WorldWideScience

Sample records for models including mice

  1. Modelling diabetic nephropathy in mice.

    Science.gov (United States)

    Azushima, Kengo; Gurley, Susan B; Coffman, Thomas M

    2018-01-01

    Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in the developed world. Accordingly, an urgent need exists for new, curative treatments as well as for biomarkers to stratify risk of DN among individuals with diabetes mellitus. A barrier to progress in these areas has been a lack of animal models that faithfully replicate the main features of human DN. Such models could be used to define the pathogenesis, identify drug targets and test new therapies. Owing to their tractability for genetic manipulation, mice are widely used to model human diseases, including DN. Questions have been raised, however, about the general utility of mouse models in human drug discovery. Standard mouse models of diabetes typically manifest only modest kidney abnormalities, whereas accelerated models, induced by superimposing genetic stressors, recapitulate key features of human DN. Incorporation of systems biology approaches and emerging data from genomics and metabolomics studies should enable further model refinement. Here, we discuss the current status of mouse models for DN, their limitations and opportunities for improvement. We emphasize that future efforts should focus on generating robust models that reproduce the major clinical and molecular phenotypes of human DN.

  2. SEEPAGE MODEL FOR PA INCLUDING DRIFT COLLAPSE

    International Nuclear Information System (INIS)

    C. Tsang

    2004-01-01

    The purpose of this report is to document the predictions and analyses performed using the seepage model for performance assessment (SMPA) for both the Topopah Spring middle nonlithophysal (Tptpmn) and lower lithophysal (Tptpll) lithostratigraphic units at Yucca Mountain, Nevada. Look-up tables of seepage flow rates into a drift (and their uncertainty) are generated by performing numerical simulations with the seepage model for many combinations of the three most important seepage-relevant parameters: the fracture permeability, the capillary-strength parameter 1/a, and the percolation flux. The percolation flux values chosen take into account flow focusing effects, which are evaluated based on a flow-focusing model. Moreover, multiple realizations of the underlying stochastic permeability field are conducted. Selected sensitivity studies are performed, including the effects of an alternative drift geometry representing a partially collapsed drift from an independent drift-degradation analysis (BSC 2004 [DIRS 166107]). The intended purpose of the seepage model is to provide results of drift-scale seepage rates under a series of parameters and scenarios in support of the Total System Performance Assessment for License Application (TSPA-LA). The SMPA is intended for the evaluation of drift-scale seepage rates under the full range of parameter values for three parameters found to be key (fracture permeability, the van Genuchten 1/a parameter, and percolation flux) and drift degradation shape scenarios in support of the TSPA-LA during the period of compliance for postclosure performance [Technical Work Plan for: Performance Assessment Unsaturated Zone (BSC 2002 [DIRS 160819], Section I-4-2-1)]. The flow-focusing model in the Topopah Spring welded (TSw) unit is intended to provide an estimate of flow focusing factors (FFFs) that (1) bridge the gap between the mountain-scale and drift-scale models, and (2) account for variability in local percolation flux due to

  3. Grand unified models including extra Z bosons

    International Nuclear Information System (INIS)

    Li Tiezhong

    1989-01-01

    The grand unified theories (GUT) of the simple Lie groups including extra Z bosons are discussed. Under authors's hypothesis there are only SU 5+m SO 6+4n and E 6 groups. The general discussion of SU 5+m is given, then the SU 6 and SU 7 are considered. In SU 6 the 15+6 * +6 * fermion representations are used, which are not same as others in fermion content, Yukawa coupling and broken scales. A conception of clans of particles, which are not families, is suggested. These clans consist of extra Z bosons and the corresponding fermions of the scale. The all of fermions in the clans are down quarks except for the standard model which consists of Z bosons and 15 fermions, therefore, the spectrum of the hadrons which are composed of these down quarks are different from hadrons at present

  4. An Integrated Biochemistry Laboratory, Including Molecular Modeling

    Science.gov (United States)

    Hall, Adele J. Wolfson Mona L.; Branham, Thomas R.

    1996-11-01

    ) experience with methods of protein purification; (iii) incorporation of appropriate controls into experiments; (iv) use of basic statistics in data analysis; (v) writing papers and grant proposals in accepted scientific style; (vi) peer review; (vii) oral presentation of results and proposals; and (viii) introduction to molecular modeling. Figure 1 illustrates the modular nature of the lab curriculum. Elements from each of the exercises can be separated and treated as stand-alone exercises, or combined into short or long projects. We have been able to offer the opportunity to use sophisticated molecular modeling in the final module through funding from an NSF-ILI grant. However, many of the benefits of the research proposal can be achieved with other computer programs, or even by literature survey alone. Figure 1.Design of project-based biochemistry laboratory. Modules (projects, or portions of projects) are indicated as boxes. Each of these can be treated independently, or used as part of a larger project. Solid lines indicate some suggested paths from one module to the next. The skills and knowledge required for protein purification and design are developed in three units: (i) an introduction to critical assays needed to monitor degree of purification, including an evaluation of assay parameters; (ii) partial purification by ion-exchange techniques; and (iii) preparation of a grant proposal on protein design by mutagenesis. Brief descriptions of each of these units follow, with experimental details of each project at the end of this paper. Assays for Lysozyme Activity and Protein Concentration (4 weeks) The assays mastered during the first unit are a necessary tool for determining the purity of the enzyme during the second unit on purification by ion exchange. These assays allow an introduction to the concept of specific activity (units of enzyme activity per milligram of total protein) as a measure of purity. In this first sequence, students learn a turbidimetric assay

  5. Seepage Model for PA Including Drift Collapse

    International Nuclear Information System (INIS)

    Li, G.; Tsang, C.

    2000-01-01

    The purpose of this Analysis/Model Report (AMR) is to document the predictions and analysis performed using the Seepage Model for Performance Assessment (PA) and the Disturbed Drift Seepage Submodel for both the Topopah Spring middle nonlithophysal and lower lithophysal lithostratigraphic units at Yucca Mountain. These results will be used by PA to develop the probability distribution of water seepage into waste-emplacement drifts at Yucca Mountain, Nevada, as part of the evaluation of the long term performance of the potential repository. This AMR is in accordance with the ''Technical Work Plan for Unsaturated Zone (UZ) Flow and Transport Process Model Report'' (CRWMS M andO 2000 [153447]). This purpose is accomplished by performing numerical simulations with stochastic representations of hydrological properties, using the Seepage Model for PA, and evaluating the effects of an alternative drift geometry representing a partially collapsed drift using the Disturbed Drift Seepage Submodel. Seepage of water into waste-emplacement drifts is considered one of the principal factors having the greatest impact of long-term safety of the repository system (CRWMS M andO 2000 [153225], Table 4-1). This AMR supports the analysis and simulation that are used by PA to develop the probability distribution of water seepage into drift, and is therefore a model of primary (Level 1) importance (AP-3.15Q, ''Managing Technical Product Inputs''). The intended purpose of the Seepage Model for PA is to support: (1) PA; (2) Abstraction of Drift-Scale Seepage; and (3) Unsaturated Zone (UZ) Flow and Transport Process Model Report (PMR). Seepage into drifts is evaluated by applying numerical models with stochastic representations of hydrological properties and performing flow simulations with multiple realizations of the permeability field around the drift. The Seepage Model for PA uses the distribution of permeabilities derived from air injection testing in niches and in the cross drift to

