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Sample records for modeling reduced human

  1. Dynamic Modeling of the Human Coagulation Cascade Using Reduced Order Effective Kinetic Models (Open Access)

    Science.gov (United States)

    2015-03-16

    with logical rules to simulate an archetype biochemical network, the human coagulation cascade. The model consisted of five differential equations...coagulation system. Coagulation is an archetype proteolytic cascade involving both positive and negative feedback [10–12]. Coagulation is mediated by a...purely ODE models in the literature . We estimated the model parameters from in vitro extrinsic coagulation data sets, in the presence of ATIII, with and

  2. Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model

    DEFF Research Database (Denmark)

    van den Driesche, Sander; Macdonald, Joni; Anderson, Richard A

    2015-01-01

    Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons......, but effects on fetal testosterone production have not been demonstrated. We used a validated xenograft model to expose human fetal testes to clinically relevant doses and regimens of acetaminophen. Exposure to a therapeutic dose of acetaminophen for 7 days significantly reduced plasma testosterone (45...... the final dose) in exposed host mice were substantially below those reported in humans after a therapeutic oral dose. Subsequent in utero exposure studies in rats indicated that the acetaminophen-induced reduction in testosterone likely results from reduced expression of key steroidogenic enzymes (Cyp11a1...

  3. Erythropoietin reduces neural and cognitive processing of fear in human models of antidepressant drug action

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla; O'Sullivan, Ursula; Harmer, Catherine J

    2007-01-01

    BACKGROUND: Erythropoietin (Epo) has neuroprotective and neurotrophic effects in animal models and affects cognitive and associated neural responses in humans. These effects have highlighted Epo as a candidate for treatment of psychiatric disease including schizophrenia and depression. The current......) versus saline on the neural processing of happy and fearful faces in 23 healthy volunteers. Facial expression recognition was assessed outside the scanner. RESULTS: One week after administration, Epo reduced neural response to fearful versus neutral faces in the occipito-parietal cortex consistent...... with reduced attention to fear. Erythropoietin additionally reduced recognition of fearful facial expressions without affecting recognition of other emotional expressions. These actions occurred in the absence of changes in hematological parameters. CONCLUSIONS: The present study demonstrates that Epo directly...

  4. Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS.

    Science.gov (United States)

    Hamid, U; Krasnodembskaya, A; Fitzgerald, M; Shyamsundar, M; Kissenpfennig, A; Scott, C; Lefrancais, E; Looney, M R; Verghis, R; Scott, J; Simpson, A J; McNamee, J; McAuley, D F; O'Kane, C M

    2017-11-01

    Platelets play an active role in the pathogenesis of acute respiratory distress syndrome (ARDS). Animal and observational studies have shown aspirin's antiplatelet and immunomodulatory effects may be beneficial in ARDS. To test the hypothesis that aspirin reduces inflammation in clinically relevant human models that recapitulate pathophysiological mechanisms implicated in the development of ARDS. Healthy volunteers were randomised to receive placebo or aspirin 75  or 1200 mg (1:1:1) for seven days prior to lipopolysaccharide (LPS) inhalation, in a double-blind, placebo-controlled, allocation-concealed study. Bronchoalveolar lavage (BAL) was performed 6 hours after inhaling 50 µg of LPS. The primary outcome measure was BAL IL-8. Secondary outcome measures included markers of alveolar inflammation (BAL neutrophils, cytokines, neutrophil proteases), alveolar epithelial cell injury, systemic inflammation (neutrophils and plasma C-reactive protein (CRP)) and platelet activation (thromboxane B2, TXB2). Human lungs, perfused and ventilated ex vivo (EVLP) were randomised to placebo or 24 mg aspirin and injured with LPS. BAL was carried out 4 hours later. Inflammation was assessed by BAL differential cell counts and histological changes. In the healthy volunteer (n=33) model, data for the aspirin groups were combined. Aspirin did not reduce BAL IL-8. However, aspirin reduced pulmonary neutrophilia and tissue damaging neutrophil proteases (Matrix Metalloproteinase (MMP)-8/-9), reduced BAL concentrations of tumour necrosis factor α and reduced systemic and pulmonary TXB2. There was no difference between high-dose and low-dose aspirin. In the EVLP model, aspirin reduced BAL neutrophilia and alveolar injury as measured by histological damage. These are the first prospective human data indicating that aspirin inhibits pulmonary neutrophilic inflammation, at both low and high doses. Further clinical studies are indicated to assess the role of aspirin in the

  5. HLA reduces KIR expression level and frequency in a humanized mouse model1

    Science.gov (United States)

    van Bergen, Jeroen; Thompson, Allan; Retière, Christelle; van Pel, Melissa; Salvatori, Daniela; Lemonnier, François; Raulet, David; Trowsdale, John; Koning, Frits

    2014-01-01

    Many human Natural Killer (NK) cells are prevented from killing autologous cells by virtue of inhibitory Killer cell Immunoglobulin-like Receptors (KIR) binding `self' HLA class I molecules. Individual NK cells stably express a selected set of KIR, but it is currently disputed whether the fraction of NK cells expressing a particular inhibitory KIR is influenced by the presence of the corresponding HLA ligand. This issue has been particularly hard to tackle in a statistically meaningful way due to the extreme polymorphism of the KIR and HLA loci, with widely varying affinities for individual KIR and HLA allele combinations. Here, we use a transgenic mouse model to investigate the effect of HLA on KIR repertoire and function. In this model system, a functional interaction between HLA-Cw3 and KIR2DL2 reduced both the surface expression of KIR2DL2 as well as the frequency of KIR2DL2+ cells. PMID:23390293

  6. Erythropoietin reduces neural and cognitive processing of fear in human models of antidepressant drug action

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla; O'Sullivan, Ursula; Harmer, Catherine J

    2007-01-01

    BACKGROUND: Erythropoietin (Epo) has neuroprotective and neurotrophic effects in animal models and affects cognitive and associated neural responses in humans. These effects have highlighted Epo as a candidate for treatment of psychiatric disease including schizophrenia and depression. The curren...

  7. Modeling of urban trees' effects on reducing human exposure to UV radiation in Seoul, Korea

    Science.gov (United States)

    Hang Ryeol Na; Gordon M. Heisler; David J. Nowak; Richard H. Grant

    2014-01-01

    A mathematical model isconstructed for quantifying urban trees’ effects on mitigating the intensity of ultraviolet (UV) radiation on the ground within different landuse types across a city. The model is based upon local field data, meteorological data and equations designed to predict the reduced UV fraction due to trees at the ground level. Trees in Seoul, Korea (2010...

  8. Recombinant human erythropoietin increases survival and reduces neuronal apoptosis in a murine model of cerebral malaria

    DEFF Research Database (Denmark)

    Wiese, Lothar; Hempel, Casper; Penkowa, Milena

    2008-01-01

    BACKGROUND: Cerebral malaria (CM) is an acute encephalopathy with increased pro-inflammatory cytokines, sequestration of parasitized erythrocytes and localized ischaemia. In children CM induces cognitive impairment in about 10% of the survivors. Erythropoietin (Epo) has - besides of its well known...... with recombinant human Epo (rhEpo; 50-5000 U/kg/OD, i.p.) at different time points. The effect on survival was measured. Brain pathology was investigated by TUNEL (Terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labelling), as a marker of apoptosis. Gene...

  9. Recombinant human endostatin reduces hypertrophic scar ...

    African Journals Online (AJOL)

    Background: Recombinant human endostatin (Endostar) has been widely used to suppress angiogenesis in carcinoma patients. ... Cite as: Wang P, Jiang L-Z, Xue B. Recombinant human endostatin reduces hypertrophic scar formation in rabbit ear model through ... wounds on the tail of each ear were discarded because.

  10. Nanovaccine for immunotherapy and reduced hepatitis-B virus in humanized model.

    Science.gov (United States)

    Dewangan, Hitesh Kumar; Pandey, Tarun; Singh, Sanjay

    2017-11-27

    Chronic Hepatitis B Virus (HBV) infections are severe with weak antiviral immune responses. The lack of an appropriate small animal model for chronic hepatitis, a major hurdle for studying the immunotolerance and immunopathogenesis induced by hepatitis B viral (HBV) infection. In this study, for enhancing the antibody production efficiency the prepared polymeric HBsAg-loaded nanoparticles (nanovaccine) will be tested in immune-deficit mice, which suffer from chronic Hepatitis B virus. Vaccination of Balb/c mice by this prepared nanoparticles that were engrafted with peripheral blood mononuclear cells (PBMCs), which was already lethally irradiated and transplanted by the bone marrow of NOD (knockout mice) mice. In the present study, after the vaccination detected the high frequencies of immunoglobulin G (IgG)-secreting B cells and mitogen-responsive interferon-Y (IFN-Y) secreting T cells in serum, determined by specific ELISA technique. During the entire observation period, unvaccinated animals showed lower concentration of specific IgG secreting B cells and IFN-Y secreting T cells found in comparison to vaccinated mice group. Chronic HBV carrier PBMCs transplanted into the chimera failed to produce antigen and increased the antibodies production due to vaccination. Furthermore, another advantage was that the viral gene expression and viral DNA replication was no longer observed in vaccinated group. This prepared nanovaccine formulations is better for the cure of Hepatitis B viral infection carrier. Therefore, specific memory responses were elicited by vaccination with Hepatitis B virus surface (HBsAg) antigen of chimeric mice transplanted with PBMCs derived from HBV donors.

  11. Multifunctional Effect of Human Serum Albumin Reduces Alzheimer's Disease Related Pathologies in the 3xTg Mouse Model.

    Science.gov (United States)

    Ezra, Assaf; Rabinovich-Nikitin, Inna; Rabinovich-Toidman, Polina; Solomon, Beka

    2016-01-01

    Alzheimer's disease (AD), the prevalent dementia in the elderly, involves many related and interdependent pathologies that manifests simultaneously, eventually leading to cognitive impairment and death. No treatment is currently available; however, an agent addressing several key pathologies simultaneously has a better therapeutic potential. Human serum albumin (HSA) is a highly versatile protein, harboring multifunctional properties that are relevant to key pathologies underlying AD. This study provides insight into the mechanism for HSA's therapeutic effect. In vivo, a myriad of beneficial effects were observed by pumps infusing HSA intracerebroventricularly, for the first time in an AD 3xTg mice model. A significant effect on amyloid-β (Aβ) pathology was observed. Aβ1-42, soluble oligomers, and total plaque area were reduced. Neuroblastoma SHSY5Y cell line confirmed that the reduction in Aβ1-42 toxicity was due to direct binding rather than other properties of HSA. Total and hyperphosphorylated tau were reduced along with an increase in tubulin, suggesting increased microtubule stability. HSA treatment also reduced brain inflammation, affecting both astrocytes and microglia markers. Finally, evidence for blood-brain barrier and myelin integrity repair was observed. These multidimensional beneficial effects of intracranial administrated HSA, together or individually, contributed to an improvement in cognitive tests, suggesting a non-immune or Aβ efflux dependent means for treating AD.

  12. Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia.

    Science.gov (United States)

    Asmussen, Sven; Ito, Hiroshi; Traber, Daniel L; Lee, Jae W; Cox, Robert A; Hawkins, Hal K; McAuley, Daniel F; McKenna, David H; Traber, Lillian D; Zhuo, Hanjing; Wilson, Jennifer; Herndon, David N; Prough, Donald S; Liu, Kathleen D; Matthay, Michael A; Enkhbaatar, Perenlei

    2014-09-01

    Human bone marrow-derived mesenchymal stem (stromal) cells (hMSCs) improve survival in mouse models of acute respiratory distress syndrome (ARDS) and reduce pulmonary oedema in a perfused human lung preparation injured with Escherichia coli bacteria. We hypothesised that clinical grade hMSCs would reduce the severity of acute lung injury (ALI) and would be safe in a sheep model of ARDS. Adult sheep (30-40 kg) were surgically prepared. After 5 days of recovery, ALI was induced with cotton smoke insufflation, followed by instillation of live Pseudomonas aeruginosa (2.5×10(11) CFU) into both lungs under isoflurane anaesthesia. Following the injury, sheep were ventilated, resuscitated with lactated Ringer's solution and studied for 24 h. The sheep were randomly allocated to receive one of the following treatments intravenously over 1 h in one of the following groups: (1) control, PlasmaLyte A, n=8; (2) lower dose hMSCs, 5×10(6) hMSCs/kg, n=7; and (3) higher-dose hMSCs, 10×10(6) hMSCs/kg, n=4. By 24 h, the PaO2/FiO2 ratio was significantly improved in both hMSC treatment groups compared with the control group (control group: PaO2/FiO2 of 97±15 mm Hg; lower dose: 288±55 mm Hg (p=0.003); higher dose: 327±2 mm Hg (p=0.003)). The median lung water content was lower in the higher-dose hMSC-treated group compared with the control group (higher dose: 5.0 g wet/g dry [IQR 4.9-5.8] vs control: 6.7 g wet/g dry [IQR 6.4-7.5] (p=0.01)). The hMSCs had no adverse effects. Human MSCs were well tolerated and improved oxygenation and decreased pulmonary oedema in a sheep model of severe ARDS. NCT01775774 for Phase 1. NCT02097641 for Phase 2. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. HLA reduces killer cell Ig-like receptor expression level and frequency in a humanized mouse model.

    Science.gov (United States)

    van Bergen, Jeroen; Thompson, Allan; van Pel, Melissa; Retière, Christelle; Salvatori, Daniela; Raulet, David H; Trowsdale, John; Koning, Frits

    2013-03-15

    NK cells use NK cell receptors to be able to recognize and eliminate infected, transformed, and allogeneic cells. Human NK cells are prevented from killing autologous healthy cells by virtue of inhibitory NKRs, primarily killer cell Ig-like receptors (KIR) that bind "self" HLA class I molecules. Individual NK cells stably express a selected set of KIR, but it is currently disputed whether the fraction of NK cells expressing a particular inhibitory KIR is influenced by the presence of the corresponding HLA ligand. The extreme polymorphism of the KIR and HLA loci, with wide-ranging affinities for individual KIR and HLA allele combinations, has made this issue particularly hard to tackle. In this study, we used a transgenic mouse model to investigate the effect of HLA on KIR repertoire and function in the absence of genetic variation inside and outside the KIR locus. These H-2K(b-/-) and H-2D(b-/-) mice lacked ligands for inhibitory Ly49 receptors and were transgenic for HLA-Cw3 and a KIR B haplotype. In this reductionist system, the presence of HLA-Cw3 reduced the frequency of KIR2DL2(+) cells, as well as the surface expression levels of KIR2DL2. In addition, in the presence of HLA-Cw3, the frequency of NKG2A(+) cells and the surface expression levels of NKG2A were reduced. In line with these findings, both transgene-encoded KIR and endogenous NKG2A contributed to the rejection of cells lacking HLA-Cw3. These findings support the idea that HLA influences the human KIR repertoire.

  14. The Sydney Heart Bank: improving translational research while eliminating or reducing the use of animal models of human heart disease.

    Science.gov (United States)

    Dos Remedios, C G; Lal, S P; Li, A; McNamara, J; Keogh, A; Macdonald, P S; Cooke, R; Ehler, E; Knöll, R; Marston, S B; Stelzer, J; Granzier, H; Bezzina, C; van Dijk, S; De Man, F; Stienen, G J M; Odeberg, J; Pontén, F; Linke, W; van der Velden, J

    2017-08-01

    The Sydney Heart Bank (SHB) is one of the largest human heart tissue banks in existence. Its mission is to provide high-quality human heart tissue for research into the molecular basis of human heart failure by working collaboratively with experts in this field. We argue that, by comparing tissues from failing human hearts with age-matched non-failing healthy donor hearts, the results will be more relevant than research using animal models, particularly if their physiology is very different from humans. Tissue from heart surgery must generally be used soon after collection or it significantly deteriorates. Freezing is an option but it raises concerns that freezing causes substantial damage at the cellular and molecular level. The SHB contains failing samples from heart transplant patients and others who provided informed consent for the use of their tissue for research. All samples are cryopreserved in liquid nitrogen within 40 min of their removal from the patient, and in less than 5-10 min in the case of coronary arteries and left ventricle samples. To date, the SHB has collected tissue from about 450 failing hearts (>15,000 samples) from patients with a wide range of etiologies as well as increasing numbers of cardiomyectomy samples from patients with hypertrophic cardiomyopathy. The Bank also has hearts from over 120 healthy organ donors whose hearts, for a variety of reasons (mainly tissue-type incompatibility with waiting heart transplant recipients), could not be used for transplantation. Donor hearts were collected by the St Vincent's Hospital Heart and Lung transplantation team from local hospitals or within a 4-h jet flight from Sydney. They were flushed with chilled cardioplegic solution and transported to Sydney where they were quickly cryopreserved in small samples. Failing and/or donor samples have been used by more than 60 research teams around the world, and have resulted in more than 100 research papers. The tissues most commonly requested are

  15. 1,8-Cineol Reduces Mucus-Production in a Novel Human Ex Vivo Model of Late Rhinosinusitis.

    Directory of Open Access Journals (Sweden)

    Holger Sudhoff

    Full Text Available Inflammatory diseases of the respiratory system such as rhinosinusitis, chronic obstructive pulmonary disease, or bronchial asthma are strongly associated with overproduction and hypersecretion of mucus lining the epithelial airway surface. 1,8-cineol, the active ingredient of the pharmaceutical drug Soledum, is commonly applied for treating such inflammatory airway diseases. However, its potential effects on mucus overproduction still remain unclear.In the present study, we successfully established ex vivo cultures of human nasal turbinate slices to investigate the effects of 1,8-cineol on mucus hypersecretion in experimentally induced rhinosinusitis. The presence of acetyl-α-tubulin-positive cilia confirmed the integrity of the ex vivo cultured epithelium. Mucin-filled goblet cells were also detectable in nasal slice cultures, as revealed by Alcian Blue and Periodic acid-Schiff stainings. Treatment of nasal slice cultures with lipopolysaccharides mimicking bacterial infection as observed during late rhinosinusitis led to a significantly increased number of mucin-filled goblet cells. Notably, the number of mucin-filled goblet cells was found to be significantly decreased after co-treatment with 1,8-cineol. On a molecular level, real time PCR-analysis further showed 1,8-cineol to significantly reduce the expression levels of the mucin genes MUC2 and MUC19 in close association with significantly attenuated NF-κB-activity. In conclusion, we demonstrate for the first time a 1,8-cineol-dependent reduction of mucin-filled goblet cells and MUC2-gene expression associated with an attenuated NF-κB-activity in human nasal slice cultures. Our findings suggest that these effects partially account for the clinical benefits of 1,8-cineol-based therapy during rhinosinusitis. Therefore, topical application of 1,8-cineol may offer a novel therapeutic approach to reduce bacteria-induced mucus hypersecretion.

  16. 1,8-Cineol Reduces Mucus-Production in a Novel Human Ex Vivo Model of Late Rhinosinusitis.

    Science.gov (United States)

    Sudhoff, Holger; Klenke, Christin; Greiner, Johannes F W; Müller, Janine; Brotzmann, Viktoria; Ebmeyer, Jörg; Kaltschmidt, Barbara; Kaltschmidt, Christian

    2015-01-01

    Inflammatory diseases of the respiratory system such as rhinosinusitis, chronic obstructive pulmonary disease, or bronchial asthma are strongly associated with overproduction and hypersecretion of mucus lining the epithelial airway surface. 1,8-cineol, the active ingredient of the pharmaceutical drug Soledum, is commonly applied for treating such inflammatory airway diseases. However, its potential effects on mucus overproduction still remain unclear.In the present study, we successfully established ex vivo cultures of human nasal turbinate slices to investigate the effects of 1,8-cineol on mucus hypersecretion in experimentally induced rhinosinusitis. The presence of acetyl-α-tubulin-positive cilia confirmed the integrity of the ex vivo cultured epithelium. Mucin-filled goblet cells were also detectable in nasal slice cultures, as revealed by Alcian Blue and Periodic acid-Schiff stainings. Treatment of nasal slice cultures with lipopolysaccharides mimicking bacterial infection as observed during late rhinosinusitis led to a significantly increased number of mucin-filled goblet cells. Notably, the number of mucin-filled goblet cells was found to be significantly decreased after co-treatment with 1,8-cineol. On a molecular level, real time PCR-analysis further showed 1,8-cineol to significantly reduce the expression levels of the mucin genes MUC2 and MUC19 in close association with significantly attenuated NF-κB-activity. In conclusion, we demonstrate for the first time a 1,8-cineol-dependent reduction of mucin-filled goblet cells and MUC2-gene expression associated with an attenuated NF-κB-activity in human nasal slice cultures. Our findings suggest that these effects partially account for the clinical benefits of 1,8-cineol-based therapy during rhinosinusitis. Therefore, topical application of 1,8-cineol may offer a novel therapeutic approach to reduce bacteria-induced mucus hypersecretion.

  17. Model-reduced inverse modeling

    NARCIS (Netherlands)

    Vermeulen, P.T.M.

    2006-01-01

    Although faster computers have been developed in recent years, they tend to be used to solve even more detailed problems. In many cases this will yield enormous models that can not be solved within acceptable time constraints. Therefore, there is a need for alternative methods that simulate such

  18. Determining Reduced Order Models for Optimal Stochastic Reduced Order Models

    Energy Technology Data Exchange (ETDEWEB)

    Bonney, Matthew S. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Brake, Matthew R.W. [Sandia National Lab. (SNL-CA), Livermore, CA (United States)

    2015-08-01

    The use of parameterized reduced order models(PROMs) within the stochastic reduced order model (SROM) framework is a logical progression for both methods. In this report, five different parameterized reduced order models are selected and critiqued against the other models along with truth model for the example of the Brake-Reuss beam. The models are: a Taylor series using finite difference, a proper orthogonal decomposition of the the output, a Craig-Bampton representation of the model, a method that uses Hyper-Dual numbers to determine the sensitivities, and a Meta-Model method that uses the Hyper-Dual results and constructs a polynomial curve to better represent the output data. The methods are compared against a parameter sweep and a distribution propagation where the first four statistical moments are used as a comparison. Each method produces very accurate results with the Craig-Bampton reduction having the least accurate results. The models are also compared based on time requirements for the evaluation of each model where the Meta- Model requires the least amount of time for computation by a significant amount. Each of the five models provided accurate results in a reasonable time frame. The determination of which model to use is dependent on the availability of the high-fidelity model and how many evaluations can be performed. Analysis of the output distribution is examined by using a large Monte-Carlo simulation along with a reduced simulation using Latin Hypercube and the stochastic reduced order model sampling technique. Both techniques produced accurate results. The stochastic reduced order modeling technique produced less error when compared to an exhaustive sampling for the majority of methods.

  19. On nonlinear reduced order modeling

    International Nuclear Information System (INIS)

    Abdel-Khalik, Hany S.

    2011-01-01

    When applied to a model that receives n input parameters and predicts m output responses, a reduced order model estimates the variations in the m outputs of the original model resulting from variations in its n inputs. While direct execution of the forward model could provide these variations, reduced order modeling plays an indispensable role for most real-world complex models. This follows because the solutions of complex models are expensive in terms of required computational overhead, thus rendering their repeated execution computationally infeasible. To overcome this problem, reduced order modeling determines a relationship (often referred to as a surrogate model) between the input and output variations that is much cheaper to evaluate than the original model. While it is desirable to seek highly accurate surrogates, the computational overhead becomes quickly intractable especially for high dimensional model, n ≫ 10. In this manuscript, we demonstrate a novel reduced order modeling method for building a surrogate model that employs only 'local first-order' derivatives and a new tensor-free expansion to efficiently identify all the important features of the original model to reach a predetermined level of accuracy. This is achieved via a hybrid approach in which local first-order derivatives (i.e., gradient) of a pseudo response (a pseudo response represents a random linear combination of original model’s responses) are randomly sampled utilizing a tensor-free expansion around some reference point, with the resulting gradient information aggregated in a subspace (denoted by the active subspace) of dimension much less than the dimension of the input parameters space. The active subspace is then sampled employing the state-of-the-art techniques for global sampling methods. The proposed method hybridizes the use of global sampling methods for uncertainty quantification and local variational methods for sensitivity analysis. In a similar manner to

  20. Reducing hazards for animals from humans

    Directory of Open Access Journals (Sweden)

    Paul-Pierre Pastoret

    2012-06-01

    Full Text Available If animals may be a source of hazards for humans, the reverse is equally true. The main sources of hazards from humans to animals, are the impact of human introduction of transboundary animal diseases, climate change, globalisation, introduction of invasive species and reduction of biodiversity.There is also a trend toward reducing genetic diversity in domestic animals, such as cattle; there are presently around 700 different breeds of cattle many of which at the verge of extinction (less than 100 reproductive females. The impact of humans is also indirect through detrimental effects on the environment. It is therefore urgent to implement the new concept of “one health"....

  1. Scalability of human models

    NARCIS (Netherlands)

    Rodarius, C.; Rooij, L. van; Lange, R. de

    2007-01-01

    The objective of this work was to create a scalable human occupant model that allows adaptation of human models with respect to size, weight and several mechanical parameters. Therefore, for the first time two scalable facet human models were developed in MADYMO. First, a scalable human male was

  2. Reduced Models for Gyrokinetic Turbulence

    Science.gov (United States)

    Besse, Nicolas; Bertrand, Pierre; Morel, Pierre; Gravier, Etienne

    2009-09-01

    Turbulent transport is a key issue for controlled thermonuclear fusion based on magnetic confinement. The thermal confinement of a magnetized fusion plasma is essentially determined by the turbulent heat conduction across the equilibrium magnetic field. It has long been acknowledged, that the prediction of turbulent transport requires to solve Vlasov-type gyrokinetic equations. Although the kinetic description is more accurate than fluid models (Magnetohydrodynamics (MHD), gyro-fluid), because among other things it takes into account nonlinear resonant wave-particle interaction, kinetic modeling has the drawback of a huge demand on computer resources. A unifying approach consists in considering water-bag-like weak solutions of kinetic collisionless equations, which allow to reduce the full kinetic Vlasov equation into a set of hydrodynamic equations, while keeping its kinetic behaviour. As a result this exact reduction induces a multi-fluid numerical resolution cost. Therefore, finding water-bag-like weak solutions of the gyrokinetic equations leads to the birth of the gyro-water-bag model. This model is suitable for studying linear and nonlinear low-frequency micro-instabilities and the associated anomalous transport in magnetically confined plasmas. Here we present the derivation of nonlinear gyro-water-bag models and their numerical approximations by backward Runge-Kutta semi-Lagrangian methods and forward Runge-Kutta discontinuous Galerkin schemes.

  3. Administration of the optimized β-Lapachone-poloxamer-cyclodextrin ternary system induces apoptosis, DNA damage and reduces tumor growth in a human breast adenocarcinoma xenograft mouse model.

    Science.gov (United States)

    Seoane, Samuel; Díaz-Rodríguez, Patricia; Sendon-Lago, Juan; Gallego, Rosalia; Pérez-Fernández, Román; Landin, Mariana

    2013-08-01

    β-Lapachone (β-Lap) is a 1,2-orthonaphthoquinone that selectively induces cell death in human cancer cells through NAD(P)H:quinone oxidoreductase-1 (NQO1). NQO1 is overexpressed in a variety of tumors, as compared to normal adjacent tissue. However, the low solubility and non-specific distribution of β-Lap limit its suitability for clinical assays. We formulated β-Lap in an optimal random methylated-β-cyclodextrin/poloxamer 407 mixture (i.e., β-Lap ternary system) and, using human breast adenocarcinoma MCF-7 cells and immunodeficient mice, performed in vitro and in vivo evaluation of its anti-tumor effects on proliferation, cell cycle, apoptosis, DNA damage, and tumor growth. This ternary system is fluid at room temperature, gels over 29 °C, and provides a significant amount of drug, thus facilitating intratumoral delivery, in situ gelation, and the formation of a depot for time-release. Administration of β-Lap ternary system to MCF-7 cells induces an increase in apoptosis and DNA damage, while producing no changes in cell cycle. Moreover, in a mouse xenograft tumor model, intratumoral injection of the system significantly reduces tumor volume, while increasing apoptosis and DNA damage without visible toxicity to liver or kidney. These anti-tumoral effects and lack of visible toxicity make this system a promising new therapeutic agent for breast cancer treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Phytosterol glycosides reduce cholesterol absorption in humans

    OpenAIRE

    Lin, Xiaobo; Ma, Lina; Racette, Susan B.; Anderson Spearie, Catherine L.; Ostlund, Richard E.

    2009-01-01

    Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series ...

  5. Antioxidant activity of pomegranate juice reduces emphysematous changes and injury secondary to cigarette smoke in an animal model and human alveolar cells

    Directory of Open Access Journals (Sweden)

    Husari A

    2016-02-01

    Full Text Available Ahmad Husari,1,* Yasmine Hashem,1 Hala Bitar,1 Ghassan Dbaibo,2,3 Ghazi Zaatari,4 Marwan El Sabban5,* 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, 2Department of Pediatrics and Adolescent Medicine, Division of Pediatric Infectious Diseases, 3Department of Biochemistry and Molecular Genetics, 4Department of Pathology and Laboratory Medicine, 5Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon *These authors contributed equally to this work Background: Cigarette smoke (CS increases oxidative stress (OS in the lungs. Pomegranate juice (PJ possesses potent antioxidant activities, attributed to its polyphenols. This study investigates the effects of PJ on the damaging effects of CS in an animal model and on cultured human alveolar cells (A549. Methods: Male C57BL/6J mice were divided into the following groups: Control, CS, CS + PJ, and PJ. Acute CS exposure was for 3 days, while chronic exposure was for 1 and 3 months (5 days of exposure/week. PJ groups received daily 80 µmol/kg via bottle, while other groups received distilled water. At the end of the experiments, different parameters were studied: 1 expression levels of inflammatory markers, 2 apoptosis, 3 OS, and 4 histopathological changes. In vitro, A549 cells were pretreated for 48 hours with either PJ (0.5 µM or vehicle. Cells were then exposed to increasing concentrations of CS extracted from collected filters. Cell viability was assessed by counting of live and dead cells with trypan blue staining. Results: Acutely, a significant increase in interleukin (IL-1β, IL-6, and tumor necrosis factor (TNF-α expression, apoptosis, and OS was noted in CS when compared to Control. PJ significantly attenuated the expression of inflammatory mediators, apoptosis, and OS. Chronically (at 1 and 3 months, increased expression of TNF-α was observed, and lung sections

  6. A natural human hand model

    NARCIS (Netherlands)

    Van Nierop, O.A.; Van der Helm, A.; Overbeeke, K.J.; Djajadiningrat, T.J.P.

    2007-01-01

    We present a skeletal linked model of the human hand that has natural motion. We show how this can be achieved by introducing a new biology-based joint axis that simulates natural joint motion and a set of constraints that reduce an estimated 150 possible motions to twelve. The model is based on

  7. Phytosterol glycosides reduce cholesterol absorption in humans.

    Science.gov (United States)

    Lin, Xiaobo; Ma, Lina; Racette, Susan B; Anderson Spearie, Catherine L; Ostlund, Richard E

    2009-04-01

    Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series of three single-meal tests given at intervals of 2 wk to each of 11 healthy subjects. In a randomized crossover design, participants received approximately 300 mg of added phytosterols in the form of phytosterol glycosides or phytosterol esters, or placebo in a test breakfast also containing 30 mg cholesterol-d7. Cholesterol absorption was estimated by mass spectrometry of plasma cholesterol-d7 enrichment 4-5 days after each test. Compared with the placebo test, phytosterol glycosides reduced cholesterol absorption by 37.6+/-4.8% (Pphytosterol esters 30.6+/-3.9% (P=0.0001). These results suggest that natural phytosterol glycosides purified from lecithin are bioactive in humans and should be included in methods of phytosterol analysis and tables of food phytosterol content.

  8. Human Performance in Simulated Reduced Gravity Environments

    Science.gov (United States)

    Cowley, Matthew; Harvill, Lauren; Rajulu, Sudhakar

    2014-01-01

    NASA is currently designing a new space suit capable of working in deep space and on Mars. Designing a suit is very difficult and often requires trade-offs between performance, cost, mass, and system complexity. Our current understanding of human performance in reduced gravity in a planetary environment (the moon or Mars) is limited to lunar observations, studies from the Apollo program, and recent suit tests conducted at JSC using reduced gravity simulators. This study will look at our most recent reduced gravity simulations performed on the new Active Response Gravity Offload System (ARGOS) compared to the C-9 reduced gravity plane. Methods: Subjects ambulated in reduced gravity analogs to obtain a baseline for human performance. Subjects were tested in lunar gravity (1.6 m/sq s) and Earth gravity (9.8 m/sq s) in shirt-sleeves. Subjects ambulated over ground at prescribed speeds on the ARGOS, but ambulated at a self-selected speed on the C-9 due to time limitations. Subjects on the ARGOS were given over 3 minutes to acclimate to the different conditions before data was collected. Nine healthy subjects were tested in the ARGOS (6 males, 3 females, 79.5 +/- 15.7 kg), while six subjects were tested on the C-9 (6 males, 78.8 +/- 11.2 kg). Data was collected with an optical motion capture system (Vicon, Oxford, UK) and was analyzed using customized analysis scripts in BodyBuilder (Vicon, Oxford, UK) and MATLAB (MathWorks, Natick, MA, USA). Results: In all offloaded conditions, variation between subjects increased compared to 1-g. Kinematics in the ARGOS at lunar gravity resembled earth gravity ambulation more closely than the C-9 ambulation. Toe-off occurred 10% earlier in both reduced gravity environments compared to earth gravity, shortening the stance phase. Likewise, ankle, knee, and hip angles remained consistently flexed and had reduced peaks compared to earth gravity. Ground reaction forces in lunar gravity (normalized to Earth body weight) were 0.4 +/- 0.2 on

  9. Reduced complexity modeling of Arctic delta dynamics

    Science.gov (United States)

    Piliouras, A.; Lauzon, R.; Rowland, J. C.

    2017-12-01

    How water and sediment are routed through deltas has important implications for our understanding of nutrient and sediment fluxes to the coastal ocean. These fluxes may be especially important in Arctic environments, because the Arctic ocean receives a disproportionately large amount of river discharge and high latitude regions are expected to be particularly vulnerable to climate change. The Arctic has some of the world's largest but least studied deltas. This lack of data is due to remote and hazardous conditions, sparse human populations, and limited remote sensing resources. In the absence of data, complex models may be of limited scientific utility in understanding Arctic delta dynamics. To overcome this challenge, we adapt the reduced complexity delta-building model DeltaRCM for Arctic environments to explore the influence of sea ice and permafrost on delta morphology and dynamics. We represent permafrost by increasing the threshold for sediment erosion, as permafrost has been found to increase cohesion and reduce channel migration rates. The presence of permafrost in the model results in the creation of more elongate channels, fewer active channels, and a rougher shoreline. We consider several effects of sea ice, including introducing friction which increases flow resistance, constriction of flow by landfast ice, and changes in effective water surface elevation. Flow constriction and increased friction from ice results in a rougher shoreline, more frequent channel switching, decreased channel migration rates, and enhanced deposition offshore of channel mouths. The reduced complexity nature of the model is ideal for generating a basic understanding of which processes unique to Arctic environments may have important effects on delta evolution, and it allows us to explore a variety of rules for incorporating those processes into the model to inform future Arctic delta modelling efforts. Finally, we plan to use the modeling results to determine how the presence

  10. Combination therapy of human umbilical cord blood cells and granulocyte colony stimulating factor reduces histopathological and motor impairments in an experimental model of chronic traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Sandra A Acosta

    Full Text Available Traumatic brain injury (TBI is associated with neuro-inflammation, debilitating sensory-motor deficits, and learning and memory impairments. Cell-based therapies are currently being investigated in treating neurotrauma due to their ability to secrete neurotrophic factors and anti-inflammatory cytokines that can regulate the hostile milieu associated with chronic neuroinflammation found in TBI. In tandem, the stimulation and mobilization of endogenous stem/progenitor cells from the bone marrow through granulocyte colony stimulating factor (G-CSF poses as an attractive therapeutic intervention for chronic TBI. Here, we tested the potential of a combined therapy of human umbilical cord blood cells (hUCB and G-CSF at the acute stage of TBI to counteract the progressive secondary effects of chronic TBI using the controlled cortical impact model. Four different groups of adult Sprague Dawley rats were treated with saline alone, G-CSF+saline, hUCB+saline or hUCB+G-CSF, 7-days post CCI moderate TBI. Eight weeks after TBI, brains were harvested to analyze hippocampal cell loss, neuroinflammatory response, and neurogenesis by using immunohistochemical techniques. Results revealed that the rats exposed to TBI treated with saline exhibited widespread neuroinflammation, impaired endogenous neurogenesis in DG and SVZ, and severe hippocampal cell loss. hUCB monotherapy suppressed neuroinflammation, nearly normalized the neurogenesis, and reduced hippocampal cell loss compared to saline alone. G-CSF monotherapy produced partial and short-lived benefits characterized by low levels of neuroinflammation in striatum, DG, SVZ, and corpus callosum and fornix, a modest neurogenesis, and a moderate reduction of hippocampal cells loss. On the other hand, combined therapy of hUCB+G-CSF displayed synergistic effects that robustly dampened neuroinflammation, while enhancing endogenous neurogenesis and reducing hippocampal cell loss. Vigorous and long-lasting recovery of

  11. Models of human operators

    International Nuclear Information System (INIS)

    Knee, H.E.; Schryver, J.C.

    1991-01-01

    Models of human behavior and cognition (HB and C) are necessary for understanding the total response of complex systems. Many such models have come available over the past thirty years for various applications. Unfortunately, many potential model users remain skeptical about their practicality, acceptability, and usefulness. Such hesitancy stems in part to disbelief in the ability to model complex cognitive processes, and a belief that relevant human behavior can be adequately accounted for through the use of commonsense heuristics. This paper will highlight several models of HB and C and identify existing and potential applications in attempt to dispel such notions. (author)

  12. Generalized Reduced Order Model Generation, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — M4 Engineering proposes to develop a generalized reduced order model generation method. This method will allow for creation of reduced order aeroservoelastic state...

  13. Generalized Reduced Order Model Generation Project

    Data.gov (United States)

    National Aeronautics and Space Administration — M4 Engineering proposes to develop a generalized reduced order model generation method. This method will allow for creation of reduced order aeroservoelastic state...

  14. Reduced fidelity in the Kitaev honeycomb model

    International Nuclear Information System (INIS)

    Wang, Zhi; Ma, Tianxing; Gu, Shi-Jian; Lin, Hai-Qing

    2010-01-01

    We study reduced fidelity and reduced fidelity susceptibility in the Kitaev honeycomb model. It is shown that the nearest-two-site reduced fidelity susceptibility manifests itself as a peak at the quantum phase transition point, although the one-site reduced fidelity susceptibility vanishes. Our results directly reveal that the reduced fidelity susceptibility can be used to characterize the quantum phase transition in the Kitaev honeycomb model, which suggests that, despite its local nature, the reduced fidelity susceptibility is an accurate marker of the topological phase transition when it is properly chosen.

  15. Computational human body models

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Dommelen, J.A.W. van

    2005-01-01

    Computational human body models are widely used for automotive crashsafety research and design and as such have significantly contributed to a reduction of traffic injuries and fatalities. Currently crash simulations are mainly performed using models based on crash-dummies. However crash dummies

  16. Enteral nutrients potentiate glucagon-like peptide-2 action and reduce dependence on parenteral nutrition in a rat model of human intestinal failure

    DEFF Research Database (Denmark)

    Brinkman, Adam S; Murali, Sangita G; Hitt, Stacy

    2012-01-01

    Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that shows promise for the treatment of short bowel syndrome (SBS). Our objective was to investigate how combination GLP-2 + enteral nutrients (EN) affects intestinal adaption in a rat model that mimics severe...... human SBS and requires parenteral nutrition (PN). Male Sprague-Dawley rats were assigned to one of five groups and maintained with PN for 18 days: total parenteral nutrition (TPN) alone, TPN + GLP-2 (100 μg·kg(-1)·day(-1)), PN + EN + GLP-2(7 days), PN + EN + GLP-2(18 days), and a nonsurgical oral...

  17. Human migraine models

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg

    2001-01-01

    The need for experimental models is obvious. In animal models it is possible to study vascular responses, neurogenic inflammation, c-fos expression etc. However, the pathophysiology of migraine remains unsolved, why results from animal studies not directly can be related to the migraine attack......, which is a human experience. A set-up for investigations of experimental headache and migraine in humans, has been evaluated and headache mechanisms explored by using nitroglycerin and other headache-inducing agents. Nitric oxide (NO) or other parts of the NO activated cascade seems to be responsible...... for the induced headache and migraine. Perspectives are discussed....

  18. Humans running in place on water at simulated reduced gravity.

    Directory of Open Access Journals (Sweden)

    Alberto E Minetti

    Full Text Available BACKGROUND: On Earth only a few legged species, such as water strider insects, some aquatic birds and lizards, can run on water. For most other species, including humans, this is precluded by body size and proportions, lack of appropriate appendages, and limited muscle power. However, if gravity is reduced to less than Earth's gravity, running on water should require less muscle power. Here we use a hydrodynamic model to predict the gravity levels at which humans should be able to run on water. We test these predictions in the laboratory using a reduced gravity simulator. METHODOLOGY/PRINCIPAL FINDINGS: We adapted a model equation, previously used by Glasheen and McMahon to explain the dynamics of Basilisk lizard, to predict the body mass, stride frequency and gravity necessary for a person to run on water. Progressive body-weight unloading of a person running in place on a wading pool confirmed the theoretical predictions that a person could run on water, at lunar (or lower gravity levels using relatively small rigid fins. Three-dimensional motion capture of reflective markers on major joint centers showed that humans, similarly to the Basilisk Lizard and to the Western Grebe, keep the head-trunk segment at a nearly constant height, despite the high stride frequency and the intensive locomotor effort. Trunk stabilization at a nearly constant height differentiates running on water from other, more usual human gaits. CONCLUSIONS/SIGNIFICANCE: The results showed that a hydrodynamic model of lizards running on water can also be applied to humans, despite the enormous difference in body size and morphology.

  19. Reduced penetrance in human inherited disease | Shawky ...

    African Journals Online (AJOL)

    With the advancement of molecular genetics over the last few years, some of the underlying mechanisms of reduced penetrance have been elucidated. These include, mutation type, allelic variations in gene expression, epigenetic factors, gene-environment interplay, influence of age and sex, allele dosage, oligogenic and ...

  20. Recombinant human endostatin reduces hypertrophic scar ...

    African Journals Online (AJOL)

    Methods: Sixteen New Zealand white rabbits were used to establish HS models. Then, rabbit ears containing HS were randomly assigned to either the Endostar group or the control group. The changes of appearance and histology were evaluated using the naked eye, hematoxylin eosin staining, and a scar elevation index.

  1. Risk of hormone escape in a human prostate cancer model depends on therapy modalities and can be reduced by tyrosine kinase inhibitors.

    Directory of Open Access Journals (Sweden)

    Charlotte Guyader

    Full Text Available Almost all prostate cancers respond to androgen deprivation treatment but many recur. We postulated that risk of hormone escape--frequency and delay--are influenced by hormone therapy modalities. More, hormone therapies induce crucial biological changes involving androgen receptors; some might be targets for escape prevention. We investigated the relationship between the androgen deprivation treatment and the risk of recurrence using nude mice bearing the high grade, hormone-dependent human prostate cancer xenograft PAC120. Tumor-bearing mice were treated by Luteinizing-Hormone Releasing Hormone (LHRH antagonist alone, continuous or intermittent regimen, or combined with androgen receptor (AR antagonists (bicalutamide or flutamide. Tumor growth was monitored. Biological changes were studied as for genomic alterations, AR mutations and protein expression in a large series of recurrent tumors according to hormone therapy modalities. Therapies targeting Her-2 or AKT were tested in combination with castration. All statistical tests were two-sided. Tumor growth was inhibited by continuous administration of the LH-RH antagonist degarelix (castration, but 40% of tumors recurred. Intermittent castration or complete blockade induced by degarelix and antiandrogens combination, inhibited tumor growth but increased the risk of recurrence (RR as compared to continuous castration (RR(intermittent: 14.5, RR(complete blockade: 6.5 and 1.35. All recurrent tumors displayed new quantitative genetic alterations and AR mutations, whatever the treatment modalities. AR amplification was found after complete blockade. Increased expression of Her-2/neu with frequent ERK/AKT activation was detected in all variants. Combination of castration with a Her-2/neu inhibitor decreased recurrence risk (0.17 and combination with an mTOR inhibitor prevented it. Anti-hormone treatments influence risk of recurrence although tumor growth inhibition was initially similar. Recurrent

  2. Human Alpha-1-Antitrypsin (hAAT) therapy reduces renal dysfunction and acute tubular necrosis in a murine model of bilateral kidney ischemia-reperfusion injury

    NARCIS (Netherlands)

    Maicas, Nuria; van der Vlag, Johan; Bublitz, Janin; Florquin, Sandrine; Bakker-van Bebber, Marinka; Dinarello, Charles A; Verweij, Vivienne; Masereeuw, Roos|info:eu-repo/dai/nl/155644033; Joosten, Leo A; Hilbrands, Luuk B

    2017-01-01

    Several lines of evidence have demonstrated the anti-inflammatory and cytoprotective effects of alpha-1-antitrypsin (AAT), the major serum serine protease inhibitor. The aim of the present study was to investigate the effects of human AAT (hAAT) monotherapy during the early and recovery phase of

  3. Normal Forms for Reduced Stochastic Climate Models

    Science.gov (United States)

    Franzke, C.; Majda, A.; Crommelin, D.

    2009-04-01

    The systematic development of reduced low-dimensional stochastic climate models from observations or comprehensive high-dimensional climate models is an important topic for low-frequency variability, climate sensitivity, and improved extended range forecasting. Here techniques from applied mathematics are utilized to systematically derive normal forms for reduced stochastic climate models for low-frequency variables. The use of a few Empirical Orthogonal Functions (EOF) depending on observational data to span the low-frequency subspace requires the assessment of dyad interactions besides the more familiar triads in the interaction between the low- and high-frequency subspaces of the dynamics. It will be shown that the dyad and multiplicative triad interactions combine with the climatological linear operator interactions to simultaneously produce both strong nonlinear dissipation and Correlated Additive and Multiplicative (CAM) stochastic noise. For a single low-frequency variable the dyad interactions and climatological linear operator alone produce a normal form with CAM noise from advection of the large-scales by the small scales and simultaneously strong cubic damping. This normal form should prove useful for developing systematic regression fitting strategies for stochastic models of climate data. The validity of the one and two dimensional normal forms will be presented. Also the analytical PDF form for one-dimensional reduced models will be derived. This PDF can exhibit power-law decay only over a limited range and its ultimate decay is determined by the cubic damping. This cubic damping produces a Gaussian tail.

  4. BWR stability using a reducing dynamical model

    International Nuclear Information System (INIS)

    Ballestrin Bolea, J. M.; Blazquez Martinez, J. B.

    1990-01-01

    BWR stability can be treated with reduced order dynamical models. When the parameters of the model came from dynamical models. When the parameters of the model came from experimental data, the predictions are accurate. In this work an alternative derivation for the void fraction equation is made, but remarking the physical structure of the parameters. As the poles of power/reactivity transfer function are related with the parameters, the measurement of the poles by other techniques such as noise analysis will lead to the parameters, but the system of equations is non-linear. Simple parametric calculation of decay ratio are performed, showing why BWRs become unstable when they are operated at low flow and high power. (Author)

  5. Peptide-Based Scaffolds Support Human Cortical Progenitor Graft Integration to Reduce Atrophy and Promote Functional Repair in a Model of Stroke

    Directory of Open Access Journals (Sweden)

    Fahad A. Somaa

    2017-08-01

    Full Text Available Stem cell transplants offer significant hope for brain repair following ischemic damage. Pre-clinical work suggests that therapeutic mechanisms may be multi-faceted, incorporating bone-fide circuit reconstruction by transplanted neurons, but also protection/regeneration of host circuitry. Here, we engineered hydrogel scaffolds to form “bio-bridges” within the necrotic lesion cavity, providing physical and trophic support to transplanted human embryonic stem cell-derived cortical progenitors, as well as residual host neurons. Scaffolds were fabricated by the self-assembly of peptides for a laminin-derived epitope (IKVAV, thereby mimicking the brain’s major extracellular protein. Following focal ischemia in rats, scaffold-supported cell transplants induced progressive motor improvements over 9 months, compared to cell- or scaffold-only implants. These grafts were larger, exhibited greater neuronal differentiation, and showed enhanced electrophysiological properties reflective of mature, integrated neurons. Varying graft timing post-injury enabled us to attribute repair to both neuroprotection and circuit replacement. These findings highlight strategies to improve the efficiency of stem cell grafts for brain repair.

  6. Attention reduces spatial uncertainty in human ventral temporal cortex

    Science.gov (United States)

    Kay, Kendrick N.; Weiner, Kevin S.; Grill-Spector, Kalanit

    2014-01-01

    SUMMARY Ventral temporal cortex (VTC) is the latest stage of the ventral ‘what’ visual pathway, which is thought to code the identity of a stimulus regardless of its position or size [1, 2]. Surprisingly, recent studies show that position information can be decoded from VTC [3–5]. However, the computational mechanisms by which spatial information is encoded in VTC are unknown. Furthermore, how attention influences spatial representations in human VTC is also unknown because the effect of attention on spatial representations has only been examined in the dorsal ‘where’ visual pathway [6–10]. Here we fill these significant gaps in knowledge using an approach that combines functional magnetic resonance imaging and sophisticated computational methods. We first develop a population receptive field (pRF) model [11, 12] of spatial responses in human VTC. Consisting of spatial summation followed by a compressive nonlinearity, this model accurately predicts responses of individual voxels to stimuli at any position and size, explains how spatial information is encoded, and reveals a functional hierarchy in VTC. We then manipulate attention and use our model to decipher the effects of attention. We find that attention to the stimulus systematically and selectively modulates responses in VTC, but not early visual areas. Locally, attention increases eccentricity, size, and gain of individual pRFs, thereby increasing position tolerance. However, globally, these effects reduce uncertainty regarding stimulus location and actually increase position sensitivity of distributed responses across VTC. These results demonstrate that attention actively shapes and enhances spatial representations in the ventral visual pathway. PMID:25702580

  7. Degenerate wave and capacitive coupling increase human MSC invasion and proliferation while reducing cytotoxicity in an in vitro wound healing model.

    Directory of Open Access Journals (Sweden)

    Michelle Griffin

    Full Text Available Non-unions pose complications in fracture management that can be treated using electrical stimulation (ES. Bone marrow mesenchymal stem cells (BMMSCs are essential in fracture healing; however, the effect of different clinical ES waveforms on BMMSCs cellular activities remains unknown. We compared the effects of direct current (DC, capacitive coupling (CC, pulsed electromagnetic field (PEMF and degenerate wave (DW on cellular activities including cytotoxicity, proliferation, cell-kinetics and apoptosis by stimulating human-BMMSCs 3 hours a day, up to 5 days. In addition, migration and invasion were assessed using fluorescence microscopy and by quantifying gene and protein expression. We found that DW had the greatest proliferative and least apoptotic and cytotoxic effects compared to other waveforms. DC, DW and CC stimulations resulted in a higher number of cells in S phase and G(2/M phase as shown by cell cycle analysis. CC and DW caused more cells to invade collagen and showed increased MMP-2 and MT1-MMP expression. DC increased cellular migration in a scratch-wound assay and all ES waveforms enhanced expression of migratory genes with DC having the greatest effect. All ES treated cells showed similar progenitor potential as determined by MSC differentiation assay. All above findings were shown to be statistically significant (p<0.05. We conclude that ES can influence BMMSCs activities, especially DW and CC, which show greater invasion and higher cell proliferation compared to other types of ES. Application of DW or CC to the fracture site may help in the recruitment of BMMSCs to the wound that may enhance rate of bone healing at the fracture site.

  8. Reducing Spatial Data Complexity for Classification Models

    International Nuclear Information System (INIS)

    Ruta, Dymitr; Gabrys, Bogdan

    2007-01-01

    Intelligent data analytics gradually becomes a day-to-day reality of today's businesses. However, despite rapidly increasing storage and computational power current state-of-the-art predictive models still can not handle massive and noisy corporate data warehouses. What is more adaptive and real-time operational environment requires multiple models to be frequently retrained which further hinders their use. Various data reduction techniques ranging from data sampling up to density retention models attempt to address this challenge by capturing a summarised data structure, yet they either do not account for labelled data or degrade the classification performance of the model trained on the condensed dataset. Our response is a proposition of a new general framework for reducing the complexity of labelled data by means of controlled spatial redistribution of class densities in the input space. On the example of Parzen Labelled Data Compressor (PLDC) we demonstrate a simulatory data condensation process directly inspired by the electrostatic field interaction where the data are moved and merged following the attracting and repelling interactions with the other labelled data. The process is controlled by the class density function built on the original data that acts as a class-sensitive potential field ensuring preservation of the original class density distributions, yet allowing data to rearrange and merge joining together their soft class partitions. As a result we achieved a model that reduces the labelled datasets much further than any competitive approaches yet with the maximum retention of the original class densities and hence the classification performance. PLDC leaves the reduced dataset with the soft accumulative class weights allowing for efficient online updates and as shown in a series of experiments if coupled with Parzen Density Classifier (PDC) significantly outperforms competitive data condensation methods in terms of classification performance at the

  9. Mathematical models of human retina.

    Science.gov (United States)

    Tălu, Stefan

    2011-01-01

    To describe the human retina, due the absence of complete topographical data, mathematical models are required. The mathematical formula permits a relatively simple representation to explore the physical and optical characteristics of the retina, with particular parameters. Advanced mathematical models are applied for human vision studies, solid modelling and biomechanical behavior of the retina. The accurate modelling of the retina is important in the development of visual prostheses. The objective of this paper is to present an overview of researches for human retina modelling using mathematical models.

  10. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a

  11. Floor Vibrations - as Induced and Reduced by Humans

    DEFF Research Database (Denmark)

    Pedersen, Lars

    . As for dynamic loads focus is placed on heel impact excitation and actions of jumping people causing floor vibrations. As for interaction between stationary humans and the vibrating floor focus is on modelling humans as oscillating spring-mass-damper systems attached to the floor rather than as simple added mass...

  12. BWR stability using a reduced dynamical model

    International Nuclear Information System (INIS)

    Ballestrin Bolea, J.M.; Blazquez, J.B.

    1990-01-01

    BWR stability can be treated with reduced order dynamical models. When the parameters of the model came from experimental data, the predictions are accurate. In this work an alternative derivation for the void fraction equation is made, but remarking the physical struct-ure of the parameters. As the poles of power/reactivity transfer function are related with the parameters, the measurement of the poles by other techniques such as noise analysis will lead to the parameters, but the system of equations in non-linear. Simple parametric calculat-ion of decay ratio are performed, showing why BWRs become unstable when they are operated at low flow and high power. (Author). 7 refs

  13. Stochastic Models of Human Errors

    Science.gov (United States)

    Elshamy, Maged; Elliott, Dawn M. (Technical Monitor)

    2002-01-01

    Humans play an important role in the overall reliability of engineering systems. More often accidents and systems failure are traced to human errors. Therefore, in order to have meaningful system risk analysis, the reliability of the human element must be taken into consideration. Describing the human error process by mathematical models is a key to analyzing contributing factors. Therefore, the objective of this research effort is to establish stochastic models substantiated by sound theoretic foundation to address the occurrence of human errors in the processing of the space shuttle.

  14. Integrated Environmental Modelling: Human decisions, human challenges

    Science.gov (United States)

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  15. Integrated Environmental Modelling: human decisions, human challenges

    Science.gov (United States)

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  16. Compound Stimulus Extinction Reduces Spontaneous Recovery in Humans

    Science.gov (United States)

    Coelho, Cesar A. O.; Dunsmoor, Joseph E.; Phelps, Elizabeth A.

    2015-01-01

    Fear-related behaviors are prone to relapse following extinction. We tested in humans a compound extinction design ("deepened extinction") shown in animal studies to reduce post-extinction fear recovery. Adult subjects underwent fear conditioning to a visual and an auditory conditioned stimulus (CSA and CSB, respectively) separately…

  17. Reduced order model of draft tube flow

    International Nuclear Information System (INIS)

    Rudolf, P; Štefan, D

    2014-01-01

    Swirling flow with compact coherent structures is very good candidate for proper orthogonal decomposition (POD), i.e. for decomposition into eigenmodes, which are the cornerstones of the flow field. Present paper focuses on POD of steady flows, which correspond to different operating points of Francis turbine draft tube flow. Set of eigenmodes is built using a limited number of snapshots from computational simulations. Resulting reduced order model (ROM) describes whole operating range of the draft tube. ROM enables to interpolate in between the operating points exploiting the knowledge about significance of particular eigenmodes and thus reconstruct the velocity field in any operating point within the given range. Practical example, which employs axisymmetric simulations of the draft tube flow, illustrates accuracy of ROM in regions without vortex breakdown together with need for higher resolution of the snapshot database close to location of sudden flow changes (e.g. vortex breakdown). ROM based on POD interpolation is very suitable tool for insight into flow physics of the draft tube flows (especially energy transfers in between different operating points), for supply of data for subsequent stability analysis or as an initialization database for advanced flow simulations

  18. Inhibition of fatty acid metabolism reduces human myeloma cells proliferation.

    Directory of Open Access Journals (Sweden)

    José Manuel Tirado-Vélez

    Full Text Available Multiple myeloma is a haematological malignancy characterized by the clonal proliferation of plasma cells. It has been proposed that targeting cancer cell metabolism would provide a new selective anticancer therapeutic strategy. In this work, we tested the hypothesis that inhibition of β-oxidation and de novo fatty acid synthesis would reduce cell proliferation in human myeloma cells. We evaluated the effect of etomoxir and orlistat on fatty acid metabolism, glucose metabolism, cell cycle distribution, proliferation, cell death and expression of G1/S phase regulatory proteins in myeloma cells. Etomoxir and orlistat inhibited β-oxidation and de novo fatty acid synthesis respectively in myeloma cells, without altering significantly glucose metabolism. These effects were associated with reduced cell viability and cell cycle arrest in G0/G1. Specifically, etomoxir and orlistat reduced by 40-70% myeloma cells proliferation. The combination of etomoxir and orlistat resulted in an additive inhibitory effect on cell proliferation. Orlistat induced apoptosis and sensitized RPMI-8226 cells to apoptosis induction by bortezomib, whereas apoptosis was not altered by etomoxir. Finally, the inhibitory effect of both drugs on cell proliferation was associated with reduced p21 protein levels and phosphorylation levels of retinoblastoma protein. In conclusion, inhibition of fatty acid metabolism represents a potential therapeutic approach to treat human multiple myeloma.

  19. Human mobility: Models and applications

    Science.gov (United States)

    Barbosa, Hugo; Barthelemy, Marc; Ghoshal, Gourab; James, Charlotte R.; Lenormand, Maxime; Louail, Thomas; Menezes, Ronaldo; Ramasco, José J.; Simini, Filippo; Tomasini, Marcello

    2018-03-01

    Recent years have witnessed an explosion of extensive geolocated datasets related to human movement, enabling scientists to quantitatively study individual and collective mobility patterns, and to generate models that can capture and reproduce the spatiotemporal structures and regularities in human trajectories. The study of human mobility is especially important for applications such as estimating migratory flows, traffic forecasting, urban planning, and epidemic modeling. In this survey, we review the approaches developed to reproduce various mobility patterns, with the main focus on recent developments. This review can be used both as an introduction to the fundamental modeling principles of human mobility, and as a collection of technical methods applicable to specific mobility-related problems. The review organizes the subject by differentiating between individual and population mobility and also between short-range and long-range mobility. Throughout the text the description of the theory is intertwined with real-world applications.

  20. Mathematical models of human behavior

    DEFF Research Database (Denmark)

    Møllgaard, Anders Edsberg

    During the last 15 years there has been an explosion in human behavioral data caused by the emergence of cheap electronics and online platforms. This has spawned a whole new research field called computational social science, which has a quantitative approach to the study of human behavior. Most...... studies have considered data sets with just one behavioral variable such as email communication. The Social Fabric interdisciplinary research project is an attempt to collect a more complete data set on human behavior by providing 1000 smartphones with pre-installed data collection software to students...... data set, along with work on other behavioral data. The overall goal is to contribute to a quantitative understanding of human behavior using big data and mathematical models. Central to the thesis is the determination of the predictability of different human activities. Upper limits are derived...

  1. Human Modeling For Ground Processing Human Factors Engineering Analysis

    Science.gov (United States)

    Tran, Donald; Stambolian, Damon; Henderson, Gena; Barth, Tim

    2011-01-01

    There have been many advancements and accomplishments over that last few years using human modeling for human factors engineering analysis for design of spacecraft and launch vehicles. The key methods used for this are motion capture and computer generated human models. The focus of this paper is to explain the different types of human modeling used currently and in the past at Kennedy Space Center (KSC) currently, and to explain the future plans for human modeling for future spacecraft designs.

  2. Flexible Bayesian Human Fecundity Models.

    Science.gov (United States)

    Kim, Sungduk; Sundaram, Rajeshwari; Buck Louis, Germaine M; Pyper, Cecilia

    2012-12-01

    Human fecundity is an issue of considerable interest for both epidemiological and clinical audiences, and is dependent upon a couple's biologic capacity for reproduction coupled with behaviors that place a couple at risk for pregnancy. Bayesian hierarchical models have been proposed to better model the conception probabilities by accounting for the acts of intercourse around the day of ovulation, i.e., during the fertile window. These models can be viewed in the framework of a generalized nonlinear model with an exponential link. However, a fixed choice of link function may not always provide the best fit, leading to potentially biased estimates for probability of conception. Motivated by this, we propose a general class of models for fecundity by relaxing the choice of the link function under the generalized nonlinear model framework. We use a sample from the Oxford Conception Study (OCS) to illustrate the utility and fit of this general class of models for estimating human conception. Our findings reinforce the need for attention to be paid to the choice of link function in modeling conception, as it may bias the estimation of conception probabilities. Various properties of the proposed models are examined and a Markov chain Monte Carlo sampling algorithm was developed for implementing the Bayesian computations. The deviance information criterion measure and logarithm of pseudo marginal likelihood are used for guiding the choice of links. The supplemental material section contains technical details of the proof of the theorem stated in the paper, and contains further simulation results and analysis.

  3. Modelling biased human trust dynamics

    NARCIS (Netherlands)

    Hoogendoorn, M.; Jaffry, S.W.; Maanen, P.P. van; Treur, J.

    2013-01-01

    Abstract. Within human trust related behaviour, according to the literature from the domains of Psychology and Social Sciences often non-rational behaviour can be observed. Current trust models that have been developed typically do not incorporate non-rational elements in the trust formation

  4. Human Resource Models: An Overview.

    Science.gov (United States)

    1982-11-01

    simulation models in which human performance plays an important part see, A.I. Siegel and J.J. Wolf , "Digital Behavioral Simulation--State-of-the-Art...atford and Petersen, Charles C., ’Mfaritine 421-439 Factors Adfecting Iberian Security," (Factores hbritimos Que "Northwestern University, Evanston

  5. Animal models for human diseases.

    Science.gov (United States)

    Rust, J H

    1982-01-01

    The use of animal models for the study of human disease is, for the most part, a recent development. This discussion of the use of animal models for human diseases directs attention to the sterile period, early advances, some personal experiences, the human as the model, biological oddities among common laboratory animals, malignancies in laboratory animals, problems created by federal regulations, cancer tests with animals, and what the future holds in terms of the use of animal models as an aid to understanding human disease. In terms of early use of animal models, there was a school of rabbis, some of whom were also physicians, in Babylon who studied and wrote extensively on ritual slaughter and the suitability of birds and beasts for food. Considerable detailed information on animal pathology, physiology, anatomy, and medicine in general can be found in the Soncino Babylonian Talmudic Translations. The 1906 edition of the "Jewish Encyclopedia," has been a rich resource. Although it has not been possible to establish what diseases of animals were studied and their relationship to the diseases of humans, there are fascinating clues to pursue, despite the fact that these were sterile years for research in medicine. The quotation from the Talmud is of interest: "The medical knowledge of the Talmudist was based upon tradition, the dissection of human bodies, observation of disease and experiments upon animals." A bright light in the lackluster years of medical research was provided by Galen, considered the originator of research in physiology and anatomy. His dissection of animals and work on apes and other lower animals were models for human anatomy and physiology and the bases for many treatises. Yet, Galen never seemed to suggest that animals could serve as models for human diseases. Most early physicians who can be considered to have been students of disease developed their medical knowledge by observing the sick under their care. 1 early medical investigator

  6. Sildenafil Reduces Insulin-Resistance in Human Endothelial Cells

    Science.gov (United States)

    Mammi, Caterina; Pastore, Donatella; Lombardo, Marco F.; Ferrelli, Francesca; Caprio, Massimiliano; Consoli, Claudia; Tesauro, Manfredi; Gatta, Lucia; Fini, Massimo; Federici, Massimo; Sbraccia, Paolo; Donadel, Giulia; Bellia, Alfonso; Rosano, Giuseppe M.; Fabbri, Andrea; Lauro, Davide

    2011-01-01

    Background The efficacy of Phosphodiesterase 5 (PDE5) inhibitors to re-establish endothelial function is reduced in diabetic patients. Recent evidences suggest that therapy with PDE5 inhibitors, i.e. sildenafil, may increase the expression of nitric oxide synthase (NOS) proteins in the heart and cardiomyocytes. In this study we analyzed the effect of sildenafil on endothelial cells in insulin resistance conditions in vitro. Methodology/Principal Findings Human umbilical vein endothelial cells (HUVECs) were treated with insulin in presence of glucose 30 mM (HG) and glucosamine 10 mM (Gluc-N) with or without sildenafil. Insulin increased the expression of PDE5 and eNOS mRNA assayed by Real time-PCR. Cytofluorimetric analysis showed that sildenafil significantly increased NO production in basal condition. This effect was partially inhibited by the PI3K inhibitor LY 294002 and completely inhibited by the NOS inhibitor L-NAME. Akt-1 and eNOS activation was reduced in conditions mimicking insulin resistance and completely restored by sildenafil treatment. Conversely sildenafil treatment can counteract this noxious effect by increasing NO production through eNOS activation and reducing oxidative stress induced by hyperglycaemia and glucosamine. Conclusions/Significance These data indicate that sildenafil might improve NOS activity of endothelial cells in insulin resistance conditions and suggest the potential therapeutic use of sildenafil for improving vascular function in diabetic patients. PMID:21297971

  7. Sildenafil reduces insulin-resistance in human endothelial cells.

    Directory of Open Access Journals (Sweden)

    Caterina Mammi

    Full Text Available BACKGROUND: The efficacy of Phosphodiesterase 5 (PDE5 inhibitors to re-establish endothelial function is reduced in diabetic patients. Recent evidences suggest that therapy with PDE5 inhibitors, i.e. sildenafil, may increase the expression of nitric oxide synthase (NOS proteins in the heart and cardiomyocytes. In this study we analyzed the effect of sildenafil on endothelial cells in insulin resistance conditions in vitro. METHODOLOGY/PRINCIPAL FINDINGS: Human umbilical vein endothelial cells (HUVECs were treated with insulin in presence of glucose 30 mM (HG and glucosamine 10 mM (Gluc-N with or without sildenafil. Insulin increased the expression of PDE5 and eNOS mRNA assayed by Real time-PCR. Cytofluorimetric analysis showed that sildenafil significantly increased NO production in basal condition. This effect was partially inhibited by the PI3K inhibitor LY 294002 and completely inhibited by the NOS inhibitor L-NAME. Akt-1 and eNOS activation was reduced in conditions mimicking insulin resistance and completely restored by sildenafil treatment. Conversely sildenafil treatment can counteract this noxious effect by increasing NO production through eNOS activation and reducing oxidative stress induced by hyperglycaemia and glucosamine. CONCLUSIONS/SIGNIFICANCE: These data indicate that sildenafil might improve NOS activity of endothelial cells in insulin resistance conditions and suggest the potential therapeutic use of sildenafil for improving vascular function in diabetic patients.

