paz, Rony; Vaadia, Eilon; Rotter, Stefan; Mehring, Carsten

    2011-01-01

    When faced with unpredictable environments, the human motor system has been shown to develop optimized adaptation strategies that allow for online adaptation during the control process. Such online adaptation is to be contrasted to slower over-trial learning that corresponds to a trial-by-trial update of the movement plan. Here we investigate the interplay of both processes, i.e., online adaptation and over-trial learning, in a visuomotor experiment performed by macaques. We show that simple non-adaptive control schemes fail to perform in this task, but that a previously suggested adaptive optimal feedback control model can explain the observed behavior. We also show that over-trial learning as seen in learning and aftereffect curves can be explained by learning in a radial basis function network. Our results suggest that both the process of over-trial learning and the process of online adaptation are crucial to understand visuomotor learning. PMID:21720526

  12. 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.

  13. An Evolutionary, Agent-Based Model to Aid in Computer Intrusion Detection and Prevention

    National Research Council Canada - National Science Library

    Shargel, Ben; Bonabeau, Eric; Budynek, Julien; Gaudiano, Paolo

    2005-01-01

    We have developed a realistic agent-based simulation model of hacker behavior. In the model, hacker scripts are generated using a simple but powerful hacker grammar that has the potential to cover all possible hacker scripts...

  14. Metamodeling Techniques to Aid in the Aggregation Process of Large Hierarchical Simulation Models

    National Research Council Canada - National Science Library

    Rodriguez, June F

    2008-01-01

    .... More specifically, investigating how to accurately aggregate hierarchical lower-level (higher resolution) models into the next higher-level in order to reduce the complexity of the overall simulation model...

  15. The extracellular domain of myelin oligodendrocyte glycoprotein elicits atypical experimental autoimmune encephalomyelitis in rat and Macaque species.

    Directory of Open Access Journals (Sweden)

    Alan D Curtis

    Full Text Available Atypical models of experimental autoimmune encephalomyelitis (EAE are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS. Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG in complete Freund's adjuvant (CFA followed by one or more injections of rat IgV-MOG in incomplete Freund's adjuvant (IFA. The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6-7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in

  16. The extracellular domain of myelin oligodendrocyte glycoprotein elicits atypical experimental autoimmune encephalomyelitis in rat and Macaque species.

    Science.gov (United States)

    Curtis, Alan D; Taslim, Najla; Reece, Shaun P; Grebenciucova, Elena; Ray, Richard H; Rosenbaum, Matthew D; Wardle, Robert L; Van Scott, Michael R; Mannie, Mark D

    2014-01-01

    Atypical models of experimental autoimmune encephalomyelitis (EAE) are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS). Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV)-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG) in complete Freund's adjuvant (CFA) followed by one or more injections of rat IgV-MOG in incomplete Freund's adjuvant (IFA). The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6-7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in spinal cord and

  17. 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.

  18. 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.

  19. Inundation Analysis of Reservoir Flood Based on Computer Aided Design (CAD and Digital Elevation Model (DEM

    Directory of Open Access Journals (Sweden)

    Jiqing Li

    2018-04-01

    Full Text Available GIS (Geographic Information System can be used to combine multiple hydrologic data and geographic data for FIA (Flood Impact Assessment. For a developing country like China, a lot of geographic data is in the CAD (Computer Aided Design format. The commonly used method for converting CAD into DEM may result in data loss. This paper introduces a solution for the conversion between CAD data and DEM data. The method has been applied to the FIA based on the topographic map of CAD in Hanjiang River. When compared with the other method, the new method solves the data loss problem. Besides, the paper use GIS to simulate the inundation range, area, and the depth distribution of flood backwater. Based on the analysis, the author concludes: (1 the differences of the inundation areas between the flood of HQ100 and the flood of HQ50 are small. (2 The inundation depth shows a decreasing trend along the upstream of the river. (3 The inundation area less than 4 m in flood of HQ50 is larger than that in flood of HQ100, the result is opposite when the inundation depth is greater than 4 m. (4 The flood loss is 392.32 million RMB for flood of HQ50 and 610.02 million RMB for flood of HQ100. The method can be applied to FIA.

  20. SPICE-aided modeling of high-voltage silicon carbide JFETs

    International Nuclear Information System (INIS)

    Bargieł, Kamil; Zarębski, Janusz; Bisewski, Damian

    2016-01-01

    The paper presents the static characteristics of the SiC transistor SJEP170R550 offered by SemiSouth obtained from simulations using JFET model built-in in PSPICE. Values of the model parameters were estimated using MODEL EDITOR, as well as procedure described in the literature. Simulation results were verified experimentally by comparison of results of measurements

  1. Computer-aided operations engineering with integrated models of systems and operations

    Science.gov (United States)

    Malin, Jane T.; Ryan, Dan; Fleming, Land

    1994-01-01

    CONFIG 3 is a prototype software tool that supports integrated conceptual design evaluation from early in the product life cycle, by supporting isolated or integrated modeling, simulation, and analysis of the function, structure, behavior, failures and operation of system designs. Integration and reuse of models is supported in an object-oriented environment providing capabilities for graph analysis and discrete event simulation. Integration is supported among diverse modeling approaches (component view, configuration or flow path view, and procedure view) and diverse simulation and analysis approaches. Support is provided for integrated engineering in diverse design domains, including mechanical and electro-mechanical systems, distributed computer systems, and chemical processing and transport systems. CONFIG supports abstracted qualitative and symbolic modeling, for early conceptual design. System models are component structure models with operating modes, with embedded time-related behavior models. CONFIG supports failure modeling and modeling of state or configuration changes that result in dynamic changes in dependencies among components. Operations and procedure models are activity structure models that interact with system models. CONFIG is designed to support evaluation of system operability, diagnosability and fault tolerance, and analysis of the development of system effects of problems over time, including faults, failures, and procedural or environmental difficulties.

  2. Tangible Models and Haptic Representations Aid Learning of Molecular Biology Concepts

    Science.gov (United States)

    Johannes, Kristen; Powers, Jacklyn; Couper, Lisa; Silberglitt, Matt; Davenport, Jodi

    2016-01-01

    Can novel 3D models help students develop a deeper understanding of core concepts in molecular biology? We adapted 3D molecular models, developed by scientists, for use in high school science classrooms. The models accurately represent the structural and functional properties of complex DNA and Virus molecules, and provide visual and haptic…

  3. Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel.

    Directory of Open Access Journals (Sweden)

    Martin Cranage

    2008-08-01

    Full Text Available The rectum is particularly vulnerable to HIV transmission having only a single protective layer of columnar epithelium overlying tissue rich in activated lymphoid cells; thus, unprotected anal intercourse in both women and men carries a higher risk of infection than other sexual routes. In the absence of effective prophylactic vaccines, increasing attention is being given to the use of microbicides and preventative antiretroviral (ARV drugs. To prevent mucosal transmission of HIV, a microbicide/ARV should ideally act locally at and near the virus portal of entry. As part of an integrated rectal microbicide development programme, we have evaluated rectal application of the nucleotide reverse transcriptase (RT inhibitor tenofovir (PMPA, 9-[(R-2-(phosphonomethoxy propyl] adenine monohydrate, a drug licensed for therapeutic use, for protective efficacy against rectal challenge with simian immunodeficiency virus (SIV in a well-established and standardised macaque model.A total of 20 purpose-bred Indian rhesus macaques were used to evaluate the protective efficacy of topical tenofovir. Nine animals received 1% tenofovir gel per rectum up to 2 h prior to virus challenge, four macaques received placebo gel, and four macaques remained untreated. In addition, three macaques were given tenofovir gel 2 h after virus challenge. Following intrarectal instillation of 20 median rectal infectious doses (MID50 of a noncloned, virulent stock of SIVmac251/32H, all animals were analysed for virus infection, by virus isolation from peripheral blood mononuclear cells (PBMC, quantitative proviral DNA load in PBMC, plasma viral RNA (vRNA load by sensitive quantitative competitive (qc RT-PCR, and presence of SIV-specific serum antibodies by ELISA. We report here a significant protective effect (p = 0.003; Fisher exact probability test wherein eight of nine macaques given tenofovir per rectum up to 2 h prior to virus challenge were protected from infection (n = 6 or had

  4. Decision aiding model for the evaluation of agricultural countermeasures after an accidental release of radionuclides to the environment

    International Nuclear Information System (INIS)

    Turcanu, C.

    2009-01-01

    Implementation of remedial actions after a radiological contamination of the environment has to take into account, alongside with radiological and feasibility criteria, also the acceptability of the countermeasures, ethical and environmental considerations, as well as the spatial variation and the needs of people in urban, rural and industrial environments. This highlights multi-criteria analysis as a suitable tool, since it is able to structure discussions and to facilitate a common understanding of the decision problem, with the values and priorities of the actors involved. The related theoretical framework, multi-criteria decision aid (MCDA), has emerged from the operational research field as an answer given to a couple of important questions encountered in complex decision problems. Firstly, the aim is not to replace the decision maker with a mathematical model, but to support him to construct his solution by describing and evaluating his options. Secondly, instead of using a unique criterion capturing all aspects of the problem, in MCDA one seeks to build multiple criteria, representing several points of view. The methods belonging to MCDA can be classified as multi-attribute utility/value methods, outranking methods and interactive methods. Past attempts to apply multi-criteria analysis in the context of nuclear emergency management have highlighted however the need to better integrate the operational and socio-political context of the decision-making process into the tools and models developed for decision-support. This PhD project had two main objectives: 1) to develop a multi-criteria decision aid model for the decision problem on countermeasures for contaminated milk, that better accommodates the nuclear crisis management context in Belgium and 2) to build prototype tools implementing and demonstrating the methodology developed

  5. Improved survival in rhesus macaques immunized with modified vaccinia virus Ankara recombinants expressing simian immunodeficiency virus envelope correlates with reduction in memory CD4+ T-cell loss and higher titers of neutralizing antibody.

    Science.gov (United States)

    Ourmanov, Ilnour; Kuwata, Takeo; Goeken, Robert; Goldstein, Simoy; Iyengar, Ranjani; Buckler-White, Alicia; Lafont, Bernard; Hirsch, Vanessa M

    2009-06-01

    Previous studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvirus modified vaccinia virus Ankara (MVA) provided protection from high viremia and AIDS following challenge with a pathogenic strain of SIV. Although all animals became infected, plasma viremia was significantly reduced in animals that received the MVA-SIV recombinant vaccines compared with animals that received nonrecombinant MVA. Most importantly, the reduction in viremia resulted in a significant increase in median and cumulative survival. Continued analysis of these animals over the subsequent 9 years has shown that they maintain a survival advantage, although all but two of the macaques have progressed to AIDS. Importantly, improved survival correlated with preservation of memory CD4(+) T cells in the peripheral blood. The greatest survival advantage was observed in macaques immunized with regimens containing SIV Env, and the titer of neutralizing antibodies to the challenge virus prior to or shortly following challenge correlated with preservation of CD4(+) T cells. These data are consistent with a role for neutralizing antibodies in nonsterilizing protection from high viremia and associated memory CD4(+) T-cell loss.

  6. Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques.

    Directory of Open Access Journals (Sweden)

    Félicien Moukambi

    2015-12-01

    Full Text Available Follicular T helper cells (Tfh, a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs during Aids, none has yet addressed the impact of SIV infection on the dynamics of Tfh cells in the spleen, the primary organ of B cell activation. We show here a significant decrease in splenic Tfh cells in SIVmac251-infected rhesus macaques (RMs during the acute phase of infection, which persists thereafter. This profound loss is associated with lack of sustained expression of the Tfh-defining transcription factors, Bcl-6 and c-Maf but with higher expression of the repressors KLF2 and Foxo1. In this context of Tfh abortive differentiation and loss, we found decreased percentages of memory B cell subsets and lower titers of SIV-specific IgG. We further demonstrate a drastic remodeling of the lymphoid architecture of the spleen and LNs, which disrupts the crucial cell-cell interactions necessary to maintain memory B cells and Tfh cells. Finally, our data demonstrated the early infection of Tfh cells. Paradoxically, the frequencies of SIV DNA were higher in splenic Tfh cells of RMs progressing more slowly suggesting sanctuaries for SIV in the spleen. Our findings provide important information regarding the impact of HIV/SIV infection on Tfh cells, and provide new clues for future vaccine strategies.

  7. Interaction of mathematical modeling and social and behavioral HIV/AIDS research.

    Science.gov (United States)

    Cassels, Susan; Goodreau, Steven M

    2011-03-01

    HIV is transmitted within complex biobehavioral systems. Mathematical modeling can provide insight to complex population-level outcomes of various behaviors measured at an individual level. HIV models in the social and behavioral sciences can be categorized in a number of ways; here, we consider two classes of applications common in the field generally, and in the past year in particular: those models that explore significant behavioral determinants of HIV disparities within and between populations; and those models that seek to evaluate the potential impact of specific social and behavioral interventions. We discuss two overarching issues we see in the field: the need to further systematize effectiveness models of behavioral interventions, and the need for increasing investigation of the use of behavioral data in epidemic models. We believe that a recent initiative by the National Institutes of Health will qualitatively change the relationships between epidemic modeling and sociobehavioral prevention research in the coming years.