  6. Seepage Model for PA Including Dift Collapse

    Energy Technology Data Exchange (ETDEWEB)

    G. Li; C. Tsang

    2000-12-20

    The purpose of this Analysis/Model Report (AMR) is to document the predictions and analysis performed using the Seepage Model for Performance Assessment (PA) and the Disturbed Drift Seepage Submodel for both the Topopah Spring middle nonlithophysal and lower lithophysal lithostratigraphic units at Yucca Mountain. These results will be used by PA to develop the probability distribution of water seepage into waste-emplacement drifts at Yucca Mountain, Nevada, as part of the evaluation of the long term performance of the potential repository. This AMR is in accordance with the ''Technical Work Plan for Unsaturated Zone (UZ) Flow and Transport Process Model Report'' (CRWMS M&O 2000 [153447]). This purpose is accomplished by performing numerical simulations with stochastic representations of hydrological properties, using the Seepage Model for PA, and evaluating the effects of an alternative drift geometry representing a partially collapsed drift using the Disturbed Drift Seepage Submodel. Seepage of water into waste-emplacement drifts is considered one of the principal factors having the greatest impact of long-term safety of the repository system (CRWMS M&O 2000 [153225], Table 4-1). This AMR supports the analysis and simulation that are used by PA to develop the probability distribution of water seepage into drift, and is therefore a model of primary (Level 1) importance (AP-3.15Q, ''Managing Technical Product Inputs''). The intended purpose of the Seepage Model for PA is to support: (1) PA; (2) Abstraction of Drift-Scale Seepage; and (3) Unsaturated Zone (UZ) Flow and Transport Process Model Report (PMR). Seepage into drifts is evaluated by applying numerical models with stochastic representations of hydrological properties and performing flow simulations with multiple realizations of the permeability field around the drift. The Seepage Model for PA uses the distribution of permeabilities derived from air injection testing in

  7. Enhanced battery model including temperature effects

    NARCIS (Netherlands)

    Rosca, B.; Wilkins, S.

    2013-01-01

    Within electric and hybrid vehicles, batteries are used to provide/buffer the energy required for driving. However, battery performance varies throughout the temperature range specific to automotive applications, and as such, models that describe this behaviour are required. This paper presents a

  8. Barbering in mice: a model for trichotillomania

    OpenAIRE

    Kurien, T; Gross, Tim; Scofield, R Hal

    2005-01-01

    Barbering (excessive grooming causing hair loss) in mice resembles trichotillomania (uncontrollable hair pulling) in humans in several respects and may be a useful model of trichotillomania, especially for investigating the complex genetic and environmental interactions

  9. Olkiluoto surface hydrological modelling: Update 2012 including salt transport modelling

    International Nuclear Information System (INIS)

    Karvonen, T.

    2013-11-01

    Posiva Oy is responsible for implementing a final disposal program for spent nuclear fuel of its owners Teollisuuden Voima Oyj and Fortum Power and Heat Oy. The spent nuclear fuel is planned to be disposed at a depth of about 400-450 meters in the crystalline bedrock at the Olkiluoto site. Leakages located at or close to spent fuel repository may give rise to the upconing of deep highly saline groundwater and this is a concern with regard to the performance of the tunnel backfill material after the closure of the tunnels. Therefore a salt transport sub-model was added to the Olkiluoto surface hydrological model (SHYD). The other improvements include update of the particle tracking algorithm and possibility to estimate the influence of open drillholes in a case where overpressure in inflatable packers decreases causing a hydraulic short-circuit between hydrogeological zones HZ19 and HZ20 along the drillhole. Four new hydrogeological zones HZ056, HZ146, BFZ100 and HZ039 were added to the model. In addition, zones HZ20A and HZ20B intersect with each other in the new structure model, which influences salinity upconing caused by leakages in shafts. The aim of the modelling of long-term influence of ONKALO, shafts and repository tunnels provide computational results that can be used to suggest limits for allowed leakages. The model input data included all the existing leakages into ONKALO (35-38 l/min) and shafts in the present day conditions. The influence of shafts was computed using eight different values for total shaft leakage: 5, 11, 20, 30, 40, 50, 60 and 70 l/min. The selection of the leakage criteria for shafts was influenced by the fact that upconing of saline water increases TDS-values close to the repository areas although HZ20B does not intersect any deposition tunnels. The total limit for all leakages was suggested to be 120 l/min. The limit for HZ20 zones was proposed to be 40 l/min: about 5 l/min the present day leakages to access tunnel, 25 l/min from

  10. HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation.

    Directory of Open Access Journals (Sweden)

    Jeffrey B Carroll

    Full Text Available The HTT CAG expansion mutation causes Huntington's Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue, using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219 in the striatum to 12% (25/212 in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219 of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224 in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant HdhQ111 striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and

  11. Dynamic hysteresis modeling including skin effect using diffusion equation model

    Energy Technology Data Exchange (ETDEWEB)

    Hamada, Souad, E-mail: souadhamada@yahoo.fr [LSP-IE: Research Laboratory, Electrical Engineering Department, University of Batna, 05000 Batna (Algeria); Louai, Fatima Zohra, E-mail: fz_louai@yahoo.com [LSP-IE: Research Laboratory, Electrical Engineering Department, University of Batna, 05000 Batna (Algeria); Nait-Said, Nasreddine, E-mail: n_naitsaid@yahoo.com [LSP-IE: Research Laboratory, Electrical Engineering Department, University of Batna, 05000 Batna (Algeria); Benabou, Abdelkader, E-mail: Abdelkader.Benabou@univ-lille1.fr [L2EP, Université de Lille1, 59655 Villeneuve d’Ascq (France)

    2016-07-15

    An improved dynamic hysteresis model is proposed for the prediction of hysteresis loop of electrical steel up to mean frequencies, taking into account the skin effect. In previous works, the analytical solution of the diffusion equation for low frequency (DELF) was coupled with the inverse static Jiles-Atherton (JA) model in order to represent the hysteresis behavior for a lamination. In the present paper, this approach is improved to ensure the reproducibility of measured hysteresis loops at mean frequency. The results of simulation are compared with the experimental ones. The selected results for frequencies 50 Hz, 100 Hz, 200 Hz and 400 Hz are presented and discussed.

  12. Stochastic modelling of two-phase flows including phase change

    International Nuclear Information System (INIS)

    Hurisse, O.; Minier, J.P.

    2011-01-01

    Stochastic modelling has already been developed and applied for single-phase flows and incompressible two-phase flows. In this article, we propose an extension of this modelling approach to two-phase flows including phase change (e.g. for steam-water flows). Two aspects are emphasised: a stochastic model accounting for phase transition and a modelling constraint which arises from volume conservation. To illustrate the whole approach, some remarks are eventually proposed for two-fluid models. (authors)

  13. The elicitation step of nickel allergy is promoted in mice by microbe-related substances, including some from oral bacteria.