  8. [Melatonin reduces cortisol response to ACTH in humans].

    Science.gov (United States)

    Campino, Carmen; Valenzuela, Francisco; Arteaga, Eugenio; Torres-Farfán, Claudia; Trucco, Cristián; Velasco, Alfredo; Guzmán, Sergio; Serón-Ferré, María

    2008-11-01

    Melatonin receptors are widely distributed in human tissues but they have not been reported in human adrenal gland. To assess if the human adrenal gland expresses melatonin receptors and if melatonin affects cortisol response to ACTH in dexamethasone suppressed volunteers. Adrenal glands were obtained from 4 patients undergoing unilateral nephrectomy-adrenalectomy for renal cancer. Expression of mRNA MT1 and MT2 melatonin receptors was measured by Reverse TranscriPtase Polymerase Chain Reaction (RT-PCR). The effect of melatonin on the response to intravenous (i.v.) ACTH was tested (randomized cross-over, double-blind, placebo-controlled trial) in eight young healthy males pretreated with dexamethasone (1 mg) at 23:00 h. On the next day, at 08:00 h, an i.v. line was inserted, at 08:30 h, and after a blood sample, subjects ingested 6 mg melatonin or placebo. At 09:00 h, 1-24 ACTH (Cortrosyn, 1 microg/1.73 m2 body surface area) was injected, drawing samples at 0, 15, 30, 45 and 60 minutes after. Melatonin, cortisol, cortisone, progesterone, aldosterone, DHEA-S, testosterone and prolactin were measured by immunoassay. The four adrenal glands expressed only MT1 receptor mRNA. Melatonin ingestion reduced the cortisol response to ACTH from 14.6 +/- 1.45 microg/dl at 60 min in the placebo group to 10.8 +/- 1.2 microg/dl in the melatonin group (p melatonin receptor in the human adrenal, and the melatonin reduction of ACTH-stimulated cortisol production suggest a direct melatonin action on the adrenal gland.

  9. Optimization Model for Reducing Emissions of Greenhouse ...

    Science.gov (United States)

    The EPA Vehicle Greenhouse Gas (VGHG) model is used to apply various technologies to a defined set of vehicles in order to meet a specified GHG emission target, and to then calculate the costs and benefits of doing so. To facilitate its analysis of the costs and benefits of the control of GHG emissions from cars and trucks.

  10. ADAPTATION MODEL FOR REDUCING THE MANAGERIAL STRESS

    Directory of Open Access Journals (Sweden)

    VIOLETA GLIGOROVSKI

    2017-12-01

    Full Text Available Changes are an inseparable component of the company's life cycle and they can contribute to its essential growth in the future. The purpose of this paper is to explain managerial stress caused by implementation of changes and creating an adaptation model to decrease managerial stress. How much the manager will successfully lead the project for implementation of a change and how much they will manage to amortize stress among employees, mostly depends on their expertise, knowledge and skills to accurately and comprehensively inform and integrate the employees in the overall process. The adaptation model is actually a new approach and recommendation for managers for dealing with stress when the changes are implemented. Methodology. For this purpose, the data presented, in fact, were collected through a questionnaire that was submitted to 61 respondents/ managers. The data were measured using the Likert scale from 1 to 7. Namely, with the help of the Likert scale, quantification of stress was made in relation to the various variables that were identified as the most important for the researched issues. An adaption model (new approach for amortizing changes was created using the DIA Diagram application, to show the relations between manager and the relevant amortization approaches.

  11. Human interaction and cortisol: can human contact reduce stress for shelter dogs?

    Science.gov (United States)

    Coppola, Crista L; Grandin, Temple; Enns, R Mark

    2006-03-30

    Animal shelters are an extremely stressful environment for a dog, most specifically due to social isolation and novel surroundings. The stress response of dogs housed in this environment may be alleviated through human interaction shortly after arrival. During their second day in a public animal shelter, adult stray dogs were either engaged in a human contact session or not. The session involved taking the dog into an outdoor enclosure, playing with the dog, grooming, petting and reviewing basic obedience commands. Each dog interacted with a human for approximately 45 min. Salivary cortisol levels were examined from each dog on their 2nd, 3rd, 4th and 9th day of housing. Animals that engaged in a human contact session had lower cortisol levels on day 3 than animals that did not. Breed type, sex and age did not have an effect on cortisol levels on any day measured. A human interaction session can be beneficial to both animal welfare and adoption procedures. The current study not only utilized the human contact session as a treatment to reduce stress but also as a resource for individual temperament/personality information that could be later used to facilitate compatible adoptions. Human interaction may be an effective means of reducing the cortisol response of dogs in the aversive shelter environment.

  12. Sensitivity study of reduced models of the activated sludge process ...

    African Journals Online (AJOL)

    2009-08-07

    Aug 7, 2009 ... order to fit the reduced model behaviour to the real data for the process behaviour. Keywords: wastewater treatment, activated sludge process, reduced model, model parameters, sensitivity function, Matlab simulation. Introduction. The problem of effective and optimal control of wastewater treatment plants ...

  13. Human driven transitions in complex model ecosystems

    Science.gov (United States)

    Harfoot, Mike; Newbold, Tim; Tittinsor, Derek; Purves, Drew

    2015-04-01

    Human activities have been observed to be impacting ecosystems across the globe, leading to reduced ecosystem functioning, altered trophic and biomass structure and ultimately ecosystem collapse. Previous attempts to understand global human impacts on ecosystems have usually relied on statistical models, which do not explicitly model the processes underlying the functioning of ecosystems, represent only a small proportion of organisms and do not adequately capture complex non-linear and dynamic responses of ecosystems to perturbations. We use a mechanistic ecosystem model (1), which simulates the underlying processes structuring ecosystems and can thus capture complex and dynamic interactions, to investigate boundaries of complex ecosystems to human perturbation. We explore several drivers including human appropriation of net primary production and harvesting of animal biomass. We also present an analysis of the key interactions between biotic, societal and abiotic earth system components, considering why and how we might think about these couplings. References: M. B. J. Harfoot et al., Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model., PLoS Biol. 12, e1001841 (2014).

  14. Multiscale Reduced Order Modeling of Complex Multi-Bay Structures

    Science.gov (United States)

    2013-07-01

    modeled with 96,000 degrees of freedom within Nastran . Keywords: reduced order modeling, nonlinear geometric response, finite elements 2...deformations, i.e. exhibiting geometric nonlinearity, from finite element models generated using commercial codes (e.g. Nastran , Abaqus, DYNA3D), see...reduced order model of the 9-bay panel modeled within Nastran with 96,000 degrees of freedom. An excellent agreement between the nonlinear static

  15. Zebrafish models for human cancer.

    Science.gov (United States)

    Shive, H R

    2013-05-01

    For decades, the advancement of cancer research has relied on in vivo models for examining key processes in cancer pathogenesis, including neoplastic transformation, progression, and response to therapy. These studies, which have traditionally relied on rodent models, have engendered a vast body of scientific literature. Recently, experimental cancer researchers have embraced many new and alternative model systems, including the zebrafish (Danio rerio). The general benefits of the zebrafish model for laboratory investigation, such as cost, size, fecundity, and generation time, were quickly superseded by the discovery that zebrafish are amenable to a wide range of investigative techniques, many of which are difficult or impossible to perform in mammalian models. These advantages, coupled with the finding that many aspects of carcinogenesis are conserved in zebrafish as compared with humans, have firmly established a unique niche for the zebrafish model in comparative cancer research. This article introduces methods for generating cancer models in zebrafish and reviews a range of models that have been developed for specific cancer types.

  16. Human factors interventions to reduce human errors and improve productivity in maintenance tasks

    International Nuclear Information System (INIS)

    Isoda, Hachiro; Yasutake, J.Y.

    1992-01-01

    This paper describes work in progress to develop interventions to reduce human errors and increase maintenance productivity in nuclear power plants. The effort is part of a two-phased Human Factors research program being conducted jointly by the Central Research Institute of Electric Power Industry (CRIEPI) in Japan and the Electric Power Research Institute (EPRI) in the United States. The overall objective of this joint research program is to identify critical maintenance tasks and to develop, implement and evaluate interventions which have high potential for reducing human errors or increasing maintenance productivity. As a result of the Phase 1 effort, ten critical maintenance tasks were identified. For these tasks, over 25 candidate interventions were identified for potential development. After careful analysis, seven interventions were selected for development during Phase 2. This paper describes the methodology used to analyze and identify the most critical tasks, the process of identifying and developing selected interventions and some of the initial results. (author)

  17. Reducing Psychiatric Inpatient Readmissions Using an Organizational Change Model.

    Science.gov (United States)

    Molfenter, Todd; Connor, Tim; Ford, James H; Hyatt, John; Zimmerman, Dan

    2016-06-01

    Thirty-day hospital readmission rates have become a quality indicator for many regulators and payers, but published accounts of reducing these rates across a patient population are lacking. This article describes and evaluates the Wisconsin Mental Health Readmissions Project, which aimed to reduce psychiatric inpatient 30-day readmission rates in Wisconsin. Nineteen county human services boards representing 23 of Wisconsin's 72 counties and 61% of the state's residential admissions participated in a statewide quality improvement collaborative from January 1, 2010 to December 31, 2013. Participants applied a standardized organizational change model, called NIATx, in the context of a multicounty quality improvement collaborative to reduce 30-day readmission rates. Readmission rates were tracked through national and state databases, using 2009 as a baseline, and analyzed using a chi-square analysis to test the proportion of means. The study team compared readmission rates of Wisconsin counties that participated in the statewide collaborative with those that did not. Between 2009 and 2013, the 30-day readmission rates in Wisconsin declined significantly for counties that participated in the project when compared to those that did not (2009-2013) [Χ2(4) = 54.503, P < .001], based on a 2.5% decline for participants vs a 0.7% decline for nonparticipants. Reductions to behavioral health inpatient readmission rates beyond individual case examples have been difficult to document. This analysis evaluates a method that Wisconsin behavioral health providers applied as part of a multicounty program addressing readmission rates. The findings highlight quality improvement program design elements and interventions to consider in reducing inpatient behavioral health readmissions, as well as the need for further research on this complex systems issue.

  18. Effect of amniotic membrane to reduce postlaminectomy epidural adhesion on a rat model.

    Science.gov (United States)

    Choi, Hyu Jin; Kim, Kyoung Beom; Kwon, Young-Min

    2011-06-01

    Epidural fibrosis and adhesion are the main reasons for post-laminectomy sustained pain and functional disability. In this study, the authors investigate the effect of irradiated freeze-dried human amniotic membrane on reducing epidural adhesion after laminectomy on a rat model. A total of 20 rats were divided into two groups. The group A did not receive human amniotic membrane implantation after laminectomy and group B underwent human amniotic membrane implantation after laminectomy. Gross and microscopic findings were evaluated and compared at postoperative 1, 3 and 8 weeks. The amount of scar tissue and tenacity were reduced grossly in group of rats with human amniotic membrane implantation (group B). On a microscopic evaluation, there were less inflammatory cell infiltration and fibroblast proliferation in group B. This experimental study shows that implantation of irradiated freeze-dried human amniotic membrane reduce epidural fibrosis and adhesion after spinal laminectomy in a rat model.

  19. Magnesium Sulfate Only Slightly Reduces the Shivering Threshold in Humans

    Science.gov (United States)

    Wadhwa, Anupama; Sengupta, Papiya; Durrani, Jaleel; Akça, Ozan; Lenhardt, Rainer; Sessler, Daniel I.

    2005-01-01

    Background: Hypothermia may be an effective treatment for stroke or acute myocardial infarction; however, it provokes vigorous shivering, which causes potentially dangerous hemodynamic responses and prevents further hypothermia. Magnesium is an attractive antishivering agent because it is used for treatment of postoperative shivering and provides protection against ischemic injury in animal models. We tested the hypothesis that magnesium reduces the threshold (triggering core temperature) and gain of shivering without substantial sedation or muscle weakness. Methods: We studied nine healthy male volunteers (18-40 yr) on two randomly assigned treatment days: 1) Control and 2) Magnesium (80 mg·kg-1 followed by infusion at 2 g·h-1). Lactated Ringer's solution (4°C) was infused via a central venous catheter over a period of approximately 2 hours to decrease tympanic membrane temperature ≈1.5°C·h-1. A significant and persistent increase in oxygen consumption identified the threshold. The gain of shivering was determined by the slope of oxygen consumption vs. core temperature regression. Sedation was evaluated using verbal rating score (VRS, 0-10) and bispectral index of the EEG (BIS). Peripheral muscle strength was evaluated using dynamometry and spirometry. Data were analyzed using repeated-measures ANOVA; Pshivering threshold (36.3±0.4 [mean±SD] vs. 36.6±0.3°C, P=0.040). It did not affect the gain of shivering (Control: 437±289, Magnesium: 573±370 ml·min-1·°C-1, P=0.344). The magnesium bolus did not produce significant sedation or appreciably reduce muscle strength. Conclusions: Magnesium significantly reduced the shivering threshold; however, due to the modest absolute reduction, this finding is considered to be clinically unimportant for induction of therapeutic hypothermia. PMID:15749735

  20. Counseling and Human Sexuality: A Training Model.

    Science.gov (United States)

    Fyfe, Bill

    1980-01-01

    Presents a counseling and human sexuality course model that provides counselors with an information base in human sexuality and assists them in exploring the emotional aspects of sexuality. Human sexuality is a vital aspect of personal development. (Author)

  1. Small Habitat Commonality Reduces Cost for Human Mars Missions

    Science.gov (United States)

    Griffin, Brand N.; Lepsch, Roger; Martin, John; Howard, Robert; Rucker, Michelle; Zapata, Edgar; McCleskey, Carey; Howe, Scott; Mary, Natalie; Nerren, Philip (Inventor)

    2015-01-01

    Most view the Apollo Program as expensive. It was. But, a human mission to Mars will be orders of magnitude more difficult and costly. Recently, NASA's Evolvable Mars Campaign (EMC) mapped out a step-wise approach for exploring Mars and the Mars-moon system. It is early in the planning process but because approximately 80% of the total life cycle cost is committed during preliminary design, there is an effort to emphasize cost reduction methods up front. Amongst the options, commonality across small habitat elements shows promise for consolidating the high bow-wave costs of Design, Development, Test and Evaluation (DDT&E) while still accommodating each end-item's functionality. In addition to DDT&E, there are other cost and operations benefits to commonality such as reduced logistics, simplified infrastructure integration and with inter-operability, improved safety and simplified training. These benefits are not without a cost. Some habitats are sub-optimized giving up unique attributes for the benefit of the overall architecture and because the first item sets the course for those to follow, rapidly developing technology may be excluded. The small habitats within the EMC include the pressurized crew cabins for the ascent vehicle,

  2. Autonomous exoskeleton reduces metabolic cost of human walking.

    Science.gov (United States)

    Mooney, Luke M; Rouse, Elliott J; Herr, Hugh M

    2014-11-03

    Passive exoskeletons that assist with human locomotion are often lightweight and compact, but are unable to provide net mechanical power to the exoskeletal wearer. In contrast, powered exoskeletons often provide biologically appropriate levels of mechanical power, but the size and mass of their actuator/power source designs often lead to heavy and unwieldy devices. In this study, we extend the design and evaluation of a lightweight and powerful autonomous exoskeleton evaluated for loaded walking in (J Neuroeng Rehab 11:80, 2014) to the case of unloaded walking conditions. The metabolic energy consumption of seven study participants (85 ± 12 kg body mass) was measured while walking on a level treadmill at 1.4 m/s. Testing conditions included not wearing the exoskeleton and wearing the exoskeleton, in both powered and unpowered modes. When averaged across the gait cycle, the autonomous exoskeleton applied a mean positive mechanical power of 26 ± 1 W (13 W per ankle) with 2.12 kg of added exoskeletal foot-shank mass (1.06 kg per leg). Use of the leg exoskeleton significantly reduced the metabolic cost of walking by 35 ± 13 W, which was an improvement of 10 ± 3% (p = 0.023) relative to the control condition of not wearing the exoskeleton. The results of this study highlight the advantages of developing lightweight and powerful exoskeletons that can comfortably assist the body during walking.

  3. Wall Shear Stress Distribution in a Patient-Specific Cerebral Aneurysm Model using Reduced Order Modeling

    Science.gov (United States)

    Han, Suyue; Chang, Gary Han; Schirmer, Clemens; Modarres-Sadeghi, Yahya

    2016-11-01

    We construct a reduced-order model (ROM) to study the Wall Shear Stress (WSS) distributions in image-based patient-specific aneurysms models. The magnitude of WSS has been shown to be a critical factor in growth and rupture of human aneurysms. We start the process by running a training case using Computational Fluid Dynamics (CFD) simulation with time-varying flow parameters, such that these parameters cover the range of parameters of interest. The method of snapshot Proper Orthogonal Decomposition (POD) is utilized to construct the reduced-order bases using the training CFD simulation. The resulting ROM enables us to study the flow patterns and the WSS distributions over a range of system parameters computationally very efficiently with a relatively small number of modes. This enables comprehensive analysis of the model system across a range of physiological conditions without the need to re-compute the simulation for small changes in the system parameters.

  4. A Reduced Wind Power Grid Model for Research and Education

    DEFF Research Database (Denmark)

    Akhmatov, Vladislav; Lund, Torsten; Hansen, Anca Daniela

    2007-01-01

    A reduced grid model of a transmission system with a number of central power plants, consumption centers, local wind turbines and a large offshore wind farm is developed and implemented in the simulation tool PowerFactory (DIgSILENT). The reduced grid model is given by Energinet.dk, Transmission...

  5. Modeling Forces on the Human Body.

    Science.gov (United States)

    Pagonis, Vasilis; Drake, Russel; Morgan, Michael; Peters, Todd; Riddle, Chris; Rollins, Karen

    1999-01-01

    Presents five models of the human body as a mechanical system which can be used in introductory physics courses: human arms as levers, humans falling from small heights, a model of the human back, collisions during football, and the rotating gymnast. Gives ideas for discussions and activities, including Interactive Physics (TM) simulations. (WRM)

  6. 76 FR 58517 - Public Health Service Guideline for Reducing Transmission of Human Immunodeficiency Virus (HIV...

    Science.gov (United States)

    2011-09-21

    ...-2011-0011] Public Health Service Guideline for Reducing Transmission of Human Immunodeficiency Virus... public comment on the draft Public Health Service Guideline for Reducing Transmission of Human..., Attn: Public Health Service Guideline for Reducing Transmission of Human Immunodeficiency Virus (HIV...

  7. A reduced order model of a quadruped walking system

    International Nuclear Information System (INIS)

    Sano, Akihito; Furusho, Junji; Naganuma, Nobuyuki

    1990-01-01

    Trot walking has recently been studied by several groups because of its stability and realizability. In the trot, diagonally opposed legs form pairs. While one pair of legs provides support, the other pair of legs swings forward in preparation for the next step. In this paper, we propose a reduced order model for the trot walking. The reduced order model is derived by using two dominant modes of the closed loop system in which the local feedback at each joint is implemented. It is shown by numerical examples that the obtained reduced order model can well approximate the original higher order model. (author)

  8. Massage increases oxytocin and reduces adrenocorticotropin hormone in humans.

    Science.gov (United States)

    Morhenn, Vera; Beavin, Laura E; Zak, Paul J

    2012-01-01

    Human beings are highly social creatures who often touch each other during social interactions. Although the physiologic effects of touch are not understood fully, it appears to sustain social bonds and to increase cooperative behaviors. Oxytocin (OT) is a hormone known to facilitate social bonding, and touch may affect OT release. Previous studies seeking to relate massage and oxytocin in humans have been inconsistent in their findings. This study examined the effect of massage on oxytocin and also measured its effect on other physiologic factors, including adrenocorticotropin hormone (ACTH), nitric oxide (NO), and beta-endorphin (BE). The research team advertised that the trial would study relaxation and assigned participants randomly to the intervention or the control group. A lab administrator assigned a random numeric code to participants to mask their identities. The study took place at the University of California Los Angeles (UCLA), Los Angeles, CA. Ninety-five people from UCLA gave written informed consent for participation in the study, with the team paying them to participate. The intervention group included 65 participants and the control group 30 participants. For the intervention (massage) group, the research team drew participants' blood and followed the blood draw with 15 minutes of moderate-pressure massage of the upper back. The control (rest) group rested quietly for 15 minutes after the blood draw. A second blood draw followed for both groups. The research team assayed OT, ACTH, NO, and BE. The team used four survey instruments to examine the relationship between personality factors and the physiologic measures of interest. The team analyzed data using SPSS 15.0 for Windows. Massage was associated with an increase in OT and reductions in ACTH, NO, and BE. Comparing the effects of massage for the massage group with those for the rest group, the research team found significant differences between groups for changes in OT, ACTH, NO, and BE. This

  9. Vicarious Learning from Human Models in Monkeys

    OpenAIRE

    Falcone, Rossella; Brunamonti, Emiliano; Genovesio, Aldo

    2012-01-01

    We examined whether monkeys can learn by observing a human model, through vicarious learning. Two monkeys observed a human model demonstrating an object-reward association and consuming food found underneath an object. The monkeys observed human models as they solved more than 30 learning problems. For each problem, the human models made a choice between two objects, one of which concealed a piece of apple. In the test phase afterwards, the monkeys made a choice of their own. Learning was app...

  10. Deformable human body model development

    Energy Technology Data Exchange (ETDEWEB)

    Wray, W.O.; Aida, T.

    1998-11-01

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). A Deformable Human Body Model (DHBM) capable of simulating a wide variety of deformation interactions between man and his environment has been developed. The model was intended to have applications in automobile safety analysis, soldier survivability studies and assistive technology development for the disabled. To date, we have demonstrated the utility of the DHBM in automobile safety analysis and are currently engaged in discussions with the U.S. military involving two additional applications. More specifically, the DHBM has been incorporated into a Virtual Safety Lab (VSL) for automobile design under contract to General Motors Corporation. Furthermore, we have won $1.8M in funding from the U.S. Army Medical Research and Material Command for development of a noninvasive intracranial pressure measurement system. The proposed research makes use of the detailed head model that is a component of the DHBM; the project duration is three years. In addition, we have been contacted by the Air Force Armstrong Aerospace Medical Research Laboratory concerning possible use of the DHBM in analyzing the loads and injury potential to pilots upon ejection from military aircraft. Current discussions with Armstrong involve possible LANL participation in a comparison between DHBM and the Air Force Articulated Total Body (ATB) model that is the current military standard.

  11. Human responses to augmented virtual scaffolding models.

    Science.gov (United States)

    Hsiao, Hongwei; Simeonov, Peter; Dotson, Brian; Ammons, Douglas; Kau, Tsui-Ying; Chiou, Sharon

    2005-08-15

    This study investigated the effect of adding real planks, in virtual scaffolding models of elevation, on human performance in a surround-screen virtual reality (SSVR) system. Twenty-four construction workers and 24 inexperienced controls performed walking tasks on real and virtual planks at three virtual heights (0, 6 m, 12 m) and two scaffolding-platform-width conditions (30, 60 cm). Gait patterns, walking instability measurements and cardiovascular reactivity were assessed. The results showed differences in human responses to real vs. virtual planks in walking patterns, instability score and heart-rate inter-beat intervals; it appeared that adding real planks in the SSVR virtual scaffolding model enhanced the quality of SSVR as a human - environment interface research tool. In addition, there were significant differences in performance between construction workers and the control group. The inexperienced participants were more unstable as compared to construction workers. Both groups increased their stride length with repetitions of the task, indicating a possibly confidence- or habit-related learning effect. The practical implications of this study are in the adoption of augmented virtual models of elevated construction environments for injury prevention research, and the development of programme for balance-control training to reduce the risk of falls at elevation before workers enter a construction job.

  12. Vicarious learning from human models in monkeys.

    Science.gov (United States)

    Falcone, Rossella; Brunamonti, Emiliano; Genovesio, Aldo

    2012-01-01

    We examined whether monkeys can learn by observing a human model, through vicarious learning. Two monkeys observed a human model demonstrating an object-reward association and consuming food found underneath an object. The monkeys observed human models as they solved more than 30 learning problems. For each problem, the human models made a choice between two objects, one of which concealed a piece of apple. In the test phase afterwards, the monkeys made a choice of their own. Learning was apparent from the first trial of the test phase, confirming the ability of monkeys to learn by vicarious observation of human models.

  13. Vicarious learning from human models in monkeys.

    Directory of Open Access Journals (Sweden)

    Rossella Falcone

    Full Text Available We examined whether monkeys can learn by observing a human model, through vicarious learning. Two monkeys observed a human model demonstrating an object-reward association and consuming food found underneath an object. The monkeys observed human models as they solved more than 30 learning problems. For each problem, the human models made a choice between two objects, one of which concealed a piece of apple. In the test phase afterwards, the monkeys made a choice of their own. Learning was apparent from the first trial of the test phase, confirming the ability of monkeys to learn by vicarious observation of human models.

  14. Human Performance Modeling for Dynamic Human Reliability Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Boring, Ronald Laurids [Idaho National Laboratory; Joe, Jeffrey Clark [Idaho National Laboratory; Mandelli, Diego [Idaho National Laboratory

    2015-08-01

    Part of the U.S. Department of Energy’s (DOE’s) Light Water Reac- tor Sustainability (LWRS) Program, the Risk-Informed Safety Margin Charac- terization (RISMC) Pathway develops approaches to estimating and managing safety margins. RISMC simulations pair deterministic plant physics models with probabilistic risk models. As human interactions are an essential element of plant risk, it is necessary to integrate human actions into the RISMC risk framework. In this paper, we review simulation based and non simulation based human reliability analysis (HRA) methods. This paper summarizes the founda- tional information needed to develop a feasible approach to modeling human in- teractions in RISMC simulations.

  15. Human papilloma virus DNAs immortalize normal human mammary epithelial cells and reduce their growth factor requirements

    Energy Technology Data Exchange (ETDEWEB)

    Band, V.; Zajchowski, D.; Kulesa, V.; Sager, R. (Dana-Farber Cancer Institute, Boston, MA (USA))

    1990-01-01

    Human papilloma virus (HPV) types 16 and 18 are most commonly associated with cervical carcinoma in patients and induce immortalization of human keratinocytes in culture. HPV has not been associated with breast cancer. This report describes the immortalization of normal human mammary epithelial cells (76N) by plasmid pHPV18 or pHPV16, each containing the linearized viral genome. Transfectants were grown continuously for more than 60 passages, whereas 76N cells senesce after 18-20 passages. The transfectants also differ from 76N cells in cloning in a completely defined medium called D2 and growing a minimally supplemented defined medium (D3) containing epidermal growth factor. All transfectant tested contain integrated HPV DNA, express HPV RNA, and produce HPV E7 protein. HPV transfectants do not form tumors in a nude mouse assay. It is concluded that products of the HPV genome induce immortalization of human breast epithelial cells and reduce their growth factor requirements. This result raises the possibility that HPV might be involved in breast cancer. Furthermore, other tissue-specific primary epithelial cells that are presently difficult to grown and investigate may also be immortalized by HPV.

  16. Dengue human infection models supporting drug development.

    Science.gov (United States)

    Whitehorn, James; Van, Vinh Chau Nguyen; Simmons, Cameron P

    2014-06-15

    Dengue is a arboviral infection that represents a major global health burden. There is an unmet need for effective dengue therapeutics to reduce symptoms, duration of illness and incidence of severe complications. Here, we consider the merits of a dengue human infection model (DHIM) for drug development. A DHIM could allow experimentally controlled studies of candidate therapeutics in preselected susceptible volunteers, potentially using smaller sample sizes than trials that recruited patients with dengue in an endemic country. In addition, the DHIM would assist the conduct of intensive pharmacokinetic and basic research investigations and aid in determining optimal drug dosage. Furthermore, a DHIM could help establish proof of concept that chemoprophylaxis against dengue is feasible. The key challenge in developing the DHIM for drug development is to ensure the model reliably replicates the typical clinical and laboratory features of naturally acquired, symptomatic dengue. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  17. Crowd Human Behavior for Modeling and Simulation

    Science.gov (United States)

    2009-08-06

    Crowd Human Behavior for Modeling and Simulation Elizabeth Mezzacappa, Ph.D. & Gordon Cooke, MEME Target Behavioral Response Laboratory, ARDEC...TYPE Conference Presentation 3. DATES COVERED 00-00-2008 to 00-00-2009 4. TITLE AND SUBTITLE Crowd Human Behavior for Modeling and Simulation...34understanding human behavior " and "model validation and verification" and will focus on modeling and simulation of crowds from a social scientist???s

  18. Hazards caused by human failure and measures to reduce them

    International Nuclear Information System (INIS)

    Hartmann, W.; Hartmann, L.

    1985-01-01

    The safety engineer's method of thinking is discussed especially in the context of a nuclear power plant. The importance of human and medical factors in safety is stressed. A comparison with safety measures in the chemical industry is given

  19. Biomechanical Modeling of the Human Head

    Science.gov (United States)

    2017-10-03

    Experimental Animal Models for Studies on the Mechanisms of Blast- Induced Neurotrauma,” Frontiers in Neurology 3, 30 (2012). 13. R. A. Bauman, G. Ling...modeling, of both humans and animals , has gained momentum for the investigation of traumatic brain injury. These models require both accurate geometric...between model predictions and experimental data. This report details model calibration for all materials identified in models of a human head and

  20. Isometric exercises reduce temporal summation of pressure pain in humans

    DEFF Research Database (Denmark)

    Vaegter, H B; Handberg, G; Graven-Nielsen, T

    2015-01-01

    tolerance (PTT) and reduce TSP with greater effects after higher-intensity exercises. METHODS: One hundred thirty-six healthy subjects (18-65 years; 68 women) participated in two randomized crossover experiments with trials on two different days. PTT and TSP were assessed before and after bicycling...... when assessed at the leg (p reduced VAS scores to sequential stimulation at the arm and leg (p ... of hypoalgesia between aerobic and isometric exercises were found. Isometric exercises reduced temporal summation illustrating the potential for exercise as a rehabilitation procedure also targeting the central mechanisms....

  1. Reduced order modeling of some fluid flows of industrial interest

    International Nuclear Information System (INIS)

    Alonso, D; Terragni, F; Velazquez, A; Vega, J M

    2012-01-01

    Some basic ideas are presented for the construction of robust, computationally efficient reduced order models amenable to be used in industrial environments, combined with somewhat rough computational fluid dynamics solvers. These ideas result from a critical review of the basic principles of proper orthogonal decomposition-based reduced order modeling of both steady and unsteady fluid flows. In particular, the extent to which some artifacts of the computational fluid dynamics solvers can be ignored is addressed, which opens up the possibility of obtaining quite flexible reduced order models. The methods are illustrated with the steady aerodynamic flow around a horizontal tail plane of a commercial aircraft in transonic conditions, and the unsteady lid-driven cavity problem. In both cases, the approximations are fairly good, thus reducing the computational cost by a significant factor. (review)

  2. Reduced order modeling of some fluid flows of industrial interest

    Energy Technology Data Exchange (ETDEWEB)

    Alonso, D; Terragni, F; Velazquez, A; Vega, J M, E-mail: josemanuel.vega@upm.es [E.T.S.I. Aeronauticos, Universidad Politecnica de Madrid, 28040 Madrid (Spain)

    2012-06-01

    Some basic ideas are presented for the construction of robust, computationally efficient reduced order models amenable to be used in industrial environments, combined with somewhat rough computational fluid dynamics solvers. These ideas result from a critical review of the basic principles of proper orthogonal decomposition-based reduced order modeling of both steady and unsteady fluid flows. In particular, the extent to which some artifacts of the computational fluid dynamics solvers can be ignored is addressed, which opens up the possibility of obtaining quite flexible reduced order models. The methods are illustrated with the steady aerodynamic flow around a horizontal tail plane of a commercial aircraft in transonic conditions, and the unsteady lid-driven cavity problem. In both cases, the approximations are fairly good, thus reducing the computational cost by a significant factor. (review)

  3. Sensitivity study of reduced models of the activated sludge process ...

    African Journals Online (AJOL)

    The problem of derivation and calculation of sensitivity functions for all parameters of the mass balance reduced model of the COST benchmark activated sludge plant is formulated and solved. The sensitivity functions, equations and augmented sensitivity state space models are derived for the cases of ASM1 and UCT ...

  4. Bilinear reduced order approximate model of parabolic distributed solar collectors

    KAUST Repository

    Elmetennani, Shahrazed

    2015-07-01

    This paper proposes a novel, low dimensional and accurate approximate model for the distributed parabolic solar collector, by means of a modified gaussian interpolation along the spatial domain. The proposed reduced model, taking the form of a low dimensional bilinear state representation, enables the reproduction of the heat transfer dynamics along the collector tube for system analysis. Moreover, presented as a reduced order bilinear state space model, the well established control theory for this class of systems can be applied. The approximation efficiency has been proven by several simulation tests, which have been performed considering parameters of the Acurex field with real external working conditions. Model accuracy has been evaluated by comparison to the analytical solution of the hyperbolic distributed model and its semi discretized approximation highlighting the benefits of using the proposed numerical scheme. Furthermore, model sensitivity to the different parameters of the gaussian interpolation has been studied.

  5. Reducing Human Radiation Risks on Deep Space Missions

    Science.gov (United States)

    2017-09-01

    Clinical Biochemistry and Nutrition 50(1): 2–8. doi:10.3164/jcbn.D-11-00021. Barcellos-Hoff, Mary Helen, Eleanor A. Blakely, Sandeep Burma, Albert J...Assurance. 156 Drake, Bret G, Stephen J Hoffman , and Kevin D Watts. 2009. Human Exploration of Mars Design Reference Architecture 5.0 Addendum. NASA

  6. Humanized mouse model for assessing the human immune response to xenogeneic and allogeneic decellularized biomaterials.

    Science.gov (United States)

    Wang, Raymond M; Johnson, Todd D; He, Jingjin; Rong, Zhili; Wong, Michelle; Nigam, Vishal; Behfar, Atta; Xu, Yang; Christman, Karen L

    2017-06-01

    Current assessment of biomaterial biocompatibility is typically implemented in wild type rodent models. Unfortunately, different characteristics of the immune systems in rodents versus humans limit the capability of these models to mimic the human immune response to naturally derived biomaterials. Here we investigated the utility of humanized mice as an improved model for testing naturally derived biomaterials. Two injectable hydrogels derived from decellularized porcine or human cadaveric myocardium were compared. Three days and one week after subcutaneous injection, the hydrogels were analyzed for early and mid-phase immune responses, respectively. Immune cells in the humanized mouse model, particularly T-helper cells, responded distinctly between the xenogeneic and allogeneic biomaterials. The allogeneic extracellular matrix derived hydrogels elicited significantly reduced total, human specific, and CD4 + T-helper cell infiltration in humanized mice compared to xenogeneic extracellular matrix hydrogels, which was not recapitulated in wild type mice. T-helper cells, in response to the allogeneic hydrogel material, were also less polarized towards a pro-remodeling Th2 phenotype compared to xenogeneic extracellular matrix hydrogels in humanized mice. In both models, both biomaterials induced the infiltration of macrophages polarized towards a M2 phenotype and T-helper cells polarized towards a Th2 phenotype. In conclusion, these studies showed the importance of testing naturally derived biomaterials in immune competent animals and the potential of utilizing this humanized mouse model for further studying human immune cell responses to biomaterials in an in vivo environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Transgenic Mouse Model for Reducing Oxidative Damage in Bone

    Science.gov (United States)

    Schreurs, Ann-Sofie; Torres, S.; Truong, T.; Moyer, E. L.; Kumar, A.; Tahimic, Candice C. G.; Alwood, J. S.; Limoli, C. L.; Globus, R. K.

    2016-01-01

    Bone loss can occur due to many challenges such age, radiation, microgravity, and Reactive Oxygen Species (ROS) play a critical role in bone resorption by osteoclasts (Bartell et al. 2014). We hypothesize that suppression of excess ROS in skeletal cells, both osteoblasts and osteoclasts, regulates skeletal growth and remodeling. To test our hypothesis, we used transgenic mCAT mice which overexpress the human anti-oxidant catalase gene targeted to the mitochondria, the main site for endogenous ROS production. mCAT mice have a longer life-span than wildtype controls and have been used to study various age-related disorders. To stimulate remodeling, 16 week old mCAT mice or wildtype mice were exposed to treatment (hindlimb-unloading and total body-irradiation) or sham treatment conditions (control). Tissues were harvested 2 weeks later for skeletal analysis (microcomputed tomography), biochemical analysis (gene expression and oxidative damage measurements), and ex vivo bone marrow derived cell culture (osteoblastogenesis and osteoclastogenesis). mCAT mice expressed the transgene and displayed elevated catalase activity in skeletal tissue and marrow-derived osteoblasts and osteoclasts grown ex vivo. In addition, when challenged with treatment, bone tissues from wildtype mice showed elevated levels of malondialdehyde (MDA), indicating oxidative damage) whereas mCAT mice did not. Correlation analysis revealed that increased catalase activity significantly correlated with decreased MDA levels and that increased oxidative damage correlated with decreased percent bone volume (BVTV). In addition, ex-vivo cultured osteoblast colony growth correlated with catalase activity in the osteoblasts. Thus, we showed that these transgenic mice can be used as a model to study the relationship between markers of oxidative damage and skeletal properties. mCAT mice displayed reduced BVTV and trabecular number relative to wildtype mice, as well as increased structural model index in the

  8. In-Situ Residual Tracking in Reduced Order Modelling

    Directory of Open Access Journals (Sweden)

    Joseph C. Slater

    2002-01-01

    Full Text Available Proper orthogonal decomposition (POD based reduced-order modelling is demonstrated to be a weighted residual technique similar to Galerkin's method. Estimates of weighted residuals of neglected modes are used to determine relative importance of neglected modes to the model. The cumulative effects of neglected modes can be used to estimate error in the reduced order model. Thus, once the snapshots have been obtained under prescribed training conditions, the need to perform full-order simulations for comparison is eliminates. This has the potential to allow the analyst to initiate further training when the reduced modes are no longer sufficient to accurately represent the predominant phenomenon of interest. The response of a fluid moving at Mach 1.2 above a panel to a forced localized oscillation of the panel at and away from the training operating conditions is used to demonstrate the evaluation method.

  9. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

    Science.gov (United States)

    Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

    2015-02-01

    During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

  10. Cerebral oxygenation is reduced during hyperthermic exercise in humans

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Nybo, Lars; Volianitis, S.

    2010-01-01

    (CBF). Heat stress challenges exercise capacity as expressed by increased rating of perceived exertion (RPE). Methods: This study evaluated the effect of heat stress during exercise on P(mito)O(2) calculated based on a Kety-Schmidt-determined CBF and the arterial-to-jugular venous oxygen differences...... was reduced by 15 +/- 13% (P exercise with heat stress, RPE increased to 19 (19-20; P exercise in the heat lowers cerebral P(mito)O(2), and that exercise capacity......Abstract Aim: Cerebral mitochondrial oxygen tension (P(mito)O(2)) is elevated during moderate exercise, while it is reduced when exercise becomes strenuous, reflecting an elevated cerebral metabolic rate for oxygen (CMRO(2)) combined with hyperventilation-induced attenuation of cerebral blood flow...

  11. On scaling of human body models

    Directory of Open Access Journals (Sweden)

    Hynčík L.

    2007-10-01

    Full Text Available Human body is not an unique being, everyone is another from the point of view of anthropometry and mechanical characteristics which means that division of the human body population to categories like 5%-tile, 50%-tile and 95%-tile from the application point of view is not enough. On the other hand, the development of a particular human body model for all of us is not possible. That is why scaling and morphing algorithms has started to be developed. The current work describes the development of a tool for scaling of the human models. The idea is to have one (or couple of standard model(s as a base and to create other models based on these basic models. One has to choose adequate anthropometrical and biomechanical parameters that describe given group of humans to be scaled and morphed among.

  12. Reverse time migration by Krylov subspace reduced order modeling

    Science.gov (United States)

    Basir, Hadi Mahdavi; Javaherian, Abdolrahim; Shomali, Zaher Hossein; Firouz-Abadi, Roohollah Dehghani; Gholamy, Shaban Ali

    2018-04-01

    Imaging is a key step in seismic data processing. To date, a myriad of advanced pre-stack depth migration approaches have been developed; however, reverse time migration (RTM) is still considered as the high-end imaging algorithm. The main limitations associated with the performance cost of reverse time migration are the intensive computation of the forward and backward simulations, time consumption, and memory allocation related to imaging condition. Based on the reduced order modeling, we proposed an algorithm, which can be adapted to all the aforementioned factors. Our proposed method benefit from Krylov subspaces method to compute certain mode shapes of the velocity model computed by as an orthogonal base of reduced order modeling. Reverse time migration by reduced order modeling is helpful concerning the highly parallel computation and strongly reduces the memory requirement of reverse time migration. The synthetic model results showed that suggested method can decrease the computational costs of reverse time migration by several orders of magnitudes, compared with reverse time migration by finite element method.

  13. Computer modeling of human decision making

    Science.gov (United States)

    Gevarter, William B.

    1991-01-01

    Models of human decision making are reviewed. Models which treat just the cognitive aspects of human behavior are included as well as models which include motivation. Both models which have associated computer programs, and those that do not, are considered. Since flow diagrams, that assist in constructing computer simulation of such models, were not generally available, such diagrams were constructed and are presented. The result provides a rich source of information, which can aid in construction of more realistic future simulations of human decision making.

  14. Human Performance Models of Pilot Behavior

    Science.gov (United States)

    Foyle, David C.; Hooey, Becky L.; Byrne, Michael D.; Deutsch, Stephen; Lebiere, Christian; Leiden, Ken; Wickens, Christopher D.; Corker, Kevin M.

    2005-01-01

    Five modeling teams from industry and academia were chosen by the NASA Aviation Safety and Security Program to develop human performance models (HPM) of pilots performing taxi operations and runway instrument approaches with and without advanced displays. One representative from each team will serve as a panelist to discuss their team s model architecture, augmentations and advancements to HPMs, and aviation-safety related lessons learned. Panelists will discuss how modeling results are influenced by a model s architecture and structure, the role of the external environment, specific modeling advances and future directions and challenges for human performance modeling in aviation.

  15. Reduced Models in Chemical Kinetics via Nonlinear Data-Mining

    Directory of Open Access Journals (Sweden)

    Eliodoro Chiavazzo

    2014-01-01

    Full Text Available The adoption of detailed mechanisms for chemical kinetics often poses two types of severe challenges: First, the number of degrees of freedom is large; and second, the dynamics is characterized by widely disparate time scales. As a result, reactive flow solvers with detailed chemistry often become intractable even for large clusters of CPUs, especially when dealing with direct numerical simulation (DNS of turbulent combustion problems. This has motivated the development of several techniques for reducing the complexity of such kinetics models, where, eventually, only a few variables are considered in the development of the simplified model. Unfortunately, no generally applicable a priori recipe for selecting suitable parameterizations of the reduced model is available, and the choice of slow variables often relies upon intuition and experience. We present an automated approach to this task, consisting of three main steps. First, the low dimensional manifold of slow motions is (approximately sampled by brief simulations of the detailed model, starting from a rich enough ensemble of admissible initial conditions. Second, a global parametrization of the manifold is obtained through the Diffusion Map (DMAP approach, which has recently emerged as a powerful tool in data analysis/machine learning. Finally, a simplified model is constructed and solved on the fly in terms of the above reduced (slow variables. Clearly, closing this latter model requires nontrivial interpolation calculations, enabling restriction (mapping from the full ambient space to the reduced one and lifting (mapping from the reduced space to the ambient one. This is a key step in our approach, and a variety of interpolation schemes are reported and compared. The scope of the proposed procedure is presented and discussed by means of an illustrative combustion example.

  16. AN OVERVIEW OF REDUCED ORDER MODELING TECHNIQUES FOR SAFETY APPLICATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Mandelli, D.; Alfonsi, A.; Talbot, P.; Wang, C.; Maljovec, D.; Smith, C.; Rabiti, C.; Cogliati, J.

    2016-10-01

    The RISMC project is developing new advanced simulation-based tools to perform Computational Risk Analysis (CRA) for the existing fleet of U.S. nuclear power plants (NPPs). These tools numerically model not only the thermal-hydraulic behavior of the reactors primary and secondary systems, but also external event temporal evolution and component/system ageing. Thus, this is not only a multi-physics problem being addressed, but also a multi-scale problem (both spatial, µm-mm-m, and temporal, seconds-hours-years). As part of the RISMC CRA approach, a large amount of computationally-expensive simulation runs may be required. An important aspect is that even though computational power is growing, the overall computational cost of a RISMC analysis using brute-force methods may be not viable for certain cases. A solution that is being evaluated to assist the computational issue is the use of reduced order modeling techniques. During the FY2015, we investigated and applied reduced order modeling techniques to decrease the RISMC analysis computational cost by decreasing the number of simulation runs; for this analysis improvement we used surrogate models instead of the actual simulation codes. This article focuses on the use of reduced order modeling techniques that can be applied to RISMC analyses in order to generate, analyze, and visualize data. In particular, we focus on surrogate models that approximate the simulation results but in a much faster time (microseconds instead of hours/days).

  17. Robust simulation of buckled structures using reduced order modeling

    International Nuclear Information System (INIS)

    Wiebe, R.; Perez, R.A.; Spottswood, S.M.

    2016-01-01

    Lightweight metallic structures are a mainstay in aerospace engineering. For these structures, stability, rather than strength, is often the critical limit state in design. For example, buckling of panels and stiffeners may occur during emergency high-g maneuvers, while in supersonic and hypersonic aircraft, it may be induced by thermal stresses. The longstanding solution to such challenges was to increase the sizing of the structural members, which is counter to the ever present need to minimize weight for reasons of efficiency and performance. In this work we present some recent results in the area of reduced order modeling of post- buckled thin beams. A thorough parametric study of the response of a beam to changing harmonic loading parameters, which is useful in exposing complex phenomena and exercising numerical models, is presented. Two error metrics that use but require no time stepping of a (computationally expensive) truth model are also introduced. The error metrics are applied to several interesting forcing parameter cases identified from the parametric study and are shown to yield useful information about the quality of a candidate reduced order model. Parametric studies, especially when considering forcing and structural geometry parameters, coupled environments, and uncertainties would be computationally intractable with finite element models. The goal is to make rapid simulation of complex nonlinear dynamic behavior possible for distributed systems via fast and accurate reduced order models. This ability is crucial in allowing designers to rigorously probe the robustness of their designs to account for variations in loading, structural imperfections, and other uncertainties. (paper)

  18. Animal models for human genetic diseases

    African Journals Online (AJOL)

    Sharif Sons

    to be the prime model of inherited human disease and share 99% of their ... disturbances (including anxiety and depression) ..... Leibovici M, Safieddine S, Petit C (2008). Mouse models for human hereditary deafness. Curr. Top. Dev. Biol. 84:385-429. Levi YF, Meiner Z, Canello T, Frid K, Kovacs GG, Budka H, Avrahami.

  19. Effects of Peer Modelling Technique in Reducing Substance Abuse ...

    African Journals Online (AJOL)

    The study investigated the effects of peer modelling techniques in reducing substance abuse among undergraduates in Nigeria. The participants were one hundred and twenty (120) undergraduate students in 100 and 400 levels respectively. There are two groups: one treatment group and one control group.

  20. Reduced order modelling and predictive control of multivariable ...

    Indian Academy of Sciences (India)

    Anuj Abraham

    2018-03-16

    Mar 16, 2018 ... The performance of constraint generalized predictive control scheme is found to be superior to that of the conventional PID controller in terms of overshoot, settling time and performance indices, mainly ISE, IAE and MSE. Keywords. Predictive control; distillation column; reduced order model; dominant pole; ...

  1. Rapid Analysis Model: Reducing Analysis Time without Sacrificing Quality.

    Science.gov (United States)

    Lee, William W.; Owens, Diana

    2001-01-01

    Discusses the performance technology design process and the fact that the analysis phase is often being eliminated to speed up the process. Proposes a rapid analysis model that reduces time needed for analysis and still ensures more successful value-added solutions that focus on customer satisfaction. (LRW)

  2. On reducibility and ergodicity of population projection matrix models

    DEFF Research Database (Denmark)

    Stott, Iain; Townley, Stuart; Carslake, David

    2010-01-01

    1. Population projection matrices (PPMs) are probably the most commonly used empirical population models. To be useful for predictive or prospective analyses, PPM models should generally be irreducible (the associated life cycle graph contains the necessary transition rates to facilitate pathways...... structure used in the population projection). In our sample of published PPMs, 15·6% are non-ergodic. 3. This presents a problem: reducible–ergodic models often defy biological rationale in their description of the life cycle but may or may not prove problematic for analysis as they often behave similarly...... to irreducible models. Reducible–non-ergodic models will usually defy biological rationale in their description of the both the life cycle and population dynamics, hence contravening most analytical methods. 4. We provide simple methods to evaluate reducibility and ergodicity of PPM models, present illustrative...

  3. Establishing the Human Firewall: Reducing an Individual’s Vulnerability to Social Engineering Attacks

    Science.gov (United States)

    2008-03-01

    1988) Bolstering attitudes by autobiographical recall: Attitude persistence and selective memory . Personality and Social Psychology Bulletin, 14...ESTABLISHING THE HUMAN FIREWALL: REDUCING AN INDIVIDUAL’S VULNERABILITY TO SOCIAL ENGINEERING ATTACKS...AFIT/GIR/ENG/08-04 ESTABLISHING THE HUMAN FIREWALL: REDUCING AN INDIVIDUAL’S VULNERABILITY TO SOCIAL ENGINEERING THESIS Presented to the

  4. Hidden Markov Models for Human Genes

    DEFF Research Database (Denmark)

    Baldi, Pierre; Brunak, Søren; Chauvin, Yves

    1997-01-01

    We analyse the sequential structure of human genomic DNA by hidden Markov models. We apply models of widely different design: conventional left-right constructs and models with a built-in periodic architecture. The models are trained on segments of DNA sequences extracted such that they cover com...

  5. Automation of Commanding at NASA: Reducing Human Error in Space Flight

    Science.gov (United States)

    Dorn, Sarah J.

    2010-01-01

    Automation has been implemented in many different industries to improve efficiency and reduce human error. Reducing or eliminating the human interaction in tasks has been proven to increase productivity in manufacturing and lessen the risk of mistakes by humans in the airline industry. Human space flight requires the flight controllers to monitor multiple systems and react quickly when failures occur so NASA is interested in implementing techniques that can assist in these tasks. Using automation to control some of these responsibilities could reduce the number of errors the flight controllers encounter due to standard human error characteristics. This paper will investigate the possibility of reducing human error in the critical area of manned space flight at NASA.

  6. Human tissue models in cancer research: looking beyond the mouse.

    Science.gov (United States)

    Jackson, Samuel J; Thomas, Gareth J

    2017-08-01

    Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of 'non-animal human tissue' models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models. © 2017. Published by The Company of Biologists Ltd.

  7. Human tissue models in cancer research: looking beyond the mouse

    Directory of Open Access Journals (Sweden)

    Samuel J. Jackson

    2017-08-01

    Full Text Available Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of ‘non-animal human tissue’ models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models.

  8. Epigallocatechin gallate reduces human monocyte mobility and adhesion in vitro.

    Science.gov (United States)

    Melgarejo, Esther; Medina, Miguel Angel; Sánchez-Jiménez, Francisca; Urdiales, José Luis

    2009-12-01

    Monocytes/macrophages are an important population of immune inflammatory cells that have diverse effector functions in which their mobility and adhesion play a very relevant role. Epigallocatechin gallate (EGCG), a major component of green tea, has been reported to have anti-allergic and anti-inflammatory activities, but its effects on monocytes remain to be determined. Here we investigated the effects of EGCG on the migration and adhesion of monocytes. We used a human monocyte cell line (THP-1) to analyse the effects of treatment with EGCG under non-cytotoxic conditions on the expression levels of the monocyte chemotactic protein-1 (MCP-1) and of the MCP-1 receptor (CCR2) and on the activation of beta1 integrin. A functional validation was carried out by evaluating the inhibitory effect of EGCG on monocyte adhesiveness and migration in vitro. Treatment of THP-1 cells with EGCG decreased MCP-1 and CCR2 gene expression, together with MCP-1 secretion and CCR2 expression at the cell surface. EGCG also inhibited beta1 integrin activation. The effects on these molecular targets were in agreement with the EGCG-induced inhibition of THP-1 migration in response to MCP-1 and adhesion to fibronectin. Under our experimental conditions, EGCG treatment inhibited the migration and adhesion of monocytes. These inhibitory effects of EGCG on monocyte function should be considered as a promising new anti-inflammatory response with a potential therapeutic role in the treatment of inflammation-dependent diseases.

  9. Reduced Complexity Channel Models for IMT-Advanced Evaluation

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2009-01-01

    Full Text Available Accuracy and complexity are two crucial aspects of the applicability of a channel model for wideband multiple input multiple output (MIMO systems. For small number of antenna element pairs, correlation-based models have lower computational complexity while the geometry-based stochastic models (GBSMs can provide more accurate modeling of real radio propagation. This paper investigates several potential simplifications of the GBSM to reduce the complexity with minimal impact on accuracy. In addition, we develop a set of broadband metrics which enable a thorough investigation of the differences between the GBSMs and the simplified models. The impact of various random variables which are employed by the original GBSM on the system level simulation are also studied. Both simulation results and a measurement campaign show that complexity can be reduced significantly with a negligible loss of accuracy in the proposed metrics. As an example, in the presented scenarios, the computational time can be reduced by up to 57% while keeping the relative deviation of 5% outage capacity within 5%.

  10. Reduced order modeling of fluid/structure interaction.

    Energy Technology Data Exchange (ETDEWEB)

    Barone, Matthew Franklin; Kalashnikova, Irina; Segalman, Daniel Joseph; Brake, Matthew Robert

    2009-11-01

    This report describes work performed from October 2007 through September 2009 under the Sandia Laboratory Directed Research and Development project titled 'Reduced Order Modeling of Fluid/Structure Interaction.' This project addresses fundamental aspects of techniques for construction of predictive Reduced Order Models (ROMs). A ROM is defined as a model, derived from a sequence of high-fidelity simulations, that preserves the essential physics and predictive capability of the original simulations but at a much lower computational cost. Techniques are developed for construction of provably stable linear Galerkin projection ROMs for compressible fluid flow, including a method for enforcing boundary conditions that preserves numerical stability. A convergence proof and error estimates are given for this class of ROM, and the method is demonstrated on a series of model problems. A reduced order method, based on the method of quadratic components, for solving the von Karman nonlinear plate equations is developed and tested. This method is applied to the problem of nonlinear limit cycle oscillations encountered when the plate interacts with an adjacent supersonic flow. A stability-preserving method for coupling the linear fluid ROM with the structural dynamics model for the elastic plate is constructed and tested. Methods for constructing efficient ROMs for nonlinear fluid equations are developed and tested on a one-dimensional convection-diffusion-reaction equation. These methods are combined with a symmetrization approach to construct a ROM technique for application to the compressible Navier-Stokes equations.

  11. Accelerating transient simulation of linear reduced order models.

    Energy Technology Data Exchange (ETDEWEB)

    Thornquist, Heidi K.; Mei, Ting; Keiter, Eric Richard; Bond, Brad

    2011-10-01

    Model order reduction (MOR) techniques have been used to facilitate the analysis of dynamical systems for many years. Although existing model reduction techniques are capable of providing huge speedups in the frequency domain analysis (i.e. AC response) of linear systems, such speedups are often not obtained when performing transient analysis on the systems, particularly when coupled with other circuit components. Reduced system size, which is the ostensible goal of MOR methods, is often insufficient to improve transient simulation speed on realistic circuit problems. It can be shown that making the correct reduced order model (ROM) implementation choices is crucial to the practical application of MOR methods. In this report we investigate methods for accelerating the simulation of circuits containing ROM blocks using the circuit simulator Xyce.

  12. Reduced Complexity Volterra Models for Nonlinear System Identification

    Directory of Open Access Journals (Sweden)

    Hacıoğlu Rıfat

    2001-01-01

    Full Text Available A broad class of nonlinear systems and filters can be modeled by the Volterra series representation. However, its practical use in nonlinear system identification is sometimes limited due to the large number of parameters associated with the Volterra filter′s structure. The parametric complexity also complicates design procedures based upon such a model. This limitation for system identification is addressed in this paper using a Fixed Pole Expansion Technique (FPET within the Volterra model structure. The FPET approach employs orthonormal basis functions derived from fixed (real or complex pole locations to expand the Volterra kernels and reduce the number of estimated parameters. That the performance of FPET can considerably reduce the number of estimated parameters is demonstrated by a digital satellite channel example in which we use the proposed method to identify the channel dynamics. Furthermore, a gradient-descent procedure that adaptively selects the pole locations in the FPET structure is developed in the paper.

  13. Model predictive control based on reduced order models applied to belt conveyor system.

    Science.gov (United States)

    Chen, Wei; Li, Xin

    2016-11-01

    In the paper, a model predictive controller based on reduced order model is proposed to control belt conveyor system, which is an electro-mechanics complex system with long visco-elastic body. Firstly, in order to design low-degree controller, the balanced truncation method is used for belt conveyor model reduction. Secondly, MPC algorithm based on reduced order model for belt conveyor system is presented. Because of the error bound between the full-order model and reduced order model, two Kalman state estimators are applied in the control scheme to achieve better system performance. Finally, the simulation experiments are shown that balanced truncation method can significantly reduce the model order with high-accuracy and model predictive control based on reduced-model performs well in controlling the belt conveyor system. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

  14. Reduced-form air quality modeling for community-scale ...

    Science.gov (United States)

    Transportation plays an important role in modern society, but its impact on air quality has been shown to have significant adverse effects on public health. Numerous reviews (HEI, CDC, WHO) summarizing findings of hundreds of studies conducted mainly in the last decade, conclude that exposures to traffic emissions near roads are a public health concern. The Community LINE Source Model (C-LINE) is a web-based model designed to inform the community user of local air quality impacts due to roadway vehicles in their region of interest using a simplified modeling approach. Reduced-form air quality modeling is a useful tool for examining what-if scenarios of changes in emissions, such as those due to changes in traffic volume, fleet mix, or vehicle speed. Examining various scenarios of air quality impacts in this way can identify potentially at-risk populations located near roadways, and the effects that a change in traffic activity may have on them. C-LINE computes dispersion of primary mobile source pollutants using meteorological conditions for the region of interest and computes air-quality concentrations corresponding to these selected conditions. C-LINE functionality has been expanded to model emissions from port-related activities (e.g. ships, trucks, cranes, etc.) in a reduced-form modeling system for local-scale near-port air quality analysis. This presentation describes the Community modeling tools C-LINE and C-PORT that are intended to be used by local gove

  15. Empirical Reduced-Order Modeling for Boundary Feedback Flow Control

    Directory of Open Access Journals (Sweden)

    Seddik M. Djouadi

    2008-01-01

    Full Text Available This paper deals with the practical and theoretical implications of model reduction for aerodynamic flow-based control problems. Various aspects of model reduction are discussed that apply to partial differential equation- (PDE- based models in general. Specifically, the proper orthogonal decomposition (POD of a high dimension system as well as frequency domain identification methods are discussed for initial model construction. Projections on the POD basis give a nonlinear Galerkin model. Then, a model reduction method based on empirical balanced truncation is developed and applied to the Galerkin model. The rationale for doing so is that linear subspace approximations to exact submanifolds associated with nonlinear controllability and observability require only standard matrix manipulations utilizing simulation/experimental data. The proposed method uses a chirp signal as input to produce the output in the eigensystem realization algorithm (ERA. This method estimates the system's Markov parameters that accurately reproduce the output. Balanced truncation is used to show that model reduction is still effective on ERA produced approximated systems. The method is applied to a prototype convective flow on obstacle geometry. An H∞ feedback flow controller is designed based on the reduced model to achieve tracking and then applied to the full-order model with excellent performance.

  16. Transgenic Mouse Model for Reducing Oxidative Damage in Bone

    Science.gov (United States)

    Schreurs, A.-S.; Torres, S.; Truong, T.; Kumar, A.; Alwood, J. S.; Limoli, C. L.; Globus, R. K.

    2014-01-01

    Exposure to musculoskeletal disuse and radiation result in bone loss; we hypothesized that these catabolic treatments cause excess reactive oxygen species (ROS), and thereby alter the tight balance between bone resorption by osteoclasts and bone formation by osteoblasts, culminating in bone loss. To test this, we used transgenic mice which over-express the human gene for catalase, targeted to mitochondria (MCAT). Catalase is an anti-oxidant that converts the ROS hydrogen peroxide into water and oxygen. MCAT mice were shown previously to display reduced mitochondrial oxidative stress and radiosensitivity of the CNS compared to wild type controls (WT). As expected, MCAT mice expressed the transgene in skeletal tissue, and in marrow-derived osteoblasts and osteoclast precursors cultured ex vivo, and also showed greater catalase activity compared to wildtype (WT) mice (3-6 fold). Colony expansion in marrow cells cultured under osteoblastogenic conditions was 2-fold greater in the MCAT mice compared to WT mice, while the extent of mineralization was unaffected. MCAT mice had slightly longer tibiae than WT mice (2%, P less than 0.01), although cortical bone area was slightly lower in MCAT mice than WT mice (10%, p=0.09). To challenge the skeletal system, mice were treated by exposure to combined disuse (2 wk Hindlimb Unloading) and total body irradiation Cs(137) (2 Gy, 0.8 Gy/min), then bone parameters were analyzed by 2-factor ANOVA to detect possible interaction effects. Treatment caused a 2-fold increase (p=0.015) in malondialdehyde levels of bone tissue (ELISA) in WT mice, but had no effect in MCAT mice. These findings indicate that the transgene conferred protection from oxidative damage caused by treatment. Unexpected differences between WT and MCAT mice emerged in skeletal responses to treatment.. In WT mice, treatment did not alter osteoblastogenesis, cortical bone area, moment of inertia, or bone perimeter, whereas in MCAT mice, treatment increased these

  17. Human Centered Hardware Modeling and Collaboration

    Science.gov (United States)

    Stambolian Damon; Lawrence, Brad; Stelges, Katrine; Henderson, Gena

    2013-01-01

    In order to collaborate engineering designs among NASA Centers and customers, to in clude hardware and human activities from multiple remote locations, live human-centered modeling and collaboration across several sites has been successfully facilitated by Kennedy Space Center. The focus of this paper includes innovative a pproaches to engineering design analyses and training, along with research being conducted to apply new technologies for tracking, immersing, and evaluating humans as well as rocket, vehic le, component, or faci lity hardware utilizing high resolution cameras, motion tracking, ergonomic analysis, biomedical monitoring, wor k instruction integration, head-mounted displays, and other innovative human-system integration modeling, simulation, and collaboration applications.

  18. MODELING CONTROLLED ASYNCHRONOUS ELECTRIC DRIVES WITH MATCHING REDUCERS AND TRANSFORMERS

    Directory of Open Access Journals (Sweden)

    V. S. Petrushin

    2015-04-01

    Full Text Available Purpose. Working out of mathematical models of the speed-controlled induction electric drives ensuring joint consideration of transformers, motors and loadings, and also matching reducers and transformers, both in static, and in dynamic regimes for the analysis of their operating characteristics. Methodology. At mathematical modelling are considered functional, mass, dimensional and cost indexes of reducers and transformers that allows observing engineering and economic aspects of speed-controlled induction electric drives. The mathematical models used for examination of the transitive electromagnetic and electromechanical processes, are grounded on systems of nonlinear differential equations with nonlinear coefficients (parameters of equivalent circuits of motors, varying in each operating point, including owing to appearances of saturation of magnetic system and current displacement in a winding of a rotor of an induction motor. For the purpose of raise of level of adequacy of models a magnetic circuit iron, additional and mechanical losses are considered. Results. Modelling of the several speed-controlled induction electric drives, different by components, but working on a loading equal on character, magnitude and a demanded control range is executed. At use of characteristic families including mechanical, at various parameters of regulating on which performances of the load mechanism are superimposed, the adjusting characteristics representing dependences of a modification of electrical, energy and thermal magnitudes from an angular speed of motors are gained. Originality. The offered complex models of speed-controlled induction electric drives with matching reducers and transformers, give the chance to realize well-founded sampling of components of drives. They also can be used as the design models by working out of speed-controlled induction motors. Practical value. Operating characteristics of various speed-controlled induction electric

  19. Identification of the reduced order models of a BWR reactor

    International Nuclear Information System (INIS)

    Hernandez S, A.