  8. Factors increasing snake detection and perceived threat in captive rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Etting, Stephanie F; Isbell, Lynne A; Grote, Mark N

    2014-02-01

    The primary predators of primates are all ambush hunters, and yet felids, raptors, and snakes differ in aspects of their ecology that affect the evasive strategies of their primate prey. Felids and raptors can traverse long distances quickly, thus the urgency of threat they present increases as they come closer in proximity to primates. In contrast, snakes do not move rapidly over long distances, and so primates may be reasonably safe even at close distances provided snakes can be detected and monitored. We investigated the ability of captive rhesus macaques (Macaca mulatta) to detect snakes at distances ranging from 15 to 1.5 m. We also examined variation in intensity of perceived threat by applying a Hidden Markov Model to infer changes in underlying state from observable behaviors, that is, increased attention and mobbing. We found that the macaques often failed to detect snake models but that closer proximity improved snake detection, which is necessary before threat can be perceived. We also found that having only one individual in fairly close proximity (≤ 7.5 m) was sufficient to alert the rest of the group and so the chances of detection did not increase with increasing group size. Finally, we found that when the snakes were perceived, they did not elicit greater intensity of response with closer proximity. These results provide evidence that the threat from snakes is greatest when they are in proximity to primates but are unseen. When snakes are seen, however, distance appears not to affect primates' perceived risk, in contrast to their perceived risk from raptors and felids. © 2013 Wiley Periodicals, Inc.

  9. Age-dependent changes in innate immune phenotype and function in rhesus macaques (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Mark Asquith

    2012-06-01

    Full Text Available Aged individuals are more susceptible to infections due to a general decline in immune function broadly referred to as immune senescence. While age-related changes in the adaptive immune system are well documented, aging of the innate immune system remains less well understood, particularly in nonhuman primates. A more robust understanding of age-related changes in innate immune function would provide mechanistic insight into the increased susceptibility of the elderly to infection. Rhesus macaques have proved a critical translational model for aging research, and present a unique opportunity to dissect age-dependent modulation of the innate immune system. We examined age-related changes in: (i innate immune cell frequencies; (ii expression of pattern recognition receptors (PRRs and innate signaling molecules; (iii cytokine responses of monocytes and dendritic cells (DC following stimulation with PRR agonists; and (iv plasma cytokine levels in this model. We found marked changes in both the phenotype and function of innate immune cells. This included an age-associated increased frequency of myeloid DC (mDC. Moreover, we found toll-like receptor (TLR agonists lipopolysaccharide (TLR4, fibroblast stimulating ligand-1 (TLR2/6, and ODN2006 (TLR7/9 induced reduced cytokine responses in aged mDC. Interestingly, with the exception of the monocyte-derived TNFα response to LPS, which increased with age, TNFα, IL-6, and IFNα responses declined with age. We also found that TLR4, TLR5, and innate negative regulator, sterile alpha and TIR motif containing protein (SARM, were all expressed at lower levels in young animals. By contrast, absent in melanoma 2 and retinoic acid-inducible gene I expression was lowest in aged animals. Together, these observations indicate that several parameters of innate immunity are significantly modulated by age and contribute to differential immune function in aged macaques.

  10. The ORF59 DNA polymerase processivity factor homologs of Old World primate RV2 rhadinoviruses are highly conserved nuclear antigens expressed in differentiated epithelium in infected macaques

    Directory of Open Access Journals (Sweden)

    Burnside Kellie L

    2009-11-01

    Full Text Available Abstract Background ORF59 DNA polymerase processivity factor of the human rhadinovirus, Kaposi's sarcoma-associated herpesvirus (KSHV, is required for efficient copying of the genome during virus replication. KSHV ORF59 is antigenic in the infected host and is used as a marker for virus activation and replication. Results We cloned, sequenced and expressed the genes encoding related ORF59 proteins from the RV1 rhadinovirus homologs of KSHV from chimpanzee (PtrRV1 and three species of macaques (RFHVMm, RFHVMn and RFHVMf, and have compared them with ORF59 proteins obtained from members of the more distantly-related RV2 rhadinovirus lineage infecting the same non-human primate species (PtrRV2, RRV, MneRV2, and MfaRV2, respectively. We found that ORF59 homologs of the RV1 and RV2 Old World primate rhadinoviruses are highly conserved with distinct phylogenetic clustering of the two rhadinovirus lineages. RV1 and RV2 ORF59 C-terminal domains exhibit a strong lineage-specific conservation. Rabbit antiserum was developed against a C-terminal polypeptide that is highly conserved between the macaque RV2 ORF59 sequences. This anti-serum showed strong reactivity towards ORF59 encoded by the macaque RV2 rhadinoviruses, RRV (rhesus and MneRV2 (pig-tail, with no cross reaction to human or macaque RV1 ORF59 proteins. Using this antiserum and RT-qPCR, we determined that RRV ORF59 is expressed early after permissive infection of both rhesus primary fetal fibroblasts and African green monkey kidney epithelial cells (Vero in vitro. RRV- and MneRV2-infected foci showed strong nuclear expression of ORF59 that correlated with production of infectious progeny virus. Immunohistochemical studies of an MneRV2-infected macaque revealed strong nuclear expression of ORF59 in infected cells within the differentiating layer of epidermis corroborating previous observations that differentiated epithelial cells are permissive for replication of KSHV-like rhadinoviruses

  11. Effect of plasma viremia on apoptosis and immunophenotype of dendritic cells subsets in acute SIVmac239 infection of Chinese rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Hou-Jun Xia

    Full Text Available Non-human primates such as Chinese rhesus macaques (Ch Rhs provide good animal models for research on human infectious diseases. Similar to humans, there are two principal subsets of dendritic cells (DCs in the peripheral blood of Ch Rhs: myeloid DCs (mDCs and plasmacytoid DCs (pDCs. In this study, two-color fluorescence-activated cell sorting (FACS analyses were used to identify the main DC subsets, namely CD1c(+ mDCs and pDCs from Ch Rhs. Then, the apoptosis and immunophenotype changes of DCs subsets were first described during the acute phase of SIVmac239 infection. Both the DCs subsets showed decreased CD4 expression and enhanced CCR5 expression; in particular, those of pDCs significantly changed at most time points. Interestingly, the plasma viral loads were negatively correlated with CD4 expression, but were positively correlated with CCR5 expression of pDCs. During this period, both CD1c(+ mDCs and pDCs were activated by enhancing expressions of co-stimulatory molecules, accompanied with increase in CCR7. Either CD80 or CD86 expressed on CD1c(+ mDCs and pDCs was positively correlated with the plasma viral loads. Our analysis demonstrates that the pDCs were more prone to apoptosis after infection during the acute phase of SIVmac239 infection, which may be due to their high expressions of CD4 and CCR5. Both DCs subsets activated through elevating the expression of co-stimulatory molecules, which was beneficial in controlling the replication of SIV. However, a mere broad immune activation initiated by activated DCs may lead to tragic AIDS progression.

  12. Manipulating the Geometric Computer-aided Design of the Operational Requirements-based Casualty Assessment Model within BRL-CAD

    Science.gov (United States)

    2018-03-30

    aided Design of the Operational Requirements-based Casualty Assessment Model within BRL-CAD 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ...upper_arm_r.s upper_arm_r.s-bool r upper_leg_l.r - lower_leg_l.s-bool r upper_leg_r.r - lower_leg_r.s-bool r upper_arm_r.r - lower_arm_r.s-bool r ...upper_arm_l.r - lower_arm_l.s-bool r pelvis.r - hip_l.s-bool - hip_r.s-bool - upper_leg_l.s-bool - upper_leg_r.s-bool r thorax.r - shoulder_l.s-bool

  13. Pathology of experimental Machupo virus infection, Chicava strain, in cynomolgus macaques (Macaca fascicularis) by intramuscular and aerosol exposure.

    Science.gov (United States)

    Bell, T M; Shaia, C I; Bunton, T E; Robinson, C G; Wilkinson, E R; Hensley, L E; Cashman, K A

    2015-01-01

    Machupo virus, the causative agent of Bolivian hemorrhagic fever (BHF), is a highly lethal viral hemorrhagic fever of which little is known and for which no Food and Drug Administration-approved vaccines or therapeutics are available. This study evaluated the cynomolgus macaque as an animal model using the Machupo virus, Chicava strain, via intramuscular and aerosol challenge. The incubation period was 6 to 10 days with initial signs of depression, anorexia, diarrhea, mild fever, and a petechial skin rash. These were often followed by neurologic signs and death within an average of 18 days. Complete blood counts revealed leukopenia as well as marked thrombocytopenia. Serum chemistry values identified a decrease in total protein, marked increases in alanine aminotransferase and aspartate aminotransferase, and moderate increases in alkaline phosphatase. Gross pathology findings included a macular rash extending across the axillary and inguinal regions beginning at approximately 10 days postexposure as well as enlarged lymph nodes and spleen, enlarged and friable liver, and sporadic hemorrhages along the gastrointestinal mucosa and serosa. Histologic lesions consisted of foci of degeneration and necrosis/apoptosis in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, stomach, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system (nonsuppurative encephalitis) was histologically apparent approximately 16 days postexposure and was generally progressive. This study provides insight into the course of Machupo virus infection in cynomolgus macaques and supports the usefulness of cynomolgus macaques as a viable model of human Machupo virus infection. © The Author(s) 2014.

  14. MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa.

    Science.gov (United States)

    Calenda, Giulia; Villegas, Guillermo; Barnable, Patrick; Litterst, Claudia; Levendosky, Keith; Gettie, Agegnehu; Cooney, Michael L; Blanchard, James; Fernández-Romero, José A; Zydowsky, Thomas M; Teleshova, Natalia

    2017-03-01

    The Population Council's microbicide gel MZC (also known as PC-1005) containing MIV-150 and zinc acetate dihydrate (ZA) in carrageenan (CG) has shown promise as a broad-spectrum microbicide against HIV, herpes simplex virus (HSV), and human papillomavirus. Previous data show antiviral activity against these viruses in cell-based assays, prevention of vaginal and rectal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) infection, and reduction of vaginal HSV shedding in rhesus macaques and also excellent antiviral activity against HSV and human papillomavirus in murine models. Recently, we demonstrated that MZC is safe and effective against SHIV-RT in macaque vaginal explants. Here we established models of ex vivo SHIV-RT/HSV-2 coinfection of vaginal mucosa and SHIV-RT infection of rectal mucosa in macaques (challenge of rectal mucosa with HSV-2 did not result in reproducible tissue infection), evaluated antiviral activity of MZC, and compared quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay readouts for monitoring SHIV-RT infection. MZC (at nontoxic dilutions) significantly inhibited SHIV-RT in vaginal and rectal mucosas and HSV-2 in vaginal mucosa when present during viral challenge. Analysis of SHIV-RT infection and MZC activity by 1-step simian immunodeficiency virus gag quantitative RT-PCR and p27 enzyme-linked immunosorbent assay demonstrated similar virus growth dynamics and MZC activity by both methods and higher sensitivity of quantitative RT-PCR. Our data provide more evidence that MZC is a promising dual compartment multipurpose prevention technology candidate.

  15. Rapid Expansion of Phenylthiocarbamide Non-Tasters among Japanese Macaques.

    Directory of Open Access Journals (Sweden)

    Nami Suzuki-Hashido

    Full Text Available Bitter taste receptors (TAS2R proteins allow mammals to detect and avoid ingestion of toxins in food. Thus, TAS2Rs play an important role in food choice and are subject to complex natural selection pressures. In our previous study, we examined nucleotide variation in TAS2R38, a gene expressing bitter taste receptor for phenylthiocarbamide (PTC, in 333 Japanese macaques (Macaca fuscata from 9 local populations in Japan. We identified a PTC "non-taster" TAS2R38 allele in Japanese macaques that was caused by a loss of the start codon. This PTC non-taster allele was only found in a limited local population (the Kii area, at a frequency of 29%. In this study, we confirmed that this allele was present in only the Kii population by analyzing an additional 264 individuals from eight new populations. Using cellular and behavioral experiments, we found that this allele lost its receptor function for perceiving PTC. The nucleotide sequences of the allele including flanking regions (of about 10 kb from 23 chromosomes were identical, suggesting that a non-taster allele arose and expanded in the Kii population during the last 13,000 years. Genetic analyses of non-coding regions in Kii individuals and neighboring populations indicated that the high allele frequency in the Kii population could not be explained by demographic history, suggesting that positive selection resulted in a rapid increase in PTC non-tasters in the Kii population. The loss-of-function that occurred at the TAS2R38 locus presumably provided a fitness advantage to Japanese macaques in the Kii population. Because TAS2R38 ligands are often found in plants, this functional change in fitness is perhaps related to feeding habit specificity. These findings should provide valuable insights for elucidating adaptive evolutionary changes with respect to various environments in wild mammals.

  16. Computer-Aided Modelling of Short-Path Evaporation for Chemical Product Purification, Analysis and Design

    DEFF Research Database (Denmark)

    Sales-Cruz, Alfonso Mauricio; Gani, Rafiqul

    2006-01-01

    method, suitable for separation and purification of thermally unstable materials whose design and analysis can be efficiently performed through reliable model-based techniques. This paper presents a generalized model for short-path evaporation and highlights its development, implementation and solution...

  17. Management model for HIV/AIDS in a South African rural-based ...

    African Journals Online (AJOL)

    The model stemmed from the management framework based on the four fundamental tasks of management which are planning, organising, leading and controlling. The model was organised using Walker and Avant's (1995) basic approaches to theory building: analysis, synthesis and derivation, integrated with Dickoff, ...

  18. Using Consumer Behavior and Decision Models to Aid Students in Choosing a Major.

    Science.gov (United States)

    Kaynama, Shohreh A.; Smith, Louise W.