    Science.gov (United States)

    Huang, Ling; Kinbara, Masayuki; Funayama, Hiromi; Takada, Haruhiko; Sugawara, Shunji; Endo, Yasuo

    2011-11-01

    Microbial components activate the host's innate immunity via interactions with molecules including TLRs and NODs. We previously reported that in mice (i) Escherichia coli lipopolysaccharide (LPS; TLR4 agonist) promotes Ni-allergy even in T-cell-deficient mice, (ii) E. coli LPS reduces the minimum allergy-inducing concentrations of Ni at both the sensitization and elicitation steps, and (iii) various microbe-related substances promote sensitization to Ni. Here, we examined the effects of microbe-related substances at the elicitation step. Mice (except for TLR4-mutated C3H/HeJ mice) were sensitized to Ni by intraperitoneal injection of NiCl(2) + E. coli LPS. Ten days later their ear-pinnas were challenged with 1 μM NiCl(2) with or without a test substance. Although NiCl(2) alone at this concentration does not induce Ni-allergy, its combination with the following substances induced Ni-allergy in BALB/c mice: LPS preparations from oral gram-negative bacteria (Prevotella intermedia and Porphyromonas gingivalis), a mannan preparation from a fungus (Saccharomyces cerevisiae), and synthetic NOD2 and TLR2 agonists. The effect of the mannan preparation was small in C3H/HeJ mice (sensitized with NiCl(2) + the P. intermedia preparation). The P. intermedia preparation promoted Ni-allergy in C3H/HeJ and nude mice, but not in mice deficient in either TLR2 or histidine decarboxylase. Intragingival injection of the P. intermedia preparation and later challenge with NiCl(2) alone to ear-pinnas also promoted Ni-allergy. These results indicate that (i) in Ni-allergy, a microbial milieu or innate immunity is important at the elicitation step, too, and (ii) some oral bacteria may promote Ni-allergy via TLR2-stimulant(s) production. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Modeling Electric Double-Layers Including Chemical Reaction Effects

    DEFF Research Database (Denmark)

    Paz-Garcia, Juan Manuel; Johannesson, Björn; Ottosen, Lisbeth M.

    2014-01-01

    A physicochemical and numerical model for the transient formation of an electric double-layer between an electrolyte and a chemically-active flat surface is presented, based on a finite elements integration of the nonlinear Nernst-Planck-Poisson model including chemical reactions. The model works...

  15. NIAM-deficient mice are predisposed to the development of proliferative lesions including B-cell lymphomas.

    Directory of Open Access Journals (Sweden)

    Sara M Reed

    Full Text Available Nuclear Interactor of ARF and Mdm2 (NIAM, gene designation Tbrg1 is a largely unstudied inhibitor of cell proliferation that helps maintain chromosomal stability. It is a novel activator of the ARF-Mdm2-Tip60-p53 tumor suppressor pathway as well as other undefined pathways important for genome maintenance. To examine its predicted role as a tumor suppressor, we generated NIAM mutant (NIAM(m/m mice homozygous for a β-galactosidase expressing gene-trap cassette in the endogenous gene. The mutant mice expressed significantly lower levels of NIAM protein in tissues compared to wild-type animals. Fifty percent of aged NIAM deficient mice (14 to 21 months developed proliferative lesions, including a uterine hemangioma, pulmonary papillary adenoma, and a Harderian gland adenoma. No age-matched wild-type or NIAM(+/m heterozygous animals developed lesions. In the spleen, NIAM(m/m mice had prominent white pulp expansion which correlated with enhanced increased reactive lymphoid hyperplasia and evidence of systemic inflammation. Notably, 17% of NIAM mutant mice had splenic white pulp features indicating early B-cell lymphoma. This correlated with selective expansion of marginal zone B cells in the spleens of younger, tumor-free NIAM-deficient mice. Unexpectedly, basal p53 expression and activity was largely unaffected by NIAM loss in isolated splenic B cells. In sum, NIAM down-regulation in vivo results in a significant predisposition to developing benign tumors or early stage cancers. These mice represent an outstanding platform for dissecting NIAM's role in tumorigenesis and various anti-cancer pathways, including p53 signaling.

  16. Enhanced Nociception in Angelman Syndrome Model Mice.

    Science.gov (United States)

    McCoy, Eric S; Taylor-Blake, Bonnie; Aita, Megumi; Simon, Jeremy M; Philpot, Benjamin D; Zylka, Mark J

    2017-10-18

    Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by mutation or deletion of the maternal UBE3A allele. The maternal UBE3A allele is expressed in nearly all neurons of the brain and spinal cord, whereas the paternal UBE3A allele is repressed by an extremely long antisense transcript ( UBE3A-ATS ). Little is known about expression of UBE3A in the peripheral nervous system, where loss of maternal UBE3A might contribute to AS phenotypes. Here we sought to examine maternal and paternal Ube3a expression in DRGs neurons and to evaluate whether nociceptive responses were affected in AS model mice (global deletion of maternal Ube3a allele; Ube3a m -/ p + ). We found that most large-diameter proprioceptive and mechanosensitive DRG neurons expressed maternal Ube3a and paternal Ube3a-ATS In contrast, most small-diameter neurons expressed Ube3a biallelically and had low to undetectable levels of Ube3a-ATS Analysis of single-cell DRG transcriptomes further suggested that Ube3a is expressed monoallelically in myelinated large-diameter neurons and biallelically in unmyelinated small-diameter neurons. Behavioral responses to some noxious thermal and mechanical stimuli were enhanced in male and female AS model mice; however, nociceptive responses were not altered by the conditional deletion of maternal Ube3a in the DRG. These data suggest that the enhanced nociceptive responses in AS model mice are due to loss of maternal Ube3a in the central, but not peripheral, nervous system. Our study provides new insights into sensory processing deficits associated with AS. SIGNIFICANCE STATEMENT Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss or mutation of the maternal UBE3A allele. While sensory processing deficits are frequently associated with AS, it is currently unknown whether Ube3a is expressed in peripheral sensory neurons or whether maternal deletion of Ube3a affects somatosensory responses. Here, we found that Ube3a is primarily expressed

  17. Including investment risk in large-scale power market models

    DEFF Research Database (Denmark)

    Lemming, Jørgen Kjærgaard; Meibom, P.

    2003-01-01

    can be included in large-scale partial equilibrium models of the power market. The analyses are divided into a part about risk measures appropriate for power market investors and a more technical part about the combination of a risk-adjustment model and a partial-equilibrium model. To illustrate...... the analyses quantitatively, a framework based on an iterative interaction between the equilibrium model and a separate risk-adjustment module was constructed. To illustrate the features of the proposed modelling approach we examined how uncertainty in demand and variable costs affects the optimal choice...

  18. Progressive IRP Models for Power Resources Including EPP

    Directory of Open Access Journals (Sweden)

    Yiping Zhu

    2017-01-01

    Full Text Available In the view of optimizing regional power supply and demand, the paper makes effective planning scheduling of supply and demand side resources including energy efficiency power plant (EPP, to achieve the target of benefit, cost, and environmental constraints. In order to highlight the characteristics of different supply and demand resources in economic, environmental, and carbon constraints, three planning models with progressive constraints are constructed. Results of three models by the same example show that the best solutions to different models are different. The planning model including EPP has obvious advantages considering pollutant and carbon emission constraints, which confirms the advantages of low cost and emissions of EPP. The construction of progressive IRP models for power resources considering EPP has a certain reference value for guiding the planning and layout of EPP within other power resources and achieving cost and environmental objectives.