    2004-01-01

    The present work has as objective to analyze the relative stability of a BWR type reactor. It is analyzed that so adaptive it turns out to identify the parameters of a model of reduced order so that this it reproduces a condition of given uncertainty. This will take of a real fact happened in the La Salle plant under certain operation conditions of power and flow of coolant. The parametric identification is carried out by means of an algorithm of recursive least square and an Output Error model (Output Error), measuring the output power of the reactor when the instability is present, and considering that it is produced by a change in the reactivity of the system in the same way that a sign of type step. Also it is carried out an analytic comparison of the relative stability, analyzing two types of answers: the original answer of the uncertainty of the reactor vs. the obtained response identifying the parameters of the model of reduced order, reaching the conclusion that it is very viable to adapt a model of reduced order to study the stability of a reactor, under the only condition to consider that the dynamics of the reactivity is of step type. (Author)

  20. Integrated Human Behavior Modeling and Stochastic Control (IHBMSC)

    Science.gov (United States)

    2014-08-01

    angle, dwell time, workload). For a 50% target density scenario where the operator discrimination task is fairly difficult, the integrated human ... behavior model and stochastic controller (IHBMSC) was shown to reduce the FA rate from 35% to 5%. Also, the IHBMSC performance was found to be quite robust for lower target densities (5%) and different operators.

  1. Human Adaptive Mechatronics and Human-System Modelling

    Directory of Open Access Journals (Sweden)

    Satoshi Suzuki

    2013-03-01

    Full Text Available Several topics in projects for mechatronics studies, which are 'Human Adaptive Mechatronics (HAM' and 'Human-System Modelling (HSM', are presented in this paper. The main research theme of the HAM project is a design strategy for a new intelligent mechatronics system, which enhances operators' skills during machine operation. Skill analyses and control system design have been addressed. In the HSM project, human modelling based on hierarchical classification of skills was studied, including the following five types of skills: social, planning, cognitive, motion and sensory-motor skills. This paper includes digests of these research topics and the outcomes concerning each type of skill. Relationships with other research activities, knowledge and information that will be helpful for readers who are trying to study assistive human-mechatronics systems are also mentioned.

  2. Animal Models of Human Placentation - A Review

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2007-01-01

    This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. There are, however...... and delivers poorly developed young. Guinea pig is a good alternative rodent model and among the few species known to develop pregnancy toxaemia. The sheep is well established as a model in fetal physiology but is of limited value for placental research. The ovine placenta is epitheliochorial...

  3. Can agent based models effectively reduce fisheries management implementation uncertainty?

    Science.gov (United States)

    Drexler, M.

    2016-02-01

    Uncertainty is an inherent feature of fisheries management. Implementation uncertainty remains a challenge to quantify often due to unintended responses of users to management interventions. This problem will continue to plague both single species and ecosystem based fisheries management advice unless the mechanisms driving these behaviors are properly understood. Equilibrium models, where each actor in the system is treated as uniform and predictable, are not well suited to forecast the unintended behaviors of individual fishers. Alternatively, agent based models (AMBs) can simulate the behaviors of each individual actor driven by differing incentives and constraints. This study evaluated the feasibility of using AMBs to capture macro scale behaviors of the US West Coast Groundfish fleet. Agent behavior was specified at the vessel level. Agents made daily fishing decisions using knowledge of their own cost structure, catch history, and the histories of catch and quota markets. By adding only a relatively small number of incentives, the model was able to reproduce highly realistic macro patterns of expected outcomes in response to management policies (catch restrictions, MPAs, ITQs) while preserving vessel heterogeneity. These simulations indicate that agent based modeling approaches hold much promise for simulating fisher behaviors and reducing implementation uncertainty. Additional processes affecting behavior, informed by surveys, are continually being added to the fisher behavior model. Further coupling of the fisher behavior model to a spatial ecosystem model will provide a fully integrated social, ecological, and economic model capable of performing management strategy evaluations to properly consider implementation uncertainty in fisheries management.

  4. Bayesian analysis of a reduced-form air quality model.

    Science.gov (United States)

    Foley, Kristen M; Reich, Brian J; Napelenok, Sergey L

    2012-07-17

    Numerical air quality models are being used for assessing emission control strategies for improving ambient pollution levels across the globe. This paper applies probabilistic modeling to evaluate the effectiveness of emission reduction scenarios aimed at lowering ground-level ozone concentrations. A Bayesian hierarchical model is used to combine air quality model output and monitoring data in order to characterize the impact of emissions reductions while accounting for different degrees of uncertainty in the modeled emissions inputs. The probabilistic model predictions are weighted based on population density in order to better quantify the societal benefits/disbenefits of four hypothetical emission reduction scenarios in which domain-wide NO(x) emissions from various sectors are reduced individually and then simultaneously. Cross validation analysis shows the statistical model performs well compared to observed ozone levels. Accounting for the variability and uncertainty in the emissions and atmospheric systems being modeled is shown to impact how emission reduction scenarios would be ranked, compared to standard methodology.

  5. Mechanistically Consistent Reduced Models of Synthetic Gene Networks

    Science.gov (United States)

    Mier-y-Terán-Romero, Luis; Silber, Mary; Hatzimanikatis, Vassily

    2013-01-01

    Designing genetic networks with desired functionalities requires an accurate mathematical framework that accounts for the essential mechanistic details of the system. Here, we formulate a time-delay model of protein translation and mRNA degradation by systematically reducing a detailed mechanistic model that explicitly accounts for the ribosomal dynamics and the cleaving of mRNA by endonucleases. We exploit various technical and conceptual advantages that our time-delay model offers over the mechanistic model to probe the behavior of a self-repressing gene over wide regions of parameter space. We show that a heuristic time-delay model of protein synthesis of a commonly used form yields a notably different prediction for the parameter region where sustained oscillations occur. This suggests that such heuristics can lead to erroneous results. The functional forms that arise from our systematic reduction can be used for every system that involves transcription and translation and they could replace the commonly used heuristic time-delay models for these processes. The results from our analysis have important implications for the design of synthetic gene networks and stress that such design must be guided by a combination of heuristic models and mechanistic models that include all relevant details of the process. PMID:23663853

  6. Underwater drag-reducing effect of superhydrophobic submarine model.

    Science.gov (United States)

    Zhang, Songsong; Ouyang, Xiao; Li, Jie; Gao, Shan; Han, Shihui; Liu, Lianhe; Wei, Hao

    2015-01-01

    To address the debates on whether superhydrophobic coatings can reduce fluid drag for underwater motions, we have achieved an underwater drag-reducing effect of large superhydrophobic submarine models with a feature size of 3.5 cm × 3.7 cm × 33.0 cm through sailing experiments of submarine models, modified with and without superhydrophobic surface under similar power supply and experimental conditions. The drag reduction rate reached as high as 15%. The fabrication of superhydrophobic coatings on a large area of submarine model surfaces was realized by immobilizing hydrophobic copper particles onto a precross-linked polydimethylsiloxane (PDMS) surface. The pre-cross-linking time was optimized at 20 min to obtain good superhydrophobicity for the underwater drag reduction effect by investigating the effect of pre-cross-linking on surface wettability and water adhesive property. We do believe that superhydrophobic coatings may provide a promising application in the field of drag-reducing of vehicle motions on or under the water surface.

  7. Vortex network community based reduced-order force model

    Science.gov (United States)

    Gopalakrishnan Meena, Muralikrishnan; Nair, Aditya; Taira, Kunihiko

    2017-11-01

    We characterize the vortical wake interactions by utilizing network theory and cluster-based approaches, and develop a data-inspired unsteady force model. In the present work, the vortical interaction network is defined by nodes representing vortical elements and the edges quantified by induced velocity measures amongst the vortices. The full vorticity field is reduced to a finite number of vortical clusters based on network community detection algorithm, which serves as a basis for a skeleton network that captures the essence of the wake dynamics. We use this reduced representation of the wake to develop a data-inspired reduced-order force model that can predict unsteady fluid forces on the body. The overall formulation is demonstrated for laminar flows around canonical bluff body wake and stalled flow over an airfoil. We also show the robustness of the present network-based model against noisy data, which motivates applications towards turbulent flows and experimental measurements. Supported by the National Science Foundation (Grant 1632003).

  8. Towards a Wind Turbine Wake Reduced-Order Model

    Science.gov (United States)

    Hamilton, Nicholas; Viggiano, Bianca; Calaf, Marc; Tutkun, Murat; Cal, Raúl Bayoán

    2017-11-01

    A reduced-order model for a wind turbine wake is sought for prediction and control. Basis functions from the proper orthogonal decomposition (POD) represent the spatially coherent turbulence structures in the wake; eigenvalues delineate the turbulence kinetic energy associated with each mode. Back-projecting the POD modes onto the velocity snapshots produces coefficients that express the amplitude of each mode in time. A reduced-order model of the wind turbine wake (wakeROM) is defined through a series of polynomial parameters that quantify mode interaction and the evolution of each mode coefficient. Tikhonov regularization is employed to recalibrate the dynamical system, reducing error in the modeled mode coefficients and adding stability to the system. The wakeROM is periodically reinitialized by relating the incoming turbulent velocity to the POD mode coefficients. A high-level view of the wakeROM provides as a platform to discuss promising research direction, alternate processes that will enhance stability, and portability to control methods. NSF- ECCS-1032647, NSF-CBET-1034581, Research Council of Norway Project Number 231491.

  9. Systematic development of reduced reaction mechanisms for dynamic modeling

    Science.gov (United States)

    Frenklach, M.; Kailasanath, K.; Oran, E. S.

    1986-01-01

    A method for systematically developing a reduced chemical reaction mechanism for dynamic modeling of chemically reactive flows is presented. The method is based on the postulate that if a reduced reaction mechanism faithfully describes the time evolution of both thermal and chain reaction processes characteristic of a more complete mechanism, then the reduced mechanism will describe the chemical processes in a chemically reacting flow with approximately the same degree of accuracy. Here this postulate is tested by producing a series of mechanisms of reduced accuracy, which are derived from a full detailed mechanism for methane-oxygen combustion. These mechanisms were then tested in a series of reactive flow calculations in which a large-amplitude sinusoidal perturbation is applied to a system that is initially quiescent and whose temperature is high enough to start ignition processes. Comparison of the results for systems with and without convective flow show that this approach produces reduced mechanisms that are useful for calculations of explosions and detonations. Extensions and applicability to flames are discussed.

  10. The Human-Artifact Model

    DEFF Research Database (Denmark)

    Bødker, Susanne; Klokmose, Clemens Nylandsted

    2011-01-01

    needs to support such development through concepts and methods. This leads to a methodological approach that focuses on new artifacts to supplement and substitute existing artifacts. Through a design case, we develop the methodological approach and illustrate how the human–artifact model can be applied...... to analyze present artifacts and to design future ones. The model is used to structure such analysis and to reason about findings while providing leverage from activity theoretical insights on mediation, dialectics, and levels of activity....

  11. Topically applied L-carnitine effectively reduces sebum secretion in human skin.

    Science.gov (United States)

    Peirano, Reto I; Hamann, Tina; Düsing, Hans-Jürgen; Akhiani, Mehdi; Koop, Urte; Schmidt-Rose, Thomas; Wenck, Horst

    2012-03-01

      Oily skin condition is caused by an excessive sebaceous gland activity, resulting in an overproduction of sebum, giving the skin an undesired shiny, oily appearance.   To identify an active substance that reduces sebum production in human sebaceous glands by regulating fat metabolism in a natural way.   The effects of L-carnitine on β-oxidation and intracellular lipid content were investigated in vitro using the human sebaceous cell line SZ95. Penetration experiments utilizing pig skin as a model system were performed with a cosmetic formulation containing radioactively labeled L-carnitine. To determine the in vivo effects, a vehicle-controlled, randomized study was carried out using a cosmetic formulation containing 2%l-carnitine for 3 weeks. Sebum production was investigated utilizing the lipid-absorbent Sebutape(®).   SZ95 cells treated with 0.5% or 1% L-carnitine demonstrated a significant concentration-dependent increase in β-oxidation compared to control cells. Following the treatment with L-carnitine, intracellular lipid concentrations decreased significantly in a dose-dependent manner compared with untreated control cells. In skin penetration experiments, topically applied L-carnitine reached the dermis. In addition, topical in vivo application of a formulation containing 2% L-carnitine for 3 weeks significantly decreased the sebum secretion rate compared to the treatment with vehicle.   Our results show that the treatment of human sebocytes with L-carnitine significantly augments β-oxidation and significantly decreases intracellular lipid content in human sebocytes. Topically applied L-carnitine is bioavailable and leads to a significant sebum reduction in vivo. In conclusion, L-carnitine represents a valuable compound, produced naturally within the body, for the topical treatment of oily skin in humans. © 2012 Wiley Periodicals, Inc.

  12. Advanced Fluid Reduced Order Models for Compressible Flow.

    Energy Technology Data Exchange (ETDEWEB)

    Tezaur, Irina Kalashnikova [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Fike, Jeffrey A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Carlberg, Kevin Thomas [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Barone, Matthew F. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Maddix, Danielle [Stanford Univ., CA (United States); Mussoni, Erin E. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Balajewicz, Maciej [Univ. of Illinois, Urbana-Champaign, IL (United States)

    2017-09-01

    This report summarizes fiscal year (FY) 2017 progress towards developing and implementing within the SPARC in-house finite volume flow solver advanced fluid reduced order models (ROMs) for compressible captive-carriage flow problems of interest to Sandia National Laboratories for the design and qualification of nuclear weapons components. The proposed projection-based model order reduction (MOR) approach, known as the Proper Orthogonal Decomposition (POD)/Least- Squares Petrov-Galerkin (LSPG) method, can substantially reduce the CPU-time requirement for these simulations, thereby enabling advanced analyses such as uncertainty quantification and de- sign optimization. Following a description of the project objectives and FY17 targets, we overview briefly the POD/LSPG approach to model reduction implemented within SPARC . We then study the viability of these ROMs for long-time predictive simulations in the context of a two-dimensional viscous laminar cavity problem, and describe some FY17 enhancements to the proposed model reduction methodology that led to ROMs with improved predictive capabilities. Also described in this report are some FY17 efforts pursued in parallel to the primary objective of determining whether the ROMs in SPARC are viable for the targeted application. These include the implemen- tation and verification of some higher-order finite volume discretization methods within SPARC (towards using the code to study the viability of ROMs on three-dimensional cavity problems) and a novel structure-preserving constrained POD/LSPG formulation that can improve the accuracy of projection-based reduced order models. We conclude the report by summarizing the key takeaways from our FY17 findings, and providing some perspectives for future work.

  13. Human BDCM Mulit-Route PBPK Model

    Data.gov (United States)

    U.S. Environmental Protection Agency — This data set contains the code for the BDCM human multi-route model written in the programming language acsl. The final published manuscript is provided since it...

  14. Comparison of the Gene Expression Profiles of Human Hematopoietic Stem Cells between Humans and a Humanized Xenograft Model.

    Science.gov (United States)

    Matsuzawa, Hideyuki; Matsushita, Hiromichi; Yahata, Takashi; Tanaka, Masayuki; Ando, Kiyoshi

    2017-04-20

    The aim of this study is to evaluate the feasibility of NOD/Shi-scid-IL2Rγ null (NOG) mice transplanted with human CD34 + /CD38 - /Lin -/low hematopoietic cells from cord blood (CB) as an experimental model of the gene expression in human hematopoiesis. We compared the gene expressions of human CD34 + /CD38 - /Lin -/low cells from human bone marrow (BM) and in xenograft models. The microarray data revealed that 25 KEGG pathways were extracted from the comparison of human CD34 + /CD38 - /Lin -/low HSCs between CB and BM, and that 17 of them--which were mostly related to cellular survival, RNA metabolism and lymphoid development--were shared with the xenograft model. When the probes that were commonly altered in CD34 + /CD38 - /Lin -/low cells from both human and xenograft BM were analyzed, most of them, including the genes related hypoxia, hematopoietic differentiation, epigenetic modification, translation initiation, and RNA degradation, were downregulated. These alterations of gene expression suggest a reduced differentiation capacity and likely include key alterations of gene expression for settlement of CB CD34 + /CD38 - /Lin -/low cells in BM. Our findings demonstrate that the xenograft model of human CB CD34 + /CD38 - /Lin -/low cells using NOG mice was useful, at least in part, for the evaluation of the gene expression profile of human hematopoietic stem cells.

  15. Predictive models reduce talent development costs in female gymnastics.

    Science.gov (United States)

    Pion, Johan; Hohmann, Andreas; Liu, Tianbiao; Lenoir, Matthieu; Segers, Veerle

    2017-04-01

    This retrospective study focuses on the comparison of different predictive models based on the results of a talent identification test battery for female gymnasts. We studied to what extent these models have the potential to optimise selection procedures, and at the same time reduce talent development costs in female artistic gymnastics. The dropout rate of 243 female elite gymnasts was investigated, 5 years past talent selection, using linear (discriminant analysis) and non-linear predictive models (Kohonen feature maps and multilayer perceptron). The coaches classified 51.9% of the participants correct. Discriminant analysis improved the correct classification to 71.6% while the non-linear technique of Kohonen feature maps reached 73.7% correctness. Application of the multilayer perceptron even classified 79.8% of the gymnasts correctly. The combination of different predictive models for talent selection can avoid deselection of high-potential female gymnasts. The selection procedure based upon the different statistical analyses results in decrease of 33.3% of cost because the pool of selected athletes can be reduced to 92 instead of 138 gymnasts (as selected by the coaches). Reduction of the costs allows the limited resources to be fully invested in the high-potential athletes.

  16. Modeling Human Cancers in Drosophila.

    Science.gov (United States)

    Sonoshita, M; Cagan, R L

    2017-01-01

    Cancer is a complex disease that affects multiple organs. Whole-body animal models provide important insights into oncology that can lead to clinical impact. Here, we review novel concepts that Drosophila studies have established for cancer biology, drug discovery, and patient therapy. Genetic studies using Drosophila have explored the roles of oncogenes and tumor-suppressor genes that when dysregulated promote cancer formation, making Drosophila a useful model to study multiple aspects of transformation. Not limited to mechanism analyses, Drosophila has recently been showing its value in facilitating drug development. Flies offer rapid, efficient platforms by which novel classes of drugs can be identified as candidate anticancer leads. Further, we discuss the use of Drosophila as a platform to develop therapies for individual patients by modeling the tumor's genetic complexity. Drosophila provides both a classical and a novel tool to identify new therapeutics, complementing other more traditional cancer tools. © 2017 Elsevier Inc. All rights reserved.

  17. Modeling human learning involved in car driving

    OpenAIRE

    Wewerinke, P.H.

    1994-01-01

    In this paper, car driving is considered at the level of human tracking and maneuvering in the context of other traffic. A model analysis revealed the most salient features determining driving performance and safety. Learning car driving is modelled based on a system theoretical approach and based on a neural network approach. The aim of this research is to assess the relative merit of both approaches to describe human learning behavior in car driving specifically and in operating dynamic sys...

  18. Modeling of automotive driveline system for reducing gear rattles

    Science.gov (United States)

    Shangguan, Wen-Bin; Liu, Xue-Lai; Yin, Yuming; Rakheja, Subhash

    2018-03-01

    A nonlinear torsional model for a driveline system with 4 degrees of freedom is proposed for studying gear rattle if a car is at idle. The time-varying meshing stiffness of geared teeth, gear backlash, and the damping from oil film are included in the model. The dynamic responses of the driveline system, such as clutch angular displacement, meshing force and relative displacement between geared teeth, are calculated using the presented model. The influences of stiffness and damping of a clutch on gear rattle of geared teeth in a generic transmission are investigated. Based on the calculation and analysis results, a design guideline to select clutch's stiffness and damping is developed to reduce gear rattle for a car at idle. Taking a generic driveline system of a passenger car as an example, the developed method is experimentally validated by comparing the baseline clutch and revised clutch, in terms of the measured noise inside engine compartment and cab and vibrations at transmission housing.

  19. Reduced order methods for modeling and computational reduction

    CERN Document Server

    Rozza, Gianluigi

    2014-01-01

    This monograph addresses the state of the art of reduced order methods for modeling and computational reduction of complex parametrized systems, governed by ordinary and/or partial differential equations, with a special emphasis on real time computing techniques and applications in computational mechanics, bioengineering and computer graphics.  Several topics are covered, including: design, optimization, and control theory in real-time with applications in engineering; data assimilation, geometry registration, and parameter estimation with special attention to real-time computing in biomedical engineering and computational physics; real-time visualization of physics-based simulations in computer science; the treatment of high-dimensional problems in state space, physical space, or parameter space; the interactions between different model reduction and dimensionality reduction approaches; the development of general error estimation frameworks which take into account both model and discretization effects. This...

  20. Probabilistic Rotor Life Assessment Using Reduced Order Models

    Directory of Open Access Journals (Sweden)

    Brian K. Beachkofski

    2009-01-01

    Full Text Available Probabilistic failure assessments for integrally bladed disks are system reliability problems where a failure in at least one blade constitutes a rotor system failure. Turbine engine fan and compressor blade life is dominated by High Cycle Fatigue (HCF initiated either by pure HCF or Foreign Object Damage (FOD. To date performing an HCF life assessment for the entire rotor system has been too costly in analysis time to be practical. Although the substantial run-time has previously precluded a full-rotor probabilistic analysis, reduced order models make this process tractable as demonstrated in this work. The system model includes frequency prediction, modal stress variation, mistuning amplification, FOD effect, and random material capability. The model has many random variables which are most easily handled through simple random sampling.

  1. Auditory-somatosensory bimodal stimulation desynchronizes brain circuitry to reduce tinnitus in guinea pigs and humans.

    Science.gov (United States)

    Marks, Kendra L; Martel, David T; Wu, Calvin; Basura, Gregory J; Roberts, Larry E; Schvartz-Leyzac, Kara C; Shore, Susan E

    2018-01-03

    The dorsal cochlear nucleus is the first site of multisensory convergence in mammalian auditory pathways. Principal output neurons, the fusiform cells, integrate auditory nerve inputs from the cochlea with somatosensory inputs from the head and neck. In previous work, we developed a guinea pig model of tinnitus induced by noise exposure and showed that the fusiform cells in these animals exhibited increased spontaneous activity and cross-unit synchrony, which are physiological correlates of tinnitus. We delivered repeated bimodal auditory-somatosensory stimulation to the dorsal cochlear nucleus of guinea pigs with tinnitus, choosing a stimulus interval known to induce long-term depression (LTD). Twenty minutes per day of LTD-inducing bimodal (but not unimodal) stimulation reduced physiological and behavioral evidence of tinnitus in the guinea pigs after 25 days. Next, we applied the same bimodal treatment to 20 human subjects with tinnitus using a double-blinded, sham-controlled, crossover study. Twenty-eight days of LTD-inducing bimodal stimulation reduced tinnitus loudness and intrusiveness. Unimodal auditory stimulation did not deliver either benefit. Bimodal auditory-somatosensory stimulation that induces LTD in the dorsal cochlear nucleus may hold promise for suppressing chronic tinnitus, which reduces quality of life for millions of tinnitus sufferers worldwide. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  2. Construction of energy-stable Galerkin reduced order models.

    Energy Technology Data Exchange (ETDEWEB)

    Kalashnikova, Irina; Barone, Matthew Franklin; Arunajatesan, Srinivasan; van Bloemen Waanders, Bart Gustaaf

    2013-05-01

    This report aims to unify several approaches for building stable projection-based reduced order models (ROMs). Attention is focused on linear time-invariant (LTI) systems. The model reduction procedure consists of two steps: the computation of a reduced basis, and the projection of the governing partial differential equations (PDEs) onto this reduced basis. Two kinds of reduced bases are considered: the proper orthogonal decomposition (POD) basis and the balanced truncation basis. The projection step of the model reduction can be done in two ways: via continuous projection or via discrete projection. First, an approach for building energy-stable Galerkin ROMs for linear hyperbolic or incompletely parabolic systems of PDEs using continuous projection is proposed. The idea is to apply to the set of PDEs a transformation induced by the Lyapunov function for the system, and to build the ROM in the transformed variables. The resulting ROM will be energy-stable for any choice of reduced basis. It is shown that, for many PDE systems, the desired transformation is induced by a special weighted L2 inner product, termed the %E2%80%9Csymmetry inner product%E2%80%9D. Attention is then turned to building energy-stable ROMs via discrete projection. A discrete counterpart of the continuous symmetry inner product, a weighted L2 inner product termed the %E2%80%9CLyapunov inner product%E2%80%9D, is derived. The weighting matrix that defines the Lyapunov inner product can be computed in a black-box fashion for a stable LTI system arising from the discretization of a system of PDEs in space. It is shown that a ROM constructed via discrete projection using the Lyapunov inner product will be energy-stable for any choice of reduced basis. Connections between the Lyapunov inner product and the inner product induced by the balanced truncation algorithm are made. Comparisons are also made between the symmetry inner product and the Lyapunov inner product. The performance of ROMs constructed

  3. Computational Intelligence in a Human Brain Model

    Directory of Open Access Journals (Sweden)

    Viorel Gaftea

    2016-06-01

    Full Text Available This paper focuses on the current trends in brain research domain and the current stage of development of research for software and hardware solutions, communication capabilities between: human beings and machines, new technologies, nano-science and Internet of Things (IoT devices. The proposed model for Human Brain assumes main similitude between human intelligence and the chess game thinking process. Tactical & strategic reasoning and the need to follow the rules of the chess game, all are very similar with the activities of the human brain. The main objective for a living being and the chess game player are the same: securing a position, surviving and eliminating the adversaries. The brain resolves these goals, and more, the being movement, actions and speech are sustained by the vital five senses and equilibrium. The chess game strategy helps us understand the human brain better and easier replicate in the proposed ‘Software and Hardware’ SAH Model.

  4. Human flexor tendon tissue engineering: decellularization of human flexor tendons reduces immunogenicity in vivo.

    Science.gov (United States)

    Raghavan, Shyam S; Woon, Colin Y L; Kraus, Armin; Megerle, Kai; Choi, Matthew S S; Pridgen, Brian C; Pham, Hung; Chang, James

    2012-04-01

    In mutilating hand injuries, tissue engineered tendon grafts may provide a reconstructive solution. We have previously described a method to decellularize cadaveric human flexor tendons while preserving mechanical properties and biocompatibility. The purpose of this study is to evaluate the immunogenicity and strength of these grafts when implanted into an immunocompetent rat model. Cadaveric human flexor tendons were divided into two groups. Group 1 was untreated, and Group 2 was decellularized by treatment with sodium dodecyl sulfate (SDS), ethylenediaminetetraacetic acid (EDTA), and peracetic acid (PAA). Both groups were then analyzed for the presence of major histocompatibility complexes by immunohistochemistry (IHC). Pair-matched tendons from each group were then placed into the dorsal subcutaneous tissue and anchored to the spinal ligaments of Wistar rats for 2 or 4 weeks, and harvested. The infiltration of B-cells and macrophages was determined using IHC. The explants where then subjected to mechanical testing to determine the ultimate tensile stress (UTS) and elastic modulus (EM). Statistical analysis was performed using a paired Student's t-test. The decellularization protocol successfully removed cells and MHC-1 complexes. At 2 weeks after implantation, there was increased infiltration of B-cells in Group 1 (untreated) compared with Group 2 (acellular), both in the capsule and tendon substance. There was improved ultimate tensile stress (UTS, 42.7 ± 8.3 vs. 22.8 ± 7.8 MPa, ptendons that were decellularized. At 4 weeks, there was continued B-cell infiltration in Group 1 (untreated) compared with Group 2 (acellular). There was no appreciable difference in macrophage infiltration at both time points. At 4 weeks Group 2 (acellular) demonstrated persistently greater UTS (40.5 ± 9.1 vs. 14.6 ± 4.2 MPa, ptendons that were decellularized with SDS, EDTA, and PAA resulted in removal of cellular antigens and a decreased immune response when placed into Wistar

  5. Aeroelastic simulation using CFD based reduced order models

    International Nuclear Information System (INIS)

    Zhang, W.; Ye, Z.; Li, H.; Yang, Q.

    2005-01-01

    This paper aims at providing an accurate and efficient method for aeroelastic simulation. System identification is used to get the reduced order models of unsteady aerodynamics. Unsteady Euler codes are used to compute the output signals while 3211 multistep input signals are utilized. LS(Least Squares) method is used to estimate the coefficients of the input-output difference model. The reduced order models are then used in place of the unsteady CFD code for aeroelastic simulation. The aeroelastic equations are marched by an improved 4th order Runge-Kutta method that only needs to compute the aerodynamic loads one time at every time step. The computed results agree well with that of the direct coupling CFD/CSD methods. The computational efficiency is improved 1∼2 orders while still retaining the high accuracy. A standard aeroelastic computing example (isogai wing) with S type flutter boundary is computed and analyzed. It is due to the system has more than one neutral points at the Mach range of 0.875∼0.9. (author)

  6. A humanized mouse model of tuberculosis.

    Directory of Open Access Journals (Sweden)

    Veronica E Calderon

    Full Text Available Mycobacterium tuberculosis (M.tb is the second leading infectious cause of death worldwide and the primary cause of death in people living with HIV/AIDS. There are several excellent animal models employed to study tuberculosis (TB, but many have limitations for reproducing human pathology and none are amenable to the direct study of HIV/M.tb co-infection. The humanized mouse has been increasingly employed to explore HIV infection and other pathogens where animal models are limiting. Our goal was to develop a small animal model of M.tb infection using the bone marrow, liver, thymus (BLT humanized mouse. NOD-SCID/γc(null mice were engrafted with human fetal liver and thymus tissue, and supplemented with CD34(+ fetal liver cells. Excellent reconstitution, as measured by expression of the human CD45 pan leukocyte marker by peripheral blood populations, was observed at 12 weeks after engraftment. Human T cells (CD3, CD4, CD8, as well as natural killer cells and monocyte/macrophages were all observed within the human leukocyte (CD45(+ population. Importantly, human T cells were functionally competent as determined by proliferative capacity and effector molecule (e.g. IFN-γ, granulysin, perforin expression in response to positive stimuli. Animals infected intranasally with M.tb had progressive bacterial infection in the lung and dissemination to spleen and liver from 2-8 weeks post infection. Sites of infection in the lung were characterized by the formation of organized granulomatous lesions, caseous necrosis, bronchial obstruction, and crystallization of cholesterol deposits. Human T cells were distributed throughout the lung, liver, and spleen at sites of inflammation and bacterial growth and were organized to the periphery of granulomas. These preliminary results demonstrate the potential to use the humanized mouse as a model of experimental TB.

  7. Glyburide reduces bacterial dissemination in a mouse model of melioidosis.

    Directory of Open Access Journals (Sweden)

    Gavin C K W Koh

    Full Text Available Burkholderia pseudomallei infection (melioidosis is an important cause of community-acquired Gram-negative sepsis in Northeast Thailand, where it is associated with a ~40% mortality rate despite antimicrobial chemotherapy. We showed in a previous cohort study that patients taking glyburide ( = glibenclamide prior to admission have lower mortality and attenuated inflammatory responses compared to patients not taking glyburide. We sought to define the mechanism underlying this observation in a murine model of melioidosis.Mice (C57BL/6 with streptozocin-induced diabetes were inoculated with ~6 × 10(2 cfu B. pseudomallei intranasally, then treated with therapeutic ceftazidime (600 mg/kg intraperitoneally twice daily starting 24 h after inoculation in order to mimic the clinical scenario. Glyburide (50 mg/kg or vehicle was started 7 d before inoculation and continued until sacrifice. The minimum inhibitory concentration of glyburide for B. pseudomallei was determined by broth microdilution. We also examined the effect of glyburide on interleukin (IL 1β by bone-marrow-derived macrophages (BMDM.Diabetic mice had increased susceptibility to melioidosis, with increased bacterial dissemination but no effect was seen of diabetes on inflammation compared to non-diabetic controls. Glyburide treatment did not affect glucose levels but was associated with reduced pulmonary cellular influx, reduced bacterial dissemination to both liver and spleen and reduced IL1β production when compared to untreated controls. Other cytokines were not different in glyburide-treated animals. There was no direct effect of glyburide on B. pseudomallei growth in vitro or in vivo. Glyburide directly reduced the secretion of IL1β by BMDMs in a dose-dependent fashion.Diabetes increases the susceptibility to melioidosis. We further show, for the first time in any model of sepsis, that glyburide acts as an anti-inflammatory agent by reducing IL1β secretion accompanied by diminished

  8. A statistical model of future human actions

    International Nuclear Information System (INIS)

    Woo, G.

    1992-02-01

    A critical review has been carried out of models of future human actions during the long term post-closure period of a radioactive waste repository. Various Markov models have been considered as alternatives to the standard Poisson model, and the problems of parameterisation have been addressed. Where the simplistic Poisson model unduly exaggerates the intrusion risk, some form of Markov model may have to be introduced. This situation may well arise for shallow repositories, but it is less likely for deep repositories. Recommendations are made for a practical implementation of a computer based model and its associated database. (Author)

  9. Benchmarking Water Quality from Wastewater to Drinking Waters Using Reduced Transcriptome of Human Cells.

    Science.gov (United States)

    Xia, Pu; Zhang, Xiaowei; Zhang, Hanxin; Wang, Pingping; Tian, Mingming; Yu, Hongxia

    2017-08-15

    One of the major challenges in environmental science is monitoring and assessing the risk of complex environmental mixtures. In vitro bioassays with limited key toxicological end points have been shown to be suitable to evaluate mixtures of organic pollutants in wastewater and recycled water. Omics approaches such as transcriptomics can monitor biological effects at the genome scale. However, few studies have applied omics approach in the assessment of mixtures of organic micropollutants. Here, an omics approach was developed for profiling bioactivity of 10 water samples ranging from wastewater to drinking water in human cells by a reduced human transcriptome (RHT) approach and dose-response modeling. Transcriptional expression of 1200 selected genes were measured by an Ampliseq technology in two cell lines, HepG2 and MCF7, that were exposed to eight serial dilutions of each sample. Concentration-effect models were used to identify differentially expressed genes (DEGs) and to calculate effect concentrations (ECs) of DEGs, which could be ranked to investigate low dose response. Furthermore, molecular pathways disrupted by different samples were evaluated by Gene Ontology (GO) enrichment analysis. The ability of RHT for representing bioactivity utilizing both HepG2 and MCF7 was shown to be comparable to the results of previous in vitro bioassays. Finally, the relative potencies of the mixtures indicated by RHT analysis were consistent with the chemical profiles of the samples. RHT analysis with human cells provides an efficient and cost-effective approach to benchmarking mixture of micropollutants and may offer novel insight into the assessment of mixture toxicity in water.

  10. 76 FR 72417 - Public Health Service Guideline for Reducing Transmission of Human Immunodeficiency Virus (HIV...

    Science.gov (United States)

    2011-11-23

    ... (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) Through Solid Organ Transplantation AGENCY... Reducing Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus... Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) through...

  11. Campylobacter in primary animal production and control strategies to reduce the burden of human campylobacteriosis

    NARCIS (Netherlands)

    Wagenaar, J.A.; Mevius, D.J.; Havelaar, A.H.

    2006-01-01

    Campylobacteriosis is one of the most important bacterial food-borne illnesses in humans. One significant source of infection is the handling and consumption of poultry meat, although other sources also contribute considerably. Controlling Campylobacter in broilers reduces the human burden of

  12. Reduced influenza viral neutralizing activity of natural human trimers of surfactant protein D

    DEFF Research Database (Denmark)

    Hartshorn, Kevan L; White, Mitchell R; Tecle, Tesfaldet

    2007-01-01

    human SP-D multimers as well as reduced hemagglutination inhibiting activity against several strains of IAV. Natural SP-D trimers also had different interactions with human neutrophil peptide defensins (HNPs) in viral neutralization assays as compared to multimeric SP-D. CONCLUSION: These studies...

  13. 76 FR 54408 - Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing...

    Science.gov (United States)

    2011-09-01

    ... and Drug Administration 21 CFR Parts 50 and 56 Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing Burden, Delay, and Ambiguity for Investigators; Extension of... Secretary of the Department of Health and Human Services (HHS) in coordination with the Office of Science...

  14. Material Models for the Human Torso Finite Element Model

    Science.gov (United States)

    2018-04-04

    ARL-TR-8338 ● Apr 2018 US Army Research Laboratory Material Models for the Human Torso Finite Element Model by Carolyn E...longer needed. Do not return it to the originator. ARL-TR-8338 ● Apr 2018 US Army Research Laboratory Material Models for the...Weapons and Materials Research Directorate, ARL Approved for public release; distribution is unlimited. ii REPORT

  15. Modeling human learning involved in car driving

    NARCIS (Netherlands)

    Wewerinke, P.H.

    1994-01-01

    In this paper, car driving is considered at the level of human tracking and maneuvering in the context of other traffic. A model analysis revealed the most salient features determining driving performance and safety. Learning car driving is modelled based on a system theoretical approach and based

  16. A Model of the Human Eye

    Science.gov (United States)

    Colicchia, G.; Wiesner, H.; Waltner, C.; Zollman, D.

    2008-01-01

    We describe a model of the human eye that incorporates a variable converging lens. The model can be easily constructed by students with low-cost materials. It shows in a comprehensible way the functionality of the eye's optical system. Images of near and far objects can be focused. Also, the defects of near and farsighted eyes can be demonstrated.

  17. Mathematical human body modelling for impact loading

    NARCIS (Netherlands)

    Happee, R.; Morsink, P.L.J.; Wismans, J.S.H.M.

    1999-01-01

    Mathematical modelling of the human body is widely used for automotive crash safety research and design. Simulations have contributed to a reduction of injury numbers by optimisation of vehicle structures and restraint systems. Currently such simulations are largely performed using occupant models

  18. Escitalopram reduces increased hippocampal cytogenesis in a genetic rat depression model

    DEFF Research Database (Denmark)

    Petersén, Asa; Wörtwein, Gitta; Gruber, Susanne H M

    2008-01-01

    ) reduced by escitalopram treatment in maternally separated animals to the level found in non-separated animals. These results argue against the prevailing hypothesis that adult cytogenesis is reduced in depression and that the common mechanism underlying antidepressant treatments is to increase adult...... cytogenesis. The results also point to the importance of using a disease model and not healthy animals for testing effects of potential treatments for human depression and suggest other cellular mechanisms of action than those that had previously been proposed for escitalopram....

  19. Mathematical models of human african trypanosomiasis epidemiology.

    Science.gov (United States)

    Rock, Kat S; Stone, Chris M; Hastings, Ian M; Keeling, Matt J; Torr, Steve J; Chitnis, Nakul

    2015-03-01

    Human African trypanosomiasis (HAT), commonly called sleeping sickness, is caused by Trypanosoma spp. and transmitted by tsetse flies (Glossina spp.). HAT is usually fatal if untreated and transmission occurs in foci across sub-Saharan Africa. Mathematical modelling of HAT began in the 1980s with extensions of the Ross-Macdonald malaria model and has since consisted, with a few exceptions, of similar deterministic compartmental models. These models have captured the main features of HAT epidemiology and provided insight on the effectiveness of the two main control interventions (treatment of humans and tsetse fly control) in eliminating transmission. However, most existing models have overestimated prevalence of infection and ignored transient dynamics. There is a need for properly validated models, evolving with improved data collection, that can provide quantitative predictions to help guide control and elimination strategies for HAT. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Human models of acute lung injury

    Directory of Open Access Journals (Sweden)

    Alastair G. Proudfoot

    2011-03-01

    Full Text Available Acute lung injury (ALI is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome.

  1. Sparsity enabled cluster reduced-order models for control

    Science.gov (United States)

    Kaiser, Eurika; Morzyński, Marek; Daviller, Guillaume; Kutz, J. Nathan; Brunton, Bingni W.; Brunton, Steven L.

    2018-01-01

    Characterizing and controlling nonlinear, multi-scale phenomena are central goals in science and engineering. Cluster-based reduced-order modeling (CROM) was introduced to exploit the underlying low-dimensional dynamics of complex systems. CROM builds a data-driven discretization of the Perron-Frobenius operator, resulting in a probabilistic model for ensembles of trajectories. A key advantage of CROM is that it embeds nonlinear dynamics in a linear framework, which enables the application of standard linear techniques to the nonlinear system. CROM is typically computed on high-dimensional data; however, access to and computations on this full-state data limit the online implementation of CROM for prediction and control. Here, we address this key challenge by identifying a small subset of critical measurements to learn an efficient CROM, referred to as sparsity-enabled CROM. In particular, we leverage compressive measurements to faithfully embed the cluster geometry and preserve the probabilistic dynamics. Further, we show how to identify fewer optimized sensor locations tailored to a specific problem that outperform random measurements. Both of these sparsity-enabled sensing strategies significantly reduce the burden of data acquisition and processing for low-latency in-time estimation and control. We illustrate this unsupervised learning approach on three different high-dimensional nonlinear dynamical systems from fluids with increasing complexity, with one application in flow control. Sparsity-enabled CROM is a critical facilitator for real-time implementation on high-dimensional systems where full-state information may be inaccessible.

  2. Optimizing Crawler4j using MapReduce Programming Model

    Science.gov (United States)

    Siddesh, G. M.; Suresh, Kavya; Madhuri, K. Y.; Nijagal, Madhushree; Rakshitha, B. R.; Srinivasa, K. G.

    2017-06-01

    World wide web is a decentralized system that consists of a repository of information on the basis of web pages. These web pages act as a source of information or data in the present analytics world. Web crawlers are used for extracting useful information from web pages for different purposes. Firstly, it is used in web search engines where the web pages are indexed to form a corpus of information and allows the users to query on the web pages. Secondly, it is used for web archiving where the web pages are stored for later analysis phases. Thirdly, it can be used for web mining where the web pages are monitored for copyright purposes. The amount of information processed by the web crawler needs to be improved by using the capabilities of modern parallel processing technologies. In order to solve the problem of parallelism and the throughput of crawling this work proposes to optimize the Crawler4j using the Hadoop MapReduce programming model by parallelizing the processing of large input data. Crawler4j is a web crawler that retrieves useful information about the pages that it visits. The crawler Crawler4j coupled with data and computational parallelism of Hadoop MapReduce programming model improves the throughput and accuracy of web crawling. The experimental results demonstrate that the proposed solution achieves significant improvements with respect to performance and throughput. Hence the proposed approach intends to carve out a new methodology towards optimizing web crawling by achieving significant performance gain.

  3. Improving Saliency Models by Predicting Human Fixation Patches

    KAUST Repository

    Dubey, Rachit

    2015-04-16

    There is growing interest in studying the Human Visual System (HVS) to supplement and improve the performance of computer vision tasks. A major challenge for current visual saliency models is predicting saliency in cluttered scenes (i.e. high false positive rate). In this paper, we propose a fixation patch detector that predicts image patches that contain human fixations with high probability. Our proposed model detects sparse fixation patches with an accuracy of 84 % and eliminates non-fixation patches with an accuracy of 84 % demonstrating that low-level image features can indeed be used to short-list and identify human fixation patches. We then show how these detected fixation patches can be used as saliency priors for popular saliency models, thus, reducing false positives while maintaining true positives. Extensive experimental results show that our proposed approach allows state-of-the-art saliency methods to achieve better prediction performance on benchmark datasets.

  4. Informing Investment to Reduce Inequalities: A Modelling Approach.

    Science.gov (United States)

    McAuley, Andrew; Denny, Cheryl; Taulbut, Martin; Mitchell, Rory; Fischbacher, Colin; Graham, Barbara; Grant, Ian; O'Hagan, Paul; McAllister, David; McCartney, Gerry

    2016-01-01

    Reducing health inequalities is an important policy objective but there is limited quantitative information about the impact of specific interventions. To provide estimates of the impact of a range of interventions on health and health inequalities. Literature reviews were conducted to identify the best evidence linking interventions to mortality and hospital admissions. We examined interventions across the determinants of health: a 'living wage'; changes to benefits, taxation and employment; active travel; tobacco taxation; smoking cessation, alcohol brief interventions, and weight management services. A model was developed to estimate mortality and years of life lost (YLL) in intervention and comparison populations over a 20-year time period following interventions delivered only in the first year. We estimated changes in inequalities using the relative index of inequality (RII). Introduction of a 'living wage' generated the largest beneficial health impact, with modest reductions in health inequalities. Benefits increases had modest positive impacts on health and health inequalities. Income tax increases had negative impacts on population health but reduced inequalities, while council tax increases worsened both health and health inequalities. Active travel increases had minimally positive effects on population health but widened health inequalities. Increases in employment reduced inequalities only when targeted to the most deprived groups. Tobacco taxation had modestly positive impacts on health but little impact on health inequalities. Alcohol brief interventions had modestly positive impacts on health and health inequalities only when strongly socially targeted, while smoking cessation and weight-reduction programmes had minimal impacts on health and health inequalities even when socially targeted. Interventions have markedly different effects on mortality, hospitalisations and inequalities. The most effective (and likely cost-effective) interventions for

  5. Informing Investment to Reduce Inequalities: A Modelling Approach.

    Directory of Open Access Journals (Sweden)

    Andrew McAuley

    Full Text Available Reducing health inequalities is an important policy objective but there is limited quantitative information about the impact of specific interventions.To provide estimates of the impact of a range of interventions on health and health inequalities.Literature reviews were conducted to identify the best evidence linking interventions to mortality and hospital admissions. We examined interventions across the determinants of health: a 'living wage'; changes to benefits, taxation and employment; active travel; tobacco taxation; smoking cessation, alcohol brief interventions, and weight management services. A model was developed to estimate mortality and years of life lost (YLL in intervention and comparison populations over a 20-year time period following interventions delivered only in the first year. We estimated changes in inequalities using the relative index of inequality (RII.Introduction of a 'living wage' generated the largest beneficial health impact, with modest reductions in health inequalities. Benefits increases had modest positive impacts on health and health inequalities. Income tax increases had negative impacts on population health but reduced inequalities, while council tax increases worsened both health and health inequalities. Active travel increases had minimally positive effects on population health but widened health inequalities. Increases in employment reduced inequalities only when targeted to the most deprived groups. Tobacco taxation had modestly positive impacts on health but little impact on health inequalities. Alcohol brief interventions had modestly positive impacts on health and health inequalities only when strongly socially targeted, while smoking cessation and weight-reduction programmes had minimal impacts on health and health inequalities even when socially targeted.Interventions have markedly different effects on mortality, hospitalisations and inequalities. The most effective (and likely cost

  6. Drinking beer reduces radiation-induced chromosome aberrations in human lymphocytes

    International Nuclear Information System (INIS)

    Monobe, Manami

    2002-01-01

    We here investigated and reported the effects of beer drinking on radiation-induced chromosome aberrations in blood lymphocytes. Human blood that was collected either before or after drinking a 700 ml beer was in vitro irradiated with 200 kVp X rays or 50 keV/μm carbon ions. The relation between the radiation dose and the aberration frequencies (fragments and dicentrics) was significantly (P<0.05) lower for lymphocytes collected 3 h after beer drinking than those before drinking. Fitting the dose response to a linear quadratic model showed that the alpha term of carbon ions was significantly (P<0.05) decreased by beer drinking. A decrease of dicentric formation was detected as early as 0.5 h after beer drinking, and lasted not shorter than 4.5 h. The mitotic index of lymphocytes was higher after beer drinking than before, indicating that a division delay would not be responsible for the low aberrations induced by beer drinking. An in vitro treatment of normal lymphocytes with 0.1 M ethanol, which corresponded to a concentration of 6-times higher than the maximum ethanol concentration in the blood after beer drinking, reduced the dicentric formation caused by X-ray irradiation, but not by carbon-ion irradiation. The beer-induced reduction of dicentric formation was not affected by serum. It is concluded that beer could contain non-ethanol elements that reduce the chromosome damage of lymphocytes induced by high-LET radiation. (author)

  7. Integrated Human Futures Modeling in Egypt

    Energy Technology Data Exchange (ETDEWEB)

    Passell, Howard D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Aamir, Munaf Syed [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bernard, Michael Lewis [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Beyeler, Walter E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Fellner, Karen Marie [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hayden, Nancy Kay [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jeffers, Robert Fredric [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Keller, Elizabeth James Kistin [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Malczynski, Leonard A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Mitchell, Michael David [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Silver, Emily [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Tidwell, Vincent C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Villa, Daniel [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Vugrin, Eric D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Engelke, Peter [Atlantic Council, Washington, D.C. (United States); Burrow, Mat [Atlantic Council, Washington, D.C. (United States); Keith, Bruce [United States Military Academy, West Point, NY (United States)

    2016-01-01

    The Integrated Human Futures Project provides a set of analytical and quantitative modeling and simulation tools that help explore the links among human social, economic, and ecological conditions, human resilience, conflict, and peace, and allows users to simulate tradeoffs and consequences associated with different future development and mitigation scenarios. In the current study, we integrate five distinct modeling platforms to simulate the potential risk of social unrest in Egypt resulting from the Grand Ethiopian Renaissance Dam (GERD) on the Blue Nile in Ethiopia. The five platforms simulate hydrology, agriculture, economy, human ecology, and human psychology/behavior, and show how impacts derived from development initiatives in one sector (e.g., hydrology) might ripple through to affect other sectors and how development and security concerns may be triggered across the region. This approach evaluates potential consequences, intended and unintended, associated with strategic policy actions that span the development-security nexus at the national, regional, and international levels. Model results are not intended to provide explicit predictions, but rather to provide system-level insight for policy makers into the dynamics among these interacting sectors, and to demonstrate an approach to evaluating short- and long-term policy trade-offs across different policy domains and stakeholders. The GERD project is critical to government-planned development efforts in Ethiopia but is expected to reduce downstream freshwater availability in the Nile Basin, fueling fears of negative social and economic impacts that could threaten stability and security in Egypt. We tested these hypotheses and came to the following preliminary conclusions. First, the GERD will have an important short-term impact on water availability, food production, and hydropower production in Egypt, depending on the short- term reservoir fill rate. Second, the GERD will have a very small impact on

  8. Identification of walking human model using agent-based modelling

    Science.gov (United States)

    Shahabpoor, Erfan; Pavic, Aleksandar; Racic, Vitomir

    2018-03-01

    The interaction of walking people with large vibrating structures, such as footbridges and floors, in the vertical direction is an important yet challenging phenomenon to describe mathematically. Several different models have been proposed in the literature to simulate interaction of stationary people with vibrating structures. However, the research on moving (walking) human models, explicitly identified for vibration serviceability assessment of civil structures, is still sparse. In this study, the results of a comprehensive set of FRF-based modal tests were used, in which, over a hundred test subjects walked in different group sizes and walking patterns on a test structure. An agent-based model was used to simulate discrete traffic-structure interactions. The occupied structure modal parameters found in tests were used to identify the parameters of the walking individual's single-degree-of-freedom (SDOF) mass-spring-damper model using 'reverse engineering' methodology. The analysis of the results suggested that the normal distribution with the average of μ = 2.85Hz and standard deviation of σ = 0.34Hz can describe human SDOF model natural frequency. Similarly, the normal distribution with μ = 0.295 and σ = 0.047 can describe the human model damping ratio. Compared to the previous studies, the agent-based modelling methodology proposed in this paper offers significant flexibility in simulating multi-pedestrian walking traffics, external forces and simulating different mechanisms of human-structure and human-environment interaction at the same time.

  9. Stochastic reduced order models for inverse problems under uncertainty.

    Science.gov (United States)

    Warner, James E; Aquino, Wilkins; Grigoriu, Mircea D

    2015-03-01

    This work presents a novel methodology for solving inverse problems under uncertainty using stochastic reduced order models (SROMs). Given statistical information about an observed state variable in a system, unknown parameters are estimated probabilistically through the solution of a model-constrained, stochastic optimization problem. The point of departure and crux of the proposed framework is the representation of a random quantity using a SROM - a low dimensional, discrete approximation to a continuous random element that permits e cient and non-intrusive stochastic computations. Characterizing the uncertainties with SROMs transforms the stochastic optimization problem into a deterministic one. The non-intrusive nature of SROMs facilitates e cient gradient computations for random vector unknowns and relies entirely on calls to existing deterministic solvers. Furthermore, the method is naturally extended to handle multiple sources of uncertainty in cases where state variable data, system parameters, and boundary conditions are all considered random. The new and widely-applicable SROM framework is formulated for a general stochastic optimization problem in terms of an abstract objective function and constraining model. For demonstration purposes, however, we study its performance in the specific case of inverse identification of random material parameters in elastodynamics. We demonstrate the ability to efficiently recover random shear moduli given material displacement statistics as input data. We also show that the approach remains effective for the case where the loading in the problem is random as well.

  10. Numerical modelling of pyrolysis in normal and reduced oxygen concentration

    International Nuclear Information System (INIS)

    Kacem, Ahmed

    2016-01-01

    The predictive capability of computational fluid dynamics (CFD) fire models depends on the accuracy with which the source term due to fuel pyrolysis can be determined. The pyrolysis rate is a key parameter controlling fire behavior, which in turn drives the heat feedback from the flame to the fuel surface. In the present study an in-depth pyrolysis model of a semi-transparent solid fuel (here, clear polymethyl methacrylate or PMMA) with spectrally-resolved radiation and a moving gas/solid interface was coupled with the CFD code ISIS of the IRSN which included turbulence, combustion and radiation for the gas phase. A combined genetic algorithm/pyrolysis model was used with Cone Calorimeter data from a pure pyrolysis experiment to estimate a unique set of kinetic parameters for PMMA pyrolysis. In order to validate the coupled model, ambient air flaming experiments were conducted on square slabs of PMMA with side lengths of 10, 20 and 40 cm. From measurements at the center of the slab, it was found that i) for any sample size, the experimental regression rate becomes almost constant with time, and ii) although the radiative and total heat transfers increase significantly with the sample size, the radiative contribution to the total heat flux remains almost constant (∼80%). Coupled model results show a fairly good agreement with the literature and with current measurements of the heat fluxes, gas temperature and regressing surface rate at the center of the slabs. Discrepancies between predicted and measured total pyrolysis rate are observed, which result from the underestimation of the flame heat flux feedback at the edges of the slab, as confirmed by the comparison between predicted and observed topography of burned samples. Predicted flame heights based on a threshold temperature criterion were found to be close to those deduced from the correlation of Heskestad. Finally, in order to predict the pyrolysis of PMMA under reduced ambient oxygen concentration, a two

  11. Reduced Lorenz models for anomalous transport and profile resilience

    DEFF Research Database (Denmark)

    Rypdal, K.; Garcia, Odd Erik

    2007-01-01

    The physical basis for the Lorenz equations for convective cells in stratified fluids, and for magnetized plasmas imbedded in curved magnetic fields, are reexamined with emphasis on anomalous transport. It is shown that the Galerkin truncation leading to the Lorenz equations for the closed boundary...... problem is incompatible with finite fluxes through the system in the limit of vanishing diffusion. An alternative formulation leading to the Lorenz equations is proposed, invoking open boundaries and the notion of convective streamers and their back-reaction on the profile gradient, giving rise...... to resilience of the profile. Particular emphasis is put on the diffusionless limit, where these equations reduce to a simple dynamical system depending only on one single forcing parameter. This model is studied numerically, stressing experimentally observable signatures, and some of the perils of dimension...

  12. Reduced Order Modeling of Combustion Instability in a Gas Turbine Model Combustor

    Science.gov (United States)

    Arnold-Medabalimi, Nicholas; Huang, Cheng; Duraisamy, Karthik

    2017-11-01

    Hydrocarbon fuel based propulsion systems are expected to remain relevant in aerospace vehicles for the foreseeable future. Design of these devices is complicated by combustion instabilities. The capability to model and predict these effects at reduced computational cost is a requirement for both design and control of these devices. This work focuses on computational studies on a dual swirl model gas turbine combustor in the context of reduced order model development. Full fidelity simulations are performed utilizing URANS and Hybrid RANS-LES with finite rate chemistry. Following this, data decomposition techniques are used to extract a reduced basis representation of the unsteady flow field. These bases are first used to identify sensor locations to guide experimental interrogations and controller feedback. Following this, initial results on developing a control-oriented reduced order model (ROM) will be presented. The capability of the ROM will be further assessed based on different operating conditions and geometric configurations.

  13. State reduced order models for the modelling of the thermal behavior of buildings

    Energy Technology Data Exchange (ETDEWEB)

    Menezo, Christophe; Bouia, Hassan; Roux, Jean-Jacques; Depecker, Patrick [Institute National de Sciences Appliquees de Lyon, Villeurbanne Cedex, (France). Centre de Thermique de Lyon (CETHIL). Equipe Thermique du Batiment]. E-mail: menezo@insa-cethil-etb.insa-lyon.fr; bouia@insa-cethil-etb.insa-lyon.fr; roux@insa-cethil-etb.insa-lyon.fr; depecker@insa-cethil-etb.insa-lyon.fr

    2000-07-01

    This work is devoted to the field of building physics and related to the reduction of heat conduction models. The aim is to enlarge the model libraries of heat and mass transfer codes through limiting the considerable dimensions reached by the numerical systems during the modelling process of a multizone building. We show that the balanced realization technique, specifically adapted to the coupling of reduced order models with the other thermal phenomena, turns out to be very efficient. (author)

  14. Analisis Model Pengukuran Human Capital dalam Organisasi

    Directory of Open Access Journals (Sweden)

    Cecep Hidayat

    2013-11-01

    Full Text Available Measurement of human capital is not an easy to do because it is dynamic and always changing in accordance with the changing circumstances. Determination of dimensions and indicators of measurement needs to consider various factors such as situations and also the research scopes. This article has objectives to review the concepts, dimensions and measurement models of human capital. The research method used was literature study with a major reference source from current journal articles that discuss the measurement of human capital. Results of the study showed that basically the definition set forth in any dimension containing either explicitly or implicitly. In addition, the result indicated that there are three main categories of equality among researchers regarding the definition of human capital which emphasizes on: economic value/productivity, education, and abilities/competencies. The results also showed that the use of definitions, dimensions, and indicators for measurement of human capital depends on the situation, the scope of research, and the size of the organization. The conclusion of the study indicated that the measurement model and determination of dimensions and indicators of human capital measurement will determine the effectiveness of the measurement, and will have an impact on organizational performance.

  15. Modeling the exergy behavior of human body

    International Nuclear Information System (INIS)

    Keutenedjian Mady, Carlos Eduardo; Silva Ferreira, Maurício; Itizo Yanagihara, Jurandir; Hilário Nascimento Saldiva, Paulo; Oliveira Junior, Silvio de

    2012-01-01

    Exergy analysis is applied to assess the energy conversion processes that take place in the human body, aiming at developing indicators of health and performance based on the concepts of exergy destroyed rate and exergy efficiency. The thermal behavior of the human body is simulated by a model composed of 15 cylinders with elliptical cross section representing: head, neck, trunk, arms, forearms, hands, thighs, legs, and feet. For each, a combination of tissues is considered. The energy equation is solved for each cylinder, being possible to obtain transitory response from the body due to a variation in environmental conditions. With this model, it is possible to obtain heat and mass flow rates to the environment due to radiation, convection, evaporation and respiration. The exergy balances provide the exergy variation due to heat and mass exchange over the body, and the exergy variation over time for each compartments tissue and blood, the sum of which leads to the total variation of the body. Results indicate that exergy destroyed and exergy efficiency decrease over lifespan and the human body is more efficient and destroys less exergy in lower relative humidities and higher temperatures. -- Highlights: ► In this article it is indicated an overview of the human thermal model. ► It is performed the energy and exergy analysis of the human body. ► Exergy destruction and exergy efficiency decreases with lifespan. ► Exergy destruction and exergy efficiency are a function of environmental conditions.

  16. Models of the Human in Tantric Hinduism

    DEFF Research Database (Denmark)

    Olesen, Bjarne Wernicke; Flood, Gavin

    2019-01-01

    This research project explores the origins, developments and transformations of yogic models of the human (e.g. kuṇḍalinī yoga, the cakra system and ritual sex) in the tantric goddess traditions or what might be called Śāktism of medieval India. These Śākta models of esoteric anatomy originating...... in medieval ascetic traditions became highly influential in South Asia and were popularized in the West....

  17. Mining on Big Data Using Hadoop MapReduce Model

    Science.gov (United States)

    Salman Ahmed, G.; Bhattacharya, Sweta

    2017-11-01

    Customary parallel calculations for mining nonstop item create opportunity to adjust stack of similar data among hubs. The paper aims to review this process by analyzing the critical execution downside of the common parallel recurrent item-set mining calculations. Given a larger than average dataset, data apportioning strategies inside the current arrangements endure high correspondence and mining overhead evoked by repetitive exchanges transmitted among registering hubs. We tend to address this downside by building up a learning apportioning approach referred as Hadoop abuse using the map-reduce programming model. All objectives of Hadoop are to zest up the execution of parallel recurrent item-set mining on Hadoop bunches. Fusing the comparability metric and furthermore the locality-sensitive hashing procedure, Hadoop puts to a great degree comparative exchanges into an information segment to lift neighborhood while not making AN exorbitant assortment of excess exchanges. We tend to execute Hadoop on a 34-hub Hadoop bunch, driven by a decent change of datasets made by IBM quest market-basket manufactured data generator. Trial uncovers the fact that Hadoop contributes towards lessening system and processing masses by the uprightness of dispensing with excess exchanges on Hadoop hubs. Hadoop impressively outperforms and enhances the other models considerably.

  18. Are animal models predictive for humans?

    Directory of Open Access Journals (Sweden)

    Greek Ray

    2009-01-01

    Full Text Available Abstract It is one of the central aims of the philosophy of science to elucidate the meanings of scientific terms and also to think critically about their application. The focus of this essay is the scientific term predict and whether there is credible evidence that animal models, especially in toxicology and pathophysiology, can be used to predict human outcomes. Whether animals can be used to predict human response to drugs and other chemicals is apparently a contentious issue. However, when one empirically analyzes animal models using scientific tools they fall far short of being able to predict human responses. This is not surprising considering what we have learned from fields such evolutionary and developmental biology, gene regulation and expression, epigenetics, complexity theory, and comparative genomics.

  19. [Primate models of human viral hepatitis].

    Science.gov (United States)

    Poleshchuk, V F; Mikhaĭlov, M I; Zamiatina, N A

    2006-01-01

    The paper summarizes the updates available in the literature and the authors' own data on the etiology of hepatitis, its models, and experimental studies on susceptible simian types. A comparative analysis of the etiological agents--the causative agents of simian and human hepatitis will give a better insight into the evolution of its viruses.

  20. Quality assessment of human behavior models

    NARCIS (Netherlands)

    Doesburg, W.A. van

    2007-01-01

    Accurate and efficient models of human behavior offer great potential in military and crisis management applications. However, little attention has been given to the man ner in which it can be determined if this potential is actually realized. In this study a quality assessment approach that

  1. Future of human models for crash analysis

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Hoof, J.F.A.M. van; Lange, R. de

    2001-01-01

    In the crash safety field mathematical models can be applied in practically all area's of research and development including: reconstruction of actual accidents, design (CAD) of the crash response of vehicles, safety devices and roadside facilities and in support of human impact biomechanical

  2. Optical models of the human eye.

    Science.gov (United States)

    Atchison, David A; Thibos, Larry N

    2016-03-01

    Optical models of the human eye have been used in visual science for purposes such as providing a framework for explaining optical phenomena in vision, for predicting how refraction and aberrations are affected by change in ocular biometry and as computational tools for exploring the limitations imposed on vision by the optical system of the eye. We address the issue of what is understood by optical model eyes, discussing the 'encyclopaedia' and 'toy train' approaches to modelling. An extensive list of purposes of models is provided. We discuss many of the theoretical types of optical models (also schematic eyes) of varying anatomical accuracy, including single, three and four refracting surface variants. We cover the models with lens structure in the form of nested shells and gradient index. Many optical eye models give accurate predictions only for small angles and small fields of view. If aberrations and image quality are important to consider, such 'paraxial' model eyes must be replaced by 'finite model' eyes incorporating features such as aspheric surfaces, tilts and decentrations, wavelength-dependent media and curved retinas. Many optical model eyes are population averages and must become adaptable to account for age, gender, ethnicity, refractive error and accommodation. They can also be customised for the individual when extensive ocular biometry and optical performance data are available. We consider which optical model should be used for a particular purpose, adhering to the principle that the best model is the simplest fit for the task. We provide a glimpse into the future of optical models of the human eye. This review is interwoven with historical developments, highlighting the important people who have contributed so richly to our understanding of visual optics. © 2016 The Authors. Clinical and Experimental Optometry © 2016 Optometry Australia.

  3. Modelling of Joint Crowd-Structure System Using Equivalent Reduced-DOF System

    Directory of Open Access Journals (Sweden)

    Jackie Sim

    2007-01-01

    Full Text Available For human assembly structures in which the mass of the crowd is significant compared to that of the structure, it is necessary to model the passive crowd as a dynamic system added to the main structural system. Earlier work by the authors has analysed the frequency response of a joint crowd-structure system in which the structure is treated as a single degree-of-freedom (SDOF system and the seated and standing crowds are each modelled as a two degree-of-freedom (2DOF system. It was found that the occupied structure has dynamic properties different to the empty structure. This paper investigates representing the joint crowd-structure system as an equivalent reduced-DOF system that would have the advantage of simplifying the analysis. The modal properties of the equivalent reduced-DOF system, if known, can give a useful indication of how the passive crowd affects the modal properties of the occupied structure. Two equivalent reduced-DOF systems are investigated – SDOF and 3DOF systems. The errors between the responses of the equivalent systems and the full model are calculated and presented in the paper. The results show that the full model exhibits the behaviour of a SDOF system for structures with natural frequencies less than 4 Hz (when empty, whereas for structures with natural frequencies above 4 Hz the equivalent 3DOF system gives a better fit to the full model.