    1996-01-01

    A study found that using consumer behavior and decision models to guide students to a major can be useful and enjoyable for students. Students consider many of the basic parameters through multi-attribute and decision-analysis models, so time with professors, who were found to be the most influential group, can be used for more individual and…

  19. An effective automatic procedure for testing parameter identifiability of HIV/AIDS models.

    Science.gov (United States)

    Saccomani, Maria Pia

    2011-08-01

    Realistic HIV models tend to be rather complex and many recent models proposed in the literature could not yet be analyzed by traditional identifiability testing techniques. In this paper, we check a priori global identifiability of some of these nonlinear HIV models taken from the recent literature, by using a differential algebra algorithm based on previous work of the author. The algorithm is implemented in a software tool, called DAISY (Differential Algebra for Identifiability of SYstems), which has been recently released (DAISY is freely available on the web site http://www.dei.unipd.it/~pia/ ). The software can be used to automatically check global identifiability of (linear and) nonlinear models described by polynomial or rational differential equations, thus providing a general and reliable tool to test global identifiability of several HIV models proposed in the literature. It can be used by researchers with a minimum of mathematical background.

  20. Assessing the performance of a computer-based policy model of HIV and AIDS.

    Science.gov (United States)

    Rydzak, Chara E; Cotich, Kara L; Sax, Paul E; Hsu, Heather E; Wang, Bingxia; Losina, Elena; Freedberg, Kenneth A; Weinstein, Milton C; Goldie, Sue J

    2010-09-09

    Model-based analyses, conducted within a decision analytic framework, provide a systematic way to combine information about the natural history of disease and effectiveness of clinical management strategies with demographic and epidemiological characteristics of the population. Among the challenges with disease-specific modeling include the need to identify influential assumptions and to assess the face validity and internal consistency of the model. We describe a series of exercises involved in adapting a computer-based simulation model of HIV disease to the Women's Interagency HIV Study (WIHS) cohort and assess model performance as we re-parameterized the model to address policy questions in the U.S. relevant to HIV-infected women using data from the WIHS. Empiric calibration targets included 24-month survival curves stratified by treatment status and CD4 cell count. The most influential assumptions in untreated women included chronic HIV-associated mortality following an opportunistic infection, and in treated women, the 'clinical effectiveness' of HAART and the ability of HAART to prevent HIV complications independent of virologic suppression. Good-fitting parameter sets required reductions in the clinical effectiveness of 1st and 2nd line HAART and improvements in 3rd and 4th line regimens. Projected rates of treatment regimen switching using the calibrated cohort-specific model closely approximated independent analyses published using data from the WIHS. The model demonstrated good internal consistency and face validity, and supported cohort heterogeneities that have been reported in the literature. Iterative assessment of model performance can provide information about the relative influence of uncertain assumptions and provide insight into heterogeneities within and between cohorts. Description of calibration exercises can enhance the transparency of disease-specific models.

  1. Assessing the performance of a computer-based policy model of HIV and AIDS.

    Directory of Open Access Journals (Sweden)

    Chara E Rydzak

    2010-09-01

    Full Text Available Model-based analyses, conducted within a decision analytic framework, provide a systematic way to combine information about the natural history of disease and effectiveness of clinical management strategies with demographic and epidemiological characteristics of the population. Among the challenges with disease-specific modeling include the need to identify influential assumptions and to assess the face validity and internal consistency of the model.We describe a series of exercises involved in adapting a computer-based simulation model of HIV disease to the Women's Interagency HIV Study (WIHS cohort and assess model performance as we re-parameterized the model to address policy questions in the U.S. relevant to HIV-infected women using data from the WIHS. Empiric calibration targets included 24-month survival curves stratified by treatment status and CD4 cell count. The most influential assumptions in untreated women included chronic HIV-associated mortality following an opportunistic infection, and in treated women, the 'clinical effectiveness' of HAART and the ability of HAART to prevent HIV complications independent of virologic suppression. Good-fitting parameter sets required reductions in the clinical effectiveness of 1st and 2nd line HAART and improvements in 3rd and 4th line regimens. Projected rates of treatment regimen switching using the calibrated cohort-specific model closely approximated independent analyses published using data from the WIHS.The model demonstrated good internal consistency and face validity, and supported cohort heterogeneities that have been reported in the literature. Iterative assessment of model performance can provide information about the relative influence of uncertain assumptions and provide insight into heterogeneities within and between cohorts. Description of calibration exercises can enhance the transparency of disease-specific models.

  2. Autotransplantation of immature third molars using a computer-aided rapid prototyping model: a report of 4 cases.

    Science.gov (United States)

    Jang, Ji-Hyun; Lee, Seung-Jong; Kim, Euiseong

    2013-11-01

    Autotransplantation of immature teeth can be an option for premature tooth loss in young patients as an alternative to immediately replacing teeth with fixed or implant-supported prostheses. The present case series reports 4 successful autotransplantation cases using computer-aided rapid prototyping (CARP) models with immature third molars. The compromised upper and lower molars (n = 4) of patients aged 15-21 years old were transplanted with third molars using CARP models. Postoperatively, the pulp vitality and the development of the roots were examined clinically and radiographically. The patient follow-up period was 2-7.5 years after surgery. The long-term follow-up showed that all of the transplants were asymptomatic and functional. Radiographic examination indicated that the apices developed continuously and the root length and thickness increased. The final follow-up examination revealed that all of the transplants kept the vitality, and the apices were fully developed with normal periodontal ligaments and trabecular bony patterns. Based on long-term follow-up observations, our 4 cases of autotransplantation of immature teeth using CARP models resulted in favorable prognoses. The CARP model assisted in minimizing the extraoral time and the possible Hertwig epithelial root sheath injury of the transplanted tooth. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  3. A model based on feature objects aided strategy to evaluate the methane generation from food waste by anaerobic digestion.

    Science.gov (United States)

    Yu, Meijuan; Zhao, Mingxing; Huang, Zhenxing; Xi, Kezhong; Shi, Wansheng; Ruan, Wenquan

    2018-02-01

    A model based on feature objects (FOs) aided strategy was used to evaluate the methane generation from food waste by anaerobic digestion. The kinetics of feature objects was tested by the modified Gompertz model and the first-order kinetic model, and the first-order kinetic hydrolysis constants were used to estimate the reaction rate of homemade and actual food waste. The results showed that the methane yields of four feature objects were significantly different. The anaerobic digestion of homemade food waste and actual food waste had various methane yields and kinetic constants due to the different contents of FOs in food waste. Combining the kinetic equations with the multiple linear regression equation could well express the methane yield of food waste, as the R 2 of food waste was more than 0.9. The predictive methane yields of the two actual food waste were 528.22 mL g -1  TS and 545.29 mL g -1  TS with the model, while the experimental values were 527.47 mL g -1  TS and 522.1 mL g -1  TS, respectively. The relative error between the experimental cumulative methane yields and the predicted cumulative methane yields were both less than 5%. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Hearing aid adjustment

    DEFF Research Database (Denmark)

    Heinemann, Trine; Matthews, Ben; Raudaskoski, Pirkko Liisa

    2012-01-01

    to the interaction during hearing aid fitting. This report of a Danish pilot study describes two such problems. The first problem arises from the requirement that the audiologist needs to ‘translate’ the patient’s subjective hearing description for making technological decisions. The second problem is the way...... in which the hearing aid user’s implicit and often unrealistic expectations are handled. This kind of research has potential application for developing a model of best practices....

  5. HIV / AIDS

    Science.gov (United States)

    ... Relations Cyber Infrastructure Computational Biology Equal Employment Opportunity Ethics Global Research Office of Mission Integration and Financial Management Strategic Planning Workforce Effectiveness Workplace Solutions Technology Transfer Intellectual Property Division of AIDS ...

  6. The framework of a UAS-aided flash flood modeling system for coastal regions

    Science.gov (United States)

    Zhang, H.; Xu, H.

    2016-02-01

    Flash floods cause severe economic damage and are one of the leading causes of fatalities connected with natural disasters in the Gulf Coast region. Current flash flood modeling systems rely on empirical hydrological models driven by precipitation estimates only. Although precipitation is the driving factor for flash floods, soil moisture, urban drainage system and impervious surface have been recognized to have significant impacts on the development of flash floods. We propose a new flash flooding modeling system that integrates 3-D hydrological simulation with satellite and multi-UAS observations. It will have three advantages over existing modeling systems. First, it will incorporate 1-km soil moisture data through integrating satellite images from European SMOS mission and NASA's SMAP mission. The utilization of high-resolution satellite images will provide essential information to determine antecedent soil moisture condition, which is an essential control on flood generation. Second, this system is able to adjust flood forecasting based on real-time inundation information collected by multi-UAS. A group of UAS will be deployed during storm events to capture the changing extent of flooded areas and water depth at multiple critical locations simultaneously. Such information will be transmitted to a hydrological model to validate and improve flood simulation. Third, the backbone of this system is a state-of-the-art 3-D hydrological model that assimilates the hydrological information from satellites and multi-UAS. The model is able to address surface water-groundwater interactions and reflect the effects of various infrastructures. Using Web-GIS technologies, the modeling results will be available online as interactive flood maps accessible to the public. To support the development and verification of this modeling system, surface and subsurface hydrological observations will be conducted in a number of small watersheds in the Coastal Bend region. We envision this

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

    Directory of Open Access Journals (Sweden)

    Ilhem Messaoudi

    2009-11-01

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

  8. Principles and models of a co-operative systems of a supervision aid; SCAS: principes et modeles d`un systeme cooperatif d`assistance a la supervision

    Energy Technology Data Exchange (ETDEWEB)

    Penalva, J.M. [CEA Centre d`Etudes de la Vallee du Rhone, 30 - Marcoule (France). Dept. d`Exploitation du Retraitement et de Demantelement; Cases, E. [CEA Centre d`Etudes de la Vallee du Rhone, 30 - Marcoule (France). Dept. d`Exploitation du Retraitement et de Demantelement]|[Paris-6 Univ., 75 (France); Brezillon, P. [Paris-6 Univ., 75 (France); Minault, S.

    1994-12-31

    This paper presents the functioning principles and the necessary models for a cooperative system of supervision aid (SCAS) used for a high-automated workshop. A meta-system of supervision is made up of the operator and the SCAS. The SCAS can operate under 2 different modes: wakefulness and cooperation. On the first one the behaviours of the process and the operator is observed and analysed. On the second one, it helps to solve the problems occurred by the operator. (TEC). 3 refs.

  9. A novel low-parameter computational model to aid in-silico glycoengineering

    DEFF Research Database (Denmark)

    Spahn, Philipp N.; Hansen, Anders Holmgaard; Hansen, Henning Gram

    2015-01-01

    benefit from computational models that would better meet the requirements for industrial utilization. Here, we introduce a novel approach combining constraints-based and stochastic techniques to derive a computational model that can predict the effects of gene knockouts on protein glycoprofiles while...... it does not follow any direct equivalent of a genetic code. Instead, its complex biogenesis in the Golgi apparatus (Figure 1A) integrates a variety of influencing factors most of which are only incompletely understood. Various attempts have been undertaken so far to computationally model the process...

  10. Computer-aided design of curved surfaces with automatic model generation

    Science.gov (United States)

    Staley, S. M.; Jerard, R. B.; White, P. R.

    1980-01-01

    The design and visualization of three-dimensional objects with curved surfaces have always been difficult. The paper given below describes a computer system which facilitates both the design and visualization of such surfaces. The system enhances the design of these surfaces by virtue of various interactive techniques coupled with the application of B-Spline theory. Visualization is facilitated by including a specially built model-making machine which produces three-dimensional foam models. Thus, the system permits the designer to produce an inexpensive model of the object which is suitable for evaluation and presentation.

  11. One-equation near-wall turbulence modeling with the aid of direct simulation data

    Science.gov (United States)

    Rodi, W.; Mansour, N. N.; Michelassi, V.

    1993-01-01

    The length scales appearing in the relations for the eddy viscosity and dissipation rate in one-equation models were evaluated from direct numerical (DNS) simulation data for developed channel and boundary-layer flow at two Reynolds numbers each. To prepare the ground for the evaluation, the distribution of the most relevant mean-flow and turbulence quantities is presented and discussed, also with respect to Reynolds-number influence and to differences between channel and boundary-layer flow. An alternative model is tested as near wall component of a two-layer model by application to developed-channel, boundary-layer and backward-facing-step flows.

  12. MIV-150-containing intravaginal rings protect macaque vaginal explants against SHIV-RT infection.

    Science.gov (United States)

    Ouattara, Louise A; Barnable, Patrick; Mawson, Paul; Seidor, Samantha; Zydowsky, Thomas M; Kizima, Larisa; Rodriguez, Aixa; Fernández-Romero, José A; Cooney, Michael L; Roberts, Kevin D; Gettie, Agegnehu; Blanchard, James; Robbiani, Melissa; Teleshova, Natalia

    2014-05-01

    Recent studies demonstrated that intravaginal rings (IVRs) containing 100 mg of the nonnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 significantly protect macaques against a chimeric simian-human immunodeficiency virus that expresses the HIV-1 HxB2 reverse transcriptase (SHIV-RT) when present before and after vaginal challenge. The objectives of this study were to (i) evaluate the pharmacodynamics (PD) of MIV-150 in vaginal fluids (VF) and in ectocervical and vaginal tissues following 100-mg MIV-150 IVR exposure and to (ii) gain more insight whether pharmacokinetics (PK) of MIV-150 can predict PD. MIV-150 in VF collected at 1 day and 14 days post-MIV-150 IVR insertion inhibited ex vivo SHIV-RT infection in vaginal biopsy specimens from untreated animals (not carrying IVRs) in a dose-dependent manner. Previous PK studies demonstrated a significant increase of ectocervical and vaginal tissue MIV-150 concentrations 14 days versus 1 day post-IVR insertion, with the highest increase in vaginal tissue. Therefore, we tested PD of MIV-150 in tissues 14 days post-MIV-150 IVR insertion. Ex vivo SHIV-RT infection of vaginal, but not ectocervical, tissues collected 14 days post-MIV-150 IVR insertion was significantly inhibited compared to infection at the baseline (prior to MIV-150 IVR exposure). No changes in vaginal and ectocervical tissue infection were observed after placebo IVR exposure. Overall, these data underscore the use of the ex vivo macaque explant challenge models to evaluate tissue and VF PK/PD of candidate microbicides before in vivo animal efficacy studies. The data support further development of MIV-150-containing IVRs.