  19. Modeling heart rate variability including the effect of sleep stages

    Science.gov (United States)

    Soliński, Mateusz; Gierałtowski, Jan; Żebrowski, Jan

    2016-02-01

    We propose a model for heart rate variability (HRV) of a healthy individual during sleep with the assumption that the heart rate variability is predominantly a random process. Autonomic nervous system activity has different properties during different sleep stages, and this affects many physiological systems including the cardiovascular system. Different properties of HRV can be observed during each particular sleep stage. We believe that taking into account the sleep architecture is crucial for modeling the human nighttime HRV. The stochastic model of HRV introduced by Kantelhardt et al. was used as the initial starting point. We studied the statistical properties of sleep in healthy adults, analyzing 30 polysomnographic recordings, which provided realistic information about sleep architecture. Next, we generated synthetic hypnograms and included them in the modeling of nighttime RR interval series. The results of standard HRV linear analysis and of nonlinear analysis (Shannon entropy, Poincaré plots, and multiscale multifractal analysis) show that—in comparison with real data—the HRV signals obtained from our model have very similar properties, in particular including the multifractal characteristics at different time scales. The model described in this paper is discussed in the context of normal sleep. However, its construction is such that it should allow to model heart rate variability in sleep disorders. This possibility is briefly discussed.

  20. Anti-diabetic effects including diabetic nephropathy of anti-osteoporotic trace minerals on diabetic mice.

    Science.gov (United States)

    Maehira, Fusako; Ishimine, Nau; Miyagi, Ikuko; Eguchi, Yukinori; Shimada, Katsumasa; Kawaguchi, Daisuke; Oshiro, Yoshihide

    2011-04-01

    In our previous study to evaluate the effects of soluble silicon (Si) on bone metabolism, Si and coral sand (CS) as a natural Si-containing material suppressed peroxisome proliferator-activated receptor γ (PPARγ), which regulates both glucose and bone metabolism and increases adipogenesis at the expense of osteogenesis, leading to bone loss. In this study, we investigated the anti-diabetic effects of bone-seeking elements, Si and stable strontium (Sr), and CS as a natural material containing these elements using obese diabetic KKAy mice. Weanling male mice were fed diets containing 1% Ca supplemented with CaCO(3) as the control and CS, and diets supplemented with 50 ppm Si or 750 ppm Sr to control diet for 56 d. The mRNA expressions related to energy expenditure in the pancreas and kidney were quantified by real-time polymerase chain reaction. At the end of feeding, plasma glucose, insulin, leptin, and adiponectin levels decreased significantly in three test groups, while pancreatic PPARγ and adiponectin mRNA expression levels increased significantly toward the normal level, improving the glucose sensitivity of β-cells and inducing a significant decrease in insulin expression. The renal PPARγ, PPARα, and adiponectin expression levels, histologic indices of diabetic glomerulopathy, and plasma indices of renal function were also improved significantly in the test groups. Taken together, anti-osteoporotic trace minerals, Si and Sr, and CS containing them showed novel anti-diabetic effects of lowering blood glucose level, improving the tolerance to insulin, leptin, and adiponectin, and reducing the risk of glomerulopathy through modulation of related gene expression in the pancreas and kidney. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. A hydrodynamic model for granular material flows including segregation effects

    Directory of Open Access Journals (Sweden)

    Gilberg Dominik

    2017-01-01

    Full Text Available The simulation of granular flows including segregation effects in large industrial processes using particle methods is accurate, but very time-consuming. To overcome the long computation times a macroscopic model is a natural choice. Therefore, we couple a mixture theory based segregation model to a hydrodynamic model of Navier-Stokes-type, describing the flow behavior of the granular material. The granular flow model is a hybrid model derived from kinetic theory and a soil mechanical approach to cover the regime of fast dilute flow, as well as slow dense flow, where the density of the granular material is close to the maximum packing density. Originally, the segregation model has been formulated by Thornton and Gray for idealized avalanches. It is modified and adapted to be in the preferred form for the coupling. In the final coupled model the segregation process depends on the local state of the granular system. On the other hand, the granular system changes as differently mixed regions of the granular material differ i.e. in the packing density. For the modeling process the focus lies on dry granular material flows of two particle types differing only in size but can be easily extended to arbitrary granular mixtures of different particle size and density. To solve the coupled system a finite volume approach is used. To test the model the rotational mixing of small and large particles in a tumbler is simulated.

  2. A hydrodynamic model for granular material flows including segregation effects

    Science.gov (United States)

    Gilberg, Dominik; Klar, Axel; Steiner, Konrad

    2017-06-01

    The simulation of granular flows including segregation effects in large industrial processes using particle methods is accurate, but very time-consuming. To overcome the long computation times a macroscopic model is a natural choice. Therefore, we couple a mixture theory based segregation model to a hydrodynamic model of Navier-Stokes-type, describing the flow behavior of the granular material. The granular flow model is a hybrid model derived from kinetic theory and a soil mechanical approach to cover the regime of fast dilute flow, as well as slow dense flow, where the density of the granular material is close to the maximum packing density. Originally, the segregation model has been formulated by Thornton and Gray for idealized avalanches. It is modified and adapted to be in the preferred form for the coupling. In the final coupled model the segregation process depends on the local state of the granular system. On the other hand, the granular system changes as differently mixed regions of the granular material differ i.e. in the packing density. For the modeling process the focus lies on dry granular material flows of two particle types differing only in size but can be easily extended to arbitrary granular mixtures of different particle size and density. To solve the coupled system a finite volume approach is used. To test the model the rotational mixing of small and large particles in a tumbler is simulated.

  3. Craniofacial Statistical Deformation Models of Wild-type mice and Crouzon mice

    DEFF Research Database (Denmark)

    Ólafsdóttir, Hildur; Darvann, Tron Andre; Ersbøll, Bjarne Kjær

    2007-01-01

    of Micro CT scannings of the heads of wild-type (normal) mice and Crouzon mice were investigated. Statistical deformation models were built to assess the anatomical differences between the groups, as well as the within-group anatomical variation. Following the approach by Rueckert et al. we built an atlas...

  4. Development of a Model for Marburgvirus Based on Severe-Combined Immunodeficiency Mice

    National Research Council Canada - National Science Library

    Warfield, Kelly L; Alves, Derron A; Bradfute, Steven B; Reed, Daniel K; Kalina, Warren V; Olinger, Gene G; Bavari, Sina; VanTongeren, Sean

    2007-01-01

    ...). Evaluation of this model identified many similarities between infection in mice and nonhuman primates, including viral tropism for antigen-presenting cells, high viral titers in the spleen and liver...