  4. A Novel Ras Inhibitor (MDC-1016 Reduces Human Pancreatic Tumor Growth in Mice

    Directory of Open Access Journals (Sweden)

    Gerardo G Mackenzie

    2013-10-01

    Full Text Available Pancreatic cancer has one of the poorest prognoses among all cancers partly because of its persistent resistance to chemotherapy. The currently limited treatment options for pancreatic cancer underscore the need for more efficient agents. Because activating Kras mutations initiate and maintain pancreatic cancer, inhibition of this pathway should have a major therapeutic impact. We synthesized phospho-farnesylthiosalicylic acid (PFTS; MDC-1016 and evaluated its efficacy, safety, and metabolism in preclinical models of pancreatic cancer. PFTS inhibited the growth of human pancreatic cancer cells in culture in a concentration- and time-dependent manner. In an MIA PaCa-2 xenograft mouse model, PFTS at a dose of 50 and 100 mg/kg significantly reduced tumor growth by 62% and 65% (P < .05 vs vehicle control. Furthermore, PFTS prevented pancreatitis-accelerated acinar-to-ductal metaplasia in mice with activated Kras. PFTS appeared to be safe, with the animals showing no signs of toxicity during treatment. Following oral administration, PFTS was rapidly absorbed, metabolized to FTS and FTS glucuronide, and distributed through the blood to body organs. Mechanistically, PFTS inhibited Ras-GTP, the active form of Ras, both in vitro and in vivo, leading to the inhibition of downstream effector pathways c-RAF/mitogen-activated protein-extracellular signal-regulated kinase (ERK kinase (MEK/ERK1/2 kinase and phosphatidylinositol 3-kinase/AKT. In addition, PFTS proved to be a strong combination partner with phospho-valproic acid, a novel signal transducer and activator of transcription 3 (STAT3 inhibitor, displaying synergy in the inhibition of pancreatic cancer growth. In conclusion, PFTS, a direct Ras inhibitor, is an efficacious agent for the treatment of pancreatic cancer in preclinical models, deserving further evaluation.

  5. Modelling obesity outcomes: reducing obesity risk in adulthood may have grater impact than reducing obesity prevalence in childhood

    NARCIS (Netherlands)

    Lhachimi, S.K.; Nusselder, W.J.; Lobstein, T.J.; Smit, H.A.; Baili, P.; Bennett, K.; Kulik, M.C.; Jackson-Leach, R.; Boshuizen, H.C.; Mackenbach, J.P.

    2013-01-01

    A common policy response to the rise in obesity prevalence is to undertake interventions in childhood, but it is an open question whether this is more effective than reducing the risk of becoming obese during adulthood. In this paper, we model the effect on health outcomes of (i) reducing the

  6. A mathematical model for reducing the composting time

    Directory of Open Access Journals (Sweden)

    Estefanía Larreategui

    2014-06-01

    Full Text Available The environment is still affected by the inappropriate use of organic matter waste, but a culture of recycling and reuse has been promoted in Ecuador to reduce carbon footprint. The composting, a technique to digest organic matter, which traditionally takes 16-24 weeks, is still inefficient to use. Therefore, this paper concerns the optimization of the composting process in both quality and production time. The variables studied were: type of waste (fruits and vegetables and type of bioaccelerator (yeast and indigenous microorganisms. By using a full factorial random design 22, a quality compost was obtained in 7 weeks of processing. Quality factors as temperature, density, moisture content, pH and carbon-nitrogen ratio allowed the best conditions for composting in the San Gabriel del Baba community (Santo Domingo de los Colorados, Ecuador. As a result of this study, a mathematical surface model which explains the relationship between the temperature and the digestion time of organic matter was obtained.

  7. Stabilization Approaches for Linear and Nonlinear Reduced Order Models

    Science.gov (United States)

    Rezaian, Elnaz; Wei, Mingjun

    2017-11-01

    It has been a major concern to establish reduced order models (ROMs) as reliable representatives of the dynamics inherent in high fidelity simulations, while fast computation is achieved. In practice it comes to stability and accuracy of ROMs. Given the inviscid nature of Euler equations it becomes more challenging to achieve stability, especially where moving discontinuities exist. Originally unstable linear and nonlinear ROMs are stabilized here by two approaches. First, a hybrid method is developed by integrating two different stabilization algorithms. At the same time, symmetry inner product is introduced in the generation of ROMs for its known robust behavior for compressible flows. Results have shown a notable improvement in computational efficiency and robustness compared to similar approaches. Second, a new stabilization algorithm is developed specifically for nonlinear ROMs. This method adopts Particle Swarm Optimization to enforce a bounded ROM response for minimum discrepancy between the high fidelity simulation and the ROM outputs. Promising results are obtained in its application on the nonlinear ROM of an inviscid fluid flow with discontinuities. Supported by ARL.

  8. Inhibition of TRPM8 channels reduces pain in the cold pressor test in humans.

    Science.gov (United States)

    Winchester, Wendy J; Gore, Katrina; Glatt, Sophie; Petit, Wendy; Gardiner, Jennifer C; Conlon, Kelly; Postlethwaite, Michael; Saintot, Pierre-Philippe; Roberts, Sonia; Gosset, James R; Matsuura, Tomomi; Andrews, Mark D; Glossop, Paul A; Palmer, Michael J; Clear, Nicola; Collins, Susie; Beaumont, Kevin; Reynolds, David S

    2014-11-01

    The transient receptor potential (subfamily M, member 8; TRPM8) is a nonselective cation channel localized in primary sensory neurons, and is a candidate for cold thermosensing, mediation of cold pain, and bladder overactivity. Studies with TRPM8 knockout mice and selective TRPM8 channel blockers demonstrate a lack of cold sensitivity and reduced cold pain in various rodent models. Furthermore, TRPM8 blockers significantly lower body temperature. We have identified a moderately potent (IC50 = 103 nM), selective TRPM8 antagonist, PF-05105679 [(R)-3-[(1-(4-fluorophenyl)ethyl)(quinolin-3-ylcarbonyl)amino]methylbenzoic acid]. It demonstrated activity in vivo in the guinea pig bladder ice water and menthol challenge tests with an IC50 of 200 nM and reduced core body temperature in the rat (at concentrations >1219 nM). PF-05105679 was suitable for acute administration to humans and was evaluated for effects on core body temperature and experimentally induced cold pain, using the cold pressor test. Unbound plasma concentrations greater than the IC50 were achieved with 600- and 900-mg doses. The compound displayed a significant inhibition of pain in the cold pressor test, with efficacy equivalent to oxycodone (20 mg) at 1.5 hours postdose. No effect on core body temperature was observed. An unexpected adverse event (hot feeling) was reported, predominantly periorally, in 23 and 36% of volunteers (600- and 900-mg dose, respectively), which in two volunteers was nontolerable. In conclusion, this study supports a role for TRPM8 in acute cold pain signaling at doses that do not cause hypothermia. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  9. Modeling Operations Costs for Human Exploration Architectures

    Science.gov (United States)

    Shishko, Robert

    2013-01-01

    Operations and support (O&S) costs for human spaceflight have not received the same attention in the cost estimating community as have development costs. This is unfortunate as O&S costs typically comprise a majority of life-cycle costs (LCC) in such programs as the International Space Station (ISS) and the now-cancelled Constellation Program. Recognizing this, the Constellation Program and NASA HQs supported the development of an O&S cost model specifically for human spaceflight. This model, known as the Exploration Architectures Operations Cost Model (ExAOCM), provided the operations cost estimates for a variety of alternative human missions to the moon, Mars, and Near-Earth Objects (NEOs) in architectural studies. ExAOCM is philosophically based on the DoD Architecture Framework (DoDAF) concepts of operational nodes, systems, operational functions, and milestones. This paper presents some of the historical background surrounding the development of the model, and discusses the underlying structure, its unusual user interface, and lastly, previous examples of its use in the aforementioned architectural studies.

  10. 76 FR 44512 - Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing...

    Science.gov (United States)

    2011-07-26

    ... research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the... and Drug Administration 21 CFR Parts 50 and 56 Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing Burden, Delay, and Ambiguity for Investigators AGENCIES: The...

  11. Human factors study of driver assistance systems to reduce lane departures and side collision accidents.

    Science.gov (United States)

    2008-07-01

    This study investigated the human factors issues related to the implementation of lane departure warning systems (LDWS) to reduce side collision and run-off-road crashes for heavy trucks. Lane departures can be either intentional (e.g., to pass anoth...

  12. Retaining Educational Fundraisers: Reducing Turnover by Investing in Human Capital Management

    Science.gov (United States)

    Thomas, Christy

    2010-01-01

    This article outlines an approach to reducing gift officer turnover during comprehensive campaigns by investing in the human capital management (HCM) program. While many universities have begun to create HCM programs, I suggest creating a position specifically focused on the retention of gift offices to ensure that universities and non-profits can…

  13. Reducing consistency in human realism increases the uncanny valley effect; increasing category uncertainty does not.

    Science.gov (United States)

    MacDorman, Karl F; Chattopadhyay, Debaleena

    2016-01-01

    Human replicas may elicit unintended cold, eerie feelings in viewers, an effect known as the uncanny valley. Masahiro Mori, who proposed the effect in 1970, attributed it to inconsistencies in the replica's realism with some of its features perceived as human and others as nonhuman. This study aims to determine whether reducing realism consistency in visual features increases the uncanny valley effect. In three rounds of experiments, 548 participants categorized and rated humans, animals, and objects that varied from computer animated to real. Two sets of features were manipulated to reduce realism consistency. (For humans, the sets were eyes-eyelashes-mouth and skin-nose-eyebrows.) Reducing realism consistency caused humans and animals, but not objects, to appear eerier and colder. However, the predictions of a competing theory, proposed by Ernst Jentsch in 1906, were not supported: The most ambiguous representations-those eliciting the greatest category uncertainty-were neither the eeriest nor the coldest. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Computer Modeling of Human Delta Opioid Receptor

    Directory of Open Access Journals (Sweden)

    Tatyana Dzimbova

    2013-04-01

    Full Text Available The development of selective agonists of δ-opioid receptor as well as the model of interaction of ligands with this receptor is the subjects of increased interest. In the absence of crystal structures of opioid receptors, 3D homology models with different templates have been reported in the literature. The problem is that these models are not available for widespread use. The aims of our study are: (1 to choose within recently published crystallographic structures templates for homology modeling of the human δ-opioid receptor (DOR; (2 to evaluate the models with different computational tools; and (3 to precise the most reliable model basing on correlation between docking data and in vitro bioassay results. The enkephalin analogues, as ligands used in this study, were previously synthesized by our group and their biological activity was evaluated. Several models of DOR were generated using different templates. All these models were evaluated by PROCHECK and MolProbity and relationship between docking data and in vitro results was determined. The best correlations received for the tested models of DOR were found between efficacy (erel of the compounds, calculated from in vitro experiments and Fitness scoring function from docking studies. New model of DOR was generated and evaluated by different approaches. This model has good GA341 value (0.99 from MODELLER, good values from PROCHECK (92.6% of most favored regions and MolProbity (99.5% of favored regions. Scoring function correlates (Pearson r = -0.7368, p-value = 0.0097 with erel of a series of enkephalin analogues, calculated from in vitro experiments. So, this investigation allows suggesting a reliable model of DOR. Newly generated model of DOR receptor could be used further for in silico experiments and it will give possibility for faster and more correct design of selective and effective ligands for δ-opioid receptor.

  15. To Reduce the Global Burden of Human Schistosomiasis, Use 'Old Fashioned' Snail Control.

    Science.gov (United States)

    Sokolow, Susanne H; Wood, Chelsea L; Jones, Isabel J; Lafferty, Kevin D; Kuris, Armand M; Hsieh, Michael H; De Leo, Giulio A

    2018-01-01

    Control strategies to reduce human schistosomiasis have evolved from 'snail picking' campaigns, a century ago, to modern wide-scale human treatment campaigns, or preventive chemotherapy. Unfortunately, despite the rise in preventive chemotherapy campaigns, just as many people suffer from schistosomiasis today as they did 50 years ago. Snail control can complement preventive chemotherapy by reducing the risk of transmission from snails to humans. Here, we present ideas for modernizing and scaling up snail control, including spatiotemporal targeting, environmental diagnostics, better molluscicides, new technologies (e.g., gene drive), and 'outside the box' strategies such as natural enemies, traps, and repellants. We conclude that, to achieve the World Health Assembly's stated goal to eliminate schistosomiasis, it is time to give snail control another look. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. To reduce the global burden of human schistosomiasis, use ‘old fashioned’ snail control

    Science.gov (United States)

    Sokolow, Susanne H.; Wood, Chelsea L.; Jones, Isabel J.; Lafferty, Kevin D.; Kuris, Armand; Hsieh, Michael H.; De Leo, Giulio A.

    2018-01-01

    Control strategies to reduce human schistosomiasis have evolved from ‘snail picking’ campaigns, a century ago, to modern wide-scale human treatment campaigns, or preventive chemotherapy. Unfortunately, despite the rise in preventive chemotherapy campaigns, just as many people suffer from schistosomiasis today as they did 50 years ago. Snail control can complement preventive chemotherapy by reducing the risk of transmission from snails to humans. Here, we present ideas for modernizing and scaling up snail control, including spatiotemporal targeting, environmental diagnostics, better molluscicides, new technologies (e.g., gene drive), and ‘outside the box’ strategies such as natural enemies, traps, and repellants. We conclude that, to achieve the World Health Assembly’s stated goal to eliminate schistosomiasis, it is time to give snail control another look.

  17. Human physiologically based pharmacokinetic model for propofol

    Directory of Open Access Journals (Sweden)

    Schnider Thomas W

    2005-04-01

    Full Text Available Abstract Background Propofol is widely used for both short-term anesthesia and long-term sedation. It has unusual pharmacokinetics because of its high lipid solubility. The standard approach to describing the pharmacokinetics is by a multi-compartmental model. This paper presents the first detailed human physiologically based pharmacokinetic (PBPK model for propofol. Methods PKQuest, a freely distributed software routine http://www.pkquest.com, was used for all the calculations. The "standard human" PBPK parameters developed in previous applications is used. It is assumed that the blood and tissue binding is determined by simple partition into the tissue lipid, which is characterized by two previously determined set of parameters: 1 the value of the propofol oil/water partition coefficient; 2 the lipid fraction in the blood and tissues. The model was fit to the individual experimental data of Schnider et. al., Anesthesiology, 1998; 88:1170 in which an initial bolus dose was followed 60 minutes later by a one hour constant infusion. Results The PBPK model provides a good description of the experimental data over a large range of input dosage, subject age and fat fraction. Only one adjustable parameter (the liver clearance is required to describe the constant infusion phase for each individual subject. In order to fit the bolus injection phase, for 10 or the 24 subjects it was necessary to assume that a fraction of the bolus dose was sequestered and then slowly released from the lungs (characterized by two additional parameters. The average weighted residual error (WRE of the PBPK model fit to the both the bolus and infusion phases was 15%; similar to the WRE for just the constant infusion phase obtained by Schnider et. al. using a 6-parameter NONMEM compartmental model. Conclusion A PBPK model using standard human parameters and a simple description of tissue binding provides a good description of human propofol kinetics. The major advantage of a

  18. Fluphenazine reduces proteotoxicity in C. elegans and mammalian models of alpha-1-antitrypsin deficiency.

    Directory of Open Access Journals (Sweden)

    Jie Li

    Full Text Available The classical form of α1-antitrypsin deficiency (ATD is associated with hepatic fibrosis and hepatocellular carcinoma. It is caused by the proteotoxic effect of a mutant secretory protein that aberrantly accumulates in the endoplasmic reticulum of liver cells. Recently we developed a model of this deficiency in C. elegans and adapted it for high-content drug screening using an automated, image-based array scanning. Screening of the Library of Pharmacologically Active Compounds identified fluphenazine (Flu among several other compounds as a drug which reduced intracellular accumulation of mutant α1-antitrypsin Z (ATZ. Because it is representative of the phenothiazine drug class that appears to have autophagy enhancer properties in addition to mood stabilizing activity, and can be relatively easily re-purposed, we further investigated its effects on mutant ATZ. The results indicate that Flu reverses the phenotypic effects of ATZ accumulation in the C. elegans model of ATD at doses which increase the number of autophagosomes in vivo. Furthermore, in nanomolar concentrations, Flu enhances the rate of intracellular degradation of ATZ and reduces the cellular ATZ load in mammalian cell line models. In the PiZ mouse model Flu reduces the accumulation of ATZ in the liver and mediates a decrease in hepatic fibrosis. These results show that Flu can reduce the proteotoxicity of ATZ accumulation in vivo and, because it has been used safely in humans, this drug can be moved rapidly into trials for liver disease due to ATD. The results also provide further validation for drug discovery using C. elegans models that can be adapted to high-content drug screening platforms and used together with mammalian cell line and animal models.

  19. Model Dinamik Penularan Human Immunodeficiency Virus (HIV)

    OpenAIRE

    Sutimin, Sutimin; Imamudin, Imamudin

    2009-01-01

    -Human Immunodeficiency Virus (HIV) adalah virus yang dapat merusak sistem kekebalan tubuh manusia Virus HIV dapat menyerang orang yang rentan ketika orang yang rentan itu melakukan kontak dengan penderita virus HIV hingga terinfeksi virus HIV pada akhirnya dapat menderita AIDS atau seropositif non-AIDS. Dengan asumsi-asumsi tentang penularan virus HIV dapat diformulasikan suatu model matematika tentang perpindahan antar orang-orang rentan ke infeksi HIV, penderita AIDS dan seropositif non-A...

  20. Modeling human influenza infection in the laboratory

    Directory of Open Access Journals (Sweden)

    Radigan KA

    2015-08-01

    Full Text Available Kathryn A Radigan,1 Alexander V Misharin,2 Monica Chi,1 GR Scott Budinger11Division of Pulmonary and Critical Care Medicine, 2Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USAAbstract: Influenza is the leading cause of death from an infectious cause. Because of its clinical importance, many investigators use animal models to understand the biologic mechanisms of influenza A virus replication, the immune response to the virus, and the efficacy of novel therapies. This review will focus on the biosafety, biosecurity, and ethical concerns that must be considered in pursuing influenza research, in addition to focusing on the two animal models – mice and ferrets – most frequently used by researchers as models of human influenza infection.Keywords: mice, ferret, influenza, animal model, biosafety

  1. Optimization of experimental human leukemia models (review

    Directory of Open Access Journals (Sweden)

    D. D. Pankov

    2012-01-01

    Full Text Available Actual problem of assessing immunotherapy prospects including antigenpecific cell therapy using animal models was covered in this review.Describe the various groups of currently existing animal models and methods of their creating – from different immunodeficient mice to severalvariants of tumor cells engraftment in them. The review addresses the possibility of tumor stem cells studying using mouse models for the leukemia treatment with adoptive cell therapy including WT1. Also issues of human leukemia cells migration and proliferation in a mice withdifferent immunodeficiency degree are discussed. To assess the potential immunotherapy efficacy comparison of immunodeficient mouse model with clinical situation in oncology patients after chemotherapy is proposed.

  2. Reduced Order Aeroservoelastic Models with Rigid Body Modes, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Complex aeroelastic and aeroservoelastic phenomena can be modeled on complete aircraft configurations generating models with millions of degrees of freedom. Starting...

  3. Modeling Oxygen Transport in the Human Placenta

    Science.gov (United States)

    Serov, Alexander; Filoche, Marcel; Salafia, Carolyn; Grebenkov, Denis

    Efficient functioning of the human placenta is crucial for the favorable pregnancy outcome. We construct a 3D model of oxygen transport in the placenta based on its histological cross-sections. The model accounts for both diffusion and convention of oxygen in the intervillous space and allows one to estimate oxygen uptake of a placentone. We demonstrate the existence of an optimal villi density maximizing the uptake and explain it as a trade-off between the incoming oxygen flow and the absorbing villous surface. Calculations performed for arbitrary shapes of fetal villi show that only two geometrical characteristics - villi density and the effective villi radius - are required to predict fetal oxygen uptake. Two combinations of physiological parameters that determine oxygen uptake are also identified: maximal oxygen inflow of a placentone and the Damköhler number. An automatic image analysis method is developed and applied to 22 healthy placental cross-sections demonstrating that villi density of a healthy human placenta lies within 10% of the optimal value, while overall geometry efficiency is rather low (around 30-40%). In a perspective, the model can constitute the base of a reliable tool of post partum oxygen exchange efficiency assessment in the human placenta. Also affiliated with Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA 90095, USA.

  4. Application of Human-Autonomy Teaming (HAT) Patterns to Reduced Crew Operations (RCO)

    Science.gov (United States)

    Shively, R. Jay; Brandt, Summer L.; Lachter, Joel; Matessa, Mike; Sadler, Garrett; Battiste, Henri

    2016-01-01

    As part of the Air Force - NASA Bi-Annual Research Council Meeting, slides will be presented on recent Reduced Crew Operations (RCO) work. Unmanned aerial systems, robotics, advanced cockpits, and air traffic management are all examples of domains that are seeing dramatic increases in automation. While automation may take on some tasks previously performed by humans, humans will still be required, for the foreseeable future, to remain in the system. The collaboration with humans and these increasingly autonomous systems will begin to resemble cooperation between teammates, rather than simple task allocation. It is critical to understand this human-autonomy teaming (HAT) to optimize these systems in the future. One methodology to understand HAT is by identifying recurring patterns of HAT that have similar characteristics and solutions. A methodology for identifying HAT patterns to an advanced cockpit project is discussed.

  5. Anodal transcranial direct current stimulation reduces psychophysically measured surround suppression in the human visual cortex.

    Directory of Open Access Journals (Sweden)

    Daniel P Spiegel

    Full Text Available Transcranial direct current stimulation (tDCS is a safe, non-invasive technique for transiently modulating the balance of excitation and inhibition within the human brain. It has been reported that anodal tDCS can reduce both GABA mediated inhibition and GABA concentration within the human motor cortex. As GABA mediated inhibition is thought to be a key modulator of plasticity within the adult brain, these findings have broad implications for the future use of tDCS. It is important, therefore, to establish whether tDCS can exert similar effects within non-motor brain areas. The aim of this study was to assess whether anodal tDCS could reduce inhibitory interactions within the human visual cortex. Psychophysical measures of surround suppression were used as an index of inhibition within V1. Overlay suppression, which is thought to originate within the lateral geniculate nucleus (LGN, was also measured as a control. Anodal stimulation of the occipital poles significantly reduced psychophysical surround suppression, but had no effect on overlay suppression. This effect was specific to anodal stimulation as cathodal stimulation had no effect on either measure. These psychophysical results provide the first evidence for tDCS-induced reductions of intracortical inhibition within the human visual cortex.

  6. Human Milk Management Redesign: Improving Quality and Safety and Reducing Neonatal Intensive Care Unit Nurse Stress.

    Science.gov (United States)

    Settle, Margaret Doyle; Coakley, Amanda Bulette; Annese, Christine Donahue

    2017-02-01

    Human milk provides superior nutritional value for infants in the neonatal intensive care unit and is the enteral feeding of choice. Our hospital used the system engineering initiative for patient safety model to evaluate the human milk management system in our neonatal intensive care unit. Nurses described the previous process in a negative way, fraught with opportunities for error, increased stress for nurses, and the need to be away from the bedside and their patients. The redesigned process improved the quality and safety of human milk management and created time for the nurses to spend with their patients.

  7. What Can Human Geography Offer Climate Change Modelling?

    DEFF Research Database (Denmark)

    Grindsted, Thomas Skou

    2014-01-01

    The discipline of Geography may be one of the most prominent and oldest disciplines in the conceptualization of human–environment interactions that integrates elements from both natural and social sciences. Yet, much research on society–environment interactions on climate change reduces human...... conceptual modelling of climate change adaption and mitigation. In other words, geographical representations do matter. In the following we will first reflect upon what I shall call spatio-temporal tides and waves of the human environment theme to examine the methodological grounds on which climate change...... regularities, rationalities, and pre-analytic assumptions. Lastly we discuss challenges of constructing nature(s) and how we better understand the (geo) politics of climate change modeling....

  8. A dynamic model of human physiology

    Science.gov (United States)

    Green, Melissa; Kaplan, Carolyn; Oran, Elaine; Boris, Jay

    2010-11-01

    To study the systems-level transport in the human body, we develop the Computational Man (CMAN): a set of one-dimensional unsteady elastic flow simulations created to model a variety of coupled physiological systems including the circulatory, respiratory, excretory, and lymphatic systems. The model systems are collapsed from three spatial dimensions and time to one spatial dimension and time by assuming axisymmetric vessel geometry and a parabolic velocity profile across the cylindrical vessels. To model the actions of a beating heart or expanding lungs, the flow is driven by user-defined changes to the equilibrium areas of the elastic vessels. The equations are then iteratively solved for pressure, area, and average velocity. The model is augmented with valves and contractions to resemble the biological structure of the different systems. CMAN will be used to track material transport throughout the human body for diagnostic and predictive purposes. Parameters will be adjustable to match those of individual patients. Validation of CMAN has used both higher-dimensional simulations of similar geometries and benchmark measurement from medical literature.

  9. Regional climate models reduce biases of global models and project smaller European summer warming

    Science.gov (United States)

    Soerland, S.; Schar, C.; Lüthi, D.; Kjellstrom, E.

    2017-12-01

    The assessment of regional climate change and the associated planning of adaptation and response strategies are often based on complex model chains. Typically, these model chains employ global and regional climate models (GCMs and RCMs), as well as one or several impact models. It is a common belief that the errors in such model chains behave approximately additive, thus the uncertainty should increase with each modeling step. If this hypothesis were true, the application of RCMs would not lead to any intrinsic improvement (beyond higher-resolution detail) of the GCM results. Here, we investigate the bias patterns (offset during the historical period against observations) and climate change signals of two RCMs that have downscaled a comprehensive set of GCMs following the EURO-CORDEX framework. The two RCMs reduce the biases of the driving GCMs, reduce the spread and modify the amplitude of the GCM projected climate change signal. The GCM projected summer warming at the end of the century is substantially reduced by both RCMs. These results are important, as the projected summer warming and its likely impact on the water cycle are among the most serious concerns regarding European climate change.

  10. Simulation study of a rectifying bipolar ion channel: Detailed model versus reduced model

    Directory of Open Access Journals (Sweden)

    Z. Ható

    2016-02-01

    Full Text Available We study a rectifying mutant of the OmpF porin ion channel using both all-atom and reduced models. The mutant was created by Miedema et al. [Nano Lett., 2007, 7, 2886] on the basis of the NP semiconductor diode, in which an NP junction is formed. The mutant contains a pore region with positive amino acids on the left-hand side and negative amino acids on the right-hand side. Experiments show that this mutant rectifies. Although we do not know the structure of this mutant, we can build an all-atom model for it on the basis of the structure of the wild type channel. Interestingly, molecular dynamics simulations for this all-atom model do not produce rectification. A reduced model that contains only the important degrees of freedom (the positive and negative amino acids and free ions in an implicit solvent, on the other hand, exhibits rectification. Our calculations for the reduced model (using the Nernst-Planck equation coupled to Local Equilibrium Monte Carlo simulations reveal a rectification mechanism that is different from that seen for semiconductor diodes. The basic reason is that the ions are different in nature from electrons and holes (they do not recombine. We provide explanations for the failure of the all-atom model including the effect of all the other atoms in the system as a noise that inhibits the response of ions (that would be necessary for rectification to the polarizing external field.

  11. 3D active workspace of human hand anatomical model

    Directory of Open Access Journals (Sweden)

    Ungureanu Loredana

    2007-05-01

    Full Text Available Abstract Background If the model of the human hand is created with accuracy by respecting the type of motion provided by each articulation and the dimensions of articulated bones, it can function as the real organ providing the same motions. Unfortunately, the human hand is hard to model due to its kinematical chains submitted to motion constraints. On the other hand, if an application does not impose a fine manipulation it is not necessary to create a model as complex as the human hand is. But always the hand model has to perform a certain space of motions in imposed workspace architecture no matter what the practical application does. Methods Based on Denavit-Hartenberg convention, we conceived the kinematical model of the human hand, having in mind the structure and the behavior of the natural model. We obtained the kinematical equations describing the motion of every fingertip with respect to the general coordinate system, placed on the wrist. For every joint variable, a range of motion was established. Dividing these joint variables to an appropriate number of intervals and connecting them, the complex surface bordering the active hand model workspace was obtained. Results Using MATLAB 7.0, the complex surface described by fingertips, when hand articulations are all simultaneously moving, was obtained. It can be seen that any point on surface has its own coordinates smaller than the maximum length of the middle finger in static position. Therefore, a sphere having the centre in the origin of the general coordinate system and the radius which equals this length covers the represented complex surface. Conclusion We propose a human hand model that represents a new solution compared to the existing ones. This model is capable to make special movements like power grip and dexterous manipulations. During them, the fingertips do not exceed the active workspace encapsulated by determined surfaces. The proposed kinematical model can help to choose

  12. Modeling and Visualization of Human Activities for Multicamera Networks

    Directory of Open Access Journals (Sweden)

    Aswin C. Sankaranarayanan

    2009-01-01

    Full Text Available Multicamera networks are becoming complex involving larger sensing areas in order to capture activities and behavior that evolve over long spatial and temporal windows. This necessitates novel methods to process the information sensed by the network and visualize it for an end user. In this paper, we describe a system for modeling and on-demand visualization of activities of groups of humans. Using the prior knowledge of the 3D structure of the scene as well as camera calibration, the system localizes humans as they navigate the scene. Activities of interest are detected by matching models of these activities learnt a priori against the multiview observations. The trajectories and the activity index for each individual summarize the dynamic content of the scene. These are used to render the scene with virtual 3D human models that mimic the observed activities of real humans. In particular, the rendering framework is designed to handle large displays with a cluster of GPUs as well as reduce the cognitive dissonance by rendering realistic weather effects and illumination. We envision use of this system for immersive visualization as well as summarization of videos that capture group behavior.

  13. Is it possible to reduce foodborne Campylobacter infections in humans through vaccination of animals?

    DEFF Research Database (Denmark)

    Hoorfar, Jeffrey

    2012-01-01

    Vaccination has been used successfully over the years to eradicate many serious diseases, but what about human foodborne pathogens, such as Campylobacter? Most human cases of Campylobacter infection are associated with consumption of poultry products. Vaccination of poultry to prevent early...... colonization or to reduce the Campylobacter colonization level may be a viable intervention strategy in the future; however, no commercial Campylobacter vaccine is currently available. This case considers the rationale for such a strategy, the forms it could take and the challenges it would involve....

  14. Caries risk assessment in school children using a reduced Cariogram model without saliva tests

    DEFF Research Database (Denmark)

    Petersson, Gunnel Hänsel; Isberg, Per-Erik; Twetman, Svante

    2010-01-01

    To investigate the caries predictive ability of a reduced Cariogram model without salivary tests in schoolchildren.......To investigate the caries predictive ability of a reduced Cariogram model without salivary tests in schoolchildren....

  15. The Five Key Questions of Human Performance Modeling.

    Science.gov (United States)

    Wu, Changxu

    2018-01-01

    Via building computational (typically mathematical and computer simulation) models, human performance modeling (HPM) quantifies, predicts, and maximizes human performance, human-machine system productivity and safety. This paper describes and summarizes the five key questions of human performance modeling: 1) Why we build models of human performance; 2) What the expectations of a good human performance model are; 3) What the procedures and requirements in building and verifying a human performance model are; 4) How we integrate a human performance model with system design; and 5) What the possible future directions of human performance modeling research are. Recent and classic HPM findings are addressed in the five questions to provide new thinking in HPM's motivations, expectations, procedures, system integration and future directions.

  16. Human reliability data collection and modelling

    International Nuclear Information System (INIS)

    1991-09-01

    The main purpose of this document is to review and outline the current state-of-the-art of the Human Reliability Assessment (HRA) used for quantitative assessment of nuclear power plants safe and economical operation. Another objective is to consider Human Performance Indicators (HPI) which can alert plant manager and regulator to departures from states of normal and acceptable operation. These two objectives are met in the three sections of this report. The first objective has been divided into two areas, based on the location of the human actions being considered. That is, the modelling and data collection associated with control room actions are addressed first in chapter 1 while actions outside the control room (including maintenance) are addressed in chapter 2. Both chapters 1 and 2 present a brief outline of the current status of HRA for these areas, and major outstanding issues. Chapter 3 discusses HPI. Such performance indicators can signal, at various levels, changes in factors which influence human performance. The final section of this report consists of papers presented by the participants of the Technical Committee Meeting. A separate abstract was prepared for each of these papers. Refs, figs and tabs

  17. Zebrafish Models for Human Acute Organophosphorus Poisoning.

    Science.gov (United States)

    Faria, Melissa; Garcia-Reyero, Natàlia; Padrós, Francesc; Babin, Patrick J; Sebastián, David; Cachot, Jérôme; Prats, Eva; Arick Ii, Mark; Rial, Eduardo; Knoll-Gellida, Anja; Mathieu, Guilaine; Le Bihanic, Florane; Escalon, B Lynn; Zorzano, Antonio; Soares, Amadeu M V M; Raldúa, Demetrio

    2015-10-22

    Terrorist use of organophosphorus-based nerve agents and toxic industrial chemicals against civilian populations constitutes a real threat, as demonstrated by the terrorist attacks in Japan in the 1990 s or, even more recently, in the Syrian civil war. Thus, development of more effective countermeasures against acute organophosphorus poisoning is urgently needed. Here, we have generated and validated zebrafish models for mild, moderate and severe acute organophosphorus poisoning by exposing zebrafish larvae to different concentrations of the prototypic organophosphorus compound chlorpyrifos-oxon. Our results show that zebrafish models mimic most of the pathophysiological mechanisms behind this toxidrome in humans, including acetylcholinesterase inhibition, N-methyl-D-aspartate receptor activation, and calcium dysregulation as well as inflammatory and immune responses. The suitability of the zebrafish larvae to in vivo high-throughput screenings of small molecule libraries makes these models a valuable tool for identifying new drugs for multifunctional drug therapy against acute organophosphorus poisoning.

  18. Human IgG lacking effector functions demonstrate lower FcRn-binding and reduced transplacental transport.

    Science.gov (United States)

    Stapleton, Nigel M; Armstrong-Fisher, Sylvia S; Andersen, Jan Terje; van der Schoot, C Ellen; Porter, Charlene; Page, Kenneth R; Falconer, Donald; de Haas, Masja; Williamson, Lorna M; Clark, Michael R; Vidarsson, Gestur; Armour, Kathryn L

    2018-03-01

    We have previously generated human IgG1 antibodies that were engineered for reduced binding to the classical Fcγ receptors (FcγRI-III) and C1q, thereby eliminating their destructive effector functions (constant region G1Δnab). In their potential use as blocking agents, favorable binding to the neonatal Fc receptor (FcRn) is important to preserve the long half-life typical of IgG. An ability to cross the placenta, which is also mediated, at least in part, by FcRn is desirable in some indications, such as feto-maternal alloimmune disorders. Here, we show that G1Δnab mutants retain pH-dependent binding to human FcRn but that the amino acid alterations reduce the affinity of the IgG1:FcRn interaction by 2.0-fold and 1.6-fold for the two antibodies investigated. The transport of the modified G1Δnab mutants across monolayers of human cell lines expressing FcRn was approximately 75% of the wild-type, except that no difference was observed with human umbilical vein endothelial cells. G1Δnab mutation also reduced transport in an ex vivo placenta model. In conclusion, we demonstrate that, although the G1Δnab mutations are away from the FcRn-binding site, they have long-distance effects, modulating FcRn binding and transcellular transport. Our findings have implications for the design of therapeutic human IgG with tailored effector functions. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Reducing the computational cost of automatic calibration through model preemption

    Science.gov (United States)

    Razavi, Saman; Tolson, Bryan A.; Matott, L. Shawn; Thomson, Neil R.; Maclean, Angela; Seglenieks, Frank R.

    2010-11-01

    Computational budget is frequently a limiting factor in both uncertainty-based (e.g., through generalized likelihood uncertainty estimation (GLUE)) and optimization-based (e.g., through least squares minimization) calibration of computationally intensive environmental simulation models. This study introduces and formalizes the concept of simulation model preemption during automatic calibration. The proposed "model preemption" method terminates a simulation model early to save computational budget if it is recognized through intermediate simulation model results that a given solution (model parameter set) is so poor that it will not benefit the search strategy. The methodology proposed here is referred to as deterministic model preemption because it leads to exactly the same calibration result as when deterministic preemption is not applied. As such, deterministic preemption-enabled calibration algorithms which make no approximations to the mathematical simulation model are a simple alternative to the increasingly common and more complex approach of metamodeling for computationally constrained model calibration. Despite its simplicity, the deterministic model preemption concept is a promising concept that has yet to be formalized in the environmental simulation model automatic calibration literature. The model preemption concept can be applied to a subset of uncertainty-based and optimization-based automatic calibration strategies using a variety of different objective functions. Results across multiple calibration case studies demonstrate actual preemption computational savings ranging from 14% to 49%, 34% to 59%, and 52% to 96% for the dynamically dimensioned search, particle swarm optimization, and GLUE automatic calibration methods, respectively.

  20. Scoring predictive models using a reduced representation of proteins: model and energy definition

    Directory of Open Access Journals (Sweden)

    Corazza Alessandra

    2007-03-01

    Full Text Available Abstract Background Reduced representations of proteins have been playing a keyrole in the study of protein folding. Many such models are available, with different representation detail. Although the usefulness of many such models for structural bioinformatics applications has been demonstrated in recent years, there are few intermediate resolution models endowed with an energy model capable, for instance, of detecting native or native-like structures among decoy sets. The aim of the present work is to provide a discrete empirical potential for a reduced protein model termed here PC2CA, because it employs a PseudoCovalent structure with only 2 Centers of interactions per Amino acid, suitable for protein model quality assessment. Results All protein structures in the set top500H have been converted in reduced form. The distribution of pseudobonds, pseudoangle, pseudodihedrals and distances between centers of interactions have been converted into potentials of mean force. A suitable reference distribution has been defined for non-bonded interactions which takes into account excluded volume effects and protein finite size. The correlation between adjacent main chain pseudodihedrals has been converted in an additional energetic term which is able to account for cooperative effects in secondary structure elements. Local energy surface exploration is performed in order to increase the robustness of the energy function. Conclusion The model and the energy definition proposed have been tested on all the multiple decoys' sets in the Decoys'R'us database. The energetic model is able to recognize, for almost all sets, native-like structures (RMSD less than 2.0 Å. These results and those obtained in the blind CASP7 quality assessment experiment suggest that the model compares well with scoring potentials with finer granularity and could be useful for fast exploration of conformational space. Parameters are available at the url: http://www.dstb.uniud.it/~ffogolari/download/.

  1. Scoring predictive models using a reduced representation of proteins: model and energy definition.

    Science.gov (United States)

    Fogolari, Federico; Pieri, Lidia; Dovier, Agostino; Bortolussi, Luca; Giugliarelli, Gilberto; Corazza, Alessandra; Esposito, Gennaro; Viglino, Paolo

    2007-03-23

    Reduced representations of proteins have been playing a keyrole in the study of protein folding. Many such models are available, with different representation detail. Although the usefulness of many such models for structural bioinformatics applications has been demonstrated in recent years, there are few intermediate resolution models endowed with an energy model capable, for instance, of detecting native or native-like structures among decoy sets. The aim of the present work is to provide a discrete empirical potential for a reduced protein model termed here PC2CA, because it employs a PseudoCovalent structure with only 2 Centers of interactions per Amino acid, suitable for protein model quality assessment. All protein structures in the set top500H have been converted in reduced form. The distribution of pseudobonds, pseudoangle, pseudodihedrals and distances between centers of interactions have been converted into potentials of mean force. A suitable reference distribution has been defined for non-bonded interactions which takes into account excluded volume effects and protein finite size. The correlation between adjacent main chain pseudodihedrals has been converted in an additional energetic term which is able to account for cooperative effects in secondary structure elements. Local energy surface exploration is performed in order to increase the robustness of the energy function. The model and the energy definition proposed have been tested on all the multiple decoys' sets in the Decoys'R'us database. The energetic model is able to recognize, for almost all sets, native-like structures (RMSD less than 2.0 A). These results and those obtained in the blind CASP7 quality assessment experiment suggest that the model compares well with scoring potentials with finer granularity and could be useful for fast exploration of conformational space. Parameters are available at the url: http://www.dstb.uniud.it/~ffogolari/download/.

  2. Reduced expression of aquaporins in human intestinal mucosa in early stage inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Ricanek P

    2015-01-01

    -dimensional structures of AQP1, 3, 7, and 8 were modeled. Results: AQP1, 3, 7, and 8 mRNAs were detected in all parts of the intestinal mucosa. Notably, AQP1 and AQP3 mRNA levels were reduced in the ileum of patients with Crohn's disease, and AQP7 and AQP8 mRNA levels were reduced in the ileum and the colon of patients with ulcerative colitis. Immunofluorescence confocal microscopy showed localization of AQP3, 7, and 8 at the mucosal epithelium, whereas the expression of AQP1 was mainly confined to the endothelial cells and erythrocytes. The reduction in the level of AQP3, 7, and 8 mRNA was confirmed by immunofluorescence, which also indicated a reduction of apical immunolabeling for AQP8 in the colonic surface epithelium and crypts of the IBD samples. This could indicate loss of epithelial polarity in IBD, leading to disrupted barrier function. Conclusion: AQPs 1 and 8 and the aquaglyceroporins AQPs 3 and 7 are the AQPs predominantly expressed in the lower intestinal tract of humans. Their expression is significantly reduced in patients with IBD, and they are differentially expressed in specific bowel segments in patients with Crohn's disease and ulcerative colitis. The data present a link between gut inflammation and water/solute homeostasis, suggesting that AQPs may play a significant role in IBD pathophysiology. Keywords: inflammatory bowel disease, Crohn's disease, ulcerative colitis, aquaporins, aquaglyceroporins

  3. The quantitative modelling of human spatial habitability

    Science.gov (United States)

    Wise, J. A.

    1985-01-01

    A model for the quantitative assessment of human spatial habitability is presented in the space station context. The visual aspect assesses how interior spaces appear to the inhabitants. This aspect concerns criteria such as sensed spaciousness and the affective (emotional) connotations of settings' appearances. The kinesthetic aspect evaluates the available space in terms of its suitability to accommodate human movement patterns, as well as the postural and anthrometric changes due to microgravity. Finally, social logic concerns how the volume and geometry of available space either affirms or contravenes established social and organizational expectations for spatial arrangements. Here, the criteria include privacy, status, social power, and proxemics (the uses of space as a medium of social communication).

  4. Modelling human eye under blast loading.

    Science.gov (United States)

    Esposito, L; Clemente, C; Bonora, N; Rossi, T

    2015-01-01

    Primary blast injury (PBI) is the general term that refers to injuries resulting from the mere interaction of a blast wave with the body. Although few instances of primary ocular blast injury, without a concomitant secondary blast injury from debris, are documented, some experimental studies demonstrate its occurrence. In order to investigate PBI to the eye, a finite element model of the human eye using simple constitutive models was developed. The material parameters were calibrated by a multi-objective optimisation performed on available eye impact test data. The behaviour of the human eye and the dynamics of mechanisms occurring under PBI loading conditions were modelled. For the generation of the blast waves, different combinations of explosive (trinitrotoluene) mass charge and distance from the eye were analysed. An interpretation of the resulting pressure, based on the propagation and reflection of the waves inside the eye bulb and orbit, is proposed. The peculiar geometry of the bony orbit (similar to a frustum cone) can induce a resonance cavity effect and generate a pressure standing wave potentially hurtful for eye tissues.

  5. Aromatherapy with two essential oils from Satureja genre and mindfulness meditation to reduce anxiety in humans

    OpenAIRE

    Soto-V?squez, Maril? Roxana; Alvarado-Garc?a, Pa?l Alan Arkin

    2016-01-01

    The goal of this study was to verify whether association of aromatherapy with essential oils of Satureja brevicalyx or Satureja boliviana and mindfulness meditation can reduce anxiety levels in humans. A randomized experimental trial was carried out with 108 participants who were divided into 6 groups, comprising a waiting list control group and five experimental groups. Aromatherapy was carried out by inhalation of essential oils while mindfulness intervention program was focused on “flow me...

  6. Human cardiac-derived adherent proliferating cells reduce murine acute Coxsackievirus B3-induced myocarditis.

    Directory of Open Access Journals (Sweden)

    Kapka Miteva

    Full Text Available BACKGROUND: Under conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. We recently isolated and identified novel cardiac-derived cells from human cardiac biopsies: cardiac-derived adherent proliferating cells (CAPs. They have similarities with mesenchymal stromal cells, which are known for their anti-apoptotic and immunomodulatory properties. We explored whether CAPs application could be a novel strategy to improve acute Coxsackievirus B3 (CVB3-induced myocarditis. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the safety of our approach, we first analyzed the expression of the coxsackie- and adenovirus receptor (CAR and the co-receptor CD55 on CAPs, which are both required for effective CVB3 infectivity. We could demonstrate that CAPs only minimally express both receptors, which translates to minimal CVB3 copy numbers, and without viral particle release after CVB3 infection. Co-culture of CAPs with CVB3-infected HL-1 cardiomyocytes resulted in a reduction of CVB3-induced HL-1 apoptosis and viral progeny release. In addition, CAPs reduced CD4 and CD8 T cell proliferation. All CAPs-mediated protective effects were nitric oxide- and interleukin-10-dependent and required interferon-γ. In an acute murine model of CVB3-induced myocarditis, application of CAPs led to a decrease of cardiac apoptosis, cardiac CVB3 viral load and improved left ventricular contractility parameters. This was associated with a decline in cardiac mononuclear cell activity, an increase in T regulatory cells and T cell apoptosis, and an increase in left ventricular interleukin-10 and interferon-γ mRNA expression. CONCLUSIONS: We conclude that CAPs are a unique type of cardiac-derived cells and promising tools to improve acute CVB3-induced myocarditis.

  7. Modeling human comprehension of data visualizations

    Energy Technology Data Exchange (ETDEWEB)

    Matzen, Laura E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Haass, Michael Joseph [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Divis, Kristin Marie [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wilson, Andrew T. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-09-01

    This project was inspired by two needs. The first is a need for tools to help scientists and engineers to design effective data visualizations for communicating information, whether to the user of a system, an analyst who must make decisions based on complex data, or in the context of a technical report or publication. Most scientists and engineers are not trained in visualization design, and they could benefit from simple metrics to assess how well their visualization's design conveys the intended message. In other words, will the most important information draw the viewer's attention? The second is the need for cognition-based metrics for evaluating new types of visualizations created by researchers in the information visualization and visual analytics communities. Evaluating visualizations is difficult even for experts. However, all visualization methods and techniques are intended to exploit the properties of the human visual system to convey information efficiently to a viewer. Thus, developing evaluation methods that are rooted in the scientific knowledge of the human visual system could be a useful approach. In this project, we conducted fundamental research on how humans make sense of abstract data visualizations, and how this process is influenced by their goals and prior experience. We then used that research to develop a new model, the Data Visualization Saliency Model, that can make accurate predictions about which features in an abstract visualization will draw a viewer's attention. The model is an evaluation tool that can address both of the needs described above, supporting both visualization research and Sandia mission needs.

  8. Phenolic compounds apigenin, hesperidin and kaempferol reduce in vitro lipid accumulation in human adipocytes.

    Science.gov (United States)

    Gómez-Zorita, Saioa; Lasa, Arrate; Abendaño, Naiara; Fernández-Quintela, Alfredo; Mosqueda-Solís, Andrea; Garcia-Sobreviela, Maria Pilar; Arbonés-Mainar, Jose M; Portillo, Maria P

    2017-11-21

    Adipocytes derived from human mesenchymal stem cells (MSCs) are widely used to investigate adipogenesis. Taking into account both the novelty of these MSCs and the scarcity of studies focused on the effects of phenolic compounds, the aim of the present study was to analyze the effect of apigenin, hesperidin and kaempferol on pre-adipocyte and mature adipocytes derived from this type of cells. In addition, the expression of genes involved in TG accumulation was also measured. Pre-adipocytes were cultured from day 0 to day 8 and mature adipocytes for 48 h with the polyphenols at doses of 1, 10 and 25 µM. Apigenin did not show an anti-adipogenic action. Pre-adipocytes treated with hesperidin and kaempferol showed reduced TG content at the three experimental doses. Apigenin did not modify the expression of the main adipogenic genes (c/ebpβ, c/ebpα, pparγ and srebp1c), hesperidin inhibited genes involved in the three phases of adipogenesis (c/ebpβ, srebp1c and perilipin) and kaempferol reduced c/ebpβ. In mature adipocytes, the three polyphenols reduced TG accumulation at the dose of 25 µM, but not at lower doses. All compounds increased mRNA levels of atgl. Apigenin and hesperidin decreased fasn expression. The present study shows the anti-adipogenic effect and delipidating effects of apigenin, hesperidin and kaempferol in human adipocytes derived from hMSCs. While hesperidin blocks all the stages of adipogenesis, kaempferol only inhibits the early stage. Regarding mature adipocytes, the three compounds reduce TG accumulation by activating, at least in part, lipolysis, and in the case of hesperidin and apigenin, also by reducing lipogenesis. The present study shows for the first time the anti-adipogenic effect and delipidating effect of apigenin, hesperidin and kaempferol in human adipocytes derived from MSCs for the first time.

  9. Human endometrial cell coculture reduces the endocrine disruptor toxicity on mouse embryo development

    Directory of Open Access Journals (Sweden)

    Lee Myeong-Seop

    2012-04-01

    Full Text Available Abstract Backgrounds Previous studies suggested that endocrine disruptors (ED are toxic on preimplantation embryos and inhibit development of embryos in vitro culture. However, information about the toxicity of endocrine disruptors on preimplantation development of embryo in human reproductive environment is lacking. Methods Bisphenol A (BPA and Aroclor 1254 (polychlorinated biphenyls were used as endocrine disruptors in this study. Mouse 2-cell embryos were cultured in medium alone or vehicle or co-cultured with human endometrial epithelial layers in increasing ED concentrations. Results At 72 hours the percentage of normal blastocyst were decreased by ED in a dose-dependent manner while the co-culture system significantly enhanced the rate and reduced the toxicity of endocrine disruptors on the embryonic development in vitro. Conclusions In conclusion, although EDs have the toxic effect on embryo development, the co-culture with human endometrial cell reduced the preimplantation embryo from it thereby making human reproductive environment protective to preimplantation embryo from the toxicity of endocrine disruptors.

  10. Within-group competition reduces cooperation and payoffs in human groups

    DEFF Research Database (Denmark)

    Barker, Jessie; Barclay, Pat; Reeve, H. Kern

    2012-01-01

    cooperation, which has focused on noncontestable public goods. In this study, we allow for the potential of within-group competition over cooperatively produced resources and use a game theoretic “tug-of-war” model and empirical test to show that such competition decreases the degree of cooperation within......Social organisms in many taxa cooperate to produce resources that are shared among group members. Some cooperatively produced resources may be monopolized by individuals who invest in within-group competition, but these have largely been overlooked in empirical and theoretical research on human...... human groups and hence decreases group members' payoffs. Our study thus sheds light on how cooperative production and equal division of shared resources may have evolved, expands on current models of human cooperation to reflect the many natural conditions with opportunities for within-group competition...

  11. Virtual pharmacokinetic model of human eye.

    Science.gov (United States)

    Kotha, Sreevani; Murtomäki, Lasse

    2014-07-01

    A virtual pharmacokinetic 3D model of the human eye is built using Comsol Multiphysics® software, which is based on the Finite Element Method (FEM). The model considers drug release from a polymer patch placed on sclera. The model concentrates on the posterior part of the eye, retina being the target tissue, and comprises the choroidal blood flow, partitioning of the drug between different tissues and active transport at the retina pigment epithelium (RPE)-choroid boundary. Although most straightforward, in order to check the mass balance, no protein binding or metabolism is yet included. It appeared that the most important issue in obtaining reliable simulation results is the finite element mesh, while time stepping has hardly any significance. Simulations were extended to 100,000 s. The concentration of a drug is shown as a function of time at various points of retina, as well as its average value, varying several parameters in the model. This work demonstrates how anybody with basic knowledge of calculus is able to build physically meaningful models of quite complex biological systems. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Crop Model Improvement Reduces the Uncertainty of the Response to Temperature of Multi-Model Ensembles

    Science.gov (United States)

    Maiorano, Andrea; Martre, Pierre; Asseng, Senthold; Ewert, Frank; Mueller, Christoph; Roetter, Reimund P.; Ruane, Alex C.; Semenov, Mikhail A.; Wallach, Daniel; Wang, Enli

    2016-01-01

    To improve climate change impact estimates and to quantify their uncertainty, multi-model ensembles (MMEs) have been suggested. Model improvements can improve the accuracy of simulations and reduce the uncertainty of climate change impact assessments. Furthermore, they can reduce the number of models needed in a MME. Herein, 15 wheat growth models of a larger MME were improved through re-parameterization and/or incorporating or modifying heat stress effects on phenology, leaf growth and senescence, biomass growth, and grain number and size using detailed field experimental data from the USDA Hot Serial Cereal experiment (calibration data set). Simulation results from before and after model improvement were then evaluated with independent field experiments from a CIMMYT worldwide field trial network (evaluation data set). Model improvements decreased the variation (10th to 90th model ensemble percentile range) of grain yields simulated by the MME on average by 39% in the calibration data set and by 26% in the independent evaluation data set for crops grown in mean seasonal temperatures greater than 24 C. MME mean squared error in simulating grain yield decreased by 37%. A reduction in MME uncertainty range by 27% increased MME prediction skills by 47%. Results suggest that the mean level of variation observed in field experiments and used as a benchmark can be reached with half the number of models in the MME. Improving crop models is therefore important to increase the certainty of model-based impact assessments and allow more practical, i.e. smaller MMEs to be used effectively.

  13. Mycorrhizal fungi reduce nutrient loss from model grassland ecosystems.

    NARCIS (Netherlands)

    van der Heijden, M.G.A.

    2010-01-01

    Nutrient loss from ecosystems is among the top environmental threats to ecosystems worldwide, leading to reduced plant productivity in nutrient-poor ecosystems and eutrophication of surface water near nutrient-rich ecosystems. Hence, it is of pivotal importance to understand which factors influence

  14. LQG controller designs from reduced order models for a launch ...

    Indian Academy of Sciences (India)

    This paper describes the effort of a multivariable control approach applied to the Geosynchronous Satellite Launch Vehicle (GSLV) of the Indian Space Research Organization (ISRO) during a certain stage of its launch. The fuel slosh dynamics are modelled using a pendulum model analogy. We describe two design ...

  15. Model-reduced gradient-based history matching

    NARCIS (Netherlands)

    Kaleta, M.P.

    2011-01-01

    Since the world's energy demand increases every year, the oil & gas industry makes a continuous effort to improve fossil fuel recovery. Physics-based petroleum reservoir modeling and closed-loop model-based reservoir management concept can play an important role here. In this concept measured data

  16. Plasmid deficiency in urogenital isolates of Chlamydia trachomatis reduces infectivity and virulence in a mouse model.

    Science.gov (United States)

    Sigar, Ira M; Schripsema, Justin H; Wang, Yibing; Clarke, Ian N; Cutcliffe, Lesley T; Seth-Smith, Helena M B; Thomson, Nicholas R; Bjartling, Carina; Unemo, Magnus; Persson, Kenneth; Ramsey, Kyle H

    2014-02-01

    We hypothesized that the plasmid of urogenital isolates of Chlamydia trachomatis would modulate infectivity and virulence in a mouse model. To test this hypothesis, we infected female mice in the respiratory or urogenital tract with graded doses of a human urogenital isolate of C. trachomatis, serovar F, possessing the cognate plasmid. For comparison, we inoculated mice with a plasmid-free serovar F isolate. Following urogenital inoculation, the plasmid-free isolate displayed significantly reduced infectivity compared with the wild-type strain with the latter yielding a 17-fold lower infectious dose to yield 50% infection. When inoculated via the respiratory tract, the plasmid-free isolate exhibited reduced infectivity and virulence (as measured by weight change) when compared to the wild-type isolate. Further, differences in infectivity, but not in virulence were observed in a C. trachomatis, serovar E isolate with a deletion within the plasmid coding sequence 1 when compared to a serovar E isolate with no mutations in the plasmid. We conclude that plasmid loss reduces virulence and infectivity in this mouse model. These findings further support a role for the chlamydial plasmid in infectivity and virulence in vivo. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  17. Human factors engineering program review model

    International Nuclear Information System (INIS)

    1994-07-01

    The staff of the Nuclear Regulatory Commission is performing nuclear power plant design certification reviews based on a design process plan that describes the human factors engineering (HFE) program elements that are necessary and sufficient to develop an acceptable detailed design specification and an acceptable implemented design. There are two principal reasons for this approach. First, the initial design certification applications submitted for staff review did not include detailed design information. Second, since human performance literature and industry experiences have shown that many significant human factors issues arise early in the design process, review of the design process activities and results is important to the evaluation of an overall design. However, current regulations and guidance documents do not address the criteria for design process review. Therefore, the HFE Program Review Model (HFE PRM) was developed as a basis for performing design certification reviews that include design process evaluations as well as review of the final design. A central tenet of the HFE PRM is that the HFE aspects of the plant should be developed, designed, and evaluated on the basis of a structured top-down system analysis using accepted HFE principles. The HFE PRM consists of ten component elements. Each element in divided into four sections: Background, Objective, Applicant Submittals, and Review Criteria. This report describes the development of the HFE PRM and gives a detailed description of each HFE review element

  18. A human neurodevelopmental model for Williams syndrome.

    Science.gov (United States)

    Chailangkarn, Thanathom; Trujillo, Cleber A; Freitas, Beatriz C; Hrvoj-Mihic, Branka; Herai, Roberto H; Yu, Diana X; Brown, Timothy T; Marchetto, Maria C; Bardy, Cedric; McHenry, Lauren; Stefanacci, Lisa; Järvinen, Anna; Searcy, Yvonne M; DeWitt, Michelle; Wong, Wenny; Lai, Philip; Ard, M Colin; Hanson, Kari L; Romero, Sarah; Jacobs, Bob; Dale, Anders M; Dai, Li; Korenberg, Julie R; Gage, Fred H; Bellugi, Ursula; Halgren, Eric; Semendeferi, Katerina; Muotri, Alysson R

    2016-08-18

    Williams syndrome is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with Williams syndrome lack precisely the same set of genes, with breakpoints in chromosome band 7q11.23 (refs 1-5). The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioural pathologies in humans, remains largely unexplored. Here we investigate neural progenitor cells and cortical neurons derived from Williams syndrome and typically developing induced pluripotent stem cells. Neural progenitor cells in Williams syndrome have an increased doubling time and apoptosis compared with typically developing neural progenitor cells. Using an individual with atypical Williams syndrome, we narrowed this cellular phenotype to a single gene candidate, frizzled 9 (FZD9). At the neuronal stage, layer V/VI cortical neurons derived from Williams syndrome were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in neurons from Williams syndrome were validated after Golgi staining of post-mortem layer V/VI cortical neurons. This model of human induced pluripotent stem cells fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain.

  19. Human factors engineering program review model

    Energy Technology Data Exchange (ETDEWEB)

    1994-07-01

    The staff of the Nuclear Regulatory Commission is performing nuclear power plant design certification reviews based on a design process plan that describes the human factors engineering (HFE) program elements that are necessary and sufficient to develop an acceptable detailed design specification and an acceptable implemented design. There are two principal reasons for this approach. First, the initial design certification applications submitted for staff review did not include detailed design information. Second, since human performance literature and industry experiences have shown that many significant human factors issues arise early in the design process, review of the design process activities and results is important to the evaluation of an overall design. However, current regulations and guidance documents do not address the criteria for design process review. Therefore, the HFE Program Review Model (HFE PRM) was developed as a basis for performing design certification reviews that include design process evaluations as well as review of the final design. A central tenet of the HFE PRM is that the HFE aspects of the plant should be developed, designed, and evaluated on the basis of a structured top-down system analysis using accepted HFE principles. The HFE PRM consists of ten component elements. Each element in divided into four sections: Background, Objective, Applicant Submittals, and Review Criteria. This report describes the development of the HFE PRM and gives a detailed description of each HFE review element.

  20. A modular approach to numerical human body modeling

    NARCIS (Netherlands)

    Forbes, P.A.; Griotto, G.; Rooij, L. van

    2007-01-01

    The choice of a human body model for a simulated automotive impact scenario must take into account both accurate model response and computational efficiency as key factors. This study presents a "modular numerical human body modeling" approach which allows the creation of a customized human body

  1. Reducing uncertainty in high-resolution sea ice models.

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, Kara J.; Bochev, Pavel Blagoveston

    2013-07-01

    Arctic sea ice is an important component of the global climate system, reflecting a significant amount of solar radiation, insulating the ocean from the atmosphere and influencing ocean circulation by modifying the salinity of the upper ocean. The thickness and extent of Arctic sea ice have shown a significant decline in recent decades with implications for global climate as well as regional geopolitics. Increasing interest in exploration as well as climate feedback effects make predictive mathematical modeling of sea ice a task of tremendous practical import. Satellite data obtained over the last few decades have provided a wealth of information on sea ice motion and deformation. The data clearly show that ice deformation is focused along narrow linear features and this type of deformation is not well-represented in existing models. To improve sea ice dynamics we have incorporated an anisotropic rheology into the Los Alamos National Laboratory global sea ice model, CICE. Sensitivity analyses were performed using the Design Analysis Kit for Optimization and Terascale Applications (DAKOTA) to determine the impact of material parameters on sea ice response functions. Two material strength parameters that exhibited the most significant impact on responses were further analyzed to evaluate their influence on quantitative comparisons between model output and data. The sensitivity analysis along with ten year model runs indicate that while the anisotropic rheology provides some benefit in velocity predictions, additional improvements are required to make this material model a viable alternative for global sea ice simulations.

  2. Human growth and body weight dynamics: an integrative systems model.

    Science.gov (United States)

    Rahmandad, Hazhir

    2014-01-01

    Quantifying human weight and height dynamics due to growth, aging, and energy balance can inform clinical practice and policy analysis. This paper presents the first mechanism-based model spanning full individual life and capturing changes in body weight, composition and height. Integrating previous empirical and modeling findings and validated against several additional empirical studies, the model replicates key trends in human growth including A) Changes in energy requirements from birth to old ages. B) Short and long-term dynamics of body weight and composition. C) Stunted growth with chronic malnutrition and potential for catch up growth. From obesity policy analysis to treating malnutrition and tracking growth trajectories, the model can address diverse policy questions. For example I find that even without further rise in obesity, the gap between healthy and actual Body Mass Indexes (BMIs) has embedded, for different population groups, a surplus of 14%-24% in energy intake which will be a source of significant inertia in obesity trends. In another analysis, energy deficit percentage needed to reduce BMI by one unit is found to be relatively constant across ages. Accompanying documented and freely available simulation model facilitates diverse applications customized to different sub-populations.

  3. Ecto-5'-Nucleotidase Overexpression Reduces Tumor Growth in a Xenograph Medulloblastoma Model.

    Directory of Open Access Journals (Sweden)

    Angélica R Cappellari

    Full Text Available Ecto-5'-nucleotidase/CD73 (ecto-5'-NT participates in extracellular ATP catabolism by converting adenosine monophosphate (AMP into adenosine. This enzyme affects the progression and invasiveness of different tumors. Furthermore, the expression of ecto-5'-NT has also been suggested as a favorable prognostic marker, attributing to this enzyme contradictory functions in cancer. Medulloblastoma (MB is the most common brain tumor of the cerebellum and affects mainly children.The effects of ecto-5'-NT overexpression on human MB tumor growth were studied in an in vivo model. Balb/c immunodeficient (nude 6 to 14-week-old mice were used for dorsal subcutaneous xenograph tumor implant. Tumor development was evaluated by pathophysiological analysis. In addition, the expression patterns of adenosine receptors were verified.The human MB cell line D283, transfected with ecto-5'-NT (D283hCD73, revealed reduced tumor growth compared to the original cell line transfected with an empty vector. D283hCD73 generated tumors with a reduced proliferative index, lower vascularization, the presence of differentiated cells and increased active caspase-3 expression. Prominent A1 adenosine receptor expression rates were detected in MB cells overexpressing ecto-5'-NT.This work suggests that ecto-5'-NT promotes reduced tumor growth to reduce cell proliferation and vascularization, promote higher differentiation rates and initiate apoptosis, supposedly by accumulating adenosine, which then acts through A1 adenosine receptors. Therefore, ecto-5'-NT might be considered an important prognostic marker, being associated with good prognosis and used as a potential target for therapy.

  4. Ecto-5’-Nucleotidase Overexpression Reduces Tumor Growth in a Xenograph Medulloblastoma Model

    Science.gov (United States)

    Cappellari, Angélica R.; Pillat, Micheli M.; Souza, Hellio D. N.; Dietrich, Fabrícia; Oliveira, Francine H.; Figueiró, Fabrício; Abujamra, Ana L.; Roesler, Rafael; Lecka, Joanna; Sévigny, Jean; Battastini, Ana Maria O.; Ulrich, Henning

    2015-01-01

    Background Ecto-5’-nucleotidase/CD73 (ecto-5’-NT) participates in extracellular ATP catabolism by converting adenosine monophosphate (AMP) into adenosine. This enzyme affects the progression and invasiveness of different tumors. Furthermore, the expression of ecto-5’-NT has also been suggested as a favorable prognostic marker, attributing to this enzyme contradictory functions in cancer. Medulloblastoma (MB) is the most common brain tumor of the cerebellum and affects mainly children. Materials and Methods The effects of ecto-5’-NT overexpression on human MB tumor growth were studied in an in vivo model. Balb/c immunodeficient (nude) 6 to 14-week-old mice were used for dorsal subcutaneous xenograph tumor implant. Tumor development was evaluated by pathophysiological analysis. In addition, the expression patterns of adenosine receptors were verified. Results The human MB cell line D283, transfected with ecto-5’-NT (D283hCD73), revealed reduced tumor growth compared to the original cell line transfected with an empty vector. D283hCD73 generated tumors with a reduced proliferative index, lower vascularization, the presence of differentiated cells and increased active caspase-3 expression. Prominent A1 adenosine receptor expression rates were detected in MB cells overexpressing ecto-5’-NT. Conclusion This work suggests that ecto-5’-NT promotes reduced tumor growth to reduce cell proliferation and vascularization, promote higher differentiation rates and initiate apoptosis, supposedly by accumulating adenosine, which then acts through A1 adenosine receptors. Therefore, ecto-5’-NT might be considered an important prognostic marker, being associated with good prognosis and used as a potential target for therapy. PMID:26491983

  5. Agronomic Approach of Zinc Biofortification Can Increase Zinc Bioavailability in Wheat Flour and thereby Reduce Zinc Deficiency in Humans.