  13. Comparison of energy balance between two different-sized groups of Japanese macaques (Macaca fuscata yakui).

    Science.gov (United States)

    Kurihara, Yosuke; Hanya, Goro

    2017-07-01

    Quantifying the energy balance is essential for testing socio-ecological models. To reveal costs and benefits of group living in Japanese macaques from the perspective of feeding competition, Kurihara and Hanya (Am J Primatol 77:986-1000, 2015) previously compared feeding behavior between two different-sized groups of macaques (larger group 30-35 individuals; smaller group 13-15 individuals) in the coastal forest of Yakushima, Japan. The results suggested that the larger group exhibited greater feeding effort because of intragroup scramble competition and that the smaller group suffered from higher travel costs, possibly owing to intergroup contest competition. However, it remained unclear whether the behavioral differences affected their energy budgets. The present study examined energetic consequences of the different feeding behaviors in the two groups. Using behavioral data from 10 to 13 adult females and nutritional composition of food items, we compared ingestion rates, energetic/nutritional content of diet, and energy budgets between the two groups. Ingestion rates and energetic/nutritional content of diet did not differ between the two groups. Despite the higher feeding effort of the larger group, energy intake did not differ between the two groups. Energy expenditure did not differ between the two groups because higher travel costs were negated by lower feeding effort in the smaller group. Consequently, the energy balance did not differ between the two groups. We demonstrated that the behavioral measures of feeding competition were not translated into their energetic condition; moreover, our findings re-emphasize the importance of quantifying behavioral and fitness measures for interpreting variation in feeding behavior properly.

  14. Sex Differences in the Development of Social Relationships in Rhesus Macaques (Macaca mulatta)

    Science.gov (United States)

    Amici, Federica; Langos, Doreen; Widdig, Anja

    2015-01-01

    Several studies have documented the importance of social bonding for the enhancement of individual fitness. However, little is known about how social relationships develop through ontogeny, and whether their development follows the same trajectory in males and females. Here we analyzed affiliative interactions (proximity, social grooming, play) combined with demographic and genetic data in semi-free-ranging rhesus macaques (Macaca mulatta) on Cayo Santiago over their first 4 yr of life (from birth to sexual maturation) to understand how these interactions change through development in both sexes. Generalized linear mixed models revealed that social behaviors mostly followed different developmental trajectories in males and females and were highly dependent on the social context. In particular, sex differences in social behavior varied through development depending on the partner’s sex and age. Females engaged in more social interactions than males, especially with other females, and were more involved in grooming around the time of maturation. In contrast, males interacted more with males and age peers, especially around maturation. Sex differences in social behavior varied through development, but also depended on rank, partner’s rank, and kin line, although not consistently. High-ranking individuals, especially older females, were generally preferred as social partners. Moreover, both male and female individuals interacted mostly with maternal kin, although males also preferred paternal kin over nonkin. Importantly, most developmental changes in sociality happened when individuals were ca. 2 yr old, suggesting that this might be a milestone in the development of sociality in rhesus macaques. The only notable exception to this pattern was play, which was more pronounced in males from the beginning of their lives. We propose that play might serve as a trigger of sex differences in social behavior, with sex differences emerging early in development and

  15. Sex Differences in the Development of Social Relationships in Rhesus Macaques (Macaca mulatta).

    Science.gov (United States)

    Kulik, Lars; Amici, Federica; Langos, Doreen; Widdig, Anja

    2015-04-01

    Several studies have documented the importance of social bonding for the enhancement of individual fitness. However, little is known about how social relationships develop through ontogeny, and whether their development follows the same trajectory in males and females. Here we analyzed affiliative interactions (proximity, social grooming, play) combined with demographic and genetic data in semi-free-ranging rhesus macaques ( Macaca mulatta ) on Cayo Santiago over their first 4 yr of life (from birth to sexual maturation) to understand how these interactions change through development in both sexes. Generalized linear mixed models revealed that social behaviors mostly followed different developmental trajectories in males and females and were highly dependent on the social context. In particular, sex differences in social behavior varied through development depending on the partner's sex and age. Females engaged in more social interactions than males, especially with other females, and were more involved in grooming around the time of maturation. In contrast, males interacted more with males and age peers, especially around maturation. Sex differences in social behavior varied through development, but also depended on rank, partner's rank, and kin line, although not consistently. High-ranking individuals, especially older females, were generally preferred as social partners. Moreover, both male and female individuals interacted mostly with maternal kin, although males also preferred paternal kin over nonkin. Importantly, most developmental changes in sociality happened when individuals were ca . 2 yr old, suggesting that this might be a milestone in the development of sociality in rhesus macaques. The only notable exception to this pattern was play, which was more pronounced in males from the beginning of their lives. We propose that play might serve as a trigger of sex differences in social behavior, with sex differences emerging early in development and increasing

  16. AIDS guidelines.

    Science.gov (United States)

    Berger, R

    1986-04-30

    The Sun article, "Employers finding that AIDS in the workplace is a managerial nightmare" (April 3), did not accurately portray the status of AIDS in the workplace. The AIDS virus, HTLV III, is transmitted by body fluids, primarily semen and blood, and there is no known risk of transmitting the virus by casual contact in the workplace. The Center for Disease Control (CDC) released guidelines for child care workers last August. Guidelines on preventing transmission of AIDS in the workplace were issued by CDC in November 1985. These guidelines specifically discussed health care, personal service, and food service workers. The recommendations were against routine screening. Furthermore, employment should not be restricted on the basis of a positive HTLV III antibody test. A person with HTLV III infection should be exempt from the workplace only if there are circumstances interfering with job performance. In Maryland, the Governor's Task Force on AIDS has gone on record as endorsing CDC guidelines related to employment. Furthermore, the task force condemns discrimination based on the disease AIDS, AIDS Related Complex (ARC), or HTLV III infection. Increasingly AIDS patients are being considered legally disabled and therefore are protected by federal and state laws prohibiting discrimination on the basis of a handicap. Marylanders who are subjected to mandatory HTLV III screening in the workplace, or if discriminated against on the basis of HTLV III inefction, should contact the Maryland Commission on Human Relations, the Maryland Department of Health and Mental Hygiene, or the Health Education Resource Organization (HERO). All 3 of these resources guarantee confidentiality. It is only by employees reporting incidents that a nightmare in the workplace can be avoided in Maryland. full text

  17. Complete Unique Genome Sequence, Expression Profile, and Salivary Gland Tissue Tropism of the Herpesvirus 7 Homolog in Pigtailed Macaques.

    Science.gov (United States)

    Staheli, Jeannette P; Dyen, Michael R; Deutsch, Gail H; Basom, Ryan S; Fitzgibbon, Matthew P; Lewis, Patrick; Barcy, Serge

    2016-08-01

    Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses and are highly prevalent in the human population. Roseolovirus reactivation in an immunocompromised host can cause severe pathologies. While the pathogenic potential of HHV-7 is unclear, it can reactivate HHV-6 from latency and thus contributes to severe pathological conditions associated with HHV-6. Because of the ubiquitous nature of roseoloviruses, their roles in such interactions and the resulting pathological consequences have been difficult to study. Furthermore, the lack of a relevant animal model for HHV-7 infection has hindered a better understanding of its contribution to roseolovirus-associated diseases. Using next-generation sequencing analysis, we characterized the unique genome of an uncultured novel pigtailed macaque roseolovirus. Detailed genomic analysis revealed the presence of gene homologs to all 84 known HHV-7 open reading frames. Phylogenetic analysis confirmed that the virus is a macaque homolog of HHV-7, which we have provisionally named Macaca nemestrina herpesvirus 7 (MneHV7). Using high-throughput RNA sequencing, we observed that the salivary gland tissue samples from nine different macaques had distinct MneHV7 gene expression patterns and that the overall number of viral transcripts correlated with viral loads in parotid gland tissue and saliva. Immunohistochemistry staining confirmed that, like HHV-7, MneHV7 exhibits a natural tropism for salivary gland ductal cells. We also observed staining for MneHV7 in peripheral nerve ganglia present in salivary gland tissues, suggesting that HHV-7 may also have a tropism for the peripheral nervous system. Our data demonstrate that MneHV7-infected macaques represent a relevant animal model that may help clarify the causality between roseolovirus reactivation and diseases. Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses. We have recently discovered that pigtailed macaques are naturally

  18. Modelling the spread of HIV/AIDS epidemic in the presence of ...

    African Journals Online (AJOL)

    The model analysis shows that the disease-free equilibrium is always locally asymptotically stable and in such a case the basic reproductive number R01, the endemic equilibrium exists and the disease remains in the ...

  19. Computer-Aided Design Methods for Model-Based Nonlinear Engine Control Systems, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Traditional design methods for aircraft turbine engine control systems have relied on the use of linearized models and linear control theory. While these controllers...

  20. Computer aided system engineering and analysis (CASE/A) modeling package for ECLS systems - An overview

    Science.gov (United States)

    Dalee, Robert C.; Bacskay, Allen S.; Knox, James C.

    1990-01-01

    An overview of the CASE/A-ECLSS series modeling package is presented. CASE/A is an analytical tool that has supplied engineering productivity accomplishments during ECLSS design activities. A components verification program was performed to assure component modeling validity based on test data from the Phase II comparative test program completed at the Marshall Space Flight Center. An integrated plotting feature has been added to the program which allows the operator to analyze on-screen data trends or get hard copy plots from within the CASE/A operating environment. New command features in the areas of schematic, output, and model management, and component data editing have been incorporated to enhance the engineer's productivity during a modeling program.

  1. Predicting Proliferation: High Reliability Forecasting Models of Nuclear Proliferation as a Policy & Analytical Aid

    OpenAIRE

    Center on Contemporary Conflict; Gartzke, Erik

    2015-01-01

    Performer: University of California at San Diego Project Lead: Erik Gartzke Project Cost: $121,000 FY15-16 Objective: Scholars have spent decades studying and explaining nuclear proliferation. This project will develop a model to predict the behavior of states regarding their pursuit and acquisition of nuclear weapons. An accurate prediction model will allow for action against potential suppliers, interdiction of nuclear trade, intelligence collection on covert nuclea...

  2. Robust vaginal colonization of macaques with a novel vaginally disintegrating tablet containing a live biotherapeutic product to prevent HIV infection in women.

    Directory of Open Access Journals (Sweden)

    Laurel A Lagenaur

    Full Text Available MucoCept is a biotherapeutic for prevention of HIV-1 infection in women and contains a human, vaginal Lactobacillus jensenii that has been genetically enhanced to express the HIV-1 entry inhibitor, modified cyanovirin-N (mCV-N. The objective of this study was to develop a solid vaginal dosage form that supports sustained vaginal colonization of the MucoCept Lactobacillus at levels previously shown, with freshly prepared cultures, to protect macaques from SHIV infection and to test this formulation in a macaque vaginal colonization model. Vaginally disintegrating tablets were prepared by lyophilizing the formulated bacteria in tablet-shaped molds, then packaging in foil pouches with desiccant. Disintegration time, potency and stability of the tablets were assessed. For colonization, non-synchronized macaques were dosed vaginally with either one tablet or five tablets delivered over five days. Vaginal samples were obtained at three, 14, and 21 days post-dosing and cultured to determine Lactobacillus colonization levels. To confirm identity of the MucoCept Lactobacillus strain, genomic DNA was extracted from samples on days 14 and 21 and a strain-specific PCR was performed. Supernatants from bacteria were tested for the presence of the mCV-N protein by Western blot. The tablets were easy to handle, disintegrated within two minutes, potent (5.7x1011 CFU/g, and stable at 4°C and 25°C. Vaginal administration of the tablets to macaques resulted in colonization of the MucoCept Lactobacillus in 66% of macaques at 14 days post-dosing and 83% after 21 days. There was no significant difference in colonization levels for the one or five tablet dosing regimens (p=0.88 Day 14, p=0.99 Day 21. Strain-specific PCR confirmed the presence of the bacteria even in culture-negative macaques. Finally, the presence of mCV-N protein was confirmed by Western blot analysis using a specific anti-mCV-N antibody.

  3. Robust vaginal colonization of macaques with a novel vaginally disintegrating tablet containing a live biotherapeutic product to prevent HIV infection in women.