  5. Simple suggestions for including vertical physics in oil spill models

    International Nuclear Information System (INIS)

    D'Asaro, Eric; University of Washington, Seatle, WA

    2001-01-01

    Current models of oil spills include no vertical physics. They neglect the effect of vertical water motions on the transport and concentration of floating oil. Some simple ways to introduce vertical physics are suggested here. The major suggestion is to routinely measure the density stratification of the upper ocean during oil spills in order to develop a database on the effect of stratification. (Author)

  6. Imunocompetent Mice Model for Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Denise Gonçalves

    2012-01-01

    Full Text Available Dengue fever is a noncontagious infectious disease caused by dengue virus (DENV. DENV belongs to the family Flaviviridae, genus Flavivirus, and is classified into four antigenically distinct serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. The number of nations and people affected has increased steadily and today is considered the most widely spread arbovirus (arthropod-borne viral disease in the world. The absence of an appropriate animal model for studying the disease has hindered the understanding of dengue pathogenesis. In our study, we have found that immunocompetent C57BL/6 mice infected intraperitoneally with DENV-1 presented some signs of dengue disease such as thrombocytopenia, spleen hemorrhage, liver damage, and increase in production of IFNγ and TNFα cytokines. Moreover, the animals became viremic and the virus was detected in several organs by real-time RT-PCR. Thus, this animal model could be used to study mechanism of dengue virus infection, to test antiviral drugs, as well as to evaluate candidate vaccines.

  7. Novel, high incidence exercise-induced muscle bleeding model in hemophilia B mice

    DEFF Research Database (Denmark)

    Tranholm, M.; Kristensen, Annemarie Thuri; Broberg, M. L.

    2015-01-01

    INTRODUCTION: Muscle hematomas are the second most common complication of hemophilia and insufficient treatment may result in serious and even life-threatening complications. Hemophilic dogs and rats do experience spontaneous muscle bleeding, but currently, no experimental animal model is available...... specifically investigating spontaneous muscle bleeds in a hemophilic setting. AIM: The objective of this study was to develop a model of spontaneous muscle bleeds in hemophilia B mice. We hypothesized that treadmill exercise would induce muscle bleeds in hemophilia B mice but not in normal non-hemophilic mice...... and that treatment with recombinant factor IX (rFIX) before treadmill exercise could prevent the occurrence of pathology. METHODS: A total of 203 mice (123 F9-KO and 80 C57BL/6NTac) were included in three separate studies: (i) the model implementation study investigating the bleeding pattern in hemophilia B mice...

  8. Of Men and Mice: Modeling the Fragile X Syndrome

    Science.gov (United States)

    Dahlhaus, Regina

    2018-01-01

    The Fragile X Syndrome (FXS) is one of the most common forms of inherited intellectual disability in all human societies. Caused by the transcriptional silencing of a single gene, the fragile x mental retardation gene FMR1, FXS is characterized by a variety of symptoms, which range from mental disabilities to autism and epilepsy. More than 20 years ago, a first animal model was described, the Fmr1 knock-out mouse. Several other models have been developed since then, including conditional knock-out mice, knock-out rats, a zebrafish and a drosophila model. Using these model systems, various targets for potential pharmaceutical treatments have been identified and many treatments have been shown to be efficient in preclinical studies. However, all attempts to turn these findings into a therapy for patients have failed thus far. In this review, I will discuss underlying difficulties and address potential alternatives for our future research. PMID:29599705

  9. Exclusive queueing model including the choice of service windows

    Science.gov (United States)

    Tanaka, Masahiro; Yanagisawa, Daichi; Nishinari, Katsuhiro

    2018-01-01

    In a queueing system involving multiple service windows, choice behavior is a significant concern. This paper incorporates the choice of service windows into a queueing model with a floor represented by discrete cells. We contrived a logit-based choice algorithm for agents considering the numbers of agents and the distances to all service windows. Simulations were conducted with various parameters of agent choice preference for these two elements and for different floor configurations, including the floor length and the number of service windows. We investigated the model from the viewpoint of transit times and entrance block rates. The influences of the parameters on these factors were surveyed in detail and we determined that there are optimum floor lengths that minimize the transit times. In addition, we observed that the transit times were determined almost entirely by the entrance block rates. The results of the presented model are relevant to understanding queueing systems including the choice of service windows and can be employed to optimize facility design and floor management.

  10. Prospects for genetically modified non-human primate models, including the common marmoset.

    Science.gov (United States)

    Sasaki, Erika

    2015-04-01

    Genetically modified mice have contributed much to studies in the life sciences. In some research fields, however, mouse models are insufficient for analyzing the molecular mechanisms of pathology or as disease models. Often, genetically modified non-human primate (NHP) models are desired, as they are more similar to human physiology, morphology, and anatomy. Recent progress in studies of the reproductive biology in NHPs has enabled the introduction of exogenous genes into NHP genomes or the alteration of endogenous NHP genes. This review summarizes recent progress in the production of genetically modified NHPs, including the common marmoset, and future perspectives for realizing genetically modified NHP models for use in life sciences research. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  11. NSG Mice Provide a Better Spontaneous Model of Breast Cancer Metastasis than Athymic (Nude Mice.

    Directory of Open Access Journals (Sweden)

    Madhavi Puchalapalli

    Full Text Available Metastasis is the most common cause of mortality in breast cancer patients worldwide. To identify improved mouse models for breast cancer growth and spontaneous metastasis, we examined growth and metastasis of both estrogen receptor positive (T47D and negative (MDA-MB-231, SUM1315, and CN34BrM human breast cancer cells in nude and NSG mice. Both primary tumor growth and spontaneous metastases were increased in NSG mice compared to nude mice. In addition, a pattern of metastasis similar to that observed in human breast cancer patients (metastases to the lungs, liver, bones, brain, and lymph nodes was found in NSG mice. Furthermore, there was an increase in the metastatic burden in NSG compared to nude mice that were injected with MDA-MB-231 breast cancer cells in an intracardiac experimental metastasis model. This data demonstrates that NSG mice provide a better model for studying human breast cancer metastasis compared to the current nude mouse model.

  12. Chemostat modeling of Escherichia coli persistence in conventionalized mono-associated and streptomycin-treated mice.

    Science.gov (United States)

    Rang, C; Midtvedt, T; Molin, S; Chao, L

    2001-01-01

    We have previously shown that Escherichia coli BJ4 has similar doubling time in mice that are mono-associated (having only the inoculated E. coli BJ4) or streptomycin-treated (having mainly gram-positive bacteria plus the inoculated E. coli BJ4). We also showed that when the mice were conventionalized (fed cecum homogenate from conventional mice or ones with a complete microbial flora), the introduction of complete flora in both cases increased the in vivo doubling time, while decreasing the colony counts in fecal samples. To determine whether the increase in doubling time could explain the decrease in colony counts, we analyzed our previous results by a chemostat model. The analysis shows that the increasing doubling time alone is sufficient to explain the decrease in colony counts in mono-associated mice, but not in the streptomycin-treated mice. The observed decreasing rate in colony counts in streptomycin-treated mice is slower than predicted. Furthermore, whereas the model predicted a decrease to extinction in both mice, the E. coli persist at a frequency 10-80 times higher in streptomycin-treated mice than in mono-associated mice. Thus, while a chemostat model is able to explain some of the population dynamics of intestinal bacteria in mice, additional factors not included in the model are stabilizing the system. Because we find that E. coli declines more slowly and to a higher stabilization frequency in streptomycin-treated mice, which have a more diverse flora before conventionalization, we take these results to suggest that the persistence of E. coli populations is promoted by species diversity. We propose that a mechanism for the persistence may be the presence of new E. coli niches created by keystone species in the more diverse flora.