    Science.gov (United States)

    Liu, Dunyi; Liu, Yumin; Zhang, Wei; Chen, Xinping; Zou, Chunqin

    2017-05-06

    Zinc (Zn) deficiency is a common disorder of humans in developing countries. The effect of Zn biofortification (via application of six rates of Zn fertilizer to soil) on Zn bioavailability in wheat grain and flour and its impacts on human health was evaluated. Zn bioavailability was estimated with a trivariate model that included Zn homeostasis in the human intestine. As the rate of Zn fertilization increased, the Zn concentration increased in all flour fractions, but the percentages of Zn in standard flour (25%) and bran (75%) relative to total grain Zn were constant. Phytic acid (PA) concentrations in grain and flours were unaffected by Zn biofortification. Zn bioavailability and the health impact, as indicated by disability-adjusted life years (DALYs) saved, increased with the Zn application rate and were greater in standard and refined flour than in whole grain and coarse flour. The biofortified standard and refined flour obtained with application of 50 kg/ha ZnSO₄·7H₂O met the health requirement (3 mg of Zn obtained from 300 g of wheat flour) and reduced DALYs by >20%. Although Zn biofortification increased Zn bioavailability in standard and refined flour, it did not reduce the bioavailability of iron, manganese, or copper in wheat flour.

  6. Vaccination of dogs in an African city interrupts rabies transmission and reduces human exposure.

    Science.gov (United States)

    Zinsstag, Jakob; Lechenne, Monique; Laager, Mirjam; Mindekem, Rolande; Naïssengar, Service; Oussiguéré, Assandi; Bidjeh, Kebkiba; Rives, Germain; Tessier, Julie; Madjaninan, Seraphin; Ouagal, Mahamat; Moto, Daugla D; Alfaroukh, Idriss O; Muthiani, Yvonne; Traoré, Abdallah; Hattendorf, Jan; Lepelletier, Anthony; Kergoat, Lauriane; Bourhy, Hervé; Dacheux, Laurent; Stadler, Tanja; Chitnis, Nakul

    2017-12-20

    Despite the existence of effective rabies vaccines for dogs, dog-transmitted human rabies persists and has reemerged in Africa. Two consecutive dog vaccination campaigns took place in Chad in 2012 and 2013 (coverage of 71% in both years) in the capital city of N'Djaména, as previously published. We developed a deterministic model of dog-human rabies transmission fitted to weekly incidence data of rabid dogs and exposed human cases in N'Djaména. Our analysis showed that the effective reproductive number, that is, the number of new dogs infected by a rabid dog, fell to below one through November 2014. The modeled incidence of human rabies exposure fell to less than one person per million people per year. A phylodynamic estimation of the effective reproductive number from 29 canine rabies virus genetic sequences of the viral N-protein confirmed the results of the deterministic transmission model, implying that rabies transmission between dogs was interrupted for 9 months. However, new dog rabies cases appeared earlier than the transmission and phylodynamic models predicted. This may have been due to the continuous movement of rabies-exposed dogs into N'Djaména from outside the city. Our results show that canine rabies transmission to humans can be interrupted in an African city with currently available dog rabies vaccines, provided that the vaccination area includes larger adjacent regions, and local communities are informed and engaged. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  7. Comparison of human exposure pathways in an urban brownfield: reduced risk from paving roads.

    Science.gov (United States)

    James, Kyle; Farrell, Richard E; Siciliano, Steven D

    2012-10-01

    Risk assessments often do not quantify the risk associated with soil inhalation. This pathway generally makes a negligible contribution to the cumulative risk, because soil ingestion is typically the dominant exposure pathway. Conditions in northern or rural centers in Canada characterized by large areas of exposed soil, including unpaved roads, favor the resuspension of soil particles, making soil inhalation a relevant risk pathway. The authors determined and compared human exposure to metals and polycyclic aromatic hydrocarbons (PAHs) from soil ingestion and inhalation and analyzed the carcinogenic and noncarcinogenic risks before and after roads were paved in a northern community. To determine the inhalation exposure, three size fractions of airborne particulate matter were collected (total suspended particulates [TSP], particulate matter with an aerodynamic diameter less than 10 µm [PM10], and particulate matter with an aerodynamic diameter less than 2.5 µm [PM2.5]) before and after roads were paved. Road paving reduced the concentration of many airborne contaminants by 25 to 75%, thus reducing risk. For example, before paving, the carcinogenic risk associated with inhalation of Cr was 3.4 excess cancers per 100,000 people exposed, whereas after paving, this risk was reduced to 1.6 in 100,000. Paving roads reduced the concentrations of total suspended particulates (TSP; p paving roads is an effective method of reducing risk from the inhalation of soil particles. Copyright © 2012 SETAC.

  8. Impact of AMS-02 Measurements on Reducing GCR Model Uncertainties

    Science.gov (United States)

    Slaba, T. C.; O'Neill, P. M.; Golge, S.; Norbury, J. W.

    2015-01-01

    For vehicle design, shield optimization, mission planning, and astronaut risk assessment, the exposure from galactic cosmic rays (GCR) poses a significant and complex problem both in low Earth orbit and in deep space. To address this problem, various computational tools have been developed to quantify the exposure and risk in a wide range of scenarios. Generally, the tool used to describe the ambient GCR environment provides the input into subsequent computational tools and is therefore a critical component of end-to-end procedures. Over the past few years, several researchers have independently and very carefully compared some of the widely used GCR models to more rigorously characterize model differences and quantify uncertainties. All of the GCR models studied rely heavily on calibrating to available near-Earth measurements of GCR particle energy spectra, typically over restricted energy regions and short time periods. In this work, we first review recent sensitivity studies quantifying the ions and energies in the ambient GCR environment of greatest importance to exposure quantities behind shielding. Currently available measurements used to calibrate and validate GCR models are also summarized within this context. It is shown that the AMS-II measurements will fill a critically important gap in the measurement database. The emergence of AMS-II measurements also provides a unique opportunity to validate existing models against measurements that were not used to calibrate free parameters in the empirical descriptions. Discussion is given regarding rigorous approaches to implement the independent validation efforts, followed by recalibration of empirical parameters.

  9. Basic physical processes and reduced models for plasma detachment

    Science.gov (United States)

    Stangeby, P. C.

    2018-04-01

    The divertor of a tokamak reactor will have to satisfy a number of critical constraints, the first of which is that the divertor targets not fail due to excessive heating or sputter-erosion. This paramount constraint of target survival defines the operating window for the principal plasma properties at the divertor target, the density n t and temperature, T t. In particular T et level of radiative cooling in the divertor, and (b) the ion flux to the target in the presence of volumetric loss of particles, momentum and power in the divertor. The 2 Point Model, 2PM, is a widely used analytic model for relating (T t, n t) to the controlling upstream conditions. The 2PM is derived here for various levels of complexity regarding the effects included. Analytic models of divertor detachment provide valuable insight and useful approximations, but more complete modeling requires the use of edge codes such as EDGE2D, SOLPS, SONIC, UEDGE, etc. Edge codes have grown to become quite sophisticated and now constitute, in effect, ‘code-experiments’ that—just as for actual experiments—can benefit from interpretation in terms of simple conceptual frameworks. 2 Point Model Formatting, 2PMF, of edge code output can provide such a conceptual framework. Methods of applying 2PMF are illustrated here with some examples.

  10. Generation of Humanized Mouse Models with Focus on Antithrombin Deficiency

    DEFF Research Database (Denmark)

    Jensen, Astrid Bøgh

    2015-01-01

    transgene. The CRISPR/Cas9 system is a relatively new and innovative method for targeted mutagenesis. The Cas9 nuclease introduces a double stranded break in the DNA, which can be repaired through homologous recombination of a targeting vector. A mutated Cas9n (Cas9 nickase) has been designed, which only...... cuts one of the DNA strands. With this enzyme, two target sites have to be located close to each other in order to create double strand break. This will lower the risk for off target mutations, but might reduce the efficiency of targeting. In order to control the expression of the human antithrombin...... found that homozygous knockout embryos have a significantly increased level of systemic inflammation, around their time of death. Furthermore, the embryos show signs of hypertension, already at day 12 of gestation, possible due to kidney failure. A humanized mouse model for antithrombin deficiency can...

  11. Current and Potential Treatments for Reducing Campylobacter Colonization in Animal Hosts and Disease in Humans

    Science.gov (United States)

    Johnson, Tylor J.; Shank, Janette M.; Johnson, Jeremiah G.

    2017-01-01

    Campylobacter jejuni is the leading cause of bacteria-derived gastroenteritis worldwide. In the developed world, Campylobacter is usually acquired by consuming under-cooked poultry, while in the developing world it is often obtained through drinking contaminated water. Once consumed, the bacteria adhere to the intestinal epithelium or mucus layer, causing toxin-mediated inhibition of fluid reabsorption from the intestine and invasion-induced inflammation and diarrhea. Traditionally, severe or prolonged cases of campylobacteriosis have been treated with antibiotics; however, overuse of these antibiotics has led to the emergence of antibiotic-resistant strains. As the incidence of antibiotic resistance, emergence of post-infectious diseases, and economic burden associated with Campylobacter increases, it is becoming urgent that novel treatments are developed to reduce Campylobacter numbers in commercial poultry and campylobacteriosis in humans. The purpose of this review is to provide the current status of present and proposed treatments to combat Campylobacter infection in humans and colonization in animal reservoirs. These treatments include anti-Campylobacter compounds, probiotics, bacteriophage, vaccines, and anti-Campylobacter bacteriocins, all of which may be successful at reducing the incidence of campylobacteriosis in humans and/or colonization loads in poultry. In addition to reviewing treatments, we will also address several proposed targets that may be used in future development of novel anti-Campylobacter treatments. PMID:28386253

  12. Reproductive physiology of a humanized GnRH receptor mouse model: application in evaluation of human-specific analogs.

    Science.gov (United States)

    Tello, Javier A; Kohout, Trudy; Pineda, Rafael; Maki, Richard A; Scott Struthers, R; Millar, Robert P

    2013-07-01

    The human GnRH receptor (GNRHR1) has a specific set of properties with physiological and pharmacological influences not appropriately modeled in laboratory animals or cell-based systems. To address this deficiency, we have generated human GNRHR1 knock-in mice and described their reproductive phenotype. Measurement of pituitary GNRHR1 transcripts from homozygous human GNRHR1 knock-in (ki/ki) mice revealed a severe reduction (7- to 8-fold) compared with the mouse Gnrhr1 in wild-type mice. ¹²⁵I-GnRH binding assays on pituitary membrane fractions corroborated reduced human GNRHR1 protein expression in ki/ki mice, as occurs with transfection of human GNRHR1 in cell lines. Female homozygous knock-in mice displayed normal pubertal onset, indicating that a large reduction in GNRHR1 expression is sufficient for this process. However, ki/ki females exhibited periods of prolonged estrous and/or metestrous and reduced fertility. No impairment was found in reproductive maturity or adult fertility in male ki/ki mice. Interestingly, the serum LH response to GnRH challenge was reduced in both knock-in males and females, indicating a reduced GNRHR1 signaling capacity. Small molecules targeting human GPCRs usually have poor activities at homologous rodent receptors, thus limiting their use in preclinical development. Therefore, we tested a human-specific GnRH1 antagonist, NBI-42902, in our mouse model and demonstrated abrogation of a GnRH1-induced serum LH rise in ki/ki mice and an absence of effect in littermates expressing the wild-type murine receptor. This novel model provides the opportunity to study the human receptor in vivo and for screening the activity of human-specific GnRH analogs.

  13. Campylobacter in primary animal production and control strategies to reduce the burden of human campylobacteriosis.

    Science.gov (United States)

    Wagenaar, J A; Mevius, D J; Havelaar, A H

    2006-08-01

    Campylobacteriosis is one of the most important bacterial food-borne illnesses in humans. One significant source of infection is the handling and consumption of poultry meat, although other sources also contribute considerably. Controlling Campylobacter in broilers reduces the human burden of illness. Broilers can easily become colonised with Campylobacter and preventive measures in primary production have a limited and unpredictable effect. Vaccination, competitive exclusion, bacteriophage therapy and the use of bacteriocins are not yet commercially available. However, measures in the slaughterhouse can reduce contamination in the final product. At present, the most promising control strategy is to keep colonised and non-colonised flocks separate during slaughter ('scheduled processing'). The virtually Campylobacter-free meat can supply the fresh poultry meat market, while the meat from infected flocks can be treated to reduce the Campylobacter concentration. Meat from infected flocks can be treated by freezing but chemical decontamination appears to be more cost effective. A variant of this scenario is to treat only highly contaminated meat. The authors conclude that, until new techniques become commercially available, scheduled processing is the most cost-effective approach. Finally, the authors describe trends in antimicrobial resistance in Campylobacter.

  14. Earthing (Grounding) the Human Body Reduces Blood Viscosity—a Major Factor in Cardiovascular Disease

    Science.gov (United States)

    Chevalier, Gaétan; Sinatra, Stephen T.; Delany, Richard M.

    2013-01-01

    Abstract Objectives Emerging research is revealing that direct physical contact of the human body with the surface of the earth (grounding or earthing) has intriguing effects on human physiology and health, including beneficial effects on various cardiovascular risk factors. This study examined effects of 2 hours of grounding on the electrical charge (zeta potential) on red blood cells (RBCs) and the effects on the extent of RBC clumping. Design/interventions Subjects were grounded with conductive patches on the soles of their feet and palms of their hands. Wires connected the patches to a stainless-steel rod inserted in the earth outdoors. Small fingertip pinprick blood samples were placed on microscope slides and an electric field was applied to them. Electrophoretic mobility of the RBCs was determined by measuring terminal velocities of the cells in video recordings taken through a microscope. RBC aggregation was measured by counting the numbers of clustered cells in each sample. Settings/location Each subject sat in a comfortable reclining chair in a soundproof experiment room with the lights dimmed or off. Subjects Ten (10) healthy adult subjects were recruited by word-of-mouth. Results Earthing or grounding increased zeta potentials in all samples by an average of 2.70 and significantly reduced RBC aggregation. Conclusions Grounding increases the surface charge on RBCs and thereby reduces blood viscosity and clumping. Grounding appears to be one of the simplest and yet most profound interventions for helping reduce cardiovascular risk and cardiovascular events. PMID:22757749

  15. Earthing (grounding) the human body reduces blood viscosity-a major factor in cardiovascular disease.

    Science.gov (United States)

    Chevalier, Gaétan; Sinatra, Stephen T; Oschman, James L; Delany, Richard M

    2013-02-01

    Emerging research is revealing that direct physical contact of the human body with the surface of the earth (grounding or earthing) has intriguing effects on human physiology and health, including beneficial effects on various cardiovascular risk factors. This study examined effects of 2 hours of grounding on the electrical charge (zeta potential) on red blood cells (RBCs) and the effects on the extent of RBC clumping. SUBJECTS were grounded with conductive patches on the soles of their feet and palms of their hands. Wires connected the patches to a stainless-steel rod inserted in the earth outdoors. Small fingertip pinprick blood samples were placed on microscope slides and an electric field was applied to them. Electrophoretic mobility of the RBCs was determined by measuring terminal velocities of the cells in video recordings taken through a microscope. RBC aggregation was measured by counting the numbers of clustered cells in each sample. Each subject sat in a comfortable reclining chair in a soundproof experiment room with the lights dimmed or off. Ten (10) healthy adult subjects were recruited by word-of-mouth. Earthing or grounding increased zeta potentials in all samples by an average of 2.70 and significantly reduced RBC aggregation. Grounding increases the surface charge on RBCs and thereby reduces blood viscosity and clumping. Grounding appears to be one of the simplest and yet most profound interventions for helping reduce cardiovascular risk and cardiovascular events.

  16. Analysis of Potential Alternatives to Reduce NASA's Cost of Human Access to Space

    Science.gov (United States)

    1998-01-01

    The purpose of this report is to analyze NASA's potential options for significantly reducing the cost of human access to space. The opinions expressed in this report are based on Hawthorne, Krauss & Associates' ("HKA") interaction with NASA and several of its key contractors over the past nine months. This report is not intended to be an exhaustive quantitative analysis of the various options available to NASA. Instead, its purpose is to outline key decision-related issues that the agency should consider prior to making a decision as to which option to pursue. This report attempts to bring a private-sector perspective to bear on the issue of reducing the cost of human access to space. HKA believes that the key to the NASA's success in reducing those costs over the long-term is the involvement of the private-sector incentives and disciplines--which is achieved only through the assumption of risk by the private sector, not through a traditional contractor relationship--is essential to achieve significant long-term cost reductions.

  17. Monitoring and modeling human interactions with ecosystems

    Science.gov (United States)

    Milesi, Cristina

    With rapidly increasing consumption rates and global population, there is a growing interest in understanding how to balance human activities with the other components of the Earth system. Humans alter ecosystem functioning with land cover changes, greenhouse gas emissions and overexploitation of natural resources. On the other side, climate and its inherent interannual variability drive global Net Primary Productivity (NPP), the base of energy for all trophic levels, shaping humans' distribution on the land surface and their sensitivity to natural and accelerated patterns of variation in ecosystem processes. In this thesis, I analyzed anthropogenic influences on ecosystems and ecosystems impacts on humans through a multi-scale approach. Anthropogenic influences were analyzed with a special focus on urban ecosystems, the living environment of nearly half of the global population and almost 90% of the population in the industrialized countries. A poorly quantified aspect of urban ecosystems is the biogeochemistry of urban vegetation, intensively managed through fertilization and irrigation. In chapter 1, adapting the ecosystem model Biome-BGC, I simulated the growth of turf grasses across the United States, and estimated their potential impact on the continental water and carbon budget. Using a remote sensing-based approach, I also developed a methodology to estimate the impact of land cover changes due to urbanization on the regional photosynthetic capacity (chapter 2), finding that low-density urbanization can retain high levels of net primary productivity, although at the expense of inefficient sprawl. One of the feedbacks of urbanization is the urban heat island effect, which I analyzed in conjunction with a remote sensing based estimate of fractional impervious surface area, showing how this is related to increases in land surface temperatures, independently from geographic location and population density (chapter 3). Finally, in chapter 4, I described the

  18. Measurement and Modelling of Blast Movement to Reduce Ore ...

    African Journals Online (AJOL)

    user

    with comprehensive monitoring using high speed video and blast movement markers. 2. Develop site specific models ... The Blast Movement Monitor (BMM) is a system developed and patented by the JKMRC, University .... at Ahafo mine, the current practice was to mine to pre-blast grade boundaries (from blast hole drilling.

  19. Measurement and Modelling of Blast Movement to Reduce Ore ...

    African Journals Online (AJOL)

    This paper describes the application of the latest measurements and modelling techniques in understanding the blast dynamics and develops site specific solutions to minimise blast induced dilution and ore losses. These solutions are validated at Newmont Ahafo open pit mine through systematic trials and subsequently ...

  20. Reducing uncertainty based on model fitness: Application to a ...

    African Journals Online (AJOL)

    A weakness of global sensitivity and uncertainty analysis methodologies is the often subjective definition of prior parameter probability distributions, especially ... The reservoir representing the central part of the wetland, where flood waters separate into several independent distributaries, is a keystone area within the model.

  1. Hand-rearing reduces fear of humans in European starlings, Sturnus vulgaris.

    Directory of Open Access Journals (Sweden)

    Gesa Feenders

    2011-02-01

    Full Text Available Pending changes in European legislation ban the use of wild-caught animals in research. This change is partly justified on the assumption that captive-breeding (or hand-rearing increases welfare of captive animals because these practices result in animals with reduced fear of humans. However, there are few actual data on the long-term behavioural effects of captive-breeding in non-domestic species, and these are urgently needed in order to understand the welfare and scientific consequences of adopting this practice. We compared the response of hand-reared and wild-caught starlings to the presence of a human in the laboratory. During human presence, all birds increased their general locomotor activity but the wild-caught birds moved away from the human and were less active than the hand-reared birds. After the human departed, the wild-caught birds were slower to decrease their activity back towards baseline levels, and showed a dramatic increase in time at the periphery of the cage compared with the hand-reared birds. We interpret these data as showing evidence of a greater fear response in wild-caught birds with initial withdrawal followed by a subsequent rebound of prolonged attempts to escape the cage. We found no effects of environmental enrichment. However, birds in cages on low shelves were less active than birds on upper shelves, and showed a greater increase in the time spent at the periphery of their cages after the human departed, perhaps indicating that the lower cages were more stressful. In demonstrating reduced fear of humans in hand-reared birds, our results support one of the proposed welfare benefits of this practice, but without further data on the possible welfare costs of hand-rearing, it is not yet possible to reach a general conclusion about its net welfare impact. However, our results confirm a clear scientific impact of both hand-rearing and cage position at the behavioural level.

  2. Organ Vouchers and Barter Markets: Saving Lives, Reducing Suffering, and Trading in Human Organs.

    Science.gov (United States)

    Cherry, Mark J

    2017-10-01

    The essays in this issue of The Journal of Medicine and Philosophy explore an innovative voucher program for encouraging kidney donation. Discussions cluster around a number of central moral and political/theoretical themes: (1) What are the direct and indirect health care costs and benefits of such a voucher system in human organs? (2) Do vouchers lead to more effective and efficient organ procurement and allocation or contribute to greater inequalities and inefficiencies in the transplantation system? (3) Do vouchers contribute to the inappropriate commodification of human body parts? (4) Is there a significant moral difference between such a voucher system and a market in human organs for transplantation? This paper argues that while kidney vouchers constitute a step in the right direction, fuller utilization of market-based incentives, including, but not limited to, barter exchanges (e.g., organ exchanges, organ chains, and organ vouchers), would save more lives and further reduce human suffering. © The Author 2017. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. A Mathematical Model of the Human Small Intestine Following Acute Radiation and Burn Exposures

    Science.gov (United States)

    2016-08-01

    intestinal lumen Cell Migration Radiation damages proliferating crypt cells, causing mitotic arrest and delaying regeneration Burns can...04-08-2016 Technical Report A Mathematical Model of the Human Small Intestine Following Acute Radiation and Burn Exposures HDTRA1...the small intestine , reducing the density of the gut barrier. A reduced epithelial lining can result in suppressed nutrient absorption, bacterial

  4. Enterohemorrhagic Escherichia coli Reduces Mucus and Intermicrovillar Bridges in Human Stem Cell-Derived ColonoidsSummary

    Directory of Open Access Journals (Sweden)

    Julie In

    2016-01-01

    Full Text Available Background & Aims: Enterohemorrhagic Escherichia coli (EHEC causes over 70,000 episodes of foodborne diarrhea annually in the United States. The early sequence of events that precede life-threatening hemorrhagic colitis and hemolytic uremic syndrome is not fully understood due to the initial asymptomatic phase of the disease and the lack of a suitable animal model. We determined the initial molecular events in the interaction between EHEC and human colonic epithelium. Methods: Human colonoids derived from adult proximal colonic stem cells were developed into monolayers to study EHEC-epithelial interactions. Monolayer confluency and differentiation were monitored by transepithelial electrical resistance measurements. The monolayers were apically infected with EHEC, and the progression of epithelial damage over time was assessed using biochemical and imaging approaches. Results: Human colonoid cultures recapitulate the differential protein expression patterns characteristic of the crypt and surface colonocytes. Mucus-producing differentiated colonoid monolayers are preferentially colonized by EHEC. Upon colonization, EHEC forms characteristic attaching and effacing lesions on the apical surface of colonoid monolayers. Mucin 2, a main component of colonic mucus, and protocadherin 24 (PCDH24, a microvillar resident protein, are targeted by EHEC at early stages of infection. The EHEC-secreted serine protease EspP initiates brush border damage through PCDH24 reduction. Conclusions: Human colonoid monolayers are a relevant pathophysiologic model that allow the study of early molecular events during enteric infections. Colonoid monolayers provide access to both apical and basolateral surfaces, thus providing an advantage over three-dimensional cultures to study host–pathogen interactions in a controllable and tractable manner. EHEC reduces colonic mucus and affects the brush border cytoskeleton in the absence of commensal bacteria. Keywords

  5. Modeling and remodeling of human extraction sockets.

    Science.gov (United States)

    Trombelli, Leonardo; Farina, Roberto; Marzola, Andrea; Bozzi, Leopoldo; Liljenberg, Birgitta; Lindhe, Jan

    2008-07-01

    The available studies on extraction wound repair in humans are affected by significant limitations and have failed to evaluate tissue alterations occurring in all compartments of the hard tissue defect. To monitor during a 6-month period the healing of human extraction sockets and include a semi-quantitative analysis of tissues and cell populations involved in various stages of the processes of modeling/remodeling. Twenty-seven biopsies, representative of the early (2-4 weeks, n=10), intermediate (6-8 weeks, n=6), and late phase (12-24 weeks, n=11) of healing, were collected and analysed. Granulation tissue that was present in comparatively large amounts in the early healing phase of socket healing, was in the interval between the early and intermediate observation phase replaced with provisional matrix and woven bone. The density of vascular structures and macrophages slowly decreased from 2 to 4 weeks over time. The presence of osteoblasts peaked at 6-8 weeks and remained almost stable thereafter; a small number of osteoclasts were present in a few specimens at each observation interval. The present findings demonstrated that great variability exists in man with respect to hard tissue formation within extraction sockets. Thus, whereas a provisional connective tissue consistently forms within the first weeks of healing, the interval during which mineralized bone is laid down is much less predictable.

  6. A comparison of updating algorithms for large $N$ reduced models

    CERN Document Server

    Pérez, Margarita García; Keegan, Liam; Okawa, Masanori; Ramos, Alberto

    2015-01-01

    We investigate Monte Carlo updating algorithms for simulating $SU(N)$ Yang-Mills fields on a single-site lattice, such as for the Twisted Eguchi-Kawai model (TEK). We show that performing only over-relaxation (OR) updates of the gauge links is a valid simulation algorithm for the Fabricius and Haan formulation of this model, and that this decorrelates observables faster than using heat-bath updates. We consider two different methods of implementing the OR update: either updating the whole $SU(N)$ matrix at once, or iterating through $SU(2)$ subgroups of the $SU(N)$ matrix, we find the same critical exponent in both cases, and only a slight difference between the two.

  7. Reduced modeling and state observation of an activated sludge process.

    Science.gov (United States)

    Queinnec, Isabelle; Gómez-Quintero, Claudia-Sophya

    2009-01-01

    This article first proposes a reduction strategy of the activated sludge process model with alternated aeration. Initiated with the standard activated sludge model (ASM1), the reduction is based on some biochemical considerations followed by linear approximations of nonlinear terms. Two submodels are then obtained, one for the aerobic phase and one for the anoxic phase, using four state variables related to the organic substrate concentration, the ammonium and nitrate-nitrite nitrogen, and the oxygen concentration. Then, a two-step robust estimation strategy is used to estimate both the unmeasured state variables and the unknown inflow ammonium nitrogen concentration. Parameter uncertainty is considered in the dynamics and input matrices of the system. 2009 American Institute of Chemical Engineers

  8. A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Van Leuven Fred

    2005-10-01

    Full Text Available Abstract Background Alzheimer's disease (AD is a progressive neurodegenerative disorder that primarily strikes the elderly. Studies in both humans and animal models have linked the consumption of cholesterol and saturated fats with amyloid-β (Aβ deposition and development of AD. Yet, these studies did not examine high fat diets in combination with reduced carbohydrate intake. Here we tested the effect of a high saturated fat/low carbohydrate diet on a transgenic mouse model of AD. Results Starting at three months of age, two groups of female transgenic mice carrying the "London" APP mutation (APP/V717I were fed either, a standard diet (SD composed of high carbohydrate/low fat chow, or a ketogenic diet (KD composed of very low carbohydrate/high saturated fat chow for 43 days. Animals fed the KD exhibited greatly elevated serum ketone body levels, as measured by β-hydroxybutyrate (3.85 ± 2.6 mM, compared to SD fed animals (0.29 ± 0.06 mM. In addition, animals fed the KD lost body weight (SD 22.2 ± 0.6 g vs. KD 17.5 ± 1.4 g, p = 0.0067. In contrast to earlier studies, the brief KD feeding regime significantly reduced total brain Aβ levels by approximately 25%. Despite changes in ketone levels, body weight, and Aβ levels, the KD diet did not alter behavioral measures. Conclusion Previous studies have suggested that diets rich in cholesterol and saturated fats increased the deposition of Aβ and the risk of developing AD. Here we demonstrate that a diet rich in saturated fats and low in carbohydrates can actually reduce levels of Aβ. Therefore, dietary strategies aimed at reducing Aβ levels should take into account interactions of dietary components and the metabolic outcomes, in particular, levels of carbohydrates, total calories, and presence of ketone bodies should be considered.

  9. Molecular Modeling of Prion Transmission to Humans

    Directory of Open Access Journals (Sweden)

    Etienne Levavasseur

    2014-10-01

    Full Text Available Using different prion strains, such as the variant Creutzfeldt-Jakob disease agent and the atypical bovine spongiform encephalopathy agents, and using transgenic mice expressing human or bovine prion protein, we assessed the reliability of protein misfolding cyclic amplification (PMCA to model interspecies and genetic barriers to prion transmission. We compared our PMCA results with in vivo transmission data characterized by attack rates, i.e., the percentage of inoculated mice that developed the disease. Using 19 seed/substrate combinations, we observed that a significant PMCA amplification was only obtained when the mouse line used as substrate is susceptible to the corresponding strain. Our results suggest that PMCA provides a useful tool to study genetic barriers to transmission and to study the zoonotic potential of emerging prion strains.

  10. Multivariable robust adaptive controller using reduced-order model

    Directory of Open Access Journals (Sweden)

    Wei Wang

    1990-04-01

    Full Text Available In this paper a multivariable robust adaptive controller is presented for a plant with bounded disturbances and unmodeled dynamics due to plant-model order mismatches. The robust stability of the closed-loop system is achieved by using the normalization technique and the least squares parameter estimation scheme with dead zones. The weighting polynomial matrices are incorporated into the control law, so that the open-loop unstable or/and nonminimum phase plants can be handled.

  11. LQG controller designs from reduced order models for a launch ...

    Indian Academy of Sciences (India)

    Performing the indicated operations, assuming τpi and ˙τpi are small quantities and noting that .... Sensors in Rate path. GR = ω2. 2 s2 + 2ξ2ω2s + ω2. 2. , where ω2 = 12·5 Hz = 78·54 rad/sec and ξ2 = 0·7. 3. Formulation of the state space model. The vehicle dynamics including rigid body, slosh and actuators can be written ...

  12. EDC IMPACT: Reduced sperm counts in rats exposed to human relevant mixtures of endocrine disrupters

    Directory of Open Access Journals (Sweden)

    M Axelstad

    2018-01-01

    Full Text Available Human semen quality is declining in many parts of the world, but the causes are ill defined. In rodents, impaired sperm production can be seen with early life exposure to certain endocrine-disrupting chemicals, but the effects of combined exposures are not properly investigated. In this study, we examined the effects of early exposure to the painkiller paracetamol and mixtures of human relevant endocrine-disrupting chemicals in rats. One mixture contained four estrogenic compounds; another contained eight anti-androgenic environmental chemicals and a third mixture contained estrogens, anti-androgens and paracetamol. All exposures were administered by oral gavage to time-mated Wistar dams rats (n = 16–20 throughout gestation and lactation. In the postnatal period, testicular histology was affected by the total mixture, and at the end of weaning, male testis weights were significantly increased by paracetamol and the high doses of the total and the anti-androgenic mixture, compared to controls. In all dose groups, epididymal sperm counts were reduced several months after end of exposure, i.e. at 10  months of age. Interestingly, the same pattern of effects was seen for paracetamol as for mixtures with diverse modes of action. Reduced sperm count was seen at a dose level reflecting human therapeutic exposure to paracetamol. Environmental chemical mixtures affected sperm count at the lowest mixture dose indicating an insufficient margin of safety for the most exposed humans. This causes concern for exposure of pregnant women to paracetamol as well as environmental endocrine disrupters.

  13. Botulinum toxin type A reduces histamine-induced itch and vasomotor responses in human skin

    DEFF Research Database (Denmark)

    Gazerani, Parisa; Pedersen, N. S.; Drewes, Asbjørn Mohr

    2009-01-01

    of subcutaneous administration of BoNT/A on experimentally histamine-induced itch in human skin. METHODS: In this double-blind, placebo-controlled study, 14 healthy men (mean +/- SD age 26.3 +/- 2.6 years) received BoNT/A (Botox; Allergan, Irvine, CA, U.S.A.; 5 U) and isotonic saline on the volar surface.......001) and temperature measurements (F(1,26) = 27.6, P skin...... temperature (thermographic images) were measured over the course of the trials. RESULTS: BoNT/A reduced the histamine-induced itch intensity (F(1,39) = 30.2, P

  14. Free will and punishment: a mechanistic view of human nature reduces retribution.

    Science.gov (United States)

    Shariff, Azim F; Greene, Joshua D; Karremans, Johan C; Luguri, Jamie B; Clark, Cory J; Schooler, Jonathan W; Baumeister, Roy F; Vohs, Kathleen D

    2014-08-01

    If free-will beliefs support attributions of moral responsibility, then reducing these beliefs should make people less retributive in their attitudes about punishment. Four studies tested this prediction using both measured and manipulated free-will beliefs. Study 1 found that people with weaker free-will beliefs endorsed less retributive, but not consequentialist, attitudes regarding punishment of criminals. Subsequent studies showed that learning about the neural bases of human behavior, through either lab-based manipulations or attendance at an undergraduate neuroscience course, reduced people's support for retributive punishment (Studies 2-4). These results illustrate that exposure to debates about free will and to scientific research on the neural basis of behavior may have consequences for attributions of moral responsibility. © The Author(s) 2014.

  15. Osteopontin reduces biofilm formation in a multi-species model of dental biofilm.

    Science.gov (United States)

    Schlafer, Sebastian; Raarup, Merete K; Wejse, Peter L; Nyvad, Bente; Städler, Brigitte M; Sutherland, Duncan S; Birkedal, Henrik; Meyer, Rikke L

    2012-01-01

    Combating dental biofilm formation is the most effective means for the prevention of caries, one of the most widespread human diseases. Among the chemical supplements to mechanical tooth cleaning procedures, non-bactericidal adjuncts that target the mechanisms of bacterial biofilm formation have gained increasing interest in recent years. Milk proteins, such as lactoferrin, have been shown to interfere with bacterial colonization of saliva-coated surfaces. We here study the effect of bovine milk osteopontin (OPN), a highly phosphorylated whey glycoprotein, on a multispecies in vitro model of dental biofilm. While considerable research effort focuses on the interaction of OPN with mammalian cells, there are no data investigating the influence of OPN on bacterial biofilms. Biofilms consisting of Streptococcus oralis, Actinomyces naeslundii, Streptococcus mitis, Streptococcus downei and Streptococcus sanguinis were grown in a flow cell system that permitted in situ microscopic analysis. Crystal violet staining showed significantly less biofilm formation in the presence of OPN, as compared to biofilms grown without OPN or biofilms grown in the presence of caseinoglycomacropeptide, another phosphorylated milk protein. Confocal microscopy revealed that OPN bound to the surface of bacterial cells and reduced mechanical stability of the biofilms without affecting cell viability. The bacterial composition of the biofilms, determined by fluorescence in situ hybridization, changed considerably in the presence of OPN. In particular, colonization of S. mitis, the best biofilm former in the model, was reduced dramatically. OPN strongly reduces the amount of biofilm formed in a well-defined laboratory model of acidogenic dental biofilm. If a similar effect can be observed in vivo, OPN might serve as a valuable adjunct to mechanical tooth cleaning procedures.

  16. Culturally relevant model program to prevent and reduce agricultural injuries.

    Science.gov (United States)

    Helitzer, D L; Hathorn, G; Benally, J; Ortega, C

    2014-07-01

    Limited research has explored pesticide injury prevention among American Indian farmers. In a five-year agricultural intervention, a university-community partnership, including the University of New Mexico School of Medicine, New Mexico State University, Shiprock Area Cooperative Extension Service, and Navajo Nation communities, used a culturally relevant model to introduce and maintain safe use of integrated pest management techniques. We applied the Diffusion of Innovations theory and community-based approaches to tailor health promotion strategies for our intervention. In a longitudinal study with repeated measures, we trained six "model farmers" to be crop management experts in pesticide safety, application, and control. Subsequently, these model farmers worked with 120 farm families randomized into two groups: intervention (Group 1) and delayed intervention (Group 2). Measurements included a walk-through analysis, test of knowledge and attitudes, and yield analysis. Both groups demonstrated improvements in pesticide storage behaviors after training. Test scores regarding safety practices improved significantly: from 57.3 to 72.4 for Group 1 and from 52.6 to 76.3 for Group 2. Group 1 maintained their knowledge and safety practices after the intervention. Attitudes about pesticides and communication of viewpoints changed across the study years. With pesticides and fertilizer, the number of corn ears increased by 56.3% and yield (kg m(-2)) of alfalfa increased by 41.2%. The study combined traditional farming practices with culturally relevant approaches and behavior change theory to affect knowledge, safety practices, attitudes, communication channels, and crop yield. Storage behaviors, use of pesticides and safety and application equipment, and safety practice knowledge changed significantly, as did attitudes about social networking, social support, and the compatibility and relative advantage of pesticides for farms.

  17. Supersymmetric reduced minimal 3-3-1 model

    Energy Technology Data Exchange (ETDEWEB)

    Huong, D.T., E-mail: dthuong@iop.vast.ac.vn [Institute of Physics, Vietnam Academy of Science and Technology, 10 Dao Tan, Ba Dinh, Hanoi (Viet Nam); Hue, L.T., E-mail: lthue@iop.vast.ac.vn [Institute of Physics, Vietnam Academy of Science and Technology, 10 Dao Tan, Ba Dinh, Hanoi (Viet Nam); Rodriguez, M.C., E-mail: marcosrodriguez@furg.br [Fundação Universidade Federal do Rio Grande-FURG, Instituto de Matemática, Estatística e Física-IMEF, Av. Itália, km 8, Campus Carreiros, 96201-900 Rio Grande, RS (Brazil); Long, H.N., E-mail: hnlong@iop.vast.ac.vn [Institute of Physics, Vietnam Academy of Science and Technology, 10 Dao Tan, Ba Dinh, Hanoi (Viet Nam)

    2013-05-11

    We build a supersymmetric version of the minimal 3-3-1 model with just two Higgs triplets using the superfield formalism. We study the mass spectrum of all particles in concordance with the experimental bounds. At the tree level, the masses of charged gauge bosons are the same as those of charged Higgs bosons. We also show that the electron, muon and their neutrinos as well as down and strange quarks gain mass through the loop correction. The narrow constraint on the ratio t{sub w}=w/(w{sup ′}) is given by studying the new invisible decay mode of the Z boson.

  18. Heterogeneous Community-based mobility model for human opportunistic network

    DEFF Research Database (Denmark)

    Hu, Liang; Dittmann, Lars

    2009-01-01

    Human opportunistic networks can facilitate wireless content dissemination while humans are on the move. In such a network, content is disseminated via nodes relaying and nodes mobility (human mobility). Thus it is essential to understand and model the real human mobility. We present...... a heterogeneous community-based random way-point (HC-RWP) mobility model that captures the four important properties of real human mobility. These properties are based on both intuitive observations of daily human mobility and analysis of empirical mobility traces. By discrete event simulation, we show HC......-RWP captures essential statistic features of wide range of real human mobility traces reported in previous studies....

  19. Antioxidant oils and Salmonella enterica Typhimurium reduce tumor in an experimental model of hepatic metastasis

    Directory of Open Access Journals (Sweden)

    Sorenson BS

    2011-05-01

    Full Text Available Brent S Sorenson, Kaysie L Banton, Lance B Augustin, Arnold S Leonard, Daniel A SaltzmanDepartment of Surgery, University of Minnesota Medical School, Minneapolis, MN, USAAbstract: Fruit seeds high in antioxidants have been shown to have anticancer properties and enhance host protection against microbial infection. Recently we showed that a single oral dose of Salmonella enterica serovar Typhimurium expressing a truncated human interleukin-2 gene (SalpIL2 is avirulent, immunogenic, and reduces hepatic metastases through increased natural killer cell populations in mice. To determine whether antioxidant compounds enhance the antitumor effect seen in SalpIL2-treated animals, we assayed black cumin (BC, black raspberry (BR, and milk thistle (MT seed oils for the ability to reduce experimental hepatic metastases in mice. In animals without tumor, BC and BR oil diets altered the kinetics of the splenic lymphocyte response to SalpIL2. Consistent with previous reports, BR and BC seed oils demonstrated independent antitumor properties and moderate adjuvant potential with SalpIL2. MT oil, however, inhibited the efficacy of SalpIL2 in our model. Based on these data, we conclude that a diet high in antioxidant oils promoted a more robust immune response to SalpIL2, thus enhancing its antitumor efficacy.Keywords: antioxidants, colorectal cancer, tumor models, metastasis

  20. Azithromycin reduces inflammation in a rat model of acute conjunctivitis

    Science.gov (United States)

    Fernandez-Robredo, Patricia; Recalde, Sergio; Moreno-Orduña, Maite; García-García, Laura; Zarranz-Ventura, Javier; García-Layana, Alfredo

    2013-01-01

    Purpose Macrolide antibiotics are known to have various anti-inflammatory effects in addition to their antimicrobial activity, but the mechanisms are still unclear. The effect of azithromycin on inflammatory molecules in the lipopolysaccharide-induced rat conjunctivitis model was investigated. Methods Twenty-four Wistar rats were divided into two groups receiving topical ocular azithromycin (15 mg/g) or vehicle. In total, six doses (25 µl) were administered as one dose twice a day for three days before subconjunctival lipopolysaccharide injection (3 mg/ml). Before the rats were euthanized, mucus secretion, conjunctival and palpebral edema and redness were evaluated. Real-time polymerase chain reaction was used to determine gene expression for interleukin-6, cyclooxygenase-2, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, and MMP-9. Interleukin-6 was determined with enzyme-linked immunosorbent assay, nuclear factor-kappa B with western blot, and MMP-2 activity with gelatin zymogram. Four eyes per group were processed for histology and subsequent periodic acid-Schiff staining and CD68 for immunofluorescence. The Student t test or the Wilcoxon test for independent samples was applied (SPSS v.15.0). Results Azithromycin-treated animals showed a significant reduction in all clinical signs (pazithromycin group (p=0.063). Mucus secretion by goblet cells and the macrophage count in conjunctival tissue were also decreased in the azithromycin group (pazithromycin administration ameliorates induced inflammation effects in a rat model of acute conjunctivitis. PMID:23378729

  1. Human antibody fragments specific for Bothrops jararacussu venom reduce the toxicity of other Bothrops sp. venoms.

    Science.gov (United States)

    Roncolato, Eduardo Crosara; Pucca, Manuela Berto; Funayama, Jaqueline Carlos; Bertolini, Thaís Barboza; Campos, Lucas Benício; Barbosa, José Elpidio

    2013-01-01

    Approximately 20,000 snakebites are registered each year in Brazil. The classical treatment for venomous snakebite involves the administration of sera obtained from immunized horses. Moreover, the production and care of horses is costly, and the use of heterologous sera can cause hypersensitivity reactions. The production of human antibody fragments by phage display technology is seen as a means of overcoming some of these disadvantages. The studies here attempted to test human monoclonal antibodies specific to Bothrops jararacussu against other Bothrops sp. venoms, using the Griffin.1 library of human single-chain fragment-variable (scFv) phage antibodies. Using the Griffin.1 phage antibody library, this laboratory previously produced scFvs capable of inhibiting the phospholipase and myotoxic activities of Bothrops jararacussu venom. The structural and functional similarities of the various forms of phospholipase A2 (PLA₂) in Bothrops venom served as the basis for the present study wherein the effectiveness of those same scFvs were evaluated against B. jararaca, B. neuwiedi, and B. moojeni venoms. Each clone was found to recognize all three Bothrops venoms, and purified scFvs partially inhibited their in vitro phospholipase activity. In vivo assays demonstrated that the scFv clone P2B7 reduced myotoxicity and increased the survival of animals that received the test venoms. The results here indicate that the scFv P2B7 is a candidate for inclusion in a mixture of specific antibodies to produce a human anti-bothropic sera. This data demonstrates that the human scFv P2B7 represents an alternative therapeutic approach to heterologous anti-bothropic sera available today.

  2. Dengue human infection model performance parameters.

    Science.gov (United States)

    Endy, Timothy P

    2014-06-15

    Dengue is a global health problem and of concern to travelers and deploying military personnel with development and licensure of an effective tetravalent dengue vaccine a public health priority. The dengue viruses (DENVs) are mosquito-borne flaviviruses transmitted by infected Aedes mosquitoes. Illness manifests across a clinical spectrum with severe disease characterized by intravascular volume depletion and hemorrhage. DENV illness results from a complex interaction of viral properties and host immune responses. Dengue vaccine development efforts are challenged by immunologic complexity, lack of an adequate animal model of disease, absence of an immune correlate of protection, and only partially informative immunogenicity assays. A dengue human infection model (DHIM) will be an essential tool in developing potential dengue vaccines or antivirals. The potential performance parameters needed for a DHIM to support vaccine or antiviral candidates are discussed. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Evaluating Models of Human Performance: Safety-Critical Systems Applications

    Science.gov (United States)

    Feary, Michael S.

    2012-01-01

    This presentation is part of panel discussion on Evaluating Models of Human Performance. The purpose of this panel is to discuss the increasing use of models in the world today and specifically focus on how to describe and evaluate models of human performance. My presentation will focus on discussions of generating distributions of performance, and the evaluation of different strategies for humans performing tasks with mixed initiative (Human-Automation) systems. I will also discuss issues with how to provide Human Performance modeling data to support decisions on acceptability and tradeoffs in the design of safety critical systems. I will conclude with challenges for the future.

  4. Reduced order modeling in topology optimization of vibroacoustic problems

    DEFF Research Database (Denmark)

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

    2017-01-01

    There is an interest in introducing topology optimization techniques in the design process of structural-acoustic systems. In topology optimization, the design space must be finely meshed in order to obtain an accurate design, which results in large numbers of degrees of freedom when designing...... or size optimization in large vibroacoustic models; however, new challenges are encountered when dealing with topology optimization. Since a design parameter per element is considered, the total number of design variables becomes very large; this poses a challenge to most existing pMOR techniques, which...... suffer from the curse of dimensionality. Moreover, the fact that the nature of the elements changes throughout the optimization (material to void or material to air) makes it more difficult to create a global basis that is accurate throughout the whole design space. In this work, these challenges...

  5. Reduced activity of AMP-activated protein kinase protects against genetic models of motor neuron disease.

    Science.gov (United States)

    Lim, M A; Selak, M A; Xiang, Z; Krainc, D; Neve, R L; Kraemer, B C; Watts, J L; Kalb, R G

    2012-01-18

    A growing body of research indicates that amyotrophic lateral sclerosis (ALS) patients and mouse models of ALS exhibit metabolic dysfunction. A subpopulation of ALS patients possesses higher levels of resting energy expenditure and lower fat-free mass compared to healthy controls. Similarly, two mutant copper zinc superoxide dismutase 1 (mSOD1) mouse models of familial ALS possess a hypermetabolic phenotype. The pathophysiological relevance of the bioenergetic defects observed in ALS remains largely elusive. AMP-activated protein kinase (AMPK) is a key sensor of cellular energy status and thus might be activated in various models of ALS. Here, we report that AMPK activity is increased in spinal cord cultures expressing mSOD1, as well as in spinal cord lysates from mSOD1 mice. Reducing AMPK activity either pharmacologically or genetically prevents mSOD1-induced motor neuron death in vitro. To investigate the role of AMPK in vivo, we used Caenorhabditis elegans models of motor neuron disease. C. elegans engineered to express human mSOD1 (G85R) in neurons develops locomotor dysfunction and severe fecundity defects when compared to transgenic worms expressing human wild-type SOD1. Genetic reduction of aak-2, the ortholog of the AMPK α2 catalytic subunit in nematodes, improved locomotor behavior and fecundity in G85R animals. Similar observations were made with nematodes engineered to express mutant tat-activating regulatory (TAR) DNA-binding protein of 43 kDa molecular weight. Altogether, these data suggest that bioenergetic abnormalities are likely to be pathophysiologically relevant to motor neuron disease.

  6. Promoting Cas9 degradation reduces mosaic mutations in non-human primate embryos

    Science.gov (United States)

    Tu, Zhuchi; Yang, Weili; Yan, Sen; Yin, An; Gao, Jinquan; Liu, Xudong; Zheng, Yinghui; Zheng, Jiezhao; Li, Zhujun; Yang, Su; Li, Shihua; Guo, Xiangyu; Li, Xiao-Jiang

    2017-01-01

    CRISPR-Cas9 is a powerful new tool for genome editing, but this technique creates mosaic mutations that affect the efficiency and precision of its ability to edit the genome. Reducing mosaic mutations is particularly important for gene therapy and precision genome editing. Although the mechanisms underlying the CRSIPR/Cas9-mediated mosaic mutations remain elusive, the prolonged expression and activity of Cas9 in embryos could contribute to mosaicism in DNA mutations. Here we report that tagging Cas9 with ubiquitin-proteasomal degradation signals can facilitate the degradation of Cas9 in non-human primate embryos. Using embryo-splitting approach, we found that shortening the half-life of Cas9 in fertilized zygotes reduces mosaic mutations and increases its ability to modify genomes in non-human primate embryos. Also, injection of modified Cas9 in one-cell embryos leads to live monkeys with the targeted gene modifications. Our findings suggest that modifying Cas9 activity can be an effective strategy to enhance precision genome editing. PMID:28155910

  7. Solonamide B inhibits quorum sensing and reduces Staphylococcus aureus mediated killing of human neutrophils.

    Science.gov (United States)

    Nielsen, Anita; Månsson, Maria; Bojer, Martin S; Gram, Lone; Larsen, Thomas O; Novick, Richard P; Frees, Dorte; Frøkiær, Hanne; Ingmer, Hanne

    2014-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a serious human pathogen, and particularly the spread of community associated (CA)-MRSA strains such as USA300 is a concern, as these strains can cause severe infections in otherwise healthy adults. Recently, we reported that a cyclodepsipeptide termed Solonamide B isolated from the marine bacterium, Photobacterium halotolerans strongly reduces expression of RNAIII, the effector molecule of the agr quorum sensing system. Here we show that Solonamide B interferes with the binding of S. aureus autoinducing peptides (AIPs) to sensor histidine kinase, AgrC, of the agr two-component system. The hypervirulence of USA300 has been linked to increased expression of central virulence factors like α-hemolysin and the phenol soluble modulins (PSMs). Importantly, in strain USA300 Solonamide B dramatically reduced the activity of α-hemolysin and the transcription of psma encoding PSMs with an 80% reduction in toxicity of supernatants towards human neutrophils and rabbit erythrocytes. To our knowledge this is the first report of a compound produced naturally by a Gram-negative marine bacterium that interferes with agr and affects both RNAIII and AgrA controlled virulence gene expression in S. aureus.

  8. Solonamide B inhibits quorum sensing and reduces Staphylococcus aureus mediated killing of human neutrophils.

    Directory of Open Access Journals (Sweden)

    Anita Nielsen

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA continues to be a serious human pathogen, and particularly the spread of community associated (CA-MRSA strains such as USA300 is a concern, as these strains can cause severe infections in otherwise healthy adults. Recently, we reported that a cyclodepsipeptide termed Solonamide B isolated from the marine bacterium, Photobacterium halotolerans strongly reduces expression of RNAIII, the effector molecule of the agr quorum sensing system. Here we show that Solonamide B interferes with the binding of S. aureus autoinducing peptides (AIPs to sensor histidine kinase, AgrC, of the agr two-component system. The hypervirulence of USA300 has been linked to increased expression of central virulence factors like α-hemolysin and the phenol soluble modulins (PSMs. Importantly, in strain USA300 Solonamide B dramatically reduced the activity of α-hemolysin and the transcription of psma encoding PSMs with an 80% reduction in toxicity of supernatants towards human neutrophils and rabbit erythrocytes. To our knowledge this is the first report of a compound produced naturally by a Gram-negative marine bacterium that interferes with agr and affects both RNAIII and AgrA controlled virulence gene expression in S. aureus.

  9. Free surface modelling with two-fluid model and reduced numerical diffusion of the interface

    International Nuclear Information System (INIS)

    Strubelj, Luka; Tiselj, Izrok

    2008-01-01

    Full text of publication follows: The free surface flows are successfully modelled with one of existing free surface models, such as: level set method, volume of fluid method (with/without surface reconstruction), front tracking, two-fluid model (two momentum equations) with modified interphase force and others. The main disadvantage of two-fluid model used for simulations of free surface flows is numerical diffusion of the interface, which can be significantly reduced using the method presented in this paper. Several techniques for reduction of numerical diffusion of the interface have been implemented in the volume of fluid model and are based on modified numerical schemes for advection of volume fraction near the interface. The same approach could be used also for two-fluid method, but according to our experience more successful reduction of numerical diffusion of the interface can be achieved with conservative level set method. Within the conservative level set method, continuity equation for volume fraction is solved and after that the numerical diffusion of the interface is reduced in such a way that the thickness of the interface is kept constant during the simulation. Reduction of the interface diffusion can be also called interface sharpening. In present paper the two-fluid model with interface sharpening is validated on Rayleigh-Taylor instability. Under assumptions of isothermal and incompressible flow of two immiscible fluids, we simulated a system with the fluid of higher density located above the fluid of smaller density in two dimensions. Due to gravity in the system, fluid with higher density moves below the fluid with smaller density. Initial condition is not a flat interface between the fluids, but a sine wave with small amplitude, which develops into a mushroom-like structure. Mushroom-like structure in simulation of Rayleigh-Taylor instability later develops to small droplets as result of numerical dispersion of interface (interface sharpening

  10. Pellet culture model for human primary osteoblasts.

    Science.gov (United States)

    Jähn, K; Richards, R G; Archer, C W; Stoddart, M J

    2010-09-06

    In vitro monolayer culture of human primary osteoblasts (hOBs) often shows unsatisfactory results for extracellular matrix deposition, maturation and calcification. Nevertheless, monolayer culture is still the method of choice for in vitro differentiation of primary osteoblasts. We believe that the delay in mature ECM production by the monolayer cultured osteoblasts is determined by their state of cell maturation. A functional relationship between the inhibition of osteoblast proliferation and the induction of genes associated with matrix maturation was suggested within a monolayer culture model for rat calvarial osteoblasts. We hypothesize, that a pellet culture model could be utilized to decrease initial proliferation and increase the transformation of osteoblasts into a more mature phenotype. We performed pellet cultures using hOBs and compared their differentiation potential to 2D monolayer cultures. Using the pellet culture model, we were able to generate a population of cuboidal shaped central osteoblastic cells. Increased proliferation, as seen during low-density monolayer culture, was absent in pellet cultures and monolayers seeded at 40,000 cells/cm2. Moreover, the expression pattern of phenotypic markers Runx2, osterix, osteocalcin, col I and E11 mRNA was significantly different depending on whether the cells were cultured in low density monolayer, high density monolayer or pellet culture. We conclude that the transformation of the osteoblast phenotype in vitro to a more mature stage can be achieved more rapidly in 3D culture. Moreover, that dense monolayer leads to the formation of more mature osteoblasts than low-density seeded monolayer, while hOB cells in pellets seem to have transformed even further along the osteoblast phenotype.

  11. Pellet culture model for human primary osteoblasts

    Directory of Open Access Journals (Sweden)

    K Jähn

    2010-09-01

    Full Text Available In vitro monolayer culture of human primary osteoblasts (hOBs often shows unsatisfactory results for extracellular matrix deposition, maturation and calcification. Nevertheless, monolayer culture is still the method of choice for in vitro differentiation of primary osteoblasts. We believe that the delay in mature ECM production by the monolayer cultured osteoblasts is determined by their state of cell maturation. A functional relationship between the inhibition of osteoblast proliferation and the induction of genes associated with matrix maturation was suggested within a monolayer culture model for rat calvarial osteoblasts. We hypothesize, that a pellet culture model could be utilized to decrease initial proliferation and increase the transformation of osteoblasts into a more mature phenotype. We performed pellet cultures using hOBs and compared their differentiation potential to 2D monolayer cultures. Using the pellet culture model, we were able to generate a population of cuboidal shaped central osteoblastic cells. Increased proliferation, as seen during low-density monolayer culture, was absent in pellet cultures and monolayers seeded at 40,000 cells/cm2. Moreover, the expression pattern of phenotypic markers Runx2, osterix, osteocalcin, col I and E11 mRNA was significantly different depending on whether the cells were cultured in low density monolayer, high density monolayer or pellet culture. We conclude that the transformation of the osteoblast phenotype in vitro to a more mature stage can be achieved more rapidly in 3D culture. Moreover, that dense monolayer leads to the formation of more mature osteoblasts than low-density seeded monolayer, while hOB cells in pellets seem to have transformed even further along the osteoblast phenotype.

  12. l-cysteine suppresses ghrelin and reduces appetite in rodents and humans

    Science.gov (United States)

    McGavigan, A K; O'Hara, H C; Amin, A; Kinsey-Jones, J; Spreckley, E; Alamshah, A; Agahi, A; Banks, K; France, R; Hyberg, G; Wong, C; Bewick, G A; Gardiner, J V; Lehmann, A; Martin, N M; Ghatei, M A; Bloom, S R; Murphy, K G

    2015-01-01

    Background: High-protein diets promote weight loss and subsequent weight maintenance, but are difficult to adhere to. The mechanisms by which protein exerts these effects remain unclear. However, the amino acids produced by protein digestion may have a role in driving protein-induced satiety. Methods: We tested the effects of a range of amino acids on food intake in rodents and identified l-cysteine as the most anorexigenic. Using rodents we further studied the effect of l-cysteine on food intake, behaviour and energy expenditure. We proceeded to investigate its effect on neuronal activation in the hypothalamus and brainstem before investigating its effect on gastric emptying and gut hormone release. The effect of l-cysteine on appetite scores and gut hormone release was then investigated in humans. Results: l-Cysteine dose-dependently decreased food intake in both rats and mice following oral gavage and intraperitoneal administration. This effect did not appear to be secondary to behavioural or aversive side effects. l-Cysteine increased neuronal activation in the area postrema and delayed gastric emptying. It suppressed plasma acyl ghrelin levels and did not reduce food intake in transgenic ghrelin-overexpressing mice. Repeated l-cysteine administration decreased food intake in rats and obese mice. l-Cysteine reduced hunger and plasma acyl ghrelin levels in humans. Conclusions: Further work is required to determine the chronic effect of l-cysteine in rodents and humans on appetite and body weight, and whether l-cysteine contributes towards protein-induced satiety. PMID:25219528

  13. Application of Human-Autonomy Teaming to an Advanced Ground Station for Reduced Crew Operations

    Science.gov (United States)

    Ho, Nhut; Johnson, Walter; Panesar, Karanvir; Wakeland, Kenny; Sadler, Garrett; Wilson, Nathan; Nguyen, Bao; Lachter, Joel; Stallmann, Summer

    2017-01-01

    Within human factors there is burgeoning interest in the "human-autonomy teaming" (HAT) concept as a way to address the challenges of interacting with complex, increasingly autonomous systems. The HAT concept comes out of an aspiration to interact with increasingly autonomous systems as a team member, rather than simply use automation as a tool. The authors, and others, have proposed core tenets for HAT that include bi-directional communication, automation and system transparency, and advanced coordination between human and automated teammates via predefined, dynamic task sequences known as "plays." It is believed that, with proper implementation, HAT should foster appropriate teamwork, thus increasing trust and reliance on the system, which in turn will reduce workload, increase situation awareness, and improve performance. To this end, HAT has been demonstrated and/or studied in multiple applications including search and rescue operations, healthcare and medicine, autonomous vehicles, photography, and aviation. The current paper presents one such effort to apply HAT. It details the design of a HAT agent, developed by Human Automation Teaming Solutions, Inc., to facilitate teamwork between the automation and the human operator of an advanced ground dispatch station. This dispatch station was developed to support a NASA project investigating a concept called Reduced Crew Operations (RCO); consequently, we have named the agent R-HATS. Part of the RCO concept involves a ground operator providing enhanced support to a large number of aircraft with a single pilot on the flight deck. When assisted by R-HATS, operators can monitor and support or manage a large number of aircraft and use plays to respond in real-time to complicated, workload-intensive events (e.g., an airport closure). A play is a plan that encapsulates goals, tasks, and a task allocation strategy appropriate for a particular situation. In the current implementation, when a play is initiated by a user, R

  14. Reducing the likelihood of future human activities that could affect geologic high-level waste repositories

    International Nuclear Information System (INIS)

    1984-05-01

    The disposal of radioactive wastes in deep geologic formations provides a means of isolating the waste from people until the radioactivity has decayed to safe levels. However, isolating people from the wastes is a different problem, since we do not know what the future condition of society will be. The Human Interference Task Force was convened by the US Department of Energy to determine whether reasonable means exist (or could be developed) to reduce the likelihood of future human unintentionally intruding on radioactive waste isolation systems. The task force concluded that significant reductions in the likelihood of human interference could be achieved, for perhaps thousands of years into the future, if appropriate steps are taken to communicate the existence of the repository. Consequently, for two years the task force directed most of its study toward the area of long-term communication. Methods are discussed for achieving long-term communication by using permanent markers and widely disseminated records, with various steps taken to provide multiple levels of protection against loss, destruction, and major language/societal changes. Also developed is the concept of a universal symbol to denote Caution - Biohazardous Waste Buried Here. If used for the thousands of non-radioactive biohazardous waste sites in this country alone, a symbol could transcend generations and language changes, thereby vastly improving the likelihood of successful isolation of all buried biohazardous wastes

  15. Arterial shear stress reduces eph-b4 expression in adult human veins.

    Science.gov (United States)

    Model, Lynn S; Hall, Michael R; Wong, Daniel J; Muto, Akihito; Kondo, Yuka; Ziegler, Kenneth R; Feigel, Amanda; Quint, Clay; Niklason, Laura; Dardik, Alan

    2014-09-01

    Vein graft adaptation to the arterial environment is characterized by loss of venous identity, with reduced Ephrin type-B receptor 4 (Eph-B4) expression but without increased Ephrin-B2 expression. We examined changes of vessel identity of human saphenous veins in a flow circuit in which shear stress could be precisely controlled. Medium circulated at arterial or venous magnitudes of laminar shear stress for 24 hours; histologic, protein, and RNA analyses of vein segments were performed. Vein endothelium remained viable and functional, with platelet endothelial cell adhesion molecule (PECAM)-expressing cells on the luminal surface. Venous Eph-B4 expression diminished (p = .002), Ephrin-B2 expression was not induced (p = .268), and expression of osteopontin (p = .002) was increased with exposure to arterial magnitudes of shear stress. Similar changes were not found in veins placed under venous flow or static conditions. These data show that human saphenous veins remain viable during ex vivo application of shear stress in a bioreactor, without loss of the venous endothelium. Arterial magnitudes of shear stress cause loss of venous identity without gain of arterial identity in human veins perfused ex vivo. Shear stress alone, without immunologic or hormonal influence, is capable of inducing changes in vessel identity and, specifically, loss of venous identity.

  16. Dietary nitrate reduces resting metabolic rate: a randomized, crossover study in humans.

    Science.gov (United States)

    Larsen, Filip J; Schiffer, Tomas A; Ekblom, Björn; Mattsson, Mathias P; Checa, Antonio; Wheelock, Craig E; Nyström, Thomas; Lundberg, Jon O; Weitzberg, Eddie

    2014-04-01

    Nitrate, which is an inorganic anion abundant in vegetables, increases the efficiency of isolated human mitochondria. Such an effect might be reflected in changes in the resting metabolic rate (RMR) and formation of reactive oxygen species. The bioactivation of nitrate involves its active accumulation in saliva followed by a sequential reduction to nitrite, nitric oxide, and other reactive nitrogen species. We studied effects of inorganic nitrate, in amounts that represented a diet rich in vegetables, on the RMR in healthy volunteers. In a randomized, double-blind, crossover study, we measured the RMR by using indirect calorimetry in 13 healthy volunteers after a 3-d dietary intervention with sodium nitrate (NaNO₃) or a placebo (NaCl). The nitrate dose (0.1 mmol · kg⁻¹ · d⁻¹) corresponded to the amount in 200-300 g spinach, beetroot, lettuce, or other vegetable that was rich in nitrate. Effects of direct nitrite exposure on cell respiration were studied in cultured human primary myotubes. The RMR was 4.2% lower after nitrate compared with placebo administration, and the change correlated strongly to the degree of nitrate accumulation in saliva (r² = 0.71). The thyroid hormone status, insulin sensitivity, glucose uptake, plasma concentration of isoprostanes, and total antioxidant capacity were unaffected by nitrate. The administration of nitrite to human primary myotubes acutely inhibited respiration. Dietary inorganic nitrate reduces the RMR. This effect may have implications for the regulation of metabolic function in health and disease.

  17. Reducing the likelihood of future human activities that could affect geologic high-level waste repositories

    Energy Technology Data Exchange (ETDEWEB)

    1984-05-01

    The disposal of radioactive wastes in deep geologic formations provides a means of isolating the waste from people until the radioactivity has decayed to safe levels. However, isolating people from the wastes is a different problem, since we do not know what the future condition of society will be. The Human Interference Task Force was convened by the US Department of Energy to determine whether reasonable means exist (or could be developed) to reduce the likelihood of future human unintentionally intruding on radioactive waste isolation systems. The task force concluded that significant reductions in the likelihood of human interference could be achieved, for perhaps thousands of years into the future, if appropriate steps are taken to communicate the existence of the repository. Consequently, for two years the task force directed most of its study toward the area of long-term communication. Methods are discussed for achieving long-term communication by using permanent markers and widely disseminated records, with various steps taken to provide multiple levels of protection against loss, destruction, and major language/societal changes. Also developed is the concept of a universal symbol to denote Caution - Biohazardous Waste Buried Here. If used for the thousands of non-radioactive biohazardous waste sites in this country alone, a symbol could transcend generations and language changes, thereby vastly improving the likelihood of successful isolation of all buried biohazardous wastes.

  18. Development of a physiologically based pharmacokinetic model for assessment of human exposure to bisphenol A

    International Nuclear Information System (INIS)

    Yang, Xiaoxia; Doerge, Daniel R.; Teeguarden, Justin G.; Fisher, Jeffrey W.