    Science.gov (United States)

    Lagenaur, Laurel A; Swedek, Iwona; Lee, Peter P; Parks, Thomas P

    2015-01-01

    MucoCept is a biotherapeutic for prevention of HIV-1 infection in women and contains a human, vaginal Lactobacillus jensenii that has been genetically enhanced to express the HIV-1 entry inhibitor, modified cyanovirin-N (mCV-N). The objective of this study was to develop a solid vaginal dosage form that supports sustained vaginal colonization of the MucoCept Lactobacillus at levels previously shown, with freshly prepared cultures, to protect macaques from SHIV infection and to test this formulation in a macaque vaginal colonization model. Vaginally disintegrating tablets were prepared by lyophilizing the formulated bacteria in tablet-shaped molds, then packaging in foil pouches with desiccant. Disintegration time, potency and stability of the tablets were assessed. For colonization, non-synchronized macaques were dosed vaginally with either one tablet or five tablets delivered over five days. Vaginal samples were obtained at three, 14, and 21 days post-dosing and cultured to determine Lactobacillus colonization levels. To confirm identity of the MucoCept Lactobacillus strain, genomic DNA was extracted from samples on days 14 and 21 and a strain-specific PCR was performed. Supernatants from bacteria were tested for the presence of the mCV-N protein by Western blot. The tablets were easy to handle, disintegrated within two minutes, potent (5.7x1011 CFU/g), and stable at 4°C and 25°C. Vaginal administration of the tablets to macaques resulted in colonization of the MucoCept Lactobacillus in 66% of macaques at 14 days post-dosing and 83% after 21 days. There was no significant difference in colonization levels for the one or five tablet dosing regimens (p=0.88 Day 14, p=0.99 Day 21). Strain-specific PCR confirmed the presence of the bacteria even in culture-negative macaques. Finally, the presence of mCV-N protein was confirmed by Western blot analysis using a specific anti-mCV-N antibody.

  4. The Dynamics of an HIV/AIDS Model with Screened Disease Carriers

    Directory of Open Access Journals (Sweden)

    S. D. Hove-Musekwa

    2009-01-01

    Full Text Available The presence of carriers usually complicates the dynamics and prevention of a disease. They are not recognized as disease cases themselves unless they are screened and they usually spread the infection without them being aware. We argue that this has been one of the major causes of the spread of human immunodeficiency virus (HIV. We propose, in this paper, a model for the heterogeneous transmission of HIV/acquired immunodeficiency syndrome in the presence of disease carriers. The model allows us to assess the role of screening, as an intervention program that can slow the epidemic. A threshold value ψ*, for the screening rate is obtained. It is shown numerically that if 80% or more of the carrier population is screened, the epidemic can be contained. The qualitative analysis is done in terms of the model reproduction number R. The model has two equilibria, the disease free equilibrium and a unique endemic equilibrium. The disease free equilibrium is globally stable of R  1. A detailed discussion of the model reproduction number is given and numerical simulations are done to show the role of some of the important model parameters.

  5. ABO blood group phenotype frequency estimation using molecular phenotyping in rhesus and cynomolgus macaques.

    Science.gov (United States)

    Kanthaswamy, S; Ng, J; Oldt, R F; Valdivia, L; Houghton, P; Smith, D G

    2017-11-01

    A much larger sample (N = 2369) was used to evaluate a previously reported distribution of the A, AB and B blood group phenotypes in rhesus and cynomolgus macaques from six different regional populations. These samples, acquired from 15 different breeding and research facilities in the United States, were analyzed using a real-time quantitative polymerase chain reaction (qPCR) assay that targets single nucleotide polymorphisms (SNPs) responsible for the macaque A, B and AB phenotypes. The frequency distributions of blood group phenotypes of the two species differ significantly from each other and significant regional differentiation within the geographic ranges of each species was also observed. The B blood group phenotype was prevalent in rhesus macaques, especially those from India, while the frequencies of the A, B and AB phenotypes varied significantly among cynomolgus macaques from different geographic regions. The Mauritian cynomolgus macaques, despite having originated in Indonesia, showed significant (P ≪ .01) divergence from the Indonesian animals at the ABO blood group locus. Most Mauritian animals belonged to the B blood group while the Indonesian animals were mostly A. The close similarity in blood group frequency distributions between the Chinese rhesus and Indochinese cynomolgus macaques demonstrates that the introgression between these two species extends beyond the zone of intergradation in Indochina. This study underscores the importance of ABO blood group phenotyping of the domestic supply of macaques and their biospecimens. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Impact of oral health education by audio aids, braille and tactile models on the oral health status of visually impaired children of Bhopal City.

    Science.gov (United States)

    Gautam, Anjali; Bhambal, Ajay; Moghe, Swapnil

    2018-01-01

    Children with special needs face unique challenges in day-to-day practice. They are dependent on their close ones for everything. To improve oral hygiene in such visually impaired children, undue training and education are required. Braille is an important language for reading and writing for the visually impaired. It helps them understand and visualize the world via touch. Audio aids are being used to impart health education to the visually impaired. Tactile models help them perceive things which they cannot visualize and hence are an important learning tool. This study aimed to assess the improvement in oral hygiene by audio aids and Braille and tactile models in visually impaired children aged 6-16 years of Bhopal city. This was a prospective study. Sixty visually impaired children aged 6-16 years were selected and randomly divided into three groups (20 children each). Group A: audio aids + Braille, Group B: audio aids + tactile models, and Group C: audio aids + Braille + tactile models. Instructions were given for maintaining good oral hygiene and brushing techniques were explained to all children. After 3 months' time, the oral hygiene status was recorded and compared using plaque and gingival index. ANNOVA test was used. The present study showed a decrease in the mean plaque and gingival scores at all time intervals in individual group as compared to that of the baseline that was statistically significant. The study depicts that the combination of audio aids, Braille and tactile models is an effective way to provide oral health education and improve oral health status of visually impaired children.

  7. Impact of oral health education by audio aids, braille and tactile models on the oral health status of visually impaired children of Bhopal City

    Directory of Open Access Journals (Sweden)

    Anjali Gautam

    2018-01-01

    Full Text Available Context: Children with special needs face unique challenges in day-to-day practice. They are dependent on their close ones for everything. To improve oral hygiene in such visually impaired children, undue training and education are required. Braille is an important language for reading and writing for the visually impaired. It helps them understand and visualize the world via touch. Audio aids are being used to impart health education to the visually impaired. Tactile models help them perceive things which they cannot visualize and hence are an important learning tool. Aim: This study aimed to assess the improvement in oral hygiene by audio aids and Braille and tactile models in visually impaired children aged 6–16 years of Bhopal city. Settings and Design: This was a prospective study. Materials and Methods: Sixty visually impaired children aged 6–16 years were selected and randomly divided into three groups (20 children each. Group A: audio aids + Braille, Group B: audio aids + tactile models, and Group C: audio aids + Braille + tactile models. Instructions were given for maintaining good oral hygiene and brushing techniques were explained to all children. After 3 months' time, the oral hygiene status was recorded and compared using plaque and gingival index. Statistical Analysis Used: ANNOVA test was used. Results: The present study showed a decrease in the mean plaque and gingival scores at all time intervals in individual group as compared to that of the baseline that was statistically significant. Conclusions: The study depicts that the combination of audio aids, Braille and tactile models is an effective way to provide oral health education and improve oral health status of visually impaired children.

  8. Longitudinal analysis reveals characteristically high proportions of bacterial vaginosis-associated bacteria and temporal variability of vaginal microbiota in northern pig-tailed macaques (Macaca leonina).

    Science.gov (United States)

    Zhu, Lin; Lei, Ai-Hua; Zheng, Hong-Yi; Lyu, Long-Bao; Zhang, Zhi-Gang; Zheng, Yong-Tang

    2015-09-18

    The complex and dynamic vaginal microbial ecosystem is critical to both health and disease of the host. Studies focusing on how vaginal microbiota influences HIV-1 infection may face limitations in selecting proper animal models. Given that northern pig-tailed macaques (Macaca leonina) are susceptible to HIV-1 infection, they may be an optimal animal model for elucidating the mechanisms by which vaginal microbiota contributes to resistance and susceptibility to HIV-1 infection. However, little is known about the composition and temporal variability of vaginal microbiota of the northern pig-tailed macaque. Here, we present a comprehensive catalog of the composition and temporal dynamics of vaginal microbiota of two healthy northern pig-tailed macaques over 19 weeks using 454-pyrosequencing of 16S rRNA genes. We found remarkably high proportions of a diverse array of anaerobic bacteria associated with bacterial vaginosis. Atopobium and Sneathia were dominant genera, and interestingly, we demonstrated the presence of Lactobacillus-dominated vaginal microbiota. Moreover, longitudinal analysis demonstrated that the temporal dynamics of the vaginal microbiota were considerably individualized. Finally, network analysis revealed that vaginal pH may influence the temporal dynamics of the vaginal microbiota, suggesting that inter-subject variability of vaginal bacterial communities could be mirrored in inter-subject variation in correlation profiles of species with each other and with vaginal pH over time. Our results suggest that the northern pig-tailed macaque could be an ideal animal model for prospective investigation of the mechanisms by which vaginal microbiota influence susceptibility and resistance to HIV-1 infection in the context of highly polymicrobial and Lactobacillus-dominated states.

  9. Relationship of Estimated SHIV Acquisition Time Points During the Menstrual Cycle and Thinning of Vaginal Epithelial Layers in Pigtail Macaques.

    Science.gov (United States)

    Kersh, Ellen N; Ritter, Jana; Butler, Katherine; Ostergaard, Sharon Dietz; Hanson, Debra; Ellis, Shanon; Zaki, Sherif; McNicholl, Janet M

    2015-12-01

    HIV acquisition in the female genital tract remains incompletely understood. Quantitative data on biological HIV risk factors, the influence of reproductive hormones, and infection risk are lacking. We evaluated vaginal epithelial thickness during the menstrual cycle in pigtail macaques (Macaca nemestrina). This model previously revealed increased susceptibility to vaginal infection during and after progesterone-dominated periods in the menstrual cycle. Nucleated and nonnucleated (superficial) epithelial layers were quantitated throughout the menstrual cycle of 16 macaques. We examined the relationship with previously estimated vaginal SHIVSF162P3 acquisition time points in the cycle of 43 different animals repeatedly exposed to low virus doses. In the luteal phase (days 17 to cycle end), the mean vaginal epithelium thinned to 66% of mean follicular thickness (days 1-16; P = 0.007, Mann-Whitney test). Analyzing 4-day segments, the epithelium was thickest on days 9 to 12 and thinned to 31% thereof on days 29 to 32, with reductions of nucleated and nonnucleated layers to 36% and 15% of their previous thickness, respectively. The proportion of animals with estimated SHIV acquisition in each cycle segment correlated with nonnucleated layer thinning (Pearson r = 0.7, P layer thinning (Pearson r = 0.6, P = 0.15). These data provide a detailed picture of dynamic cycle-related changes in the vaginal epithelium of pigtail macaques. Substantial thinning occurred in the superficial, nonnucleated layer, which maintains the vaginal microbiome. The findings support vaginal tissue architecture as susceptibility factor for infection and contribute to our understanding of innate resistance to SHIV infection.

  10. Spatial model for risk prediction and sub-national prioritization to aid poliovirus eradication in Pakistan.

    Science.gov (United States)

    Mercer, Laina D; Safdar, Rana M; Ahmed, Jamal; Mahamud, Abdirahman; Khan, M Muzaffar; Gerber, Sue; O'Leary, Aiden; Ryan, Mike; Salet, Frank; Kroiss, Steve J; Lyons, Hil; Upfill-Brown, Alexander; Chabot-Couture, Guillaume

    2017-10-11

    Pakistan is one of only three countries where poliovirus circulation remains endemic. For the Pakistan Polio Eradication Program, identifying high risk districts is essential to target interventions and allocate limited resources. Using a hierarchical Bayesian framework we developed a spatial Poisson hurdle model to jointly model the probability of one or more paralytic polio cases, and the number of cases that would be detected in the event of an outbreak. Rates of underimmunization, routine immunization, and population immunity, as well as seasonality and a history of cases were used to project future risk of cases. The expected number of cases in each district in a 6-month period was predicted using indicators from the previous 6-months and the estimated coefficients from the model. The model achieves an average of 90% predictive accuracy as measured by area under the receiver operating characteristic (ROC) curve, for the past 3 years of cases. The risk of poliovirus has decreased dramatically in many of the key reservoir areas in Pakistan. The results of this model have been used to prioritize sub-national areas in Pakistan to receive additional immunization activities, additional monitoring, or other special interventions.

  11. Estimation of Shear Wave Speed in the Rhesus Macaques Uterine Cervix

    Science.gov (United States)

    Huang, Bin; Drehfal, Lindsey C.; Rosado-Mendez, Ivan M.; Guerrero, Quinton W.; Palmeri, Mark L.; Simmons, Heather A.; Feltovich, Helen; Hall, Timothy J.