  13. Including spatial data in nutrient balance modelling on dairy farms

    Science.gov (United States)

    van Leeuwen, Maricke; van Middelaar, Corina; Stoof, Cathelijne; Oenema, Jouke; Stoorvogel, Jetse; de Boer, Imke

    2017-04-01

    The Annual Nutrient Cycle Assessment (ANCA) calculates the nitrogen (N) and phosphorus (P) balance at a dairy farm, while taking into account the subsequent nutrient cycles of the herd, manure, soil and crop components. Since January 2016, Dutch dairy farmers are required to use ANCA in order to increase understanding of nutrient flows and to minimize nutrient losses to the environment. A nutrient balance calculates the difference between nutrient inputs and outputs. Nutrients enter the farm via purchased feed, fertilizers, deposition and fixation by legumes (nitrogen), and leave the farm via milk, livestock, manure, and roughages. A positive balance indicates to which extent N and/or P are lost to the environment via gaseous emissions (N), leaching, run-off and accumulation in soil. A negative balance indicates that N and/or P are depleted from soil. ANCA was designed to calculate average nutrient flows on farm level (for the herd, manure, soil and crop components). ANCA was not designed to perform calculations of nutrient flows at the field level, as it uses averaged nutrient inputs and outputs across all fields, and it does not include field specific soil characteristics. Land management decisions, however, such as the level of N and P application, are typically taken at the field level given the specific crop and soil characteristics. Therefore the information that ANCA provides is likely not sufficient to support farmers' decisions on land management to minimize nutrient losses to the environment. This is particularly a problem when land management and soils vary between fields. For an accurate estimate of nutrient flows in a given farming system that can be used to optimize land management, the spatial scale of nutrient inputs and outputs (and thus the effect of land management and soil variation) could be essential. Our aim was to determine the effect of the spatial scale of nutrient inputs and outputs on modelled nutrient flows and nutrient use efficiencies

  14. Single-Phase Bundle Flows Including Macroscopic Turbulence Model

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Jun; Yoon, Han Young [KAERI, Daejeon (Korea, Republic of); Yoon, Seok Jong; Cho, Hyoung Kyu [Seoul National University, Seoul (Korea, Republic of)

    2016-05-15

    To deal with various thermal hydraulic phenomena due to rapid change of fluid properties when an accident happens, securing mechanistic approaches as much as possible may reduce the uncertainty arising from improper applications of the experimental models. In this study, the turbulence mixing model, which is well defined in the subchannel analysis code such as VIPRE, COBRA, and MATRA by experiments, is replaced by a macroscopic k-e turbulence model, which represents the aspect of mathematical derivation. The performance of CUPID with macroscopic turbulence model is validated against several bundle experiments: CNEN 4x4 and PNL 7x7 rod bundle tests. In this study, the macroscopic k-e model has been validated for the application to subchannel analysis. It has been implemented in the CUPID code and validated against CNEN 4x4 and PNL 7x7 rod bundle tests. The results showed that the macroscopic k-e turbulence model can estimate the experiments properly.

  15. Global atmospheric model for mercury including oxidation by bromine atoms

    Directory of Open Access Journals (Sweden)

    C. D. Holmes

    2010-12-01

    Full Text Available Global models of atmospheric mercury generally assume that gas-phase OH and ozone are the main oxidants converting Hg0 to HgII and thus driving mercury deposition to ecosystems. However, thermodynamic considerations argue against the importance of these reactions. We demonstrate here the viability of atomic bromine (Br as an alternative Hg0 oxidant. We conduct a global 3-D simulation with the GEOS-Chem model assuming gas-phase Br to be the sole Hg0 oxidant (Hg + Br model and compare to the previous version of the model with OH and ozone as the sole oxidants (Hg + OH/O3 model. We specify global 3-D Br concentration fields based on our best understanding of tropospheric and stratospheric Br chemistry. In both the Hg + Br and Hg + OH/O3 models, we add an aqueous photochemical reduction of HgII in cloud to impose a tropospheric lifetime for mercury of 6.5 months against deposition, as needed to reconcile observed total gaseous mercury (TGM concentrations with current estimates of anthropogenic emissions. This added reduction would not be necessary in the Hg + Br model if we adjusted the Br oxidation kinetics downward within their range of uncertainty. We find that the Hg + Br and Hg + OH/O3 models are equally capable of reproducing the spatial distribution of TGM and its seasonal cycle at northern mid-latitudes. The Hg + Br model shows a steeper decline of TGM concentrations from the tropics to southern mid-latitudes. Only the Hg + Br model can reproduce the springtime depletion and summer rebound of TGM observed at polar sites; the snowpack component of GEOS-Chem suggests that 40% of HgII deposited to snow in the Arctic is transferred to the ocean and land reservoirs, amounting to a net deposition flux to the Arctic of 60 Mg a−1. Summertime events of depleted Hg0 at Antarctic sites due to subsidence are much better simulated by

  16. Thematic report: Macroeconomic models including specifically social and environmental aspects

    OpenAIRE

    Kratena, Kurt

    2015-01-01

    WWWforEurope Deliverable No. 8, 30 pages A significant reduction of the global environmental consequences of European consumption and production activities are the main objective of the policy simulations carried out in this paper. For this purpose three different modelling approaches have been chosen. Two macroeconomic models following the philosophy of consistent stock-flow accounting for the main institutional sectors (households, firms, banks, central bank and government) are used for...

  17. Identifying Clusters with Mixture Models that Include Radial Velocity Observations

    Science.gov (United States)

    Czarnatowicz, Alexis; Ybarra, Jason E.

    2018-01-01

    The study of stellar clusters plays an integral role in the study of star formation. We present a cluster mixture model that considers radial velocity data in addition to spatial data. Maximum likelihood estimation through the Expectation-Maximization (EM) algorithm is used for parameter estimation. Our mixture model analysis can be used to distinguish adjacent or overlapping clusters, and estimate properties for each cluster.Work supported by awards from the Virginia Foundation for Independent Colleges (VFIC) Undergraduate Science Research Fellowship and The Research Experience @Bridgewater (TREB).

  18. Unsteady panel method for complex configurations including wake modeling

    CSIR Research Space (South Africa)

    Van Zyl, Lourens H

    2008-01-01

    Full Text Available The calculation of unsteady air loads is an essential step in any aeroelastic analysis. The subsonic doublet lattice method (DLM) is used extensively for this purpose due to its simplicity and reliability. The body models available with the popular...