    2015-01-01

    A previously developed physiologically based pharmacokinetic (PBPK) model for bisphenol A (BPA) in adult rhesus monkeys was modified to characterize the pharmacokinetics of BPA and its phase II conjugates in adult humans following oral ingestion. Coupled with in vitro studies on BPA metabolism in the liver and the small intestine, the PBPK model was parameterized using oral pharmacokinetic data with deuterated-BPA (d 6 -BPA) delivered in cookies to adult humans after overnight fasting. The availability of the serum concentration time course of unconjugated d 6 -BPA offered direct empirical evidence for the calibration of BPA model parameters. The recalibrated PBPK adult human model for BPA was then evaluated against published human pharmacokinetic studies with BPA. A hypothesis of decreased oral uptake was needed to account for the reduced peak levels observed in adult humans, where d 6 -BPA was delivered in soup and food was provided prior to BPA ingestion, suggesting the potential impact of dosing vehicles and/or fasting on BPA disposition. With the incorporation of Monte Carlo analysis, the recalibrated adult human model was used to address the inter-individual variability in the internal dose metrics of BPA for the U.S. general population. Model-predicted peak BPA serum levels were in the range of pM, with 95% of human variability falling within an order of magnitude. This recalibrated PBPK model for BPA in adult humans provides a scientific basis for assessing human exposure to BPA that can serve to minimize uncertainties incurred during extrapolations across doses and species. - Highlights: • A PBPK model predicts the kinetics of bisphenol A (BPA) in adult humans. • Serum concentrations of aglycone BPA are available for model calibration. • Model predicted peak BPA serum levels for adult humans were in the range of pM. • Model predicted 95% of human variability fell within an order of magnitude.

  19. A Non-Human Primate Model of Severe Pneumococcal Pneumonia

    Science.gov (United States)

    Reyes, Luis F.; Restrepo, Marcos I.; Hinojosa, Cecilia A.; Soni, Nilam J.; Shenoy, Anukul T.; Gilley, Ryan P.; Gonzalez-Juarbe, Norberto; Noda, Julio R.; Winter, Vicki T.; de la Garza, Melissa A.; Shade, Robert E.; Coalson, Jacqueline J.; Giavedoni, Luis D.; Anzueto, Antonio; Orihuela, Carlos J.

    2016-01-01

    Rationale Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and infectious death in adults worldwide. A non-human primate model is needed to study the molecular mechanisms that underlie the development of severe pneumonia, identify diagnostic tools, explore potential therapeutic targets, and test clinical interventions during pneumococcal pneumonia. Objective To develop a non-human primate model of pneumococcal pneumonia. Methods Seven adult baboons (Papio cynocephalus) were surgically tethered to a continuous monitoring system that recorded heart rate, temperature, and electrocardiography. Animals were inoculated with 109 colony-forming units of S. pneumoniae using bronchoscopy. Three baboons were rescued with intravenous ampicillin therapy. Pneumonia was diagnosed using lung ultrasonography and ex vivo confirmation by histopathology and immunodetection of pneumococcal capsule. Organ failure, using serum biomarkers and quantification of bacteremia, was assessed daily. Results Challenged animals developed signs and symptoms of pneumonia 4 days after infection. Infection was characterized by the presence of cough, tachypnea, dyspnea, tachycardia and fever. All animals developed leukocytosis and bacteremia 24 hours after infection. A severe inflammatory reaction was detected by elevation of serum cytokines, including Interleukin (IL)1Ra, IL-6, and IL-8, after infection. Lung ultrasonography precisely detected the lobes with pneumonia that were later confirmed by pathological analysis. Lung pathology positively correlated with disease severity. Antimicrobial therapy rapidly reversed symptomology and reduced serum cytokines. Conclusions We have developed a novel animal model for severe pneumococcal pneumonia that mimics the clinical presentation, inflammatory response, and infection kinetics seen in humans. This is a novel model to test vaccines and treatments, measure biomarkers to diagnose pneumonia, and predict outcomes. PMID:27855182

  20. Bayesian Safety Risk Modeling of Human-Flightdeck Automation Interaction

    Science.gov (United States)

    Ancel, Ersin; Shih, Ann T.

    2015-01-01

    Usage of automatic systems in airliners has increased fuel efficiency, added extra capabilities, enhanced safety and reliability, as well as provide improved passenger comfort since its introduction in the late 80's. However, original automation benefits, including reduced flight crew workload, human errors or training requirements, were not achieved as originally expected. Instead, automation introduced new failure modes, redistributed, and sometimes increased workload, brought in new cognitive and attention demands, and increased training requirements. Modern airliners have numerous flight modes, providing more flexibility (and inherently more complexity) to the flight crew. However, the price to pay for the increased flexibility is the need for increased mode awareness, as well as the need to supervise, understand, and predict automated system behavior. Also, over-reliance on automation is linked to manual flight skill degradation and complacency in commercial pilots. As a result, recent accidents involving human errors are often caused by the interactions between humans and the automated systems (e.g., the breakdown in man-machine coordination), deteriorated manual flying skills, and/or loss of situational awareness due to heavy dependence on automated systems. This paper describes the development of the increased complexity and reliance on automation baseline model, named FLAP for FLightdeck Automation Problems. The model development process starts with a comprehensive literature review followed by the construction of a framework comprised of high-level causal factors leading to an automation-related flight anomaly. The framework was then converted into a Bayesian Belief Network (BBN) using the Hugin Software v7.8. The effects of automation on flight crew are incorporated into the model, including flight skill degradation, increased cognitive demand and training requirements along with their interactions. Besides flight crew deficiencies, automation system

  1. Reducing Uncertainty in Chemistry Climate Model Predictions of Stratospheric Ozone

    Science.gov (United States)

    Douglass, A. R.; Strahan, S. E.; Oman, L. D.; Stolarski, R. S.

    2014-01-01

    Chemistry climate models (CCMs) are used to predict the future evolution of stratospheric ozone as ozone-depleting substances decrease and greenhouse gases increase, cooling the stratosphere. CCM predictions exhibit many common features, but also a broad range of values for quantities such as year of ozone-return-to-1980 and global ozone level at the end of the 21st century. Multiple linear regression is applied to each of 14 CCMs to separate ozone response to chlorine change from that due to climate change. We show that the sensitivity of lower atmosphere ozone to chlorine change deltaO3/deltaCly is a near linear function of partitioning of total inorganic chlorine (Cly) into its reservoirs; both Cly and its partitioning are controlled by lower atmospheric transport. CCMs with realistic transport agree with observations for chlorine reservoirs and produce similar ozone responses to chlorine change. After 2035 differences in response to chlorine contribute little to the spread in CCM results as the anthropogenic contribution to Cly becomes unimportant. Differences among upper stratospheric ozone increases due to temperature decreases are explained by differences in ozone sensitivity to temperature change deltaO3/deltaT due to different contributions from various ozone loss processes, each with their own temperature dependence. In the lower atmosphere, tropical ozone decreases caused by a predicted speed-up in the Brewer-Dobson circulation may or may not be balanced by middle and high latitude increases, contributing most to the spread in late 21st century predictions.

  2. Overweight in young males reduce fertility in rabbit model.

    Directory of Open Access Journals (Sweden)

    Francisco Marco-Jiménez

    Full Text Available Semen quality has certainly declined over the past few decades, possibly owing to modern lifestyle factors. In this sense, the role of overweight and obesity in the development of subfertility in males has generated a considerable amount of interest in recent years. However, there is no consensus on whether overweight or obesity impaired sperm quality. Thus, based on the ongoing debate about risk factors for subfertility associated with overweight and obesity in men, this study was designed to investigate the effect of overweight on sperm quality parameters and fertility success in randomized controlled trial in a rabbit model. Fourteen male rabbits were randomly assigned to a control group in which nutritional requirements were satisfied or a group fed to satiety from 12 to 32 weeks of age. At 24 weeks of age, semen samples were analysed weekly by conventional semen analysis for 8 weeks. In addition, during the trial female rabbits were artificially inseminated by each male to assess the fertility success and the number of offspring. Young males fed to satiety were associated with a significant increase in body weight (13.6% overweight and perirenal fat thickness (5%. Male overweight presented a significant decrease in sperm concentration. There were no differences in the remaining sperm parameters. However, male overweight showed a clear and significant decrease in fertility success (control group, 64±8.9% versus fed to satiety group, 35±9.2%, but not in the number of offspring. Taken together, our findings provide new evidence on the loss of fertility induced by overweight in males.

  3. Overweight in young males reduce fertility in rabbit model.

    Science.gov (United States)

    Marco-Jiménez, Francisco; Vicente, José Salvador

    2017-01-01

    Semen quality has certainly declined over the past few decades, possibly owing to modern lifestyle factors. In this sense, the role of overweight and obesity in the development of subfertility in males has generated a considerable amount of interest in recent years. However, there is no consensus on whether overweight or obesity impaired sperm quality. Thus, based on the ongoing debate about risk factors for subfertility associated with overweight and obesity in men, this study was designed to investigate the effect of overweight on sperm quality parameters and fertility success in randomized controlled trial in a rabbit model. Fourteen male rabbits were randomly assigned to a control group in which nutritional requirements were satisfied or a group fed to satiety from 12 to 32 weeks of age. At 24 weeks of age, semen samples were analysed weekly by conventional semen analysis for 8 weeks. In addition, during the trial female rabbits were artificially inseminated by each male to assess the fertility success and the number of offspring. Young males fed to satiety were associated with a significant increase in body weight (13.6% overweight) and perirenal fat thickness (5%). Male overweight presented a significant decrease in sperm concentration. There were no differences in the remaining sperm parameters. However, male overweight showed a clear and significant decrease in fertility success (control group, 64±8.9% versus fed to satiety group, 35±9.2%), but not in the number of offspring. Taken together, our findings provide new evidence on the loss of fertility induced by overweight in males.

  4. Passiflora tarminiana fruits reduce UVB-induced photoaging in human skin fibroblasts.

    Science.gov (United States)

    Bravo, Karent; Duque, Luisa; Ferreres, Federico; Moreno, Diego A; Osorio, Edison

    2017-03-01

    Skin aging is a complex process that is strongly affected by UV radiation, which stimulates the production of reactive oxygen species (ROS) in the epidermis and dermis and subsequently causes skin damage. Among the major consequences are increased collagen degradation and reduced collagen synthesis. Previous reports have demonstrated the beneficial effects of polyphenols for healthy skin. Passiflora tarminiana Coppens & V.E. Barney, a species of the Passifloraceae family, is widely distributed in South America and is rich in flavonoids. We show that UVB radiation increases metalloproteinase 1 (MMP-1) and reduces procollagen production in human dermal fibroblast (HDF) cells in a dose- and time-dependent manner. We examined the antioxidant and antiaging effects of the extract and fractions of P. tarminiana fruits. The fractions showed high polyphenol content (620mg EAG/g) and antioxidant activity, as measured by ORAC (4097μmol ET/g) and ABTS (2992μmol ET/g) assays. The aqueous fraction drastically inhibited the collagenase enzyme (IC 50 0.43μg/mL). The extract and fractions presented photoprotective effects by reducing UVB-induced MMP-1 production, increasing UVB-inhibited procollagen production, and decreasing ROS production after UVB irradiation in HDF. Finally, the polyphenol contents of the extracts and fractions from P. tarminiana were analyzed by HPLC-DAD-ESI-MS n , and procyanidins and glycosylated flavonoids were identified. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Kiwifruit Non-Sugar Components Reduce Glycaemic Response to Co-Ingested Cereal in Humans.

    Science.gov (United States)

    Mishra, Suman; Edwards, Haley; Hedderley, Duncan; Podd, John; Monro, John

    2017-10-30

    Kiwifruit (KF) effects on the human glycaemic response to co-ingested wheat cereal were determined. Participants (n = 20) consumed four meals in random order, all being made to 40 g of the same available carbohydrate, by adding kiwifruit sugars (KF sug; glucose, fructose, sucrose 2:2:1) to meals not containing KF. The meals were flaked wheat biscuit (WB)+KFsug, WB+KF, WB+guar gum+KFsug, WB+guar gum+KF, that was ingested after fasting overnight. Blood glucose was monitored 3 h and hunger measured at 180 min post-meal using a visual analogue scale. KF and guar reduced postprandial blood glucose response amplitude, and prevented subsequent hypoglycaemia that occurred with WB+KFsug. The area between the blood glucose response curve and baseline from 0 to 180 min was not significantly different between meals, 0-120 min areas were significantly reduced by KF and/or guar. Area from 120 to 180 min was positive for KF, guar, and KF+guar, while the area for the WB meal was negative. Hunger at 180 min was significantly reduced by KF and/or guar when compared with WB. We conclude that KF components other than available carbohydrate may improve the glycaemic response profile to co-ingested cereal food.

  6. Kiwifruit Non-Sugar Components Reduce Glycaemic Response to Co-Ingested Cereal in Humans

    Directory of Open Access Journals (Sweden)

    Suman Mishra

    2017-10-01

    Full Text Available Kiwifruit (KF effects on the human glycaemic response to co-ingested wheat cereal were determined. Participants (n = 20 consumed four meals in random order, all being made to 40 g of the same available carbohydrate, by adding kiwifruit sugars (KF sug; glucose, fructose, sucrose 2:2:1 to meals not containing KF. The meals were flaked wheat biscuit (WB+KFsug, WB+KF, WB+guar gum+KFsug, WB+guar gum+KF, that was ingested after fasting overnight. Blood glucose was monitored 3 h and hunger measured at 180 min post-meal using a visual analogue scale. KF and guar reduced postprandial blood glucose response amplitude, and prevented subsequent hypoglycaemia that occurred with WB+KFsug. The area between the blood glucose response curve and baseline from 0 to 180 min was not significantly different between meals, 0–120 min areas were significantly reduced by KF and/or guar. Area from 120 to 180 min was positive for KF, guar, and KF+guar, while the area for the WB meal was negative. Hunger at 180 min was significantly reduced by KF and/or guar when compared with WB. We conclude that KF components other than available carbohydrate may improve the glycaemic response profile to co-ingested cereal food.

  7. Actinomycin D Specifically Reduces Expanded CUG Repeat RNA in Myotonic Dystrophy Models

    Directory of Open Access Journals (Sweden)

    Ruth B. Siboni

    2015-12-01

    Full Text Available Myotonic dystrophy type 1 (DM1 is an inherited disease characterized by the inability to relax contracted muscles. Affected individuals carry large CTG expansions that are toxic when transcribed. One possible treatment approach is to reduce or eliminate transcription of CTG repeats. Actinomycin D (ActD is a potent transcription inhibitor and FDA-approved chemotherapeutic that binds GC-rich DNA with high affinity. Here, we report that ActD decreased CUG transcript levels in a dose-dependent manner in DM1 cell and mouse models at significantly lower concentrations (nanomolar compared to its use as a general transcription inhibitor or chemotherapeutic. ActD also significantly reversed DM1-associated splicing defects in a DM1 mouse model, and did so within the currently approved human treatment range. RNA-seq analyses showed that low concentrations of ActD did not globally inhibit transcription in a DM1 mouse model. These results indicate that transcription inhibition of CTG expansions is a promising treatment approach for DM1.

  8. Volcanic dust veils from sixth century tree-ring isotopes linked to reduced irradiance, primary production and human health.

    Science.gov (United States)

    Helama, Samuli; Arppe, Laura; Uusitalo, Joonas; Holopainen, Jari; Mäkelä, Hanna M; Mäkinen, Harri; Mielikäinen, Kari; Nöjd, Pekka; Sutinen, Raimo; Taavitsainen, Jussi-Pekka; Timonen, Mauri; Oinonen, Markku

    2018-01-22

    The large volcanic eruptions of AD 536 and 540 led to climate cooling and contributed to hardships of Late Antiquity societies throughout Eurasia, and triggered a major environmental event in the historical Roman Empire. Our set of stable carbon isotope records from subfossil tree rings demonstrates a strong negative excursion in AD 536 and 541-544. Modern data from these sites show that carbon isotope variations are driven by solar radiation. A model based on sixth century isotopes reconstruct an irradiance anomaly for AD 536 and 541-544 of nearly three standard deviations below the mean value based on modern data. This anomaly can be explained by a volcanic dust veil reducing solar radiation and thus primary production threatening food security over a multitude of years. We offer a hypothesis that persistently low irradiance contributed to remarkably simultaneous outbreaks of famine and Justinianic plague in the eastern Roman Empire with adverse effects on crop production and photosynthesis of the vitamin D in human skin and thus, collectively, human health. Our results provide a hitherto unstudied proxy for exploring the mechanisms of 'volcanic summers' to demonstrate the post-eruption deficiencies in sunlight and to explain the human consequences during such calamity years.

  9. The Elementary Operations of Human Vision Are Not Reducible to Template-Matching.

    Directory of Open Access Journals (Sweden)

    Peter Neri

    2015-11-01

    Full Text Available It is generally acknowledged that biological vision presents nonlinear characteristics, yet linear filtering accounts of visual processing are ubiquitous. The template-matching operation implemented by the linear-nonlinear cascade (linear filter followed by static nonlinearity is the most widely adopted computational tool in systems neuroscience. This simple model achieves remarkable explanatory power while retaining analytical tractability, potentially extending its reach to a wide range of systems and levels in sensory processing. The extent of its applicability to human behaviour, however, remains unclear. Because sensory stimuli possess multiple attributes (e.g. position, orientation, size, the issue of applicability may be asked by considering each attribute one at a time in relation to a family of linear-nonlinear models, or by considering all attributes collectively in relation to a specified implementation of the linear-nonlinear cascade. We demonstrate that human visual processing can operate under conditions that are indistinguishable from linear-nonlinear transduction with respect to substantially different stimulus attributes of a uniquely specified target signal with associated behavioural task. However, no specific implementation of a linear-nonlinear cascade is able to account for the entire collection of results across attributes; a satisfactory account at this level requires the introduction of a small gain-control circuit, resulting in a model that no longer belongs to the linear-nonlinear family. Our results inform and constrain efforts at obtaining and interpreting comprehensive characterizations of the human sensory process by demonstrating its inescapably nonlinear nature, even under conditions that have been painstakingly fine-tuned to facilitate template-matching behaviour and to produce results that, at some level of inspection, do conform to linear filtering predictions. They also suggest that compliance with linear

  10. The Elementary Operations of Human Vision Are Not Reducible to Template-Matching.

    Science.gov (United States)

    Neri, Peter

    2015-11-01

    It is generally acknowledged that biological vision presents nonlinear characteristics, yet linear filtering accounts of visual processing are ubiquitous. The template-matching operation implemented by the linear-nonlinear cascade (linear filter followed by static nonlinearity) is the most widely adopted computational tool in systems neuroscience. This simple model achieves remarkable explanatory power while retaining analytical tractability, potentially extending its reach to a wide range of systems and levels in sensory processing. The extent of its applicability to human behaviour, however, remains unclear. Because sensory stimuli possess multiple attributes (e.g. position, orientation, size), the issue of applicability may be asked by considering each attribute one at a time in relation to a family of linear-nonlinear models, or by considering all attributes collectively in relation to a specified implementation of the linear-nonlinear cascade. We demonstrate that human visual processing can operate under conditions that are indistinguishable from linear-nonlinear transduction with respect to substantially different stimulus attributes of a uniquely specified target signal with associated behavioural task. However, no specific implementation of a linear-nonlinear cascade is able to account for the entire collection of results across attributes; a satisfactory account at this level requires the introduction of a small gain-control circuit, resulting in a model that no longer belongs to the linear-nonlinear family. Our results inform and constrain efforts at obtaining and interpreting comprehensive characterizations of the human sensory process by demonstrating its inescapably nonlinear nature, even under conditions that have been painstakingly fine-tuned to facilitate template-matching behaviour and to produce results that, at some level of inspection, do conform to linear filtering predictions. They also suggest that compliance with linear transduction may be

  11. Humanized In Vivo Model for Streptococcal Impetigo

    Science.gov (United States)

    Scaramuzzino, Dominick A.; McNiff, Jennifer M.; Bessen, Debra E.

    2000-01-01

    An in vivo model for group A streptococcal (GAS) impetigo was developed, whereby human neonatal foreskin engrafted onto SCID mice was superficially damaged and bacteria were topically applied. Severe infection, indicated by a purulent exudate, could be induced with as few as 1,000 CFU of a virulent strain. Early findings (48 h) showed a loss of stratum corneum and adherence of short chains of gram-positive cocci to the external surface of granular keratinocytes. This was followed by an increasing infiltration of polymorphonuclear leukocytes (neutrophils) of mouse origin, until a thick layer of pus covered an intact epidermis, with massive clumps of cocci accumulated at the outer rim of the pus layer. By 7 days postinoculation, the epidermis was heavily eroded; in some instances, the dermis contained pockets (ulcers) filled with cocci, similar to that observed for ecthyma. Importantly, virulent GAS underwent reproduction, resulting in a net increase in CFU of 20- to 14,000-fold. The majority of emm pattern D strains had a higher gross pathology score than emm pattern A, B, or C (A–C) strains, consistent with epidemiological findings that pattern D strains have a strong tendency to cause impetigo, whereas pattern A–C strains are more likely to cause pharyngitis. PMID:10768985

  12. Optimization model using Markowitz model approach for reducing the number of dengue cases in Bandung

    Science.gov (United States)

    Yong, Benny; Chin, Liem

    2017-05-01

    Dengue fever is one of the most serious diseases and this disease can cause death. Currently, Indonesia is a country with the highest cases of dengue disease in Southeast Asia. Bandung is one of the cities in Indonesia that is vulnerable to dengue disease. The sub-districts in Bandung had different levels of relative risk of dengue disease. Dengue disease is transmitted to people by the bite of an Aedesaegypti mosquito that is infected with a dengue virus. Prevention of dengue disease is by controlling the vector mosquito. It can be done by various methods, one of the methods is fogging. The efforts made by the Health Department of Bandung through fogging had constraints in terms of limited funds. This problem causes Health Department selective in fogging, which is only done for certain locations. As a result, many sub-districts are not handled properly by the Health Department because of the unequal distribution of activities to prevent the spread of dengue disease. Thus, it needs the proper allocation of funds to each sub-district in Bandung for preventing dengue transmission optimally. In this research, the optimization model using Markowitz model approach will be applied to determine the allocation of funds should be given to each sub-district in Bandung. Some constraints will be added to this model and the numerical solution will be solved with generalized reduced gradient method using Solver software. The expected result of this research is the proportion of funds given to each sub-district in Bandung correspond to the level of risk of dengue disease in each sub-district in Bandung so that the number of dengue cases in this city can be reduced significantly.

  13. The effect of reducing numbers of Campylobacter in broiler intestines on human health risk

    DEFF Research Database (Denmark)

    Nauta, Maarten; Johannessen, Gro; Laureano Adame, Laura

    2016-01-01

    in concentration on the meat and a reduction in the human health risk of campylobacteriosis. In this study, two methods are presented and compared. The first is a linear regression model, based on count data from caecal contents and skin sample data, obtained after processing from the same flocks. Alternatively...... in concentration in the intestinal content has a large impact on the risk of campylobacteriosis due to the consumption of chicken meat: a relative risk reduction between 44% and 95%. Therefore it seems promising to aim interventions at a reduction of the concentration of Campylobacter in the broiler intestines...

  14. Modeling human response errors in synthetic flight simulator domain

    Science.gov (United States)

    Ntuen, Celestine A.

    1992-01-01

    This paper presents a control theoretic approach to modeling human response errors (HRE) in the flight simulation domain. The human pilot is modeled as a supervisor of a highly automated system. The synthesis uses the theory of optimal control pilot modeling for integrating the pilot's observation error and the error due to the simulation model (experimental error). Methods for solving the HRE problem are suggested. Experimental verification of the models will be tested in a flight quality handling simulation.

  15. A long term model of circulation. [human body

    Science.gov (United States)

    White, R. J.

    1974-01-01

    A quantitative approach to modeling human physiological function, with a view toward ultimate application to long duration space flight experiments, was undertaken. Data was obtained on the effect of weightlessness on certain aspects of human physiological function during 1-3 month periods. Modifications in the Guyton model are reviewed. Design considerations for bilateral interface models are discussed. Construction of a functioning whole body model was studied, as well as the testing of the model versus available data.

  16. The let-7 microRNA reduces tumor growth in mouse models of lung cancer.

    Science.gov (United States)

    Esquela-Kerscher, Aurora; Trang, Phong; Wiggins, Jason F; Patrawala, Lubna; Cheng, Angie; Ford, Lance; Weidhaas, Joanne B; Brown, David; Bader, Andreas G; Slack, Frank J

    2008-03-15

    MicroRNAs have been increasingly implicated in human cancer and interest has grown about the potential to use microRNAs to combat cancer. Lung cancer is the most prevalent form of cancer worldwide and lacks effective therapies. Here we have used both in vitro and in vivo approaches to show that the let-7 microRNA directly represses cancer growth in the lung. We find that let-7 inhibits the growth of multiple human lung cancer cell lines in culture, as well as the growth of lung cancer cell xenografts in immunodeficient mice. Using an established orthotopic mouse lung cancer model, we show that intranasal let-7 administration reduces tumor formation in vivo in the lungs of animals expressing a G12D activating mutation for the K-ras oncogene. These findings provide direct evidence that let-7 acts as a tumor suppressor gene in the lung and indicate that this miRNA may be useful as a novel therapeutic agent in lung cancer.

  17. Case-Based Reasoning for Human Behavior Modeling

    Science.gov (United States)

    2006-02-16

    edition may be used. Case Based Reasoning for Human Behavior Modeling CDRL A002 for Contract N00014-03-C-0178 February 16, 2006 Document...maintaining a useful repository demand that reuse be supported for human behavior modeling even if other model construction aids are also available...et al. (2001). Results of the Common Human Behavior Representation And Interchange System (CHRIS) Workshop. Fall 2001 Simulation Interoperability

  18. Competency Modeling in Extension Education: Integrating an Academic Extension Education Model with an Extension Human Resource Management Model

    Science.gov (United States)

    Scheer, Scott D.; Cochran, Graham R.; Harder, Amy; Place, Nick T.

    2011-01-01

    The purpose of this study was to compare and contrast an academic extension education model with an Extension human resource management model. The academic model of 19 competencies was similar across the 22 competencies of the Extension human resource management model. There were seven unique competencies for the human resource management model.…

  19. Heatwave early warning systems and adaptation advice to reduce human health consequences of heatwaves.

    Science.gov (United States)

    Lowe, Dianne; Ebi, Kristie L; Forsberg, Bertil

    2011-12-01

    With climate change, there has been an increase in the frequency, intensity and duration of heatwave events. In response to the devastating mortality and morbidity of recent heatwave events, many countries have introduced heatwave early warning systems (HEWS). HEWS are designed to reduce the avoidable human health consequences of heatwaves through timely notification of prevention measures to vulnerable populations. To identify the key characteristics of HEWS in European countries to help inform modification of current, and development of, new systems and plans. We searched the internet to identify HEWS policy or government documents for 33 European countries and requested information from relevant organizations. We translated the HEWS documents and extracted details on the trigger indicators, thresholds for action, notification strategies, message intermediaries, communication and dissemination strategies, prevention strategies recommended and specified target audiences. Twelve European countries have HEWS. Although there are many similarities among the HEWS, there also are differences in key characteristics that could inform improvements in heatwave early warning plans.

  20. N- and S-homocysteinylation reduce the binding of human serum albumin to catechins.

    Science.gov (United States)

    Zinellu, Angelo; Sotgia, Salvatore; Scanu, Bastianina; Arru, Dionigia; Cossu, Annalisa; Posadino, Anna Maria; Giordo, Roberta; Mangoni, Arduino A; Pintus, Gianfranco; Carru, Ciriaco

    2017-03-01

    The dietary flavonoids epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) have been shown to interact with circulating albumin for transport in blood to different body tissues. This interaction may modulate their bioavailability and effectiveness. Using affinity capillary electrophoresis to assess binding constants (K b ), we investigated whether posttranslational modification of human serum albumin (HSA) through N- and S-homocysteinylation, commonly observed in hyperhomocysteinemia, may modify its interaction with catechins. S-Hcy HSA had lower K b values toward EC (14 %), EGC (18 %), ECG (24 %) and EGCG (30 %). Similarly, N-Hcy HSA had lower K b values toward EC (17 %), EGC (22 %), ECG (23 %) and EGCG (32 %). No differences were observed in the affinity between catechins, albumin and mercaptalbumin. Therefore, HSA posttranslational modifications typical of hyperhomocysteinemia reduce its affinity to catechins, potentially affecting their pharmacokinetics and availability at the active sites.

  1. Dexamethasone reduces cell surface levels of CD11b on human eosinophils

    Directory of Open Access Journals (Sweden)

    A. M. Das

    1997-01-01

    Full Text Available Overnight incubation of human eosinophils (Eøs with the glucocorticoid hormone dexamethasone (DEX; 0.1 μM resulted in lower expression of the CD11b, but not CD49d, antigen on their plasma membrane, as assessed by flow cytometry. DEX produced a consistent inhibitory effect (ranging from 16% to 20% when tested at a concentration of 0.1 μM. Eø stimulation with 100 ng/ml eotaxin produced an increase in CD11b (+26%, but not CD11c, levels and concomitantly a reduction (–25% on CD62L expression. The inhibition exerted by DEX upon CD11b levels was also evident following eotaxin upregulation, with a degree of inhibition similar to that seen on basal levels. These data highlight a novel mechanism of action by which glucocorticoid hormones may be effective in reducing Eø accumulation during allergic inflammation in man.

  2. Lycorine reduces mortality of human enterovirus 71-infected mice by inhibiting virus replication

    Directory of Open Access Journals (Sweden)

    Qin Chuan

    2011-10-01

    Full Text Available Abstract Human enterovirus 71 (EV71 infection causes hand, foot and mouth disease in children under 6 years old and this infection occasionally induces severe neurological complications. No vaccines or drugs are clinical available to control EV71 epidemics. In present study, we show that treatment with lycorine reduced the viral cytopathic effect (CPE on rhabdomyosarcoma (RD cells by inhibiting virus replication. Analysis of this inhibitory effect of lycorine on viral proteins synthesis suggests that lycorine blocks the elongation of the viral polyprotein during translation. Lycorine treatment of mice challenged with a lethal dose of EV71 resulted in reduction of mortality, clinical scores and pathological changes in the muscles of mice, which were achieved through inhibition of viral replication. When mice were infected with a moderate dose of EV71, lycorine treatment was able to protect them from paralysis. Lycorine may be a potential drug candidate for the clinical treatment of EV71-infected patients.

  3. Sensitivity of Reliability Estimates in Partially Damaged RC Structures subject to Earthquakes, using Reduced Hysteretic Models

    DEFF Research Database (Denmark)

    Iwankiewicz, R.; Nielsen, Søren R. K.; Skjærbæk, P. S.

    The subject of the paper is the investigation of the sensitivity of structural reliability estimation by a reduced hysteretic model for a reinforced concrete frame under an earthquake excitation.......The subject of the paper is the investigation of the sensitivity of structural reliability estimation by a reduced hysteretic model for a reinforced concrete frame under an earthquake excitation....

  4. A sample application of nuclear power human resources model

    International Nuclear Information System (INIS)

    Gurgen, A.; Ergun, S.

    2016-01-01

    One of the most important issues for a new comer country initializing the nuclear power plant projects is to have both quantitative and qualitative models for the human resources development. For the quantitative model of human resources development for Turkey, “Nuclear Power Human Resources (NPHR) Model” developed by the Los Alamos National Laboratory was used to determine the number of people that will be required from different professional or occupational fields in the planning of human resources for Akkuyu, Sinop and the third nuclear power plant projects. The number of people required for different professions for the Nuclear Energy Project Implementation Department, the regulatory authority, project companies, construction, nuclear power plants and the academy were calculated. In this study, a sample application of the human resources model is presented. The results of the first tries to calculate the human resources needs of Turkey were obtained. Keywords: Human Resources Development, New Comer Country, NPHR Model

  5. Benzylglucosinolate Derived Isothiocyanate from Tropaeolum majus Reduces Gluconeogenic Gene and Protein Expression in Human Cells.

    Science.gov (United States)

    Guzmán-Pérez, Valentina; Bumke-Vogt, Christiane; Schreiner, Monika; Mewis, Inga; Borchert, Andrea; Pfeiffer, Andreas F H

    2016-01-01

    Nasturtium (Tropaeolum majus L.) contains high concentrations of benzylglcosinolate. We found that a hydrolysis product of benzyl glucosinolate-the benzyl isothiocyanate (BITC)-modulates the intracellular localization of the transcription factor Forkhead box O 1 (FOXO1). FoxO transcription factors can antagonize insulin effects and trigger a variety of cellular processes involved in tumor suppression, longevity, development and metabolism. The current study evaluated the ability of BITC-extracted as intact glucosinolate from nasturtium and hydrolyzed with myrosinase-to modulate i) the insulin-signaling pathway, ii) the intracellular localization of FOXO1 and, iii) the expression of proteins involved in gluconeogenesis, antioxidant response and detoxification. Stably transfected human osteosarcoma cells (U-2 OS) with constitutive expression of FOXO1 protein labeled with GFP (green fluorescent protein) were used to evaluate the effect of BITC on FOXO1. Human hepatoma HepG2 cell cultures were selected to evaluate the effect on gluconeogenic, antioxidant and detoxification genes and protein expression. BITC reduced the phosphorylation of protein kinase B (AKT/PKB) and FOXO1; promoted FOXO1 translocation from cytoplasm into the nucleus antagonizing the insulin effect; was able to down-regulate the gene and protein expression of gluconeogenic enzymes; and induced the gene expression of antioxidant and detoxification enzymes. Knockdown analyses with specific siRNAs showed that the expression of gluconeogenic genes was dependent on nuclear factor (erythroid derived)-like2 (NRF2) and independent of FOXO1, AKT and NAD-dependent deacetylase sirtuin-1 (SIRT1). The current study provides evidence that BITC might have a role in type 2 diabetes T2D by reducing hepatic glucose production and increasing antioxidant resistance.

  6. Interferon-γ Reduces the Proliferation of Primed Human Renal Tubular Cells

    Directory of Open Access Journals (Sweden)

    Omar García-Sánchez

    2014-01-01

    Full Text Available Background/Aims: Chronic kidney disease (CKD is a progressive deterioration of the kidney function, which may eventually lead to renal failure and the need for dialysis or kidney transplant. Whether initiated in the glomeruli or the tubuli, CKD is characterized by progressive nephron loss, for which the process of tubular deletion is of key importance. Tubular deletion results from tubular epithelial cell death and defective repair, leading to scarring of the renal parenchyma. Several cytokines and signaling pathways, including transforming growth factor-β (TGF-β and the Fas pathway, have been shown to participate in vivo in tubular cell death. However, there is some controversy about their mode of action, since a direct effect on normal tubular cells has not been demonstrated. We hypothesized that epithelial cells would require specific priming to become sensitive to TGF-β or Fas stimulation and that this priming would be brought about by specific mediators found in the pathological scenario. Methods: Herein we studied whether the combined effect of several stimuli known to take part in CKD progression, namely TGF-β, tumor necrosis factor-α, interferon-γ (IFN-γ, and Fas stimulation, on primed resistant human tubular cells caused cell death or reduced proliferation. Results: We demonstrate that these cytokines have no synergistic effect on the proliferation or viability of human kidney (HK2 cells. We also demonstrate that IFN-γ, but not the other stimuli, reduces the proliferation of cycloheximide-primed HK2 cells without affecting their viability. Conclusion: Our results point at a potentially important role of IFN-γ in defective repair, leading to nephron loss during CKD.

  7. Reduced glutathione prevents camphorquinone-induced apoptosis in human oral keratinocytes.

    Science.gov (United States)

    Volk, Joachim; Leyhausen, Gabriele; Wessels, Miriam; Geurtsen, Werner

    2014-02-01

    Camphorquinone (CQ) is a widely used photoinitiator in dental visible light (VL)-cured resinous materials. However, little is known about the toxicity of CQ in human cells. This study was designed to investigate CQ induced oxidative strain and apoptosis in cultured human oral keratinocytes (OKF6/TERT 2). Furthermore, the effects of visible-light (VL)-irradiation and the reducing agent N,N-dimethyl-p-toluidine (DMT) were investigated. In addition, the preventive potential of the antioxidant glutathione (GSH) against CQ induced toxicity was analyzed as well. The fluorescent DNA-staining dye Hoechst 33342 was used to quantify total cell numbers. Intracellular levels of reactive oxygen species (ROS) were measured by the fluorescent probe 2',7'-dichlorofluorescein diacetate (DCFH-DA). Apoptosis was determined by FACS analysis (Annexin V-FITC/propidium iodide), by measuring caspase-3/7 activity (ELISA) and by DNA laddering. Our data show that CQ was dose-dependent cytotoxic and caused oxidative stress by inducing reactive oxygen species (ROS). The redistribution of phosphatidylserine (PS) to the outer layer of the plasma membrane, induction of caspase-3 enzyme activity and DNA fragmentation were also observed in CQ exposed cells. Interestingly, CQ-induced ROS generation enhanced by VL irradiation or a simultaneous treatment with DMT showed no quantitative effect on apoptosis. However, co-exposure of cells with GSH significantly reduced the intracellular ROS generation as well as apoptosis caused by CQ. This is the first report showing that ROS-induced apoptosis, which is caused by CQ, is prevented by GSH. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  8. Benzylglucosinolate Derived Isothiocyanate from Tropaeolum majus Reduces Gluconeogenic Gene and Protein Expression in Human Cells.

    Directory of Open Access Journals (Sweden)

    Valentina Guzmán-Pérez

    Full Text Available Nasturtium (Tropaeolum majus L. contains high concentrations of benzylglcosinolate. We found that a hydrolysis product of benzyl glucosinolate-the benzyl isothiocyanate (BITC-modulates the intracellular localization of the transcription factor Forkhead box O 1 (FOXO1. FoxO transcription factors can antagonize insulin effects and trigger a variety of cellular processes involved in tumor suppression, longevity, development and metabolism. The current study evaluated the ability of BITC-extracted as intact glucosinolate from nasturtium and hydrolyzed with myrosinase-to modulate i the insulin-signaling pathway, ii the intracellular localization of FOXO1 and, iii the expression of proteins involved in gluconeogenesis, antioxidant response and detoxification. Stably transfected human osteosarcoma cells (U-2 OS with constitutive expression of FOXO1 protein labeled with GFP (green fluorescent protein were used to evaluate the effect of BITC on FOXO1. Human hepatoma HepG2 cell cultures were selected to evaluate the effect on gluconeogenic, antioxidant and detoxification genes and protein expression. BITC reduced the phosphorylation of protein kinase B (AKT/PKB and FOXO1; promoted FOXO1 translocation from cytoplasm into the nucleus antagonizing the insulin effect; was able to down-regulate the gene and protein expression of gluconeogenic enzymes; and induced the gene expression of antioxidant and detoxification enzymes. Knockdown analyses with specific siRNAs showed that the expression of gluconeogenic genes was dependent on nuclear factor (erythroid derived-like2 (NRF2 and independent of FOXO1, AKT and NAD-dependent deacetylase sirtuin-1 (SIRT1. The current study provides evidence that BITC might have a role in type 2 diabetes T2D by reducing hepatic glucose production and increasing antioxidant resistance.

  9. Training Reduces Stress in Human-Socialised Wolves to the Same Degree as in Dogs.

    Science.gov (United States)

    Vasconcellos, Angélica da Silva; Virányi, Zsófia; Range, Friederike; Ades, César; Scheidegger, Jördis Kristin; Möstl, Erich; Kotrschal, Kurt

    2016-01-01

    The welfare of animals in captivity is of considerable societal concern. A major source of stress, especially for wild animals, is the lack of control over their environment, which includes not being able to avoid contact with human beings. Paradoxically, some studies have shown that interactions with human beings may improve the welfare of wild animals in captivity. Here, we investigated the behavioural (behaviours indicative of cooperation or stress) and physiological (variations in salivary cortisol concentrations) effects of the increasingly used practice of training wild animals as a way to facilitate handling and/or as behavioural enrichment. We evaluated the effects of indoor training sessions with familiar caretakers on nine human-socialised individuals of a wild species, the wolf (Canis lupus), in comparison to nine individuals of its domesticated form, the dog (Canis lupus familiaris). All animals were raised and kept in intraspecific packs under identical conditions-in accordance with the social structure of the species-in order to control for socialisation with human beings and familiarity with training. We also collected saliva samples of trainers to measure GC and testosterone concentrations, to control for the effects of trainers' stress levels on the responses of the animals. During the training sessions, separated from pack members, the animals stayed voluntarily close to the trainers and mostly adequately performed requested behaviours, indicating concentration to the task. Similarly to dogs, the salivary cortisol level of wolves-used as an index of stress-dropped during these sessions, pointing to a similar stress-reducing effect of the training interaction in both subspecies. The responses to the requested behaviours and the reduction in salivary cortisol level of wolves and dogs varied across trainers, which indicates that the relaxing effect of training has a social component. This points to another factor affecting the welfare of animals

  10. Training Reduces Stress in Human-Socialised Wolves to the Same Degree as in Dogs.

    Directory of Open Access Journals (Sweden)

    Angélica da Silva Vasconcellos

    Full Text Available The welfare of animals in captivity is of considerable societal concern. A major source of stress, especially for wild animals, is the lack of control over their environment, which includes not being able to avoid contact with human beings. Paradoxically, some studies have shown that interactions with human beings may improve the welfare of wild animals in captivity. Here, we investigated the behavioural (behaviours indicative of cooperation or stress and physiological (variations in salivary cortisol concentrations effects of the increasingly used practice of training wild animals as a way to facilitate handling and/or as behavioural enrichment. We evaluated the effects of indoor training sessions with familiar caretakers on nine human-socialised individuals of a wild species, the wolf (Canis lupus, in comparison to nine individuals of its domesticated form, the dog (Canis lupus familiaris. All animals were raised and kept in intraspecific packs under identical conditions-in accordance with the social structure of the species-in order to control for socialisation with human beings and familiarity with training. We also collected saliva samples of trainers to measure GC and testosterone concentrations, to control for the effects of trainers' stress levels on the responses of the animals. During the training sessions, separated from pack members, the animals stayed voluntarily close to the trainers and mostly adequately performed requested behaviours, indicating concentration to the task. Similarly to dogs, the salivary cortisol level of wolves-used as an index of stress-dropped during these sessions, pointing to a similar stress-reducing effect of the training interaction in both subspecies. The responses to the requested behaviours and the reduction in salivary cortisol level of wolves and dogs varied across trainers, which indicates that the relaxing effect of training has a social component. This points to another factor affecting the welfare

  11. Human bipedal instability in tree canopy environments is reduced by "light touch" fingertip support.

    Science.gov (United States)

    Johannsen, L; Coward, S R L; Martin, G R; Wing, A M; Casteren, A van; Sellers, W I; Ennos, A R; Crompton, R H; Thorpe, S K S

    2017-04-25

    Whether tree canopy habitats played a sustained role in the ecology of ancestral bipedal hominins is unresolved. Some argue that arboreal bipedalism was prohibitively risky for hominins whose increasingly modern anatomy prevented them from gripping branches with their feet. Balancing on two legs is indeed challenging for humans under optimal conditions let alone in forest canopy, which is physically and visually highly dynamic. Here we quantify the impact of forest canopy characteristics on postural stability in humans. Viewing a movie of swaying branches while standing on a branch-like bouncy springboard destabilised the participants as much as wearing a blindfold. However "light touch", a sensorimotor strategy based on light fingertip support, significantly enhanced their balance and lowered their thigh muscle activity by up to 30%. This demonstrates how a light touch strategy could have been central to our ancestor's ability to avoid falls and reduce the mechanical and metabolic cost of arboreal feeding and movement. Our results may also indicate that some adaptations in the hand that facilitated continued access to forest canopy may have complemented, rather than opposed, adaptations that facilitated precise manipulation and tool use.

  12. Reduced thoracolumbar fascia shear strain in human chronic low back pain

    Science.gov (United States)

    2011-01-01

    Background The role played by the thoracolumbar fascia in chronic low back pain (LBP) is poorly understood. The thoracolumbar fascia is composed of dense connective tissue layers separated by layers of loose connective tissue that normally allow the dense layers to glide past one another during trunk motion. The goal of this study was to quantify shear plane motion within the thoracolumbar fascia using ultrasound elasticity imaging in human subjects with and without chronic low back pain (LBP). Methods We tested 121 human subjects, 50 without LBP and 71 with LBP of greater than 12 months duration. In each subject, an ultrasound cine-recording was acquired on the right and left sides of the back during passive trunk flexion using a motorized articulated table with the hinge point of the table at L4-5 and the ultrasound probe located longitudinally 2 cm lateral to the midline at the level of the L2-3 interspace. Tissue displacement within the thoracolumbar fascia was calculated using cross correlation techniques and shear strain was derived from this displacement data. Additional measures included standard range of motion and physical performance evaluations as well as ultrasound measurement of perimuscular connective tissue thickness and echogenicity. Results Thoracolumbar fascia shear strain was reduced in the LBP group compared with the No-LBP group (56.4% ± 3.1% vs. 70.2% ± 3.6% respectively, p fascia shear strain and the following variables: perimuscular connective tissue thickness (r = -0.45, p fascia shear strain was ~20% lower in human subjects with chronic low back pain. This reduction of shear plane motion may be due to abnormal trunk movement patterns and/or intrinsic connective tissue pathology. There appears to be some sex-related differences in thoracolumbar fascia shear strain that may also play a role in altered connective tissue function. PMID:21929806

  13. Reduced thoracolumbar fascia shear strain in human chronic low back pain

    Directory of Open Access Journals (Sweden)

    Konofagou Elisa E

    2011-09-01

    Full Text Available Abstract Background The role played by the thoracolumbar fascia in chronic low back pain (LBP is poorly understood. The thoracolumbar fascia is composed of dense connective tissue layers separated by layers of loose connective tissue that normally allow the dense layers to glide past one another during trunk motion. The goal of this study was to quantify shear plane motion within the thoracolumbar fascia using ultrasound elasticity imaging in human subjects with and without chronic low back pain (LBP. Methods We tested 121 human subjects, 50 without LBP and 71 with LBP of greater than 12 months duration. In each subject, an ultrasound cine-recording was acquired on the right and left sides of the back during passive trunk flexion using a motorized articulated table with the hinge point of the table at L4-5 and the ultrasound probe located longitudinally 2 cm lateral to the midline at the level of the L2-3 interspace. Tissue displacement within the thoracolumbar fascia was calculated using cross correlation techniques and shear strain was derived from this displacement data. Additional measures included standard range of motion and physical performance evaluations as well as ultrasound measurement of perimuscular connective tissue thickness and echogenicity. Results Thoracolumbar fascia shear strain was reduced in the LBP group compared with the No-LBP group (56.4% ± 3.1% vs. 70.2% ± 3.6% respectively, p Conclusion Thoracolumbar fascia shear strain was ~20% lower in human subjects with chronic low back pain. This reduction of shear plane motion may be due to abnormal trunk movement patterns and/or intrinsic connective tissue pathology. There appears to be some sex-related differences in thoracolumbar fascia shear strain that may also play a role in altered connective tissue function.

  14. Human touch effectively and safely reduces pain in the newborn intensive care unit.

    Science.gov (United States)

    Herrington, Carolyn J; Chiodo, Lisa M

    2014-03-01

    This was a feasibility pilot study to evaluate the efficacy of the nonpharmacologic pain management technique of gentle human touch (GHT) in reducing pain response to heel stick in premature infants in the neonatal intensive care unit (NICU). Eleven premature infants ranging from 27 to 34 weeks' gestational age, in a level III NICU in a teaching hospital, were recruited and randomized to order of treatment in this repeated-measures crossover-design experiment. Containment with GHT during heel stick was compared with traditional nursery care (side lying and "nested" in an incubator). Heart rate, respiratory rate, oxygen saturation, and cry were measured continuously beginning at baseline and continuing through heel warming, heel stick, and recovery following the heel stick. Infants who did not receive GHT had decreased respiration, increased heart rate, and increased cry time during the heel stick. In contrast, infants who received GHT did not have decreased respirations, elevated heart rates, or increased cry time during the heel stick. No significant differences were noted in oxygen saturation in either group. GHT is a simple nonpharmacologic therapy that can be used by nurses and families to reduce pain of heel stick in premature infants in the NICU. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  15. Reduced sensitivity to sooner reward during intertemporal decision-making following insula damage in humans

    Directory of Open Access Journals (Sweden)

    Manuela eSellitto

    2016-01-01

    Full Text Available During intertemporal choice, humans tend to prefer small-sooner rewards over larger-delayed rewards, reflecting temporal discounting (TD of delayed outcomes. Functional neuroimaging evidence has implicated the insular cortex in time-sensitive decisions, yet it is not clear whether activity in this brain region is crucial for, or merely associated with, TD behaviour. Here, patients with damage to the insula (Insular patients, control patients with lesions outside the insula, and healthy individuals chose between smaller-sooner and larger-later monetary rewards. Insular patients were less sensitive to sooner rewards than were the control groups, exhibiting reduced TD. A Voxel-based Lesion-Symptom Mapping (VLSM analysis confirmed a statistically significant association between insular damage and reduced TD. These results indicate that the insular cortex is crucial for intertemporal choice. We suggest that he insula may be necessary to anticipate the bodily/emotional effects of receiving rewards at different delays, influencing the computation of their incentive value. Devoid of such input, insular patients’ choices would be governed by a heuristic of quantity, allowing patients to wait for larger options.

  16. Functional ADA polymorphism increases sleep depth and reduces vigilant attention in humans.

    Science.gov (United States)

    Bachmann, Valérie; Klaus, Federica; Bodenmann, Sereina; Schäfer, Nikolaus; Brugger, Peter; Huber, Susanne; Berger, Wolfgang; Landolt, Hans-Peter

    2012-04-01

    Homeostatically regulated slow-wave oscillations in non-rapid eye movement (REM) sleep may reflect synaptic changes across the sleep-wake continuum and the restorative function of sleep. The nonsynonymous c.22G>A polymorphism (rs73598374) of adenosine deaminase (ADA) reduces the conversion of adenosine to inosine and predicts baseline differences in sleep slow-wave oscillations. We hypothesized that this polymorphism affects cognitive functions, and investigated whether it modulates electroencephalogram (EEG), behavioral, subjective, and biochemical responses to sleep deprivation. Attention, learning, memory, and executive functioning were quantified in healthy adults. Right-handed carriers of the variant allele (G/A genotype, n = 29) performed worse on the d2 attention task than G/G homozygotes (n = 191). To test whether this difference reflects elevated homeostatic sleep pressure, sleep and sleep EEG before and after sleep deprivation were studied in 2 prospectively matched groups of G/A and G/G genotype subjects. Deep sleep and EEG 0.75- to 1.5-Hz oscillations in non-REM sleep were significantly higher in G/A than in G/G genotype. Moreover, attention and vigor were reduced, whereas waking EEG alpha activity (8.5-12 Hz), sleepiness, fatigue, and α-amylase in saliva were enhanced. These convergent data demonstrate that genetic reduction of ADA activity elevates sleep pressure and plays a key role in sleep and waking quality in humans.

  17. Reducing the Human Burden of Breast Cancer: Advanced Radiation Therapy Yields Improved Treatment Outcomes.

    Science.gov (United States)

    Currey, Adam D; Bergom, Carmen; Kelly, Tracy R; Wilson, J Frank

    2015-01-01

    Radiation therapy is an important modality in the treatment of patients with breast cancer. While its efficacy in the treatment of breast cancer was known shortly after the discovery of x-rays, significant advances in radiation delivery over the past 20 years have resulted in improved patient outcomes. With the development of improved systemic therapy, optimizing local control has become increasingly important and has been shown to improve survival. Better understanding of the magnitude of treatment benefit, as well as patient and biological factors that confer an increased recurrence risk, have allowed radiation oncologists to better tailor treatment decisions to individual patients. Furthermore, significant technological advances have occurred that have reduced the acute and long-term toxicity of radiation treatment. These advances continue to reduce the human burden of breast cancer. It is important for radiation oncologists and nonradiation oncologists to understand these advances, so that patients are appropriately educated about the risks and benefits of this important treatment modality. © 2015 Wiley Periodicals, Inc.

  18. Human tumor infiltrating lymphocytes cooperatively regulate prostate tumor growth in a humanized mouse model

    OpenAIRE

    Roth, Michael D; Harui, Airi

    2015-01-01

    BACKGROUND: The complex interactions that occur between human tumors, tumor infiltrating lymphocytes (TIL) and the systemic immune system are likely to define critical factors in the host response to cancer. While conventional animal models have identified an array of potential anti-tumor therapies, mouse models often fail to translate into effective human treatments. Our goal is to establish a humanized tumor model as a more effective pre-clinical platform for understanding and manipulating ...

  19. Reduced response to IKr blockade and altered hERG1a/1b stoichiometry in human heart failure.

    Science.gov (United States)

    Holzem, Katherine M; Gomez, Juan F; Glukhov, Alexey V; Madden, Eli J; Koppel, Aaron C; Ewald, Gregory A; Trenor, Beatriz; Efimov, Igor R

    2016-07-01

    Heart failure (HF) claims 250,000 lives per year in the US, and nearly half of these deaths are sudden and presumably due to ventricular tachyarrhythmias. QT interval and action potential (AP) prolongation are hallmark proarrhythmic changes in the failing myocardium, which potentially result from alterations in repolarizing potassium currents. Thus, we aimed to examine whether decreased expression of the rapid delayed rectifier potassium current, IKr, contributes to repolarization abnormalities in human HF. To map functional IKr expression across the left ventricle (LV), we optically imaged coronary-perfused LV free wall from donor and end-stage failing human hearts. The LV wedge preparation was used to examine transmural AP durations at 80% repolarization (APD80), and treatment with the IKr-blocking drug, E-4031, was utilized to interrogate functional expression. We assessed the percent change in APD80 post-IKr blockade relative to baseline APD80 (∆APD80) and found that ∆APD80s are reduced in failing versus donor hearts in each transmural region, with 0.35-, 0.43-, and 0.41-fold reductions in endo-, mid-, and epicardium, respectively (p=0.008, 0.037, and 0.022). We then assessed hERG1 isoform gene and protein expression levels using qPCR and Western blot. While we did not observe differences in hERG1a or hERG1b gene expression between donor and failing hearts, we found a shift in the hERG1a:hERG1b isoform stoichiometry at the protein level. Computer simulations were then conducted to assess IKr block under E-4031 influence in failing and nonfailing conditions. Our results confirmed the experimental observations and E-4031-induced relative APD80 prolongation was greater in normal conditions than in failing conditions, provided that the cellular model of HF included a significant downregulation of IKr. In human HF, the response to IKr blockade is reduced, suggesting decreased functional IKr expression. This attenuated functional response is associated with

  20. Mesenchymal Stem/Multipotent Stromal Cells from Human Decidua Basalis Reduce Endothelial Cell Activation.

    Science.gov (United States)

    Alshabibi, Manal A; Al Huqail, Al Joharah; Khatlani, Tanvir; Abomaray, Fawaz M; Alaskar, Ahmed S; Alawad, Abdullah O; Kalionis, Bill; Abumaree, Mohamed Hassan

    2017-09-15

    Recently, we reported the isolation and characterization of mesenchymal stem cells from the decidua basalis of human placenta (DBMSCs). These cells express a unique combination of molecules involved in many important cellular functions, which make them good candidates for cell-based therapies. The endothelium is a highly specialized, metabolically active interface between blood and the underlying tissues. Inflammatory factors stimulate the endothelium to undergo a change to a proinflammatory and procoagulant state (ie, endothelial cell activation). An initial response to endothelial cell activation is monocyte adhesion. Activation typically involves increased proliferation and enhanced expression of adhesion and inflammatory markers by endothelial cells. Sustained endothelial cell activation leads to a type of damage to the body associated with inflammatory diseases, such as atherosclerosis. In this study, we examined the ability of DBMSCs to protect endothelial cells from activation through monocyte adhesion, by modulating endothelial proliferation, migration, adhesion, and inflammatory marker expression. Endothelial cells were cocultured with DBMSCs, monocytes, monocyte-pretreated with DBMSCs and DBMSC-pretreated with monocytes were also evaluated. Monocyte adhesion to endothelial cells was examined following treatment with DBMSCs. Expression of endothelial cell adhesion and inflammatory markers was also analyzed. The interaction between DBMSCs and monocytes reduced endothelial cell proliferation and monocyte adhesion to endothelial cells. In contrast, endothelial cell migration increased in response to DBMSCs and monocytes. Endothelial cell expression of adhesion and inflammatory molecules was reduced by DBMSCs and DBMSC-pretreated with monocytes. The mechanism of reduced endothelial proliferation involved enhanced phosphorylation of the tumor suppressor protein p53. Our study shows for the first time that DBMSCs protect endothelial cells from activation by

  1. Human T Lymphotropic Virus Type 1 protein Tax reduces histone levels

    Directory of Open Access Journals (Sweden)

    Laybourn Paul J

    2008-01-01

    Full Text Available Abstract Background Human T-Lymphotropic Virus Type-1 (HTLV-1 is an oncogenic retrovirus that causes adult T-cell leukemia/lymphoma (ATLL. The virally encoded Tax protein is thought to be necessary and sufficient for T-cell leukemogenesis. Tax promotes inappropriate cellular proliferation, represses multiple DNA repair mechanisms, deregulates cell cycle checkpoints, and induces genomic instability. All of these Tax effects are thought to cooperate in the development of ATLL. Results In this study, we demonstrate that histone protein levels are reduced in HTLV-1 infected T-cell lines (HuT102, SLB-1 and C81 relative to uninfected T-cell lines (CEM, Jurkat and Molt4, while the relative amount of DNA per haploid complement is unaffected. In addition, we show that replication-dependent core and linker histone transcript levels are reduced in HTLV-1 infected T-cell lines. Furthermore, we show that Tax expression in Jurkat cells is sufficient for reduction of replication-dependent histone transcript levels. Conclusion These results demonstrate that Tax disrupts the proper regulation of replication-dependent histone gene expression. Further, our findings suggest that HTLV-1 infection uncouples replication-dependent histone gene expression and DNA replication, allowing the depletion of histone proteins with cell division. Histone proteins are involved in the regulation of all metabolic processes involving DNA including transcription, replication, repair and recombination. This study provides a previously unidentified mechanism by which Tax may directly induce chromosomal instability and deregulate gene expression through reduced histone levels.

  2. Modelling a soft composite accumulator for human mobility assist devices.

    Science.gov (United States)

    Shaheen, Robert; Doumit, Marc

    2018-04-01

    Research in the field of human mobility assist devices, aiming to reduce the metabolic cost of daily activities, is seeing the benefits of the exclusive use of accumulators to store and release energy during the gait cycle. The Pneumatic Artificial Muscle, used in a passive state, has proven to be a superior choice for these devices when compared to its alternatives, however, challenges regarding muscle pressure dissipation and a limited elongation potential have been identified. A recently developed, novel Soft Composite material has been shown to experimentally replicate the distinctive mechanical behaviour of the Pneumatic Artificial Muscle, without the need for internal pressurization. This paper presents two separate constitutive models to provide a closer insight into the behaviour of these Soft Composite accumulators. Both models were derived from methods involving finite elasticity theory and employed either a structural strain energy function of Holzapfel, Gasser, and Ogden's type or a phenomenological strain energy function of Fung's type. Both models were in good agreement with the experimental data that were collected through a modified extension-inflation test and, therefore, provide a basis for further examination as a Soft Composite design model. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Human Systems Integration (HSI) Tradeoff Model

    Science.gov (United States)

    2014-03-01

    distribution is unlimited. Release # 88ABW-2014- 1475, dated 7 Apr 2014. on grammatical and software errors and the recommendation to add a screen (Figure 17...SIGNATURE// MATTHEW T. TARANTO, Major, USAF Chief, Human Systems Analysis Division Human Systems Integration Directorate...enhancing the understanding of HSI tradeoffs. At the direction of 711 HPW/HP, the Survivability/ Vulnerability Information Analysis Center (SURVIAC

  4. A model of the human retina

    DEFF Research Database (Denmark)

    Jørgensen, John Leif

    1998-01-01

    Traditionally, the human eye is perceived as being "just" a camera, that renders an accurate, although limited, image for processing in the brain. This interpretation probably stems from the apparent similarity between a video- or photo-camera and a human eye with respect to the lens, the iris...

  5. Modelling Human Exposure to Chemicals in Food

    NARCIS (Netherlands)

    Slob W

    1993-01-01

    Exposure to foodborne chemicals is often estimated using the average consumption pattern in the human population. To protect the human population instead of the average individual, however, interindividual variability in consumption behaviour must be taken into account. This report shows how food

  6. Human-water interface in hydrological modelling

    NARCIS (Netherlands)

    Wada, Yoshihide; Bierkens, Marc F.P.; Roo, de Ad; Dirmeyer, Paul A.; Famiglietti, James S.; Hanasaki, Naota; Konar, Megan; Liu, Junguo; Schmied, Hannes Möller; Oki, Taikan; Pokhrel, Yadu; Sivapalan, Murugesu; Troy, Tara J.; Dijk, Van Albert I.J.M.; Emmerik, Van Tim; Huijgevoort, Van Marjolein H.J.; Lanen, van Henny A.J.; Vörösmarty, Charles J.; Wanders, Niko; Wheater, Howard

    2017-01-01

    Over recent decades, the global population has been rapidly increasing and human activities have altered terrestrial water fluxes to an unprecedented extent. The phenomenal growth of the human footprint has significantly modified hydrological processes in various ways (e.g. irrigation, artificial

  7. Foxa1 reduces lipid accumulation in human hepatocytes and is down-regulated in nonalcoholic fatty liver.

    Directory of Open Access Journals (Sweden)

    Marta Moya

    Full Text Available Triglyceride accumulation in nonalcoholic fatty liver (NAFL results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2 however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cultured hepatocytes and HepG2 cells, by adenoviral infection. Moreover, human and rat livers were analyzed to determine Foxa1 regulation in NAFL. Results demonstrate that Foxa1 is a potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways (e.g., GPAM, DGAT2, MTP, APOB. Moreover, Foxa1 represses the fatty acid transporter protein FATP2 and lowers fatty acid uptake. Foxa1 also increases the breakdown of fatty acids by inducing peroxisomal fatty acid β-oxidation and ketone body synthesis. Finally, Foxa1 is able to largely up-regulate UCP1, thereby dissipating energy and consistently decreasing the mitochondria membrane potential. We also report that human and rat NAFL have a reduced Foxa1 expression, possibly through a protein kinase C-dependent pathway. We conclude that Foxa1 is an antisteatotic factor that coordinately tunes several lipid metabolic pathways to block triglyceride accumulation in hepatocytes. However, Foxa1 is down-regulated in human and rat NAFL and, therefore, increasing Foxa1 levels could protect from steatosis. Altogether, we suggest that Foxa1 could be a novel therapeutic target for NAFL disease and insulin resistance.

  8. Environmental exposure to arsenic may reduce human semen quality: associations derived from a Chinese cross-sectional study

    Directory of Open Access Journals (Sweden)

    Xu Weipan

    2012-07-01

    Full Text Available Abstract Background Recent observations in in vitro and in vivo models suggest that arsenic (As is an endocrine disruptor at environmentally-relevant levels. When exposed to As, male rats and mice show steroidogenic dysfunction that can lead to infertility. However, the possible effects of As on human male semen quality remain obscure. Methods We monitored the profile of As species in the urine of a reproductive-age human cohort and assessed its association with semen quality. Men (n = 96 were recruited in an infertility clinic from July 2009 to August 2010 in the Affiliated Hospital of Chongqing Institute for Population and Family Planning. Five urinary As species were analyzed by high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry (HPLC-ICP-MS. Clinical information on the semen volume, sperm concentration and motility was employed to catalogue and evaluate semen quality according to WHO guidelines. As species concentrations in addition to other continuous variables were dichotomized by the medians and modelled as categorical variables in order to explore using the binary logistic regression possible associations between As exposure and semen quality. Results Urinary concentrations (geometric mean ± SD, μg g-1 creatinine of different As species were 7.49 (±24.8 for AsB, 20.9 (±13.7 for DMA, 2.77 (±3.33 for MMA, and 4.03 (±3.67 for Asi (AsiIII and AsiV. DMA concentrations above the median were significantly associated with below-reference sperm concentrations (P =0.02 after adjusting for age, body mass index (BMI, abstinence, smoking and drinking habits. In addition, smoking was positively associated with MMA. Conclusion Reduced parameters in human semen quality are positively associated with As exposure in a reproductive-age Chinese cohort.

  9. Cell model for efficient simulation of wave propagation in human ventricular tissue under normal and pathological conditions

    Science.gov (United States)

    Ten Tusscher, K. H. W. J.; Panfilov, A. V.

    2006-12-01

    In this paper, we formulate a model for human ventricular cells that is efficient enough for whole organ arrhythmia simulations yet detailed enough to capture the effects of cell level processes such as current blocks and channelopathies. The model is obtained from our detailed human ventricular cell model by using mathematical techniques to reduce the number of variables from 19 to nine. We carefully compare our full and reduced model at the single cell, cable and 2D tissue level and show that the reduced model has a very similar behaviour. Importantly, the new model correctly produces the effects of current blocks and channelopathies on AP and spiral wave behaviour, processes at the core of current day arrhythmia research. The new model is well over four times more efficient than the full model. We conclude that the new model can be used for efficient simulations of the effects of current changes on arrhythmias in the human heart.

  10. Cell model for efficient simulation of wave propagation in human ventricular tissue under normal and pathological conditions

    Energy Technology Data Exchange (ETDEWEB)

    Tusscher, K H W J Ten; Panfilov, A V [Department of Theoretical Biology, Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands)

    2006-12-07

    In this paper, we formulate a model for human ventricular cells that is efficient enough for whole organ arrhythmia simulations yet detailed enough to capture the effects of cell level processes such as current blocks and channelopathies. The model is obtained from our detailed human ventricular cell model by using mathematical techniques to reduce the number of variables from 19 to nine. We carefully compare our full and reduced model at the single cell, cable and 2D tissue level and show that the reduced model has a very similar behaviour. Importantly, the new model correctly produces the effects of current blocks and channelopathies on AP and spiral wave behaviour, processes at the core of current day arrhythmia research. The new model is well over four times more efficient than the full model. We conclude that the new model can be used for efficient simulations of the effects of current changes on arrhythmias in the human heart.

  11. Lessons Learned from Performance Testing of Humans in Spacesuits in Simulated Reduced Gravity

    Science.gov (United States)

    Norcross, Jason R.; Chappell, Steven P.; Gernhardt, Michael L.