    2016-01-01

    Cervical softness is a critical parameter in pregnancy. Clinically, preterm birth is associated with premature cervical softening and post-dates birth is associated with delayed cervical softening. In practice, the assessment of softness is subjective, based on digital examination. Fortunately, objective, quantitative techniques to assess softness and other parameters associated with microstructural cervical change are emerging. One of these is shear wave speed (SWS) estimation. In principle, this allows objective characterization of stiffness because waves travel more slowly in softer tissue. We are studying SWS in humans and rhesus macaques, the latter in order to accelerate translation from bench to bedside. For the current study, we estimated SWS in ex vivo cervices of rhesus macaques, n=24 nulliparous (never given birth) and n=9 multiparous (delivered at least 1 baby). Misoprostol (a prostaglandin used to soften human cervices prior to gynecological procedures) was administered to 13 macaques prior to necropsy (nulliparous: 7, multiparous: 6). SWS measurements were made at predetermined locations from the distal to proximal end of the cervix on both the anterior and posterior cervix, with 5 repeat measures at each location. The intent was to explore macaque cervical microstructure, including biological and spatial variability, to elucidate the similarities and differences between the macaque and the human cervix in order to facilitate future in vivo studies. We found that SWS is dependent on location in the normal nonpregnant macaque cervix, as in the human cervix. Unlike the human cervix, we detected no difference between ripened and unripened rhesus macaque cervix samples, nor nulliparous versus multiparous samples, although we observed a trend toward stiffer tissue in nulliparous samples. We found rhesus macaque cervix to be much stiffer than human, which is important for technique refinement. These findings are useful for guiding study of cervical

  12. How a new funding model will shift allocations from the Global Fund to Fight AIDS, tuberculosis, and malaria.

    Science.gov (United States)

    Fan, Victoria Y; Glassman, Amanda; Silverman, Rachel L

    2014-12-01

    Policy makers deciding how to fund global health programs in low- and middle-income countries face important but difficult questions about how to allocate resources across countries. In this article we present a typology of three allocation methodologies to align allocations with priorities. We then apply our typology to the Global Fund to Fight AIDS, Tuberculosis, and Malaria. We examined the Global Fund's historical HIV allocations and its predicted allocations under a new funding model that creates an explicit allocation methodology. We found that under the new funding model, substantial shifts in the Global Fund's portfolio are likely to result from concentrating resources in countries with more HIV cases and lower per capita incomes. For example, South Africa, which had 15.8 percent of global HIV cases in 2009, could see its Global Fund HIV funding more than triple, from historic levels that averaged 3.0 percent to 9.7 percent of total Global Fund allocations. The new funding model methodology is expected, but not guaranteed, to improve the efficiency of Global Fund allocations in comparison to historical practice. We conclude with recommendations for the Global Fund and other global health donors to further develop their allocation methodologies and processes to improve efficiency and transparency. Project HOPE—The People-to-People Health Foundation, Inc.

  13. Elimination of Mother-To-Child Transmission of HIV Infection: The Drug Resource Enhancement against AIDS and Malnutrition Model

    Directory of Open Access Journals (Sweden)

    Giuseppe Liotta

    2015-10-01

    Full Text Available The Drug Resource Enhancement against AIDS and Malnutrition Program (DREAM gathered professionals in the field of Elimination of HIV-Mother-To-Child Transmission (EMTCT in Maputo in 2013 to discuss obstacles and solutions for the elimination of HIV vertical transmission in sub-Saharan Africa. During this workshop, the benefits of administrating combined antiretroviral therapy (cART to HIV positive women from pregnancy throughout breastfeeding were reviewed. cART is capable of reducing vertical transmission to less than 5% at 24 months of age, as well as maternal mortality and infant mortality in both HIV infected and exposed populations to levels similar to those of uninfected individuals. The challenge for programs targeting eMTCT in developing countries is retention in care and treatment adherence. Both are intrinsically related to the model of care. The drop-out from eMTCT programs before cART initiation ranges from 33%–88% while retention rates at 18–24 months are less than 50%. Comprehensive strategies including peer-to-peer education, social support and laboratory monitoring can reduce refusals to less than 5% and attain retention rates approaching 90%. Several components of the model of care for reduction of HIV-1 MTCT are feasible and implementable in scale-up strategies. A review of this model of care for HIV eMTCT is provided.

  14. Volumetric Analysis of Alveolar Bone Defect Using Three-Dimensional-Printed Models Versus Computer-Aided Engineering.

    Science.gov (United States)

    Du, Fengzhou; Li, Binghang; Yin, Ningbei; Cao, Yilin; Wang, Yongqian

    2017-03-01

    Knowing the volume of a graft is essential in repairing alveolar bone defects. This study investigates the 2 advanced preoperative volume measurement methods: three-dimensional (3D) printing and computer-aided engineering (CAE). Ten unilateral alveolar cleft patients were enrolled in this study. Their computed tomographic data were sent to 3D printing and CAE software. A simulated graft was used on the 3D-printed model, and the graft volume was measured by water displacement. The volume calculated by CAE software used mirror-reverses technique. The authors compared the actual volumes of the simulated grafts with the CAE software-derived volumes. The average volume of the simulated bone grafts by 3D-printed models was 1.52 mL, higher than the mean volume of 1.47 calculated by CAE software. The difference between the 2 volumes was from -0.18 to 0.42 mL. The paired Student t test showed no statistically significant difference between the volumes derived from the 2 methods. This study demonstrated that the mirror-reversed technique by CAE software is as accurate as the simulated operation on 3D-printed models in unilateral alveolar cleft patients. These findings further validate the use of 3D printing and CAE technique in alveolar defect repairing.

  15. Modeling and representation of a computer-aided conceptual design system

    Energy Technology Data Exchange (ETDEWEB)

    Li, Bing; Zhang, Ju Fan [Harbin Institute of Technology, Shenzhen (China); Chen, Yuan [Shandong Univ. at Weihai, Weihai (China); Hu, Ying [The Chinese Univ. of Hong Kong, Hong Kong (China)

    2012-11-15

    A novel hierarchical function action behavior mechanism (FABM) modeling framework is proposed to conduct intelligent mapping from the overall function to the principle solution, according to the requirements of customers. Based on the hierarchical modeling framework, an object oriented representation method is developed to express the inheritance and the interconnecting characteristics between any two objects. In addition, the rules of expansion and modification in demand behavior are proposed to solve the combinational explosion problem, and the combinational rules in the mechanism behavior are developed to extend the innovation of the principle solution. A case study on the pan mechanism design for a cooking robot is presented to demonstrate the implementation of intelligent reasoning based on the FABM model.

  16. Discussion of heat transfer phenomena in fluids at supercritical pressure with the aid of CFD models

    International Nuclear Information System (INIS)

    Sharabi, Medhat; Ambrosini, Walter

    2009-01-01

    The paper discusses heat transfer enhancement and deterioration phenomena observed in experimental data for fluids at supercritical pressure. The results obtained by the application of various CFD turbulence models in the prediction of experimental data for water and carbon dioxide flowing in circular tubes are firstly described. On this basis, the capabilities of the addressed models in predicting the observed phenomena are shortly discussed. Then, the analysis focuses on further results obtained by a low-Reynolds number k - ε model addressing one of the considered experimental apparatuses by changing the operating conditions. In particular, the usual imposed heat flux boundary condition is changed to assigned wall temperature, in order to highlight effects otherwise impossible to point out. The obtained results, supported by considerations drawn from experimental information, allow comparing the trends observed for heat transfer deterioration at supercritical pressure with those typical of the thermal crisis in boiling systems, clarifying old concepts of similarity among them

  17. Petri Nets Based Modelling of Control Flow for Memory-Aid Interactive Programs in Telemedicine

    CERN Document Server

    Khoromskaia, V K

    2004-01-01

    Petri Nets (PN) based modelling of the control flow for the interactive memory assistance programs designed for personal pocket computers and having special requirements for robustness is considered. The proposed concept allows one to elaborate the programs which can give users a variety of possibilities for a day-time planning in the presence of environmental and time restrictions. First, a PN model for a known simple algorithm is constructed and analyzed using the corresponding state equations and incidence matrix. Then a PN graph for a complicated algorithm with overlapping actions and choice possibilities is designed, supplemented by an example of its analysis. Dynamic behaviour of this graph is tested by tracing of all possible paths of the flow of control using the PN simulator. It is shown that PN based modelling provides reliably predictable performance of interactive algorithms with branched structures and concurrency requirements.

  18. Modeling and representation of a computer-aided conceptual design system

    International Nuclear Information System (INIS)

    Li, Bing; Zhang, Ju Fan; Chen, Yuan; Hu, Ying

    2012-01-01

    A novel hierarchical function action behavior mechanism (FABM) modeling framework is proposed to conduct intelligent mapping from the overall function to the principle solution, according to the requirements of customers. Based on the hierarchical modeling framework, an object oriented representation method is developed to express the inheritance and the interconnecting characteristics between any two objects. In addition, the rules of expansion and modification in demand behavior are proposed to solve the combinational explosion problem, and the combinational rules in the mechanism behavior are developed to extend the innovation of the principle solution. A case study on the pan mechanism design for a cooking robot is presented to demonstrate the implementation of intelligent reasoning based on the FABM model

  19. Conceptualisation of Snowpack Isotope Dynamics in Spatially Distributed Tracer-Aided Runoff Models in Snow Influenced Northern Cathments

    Science.gov (United States)

    Ala-aho, P. O. A.; Tetzlaff, D.; Laudon, H.; McNamara, J. P.; Soulsby, C.

    2016-12-01

    We use the Spatially distributed Tracer-Aided Rainfall-Runoff (STARR) modelling framework to explore non-stationary flow and isotope response in three northern headwater catchments. The model simulates dynamic, spatially variable tracer concentration in different water stores and fluxes within a catchment, which can constrain internal catchment mixing processes, flow paths and associated water ages. To date, a major limitation in using such models in snow-dominated catchments has been the difficulties in paramaterising the isotopic transformations in snowpack accumulation and melt. We use high quality long term datasets for hydrometrics and stable water isotopes collected in three northern study catchments for model calibration and testing. The three catchments exhibit different hydroclimatic conditions, soil and vegetation types, and topographic relief, which brings about variable degree of snow dominance across the catchments. To account for the snow influence we develop novel formulations to estimate the isotope evolution in the snowpack and melt. Algorithms for the isotopic evolution parameterize an isotopic offset between snow evaporation and melt fluxes and the remaining snow storage. The model for each catchment is calibrated to match both streamflow and tracer concentration at the stream outlet to ensure internal consistency of the system behaviour. The model is able to reproduce the streamflow along with the spatio-temporal differences in tracer concentrations across the three studies catchments reasonably well. Incorporating the spatially distributed snowmelt processes and associated isotope transformations proved essential in capturing the stream tracer reponse for strongly snow-influenced cathments. This provides a transferrable tool which can be used to understand spatio-temporal variability of mixing and water ages for different storages and flow paths in other snow influenced, environments.

  20. Development of Electronic Load Controllers for Free-Piston Stirling Convertors Aided by Stirling Simulation Model

    Science.gov (United States)

    Regan, Timothy F.

    2004-01-01

    The free-piston Stirling convertor end-to-end modeling effort at the NASA Glenn Research Center has produced a software-based test bed in which free-piston Stirling convertors can be simulated and evaluated. The simulation model includes all the components of the convertor: the Stirling cycle engine, heat source, linear alternator, controller, and load. So far, it has been used in evaluating the performance of electronic controller designs. Three different controller design concepts were simulated using the model: 1) Controllers with parasitic direct current loading. 2) Controllers with parasitic alternating current loading. 3) Controllers that maintain a reference current. The free-piston Stirling convertor is an electromechanical device that operates at resonance. It is the function of the electronic load controller to ensure that the electrical load seen by the machine is always great enough to keep the amplitude of the piston and alternator oscillation at the rated value. This is done by regulating the load on the output bus. The controller monitors the instantaneous voltage, regulating it by switching loads called parasitic loads onto the bus whenever the bus voltage is too high and removing them whenever the voltage is too low. In the first type of controller, the monitor-ing and switching are done on the direct-current (dc) bus. In the second type, the alternating current bus is used. The model allows designers to test a controller concept before investing time in hardware. The simulation code used to develop the model also offers detailed models of digital and analog electronic components so that the resulting designs are realistic enough to translate directly into hardware circuits.

  1. Vascular dynamics aid a coupled neurovascular network learn sparse independent features: A computational model

    Directory of Open Access Journals (Sweden)

    Ryan Thomas Philips

    2016-02-01

    Full Text Available Cerebral vascular dynamics are generally thought to be controlled by neural activity in a unidirectional fashion. However, both computational modeling and experimental evidence point to the feedback effects of vascular dynamics on neural activity. Vascular feedback in the form of glucose and oxygen controls neuronal ATP, either directly or via the agency of astrocytes, which in turn modulates neural firing. Recently, a detailed model of the neuron-astrocyte-vessel system has shown how vasomotion can modulate neural firing. Similarly, arguing from known cerebrovascular physiology, an approach known as `hemoneural hypothesis' postulates functional modulation of neural activity by vascular feedback. To instantiate this perspective, we present a computational model in which a network of `vascular units' supplies energy to a neural network. The complex dynamics of the vascular network, modeled by a network of oscillators, turns neurons ON and OFF randomly. The informational consequence of such dynamics is explored in the context of an auto-encoder network. In the proposed model, each vascular unit supplies energy to a subset of hidden neurons of an autoencoder network, which constitutes its `projective field'. Neurons that receive adequate energy in a given trial have reduced threshold, and thus are prone to fire. Dynamics of the vascular network are governed by changes in the reconstruction error of the auto-encoder network, interpreted as the neuronal demand. Vascular feedback causes random inactivation of a subset of hidden neurons in every trial. We observe that, under conditions of desynchronized vascular dynamics, the output reconstruction error is low and the feature vectors learnt are sparse and independent. Our earlier modeling study highlighted the link between desynchronized vascular dynamics and efficient energy delivery in skeletal muscle. We now show that desynchronized vascular dynamics leads to efficient training in an auto

  2. Modeling cotton (Gossypium spp) leaves and canopy using computer aided geometric design (CAGD)

    Science.gov (United States)

    The goal of this research is to develop a geometrically accurate model of cotton crop canopies for exploring changes in canopy microenvironment and physiological function with leaf structure. We develop an accurate representation of the leaves, including changes in three-dimensional folding and orie...