  19. A thermal lens model including the Soret effect

    International Nuclear Information System (INIS)

    Cabrera, Humberto; Sira, Eloy; Rahn, Kareem; Garcia-Sucre, Maximo

    2009-01-01

    In this letter we generalize the thermal lens model to account for the Soret effect in binary liquid mixtures. This formalism permits the precise determination of the Soret coefficient in a steady-state situation. The theory is experimentally verified using the measured values in the ethanol/water mixtures. The time evolution of the Soret signal has been used to derive mass-diffusion times from which mass-diffusion coefficients were calculated. (Author)

  20. Including lateral interactions into microkinetic models of catalytic reactions

    DEFF Research Database (Denmark)

    Hellman, Anders; Honkala, Johanna Karoliina

    2007-01-01

    In many catalytic reactions lateral interactions between adsorbates are believed to have a strong influence on the reaction rates. We apply a microkinetic model to explore the effect of lateral interactions and how to efficiently take them into account in a simple catalytic reaction. Three differ...... different approximations are investigated: site, mean-field, and quasichemical approximations. The obtained results are compared to accurate Monte Carlo numbers. In the end, we apply the approximations to a real catalytic reaction, namely, ammonia synthesis....

  1. A stochastic model of gene expression including splicing events

    OpenAIRE

    Penim, Flávia Alexandra Mendes

    2014-01-01

    Tese de mestrado, Bioinformática e Biologia Computacional, Universidade de Lisboa, Faculdade de Ciências, 2014 Proteins carry out the great majority of the catalytic and structural work within an organism. The RNA templates used in their synthesis determines their identity, and this is dictated by which genes are transcribed. Therefore, gene expression is the fundamental determinant of an organism’s nature. The main objective of this thesis was to develop a stochastic computational model a...

  2. Parton recombination model including resonance production. RL-78-040

    International Nuclear Information System (INIS)

    Roberts, R.G.; Hwa, R.C.; Matsuda, S.

    1978-05-01

    Possible effects of resonance production on the meson inclusive distribution in the fragmentation region are investigated in the framework of the parton recombination model. From a detailed study of the data on vector-meson production, a reliable ratio of the vector-to-pseudoscalar rates is determined. Then the influence of the decay of the vector mesons on the pseudoscalar spectrum is examined, and the effect found to be no more than 25% for x > 0.5. The normalization of the non-strange antiquark distributions are still higher than those in a quiescent proton. The agreement between the calculated results and data remain very good. 36 references

  3. Extending PSA models including ageing and asset management - 15291

    International Nuclear Information System (INIS)

    Martorell, S.; Marton, I.; Carlos, S.; Sanchez, A.I.

    2015-01-01

    This paper proposes a new approach to Ageing Probabilistic Safety Assessment (APSA) modelling, which is intended to be used to support risk-informed decisions on the effectiveness of maintenance management programs and technical specification requirements of critical equipment of Nuclear Power Plants (NPP) within the framework of the Risk Informed Decision Making according to R.G. 1.174 principles. This approach focuses on the incorporation of not only equipment ageing but also effectiveness of maintenance and efficiency of surveillance testing explicitly into APSA models and data. This methodology is applied to a motor-operated valve of the auxiliary feed water system (AFWS) of a PWR. This simple example of application focuses on a critical safety-related equipment of a NPP in order to evaluate the risk impact of considering different approaches to APSA and the combined effect of equipment ageing and maintenance and testing alternatives along NPP design life. The risk impact of several alternatives in maintenance strategy is discussed

  4. Regulation of an Autoimmune Model for Multiple Sclerosis in Th2-Biased GATA3 Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Viromi Fernando

    2014-01-01

    Full Text Available T helper (Th2 cells have been proposed to play a neuroprotective role in multiple sclerosis (MS. This is mainly based on “loss-of-function” studies in an animal model for MS, experimental autoimmune encephalomyelitis (EAE, using blocking antibodies against Th2 related cytokines, and knockout mice lacking Th2-related molecules. We tested whether an increase of Th2 responses (“gain-of-function” approach could alter EAE, the approach of novel GATA binding protein 3 (GATA3-transgenic (tg mice that overexpress GATA3, a transcription factor required for Th2 differentiation. In EAE induced with myelin oligodendrocyte glycoprotein (MOG35−55 peptide, GATA3-tg mice had a significantly delayed onset of disease and a less severe maximum clinical score, compared with wild-type C57BL/6 mice. Histologically, GATA3-tg mice had decreased levels of meningitis and demyelination in the spinal cord, and anti-inflammatory cytokine profiles immunologically, however both groups developed similar levels of MOG-specific lymphoproliferative responses. During the early stage, we detected higher levels of interleukin (IL-4 and IL-10, with MOG and mitogen stimulation of regional lymph node cells in GATA3-tg mice. During the late stage, only mitogen stimulation induced higher IL-4 and lower interferon-γ and IL-17 production in GATA3-tg mice. These results suggest that a preexisting bias toward a Th2 immune response may reduce the severity of inflammatory demyelinating diseases, including MS.

  5. Actinic keratosis modelling in mice: A translational study.

    Directory of Open Access Journals (Sweden)

    Arnaud Pillon

    Full Text Available Actinic keratoses (AK are pre-malignant cutaneous lesions caused by prolonged exposure to ultraviolet radiation. As AKs lesions are generally accepted to be the initial lesions in a disease continuum that progresses to squamous cell carcinoma (SCC, AK lesions have to be treated. They are also the second most common reason for visits to the dermatologist. Several treatments are available but their efficacy still needs to be improved. The UV-B-induced KA lesion mouse model is used in preclinical studies to assess the efficacy of novel molecules, even though it is often more representative of advanced AK or SCC.Here we report on a translational study, comparing the various stages of AK development in humans and in the UV-B irradiated mouse model, as well as the optimization of photograph acquisition of AK lesions on mouse skin.Human and mouse skin lesions were analysed by histology and immunohistochemistry. Mouse lesions were also assessed using a digital dermatoscope.An histological and phenotypic analysis, including p53, Ki67 and CD3 expression detection, performed on human and mouse AK lesions, shows that overall AK modelling in mice is relevant in the clinical situation. Some differences are observed, such as disorganization of keratinocytes of the basal layer and a number of atypical nuclei which are more numerous in human AK, whereas much more pronounced acanthosis is observed in skin lesion in mice. Thanks to this translational study, we are able to select appropriate experimental conditions for establishing either early or advanced stage AK or an SCC model. Furthermore, we optimized photograph acquisition of AK lesions on mouse skin by using a digital dermatoscope which is also used in clinics and allows reproducible photograph acquisition for further reliable assessment of mouse lesions. Use of this camera is illustrated through a pharmacological study assessing the activity of CARAC®.These data demonstrate that this mouse model of UV

  6. Actinic keratosis modelling in mice: A translational study

    Science.gov (United States)

    Vandenberghe, Isabelle; Cartron, Valérie; Cèbe, Patrick; Blanchet, Jean-Christophe; Sibaud, Vincent; Guilbaud, Nicolas; Audoly, Laurent; Lamant, Laurence; Kruczynski, Anna