    2010-01-01

    Introduction: The overarching objective of the Integrated Suit Test (IST) series is to evaluate suited human performance using reduced-gravity analogs and learn what aspects of an EVA suit system affect human performance. For this objective to be successfully achieved, the testing methodology should be valid and reproducible, and the partial-gravity simulations must be as accurate and realistic as possible. Objectives: To highlight some of the key lessons learned about partial-gravity analogs and testing methodology, and to suggest considerations for optimizing the effectiveness and quality of results of future tests. Methods: Performance testing of suited and unsuited subjects was undertaken in different reduced-gravity analogs including the Space Vehicle Mockup Facility s Partial Gravity Simulator (POGO), parabolic flight on the C-9 aircraft, underwater environments including NASA s Extreme Environment Mission Operations (NEEMO) and the Neutral Buoyancy Lab (NBL), and in field analogs including Desert Research and Technology Studies (RATS), the Haughton Mars Project (HMP), and the JSC Rock Pile. Subjects performed level walking, incline/decline walking, running, shoveling, picking up and transferring rocks, kneeling/standing, and task boards. Lessons Learned Analogs: No single analog will properly simulate all aspects of the true partial-gravity environment. The POGO is an ideal environment from the standpoint that there are no time limits or significant volumetric constraints, but it does have several limitations. It allows only 2 translational degrees of freedom (DOF) and applies true partial-gravity offload only through the subject s center of gravity (CG). Also, when a subject is doing non-stationary tasks, significant overhead inertia from the lift column seems to have a negative impact on performance. Parabolic flight allows full translational and rotational DOF and applies offload to all parts of the body, but the simulation lasts less than 30 seconds

  12. A Simple Exoskeleton That Assists Plantarflexion Can Reduce the Metabolic Cost of Human Walking

    Science.gov (United States)

    Malcolm, Philippe; Derave, Wim; Galle, Samuel; De Clercq, Dirk

    2013-01-01

    Background Even though walking can be sustained for great distances, considerable energy is required for plantarflexion around the instant of opposite leg heel contact. Different groups attempted to reduce metabolic cost with exoskeletons but none could achieve a reduction beyond the level of walking without exoskeleton, possibly because there is no consensus on the optimal actuation timing. The main research question of our study was whether it is possible to obtain a higher reduction in metabolic cost by tuning the actuation timing. Methodology/Principal Findings We measured metabolic cost by means of respiratory gas analysis. Test subjects walked with a simple pneumatic exoskeleton that assists plantarflexion with different actuation timings. We found that the exoskeleton can reduce metabolic cost by 0.18±0.06 W kg−1 or 6±2% (standard error of the mean) (p = 0.019) below the cost of walking without exoskeleton if actuation starts just before opposite leg heel contact. Conclusions/Significance The optimum timing that we found concurs with the prediction from a mathematical model of walking. While the present exoskeleton was not ambulant, measurements of joint kinetics reveal that the required power could be recycled from knee extension deceleration work that occurs naturally during walking. This demonstrates that it is theoretically possible to build future ambulant exoskeletons that reduce metabolic cost, without power supply restrictions. PMID:23418524

  13. Paclitaxel Drug-eluting Tracheal Stent Could Reduce Granulation Tissue Formation in a Canine Model.

    Science.gov (United States)

    Wang, Ting; Zhang, Jie; Wang, Juan; Pei, Ying-Hua; Qiu, Xiao-Jian; Wang, Yu-Ling

    2016-11-20

    Currently available silicone and metallic stents for tracheal stenosis are associated with many problems. Granulation proliferation is one of the main complications. The present study aimed to evaluate the efficacy of paclitaxel drug-eluting tracheal stent in reducing granulation tissue formation in a canine model, as well as the pharmacokinetic features and safety profiles of the coated drug. Eight beagles were randomly divided into a control group (bare-metal stent group, n = 4) and an experimental group (paclitaxel-eluting stent group, n = 4). The observation period was 5 months. One beagle in both groups was sacrificed at the end of the 1st and 3rd months, respectively. The last two beagles in both groups were sacrificed at the end of 5th month. The proliferation of granulation tissue and changes in tracheal mucosa were compared between the two groups. Blood routine and liver and kidney function were monitored to evaluate the safety of the paclitaxel-eluting stent. The elution method and high-performance liquid chromatography were used to characterize the rate of in vivo release of paclitaxel from the stent. Compared with the control group, the proliferation of granulation tissue in the experimental group was significantly reduced. The drug release of paclitaxel-eluting stent was the fastest in the 1st month after implantation (up to 70.9%). Then, the release slowed down gradually. By the 5th month, the release reached up to 98.5%. During the observation period, a high concentration of the drug in the trachea (in the stented and adjacent unstented areas) and lung tissue was not noted, and the blood test showed no side effect. The paclitaxel-eluting stent could safely reduce the granulation tissue formation after stent implantation in vivo, suggesting that the paclitaxel-eluting tracheal stent might be considered for potential use in humans in the future.

  14. Reconstruction of human mammary tissues in a mouse model.

    Science.gov (United States)

    Proia, David A; Kuperwasser, Charlotte

    2006-01-01

    Establishing a model system that more accurately recapitulates both normal and neoplastic breast epithelial development in rodents is central to studying human breast carcinogenesis. However, the inability of human breast epithelial cells to colonize mouse mammary fat pads is problematic. Considering that the human breast is a more fibrous tissue than is the adipose-rich stroma of the murine mammary gland, our group sought to bypass the effects of the rodent microenvironment through incorporation of human stromal fibroblasts. We have been successful in reproducibly recreating functionally normal breast tissues from reduction mammoplasty tissues, in what we term the human-in-mouse (HIM) model. Here we describe our relatively simple and inexpensive techniques for generating this orthotopic xenograft model. Whether the model is to be applied for understanding normal human breast development or tumorigenesis, investigators with minimal animal surgery skills, basic cell culture techniques and access to human breast tissue will be able to generate humanized mouse glands within 3 months. Clearing the mouse of its endogenous epithelium with subsequent stromal humanization takes 1 month. The subsequent implantation of co-mixed human epithelial cells and stromal cells occurs 2 weeks after humanization, so investigators should expect to observe the desired outgrowths 2 months afterward. As a whole, this model system has the potential to improve the understanding of crosstalk between tissue stroma and the epithelium as well as factors involved in breast stem cell biology tumor initiation and progression.

  15. Pharmacological migraine provocation: a human model of migraine

    DEFF Research Database (Denmark)

    Ashina, Messoud; Hansen, Jakob Møller

    2010-01-01

    . If a naturally occurring substance can provoke migraine in human patients, then it is likely, although not certain, that blocking its effect will be effective in the treatment of acute migraine attacks. To this end, a human in vivo model of experimental headache and migraine in humans has been developed...

  16. Reducing the negative human-health impacts of bioenergy crop emissions through region-specific crop selection

    International Nuclear Information System (INIS)

    Porter, William C; Rosenstiel, Todd N; Barsanti, Kelley; Guenther, Alex; Lamarque, Jean-Francois

    2015-01-01

    An expected global increase in bioenergy-crop cultivation as an alternative to fossil fuels will have consequences on both global climate and local air quality through changes in biogenic emissions of volatile organic compounds (VOCs). While greenhouse gas emissions may be reduced through the substitution of next-generation bioenergy crops such as eucalyptus, giant reed, and switchgrass for fossil fuels, the choice of species has important ramifications for human health, potentially reducing the benefits of conversion due to increases in ozone (O 3 ) and fine particulate matter (PM 2.5 ) levels as a result of large changes in biogenic emissions. Using the Community Earth System Model we simulate the conversion of marginal and underutilized croplands worldwide to bioenergy crops under varying future anthropogenic emissions scenarios. A conservative global replacement using high VOC-emitting crop profiles leads to modeled population-weighted O 3 increases of 5–27 ppb in India, 1–9 ppb in China, and 1–6 ppb in the United States, with peak PM 2.5 increases of up to 2 μg m −3 . We present a metric for the regional evaluation of candidate bioenergy crops, as well as results for the application of this metric to four representative emissions profiles using four replacement scales (10–100% maximum estimated available land). Finally, we assess the total health and climate impacts of biogenic emissions, finding that the negative consequences of using high-emitting crops could exceed 50% of the positive benefits of reduced fossil fuel emissions in value. (letter)

  17. Modelling small groundwater systems - the role of targeted field investigations and observational data in reducing model uncertainty

    Science.gov (United States)

    Abesser, Corinna; Hughes, Andrew; Boon, David

    2017-04-01

    Coastal dunes are delicate systems that are under threat from a variety of human and natural influences. Groundwater modelling can provide a better understanding of how these systems operate and can be a useful tool towards the effective management of a coastal dune system, e.g. through predicting impacts from climatic change, sea level rise and land use management. Because of their small size, typically 10 - 100 km2, models representing small dune aquifer systems are more sensitive to uncertainties in input data, model geometry and model parameterisation as well as to the availability of observational data. This study describes the development of a groundwater flow model for a small (8 km2) spit dune system, Braunton Burrows, on the Southwest coast of England, UK. The system has been extensively studied and its hydrology is thought to be well understood. However, model development revealed a high degree of uncertainty relating to model structure (definition of model boundary conditions) and parameterisation (e.g., transmissivity distributions within the model domain). An iterative approach was employed, integrating (1) sensitivity analyses, (2) targeted field investigations and (3) Monte Carlo simulations within a cycle of repeated interrogation of the model outputs, observed data and conceptual understanding. Assessment of "soft information" and targeted field investigations were an important part of this iterative modelling process. For example, a passive seismic survey (TROMINO®) provided valuable new data for the characterisation of concealed bedrock topography and thickness of superficial deposits. The data confirmed a generally inclined underlying wave cut rock shelf platform (as suggested by literature sources), revealed a buried valley, and led to a more detailed delineation of transmissivity zones within the model domain. Constructing models with increasingly more complex spatial distributions of transmissivity, resulted in considerable improvements in

  18. Assessment of the capacity of vehicle cabin air inlet filters to reduce diesel exhaust-induced symptoms in human volunteers.

    Science.gov (United States)

    Muala, Ala; Sehlstedt, Maria; Bion, Anne; Osterlund, Camilla; Bosson, Jenny A; Behndig, Annelie F; Pourazar, Jamshid; Bucht, Anders; Boman, Christoffer; Mudway, Ian S; Langrish, Jeremy P; Couderc, Stephane; Blomberg, Anders; Sandström, Thomas

    2014-03-13

    Exposure to particulate matter (PM) air pollution especially derived from traffic is associated with increases in cardiorespiratory morbidity and mortality. In this study, we evaluated the ability of novel vehicle cabin air inlet filters to reduce diesel exhaust (DE)-induced symptoms and markers of inflammation in human subjects. Thirty healthy subjects participated in a randomized double-blind controlled crossover study where they were exposed to filtered air, unfiltered DE and DE filtered through two selected particle filters, one with and one without active charcoal. Exposures lasted for one hour. Symptoms were assessed before and during exposures and lung function was measured before and after each exposure, with inflammation assessed in peripheral blood five hours after exposures. In parallel, PM were collected from unfiltered and filtered DE and assessed for their capacity to drive damaging oxidation reactions in a cell-free model, or promote inflammation in A549 cells. The standard particle filter employed in this study reduced PM10 mass concentrations within the exposure chamber by 46%, further reduced to 74% by the inclusion of an active charcoal component. In addition use of the active charcoal filter was associated by a 75% and 50% reduction in NO2 and hydrocarbon concentrations, respectively. As expected, subjects reported more subjective symptoms after exposure to unfiltered DE compared to filtered air, which was significantly reduced by the filter with an active charcoal component. There were no significant changes in lung function after exposures. Similarly diesel exhaust did not elicit significant increases in any of the inflammatory markers examined in the peripheral blood samples 5 hour post-exposure. Whilst the filters reduced chamber particle concentrations, the oxidative activity of the particles themselves, did not change following filtration with either filter. In contrast, diesel exhaust PM passed through the active charcoal combination

  19. Pharmacological migraine provocation: a human model of migraine

    DEFF Research Database (Denmark)

    Ashina, Messoud; Hansen, Jakob Møller

    2010-01-01

    for migraine mechanisms. So far, however, animal models cannot predict the efficacy of new therapies for migraine. Because migraine attacks are fully reversible and can be aborted by therapy, the headache- or migraine-provoking property of naturally occurring signaling molecules can be tested in a human model....... If a naturally occurring substance can provoke migraine in human patients, then it is likely, although not certain, that blocking its effect will be effective in the treatment of acute migraine attacks. To this end, a human in vivo model of experimental headache and migraine in humans has been developed...

  20. Numerical Modeling of Electromagnetic Field Effects on the Human Body

    Directory of Open Access Journals (Sweden)

    Zuzana Psenakova

    2006-01-01

    Full Text Available Interactions of electromagnetic field (EMF with environment and with tissue of human beings are still under discussion and many research teams are investigating it. The human simulation models are used for biomedical research in a lot of areas, where it is advantage to replace real human body (tissue by the numerical model. Biological effects of EMF are one of the areas, where numerical models are used with many advantages. On the other side, this research is very specific and it is always quite hard to simulate realistic human tissue. This paper deals with different possibilities of numerical modelling of electromagnetic field effects on the human body (especially calculation of the specific absorption rate (SAR distribution in human body and thermal effect.

  1. Minimizing Human Risk: Human Performance Models in the Space Human Factors and Habitability and Behavioral Health and Performance Elements

    Science.gov (United States)

    Gore, Brian F.

    2016-01-01

    Human space exploration has never been more exciting than it is today. Human presence to outer worlds is becoming a reality as humans are leveraging much of our prior knowledge to the new mission of going to Mars. Exploring the solar system at greater distances from Earth than ever before will possess some unique challenges, which can be overcome thanks to the advances in modeling and simulation technologies. The National Aeronautics and Space Administration (NASA) is at the forefront of exploring our solar system. NASA's Human Research Program (HRP) focuses on discovering the best methods and technologies that support safe and productive human space travel in the extreme and harsh space environment. HRP uses various methods and approaches to answer questions about the impact of long duration missions on the human in space including: gravity's impact on the human body, isolation and confinement on the human, hostile environments impact on the human, space radiation, and how the distance is likely to impact the human. Predictive models are included in the HRP research portfolio as these models provide valuable insights into human-system operations. This paper will provide an overview of NASA's HRP and will present a number of projects that have used modeling and simulation to provide insights into human-system issues (e.g. automation, habitat design, schedules) in anticipation of space exploration.

  2. Obeticholic acid raises LDL-cholesterol and reduces HDL-cholesterol in the Diet-Induced NASH (DIN) hamster model.

    Science.gov (United States)

    Briand, François; Brousseau, Emmanuel; Quinsat, Marjolaine; Burcelin, Rémy; Sulpice, Thierry

    2018-01-05

    The use of rat and mouse models limits the translation to humans for developing novel drugs targeting nonalcoholic steatohepatitis (NASH). Obeticholic acid (OCA) illustrates this limitation since its dyslipidemic effect in humans cannot be observed in these rodents. Conversely, Golden Syrian hamsters have a lipoprotein metabolism mimicking human dyslipidemia since it does express the cholesteryl ester transfer protein (CETP). We therefore developed a Diet-Induced NASH (DIN) hamster model and evaluated the impact of OCA. Compared with chow fed controls, hamsters fed for 20 weeks with a free-choice (FC) diet, developed obesity, insulin resistance, dyslipidemia and NASH (microvesicular steatosis, inflammation, hepatocyte ballooning and perisinusoidal to bridging fibrosis). After 20 weeks of diet, FC fed hamsters were treated without or with obeticholic acid (15mg/kg/day) for 5 weeks. Although a non-significant trend towards higher dietary caloric intake was observed, OCA significantly lowered body weight after 5 weeks of treatment. OCA significantly increased CETP activity and LDL-C levels by 20% and 27%, and reduced HDL-C levels by 20%. OCA blunted hepatic gene expression of Cyp7a1 and Cyp8b1 and reduced fecal bile acids mass excretion by 64% (P DIN hamster replicates benefits and side effects of OCA as observed in humans, and should be useful for evaluating novel drugs targeting NASH. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Predicting Statistical Response and Extreme Events in Uncertainty Quantification through Reduced-Order Models

    Science.gov (United States)

    Qi, D.; Majda, A.

    2017-12-01

    A low-dimensional reduced-order statistical closure model is developed for quantifying the uncertainty in statistical sensitivity and intermittency in principal model directions with largest variability in high-dimensional turbulent system and turbulent transport models. Imperfect model sensitivity is improved through a recent mathematical strategy for calibrating model errors in a training phase, where information theory and linear statistical response theory are combined in a systematic fashion to achieve the optimal model performance. The idea in the reduced-order method is from a self-consistent mathematical framework for general systems with quadratic nonlinearity, where crucial high-order statistics are approximated by a systematic model calibration procedure. Model efficiency is improved through additional damping and noise corrections to replace the expensive energy-conserving nonlinear interactions. Model errors due to the imperfect nonlinear approximation are corrected by tuning the model parameters using linear response theory with an information metric in a training phase before prediction. A statistical energy principle is adopted to introduce a global scaling factor in characterizing the higher-order moments in a consistent way to improve model sensitivity. Stringent models of barotropic and baroclinic turbulence are used to display the feasibility of the reduced-order methods. Principal statistical responses in mean and variance can be captured by the reduced-order models with accuracy and efficiency. Besides, the reduced-order models are also used to capture crucial passive tracer field that is advected by the baroclinic turbulent flow. It is demonstrated that crucial principal statistical quantities like the tracer spectrum and fat-tails in the tracer probability density functions in the most important large scales can be captured efficiently with accuracy using the reduced-order tracer model in various dynamical regimes of the flow field with

  4. Animal models for human genetic diseases | Sharif | African Journal ...

    African Journals Online (AJOL)

    The study of human genetic diseases can be greatly aided by animal models because of their similarity to humans in terms of genetics. In addition to understand diverse aspects of basic biology, model organisms are extensively used in applied research in agriculture, industry, and also in medicine, where they are used to ...

  5. Enhancing Interdisciplinary Human System Risk Research Through Modeling and Network Approaches

    Science.gov (United States)

    Mindock, Jennifer; Lumpkins, Sarah; Shelhamer, Mark

    2015-01-01

    NASA's Human Research Program (HRP) supports research to reduce human health and performance risks inherent in future human space exploration missions. Understanding risk outcomes and contributing factors in an integrated manner allows HRP research to support development of efficient and effective mitigations from cross-disciplinary perspectives, and to enable resilient human and engineered systems for spaceflight. The purpose of this work is to support scientific collaborations and research portfolio management by utilizing modeling for analysis and visualization of current and potential future interdisciplinary efforts.

  6. General Computational Model for Human Musculoskeletal System of Spine

    Directory of Open Access Journals (Sweden)

    Kyungsoo Kim

    2012-01-01

    Full Text Available A general computational model of the human lumbar spine and trunk muscles including optimization formulations was provided. For a given condition, the trunk muscle forces could be predicted considering the human physiology including the follower load concept. The feasibility of the solution could be indirectly validated by comparing the compressive force, the shear force, and the joint moment. The presented general computational model and optimization technology can be fundamental tools to understand the control principle of human trunk muscles.

  7. Specific and General Human Capital in an Endogenous Growth Model

    OpenAIRE

    Evangelia Vourvachaki; Vahagn Jerbashian; : Sergey Slobodyan

    2014-01-01

    In this article, we define specific (general) human capital in terms of the occupations whose use is spread in a limited (wide) set of industries. We analyze the growth impact of an economy's composition of specific and general human capital, in a model where education and research and development are costly and complementary activities. The model suggests that a declining share of specific human capital, as observed in the Czech Republic, can be associated with a lower rate of long-term grow...

  8. Human-water interface in hydrological modelling

    OpenAIRE

    Wada, Yoshihide; Bierkens, Marc F.P.; Roo, de, Ad; Dirmeyer, Paul A.; Famiglietti, James S.; Hanasaki, Naota; Konar, Megan; Liu, Junguo; Schmied, Hannes Möller; Oki, Taikan; Pokhrel, Yadu; Sivapalan, Murugesu; Troy, Tara J.; Dijk, Van, Albert I.J.M.; Emmerik, Van, Tim

    2017-01-01

    Over recent decades, the global population has been rapidly increasing and human activities have altered terrestrial water fluxes to an unprecedented extent. The phenomenal growth of the human footprint has significantly modified hydrological processes in various ways (e.g. irrigation, artificial dams, and water diversion) and at various scales (from a watershed to the globe). During the early 1990s, awareness of the potential for increased water scarcity led to the first detailed global wate...

  9. Make it Fit, evaluating strategies to reduce the environmental impacts of meeting human needs in 2050

    Science.gov (United States)

    Reid, J.; Polasky, S.; Hawthorne, P.

    2014-12-01

    Sustainable development requires providing for human well-being by meeting basic demands for food, energy and consumer goods and services, all while maintaining an environment capable of sustaining the provisioning of those demands for future generations. Failure to meet the basic needs of human well-being is not an ethically viable option and strategies for doubling agricultural production and providing energy and goods for a growing population exist. However, the question is, at what cost to environmental quality? We developed an integrated modeling approach to test strategies for meeting multiple objectives within the limits of the earth system. We use scenarios to explore a range of assumptions on socio-economic factors like population growth, per capita income and technological change; food systems factors like food waste, production intensification and expansion, and meat demand; and technological developments in energy efficiency and wastewater treatment. We use these scenario to test the conditions in which we can fit the simultaneous goals of sustainable development.

  10. Softened food reduces weight loss in the streptozotocin-induced male mouse model of diabetic nephropathy

    DEFF Research Database (Denmark)

    Nørgaard, Sisse A; Sand, Fredrik W; Sørensen, Dorte B

    2018-01-01

    these issues, we hypothesized that supplementing STZ-induced diabetic mice with water-softened chow in addition to normal chow would reduce weight loss, lower the need for supportive treatment, and reduce the number of mice reaching the humane endpoint of 20% weight loss. In a 15 week STZ-induced DN study we...... without this supplement reached this humane endpoint ( p = 0.0027). Excretion of corticosterone metabolites in faeces was reduced in diabetic mice on softened chow ( p = 0.0007), suggesting lower levels of general stress. Finally, it was demonstrated that the water-softened chow supplement did...... demonstrated that diabetic male mice receiving softened chow had reduced acute weight loss following STZ treatment ( p = 0.045) and additionally fewer mice were euthanized due to weight loss. By supplementing the diabetic mice with softened chow, no mice reached 20% weight loss whereas 37.5% of the mice...

  11. α1-Antitrypsin reduces rhinovirus infection in primary human airway epithelial cells exposed to cigarette smoke

    Directory of Open Access Journals (Sweden)

    Berman R

    2016-06-01

    Full Text Available Reena Berman, Di Jiang, Qun Wu, Hong Wei Chu Department of Medicine, National Jewish Health, Denver, CO, USA Abstract: Human rhinovirus (HRV infections target airway epithelium and are the leading cause of acute exacerbations of COPD. Cigarette smoke (CS increases the severity of viral infections, but there is no effective therapy for HRV infection. We determined whether α1-antitrypsin (A1AT reduces HRV-16 infection in CS-exposed primary human airway epithelial cells. Brushed bronchial epithelial cells from normal subjects and patients diagnosed with COPD were cultured at air–liquid interface to induce mucociliary differentiation. These cells were treated with A1AT or bovine serum albumin for 2 hours and then exposed to air or whole cigarette smoke (WCS with or without HRV-16 (5×104 50% Tissue Culture Infective Dose [TCID50]/transwell infection for 24 hours. WCS exposure significantly increased viral load by an average of fivefold and decreased the expression of antiviral genes interferon-λ1, OAS1, and MX1. When A1AT was added to WCS-exposed cells, viral load significantly decreased by an average of 29-fold. HRV-16 infection significantly increased HRV-16 receptor intercellular adhesion molecule-1 messenger RNA expression in air-exposed cells, which was decreased by A1AT. A1AT-mediated reduction of viral load was not accompanied by increased epithelial antiviral gene expression or by inhibiting the activity of 3C protease involved in viral replication or maturation. Our findings demonstrate that A1AT treatment prevents a WCS-induced increase in viral load and for the first time suggest a therapeutic effect of A1AT on HRV infection. Keywords: α1-antitrypsin, rhinovirus, COPD, cigarette smoke, ICAM-1

  12. Reduced thoracolumbar fascia shear strain in human chronic low back pain.

    Science.gov (United States)

    Langevin, Helene M; Fox, James R; Koptiuch, Cathryn; Badger, Gary J; Greenan-Naumann, Ann C; Bouffard, Nicole A; Konofagou, Elisa E; Lee, Wei-Ning; Triano, John J; Henry, Sharon M

    2011-09-19

    The role played by the thoracolumbar fascia in chronic low back pain (LBP) is poorly understood. The thoracolumbar fascia is composed of dense connective tissue layers separated by layers of loose connective tissue that normally allow the dense layers to glide past one another during trunk motion. The goal of this study was to quantify shear plane motion within the thoracolumbar fascia using ultrasound elasticity imaging in human subjects with and without chronic low back pain (LBP). We tested 121 human subjects, 50 without LBP and 71 with LBP of greater than 12 months duration. In each subject, an ultrasound cine-recording was acquired on the right and left sides of the back during passive trunk flexion using a motorized articulated table with the hinge point of the table at L4-5 and the ultrasound probe located longitudinally 2 cm lateral to the midline at the level of the L2-3 interspace. Tissue displacement within the thoracolumbar fascia was calculated using cross correlation techniques and shear strain was derived from this displacement data. Additional measures included standard range of motion and physical performance evaluations as well as ultrasound measurement of perimuscular connective tissue thickness and echogenicity. Thoracolumbar fascia shear strain was reduced in the LBP group compared with the No-LBP group (56.4% ± 3.1% vs. 70.2% ± 3.6% respectively, p low back pain. This reduction of shear plane motion may be due to abnormal trunk movement patterns and/or intrinsic connective tissue pathology. There appears to be some sex-related differences in thoracolumbar fascia shear strain that may also play a role in altered connective tissue function.

  13. Glucosamine exposure reduces proteoglycan synthesis in primary human endothelial cells in vitro

    Directory of Open Access Journals (Sweden)

    Trine M. Reine

    2016-09-01

    Full Text Available Purpose: Glucosamine (GlcN supplements are promoted for medical reasons, for example, for patients with arthritis and other joint-related diseases. Oral intake of GlcN is followed by uptake in the intestine, transport in the circulation and thereafter delivery to chondrocytes. Here, it is postulated to have an effect on synthesis and turnover of extracellular matrix constituents expressed by these cells. Following uptake in the intestine, serum levels are transiently increased, and the endothelium is exposed to increased levels of GlcN. We investigated the possible effects of GlcN on synthesis of proteoglycans (PGs, an important matrix component, in primary human endothelial cells. Methods: Primary human endothelial cells were cultured in vitro in medium with 5 mM glucose and 0–10 mM GlcN. PGs were recovered and analysed by western blotting, or by SDS-PAGE, gel chromatography or ion-exchange chromatography of 35S-PGs after 35S-sulphate labelling of the cells. Results: The synthesis and secretion of 35S-PGs from cultured endothelial cells were reduced in a dose- and time-dependent manner after exposure to GlcN. PGs are substituted with sulphated glycosaminoglycan (GAG chains, vital for PG function. The reduction in 35S-PGs was not related to an effect on GAG chain length, number or sulphation, but rather to the total expression of PGs. Conclusion: Exposure of endothelial cells to GlcN leads to a general decrease in 35S-PG synthesis. These results suggest that exposure to high levels of GlcN can lead to decreased matrix synthesis, contrary to what has been claimed by supporters of such supplements.

  14. Reduced transmission of human schistosomiasis after restoration of a native river prawn that preys on the snail intermediate host.

    Science.gov (United States)

    Sokolow, Susanne H; Huttinger, Elizabeth; Jouanard, Nicolas; Hsieh, Michael H; Lafferty, Kevin D; Kuris, Armand M; Riveau, Gilles; Senghor, Simon; Thiam, Cheikh; N'Diaye, Alassane; Faye, Djibril Sarr; De Leo, Giulio A

    2015-08-04

    Eliminating human parasitic disease often requires interrupting complex transmission pathways. Even when drugs to treat people are available, disease control can be difficult if the parasite can persist in nonhuman hosts. Here, we show that restoration of a natural predator of a parasite's intermediate hosts may enhance drug-based schistosomiasis control. Our study site was the Senegal River Basin, where villagers suffered a massive outbreak and persistent epidemic after the 1986 completion of the Diama Dam. The dam blocked the annual migration of native river prawns (Macrobrachium vollenhoveni) that are voracious predators of the snail intermediate hosts for schistosomiasis. We tested schistosomiasis control by reintroduced river prawns in a before-after-control-impact field experiment that tracked parasitism in snails and people at two matched villages after prawns were stocked at one village's river access point. The abundance of infected snails was 80% lower at that village, presumably because prawn predation reduced the abundance and average life span of latently infected snails. As expected from a reduction in infected snails, human schistosomiasis prevalence was 18 ± 5% lower and egg burden was 50 ± 8% lower at the prawn-stocking village compared with the control village. In a mathematical model of the system, stocking prawns, coupled with infrequent mass drug treatment, eliminates schistosomiasis from high-transmission sites. We conclude that restoring river prawns could be a novel contribution to controlling, or eliminating, schistosomiasis.

  15. Grape polyphenols and propolis mixture inhibits inflammatory mediator release from human leukocytes and reduces clinical scores in experimental arthritis.

    Science.gov (United States)

    Mossalayi, M D; Rambert, J; Renouf, E; Micouleau, M; Mérillon, J M

    2014-02-15

    Polyphenols from red fruits and bee-derived propolis (PR) are bioactive natural products in various in vitro and in vivo models. The present study shows that hematotoxicity-free doses of grape polyphenols (GPE) and PR differentially decreased the secretion of pro-inflammatory cytokines from activated human peripheral blood leucocytes. While GPE inhibited the monocytes/macrophage response, propolis decreased both monokines and interferon γ (IFNγ) production. When used together, their distinct effects lead to the attenuation of all inflammatory mediators, as supported by a significant modulation of the transcriptomic profile of pro-inflammatory genes in human leukocytes. To enforce in vitro data, GPE+PR were tested for their ability to improve clinical scores and cachexia in chronic rat adjuvant-induced arthritis (AA). Extracts significantly reduced arthritis scores and cachexia, and this effect was more significant in animals receiving continuous low doses compared to those receiving five different high doses. Animals treated daily had significantly better clinical scores than corticoid-treated rats. Together, these findings indicate that the GPE+PR combination induces potent anti-inflammatory activity due to their complementary immune cell modulation. Copyright © 2013 Elsevier GmbH. All rights reserved.

  16. Reduced transmission of human schistosomiasis after restoration of a native river prawn that preys on the snail intermediate host

    Science.gov (United States)

    Sokolow, Susanne H.; Huttinger, Elizabeth; Jouanard, Nicolas; Hsieh, Michael H.; Lafferty, Kevin D.; Kuris, Armand M.; Riveau, Gilles; Senghor, Simon; Thiam, Cheikh; D'Diaye, Alassane; Faye, Djibril Sarr; De Leo, Giulio A.

    2015-01-01

    Eliminating human parasitic disease often requires interrupting complex transmission pathways. Even when drugs to treat people are available, disease control can be difficult if the parasite can persist in nonhuman hosts. Here, we show that restoration of a natural predator of a parasite’s intermediate hosts may enhance drug-based schistosomiasis control. Our study site was the Senegal River Basin, where villagers suffered a massive outbreak and persistent epidemic after the 1986 completion of the Diama Dam. The dam blocked the annual migration of native river prawns (Macrobrachium vollenhoveni) that are voracious predators of the snail intermediate hosts for schistosomiasis. We tested schistosomiasis control by reintroduced river prawns in a before-after-control-impact field experiment that tracked parasitism in snails and people at two matched villages after prawns were stocked at one village’s river access point. The abundance of infected snails was 80% lower at that village, presumably because prawn predation reduced the abundance and average life span of latently infected snails. As expected from a reduction in infected snails, human schistosomiasis prevalence was 18 ± 5% lower and egg burden was 50 ± 8% lower at the prawn-stocking village compared with the control village. In a mathematical model of the system, stocking prawns, coupled with infrequent mass drug treatment, eliminates schistosomiasis from high-transmission sites. We conclude that restoring river prawns could be a novel contribution to controlling, or eliminating, schistosomiasis.                            

  17. Reduced graphene oxide-coated hydroxyapatite composites stimulate spontaneous osteogenic differentiation of human mesenchymal stem cells

    Science.gov (United States)

    Lee, Jong Ho; Shin, Yong Cheol; Jin, Oh Seong; Kang, Seok Hee; Hwang, Yu-Shik; Park, Jong-Chul; Hong, Suck Won; Han, Dong-Wook

    2015-07-01

    Human mesenchymal stem cells (hMSCs) have great potential as cell sources for bone tissue engineering and regeneration, but the control and induction of their specific differentiation into bone cells remain challenging. Graphene-based nanomaterials are considered attractive candidates for biomedical applications such as scaffolds in tissue engineering, substrates for SC differentiation and components of implantable devices, due to their biocompatible and bioactive properties. Despite the potential biomedical applications of graphene and its derivatives, only limited information is available regarding their osteogenic activity. This study concentrates upon the effects of reduced graphene oxide (rGO)-coated hydroxyapatite (HAp) composites on osteogenic differentiation of hMSCs. The average particle sizes of HAp and rGO were 1270 +/- 476 nm and 438 +/- 180 nm, respectively. When coated on HAp particulates, rGO synergistically enhanced spontaneous osteogenic differentiation of hMSCs, without hampering their proliferation. This result was confirmed by determining alkaline phosphatase activity and mineralization of calcium and phosphate as early and late stage markers of osteogenic differentiation. It is suggested that rGO-coated HAp composites can be effectively utilized as dental and orthopedic bone fillers since these graphene-based particulate materials have potent effects on stimulating the spontaneous differentiation of MSCs and show superior bioactivity and osteoinductive potential.Human mesenchymal stem cells (hMSCs) have great potential as cell sources for bone tissue engineering and regeneration, but the control and induction of their specific differentiation into bone cells remain challenging. Graphene-based nanomaterials are considered attractive candidates for biomedical applications such as scaffolds in tissue engineering, substrates for SC differentiation and components of implantable devices, due to their biocompatible and bioactive properties. Despite

  18. Use of Paired Simple and Complex Models to Reduce Predictive Bias and Quantify Uncertainty

    DEFF Research Database (Denmark)

    Doherty, John; Christensen, Steen

    2011-01-01

    into the costs of model simplification, and into how some of these costs may be reduced. It then describes a methodology for paired model usage through which predictive bias of a simplified model can be detected and corrected, and postcalibration predictive uncertainty can be quantified. The methodology...

  19. Human-derived probiotic Lactobacillus reuteri strains differentially reduce intestinal inflammation.

    Science.gov (United States)

    Liu, Yuying; Fatheree, Nicole Y; Mangalat, Nisha; Rhoads, Jon Marc

    2010-11-01

    Lactobacillus reuteri (L. reuteri) is a probiotic that inhibits the severity of enteric infections and modulates the immune system. Human-derived L. reuteri strains DSM17938, ATCC PTA4659, ATCC PTA 5289, and ATCC PTA 6475 have demonstrated strain-specific immunomodulation in cultured monocytoid cells, but information about how these strains affect inflammation in intestinal epithelium is limited. We determined the effects of the four different L. reuteri strains on lipopolysaccharide (LPS)-induced inflammation in small intestinal epithelial cells and in the ileum of newborn rats. IPEC-J2 cells (derived from the jejunal epithelium of a neonatal piglet) and IEC-6 cells (derived from the rat crypt) were treated with L. reuteri. Newborn rat pups were gavaged cow milk formula supplemented with L. reuteri strains in the presence or absence of LPS. Protein and mRNA levels of cytokines and histological changes were measured. We demonstrate that even though one L. reuteri strain (DSM 17938) did not inhibit LPS-induced IL-8 production in cultured intestinal cells, all strains significantly reduced intestinal mucosal levels of KC/GRO (∼IL-8) and IFN-γ when newborn rat pups were fed formula containing LPS ± L. reuteri. Intestinal histological damage produced by LPS plus cow milk formula was also significantly reduced by all four strains. Cow milk formula feeding (without LPS) produced mild gut inflammation, evidenced by elevated mucosal IFN-γ and IL-13 levels, a process that could be suppressed by strain 17938. Other cytokines and chemokines were variably affected by the different strains, and there was no toxic effect of L. reuteri on intestinal cells or mucosa. In conclusion, L. reuteri strains differentially modulate LPS-induced inflammation. Probiotic interactions with both epithelial and nonepithelial cells in vivo must be instrumental in modulating intrinsic anti-inflammatory effects in the intestine. We suggest that the terms anti- and proinflammatory be used only

  20. Do leukoreduction filters passively reduce the transmission risk of human granulocytic anaplasmosis?

    Science.gov (United States)

    Proctor, Melanie C; Leiby, David A

    2015-06-01

    Human granulocytic anaplasmosis, caused by Anaplasma phagocytophilum, poses an increasing public health risk in the United States. Since 2000, case reports have increased annually; 2782 cases were reported in 2013. Despite the increasing frequency of clinical cases, only eight cases of transfusion-transmitted anaplasmosis (TTA) have been reported. We investigated if current leukoreduction practices impact transfusion risk. Whole blood units (WBUs) with integral red blood cell (RBC) leukoreduction filters were collected and spiked with A. phagocytophilum-infected HL-60 cells equivalent to 0.01, 1, or 5% of total neutrophils. After 24 hours at 4°C WBUs were processed into plasma and RBCs, the latter subsequently leukoreduced (LR RBCs). To evaluate the removal of A. phagocytophilum by filtration, pre- and postfiltration samples were compared by culture and polymerase chain reaction (PCR). Compared to Day 0 or Day 1 positive controls, LR RBCs demonstrated reduced levels of A. phagocytophilum by culture and PCR. At 0.01% infection levels LR RBCs yielded no positive cultures and a log reduction of 2.5 by PCR. Similarly, at 1 and 5% infections levels, LR RBCs produced only 44% (4/9) and 56% (5/9) positive cultures, respectively. PCR results were comparable, 3.0 log reduction for 1% and 3.3 log reduction for 5% infection levels. The recent increase in TTA suggests that A. phagocytophilum may represent an emerging blood safety issue. However, the current study indicates that the widespread practice of leukoreduction might passively reduce, but not eliminate, TTA risk. In the absence of viable testing or pathogen inactivation and/or reduction options, leukoreduction may offer some protection from transmission risk. © 2014 AABB.

  1. Pharmacological inhibition of dynamin II reduces constitutive protein secretion from primary human macrophages.

    Directory of Open Access Journals (Sweden)

    Maaike Kockx

    Full Text Available Dynamins are fission proteins that mediate endocytic and exocytic membrane events and are pharmacological therapeutic targets. These studies investigate whether dynamin II regulates constitutive protein secretion and show for the first time that pharmacological inhibition of dynamin decreases secretion of apolipoprotein E (apoE and several other proteins constitutively secreted from primary human macrophages. Inhibitors that target recruitment of dynamin to membranes (MiTMABs or directly target the GTPase domain (Dyngo or Dynole series, dose- and time- dependently reduced the secretion of apoE. SiRNA oligo's targeting all isoforms of dynamin II confirmed the involvement of dynamin II in apoE secretion. Inhibition of secretion was not mediated via effects on mRNA or protein synthesis. 2D-gel electrophoresis showed that inhibition occurred after apoE was processed and glycosylated in the Golgi and live cell imaging showed that inhibited secretion was associated with reduced post-Golgi movement of apoE-GFP-containing vesicles. The effect was not restricted to macrophages, and was not mediated by the effects of the inhibitors on microtubules. Inhibition of dynamin also altered the constitutive secretion of other proteins, decreasing the secretion of fibronectin, matrix metalloproteinase 9, Chitinase-3-like protein 1 and lysozyme but unexpectedly increasing the secretion of the inflammatory mediator cyclophilin A. We conclude that pharmacological inhibitors of dynamin II modulate the constitutive secretion of macrophage apoE as a class effect, and that their capacity to modulate protein secretion may affect a range of biological processes.

  2. Cost-effectiveness of mass dog rabies vaccination strategies to reduce human health burden in Flores Island, Indonesia.

    Science.gov (United States)

    Wera, Ewaldus; Mourits, Monique C M; Hogeveen, Henk

    2017-12-04

    The cost-effectiveness of different mass dog rabies vaccination strategies, defined as the costs per year of life lost (YLL) averted was evaluated for a period of 10 years by means of a dynamic simulation study for a typical village on Flores Island. In the base strategy (no dog vaccination and no post-exposure treatment (PET) of human bite cases), the model showed that the introduction of the virus by one infectious dog into an isolated village with 1500 inhabitants and 400 dogs resulted in 881 YLLs during a 10-year simulation period, which is equivalent to 30 human rabies cases. An annual dog vaccination campaign with a coverage of 70% using a short-acting vaccine saved 832 YLLs, while the cumulative costs for the public sector were US$3646 or US$4.38 per YLL averted. Switching to a long-acting vaccine, the annual vaccination strategies with a coverage of 50% (AV_156_50) or 70% (AV_156_70) reduced the baseline YLLs from 881 to respectively 78 and 26 YLLs with cumulative costs of US$3716 and US$2264 or US$4.63 and US$2.65 per YLL averted, respectively. In general, dog vaccination was more cost-effective than PET alone (US$2.65-4.63 per YLL averted versus US$23.29 per YLL averted). Although a combination of PET with AV_156_70 was less cost-effective compared to AV_156_70 alone, this strategy was able to prevent all human deaths due to rabies. A combination of PET with annual vaccination using a short-acting vaccine at a coverage of 50% was far from being cost-effective, suggesting that the currently applied rabies control in Flores Island is not an efficient investment in reducing human rabies burden. An increased investment in either an increase in the current coverage or in a switch from the short-acting vaccine to the long-acting vaccine type would certainly pay off. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Human amniotic epithelial cell transplantation induces markers of alternative macrophage activation and reduces established hepatic fibrosis.

    Directory of Open Access Journals (Sweden)

    Ursula Manuelpillai

    Full Text Available Chronic hepatic inflammation from multiple etiologies leads to a fibrogenic response that can progress to cirrhosis and liver failure. Transplantation of human amniotic epithelial cells (hAEC from term delivered placenta has been shown to decrease mild to moderate hepatic fibrosis in a murine model. To model advanced human liver disease and assess the efficacy of hAEC therapy, we transplanted hAEC in mice with advanced hepatic fibrosis. Immunocompetent C57BL/6 mice were administered carbon tetrachloride (CCl(4 twice weekly resulting in bridging fibrosis by 12 weeks. hAEC (2 × 10(6 were infused via the tail vein at week 8 or weeks 8 and 10 (single and double dose, respectively. Human cells were detected in mouse liver four weeks after transplantation showing hAEC engraftment. CCl(4 treated mice receiving single or double hAEC doses showed a significant but similar decrease in liver fibrosis area associated with decreased activation of collagen-producing hepatic stellate cells and decreased hepatic protein levels of the pro-fibrogenic cytokine, transforming growth factor-beta1. CCl(4 administration caused hepatic T cell infiltration that decreased significantly following hAEC transplantation. Hepatic macrophages play a crucial role in both fibrogenesis and fibrosis resolution. Mice exposed to CCl(4 demonstrated increased numbers of hepatic macrophages compared to normal mice; the number of macrophages decreased significantly in CCl(4 treated mice given hAEC. These mice had significantly lower hepatic protein levels of the chemokine monocyte chemoattractant protein-1 than mice given CCl(4 alone. Alternatively activated M2 macrophages are associated with fibrosis resolution. CCl(4 treated mice given hAEC showed increased expression of genes associated with M2 macrophages including YM-1, IL-10 and CD206. We provide novel data showing that hAEC transplantation induces a wound healing M2 macrophage phenotype associated with reduction of established

  4. Normal social seeking behavior, hypoactivity and reduced exploratory range in a mouse model of Angelman syndrome

    Directory of Open Access Journals (Sweden)

    Reiter Lawrence T

    2011-01-01

    Full Text Available Abstract Background Angelman syndrome (AS is a neurogenetic disorder characterized by severe developmental delay with mental retardation, a generally happy disposition, ataxia and characteristic behaviors such as inappropriate laughter, social-seeking behavior and hyperactivity. The majority of AS cases are due to loss of the maternal copy of the UBE3A gene. Maternal Ube3a deficiency (Ube3am-/p+, as well as complete loss of Ube3a expression (Ube3am-/p-, have been reproduced in the mouse model used here. Results Here we asked if two characteristic AS phenotypes - social-seeking behavior and hyperactivity - are reproduced in the Ube3a deficient mouse model of AS. We quantified social-seeking behavior as time spent in close proximity to a stranger mouse and activity as total time spent moving during exploration, movement speed and total length of the exploratory path. Mice of all three genotypes (Ube3am+/p+, Ube3am-/p+, Ube3am-/p- were tested and found to spend the same amount of time in close proximity to the stranger, indicating that Ube3a deficiency in mice does not result in increased social seeking behavior or social dis-inhibition. Also, Ube3a deficient mice were hypoactive compared to their wild-type littermates as shown by significantly lower levels of activity, slower movement velocities, shorter exploratory paths and a reduced exploratory range. Conclusions Although hyperactivity and social-seeking behavior are characteristic phenotypes of Angelman Syndrome in humans, the Ube3a deficient mouse model does not reproduce these phenotypes in comparison to their wild-type littermates. These phenotypic differences may be explained by differences in the size of the genetic defect as ~70% of AS patients have a deletion that includes several other genes surrounding the UBE3A locus.

  5. Metabolic disruptions induced by reduced ambulatory activity in free-living humans

    DEFF Research Database (Denmark)

    Thyfault, John P; Krogh-Madsen, Rikke

    2011-01-01

    Physical inactivity likely plays a role in the development of insulin resistance and obesity; however, direct evidence is minimal and mechanisms of action remain unknown. Studying metabolic outcomes that occur after transitioning from higher to lower levels of physical activity is the best tool...... by a large majority of the population. Recent studies have used a more applicable model in which active (∼10,000 steps/day), healthy young controls are asked to transition to an inactive lifestyle (∼1,500 steps/day) for a 14-day period. The transition to inactivity resulted in reduced insulin sensitivity...... and increased central adiposity. This review will discuss the outcomes of these studies, their implications for the cause/effect relationship between central adiposity and insulin resistance, and provide rationale for why inactivity induces these factors. In addition, the experimental challenges of directly...

  6. Hepatic glucose output in humans measured with labeled glucose to reduce negative errors

    International Nuclear Information System (INIS)

    Levy, J.C.; Brown, G.; Matthews, D.R.; Turner, R.C.

    1989-01-01

    Steele and others have suggested that minimizing changes in glucose specific activity when estimating hepatic glucose output (HGO) during glucose infusions could reduce non-steady-state errors. This approach was assessed in nondiabetic and type II diabetic subjects during constant low dose [27 mumol.kg ideal body wt (IBW)-1.min-1] glucose infusion followed by a 12 mmol/l hyperglycemic clamp. Eight subjects had paired tests with and without labeled infusions. Labeled infusion was used to compare HGO in 11 nondiabetic and 15 diabetic subjects. Whereas unlabeled infusions produced negative values for endogenous glucose output, labeled infusions largely eliminated this error and reduced the dependence of the Steele model on the pool fraction in the paired tests. By use of labeled infusions, 11 nondiabetic subjects suppressed HGO from 10.2 +/- 0.6 (SE) fasting to 0.8 +/- 0.9 mumol.kg IBW-1.min-1 after 90 min of glucose infusion and to -1.9 +/- 0.5 mumol.kg IBW-1.min-1 after 90 min of a 12 mmol/l glucose clamp, but 15 diabetic subjects suppressed only partially from 13.0 +/- 0.9 fasting to 5.7 +/- 1.2 at the end of the glucose infusion and 5.6 +/- 1.0 mumol.kg IBW-1.min-1 in the clamp (P = 0.02, 0.002, and less than 0.001, respectively)

  7. Transport phenomena in the human nasal cavity: a computational model.

    Science.gov (United States)

    Naftali, S; Schroter, R C; Shiner, R J; Elad, D

    1998-01-01

    Nasal inspiration is important for maintaining the internal milieu of the lung, since ambient air is conditioned to nearly alveolar conditions (body temperature and fully saturated with water vapor) on reaching the nasopharynx. We conducted a two-dimensional computational study of transport phenomena in model transverse cross sections of the nasal cavity of normal and diseased human noses for inspiration under various ambient conditions. The results suggest that during breathing via the normal human nose there is ample time for heat and water exchange to enable equilibration to near intraalveolar conditions. A normal nose can maintain this equilibrium under extreme environments (e.g., hot/humid, cold/dry, cold/humid). The turbinates increase the rate of local heat and moisture transport by narrowing the passageways for air and by induction of laminar swirls downstream of the turbinate wall. However, abnormal blood supply or mucous generation may reduce the rate of heat or moisture flux into the inspired air, and thereby affect the efficacy of the process.

  8. A numerical model for blast injury of human thorax based on digitized visible human.

    Science.gov (United States)

    Li, Xiao-Fang; Kuang, Jiang-Ming; Nie, Si-Bing; Xu, Jing; Zhu, Jin; Liu, Yi-He

    2017-12-04

    Knowledge of the pressure distribution around human thorax in blast help to understand the injury mechanisms and their assessment. To investigate the transmission mechanism of the pressure on human thorax in blast, a three dimension surface model of human thorax was constructed in this work. To increase the precious of this model, tetrahedron element division method was applied to transfer the rough 3D surface model to hexahedral elements model. Using this model, the high pressure duration was computationally solved using numerical simulation of the hexahedral elements. Simulation results showed that the apex of lungs was subjected to the largest stress in a blast. In order to verify this result, an animal experiment was performed on a dog. The animal experimental results was shown to have a same variation tendency with the calculation results based on our numerical model of human thorax, which made this model reliable for the blast injury research.

  9. Aromatherapy with two essential oils from Satureja genre and mindfulness meditation to reduce anxiety in humans

    Directory of Open Access Journals (Sweden)

    Marilú Roxana Soto-Vásquez

    2017-01-01

    Full Text Available The goal of this study was to verify whether association of aromatherapy with essential oils of Satureja brevicalyx or Satureja boliviana and mindfulness meditation can reduce anxiety levels in humans. A randomized experimental trial was carried out with 108 participants who were divided into 6 groups, comprising a waiting list control group and five experimental groups. Aromatherapy was carried out by inhalation of essential oils while mindfulness intervention program was focused on “flow meditation”. The anxiety index was evaluated by State-Trait Anxiety Inventory (STAI. Measures were taken two times: pretest and posttest. State and Trait anxiety scores showed a decrease in posttest study phase in comparison with pretest in all experimental groups (p < 0.005, especially in those where aromatherapy and mindfulness meditation were used together. All Cohen's d scores were over to 1 that means a large size effect in anxiety variable. Percentages of change showed reductions of anxiety variable ranging between 20% and 47%. All treatments used isolated or associated, may be considered alternative treatment options for anxiety.

  10. Traumatic Acid Reduces Oxidative Stress and Enhances Collagen Biosynthesis in Cultured Human Skin Fibroblasts.

    Science.gov (United States)

    Jabłońska-Trypuć, Agata; Pankiewicz, Walentyn; Czerpak, Romuald

    2016-09-01

    Traumatic acid (TA) is a plant hormone (cytokinin) that in terms of chemical structure belongs to the group of fatty acids derivatives. It was isolated from Phaseolus vulgaris. TA activity and its influence on human cells and organism has not previously been the subject of research. The aim of this study was to examine the effects of TA on collagen content and basic oxidative stress parameters, such as antioxidative enzyme activity, reduced glutathione, thiol group content, and lipid peroxidation in physiological conditions. The results show a stimulatory effect of TA on tested parameters. TA caused a decrease in membrane phospholipid peroxidation and exhibited protective properties against ROS production. It also increases protein and collagen biosynthesis and its secretion into the culture medium. The present findings reveal that TA exhibits multiple and complex activity in fibroblast cells in vitro. TA, with its activity similar to unsaturated fatty acids, shows antioxidant and stimulatory effects on collagen biosynthesis. It is a potentially powerful agent with applications in the treatment of many skin diseases connected with oxidative stress and collagen biosynthesis disorders.

  11. Reduced third-trimester levels of soluble human leukocyte antigen G protein in severe preeclampsia.

    Science.gov (United States)

    Hackmon, Rinat; Koifman, Arie; Hyodo, Hironobu; Hyobo, Hirohito; Glickman, Hagit; Sheiner, Eyal; Geraghty, Daniel E

    2007-09-01

    Recently, lower maternal plasma human leukocyte antigen (HLA)-G protein levels in preeclampsia (PE) in the first and second trimester was reported. Thus, we sought to evaluate the levels of HLA-G protein in patients with severe PE during the third trimester. In this prospective case control study, amniotic fluid and maternal and cord blood samples were aspirated from 50 pregnant women during the third trimester. The study group included 26 pregnant women diagnosed with severe PE and 24 women without PE serving as controls. A soluble HLA-G-specific enzyme-linked immunosorbent assay was used to measure protein levels. Statistical analysis included the Student t test and simple regression analysis. Maternal serum HLA-G levels in PE pregnancies were found to be significantly lower as compared with normal pregnancies (10.97 +/- 6.55 vs 36.05 +/- 34.53 microg/mL; P = .003). A reduced level of maternal HLA-G protein was associated with severe PE during the third trimester. This finding may suggest an essential role for HLA-G in normal and preeclamptic pregnancies.

  12. Aromatherapy with two essential oils from Satureja genre and mindfulness meditation to reduce anxiety in humans.

    Science.gov (United States)

    Soto-Vásquez, Marilú Roxana; Alvarado-García, Paúl Alan Arkin

    2017-01-01

    The goal of this study was to verify whether association of aromatherapy with essential oils of Satureja brevicalyx or Satureja boliviana and mindfulness meditation can reduce anxiety levels in humans. A randomized experimental trial was carried out with 108 participants who were divided into 6 groups, comprising a waiting list control group and five experimental groups. Aromatherapy was carried out by inhalation of essential oils while mindfulness intervention program was focused on "flow meditation". The anxiety index was evaluated by State-Trait Anxiety Inventory (STAI). Measures were taken two times: pretest and posttest. State and Trait anxiety scores showed a decrease in posttest study phase in comparison with pretest in all experimental groups (p < 0.005), especially in those where aromatherapy and mindfulness meditation were used together. All Cohen's d scores were over to 1 that means a large size effect in anxiety variable. Percentages of change showed reductions of anxiety variable ranging between 20% and 47%. All treatments used isolated or associated, may be considered alternative treatment options for anxiety.

  13. Applications and Limitations of Mouse Models for Understanding Human Atherosclerosis

    Science.gov (United States)

    von Scheidt, Moritz; Zhao, Yuqi; Kurt, Zeyneb; Pan, Calvin; Zeng, Lingyao; Yang, Xia; Schunkert, Heribert; Lusis, Aldons J.

    2017-01-01

    Most of the biological understanding of mechanisms underlying coronary artery disease (CAD) derives from studies of mouse models. The identification of multiple CAD loci and strong candidate genes in large human genome-wide association studies (GWAS) presented an opportunity to examine the relevance of mouse models for the human disease. We comprehensively reviewed the mouse literature, including 827 literature-derived genes, and compared it to human data. First, we observed striking concordance of risk factors for atherosclerosis in mice and humans. Second, there was highly significant overlap of mouse genes with human genes identified by GWAS. In particular, of the 46 genes with strong association signals in CAD-GWAS that were studied in mouse models all but one exhibited consistent effects on atherosclerosis-related phenotypes. Third, we compared 178 CAD-associated pathways derived from human GWAS with 263 from mouse studies and observed that over 50% were consistent between both species. PMID:27916529

  14. Reduced Fracture Finite Element Model Analysis of an Efficient Two-Scale Hybrid Embedded Fracture Model

    KAUST Repository

    Amir, Sahar Z.

    2017-06-09

    A Hybrid Embedded Fracture (HEF) model was developed to reduce various computational costs while maintaining physical accuracy (Amir and Sun, 2016). HEF splits the computations into fine scale and coarse scale. Fine scale solves analytically for the matrix-fracture flux exchange parameter. Coarse scale solves for the properties of the entire system. In literature, fractures were assumed to be either vertical or horizontal for simplification (Warren and Root, 1963). Matrix-fracture flux exchange parameter was given few equations built on that assumption (Kazemi, 1968; Lemonnier and Bourbiaux, 2010). However, such simplified cases do not apply directly for actual random fracture shapes, directions, orientations …etc. This paper shows that the HEF fine scale analytic solution (Amir and Sun, 2016) generates the flux exchange parameter found in literature for vertical and horizontal fracture cases. For other fracture cases, the flux exchange parameter changes according to the angle, slop, direction, … etc. This conclusion rises from the analysis of both: the Discrete Fracture Network (DFN) and the HEF schemes. The behavior of both schemes is analyzed with exactly similar fracture conditions and the results are shown and discussed. Then, a generalization is illustrated for any slightly compressible single-phase fluid within fractured porous media and its results are discussed.

  15. Zebrafish heart as a model for human cardiac electrophysiology.

    Science.gov (United States)

    Vornanen, Matti; Hassinen, Minna

    2016-01-01

    The zebrafish (Danio rerio) has become a popular model for human cardiac diseases and pharmacology including cardiac arrhythmias and its electrophysiological basis. Notably, the phenotype of zebrafish cardiac action potential is similar to the human cardiac action potential in that both have a long plateau phase. Also the major inward and outward current systems are qualitatively similar in zebrafish and human hearts. However, there are also significant differences in ionic current composition between human and zebrafish hearts, and the molecular basis and pharmacological properties of human and zebrafish cardiac ionic currents differ in several ways. Cardiac ionic currents may be produced by non-orthologous genes in zebrafish and humans, and paralogous gene products of some ion channels are expressed in the zebrafish heart. More research on molecular basis of cardiac ion channels, and regulation and drug sensitivity of the cardiac ionic currents are needed to enable rational use of the zebrafish heart as an electrophysiological model for the human heart.

  16. Mouse models for understanding human developmental anomalies

    International Nuclear Information System (INIS)

    Generoso, W.M.

    1989-01-01

    The mouse experimental system presents an opportunity for studying the nature of the underlying mutagenic damage and the molecular pathogenesis of this class of anomalies by virtue of the accessibility of the zygote and its descendant blastomeres. Such studies could contribute to the understanding of the etiology of certain sporadic but common human malformations. The vulnerability of the zygotes to mutagens as demonstrated in the studies described in this report should be a major consideration in chemical safety evaluation. It raises questions regarding the danger to human zygotes when the mother is exposed to drugs and environmental chemicals

  17. Mouse models for understanding human developmental anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Generoso, W.M.

    1989-01-01

    The mouse experimental system presents an opportunity for studying the nature of the underlying mutagenic damage and the molecular pathogenesis of this class of anomalies by virtue of the accessibility of the zygote and its descendant blastomeres. Such studies could contribute to the understanding of the etiology of certain sporadic but common human malformations. The vulnerability of the zygotes to mutagens as demonstrated in the studies described in this report should be a major consideration in chemical safety evaluation. It raises questions regarding the danger to human zygotes when the mother is exposed to drugs and environmental chemicals.

  18. Simplified human model and pedestrian simulation in the millimeter-wave region

    Science.gov (United States)

    Han, Junghwan; Kim, Seok; Lee, Tae-Yun; Ka, Min-Ho

    2016-02-01

    The 24 GHz and 77 GHz radar sensors have been studied as a strong candidate for advanced driver assistance systems(ADAS) because of their all-weather capability and accurate range and radial velocity measuring scheme. However, developing a reliable pedestrian recognition system hasmany obstacles due to the inaccurate and non-trivial radar responses at these high frequencies and the many combinations of clothes and accessories. To overcome these obstacles, many researchers used electromagnetic (EM) simulation to characterize the radar scattering response of a human. However, human simulation takes so long time because of the electrically huge size of a human in the millimeter-wave region. To reduce simulation time, some researchers assumed the skin of a human is the perfect electric conductor (PEC) and have simulated the PEC human model using physical optics (PO) algorithm without a specific explanation about how the human body could be modeled with PEC. In this study, the validity of the assumption that the surface of the human body is considered PEC in the EM simulation is verified, and the simulation result of the dry skin human model is compared with that of the PEC human model.

  19. Modeling Human Error Mechanism for Soft Control in Advanced Control Rooms (ACRs)

    International Nuclear Information System (INIS)

    Aljneibi, Hanan Salah Ali; Ha, Jun Su; Kang, Seongkeun; Seong, Poong Hyun

    2015-01-01

    To achieve the switch from conventional analog-based design to digital design in ACRs, a large number of manual operating controls and switches have to be replaced by a few common multi-function devices which is called soft control system. The soft controls in APR-1400 ACRs are classified into safety-grade and non-safety-grade soft controls; each was designed using different and independent input devices in ACRs. The operations using soft controls require operators to perform new tasks which were not necessary in conventional controls such as navigating computerized displays to monitor plant information and control devices. These kinds of computerized displays and soft controls may make operations more convenient but they might cause new types of human error. In this study the human error mechanism during the soft controls is studied and modeled to be used for analysis and enhancement of human performance (or human errors) during NPP operation. The developed model would contribute to a lot of applications to improve human performance (or reduce human errors), HMI designs, and operators' training program in ACRs. The developed model of human error mechanism for the soft control is based on assumptions that a human operator has certain amount of capacity in cognitive resources and if resources required by operating tasks are greater than resources invested by the operator, human error (or poor human performance) is likely to occur (especially in 'slip'); good HMI (Human-machine Interface) design decreases the required resources; operator's skillfulness decreases the required resources; and high vigilance increases the invested resources. In this study the human error mechanism during the soft controls is studied and modeled to be used for analysis and enhancement of human performance (or reduction of human errors) during NPP operation

  20. [Attempt at computer modeling of evolution of human society].

    Science.gov (United States)

    Levchenko, V F; Menshutkin, V V

    2009-01-01

    A model of evolution of human society and biosphere, which is based on the concepts of V. I. Vernadskii about noosphere and of L. N. Gumilev about ethnogenesis is developed and studied. The mathematical apparatus of the model is composition of finite stochastic automata. By using this model, a possibility of the global ecological crisis is demonstrated in the case of preservation of the current tendencies of interaction of the biosphere and the human civilization.

  1. Human Cancer Models Initiative | Office of Cancer Genomics

    Science.gov (United States)

    The Human Cancer Models Initiative (HCMI) is an international consortium that is generating novel human tumor-derived culture models, which are annotated with genomic and clinical data. In an effort to advance cancer research and more fully understand how in vitro findings are related to clinical biology, HCMI-developed models and related data will be available as a community resource for cancer and other research.

  2. Novel Reduced Order in Time Models for Problems in Nonlinear Aeroelasticity, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Research is proposed for the development and implementation of state of the art, reduced order models for problems in nonlinear aeroelasticity. Highly efficient and...

  3. Synthetic vision and memory model for virtual human - biomed 2010.

    Science.gov (United States)

    Zhao, Yue; Kang, Jinsheng; Wright, David

    2010-01-01

    This paper describes the methods and case studies of a novel synthetic vision and memory model for virtual human. The synthetic vision module simulates the biological / optical abilities and limitations of the human vision. The module is based on a series of collision detection between the boundary of virtual humans field of vision (FOV) volume and the surface of objects in a recreated 3D environment. The memory module simulates a short-term memory capability by employing a simplified memory structure (first-in-first-out stack). The synthetic vision and memory model has been integrated into a virtual human modelling project, Intelligent Virtual Modelling. The project aimed to improve the realism and autonomy of virtual humans.

  4. A prediction model to identify hospitalised, older adults with reduced physical performance

    DEFF Research Database (Denmark)

    Hansen Bruun, Inge; Maribo, Thomas; Nørgaard, Birgitte

    2017-01-01

    , but 76 patients (65%) had persistent reduced physical performance when compared to their baseline (30s-CST ≤ 8). The number of potential predictors was reduced in order to create a simplified prediction model based on 4 variables, namely the use of a walking aid before hospitalisation (score = 1.5), a 30...

  5. Oral Administration of Pentoxifylline Reduces Endometriosis-Like Lesions in a Nude Mouse Model.

    Science.gov (United States)

    Perelló, Maria; González-Foruria, Iñaki; Castillo, Paola; Martínez-Florensa, Mario; Lozano, Francisco; Balasch, Juan; Carmona, Francisco

    2017-06-01

    Recent reports consider endometriosis to be an immunological disorder, thus suggesting potential efficacy of immunomodulators for its treatment. The aim of this study was to assess the effects of oral administration of pentoxifylline on endometriosis-like lesions in a heterologous mice model. Human endometrial tissue obtained from women (n = 5) undergoing surgery for benign conditions was implanted in nude female mice (n = 30). The animals were distributed into 3 experimental groups receiving: saline 0.1 mL/d (control, group 1); pentoxifylline 100 mg/kg/d (group 2), and pentoxifylline 200 mg/kg/d (group 3). After 28 days, the number of implants and the total volume of surgically extracted tissue were recorded. Immunohistochemical analysis was performed to assess the area of endometriosis and vascularization of endometriosis-like lesions. Cytokine levels in peritoneal fluid samples were measured. Macroscopic quantification showed a trend to dose-dependent reduction in the number of the endometriosis-like lesions after 28 days. The volume was significantly reduced in group 3 versus group 2 and controls (399.10 ± 120.68 mm 3 vs 276.75 ± 94.30 mm 3 and 145.33 ± 38.20 mm 3 , respectively; P = .04). Similarly, the mean area of endometriosis was significantly lower in group 3 (0.12 ± 0.08 mm 2 ) versus group 2 (1.35 ± 0.43 mm 2 ) and control (2.84 ± 0.60 mm 2 ; P = .001). Vascularization and cytokine levels were also reduced posttreatment. Our results suggest that the oral administration of pentoxifylline may be an alternative to current therapies for endometriosis. Nonetheless, further studies are required.

  6. Behavior genetic modeling of human fertility

    DEFF Research Database (Denmark)

    Rodgers, J L; Kohler, H P; Kyvik, K O

    2001-01-01

    Behavior genetic designs and analysis can be used to address issues of central importance to demography. We use this methodology to document genetic influence on human fertility. Our data come from Danish twin pairs born from 1953 to 1959, measured on age at first attempt to get pregnant (First...