  3. A Socioecological Model of Rape Survivors' Decisions to Aid in Case Prosecution

    Science.gov (United States)

    Anders, Mary C.; Christopher, F. Scott

    2011-01-01

    The purpose of our study was to identify factors underlying rape survivors' post-assault prosecution decisions by testing a decision model that included the complex relations between the multiple social ecological systems within which rape survivors are embedded. We coded 440 police rape cases for characteristics of the assault and characteristics…

  4. A Model for Institutional Policy Analysis: The Case of Student Financial Aid. AIR Forum 1981 Paper.

    Science.gov (United States)

    Fenske, Robert H.; Parker, John D.

    The development of an operational model that would enable a college institutional research unit to improve administrative decision-making by expanding its data base to include new activities not widely recognized throughout the institution is considered. Attention is directed to institutional research as a function within an institution,…

  5. stability results of a mathematical model for the control of hiv/aids ...

    African Journals Online (AJOL)

    DJFLEX

    Subthreshold Domain of Bistable Equilibria for a Model of. HIV Epidemiology. International Journal of Mathematics and Mathematical Sciences, 58, 3679-3698. David R. M., 1997. Introduction to Theory of Stability. Springer-Verlag, New York, Inc. USA. Family Health International, 2007. How the Female Condom Affects Male ...

  6. Ear-to-Ear On-Body Channel Model for Hearing Aid Applications

    DEFF Research Database (Denmark)

    Kvist, Søren Helstrup; Thaysen, Jesper; Jakobsen, Kaj Bjarne

    2015-01-01

    that the head is mod- eled more accurately, and the radiation pattern is sampled in more points. The model is able to take the on-body radiation pattern of the antenna, as well as arbitrary he ad contours into account. The model is validated by the use of measurements and Ansys HFSS simulations on the specific......The deterministic ear-to-ear on-body channel is modeled by the use of a number of elliptically shaped paths. The semi-major axes of the elliptica lly shaped paths are adjusted such that they trace the outline of the head. The path gain converges when the number of paths is increased, su ch...... anthropomorphic mannequin (SAM) head. The model is used with a g enetic algorithm in order to synthesize a radiation pattern that is optimal for use with the ear-to-ear on-body channel. The radiation pattern is synthesized in terms of the spherical wave expansion coefficients of the hypothetical small antenna...

  7. Hydrodynamic and Inundation Modeling of China’s Largest Freshwater Lake Aided by Remote Sensing Data

    Directory of Open Access Journals (Sweden)

    Peng Zhang

    2015-04-01

    Full Text Available China’s largest freshwater lake, Poyang Lake, is characterized by rapid changes in its inundation area and hydrodynamics, so in this study, a hydrodynamic model of Poyang Lake was established to simulate these long-term changes. Inundation information was extracted from Moderate Resolution Imaging Spectroradiometer (MODIS remote sensing data and used to calibrate the wetting and drying parameter by assessing the accuracy of the simulated inundation area and its boundary. The bottom friction parameter was calibrated using current velocity measurements from Acoustic Doppler Current Profilers (ADCP. The results show the model is capable of predicting the inundation area dynamic through cross-validation with remotely sensed inundation data, and can reproduce the seasonal dynamics of the water level, and water discharge through a comparison with hydrological data. Based on the model results, the characteristics of the current velocities of the lake in the wet season and the dry season of the lake were explored, and the potential effect of the current dynamic on water quality patterns was discussed. The model is a promising basic tool for prediction and management of the water resource and water quality of Poyang Lake.

  8. Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain.

    Science.gov (United States)

    Noguchi, Kevin K; Johnson, Stephen A; Manzella, Francesca M; Masuoka, Kobe L; Williams, Sasha L; Martin, Lauren D; Dissen, Gregory A; Ikonomidou, Chrysanthy; Schenning, Katie J; Olney, John W; Brambrink, Ansgar M

    2018-03-28

    Caffeine is the most frequently used medication in premature infants. It is the respiratory stimulant of choice for apnea associated with prematurity and has been called the silver bullet in neonatology because of many proven benefits and few known risks. Research has revealed that sedative/anesthetic drugs trigger apoptotic death of neurons and oligodendrocytes in developing mammalian brains. Here we evaluated the influence of caffeine on the neurotoxicity of anesthesia in developing nonhuman primate brains. Fetal macaques (n = 7-8/group), at a neurodevelopmental age comparable to premature human infants, were exposed in utero for 5 hours to no drug (control), isoflurane, or isoflurane + caffeine and examined for evidence of apoptosis. Isoflurane exposure increased apoptosis 3.3 fold for neurons and 3.4 fold for oligodendrocytes compared to control brains. Isoflurane + caffeine caused neuronal apoptosis to increase 8.0 fold compared to control levels but did not augment oligoapoptosis. Neuronal death was particularly pronounced in the basal ganglia and cerebellum. Higher blood levels of caffeine within the range considered therapeutic and safe for human infants correlated with increased neuroapoptosis. Caffeine markedly augments neurotoxicity of isoflurane in the fetal macaque brain and challenges the assumption that caffeine is safe for premature infants.

  9. Astrocyte atrophy and immune dysfunction in self-harming macaques.

    Directory of Open Access Journals (Sweden)

    Kim M Lee

    Full Text Available BACKGROUND: Self-injurious behavior (SIB is a complex condition that exhibits a spectrum of abnormal neuropsychological and locomotor behaviors. Mechanisms for neuropathogenesis could include irregular immune activation, host soluble factors, and astrocyte dysfunction. METHODS: We examined the role of astrocytes as modulators of immune function in macaques with SIB. We measured changes in astrocyte morphology and function. Paraffin sections of frontal cortices from rhesus macaques identified with SIB were stained for glial fibrillary acidic protein (GFAP and Toll-like receptor 2 (TLR2. Morphologic features of astrocytes were determined using computer-assisted camera lucida. RESULTS: There was atrophy of white matter astrocyte cell bodies, decreased arbor length in both white and gray matter astrocytes, and decreased bifurcations and tips on astrocytes in animals with SIB. This was combined with a five-fold increase in the proportion of astrocytes immunopositive for TLR2. CONCLUSIONS: These results provide direct evidence that SIB induces immune activation of astrocytes concomitant with quantifiably different morphology.

  10. Grooming reciprocity in female tibetan macaques macaca thibetana.

    Science.gov (United States)

    Xia, Dongpo; Li, Jinhua; Garber, Paul A; Sun, Lixing; Zhu, Yong; Sun, Binghua

    2012-06-01

    Grooming among nonhuman primates is widespread and may represent an important service commodity that is exchanged within a biological marketplace. In this study, using focal animal sampling methods, we recorded grooming relationships among 12 adult females in a free-ranging group of Tibetan macaques (Macaca thibetana) at Huangshan, China, to determine the influence of rank and kinship on grooming relationships, and whether females act as reciprocal traders (exchange grooming received for grooming given) or interchange traders (interchange grooming for social tolerance or other commodities). The results showed that: (1) grooming given was positively correlated with grooming received; (2) kinship did not exert a significant influence on grooming reciprocity; and (3) grooming reciprocity occurred principally between individuals of adjacent rank; however, when females of different rank groomed, females tended to groom up the hierarchy (lower ranking individuals groomed higher ranking individuals more than vice versa). Our results support the contention that both grooming reciprocity and the interchange of grooming for tolerance represent important social tactics used by female Tibetan macaques. © 2012 Wiley Periodicals, Inc.

  11. Macaques can predict social outcomes from facial expressions.

    Science.gov (United States)

    Waller, Bridget M; Whitehouse, Jamie; Micheletta, Jérôme

    2016-09-01

    There is widespread acceptance that facial expressions are useful in social interactions, but empirical demonstration of their adaptive function has remained elusive. Here, we investigated whether macaques can use the facial expressions of others to predict the future outcomes of social interaction. Crested macaques (Macaca nigra) were shown an approach between two unknown individuals on a touchscreen and were required to choose between one of two potential social outcomes. The facial expressions of the actors were manipulated in the last frame of the video. One subject reached the experimental stage and accurately predicted different social outcomes depending on which facial expressions the actors displayed. The bared-teeth display (homologue of the human smile) was most strongly associated with predicted friendly outcomes. Contrary to our predictions, screams and threat faces were not associated more with conflict outcomes. Overall, therefore, the presence of any facial expression (compared to neutral) caused the subject to choose friendly outcomes more than negative outcomes. Facial expression in general, therefore, indicated a reduced likelihood of social conflict. The findings dispute traditional theories that view expressions only as indicators of present emotion and instead suggest that expressions form part of complex social interactions where individuals think beyond the present.

  12. Endodontic Treatment of an Anomalous Anterior Tooth with the Aid of a 3-dimensional Printed Physical Tooth Model.

    Science.gov (United States)

    Byun, Chanhee; Kim, Changhwan; Cho, Seungryong; Baek, Seung Hoon; Kim, Gyutae; Kim, Sahng G; Kim, Sun-Young

    2015-06-01

    Endodontic treatment of tooth formation anomalies is a challenge to clinicians and as such requires a complete understanding of the aberrant root canal anatomy followed by careful root canal disinfection and obturation. Here, we report the use of a 3-dimensional (3D) printed physical tooth model including internal root canal structures for the endodontic treatment of a challenging tooth anomaly. A 12-year-old boy was referred for endodontic treatment of tooth #8. The tooth showed class II mobility with swelling and a sinus tract in the buccal mucosa and periapical radiolucency. The tooth presented a very narrow structure between the crown and root by distal concavity and a severely dilacerated root. Moreover, a perforation site with bleeding and another ditching site were identified around the cervical area in the access cavity. A translucent physical tooth model carrying the information on internal root canal structures was built through a 3-step process: data acquisition by cone-beam computed tomographic scanning, virtual modeling by image processing, and manufacturing by 3D printing. A custom-made guide jig was then fabricated to achieve a safe and precise working path to the root canal. Endodontic procedures including access cavity preparation were performed using the physical tooth model and the guide jig. At the 7-month follow-up, the endodontically treated tooth showed complete periapical healing with no clinical signs and symptoms. This case report describes a novel method of endodontic treatment of an anomalous maxillary central incisor with the aid of a physical tooth model and a custom-made guide jig via 3D printing technique. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  13. Carpe diem, Carpe ampulla: a numerical model as an aid to the design of child-resistant closures.

    Science.gov (United States)

    Yoxall, A; Rodriguez-Falcon, E M; Luxmoore, J

    2013-01-01

    The population of most developed countries is ageing. Despite continuing medical advances, ageing brings with it a host of issues, not least a loss in strength and dexterity. One major area of concern is the ability of elderly consumers to access packaged goods such as food and medicines. In previous studies, the authors developed a numerical model of a human hand that was used to investigate the effect of physical dimensions and choice of grip on joint stresses to aid the understanding between physical effort, ability and discomfort. This previous work was supported by ethnographic studies and led to recommendations for packaging design. In this paper, a small ethnographic study is undertaken which identifies the grip types used to access to a product that is known to cause particular difficulties for the elderly, the "squeeze and turn" child-resistant closure or CRC, commonly used on medicines and cleaning products. One of the grip types used was chosen to be modelled using the numerical model developed in previous studies by the author. Model geometry and loading were adapted to simulate the "squeeze and turn" nature of the initial opening for closures of this type. A series of studies were then undertaken using different hand geometries; an average male hand, an average female hand and a fifth percentile female hand. The prediction from the model here is that female users with smaller hands will experience more discomfort when accessing squeeze and turn CRC's and that the turn process whilst maintaining the squeeze is problematic. Copyright © 2012 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  14. Computer aided design of Langasite resonant cantilevers: analytical models and simulations

    Science.gov (United States)

    Tellier, C. R.; Leblois, T. G.; Durand, S.

    2010-05-01

    Analytical models for the piezoelectric excitation and for the wet micromachining of resonant cantilevers are proposed. Firstly, computations of metrological performances of micro-resonators allow us to select special cuts and special alignment of the cantilevers. Secondly the self-elaborated simulator TENSOSIM based on the kinematic and tensorial model furnishes etching shapes of cantilevers. As the result the number of selected cuts is reduced. Finally the simulator COMSOL® is used to evaluate the influence of final etching shape on metrological performances and especially on the resonance frequency. Changes in frequency are evaluated and deviating behaviours of structures with less favourable built-ins are tested showing that the X cut is the best cut for LGS resonant cantilevers vibrating in flexural modes (type 1 and type 2) or in torsion mode.

  15. Use of empirically based corrosion model to aid steam generator life management

    Energy Technology Data Exchange (ETDEWEB)

    Angell, P.; Balakrishnan, P.V.; Turner, C.W

    2000-07-01

    Alloy 800 (N08800) tubes used in CANDU 6 steam generators have shown a low incidence of corrosion damage because of the good corrosion resistance of N08800 and successful water chemistry control strategies. However, N08800 is not immune to corrosion, especially pitting, under plausible SG conditions. Electrochemical potentials are critical in determining both susceptibility and rates of corrosion and are known to be a function of water-chemistry. Using laboratory data an empirical model for pitting and crevice corrosion has been developed for N08800. Combination of such a model with chemistry monitoring and diagnostic software makes it possible to arm the impact of plant operating conditions on SG tube corrosion for plant life management (PLIM). Possible transient chemistry regimes that could significantly shorten expected tube lifetimes have been identified and predictions continue to support the position dud under normal, low dissolved oxygen conditions, pitting of N08800 will not initiate. (author)

  16. Use of empirically based corrosion model to aid steam generator life management

    International Nuclear Information System (INIS)

    Angell, P.; Balakrishnan, P.V.; Turner, C.W.