  7. Variable structure control for three-phase LCL-filtered inverters using a reduced converter model

    OpenAIRE

    Guzmán Solà, Ramon; García de Vicuña Muñoz de la Nava, José Luis; Castilla Fernández, Miguel; Miret Tomàs, Jaume; Hoz Casas, Jordi de la

    2017-01-01

    This paper presents a new concept in active damping techniques using a reduced model of a LCL-filtered grid connected inverter. The presence of the LCL filter complicates the design of the inverter control scheme, particularly when uncertainties in the system parameters, especially in the grid inductance, are considered. The proposed control algorithm is addressed to overcome such difficulties using a reduced model of the inverter in a state observer. In this proposal, two of the three state ...

  8. Pig models for the human heart failure syndrome

    DEFF Research Database (Denmark)

    Hunter, Ingrid; Terzic, Dijana; Zois, Nora Elisabeth

    2014-01-01

    Human heart failure remains a challenging illness despite advances in the diagnosis and treatment of heart failure patients. There is a need for further improvement of our understanding of the failing myocardium and its molecular deterioration. Porcine models provide an important research tool...... in this respect as molecular changes can be examined in detail, which is simply not feasible in human patients. However, the human heart failure syndrome is based on symptoms and signs, where pig models mostly mimic the myocardial damage, but without decisive data on clinical presentation and, therefore, a heart...... to elucidate the human heart failure syndrome....

  9. Development of a model to assess acoustic treatments to reduce railway noise

    OpenAIRE

    Jeong, Hongseok; Squicciarini, Giacomo; Thompson, David; Ryue, Jungsoo

    2016-01-01

    Porous materials have recently been used in absorptive treatments around railway tracks to reduce noise emissions. To investigate the effect of porous materials, a finite element model has been developed. 2D models for porous materials have been considered either as an equivalent fluid or as a poroelastic material based on the Biot theory. The two models have been validated and compared with each other to check the effect of the skeleton vibration. The poroelastic FE model has been coupled wi...

  10. Drosophila Melanogaster as an Emerging Translational Model of Human Nephrolithiasis

    Science.gov (United States)

    Miller, Joe; Chi, Thomas; Kapahi, Pankaj; Kahn, Arnold J.; Kim, Man Su; Hirata, Taku; Romero, Michael F.; Dow, Julian A.T.; Stoller, Marshall L.

    2013-01-01

    Purpose The limitations imposed by human clinical studies and mammalian models of nephrolithiasis have hampered the development of effective medical treatments and preventative measures for decades. The simple but elegant Drosophila melanogaster is emerging as a powerful translational model of human disease, including nephrolithiasis and may provide important information essential to our understanding of stone formation. We present the current state of research using D. melanogaster as a model of human nephrolithiasis. Materials and Methods A comprehensive review of the English language literature was performed using PUBMED. When necessary, authoritative texts on relevant subtopics were consulted. Results The genetic composition, anatomic structure and physiologic function of Drosophila Malpighian tubules are remarkably similar to those of the human nephron. The direct effects of dietary manipulation, environmental alteration, and genetic variation on stone formation can be observed and quantified in a matter of days. Several Drosophila models of human nephrolithiasis, including genetically linked and environmentally induced stones, have been developed. A model of calcium oxalate stone formation is among the most recent fly models of human nephrolithiasis. Conclusions The ability to readily manipulate and quantify stone formation in D. melanogaster models of human nephrolithiasis presents the urologic community with a unique opportunity to increase our understanding of this enigmatic disease. PMID:23500641

  11. Modeling cognition and disease using human glial chimeric mice

    DEFF Research Database (Denmark)

    Goldman, Steven A.; Nedergaard, Maiken; Windrem, Martha S.

    2015-01-01

    As new methods for producing and isolating human glial progenitor cells (hGPCs) have been developed, the disorders of myelin have become especially compelling targets for cell-based therapy. Yet as animal modeling of glial progenitor cell-based therapies has progressed, it has become clear......, oligodendrocytes as well. As a result, the recipient brains may become inexorably humanized with regards to their resident glial populations, yielding human glial chimeric mouse brains. These brains provide us a fundamentally new tool by which to assess the species-specific attributes of glia in modulating human...... for studying the human-specific contributions of glia to psychopathology, as well as to higher cognition. As such, the assessment of human glial chimeric mice may provide us new insight into the species-specific contributions of glia to human cognitive evolution, as well as to the pathogenesis of human...

  12. Trypanozoon: infectivity to humans is linked to reduced transmissibility in tsetse. II. Genetic mechanisms.

    Science.gov (United States)

    Milligan, P J; Maudlin, I; Welburn, S C

    1995-11-01

    Trypanozoon infections are less likely to mature in female tsetse than in males. Analysis of maturation data from 37 Trypanozoon isolates in Glossina m. morsitans showed that while the proportion of mature infections (salivary gland infections as a proportion of established midgut infections) varied from isolate to isolate, the proportion of mature infections in female flies was consistently smaller than the proportion in male flies. The log of the probability of maturation in females is, on average, twice the log of the probability in males (estimate of the ratio of the logged proportions is 2.09, 95% confidence interval (CI) 1.8 to 2.5). Human serum-resistant isolates were less likely to mature than human serum-sensitive isolates (ratio of logged proportions maturing was 1.5, 95% CI 1.3 to 1.8, in both male and female tsetse). Data for four other trypanosome stocks show that the probability of maturation decreases as the maturation time (the delay between the infected bloodmeal and maturation) increases. The decrease is approximately exponential with twice the half-life in male flies compared to that in female flies (estimate of the ratio of the exponential parameters is 1.97, 95% CI 0.7 to 3.3). A model is proposed to explain these observations which assumes that product(s) from an X-linked gene(s) kills or otherwise prevents migrating parasites from establishing a mature infection. Longer maturation times are associated with a heavy penalty in terms of transmissibility as measured by the vectorial capacity.

  13. Human Digital Modeling & Hand Scanning Lab

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory incorporates specialized scanning equipment, computer workstations and software applications for the acquisition and analysis of digitized models of...

  14. Modelling Cerebral Blood Flow Autoregulation in Humans

    National Research Council Canada - National Science Library

    Panerai, R

    2001-01-01

    ...% of CBF regulatory,' mechanisms and their interaction with other haemodynamic variables such as intracranial pressure and blood gases, Mathematical models have been able to reproduce many known...

  15. 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.

  16. Uncertainties in radioecological assessment models-Their nature and approaches to reduce them

    International Nuclear Information System (INIS)

    Kirchner, G.; Steiner, M.

    2008-01-01

    Radioecological assessment models are necessary tools for estimating the radiation exposure of humans and non-human biota. This paper focuses on factors affecting their predictive accuracy, discusses the origin and nature of the different contributions to uncertainty and variability and presents approaches to separate and quantify them. The key role of the conceptual model, notably in relation to its structure and complexity, as well as the influence of the number and type of input parameters, are highlighted. Guidelines are provided to improve the degree of reliability of radioecological models

  17. Mechanical Impedance Modeling of Human Arm: A survey

    Science.gov (United States)

    Puzi, A. Ahmad; Sidek, S. N.; Sado, F.

    2017-03-01

    Human arm mechanical impedance plays a vital role in describing motion ability of the upper limb. One of the impedance parameters is stiffness which is defined as the ratio of an applied force to the measured deformation of the muscle. The arm mechanical impedance modeling is useful in order to develop a better controller for system that interacts with human as such an automated robot-assisted platform for automated rehabilitation training. The aim of the survey is to summarize the existing mechanical impedance models of human upper limb so to justify the need to have an improved version of the arm model in order to facilitate the development of better controller of such systems with ever increase in complexity. In particular, the paper will address the following issue: Human motor control and motor learning, constant and variable impedance models, methods for measuring mechanical impedance and mechanical impedance modeling techniques.

  18. Human Spaceflight Architecture Model (HSFAM) Data Dictionary

    Science.gov (United States)

    Shishko, Robert

    2016-01-01

    HSFAM is a data model based on the DoDAF 2.02 data model with some for purpose extensions. These extensions are designed to permit quantitative analyses regarding stakeholder concerns about technical feasibility, configuration and interface issues, and budgetary and/or economic viability.

  19. Pig models for the human heart failure syndrome

    DEFF Research Database (Denmark)

    Hunter, Ingrid; Terzic, Dijana; Zois, Nora Elisabeth

    2014-01-01

    failure diagnosis. In perspective, pig models are in need of some verification in terms of the clinical definition of the experimental condition. After all, humans are not pigs, pigs are not humans, and the difference between the species needs to be better understood before pig models can fully be used......Human heart failure remains a challenging illness despite advances in the diagnosis and treatment of heart failure patients. There is a need for further improvement of our understanding of the failing myocardium and its molecular deterioration. Porcine models provide an important research tool...

  20. A Computational Model of Human Table Tennis for Robot Application

    Science.gov (United States)

    Mülling, Katharina; Peters, Jan

    Table tennis is a difficult motor skill which requires all basic components of a general motor skill learning system. In order to get a step closer to such a generic approach to the automatic acquisition and refinement of table tennis, we study table tennis from a human motor control point of view. We make use of the basic models of discrete human movement phases, virtual hitting points, and the operational timing hypothesis. Using these components, we create a computational model which is aimed at reproducing human-like behavior. We verify the functionality of this model in a physically realistic simulation of a Barrett WAM.

  1. Human performance modeling for system of systems analytics.

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, Kevin R.; Lawton, Craig R.; Basilico, Justin Derrick; Longsine, Dennis E. (INTERA, Inc., Austin, TX); Forsythe, James Chris; Gauthier, John Henry; Le, Hai D.

    2008-10-01

    A Laboratory-Directed Research and Development project was initiated in 2005 to investigate Human Performance Modeling in a System of Systems analytic environment. SAND2006-6569 and SAND2006-7911 document interim results from this effort; this report documents the final results. The problem is difficult because of the number of humans involved in a System of Systems environment and the generally poorly defined nature of the tasks that each human must perform. A two-pronged strategy was followed: one prong was to develop human models using a probability-based method similar to that first developed for relatively well-understood probability based performance modeling; another prong was to investigate more state-of-art human cognition models. The probability-based modeling resulted in a comprehensive addition of human-modeling capability to the existing SoSAT computer program. The cognitive modeling resulted in an increased understanding of what is necessary to incorporate cognition-based models to a System of Systems analytic environment.

  2. A multisensory integration model of human stance control.

    Science.gov (United States)

    van der Kooij, H; Jacobs, R; Koopman, B; Grootenboer, H

    1999-05-01

    A model is presented to study and quantify the contribution of all available sensory information to human standing based on optimal estimation theory. In the model, delayed sensory information is integrated in such a way that a best estimate of body orientation is obtained. The model approach agrees with the present theory of the goal of human balance control. The model is not based on purely inverted pendulum body dynamics, but rather on a three-link segment model of a standing human on a movable support base. In addition, the model is non-linear and explicitly addresses the problem of multisensory integration and neural time delays. A predictive element is included in the controller to compensate for time delays, necessary to maintain erect body orientation. Model results of sensory perturbations on total body sway closely resemble experimental results. Despite internal and external perturbations, the controller is able to stabilise the model of an inherently unstable standing human with neural time delays of 100 ms. It is concluded, that the model is capable of studying and quantifying multisensory integration in human stance control. We aim to apply the model in (1) the design and development of prostheses and orthoses and (2) the diagnosis of neurological balance disorders.

  3. Development of Technosols in abandoned mine lands to reduce hazards to ecosystems and human health

    Science.gov (United States)

    Zornoza, Raúl; Martínez-Martínez, Silvia; Acosta, Jose A.; Ángeles Muñoz, M.; Gómez-Garrido, Melisa; Gabarrón, Maria; Gómez-López, Maria Dolores; Faz, Ángel

    2017-04-01

    Mine tailings and residues dumped into the environment owing to mine ore processing activities have numerous restrictions affecting their development into natural soils, such as strong acidity, high concentrations and mobility of metals and metalloids, high salinity and extremely low organic matter content, which hinders the development of vegetation. This leads to the presence of bare surfaces which act as sources of water pollution and metal containing dusts, affecting natural ecosystems and populated areas in the surroundings. Therefore, there is a need to develop strategies to reduce the impact of tailings and mine residues spread on mine landscapes to reduce environmental and public health hazards and guarantee true land reclamation. One effective remediation option is the creation of Technosols by use of different materials, wastes and amendments derived from anthropogenic activities. For this purpose, the proper selection of materials is critical to convert metals to forms less soluble, mobile and toxic, so microorganisms, vegetation and animals can grow, and erosion rates are minimized so that metals do not reach populated areas. This goal can be achieved by applying materials with metal stabilization potential, to transform bioavailable metal species into geochemically stable forms. For this purpose, we have created Technosols in different mine tailings ponds located in SE Spain by use of different materials such as pig manure, pig slurry and marble waste. After 6 months of Technosol creation in field, seedlings from different native plant species were manually introduced for afforestation of the area. To monitor the evolution of soil quality and vegetation cover, four plots (10 m x 10 m) were established in each tailings pond, which were monitored every 6 months for 3 years. Results indicated that the created Technosol was efficient at significantly decreasing metal mobility by 90-99% depending on the metal. In addition, soil quality, fertility and

  4. Evaluation of reduced chemical kinetic mechanisms used for modeling mild combustion for natural gas

    Directory of Open Access Journals (Sweden)

    Hamdi Mohamed

    2009-01-01

    Full Text Available A numerical and parametric study was performed to evaluate the potential of reduced chemistry mechanisms to model natural gas chemistry including NOx chemistry under mild combustion mode. Two reduced mechanisms, 5-step and 9-step, were tested against the GRI-Mech3.0 by comparing key species, such as NOx, CO2 and CO, and gas temperature predictions in idealized reactors codes under mild combustion conditions. It is thus concluded that the 9-step mechanism appears to be a promising reduced mechanism that can be used in multi-dimensional codes for modeling mild combustion of natural gas.

  5. An optimal control model for reducing and trading of carbon emissions

    Science.gov (United States)

    Guo, Huaying; Liang, Jin

    2016-03-01

    A stochastic optimal control model of reducing and trading for carbon emissions is established in this paper. With considerations of reducing the carbon emission growth and the price of the allowances in the market, an optimal policy is searched to have the minimum total costs to achieve the agreement of emission reduction targets. The model turns to a two-dimension HJB equation problem. By the methods of reducing dimension and Cole-Hopf transformation, a semi-closed form solution of the corresponding HJB problem under some assumptions is obtained. For more general cases, the numerical calculations, analysis and comparisons are presented.

  6. Pellet culture model for human primary osteoblasts

    OpenAIRE

    K Jähn; RG Richards; CW Archer; MJ Stoddart

    2010-01-01

    In vitro monolayer culture of human primary osteoblasts (hOBs) often shows unsatisfactory results for extracellular matrix deposition, maturation and calcification. Nevertheless, monolayer culture is still the method of choice for in vitro differentiation of primary osteoblasts. We believe that the delay in mature ECM production by the monolayer cultured osteoblasts is determined by their state of cell maturation. A functional relationship between the inhibition of osteoblast proliferation an...

  7. Human reconstructed skin xenografts on mice to model skin physiology.

    Science.gov (United States)

    Salgado, Giorgiana; Ng, Yi Zhen; Koh, Li Fang; Goh, Christabelle S M; Common, John E

    Xenograft models to study skin physiology have been popular for scientific use since the 1970s, with various developments and improvements to the techniques over the decades. Xenograft models are particularly useful and sought after due to the lack of clinically relevant animal models in predicting drug effectiveness in humans. Such predictions could in turn boost the process of drug discovery, since novel drug compounds have an estimated 8% chance of FDA approval despite years of rigorous preclinical testing and evaluation, albeit mostly in non-human models. In the case of skin research, the mouse persists as the most popular animal model of choice, despite its well-known anatomical differences with human skin. Differences in skin biology are especially evident when trying to dissect more complex skin conditions, such as psoriasis and eczema, where interactions between the immune system, epidermis and the environment likely occur. While the use of animal models are still considered the gold standard for systemic toxicity studies under controlled environments, there are now alternative models that have been approved for certain applications. To overcome the biological limitations of the mouse model, research efforts have also focused on "humanizing" the mice model to better recapitulate human skin physiology. In this review, we outline the different approaches undertaken thus far to study skin biology using human tissue xenografts in mice and the technical challenges involved. We also describe more recent developments to generate humanized multi-tissue compartment mice that carry both a functioning human immune system and skin xenografts. Such composite animal models provide promising opportunities to study drugs, disease and differentiation with greater clinical relevance. Copyright © 2017 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  8. Local Model of Arteriovenous Malformation of the Human Brain

    International Nuclear Information System (INIS)

    Telegina, Nadezhda; Chupakhin, Aleksandr; Cherevko, Aleksandr

    2013-01-01

    Vascular diseases of the human brain are one of the reasons of deaths and people's incapacitation not only in Russia, but also in the world. The danger of an arteriovenous malformation (AVM) is in premature rupture of pathological vessels of an AVM which may cause haemorrhage. Long-term prognosis without surgical treatment is unfavorable. The reduced impact method of AVM treatment is embolization of a malformation which often results in complete obliteration of an AVM. Pre-surgical mathematical modeling of an arteriovenous malformation can help surgeons with an optimal sequence of the operation. During investigations, the simple mathematical model of arteriovenous malformation is developed and calculated, and stationary and non-stationary processes of its embolization are considered. Various sequences of embolization of a malformation are also considered. Calculations were done with approximate steady flow on the basis of balanced equations derived from conservation laws. Depending on pressure difference, a fistula-type AVM should be embolized at first, and then small racemose AVMs are embolized. Obtained results are in good correspondence with neurosurgical AVM practice.

  9. A Human View Model for Socio-Technical Interactions

    Science.gov (United States)

    Handley, Holly A.; Tolk, Andreas

    2012-01-01

    The Human View was developed as an additional architectural viewpoint to focus on the human part of a system. The Human View can be used to collect and organize data in order to understand how human operators interact and impact the other elements of a system. This framework can also be used to develop a model to describe how humans interact with each other in network enabled systems. These socio-technical interactions form the foundation of the emerging area of Human Interoperability. Human Interoperability strives to understand the relationships required between human operators that impact collaboration across networked environments, including the effect of belonging to different organizations. By applying organizational relationship concepts from network theory to the Human View elements, and aligning these relationships with a model developed to identify layers of coalition interoperability, the conditions for different levels for Human Interoperability for network enabled systems can be identified. These requirements can then be captured in the Human View products to improve the overall network enabled system.

  10. Formal modelling techniques in human-computer interaction

    NARCIS (Netherlands)

    de Haan, G.; de Haan, G.; van der Veer, Gerrit C.; van Vliet, J.C.

    1991-01-01

    This paper is a theoretical contribution, elaborating the concept of models as used in Cognitive Ergonomics. A number of formal modelling techniques in human-computer interaction will be reviewed and discussed. The analysis focusses on different related concepts of formal modelling techniques in

  11. A computationally efficient electrophysiological model of human ventricular cells

    NARCIS (Netherlands)

    Bernus, O.; Wilders, R.; Zemlin, C. W.; Verschelde, H.; Panfilov, A. V.

    2002-01-01

    Recent experimental and theoretical results have stressed the importance of modeling studies of reentrant arrhythmias in cardiac tissue and at the whole heart level. We introduce a six-variable model obtained by a reformulation of the Priebe-Beuckelmann model of a single human ventricular cell. The

  12. A practical guideline for human error assessment: A causal model

    Science.gov (United States)

    Ayele, Y. Z.; Barabadi, A.

    2017-12-01

    To meet the availability target and reduce system downtime, effective maintenance have a great importance. However, maintenance performance is greatly affected in complex ways by human factors. Hence, to have an effective maintenance operation, these factors needs to be assessed and quantified. To avoid the inadequacies of traditional human error assessment (HEA) approaches, the application of Bayesian Networks (BN) is gaining popularity. The main purpose of this paper is to propose a HEA framework based on the BN for maintenance operation. The proposed framework aids for assessing the effects of human performance influencing factors on the likelihood of human error during maintenance activities. Further, the paper investigates how operational issues must be considered in system failure-rate analysis, maintenance planning, and prediction of human error in pre- and post-maintenance operations. The goal is to assess how performance monitoring and evaluation of human factors can effect better operation and maintenance.

  13. How human-made greenhouse gas emissions can (really) be reduced

    International Nuclear Information System (INIS)

    2008-01-01

    To be efficient, any action undertaken in view of mitigating Greenhouse Gas Emissions requires that the reduction of CO 2 emissions not be confused with energy savings. Indeed, there is strict correlation between the two only if the energy savings achieved lead to fossil fuel savings. If a drastic reduction of greenhouse gas emissions were not mandatory, the conversion of our energy production and use would be less pressing, the known fossil fuel reserves being sufficient to supply humanity for at least one and a half centuries. Keeping these consideration in mind, under the control of its Scientific Council and with the help of partner organizations, STC has elaborated a set of proposals to reduce the economic activity's carbon content without affecting in any fundamental way the life style of the populations concerned while leaving room for economic growth in developing countries. In this sense, the ''Negatep'' scenario put forward by STC is fundamentally different from the ''Negawatt'' type scenarios. The options we recommend are ranked according to their economic efficiency. The index that is conventionally used to compare conceivable solutions is known as the ''cost of carbon avoided'' for a given action. It consists in estimating the additional cost of the action considered in relation to the amount of carbon whose release to the atmosphere is avoided thanks to the action. The index is measured in Euros per metric ton of carbon avoided. Summary of the actions and recommendations put forward by ''Save the Climate'' for energy production and energy efficiency are argued in further detail in this document. (A.L.B.)

  14. The impact of European legislative and technology measures to reduce air pollutants on air quality, human health and climate

    Science.gov (United States)

    Turnock, S. T.; Butt, E. W.; Richardson, T. B.; Mann, G. W.; Reddington, C. L.; Forster, P. M.; Haywood, J.; Crippa, M.; Janssens-Maenhout, G.; Johnson, C. E.; Bellouin, N.; Carslaw, K. S.; Spracklen, D. V.

    2016-02-01

    European air quality legislation has reduced emissions of air pollutants across Europe since the 1970s, affecting air quality, human health and regional climate. We used a coupled composition-climate model to simulate the impacts of European air quality legislation and technology measures implemented between 1970 and 2010. We contrast simulations using two emission scenarios; one with actual emissions in 2010 and the other with emissions that would have occurred in 2010 in the absence of technological improvements and end-of-pipe treatment measures in the energy, industrial and road transport sectors. European emissions of sulphur dioxide, black carbon (BC) and organic carbon in 2010 are 53%, 59% and 32% lower respectively compared to emissions that would have occurred in 2010 in the absence of legislative and technology measures. These emission reductions decreased simulated European annual mean concentrations of fine particulate matter (PM2.5) by 35%, sulphate by 44%, BC by 56% and particulate organic matter by 23%. The reduction in PM2.5 concentrations is calculated to have prevented 80 000 (37 000-116 000, at 95% confidence intervals) premature deaths annually across the European Union, resulting in a perceived financial benefit to society of US232 billion annually (1.4% of 2010 EU GDP). The reduction in aerosol concentrations due to legislative and technology measures caused a positive change in the aerosol radiative effect at the top of atmosphere, reduced atmospheric absorption and also increased the amount of solar radiation incident at the surface over Europe. We used an energy budget approximation to estimate that these changes in the radiative balance have increased European annual mean surface temperatures and precipitation by 0.45 ± 0.11 °C and by 13 ± 0.8 mm yr-1 respectively. Our results show that the implementation of European legislation and technological improvements to reduce the emission of air pollutants has improved air quality and human

  15. Some aspects of statistical modeling of human-error probability

    International Nuclear Information System (INIS)

    Prairie, R.R.

    1982-01-01

    Human reliability analyses (HRA) are often performed as part of risk assessment and reliability projects. Recent events in nuclear power have shown the potential importance of the human element. There are several on-going efforts in the US and elsewhere with the purpose of modeling human error such that the human contribution can be incorporated into an overall risk assessment associated with one or more aspects of nuclear power. An effort that is described here uses the HRA (event tree) to quantify and model the human contribution to risk. As an example, risk analyses are being prepared on several nuclear power plants as part of the Interim Reliability Assessment Program (IREP). In this process the risk analyst selects the elements of his fault tree that could be contributed to by human error. He then solicits the HF analyst to do a HRA on this element

  16. A Simple Model for Human and Nature Interaction

    Science.gov (United States)

    Motesharrei, S.; Rivas, J.; Kalnay, E.

    2012-12-01

    There are widespread concerns that current trends in population and resource-use are unsustainable, but the possibilities of an overshoot and collapse remain unclear and controversial. Collapses of civilizations have occurred many times in the past 5000 years, often followed by centuries of economic, intellectual, and population decline. Many different natural and social phenomena have been invoked to explain specific collapses, but a general explanation remains elusive. Two important features seem to appear across societies that have collapsed: Ecological Strain and Economic Stratification. Our new model (Human And Nature DYnamics, HANDY) has just four equations that describe the evolution of Elites, Commoners, Nature, and Wealth. Mechanisms leading to collapse are discussed and the measure "Carrying Capacity" is developed and defined. The model shows that societal collapse can happen due to either one of two independent factors: (1) over-consumption of natural resources, and/or (2) deep inequity between Elites and Commoners. The model also portrays two distinct types of collapse: (i) collapse followed by recovery of nature, and (ii) full collapse. The model suggests that the estimation of Carrying Capacity is a practical means for early detection of a collapse. Collapse can be avoided, and population can reach a sustainable equilibrium, if the rate of depletion of nature is reduced to a sustainable level, and if resources are distributed in a reasonably equitable fashion.; A type-ii (full) collapse is shown in this figure. With high inequality and high depletion, societies are doomed to collapse. Wealth starts to decrease when population rises above the carrying capacity. The large gap between carrying capacity and its maximum is a result of depletion factor being much larger than the sustainable limit. ; It is possible to overshoot, oscillate, and eventually converge to an equilibrium, even in an inequitable society. However, it requires policies that control

  17. Generation of postured voxel-based human models for the study of step voltage excited by lightning current

    Science.gov (United States)

    Gao, J.; Munteanu, I.; Müller, W. F. O.; Weiland, T.

    2011-07-01

    With the development of medical technique and computational electromagnetics, high resolution anatomic human models have already been widely developed and used in computation of electromagnetic fields induced in human body. Although these so called voxel-based human models are powerful tools for research on electromagnetic safety, their unchangeable standing posture makes it impossible to simulate a realistic scenario in which people have a lot of different postures. This paper describes a poser program package which was developed as an improved version of the free-from deformation technique to overcome this problem. It can set rotation angles of different human joints and then deform the original human model to make it have different postures. The original whole-body human model can be deformed smoothly, continuity of internal tissues and organs is maintained and the mass of different tissues and organs can be conserved in a reasonable level. As a typical application of the postured human models, this paper also studies the effect of the step voltage due to a lightning strike on the human body. Two voxel-based human body models with standing and walking posture were developed and integrated into simulation models to compute the current density distribution in the human body shocked by the step voltage. In order to speed up the transient simulation, the reduced c technique was used, leading to a speedup factor of around 20. The error introduced by the reduced c technique is discussed and simulation results are presented in detail.

  18. Assessing reproductive toxicity of two environmental toxicants with a novel in vitro human spermatogenic model

    Directory of Open Access Journals (Sweden)

    Charles A. Easley, IV

    2015-05-01

    Full Text Available Environmental influences and insults by reproductive toxicant exposure can lead to impaired spermatogenesis or infertility. Understanding how toxicants disrupt spermatogenesis is critical for determining how environmental factors contribute to impaired fertility. While current animal models are available, understanding of the reproductive toxic effects on human fertility requires a more robust model system. We recently demonstrated that human pluripotent stem cells can differentiate into spermatogonial stem cells/spermatogonia, primary and secondary spermatocytes, and haploid spermatids; a model that mimics many aspects of human spermatogenesis. Here, using this model system, we examine the effects of 2-bromopropane (2-BP and 1,2,dibromo-3-chloropropane (DBCP on in vitro human spermatogenesis. 2-BP and DBCP are non-endocrine disrupting toxicants that are known to impact male fertility. We show that acute treatment with either 2-BP or DBCP induces a reduction in germ cell viability through apoptosis. 2-BP and DBCP affect viability of different cell populations as 2-BP primarily reduces spermatocyte viability, whereas DBCP exerts a much greater effect on spermatogonia. Acute treatment with 2-BP or DBCP also reduces the percentage of haploid spermatids. Both 2-BP and DBCP induce reactive oxygen species (ROS formation leading to an oxidized cellular environment. Taken together, these results suggest that acute exposure with 2-BP or DBCP causes human germ cell death in vitro by inducing ROS formation. This system represents a unique platform for assessing human reproductive toxicity potential of various environmental toxicants in a rapid, efficient, and unbiased format.

  19. A Review on Human Respiratory Modeling.

    Science.gov (United States)

    Ghafarian, Pardis; Jamaati, Hamidreza; Hashemian, Seyed Mohammadreza

    2016-01-01

    Input impedance of the respiratory system is measured by forced oscillation technique (FOT). Multiple prior studies have attempted to match the electromechanical models of the respiratory system to impedance data. Since the mechanical behavior of airways and the respiratory system as a whole are similar to an electrical circuit in a combination of series and parallel formats some theories were introduced according to this issue. It should be noted that, the number of elements used in these models might be less than those required due to the complexity of the pulmonary-chest wall anatomy. Various respiratory models have been proposed based on this idea in order to demonstrate and assess the different parts of respiratory system related to children and adults data. With regard to our knowledge, some of famous respiratory models in related to obstructive, restrictive diseases and also Acute Respiratory Distress Syndrome (ARDS) are reviewed in this article.

  20. Human Communication--A New Model.

    Science.gov (United States)

    McLeish, John

    1978-01-01

    Pavlov's organism-in-the-environment model was adapted to a functional analysis of communication, expecially abstract and symbolic activities. A classification of discrimination response and reinforcement patterns was given. (CP)

  1. Human Endothelial Cell Models in Biomaterial Research.

    Science.gov (United States)

    Hauser, Sandra; Jung, Friedrich; Pietzsch, Jens

    2017-03-01

    Endothelial cell (EC) models have evolved as important tools in biomaterial research due to ubiquitously occurring interactions between implanted materials and the endothelium. However, screening the available literature has revealed a gap between material scientists and physiologists in terms of their understanding of these biomaterial-endothelium interactions and their relative importance. Consequently, EC models are often applied in nonphysiological experimental setups, or too extensive conclusions are drawn from their results. The question arises whether this might be one reason why, among the many potential biomaterials, only a few have found their way into the clinic. In this review, we provide an overview of established EC models and possible selection criteria to enable researchers to determine the most reliable and relevant EC model to use. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. A Positive Model for Reducing and Preventing School Burnout in High School Students

    Science.gov (United States)

    Aypay, Ayse

    2017-01-01

    This study aims to develop and test the validity of a model limited to attitude towards the future and subjective well-being for reducing and preventing the school burnout that high school students can experience. The study is designed as a relational screening model conducted over 389 high school students. The data in this study are analyzed…

  3. Model-Based approaches to Human-Automation Systems Design

    DEFF Research Database (Denmark)

    Jamieson, Greg A.; Andersson, Jonas; Bisantz, Ann

    2012-01-01

    Human-automation interaction in complex systems is common, yet design for this interaction is often conducted without explicit consideration of the role of the human operator. Fortunately, there are a number of modeling frameworks proposed for supporting this design activity. However...... (and reportedly one or two critics) can engage one another on several agreed questions about such frameworks. The goal is to aid non-aligned practitioners in choosing between alternative frameworks for their human-automation interaction design challenges....

  4. Cupric ion reducing antioxidant capacity assay for antioxidants in human serum and for hydroxyl radical scavengers.

    Science.gov (United States)

    Apak, Reşat; Güçlü, Kubilay; Ozyürek, Mustafa; Bektaşoğlu, Burcu; Bener, Mustafa

    2010-01-01

    Tests measuring the combined antioxidant effect of the nonenzymatic defenses in biological fluids may be useful in providing an index of the organism's capability to counteract reactive species known as pro-oxidants, resist oxidative damage, and combat oxidative stress-related diseases. The selected chromogenic redox reagent for the assay of human serum should be easily accessible, stable, selective, and respond to all types of biologically important antioxidants such as ascorbic acid, alpha-tocopherol, beta-carotene, reduced glutathione (GSH), uric acid, and bilirubin, regardless of chemical type or hydrophilicity. Our recently developed cupric reducing antioxidant capacity (CUPRAC) spectrophotometric method for a number of polyphenols and flavonoids using the copper(II)-neocuproine reagent in ammonium acetate buffer is now applied to a complete series of plasma antioxidants for the assay of total antioxidant capacity of serum, and the resulting absorbance at 450 nm is recorded either directly (e.g., for ascorbic acid, alpha-tocopherol, and glutathione) or after incubation at 50 degrees C for 20 min (e.g., for uric acid, bilirubin, and albumin), quantitation being made by means of a calibration curve. The lipophilic antioxidants, alpha-tocopherol and beta-carotene, are assayed in dichloromethane. Lipophilic antioxidants of serum are extracted with n-hexane from an ethanolic solution of serum subjected to centrifugation. Hydrophilic antioxidants of serum are assayed in the centrifugate after perchloric acid precipitation of proteins. The CUPRAC molar absorptivities, linear ranges, and TEAC (trolox equivalent antioxidant capacity) coefficients of the serum antioxidants are established, and the results are evaluated in comparison with the findings of the ABTS/TEAC reference method. The intra- and inter-assay coefficients of variation (CVs) are 0.7 and 1.5%, respectively, for serum. The CUPRAC assay proved to be efficient for glutathione and thiol-type antioxidants

  5. Reducing the negative human-health impacts of bioenergy crop emissions through region-specific crop selection

    OpenAIRE

    Guenther, Alex; Lamarque, Jean-Francois; Barsanti, Kelley; Porter, William C.; Rosenstiel, Todd N.

    2015-01-01

    An expected global increase in bioenergy-crop cultivation as an alternative to fossil fuels will have consequences on both global climate and local air quality through changes in biogenic emissions of volatile organic compounds (VOCs). While greenhouse gas emissions may be reduced through the substitution of next-generation bioenergy crops such as eucalyptus, giant reed, and switchgrass for fossil fuels, the choice of species has important ramifications for human health, potentially reducing ...

  6. Relevance of animal models to human tardive dyskinesia

    Directory of Open Access Journals (Sweden)

    Blanchet Pierre J

    2012-03-01

    Full Text Available Abstract Tardive dyskinesia remains an elusive and significant clinical entity that can possibly be understood via experimentation with animal models. We conducted a literature review on tardive dyskinesia modeling. Subchronic antipsychotic drug exposure is a standard approach to model tardive dyskinesia in rodents. Vacuous chewing movements constitute the most common pattern of expression of purposeless oral movements and represent an impermanent response, with individual and strain susceptibility differences. Transgenic mice are also used to address the contribution of adaptive and maladaptive signals induced during antipsychotic drug exposure. An emphasis on non-human primate modeling is proposed, and past experimental observations reviewed in various monkey species. Rodent and primate models are complementary, but the non-human primate model appears more convincingly similar to the human condition and better suited to address therapeutic issues against tardive dyskinesia.

  7. PBPK modeling for PFOS and PFOA: validation with human experimental data.

    Science.gov (United States)

    Fàbrega, Francesc; Kumar, Vikas; Schuhmacher, Marta; Domingo, José L; Nadal, Martí

    2014-10-15

    In recent years, because of the potential human toxicity, concern on perfluoroalkyl substances (PFASs) has increased notably with special attention to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Unfortunately, there is currently an important knowledge gap on the burdens of these chemicals in most human tissues, as the reported studies have been mainly focused on plasma. In order to overcome these limitations, the use of physiologically-based pharmacokinetic (PBPK) models has been extended. The present study was aimed at testing an existing PBPK model for their predictability of PFOS and PFOA in a new case-study, and also to adapt it to estimate the PFAS content in human tissue compartments. Model validation was conducted by means of PFOA and PFOS concentrations in food and human drinking water from Tarragona County (Catalonia, Spain), and being the predicted results compared with those experimentally found in human tissues (blood, liver, kidney, liver and brain) of subjects from the same area of study. The use of human-derived partition coefficient (Pk) data was proven as more suitable for application to this PBPK model than rat-based Pk values. However, the uncertainty and variability of the data are still too high to get conclusive results. Consequently, further efforts should be carried out to reduce parametric uncertainty of PBPK models. More specifically, a deeper knowledge on the distribution of PFOA and PFOS within the human body should be obtained by enlarging the number of biological monitoring studies on PFASs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Computational models of human vision with applications

    Science.gov (United States)

    Wandell, Brian A.

    1987-01-01

    The research program supported by this grant was initiated in l977 by the Joint Institute for Aeronautics and Acoustics of the Department of Aeronautics and Astronautics at Stanford University. The purpose of the research was to study human performance with the goal of improving the design of flight instrumentation. By mutual agreement between the scientists at NASA-Ames and Stanford, all research activities in this area were consolidated into a single funding mechanism, NCC 2-307 (Center of Excellence Grant, 7/1/84 - present). This is the final report on this research grant.

  9. Quantitative modeling of human performance in complex, dynamic systems

    National Research Council Canada - National Science Library

    Baron, Sheldon; Kruser, Dana S; Huey, Beverly Messick

    1990-01-01

    ... Sheldon Baron, Dana S. Kruser, and Beverly Messick Huey, editors Panel on Human Performance Modeling Committee on Human Factors Commission on Behavioral and Social Sciences and Education National Research Council NATIONAL ACADEMY PRESS Washington, D.C. 1990 Copyrightoriginal retained, the be not from cannot book, paper original however, for version forma...

  10. How do humans inspect BPMN models: an exploratory study

    DEFF Research Database (Denmark)

    Haisjackl, Cornelia; Soffer, Pnina; Lim, Shao Yi

    2016-01-01

    by humans, what strategies are taken, what challenges arise, and what cognitive processes are involved. This paper contributes toward such an understanding and reports an exploratory study investigating how humans identify and classify quality issues in BPMN process models. Providing preliminary answers...

  11. Pharmacological migraine provocation: a human model of migraine

    DEFF Research Database (Denmark)

    Ashina, Messoud; Hansen, Jakob Møller

    2010-01-01

    for migraine mechanisms. So far, however, animal models cannot predict the efficacy of new therapies for migraine. Because migraine attacks are fully reversible and can be aborted by therapy, the headache- or migraine-provoking property of naturally occurring signaling molecules can be tested in a human model......In vitro studies have contributed to the characterization of receptors in cranial blood vessels and the identification of possible new antimigraine agents. Animal models enable the study of vascular responses, neurogenic inflammation, and peptide release, and thus have provided leads in the search....... If a naturally occurring substance can provoke migraine in human patients, then it is likely, although not certain, that blocking its effect will be effective in the treatment of acute migraine attacks. To this end, a human in vivo model of experimental headache and migraine in humans has been developed...

  12. Can inter-human communications be modeled as "autopoietic"?

    NARCIS (Netherlands)

    Leydesdorff, L.

    2014-01-01

    Open peer commentary on the article "Social Autopoiesis?" by Hugo Urrestarazu. Upshot: The dynamics of expectations in inter-human communications can be modelled as "autopoiesis." Consciousness and communications couple not only structurally (Maturana), but also penetrate each other reflexively

  13. Dynamic Human Body Modeling Using a Single RGB Camera.

    Science.gov (United States)

    Zhu, Haiyu; Yu, Yao; Zhou, Yu; Du, Sidan

    2016-03-18

    In this paper, we present a novel automatic pipeline to build personalized parametric models of dynamic people using a single RGB camera. Compared to previous approaches that use monocular RGB images, our system can model a 3D human body automatically and incrementally, taking advantage of human motion. Based on coarse 2D and 3D poses estimated from image sequences, we first perform a kinematic classification of human body parts to refine the poses and obtain reconstructed body parts. Next, a personalized parametric human model is generated by driving a general template to fit the body parts and calculating the non-rigid deformation. Experimental results show that our shape estimation method achieves comparable accuracy with reconstructed models using depth cameras, yet requires neither user interaction nor any dedicated devices, leading to the feasibility of using this method on widely available smart phones.

  14. Reducing the complexity of an agent-based local heroin market model.

    Science.gov (United States)

    Heard, Daniel; Bobashev, Georgiy V; Morris, Robert J

    2014-01-01

    This project explores techniques for reducing the complexity of an agent-based model (ABM). The analysis involved a model developed from the ethnographic research of Dr. Lee Hoffer in the Larimer area heroin market, which involved drug users, drug sellers, homeless individuals and police. The authors used statistical techniques to create a reduced version of the original model which maintained simulation fidelity while reducing computational complexity. This involved identifying key summary quantities of individual customer behavior as well as overall market activity and replacing some agents with probability distributions and regressions. The model was then extended to allow external market interventions in the form of police busts. Extensions of this research perspective, as well as its strengths and limitations, are discussed.

  15. Reduced Gasoline Surrogate (Toluene/n-Heptane/iso-Octane) Chemical Kinetic Model for Compression Ignition Simulations

    KAUST Repository

    Sarathy, Mani

    2018-04-03

    Toluene primary reference fuel (TPRF) (mixture of toluene, iso-octane and heptane) is a suitable surrogate to represent a wide spectrum of real fuels with varying octane sensitivity. Investigating different surrogates in engine simulations is a prerequisite to identify the best matching mixture. However, running 3D engine simulations using detailed models is currently impossible and reduction of detailed models is essential. This work presents an AramcoMech reduced kinetic model developed at King Abdullah University of Science and Technology (KAUST) for simulating complex TPRF surrogate blends. A semi-decoupling approach was used together with species and reaction lumping to obtain a reduced kinetic model. The model was widely validated against experimental data including shock tube ignition delay times and premixed laminar flame speeds. Finally, the model was utilized to simulate the combustion of a low reactivity gasoline fuel under partially premixed combustion conditions.

  16. Guanine polynucleotides are self-antigens for human natural autoantibodies and are significantly reduced in the human genome

    Science.gov (United States)

    Fattal, Ittai; Shental, Noam; Ben-Dor, Shifra; Molad, Yair; Gabrielli, Armando; Pokroy-Shapira, Elisheva; Oren, Shirly; Livneh, Avi; Langevitz, Pnina; Zandman-Goddard, Gisele; Sarig, Ofer; Margalit, Raanan; Gafter, Uzi; Domany, Eytan; Cohen, Irun R

    2015-01-01

    In the course of investigating anti-DNA autoantibodies, we examined IgM and IgG antibodies to poly-G and other oligonucleotides in the sera of healthy persons and those diagnosed with systemic lupus erythematosus (SLE), scleroderma (SSc), or pemphigus vulgaris (PV); we used an antigen microarray and informatic analysis. We now report that all of the 135 humans studied, irrespective of health or autoimmune disease, manifested relatively high amounts of IgG antibodies binding to the 20-mer G oligonucleotide (G20); no participants entirely lacked this reactivity. IgG antibodies to homo-nucleotides A20, C20 or T20 were present only in the sera of SLE patients who were positive for antibodies to dsDNA. The prevalence of anti-G20 antibodies led us to survey human, mouse and Drosophila melanogaster (fruit fly) genomes for runs of T20 and G20 or more: runs of T20 appear > 170 000 times compared with only 93 runs of G20 or more in the human genome; of these runs, 40 were close to brain-associated genes. Mouse and fruit fly genomes showed significantly lower T20/G20 ratios than did human genomes. Moreover, sera from both healthy and SLE mice contained relatively little or no anti-G20 antibodies; so natural anti-G20 antibodies appear to be characteristic of humans. These unexpected observations invite investigation of the immune functions of anti-G20 antibodies in human health and disease and of runs of G20 in the human genome. PMID:26227667

  17. Human casualties in earthquakes: Modelling and mitigation

    Science.gov (United States)

    Spence, R.J.S.; So, E.K.M.

    2011-01-01

    Earthquake risk modelling is needed for the planning of post-event emergency operations, for the development of insurance schemes, for the planning of mitigation measures in the existing building stock, and for the development of appropriate building regulations; in all of these applications estimates of casualty numbers are essential. But there are many questions about casualty estimation which are still poorly understood. These questions relate to the causes and nature of the injuries and deaths, and the extent to which they can be quantified. This paper looks at the evidence on these questions from recent studies. It then reviews casualty estimation models available, and finally compares the performance of some casualty models in making rapid post-event casualty estimates in recent earthquakes.

  18. Stress-reducing preventive maintenance model for a unit under stressful environment

    International Nuclear Information System (INIS)

    Park, J.H.; Chang, Woojin; Lie, C.H.

    2012-01-01

    We develop a preventive maintenance (PM) model for a unit operated under stressful environment. The PM model in this paper consists of a failure rate model and two cost models to determine the optimal PM scheduling which minimizes a cost rate. The assumption for the proposed model is that stressful environment accelerates the failure of the unit and periodic maintenances reduce stress from outside. The failure rate model handles the maintenance effect of PM using improvement and stress factors. The cost models are categorized into two failure recognition cases: immediate failure recognition and periodic failure detection. The optimal PM scheduling is obtained by considering the trade-off between the related cost and the lifetime of a unit in our model setting. The practical usage of our proposed model is tested through a numerical example.

  19. Generating Phenotypical Erroneous Human Behavior to Evaluate Human-automation Interaction Using Model Checking.

    Science.gov (United States)

    Bolton, Matthew L; Bass, Ellen J; Siminiceanu, Radu I

    2012-11-01

    Breakdowns in complex systems often occur as a result of system elements interacting in unanticipated ways. In systems with human operators, human-automation interaction associated with both normative and erroneous human behavior can contribute to such failures. Model-driven design and analysis techniques provide engineers with formal methods tools and techniques capable of evaluating how human behavior can contribute to system failures. This paper presents a novel method for automatically generating task analytic models encompassing both normative and erroneous human behavior from normative task models. The generated erroneous behavior is capable of replicating Hollnagel's zero-order phenotypes of erroneous action for omissions, jumps, repetitions, and intrusions. Multiple phenotypical acts can occur in sequence, thus allowing for the generation of higher order phenotypes. The task behavior model pattern capable of generating erroneous behavior can be integrated into a formal system model so that system safety properties can be formally verified with a model checker. This allows analysts to prove that a human-automation interactive system (as represented by the model) will or will not satisfy safety properties with both normative and generated erroneous human behavior. We present benchmarks related to the size of the statespace and verification time of models to show how the erroneous human behavior generation process scales. We demonstrate the method with a case study: the operation of a radiation therapy machine. A potential problem resulting from a generated erroneous human action is discovered. A design intervention is presented which prevents this problem from occurring. We discuss how our method could be used to evaluate larger applications and recommend future paths of development.

  20. Generating Phenotypical Erroneous Human Behavior to Evaluate Human-automation Interaction Using Model Checking

    Science.gov (United States)

    Bolton, Matthew L.; Bass, Ellen J.; Siminiceanu, Radu I.

    2012-01-01

    Breakdowns in complex systems often occur as a result of system elements interacting in unanticipated ways. In systems with human operators, human-automation interaction associated with both normative and erroneous human behavior can contribute to such failures. Model-driven design and analysis techniques provide engineers with formal methods tools and techniques capable of evaluating how human behavior can contribute to system failures. This paper presents a novel method for automatically generating task analytic models encompassing both normative and erroneous human behavior from normative task models. The generated erroneous behavior is capable of replicating Hollnagel’s zero-order phenotypes of erroneous action for omissions, jumps, repetitions, and intrusions. Multiple phenotypical acts can occur in sequence, thus allowing for the generation of higher order phenotypes. The task behavior model pattern capable of generating erroneous behavior can be integrated into a formal system model so that system safety properties can be formally verified with a model checker. This allows analysts to prove that a human-automation interactive system (as represented by the model) will or will not satisfy safety properties with both normative and generated erroneous human behavior. We present benchmarks related to the size of the statespace and verification time of models to show how the erroneous human behavior generation process scales. We demonstrate the method with a case study: the operation of a radiation therapy machine. A potential problem resulting from a generated erroneous human action is discovered. A design intervention is presented which prevents this problem from occurring. We discuss how our method could be used to evaluate larger applications and recommend future paths of development. PMID:23105914

  1. A model for the dynamics of human weight cycling

    Indian Academy of Sciences (India)

    A simple mathematical model for weight cycling is presented. The model is based on a feedback of psychological nature by which a subject decides to reduce dietary intake once a threshold weight is exceeded. The analysis of the model indicates that sustained oscillations in body weight occur in a parameter range ...

  2. A reduced fidelity model for the rotary chemical looping combustion reactor

    KAUST Repository

    Iloeje, Chukwunwike O.

    2017-01-11

    The rotary chemical looping combustion reactor has great potential for efficient integration with CO capture-enabled energy conversion systems. In earlier studies, we described a one-dimensional rotary reactor model, and used it to demonstrate the feasibility of continuous reactor operation. Though this detailed model provides a high resolution representation of the rotary reactor performance, it is too computationally expensive for studies that require multiple model evaluations. Specifically, it is not ideal for system-level studies where the reactor is a single component in an energy conversion system. In this study, we present a reduced fidelity model (RFM) of the rotary reactor that reduces computational cost and determines an optimal combination of variables that satisfy reactor design requirements. Simulation results for copper, nickel and iron-based oxygen carriers show a four-order of magnitude reduction in simulation time, and reasonable prediction accuracy. Deviations from the detailed reference model predictions range from 3% to 20%, depending on oxygen carrier type and operating conditions. This study also demonstrates how the reduced model can be modified to deal with both optimization and design oriented problems. A parametric study using the reduced model is then applied to analyze the sensitivity of the optimal reactor design to changes in selected operating and kinetic parameters. These studies show that temperature and activation energy have a greater impact on optimal geometry than parameters like pressure or feed fuel fraction for the selected oxygen carrier materials.

  3. Reduced-order modeling of piezoelectric energy harvesters with nonlinear circuits under complex conditions

    Science.gov (United States)

    Xiang, Hong-Jun; Zhang, Zhi-Wei; Shi, Zhi-Fei; Li, Hong

    2018-04-01

    A fully coupled modeling approach is developed for piezoelectric energy harvesters in this work based on the use of available robust finite element packages and efficient reducing order modeling techniques. At first, the harvester is modeled using finite element packages. The dynamic equilibrium equations of harvesters are rebuilt by extracting system matrices from the finite element model using built-in commands without any additional tools. A Krylov subspace-based scheme is then applied to obtain a reduced-order model for improving simulation efficiency but preserving the key features of harvesters. Co-simulation of the reduced-order model with nonlinear energy harvesting circuits is achieved in a system level. Several examples in both cases of harmonic response and transient response analysis are conducted to validate the present approach. The proposed approach allows to improve the simulation efficiency by several orders of magnitude. Moreover, the parameters used in the equivalent circuit model can be conveniently obtained by the proposed eigenvector-based model order reduction technique. More importantly, this work establishes a methodology for modeling of piezoelectric energy harvesters with any complicated mechanical geometries and nonlinear circuits. The input load may be more complex also. The method can be employed by harvester designers to optimal mechanical structures or by circuit designers to develop novel energy harvesting circuits.

  4. Modeling human disease using organotypic cultures

    DEFF Research Database (Denmark)

    Schweiger, Pawel J; Jensen, Kim B

    2016-01-01

    Reliable disease models are needed in order to improve quality of healthcare. This includes gaining better understanding of disease mechanisms, developing new therapeutic interventions and personalizing treatment. Up-to-date, the majority of our knowledge about disease states comes from in vivo...

  5. A computational model of human auditory signal processing and perception

    OpenAIRE

    Jepsen, Morten Løve; Ewert, Stephan D.; Dau, Torsten

    2008-01-01

    A model of computational auditory signal-processing and perception that accounts for various aspects of simultaneous and nonsimultaneous masking in human listeners is presented. The model is based on the modulation filterbank model described by Dau et al. [J. Acoust. Soc. Am. 102, 2892 (1997)] but includes major changes at the peripheral and more central stages of processing. The model contains outer- and middle-ear transformations, a nonlinear basilar-membrane processing stage, a hair-cell t...

  6. Building a Shared Definitional Model of Long Duration Human Spaceflight

    Science.gov (United States)

    Arias, Diana; Orr, Martin; Whitmire, Alexandra; Leveton, Lauren; Sandoval, Luis

    2012-01-01

    Objective: To establish the need for a shared definitional model of long duration human spaceflight, that would provide a framework and vision to facilitate communication, research and practice In 1956, on the eve of human space travel, Hubertus Strughold first proposed a "simple classification of the present and future stages of manned flight" that identified key factors, risks and developmental stages for the evolutionary journey ahead. As we look to new destinations, we need a current shared working definitional model of long duration human space flight to help guide our path. Here we describe our preliminary findings and outline potential approaches for the future development of a definition and broader classification system

  7. Audiovisual Material as Educational Innovation Strategy to Reduce Anxiety Response in Students of Human Anatomy

    Science.gov (United States)

    Casado, Maria Isabel; Castano, Gloria; Arraez-Aybar, Luis Alfonso

    2012-01-01

    This study presents the design, effect and utility of using audiovisual material containing real images of dissected human cadavers as an innovative educational strategy (IES) in the teaching of Human Anatomy. The goal is to familiarize students with the practice of dissection and to transmit the importance and necessity of this discipline, while…

  8. Human Responding on Random-Interval Schedules of Response-Cost Punishment: The Role of Reduced Reinforcement Density

    Science.gov (United States)

    Pietras, Cynthia J.; Brandt, Andrew E.; Searcy, Gabriel D.

    2010-01-01

    An experiment with adult humans investigated the effects of response-contingent money loss (response-cost punishment) on monetary-reinforced responding. A yoked-control procedure was used to separate the effects on responding of the response-cost contingency from the effects of reduced reinforcement density. Eight adults pressed buttons for money…

  9. Artemisinin-based combination therapy does not measurably reduce human infectiousness to vectors in a setting of intense malaria transmission

    NARCIS (Netherlands)

    Huho, Bernadette J.; Killeen, Gerard F.; Ferguson, Heather M.; Tami, Adriana; Lengeler, Christian; Charlwood, J. Derek; Kihonda, Aniset; Kihonda, Japhet; Kachur, S. Patrick; Smith, Thomas A.; Abdulla, Salim M. K.

    2012-01-01

    Background: Artemisinin-based combination therapy (ACT) for treating malaria has activity against immature gametocytes. In theory, this property may complement the effect of terminating otherwise lengthy malaria infections and reducing the parasite reservoir in the human population that can infect

  10. Humanized in vivo Model for Autoimmune Diabetes

    Science.gov (United States)

    2010-05-07

    guinea - pig polyclonal anti-insulin (1:100 dilution, Abcam Ab7842-500, Cambridge, MA) and a secondary goat anti- guinea - pig Alexa-fluor 568 (1:100 dilu...which is reported to accelerate experimental autoimmune encephalomyelitis (a mouse model of multiple sclerosis). Our reasoning was that, as T cells...HL, Sobel RA, Kuchroo VK. IL-10 is critical in the regulation of autoimmune encephalomyelitis as demonstrated by studies of IL-10- and IL-4

  11. Monte Carlo modeling of human tooth optical coherence tomography imaging

    International Nuclear Information System (INIS)

    Shi, Boya; Meng, Zhuo; Wang, Longzhi; Liu, Tiegen

    2013-01-01

    We present a Monte Carlo model for optical coherence tomography (OCT) imaging of human tooth. The model is implemented by combining the simulation of a Gaussian beam with simulation for photon propagation in a two-layer human tooth model with non-parallel surfaces through a Monte Carlo method. The geometry and the optical parameters of the human tooth model are chosen on the basis of the experimental OCT images. The results show that the simulated OCT images are qualitatively consistent with the experimental ones. Using the model, we demonstrate the following: firstly, two types of photons contribute to the information of morphological features and noise in the OCT image of a human tooth, respectively. Secondly, the critical imaging depth of the tooth model is obtained, and it is found to decrease significantly with increasing mineral loss, simulated as different enamel scattering coefficients. Finally, the best focus position is located below and close to the dental surface by analysis of the effect of focus positions on the OCT signal and critical imaging depth. We anticipate that this modeling will become a powerful and accurate tool for a preliminary numerical study of the OCT technique on diseases of dental hard tissue in human teeth. (paper)

  12. Monte Carlo modeling of human tooth optical coherence tomography imaging

    Science.gov (United States)

    Shi, Boya; Meng, Zhuo; Wang, Longzhi; Liu, Tiegen

    2013-07-01

    We present a Monte Carlo model for optical coherence tomography (OCT) imaging of human tooth. The model is implemented by combining the simulation of a Gaussian beam with simulation for photon propagation in a two-layer human tooth model with non-parallel surfaces through a Monte Carlo method. The geometry and the optical parameters of the human tooth model are chosen on the basis of the experimental OCT images. The results show that the simulated OCT images are qualitatively consistent with the experimental ones. Using the model, we demonstrate the following: firstly, two types of photons contribute to the information of morphological features and noise in the OCT image of a human tooth, respectively. Secondly, the critical imaging depth of the tooth model is obtained, and it is found to decrease significantly with increasing mineral loss, simulated as different enamel scattering coefficients. Finally, the best focus position is located below and close to the dental surface by analysis of the effect of focus positions on the OCT signal and critical imaging depth. We anticipate that this modeling will become a powerful and accurate tool for a preliminary numerical study of the OCT technique on diseases of dental hard tissue in human teeth.

  13. Strategies for Reduced-Order Models in Uncertainty Quantification of Complex Turbulent Dynamical Systems

    Science.gov (United States)

    Qi, Di

    Turbulent dynamical systems are ubiquitous in science and engineering. Uncertainty quantification (UQ) in turbulent dynamical systems is a grand challenge where the goal is to obtain statistical estimates for key physical quantities. In the development of a proper UQ scheme for systems characterized by both a high-dimensional phase space and a large number of instabilities, significant model errors compared with the true natural signal are always unavoidable due to both the imperfect understanding of the underlying physical processes and the limited computational resources available. One central issue in contemporary research is the development of a systematic methodology for reduced order models that can recover the crucial features both with model fidelity in statistical equilibrium and with model sensitivity in response to perturbations. In the first part, we discuss a general mathematical framework to construct statistically accurate reduced-order models that have skill in capturing the statistical variability in the principal directions of a general class of complex systems with quadratic nonlinearity. A systematic hierarchy of simple statistical closure schemes, which are built through new global statistical energy conservation principles combined with statistical equilibrium fidelity, are designed and tested for UQ of these problems. Second, the capacity of imperfect low-order stochastic approximations to model extreme events in a passive scalar field advected by turbulent flows is investigated. The effects in complicated flow systems are considered including strong nonlinear and non-Gaussian interactions, and much simpler and cheaper imperfect models with model error are constructed to capture the crucial statistical features in the stationary tracer field. Several mathematical ideas are introduced to improve the prediction skill of the imperfect reduced-order models. Most importantly, empirical information theory and statistical linear response theory are

  14. Reduced models of doubly fed induction generator system for wind turbine simulations

    DEFF Research Database (Denmark)

    Sørensen, Poul Ejnar; Hansen, Anca Daniela; Lund, Torsten

    2005-01-01

    This article compares three reduced models with a detailed model of a doubly fed induction generator system for wind turbine applications. The comparisons are based on simulations only. The main idea is to provide reduced generator models which are appropriate to simulate normal wind turbine...... fed induction generator system is very well represented by the dynamics due to the generator inertia and the generator control system, whereas the electromagnetic characteristics of the generator can be represented by the steady state relations. The parameters for the proposed models are derived from...... parameters typically available from the generator data sheet and from the controller settings. Thus the models are simple to apply in any case where the generator data sheet is available....

  15. A POD reduced order unstructured mesh ocean modelling method for moderate Reynolds number flows

    Science.gov (United States)

    Fang, F.; Pain, C. C.; Navon, I. M.; Gorman, G. J.; Piggott, M. D.; Allison, P. A.; Farrell, P. E.; Goddard, A. J. H.

    Herein a new approach to enhance the accuracy of a novel Proper Orthogonal Decomposition (POD) model applied to moderate Reynolds number flows (of the type typically encountered in ocean models) is presented. This approach develops the POD model of Fang et al. [Fang, F., Pain, C.C., Navon, I.M., Piggott, M.D., Gorman, G.J., Allison, P., Goddard, A.J.H., 2008. Reduced-order modelling of an adaptive mesh ocean model. International Journal for Numerical Methods in Fluids. doi:10.1002/fld.1841] used in conjunction with the Imperial College Ocean Model (ICOM), an adaptive, non-hydrostatic finite element model. Both the velocity and vorticity results of the POD reduced order model (ROM) exhibit an overall good agreement with those obtained from the full model. The accuracy of the POD-Galerkin model with the use of adaptive meshes is first evaluated using the Munk gyre flow test case with Reynolds numbers ranging between 400 and 2000. POD models using the L2 norm become oscillatory when the Reynolds number exceeds Re=400. This is because the low-order truncation of the POD basis inhibits generally all the transfers between the large and the small (unresolved) scales of the fluid flow. Accuracy is improved by using the H1 POD projector in preference to the L2 POD projector. The POD bases are constructed by incorporating gradients as well as function values in the H1 Sobolev norm. The accuracy of numerical results is further enhanced by increasing the number of snapshots and POD bases. Error estimation was used to assess the effect of truncation (involved in the POD-Galerkin approach) when adaptive meshes are used in conjunction with POD/ROM. The RMSE of velocity results between the full model and POD-Galerkin model is reduced by as much as 50% by using the H1 norm and increasing the number of snapshots and POD bases.

  16. A model for assessing human cognitive reliability in PRA studies

    International Nuclear Information System (INIS)

    Hannaman, G.W.; Spurgin, A.J.; Lukic, Y.

    1985-01-01

    This paper summarizes the status of a research project sponsored by EPRI as part of the Probabilistic Risk Assessment (PRA) technology improvement program and conducted by NUS Corporation to develop a model of Human Cognitive Reliability (HCR). The model was synthesized from features identified in a review of existing models. The model development was based on the hypothesis that the key factors affecting crew response times are separable. The inputs to the model consist of key parameters the values of which can be determined by PRA analysts for each accident situation being assessed. The output is a set of curves which represent the probability of control room crew non-response as a function of time for different conditions affecting their performance. The non-response probability is then a contributor to the overall non-success of operating crews to achieve a functional objective identified in the PRA study. Simulator data and some small scale tests were utilized to illustrate the calibration of interim HCR model coefficients for different types of cognitive processing since the data were sparse. The model can potentially help PRA analysts make human reliability assessments more explicit. The model incorporates concepts from psychological models of human cognitive behavior, information from current collections of human reliability data sources and crew response time data from simulator training exercises

  17. Lumped parametric model of the human ear for sound transmission.

    Science.gov (United States)

    Feng, Bin; Gan, Rong Z

    2004-09-01

    A lumped parametric model of the human auditoria peripherals consisting of six masses suspended with six springs and ten dashpots was proposed. This model will provide the quantitative basis for the construction of a physical model of the human middle ear. The lumped model parameters were first identified using published anatomical data, and then determined through a parameter optimization process. The transfer function of the middle ear obtained from human temporal bone experiments with laser Doppler interferometers was used for creating the target function during the optimization process. It was found that, among 14 spring and dashpot parameters, there were five parameters which had pronounced effects on the dynamic behaviors of the model. The detailed discussion on the sensitivity of those parameters was provided with appropriate applications for sound transmission in the ear. We expect that the methods for characterizing the lumped model of the human ear and the model parameters will be useful for theoretical modeling of the ear function and construction of the ear physical model.

  18. Approaches for Reduced Order Modeling of Electrically Actuated von Karman Microplates

    KAUST Repository

    Saghir, Shahid

    2016-07-25

    This article presents and compares different approaches to develop reduced order models for the nonlinear von Karman rectangular microplates actuated by nonlinear electrostatic forces. The reduced-order models aim to investigate the static and dynamic behavior of the plate under small and large actuation forces. A fully clamped microplate is considered. Different types of basis functions are used in conjunction with the Galerkin method to discretize the governing equations. First we investigate the convergence with the number of modes retained in the model. Then for validation purpose, a comparison of the static results is made with the results calculated by a nonlinear finite element model. The linear eigenvalue problem for the plate under the electrostatic force is solved for a wide range of voltages up to pull-in. Results among the various reduced-order modes are compared and are also validated by comparing to results of the finite-element model. Further, the reduced order models are employed to capture the forced dynamic response of the microplate under small and large vibration amplitudes. Comparison of the different approaches are made for this case. Keywords: electrically actuated microplates, static analysis, dynamics of microplates, diaphragm vibration, large amplitude vibrations, nonlinear dynamics

  19. Identifying the Reducing Resistance to Change Phase in an Organizational Change Model

    OpenAIRE

    Daniela Bradutanu

    2012-01-01

    In this article we examine where in an organizational change process it is better to place the reducing resistance to change phase, so that employees would accept the new changes easier and not manifest too much resistance. After analyzing twelve organizational change models we have concluded that the place of the reducing resistance to change phase in an organizational change process is not the same, it being modified according to the type of change. The results of this study are helpful for...

  20. The i-V curve characteristics of burner-stabilized premixed flames: detailed and reduced models

    KAUST Repository

    Han, Jie

    2016-07-17

    The i-V curve describes the current drawn from a flame as a function of the voltage difference applied across the reaction zone. Since combustion diagnostics and flame control strategies based on electric fields depend on the amount of current drawn from flames, there is significant interest in modeling and understanding i-V curves. We implement and apply a detailed model for the simulation of the production and transport of ions and electrons in one-dimensional premixed flames. An analytical reduced model is developed based on the detailed one, and analytical expressions are used to gain insight into the characteristics of the i-Vcurve for various flame configurations. In order for the reduced model to capture the spatial distribution of the electric field accurately, the concept of a dead zone region, where voltage is constant, is introduced, and a suitable closure for the spatial extent of the dead zone is proposed and validated. The results from the reduced modeling framework are found to be in good agreement with those from the detailed simulations. The saturation voltage is found to depend significantly on the flame location relative to the electrodes, and on the sign of the voltage difference applied. Furthermore, at sub-saturation conditions, the current is shown to increase linearly or quadratically with the applied voltage, depending on the flame location. These limiting behaviors exhibited by the reduced model elucidate the features of i-V curves observed experimentally. The reduced model relies on the existence of a thin layer where charges are produced, corresponding to the reaction zone of a flame. Consequently, the analytical model we propose is not limited to the study of premixed flames, and may be applied easily to others configurations, e.g.~nonpremixed counterflow flames.