    2000-01-01

    Alloy 800 (N08800) tubes used in CANDU 6 steam generators have shown a low incidence of corrosion damage because of the good corrosion resistance of N08800 and successful water chemistry control strategies. However, N08800 is not immune to corrosion, especially pitting, under plausible SG conditions. Electrochemical potentials are critical in determining both susceptibility and rates of corrosion and are known to be a function of water-chemistry. Using laboratory data an empirical model for pitting and crevice corrosion has been developed for N08800. Combination of such a model with chemistry monitoring and diagnostic software makes it possible to arm the impact of plant operating conditions on SG tube corrosion for plant life management (PLIM). Possible transient chemistry regimes that could significantly shorten expected tube lifetimes have been identified and predictions continue to support the position dud under normal, low dissolved oxygen conditions, pitting of N08800 will not initiate. (author)

  17. Coupled Transport/Reaction Modelling of Copper Canister Corrosion Aided by Microbial Processes

    Energy Technology Data Exchange (ETDEWEB)

    Jinsong Liu [Royal Institute of Technology, Stockholm (Sweden). Dept. of Chemical Engineering and Technology

    2006-04-15

    Copper canister corrosion is an important issue in the concept of a nuclear fuel repository. Previous studies indicate that the oxygen-free copper canister could hold its integrity for more than 100,000 years in the repository environment. Microbial processes may reduce sulphate to sulphide and considerably increase the amount of sulphides available for corrosion. In this paper, a coupled transport/reaction model is developed to account for the transport of chemical species produced by microbial processes. The corroding agents like sulphide would come not only from the groundwater flowing in a fracture that intersects the canister, but also from the reduction of sulphate near the canister. The reaction of sulphate-reducing bacteria and the transport of sulphide in the bentonite buffer are included in the model. The depth of copper canister corrosion is calculated by the model. With representative 'central values' of the concentrations of sulphate and methane at repository depth at different sites in Fennoscandian Shield the corrosion depth predicted by the model is a few millimetres during 10{sup 5} years. As the concentrations of sulphate and methane are extremely site-specific and future climate changes may significantly influence the groundwater compositions at potential repository sites, sensitivity analyses have been conducted. With a broad perspective of the measured concentrations at different sites in Sweden and in Finland, and some possible mechanisms (like the glacial meltwater intrusion and interglacial seawater intrusion) that may introduce more sulphate into the groundwater at intermediate depths during future climate changes, higher concentrations of either/both sulphate and methane than what is used as the representative 'central' values would be possible. In worst cases. locally, half of the canister thickness could possibly be corroded within 10{sup 5} years.

  18. Coupled Transport/Reaction Modelling of Copper Canister Corrosion Aided by Microbial Processes

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jinsong [Royal Institute of Technology, Stockholm (Sweden). Dept. of Chemical Engineering and Technology

    2006-04-15

    Copper canister corrosion is an important issue in the concept of a nuclear fuel repository. Previous studies indicate that the oxygen-free copper canister could hold its integrity for more than 100,000 years in the repository environment. Microbial processes may reduce sulphate to sulphide and considerably increase the amount of sulphides available for corrosion. In this paper, a coupled transport/reaction model is developed to account for the transport of chemical species produced by microbial processes. The corroding agents like sulphide would come not only from the groundwater flowing in a fracture that intersects the canister, but also from the reduction of sulphate near the canister. The reaction of sulphate-reducing bacteria and the transport of sulphide in the bentonite buffer are included in the model. The depth of copper canister corrosion is calculated by the model. With representative 'central values' of the concentrations of sulphate and methane at repository depth at different sites in Fennoscandian Shield the corrosion depth predicted by the model is a few millimetres during 10{sup 5} years. As the concentrations of sulphate and methane are extremely site-specific and future climate changes may significantly influence the groundwater compositions at potential repository sites, sensitivity analyses have been conducted. With a broad perspective of the measured concentrations at different sites in Sweden and in Finland, and some possible mechanisms (like the glacial meltwater intrusion and interglacial seawater intrusion) that may introduce more sulphate into the groundwater at intermediate depths during future climate changes, higher concentrations of either/both sulphate and methane than what is used as the representative 'central' values would be possible. In worst cases. locally, half of the canister thickness could possibly be corroded within 10{sup 5} years.

  19. Coupled Transport/Reaction Modelling of Copper Canister Corrosion Aided by Microbial Processes

    International Nuclear Information System (INIS)

    Jinsong Liu

    2006-04-01

    Copper canister corrosion is an important issue in the concept of a nuclear fuel repository. Previous studies indicate that the oxygen-free copper canister could hold its integrity for more than 100,000 years in the repository environment. Microbial processes may reduce sulphate to sulphide and considerably increase the amount of sulphides available for corrosion. In this paper, a coupled transport/reaction model is developed to account for the transport of chemical species produced by microbial processes. The corroding agents like sulphide would come not only from the groundwater flowing in a fracture that intersects the canister, but also from the reduction of sulphate near the canister. The reaction of sulphate-reducing bacteria and the transport of sulphide in the bentonite buffer are included in the model. The depth of copper canister corrosion is calculated by the model. With representative 'central values' of the concentrations of sulphate and methane at repository depth at different sites in Fennoscandian Shield the corrosion depth predicted by the model is a few millimetres during 10 5 years. As the concentrations of sulphate and methane are extremely site-specific and future climate changes may significantly influence the groundwater compositions at potential repository sites, sensitivity analyses have been conducted. With a broad perspective of the measured concentrations at different sites in Sweden and in Finland, and some possible mechanisms (like the glacial meltwater intrusion and interglacial seawater intrusion) that may introduce more sulphate into the groundwater at intermediate depths during future climate changes, higher concentrations of either/both sulphate and methane than what is used as the representative 'central' values would be possible. In worst cases. locally, half of the canister thickness could possibly be corroded within 10 5 years

  20. Inverse Modeling Using Markov Chain Monte Carlo Aided by Adaptive Stochastic Collocation Method with Transformation

    Science.gov (United States)

    Zhang, D.; Liao, Q.

    2016-12-01

    The Bayesian inference provides a convenient framework to solve statistical inverse problems. In this method, the parameters to be identified are treated as random variables. The prior knowledge, the system nonlinearity, and the measurement errors can be directly incorporated in the posterior probability density function (PDF) of the parameters. The Markov chain Monte Carlo (MCMC) method is a powerful tool to generate samples from the posterior PDF. However, since the MCMC usually requires thousands or even millions of forward simulations, it can be a computationally intensive endeavor, particularly when faced with large-scale flow and transport models. To address this issue, we construct a surrogate system for the model responses in the form of polynomials by the stochastic collocation method. In addition, we employ interpolation based on the nested sparse grids and takes into account the different importance of the parameters, under the condition of high random dimensions in the stochastic space. Furthermore, in case of low regularity such as discontinuous or unsmooth relation between the input parameters and the output responses, we introduce an additional transform process to improve the accuracy of the surrogate model. Once we build the surrogate system, we may evaluate the likelihood with very little computational cost. We analyzed the convergence rate of the forward solution and the surrogate posterior by Kullback-Leibler divergence, which quantifies the difference between probability distributions. The fast convergence of the forward solution implies fast convergence of the surrogate posterior to the true posterior. We also tested the proposed algorithm on water-flooding two-phase flow reservoir examples. The posterior PDF calculated from a very long chain with direct forward simulation is assumed to be accurate. The posterior PDF calculated using the surrogate model is in reasonable agreement with the reference, revealing a great improvement in terms of

  1. Detection of Earth impact craters aided by the detailed global gravitational model EGM2008

    Czech Academy of Sciences Publication Activity Database

    Klokočník, Jaroslav; Kostelecký, J.; Novák, P.; Wagner, C. A.

    2010-01-01

    Roč. 7, č. 1 (2010), s. 71-97 ISSN 1214-9705 R&D Projects: GA MŠk(CZ) LC506 Grant - others:ESA(XE) ESA- PECS project No.98056 Institutional research plan: CEZ:AV0Z10030501 Keywords : global gravitational model * gravity anomaly * impact craters on the Earth Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 0.452, year: 2010

  2. Realization of process improvement at a diagnostic radiology department with aid of simulation modeling.

    Science.gov (United States)

    Oh, Hong-Choon; Toh, Hong-Guan; Giap Cheong, Eddy Seng

    2011-11-01

    Using the classical process improvement framework of Plan-Do-Study-Act (PDSA), the diagnostic radiology department of a tertiary hospital identified several patient cycle time reduction strategies. Experimentation of these strategies (which included procurement of new machines, hiring of new staff, redesign of queue system, etc.) through pilot scale implementation was impractical because it might incur substantial expenditure or be operationally disruptive. With this in mind, simulation modeling was used to test these strategies via performance of "what if" analyses. Using the output generated by the simulation model, the team was able to identify a cost-free cycle time reduction strategy, which subsequently led to a reduction of patient cycle time and achievement of a management-defined performance target. As healthcare professionals work continually to improve healthcare operational efficiency in response to rising healthcare costs and patient expectation, simulation modeling offers an effective scientific framework that can complement established process improvement framework like PDSA to realize healthcare process enhancement. © 2011 National Association for Healthcare Quality.

  3. ANALYSI S ON SECONDARY I NFECTI ON- TRI GGERI NG MICROORGANISMS IN HIV/AIDS PATIENTS AS A MODEL FOR POLICY CONTROL

    Directory of Open Access Journals (Sweden)

    Retno Pudji Rahayu

    2015-01-01

    infections and have potential as model for policy control in HIV/AIDS.

  4. Influence of a patient decision aid on decisional conflict related to PSA testing: a structural equation model.

    Science.gov (United States)

    Stephens, Robert L; Xu, Ye; Volk, Robert J; Scholl, Lawrence E; Kamin, Stephanie L; Holden, E Wayne; Stroud, Leonardo A

    2008-11-01

    To examine the impact of a decision aid (DA) designed to promote informed decision making for screening with the prostate-specific antigen (PSA) test and to test a theoretical model of factors influencing decisional conflict. Structural equation modeling examined pathways between DA exposure, knowledge, schema, prostate cancer risk perceptions, decisional anxiety, and decisional conflict. Sample participants included 200 men from the general population (exclusive of African Americans) and 200 African American men. Half of the men in each subsample were randomly assigned to receive the DA. Decisional conflict regarding prostate cancer screening. The DA influences level of decisional conflict by increasing patient knowledge. This effect of knowledge on decisional conflict is indirect, however, through an association with greater perceived risk and lower decisional anxiety. Also, positive PSA schema was associated with lower decisional anxiety and decisional conflict. It is important that exposure to the DA had no impact on PSA schema. Schemas about testing must be considered in developing messages about the risks and benefits of testing. If schemas are counter to message content, mechanisms for modifying schemas must be incorporated into interventions.

  5. Psychological pathway to suicidal ideation among people living with HIV/AIDS in China: A structural equation model.

    Science.gov (United States)

    Wang, Wei; Wang, Yuanyuan; Xiao, Chenchang; Yao, Xing; Yang, Yinmei; Yan, Hong; Li, Shiyue

    2017-11-29

    People living with HIV/AIDS (PLWHA) have higher rates of suicide than does the general population. It is critical to interpret the intricate relationships among various psychological variables that increase the risk of suicidal ideation among PLWHA in China. An institutional based cross-sectional study was conducted from Jul to Aug 2016 in Nanjing, China, using a self-reporting questionnaire. A total of 465 PLWHA participated. Sociodemographic, psychological variables and suicide information about the participants were collected. Structural equation modeling (SEM)-path analysis was used to analyze the cross-sectional data. The final structural equation model had a highly satisfactory fit. Among PLWHA, perceived stigma had the greatest accumulated total effect on suicidal ideation, with both a direct effect and indirect effect through self-esteem and depression. Additionally, self-esteem had the second greatest total effect on suicidal ideation and was influenced by social support. Depression contributed directly to suicidal ideation and partly mediated the association of perceived stigma and self-esteem with suicidal ideation. These findings suggest that self-esteem and depression, particularly perceived stigma, play important roles in suicidal ideation among PLWHA. Enhancing personal self-esteem or social support might also reduce perceived stigma and may be an important target for intervention to decrease suicidal ideation among PLWHA. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Computer-Aided Evaluation of Screening Mammograms Based on Local Texture Models

    Czech Academy of Sciences Publication Activity Database

    Grim, Jiří; Somol, Petr; Haindl, Michal; Daneš, J.

    2009-01-01

    Roč. 18, č. 4 (2009), s. 765-773 ISSN 1057-7149 R&D Projects: GA ČR GA102/07/1594; GA ČR GA102/08/0593; GA MŠk 1M0572 Grant - others:GA MŠk(CZ) 2C06019 Institutional research plan: CEZ:AV0Z10750506 Keywords : Screening mammography * texture information * local statistical model * Gaussian mixture Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.848, year: 2009

  7. Computer-aided modeling of aluminophosphate zeolites as packings of building units

    KAUST Repository

    Peskov, Maxim

    2012-03-22

    New building schemes of aluminophosphate molecular sieves from packing units (PUs) are proposed. We have investigated 61 framework types discovered in zeolite-like aluminophosphates and have identified important PU combinations using a recently implemented computational algorithm of the TOPOS package. All PUs whose packing completely determines the overall topology of the aluminophosphate framework were described and catalogued. We have enumerated 235 building models for the aluminophosphates belonging to 61 zeolite framework types, from ring- or cage-like PU clusters. It is indicated that PUs can be considered as precursor species in the zeolite synthesis processes. © 2012 American Chemical Society.