    2017-01-01

    Background Actinic keratoses (AK) are pre-malignant cutaneous lesions caused by prolonged exposure to ultraviolet radiation. As AKs lesions are generally accepted to be the initial lesions in a disease continuum that progresses to squamous cell carcinoma (SCC), AK lesions have to be treated. They are also the second most common reason for visits to the dermatologist. Several treatments are available but their efficacy still needs to be improved. The UV-B-induced KA lesion mouse model is used in preclinical studies to assess the efficacy of novel molecules, even though it is often more representative of advanced AK or SCC. Objectives Here we report on a translational study, comparing the various stages of AK development in humans and in the UV-B irradiated mouse model, as well as the optimization of photograph acquisition of AK lesions on mouse skin. Methods Human and mouse skin lesions were analysed by histology and immunohistochemistry. Mouse lesions were also assessed using a digital dermatoscope. Results An histological and phenotypic analysis, including p53, Ki67 and CD3 expression detection, performed on human and mouse AK lesions, shows that overall AK modelling in mice is relevant in the clinical situation. Some differences are observed, such as disorganization of keratinocytes of the basal layer and a number of atypical nuclei which are more numerous in human AK, whereas much more pronounced acanthosis is observed in skin lesion in mice. Thanks to this translational study, we are able to select appropriate experimental conditions for establishing either early or advanced stage AK or an SCC model. Furthermore, we optimized photograph acquisition of AK lesions on mouse skin by using a digital dermatoscope which is also used in clinics and allows reproducible photograph acquisition for further reliable assessment of mouse lesions. Use of this camera is illustrated through a pharmacological study assessing the activity of CARAC®. Conclusion These data

  7. Firn Model Intercomparison Experiment (FirnMICE)

    DEFF Research Database (Denmark)

    Lundin, Jessica M.D.; Stevens, C. Max; Arthern, Robert

    2017-01-01

    Evolution of cold dry snow and firn plays important roles in glaciology; however, the physical formulation of a densification law is still an active research topic. We forced eight firn-densification models and one seasonal-snow model in six different experiments by imposing step changes in tempe......Evolution of cold dry snow and firn plays important roles in glaciology; however, the physical formulation of a densification law is still an active research topic. We forced eight firn-densification models and one seasonal-snow model in six different experiments by imposing step changes...

  8. Influence of excessive exercise on immunity, metabolism, and gut microbial diversity in an overtraining mice model.

    Science.gov (United States)

    Yuan, Xin; Xu, Shijie; Huang, Haiyang; Liang, Jian; Wu, Yayun; Li, Chujie; Yuan, Huiqi; Zhao, Xuejie; Lai, Xiaoping; Hou, Shaozhen

    2018-01-24

    The purpose of this study was to evaluate the negative influence of excessive exercise on immunity, substance and energy metabolism as well as gut microbiota in mice. Firstly, an overtraining model of Male Kunming mice was established by high-intensity swimming exercise for 4 weeks. Then, a series of evaluation indicators, including the routine blood analysis, immune organ coefficient, digestive enzymes, and aquaporins expression levels of small intestine and colon tissue, histological examinations of liver, spleen, small intestine, and colon, were determined based on this model. Furthermore, 16S rRNA gene sequencing was also employed to measure the microbial composition in gut. The results found that immune parameters, substance and energy metabolism of all mice was altered and disturbed after high-intensity swimming for 4 weeks, led to an atrophy of thymus and spleen as well as abnormal structural changes in liver when compared to non-swimming mice. Besides, excessive swimming mice had lower microbial diversity compared to non-swimming mice. However, there was no significant difference in gut microbial taxa between the two groups. The data indicated that excessive exercise exhibits negative impacts on immunity, substance and energy metabolism as well as gut microbial diversity. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Morphological Alterations in Gastrocnemius and Soleus Muscles in Male and Female Mice in a Fibromyalgia Model.

    Directory of Open Access Journals (Sweden)

    Gabriel Alejandro Bonaterra

    Full Text Available Fibromyalgia (FM is a chronic musculoskeletal pain disorder, characterized by chronic widespread pain and bodily tenderness and is often accompanied by affective disturbances, however often with unknown etiology. According to recent reports, physical and psychological stress trigger FM. To develop new treatments for FM, experimental animal models for FM are needed to be development and characterized. Using a mouse model for FM including intermittent cold stress (ICS, we hypothesized that ICS leads to morphological alterations in skeletal muscles in mice.Male and female ICS mice were kept under alternating temperature (4 °C/room temperature [22 °C]; mice constantly kept at room temperature served as control. After scarification, gastrocnemius and soleus muscles were removed and snap-frozen in liquid nitrogen-cooled isopentane or fixed for electron microscopy.In gastrocnemius/soleus muscles of male ICS mice, we found a 21.6% and 33.2% decrease of fiber cross sectional area (FCSA, which in soleus muscle concerns the loss of type IIa and IIx FCSA. This phenomenon was not seen in muscles of female ICS mice. However, this loss in male ICS mice was associated with an increase in gastrocnemius of the density of MIF+ (8.6%-, MuRF+ (14.7%-, Fbxo32+ (17.8%-cells, a 12.1% loss of capillary contacts/muscle fiber as well as a 30.7% increase of damaged mitochondria in comparison with male control mice. Moreover, significant positive correlations exist among densities (n/mm(2 of MIF+, MuRF+, Fbxo32+-cells in gastrocnemius/ soleus muscles of male ICS mice; these cell densities inversely correlate with FCSA especially in gastrocnemius muscle of male ICS mice.The ICS-induced decrease of FCSA mainly concerns gastrocnemius muscle of male mice due to an increase of inflammatory and atrogenic cells. In soleus muscle of male ICS and soleus/gastrocnemius muscles of female ICS mice morphological alterations seem to occur not at all or delayed. The sex-specificity of

  10. Mice with chimeric livers are an improved model for human lipoprotein metabolism.

    Directory of Open Access Journals (Sweden)

    Ewa C S Ellis

    Full Text Available Rodents are poor model for human hyperlipidemias because total cholesterol and low density lipoprotein levels are very low on a normal diet. Lipoprotein metabolism is primarily regulated by hepatocytes and we therefore assessed whether chimeric mice extensively repopulated with human cells can model human lipid and bile acid metabolism.FRG [ F ah(-/- R ag2(-/-Il2r g (-/-] mice were repopulated with primary human hepatocytes. Serum lipoprotein lipid composition and distribution (VLDL, LDL, and HDL was analyzed by size exclusion chromatography. Bile was analyzed by LC-MS or by GC-MS. RNA expression levels were measured by quantitative RT-PCR.Chimeric mice displayed increased LDL and VLDL fractions and a lower HDL fraction compared to wild type, thus significantly shifting the ratio of LDL/HDL towards a human profile. Bile acid analysis revealed a human-like pattern with high amounts of cholic acid and deoxycholic acid (DCA. Control mice had only taurine-conjugated bile acids as expcted, but highly repopulated mice had glycine-conjugated cholic acid as found in human bile. RNA levels of human genes involved in bile acid synthesis including CYP7A1, and CYP27A1 were significantly upregulated as compared to human control liver. However, administration of recombinant hFGF19 restored human CYP7A1 levels to normal.Humanized-liver mice showed a typical human lipoprotein profile with LDL as the predominant lipoprotein fraction even on a normal diet. The bile acid profile confirmed presence of an intact enterohepatic circulation. Although bile acid synthesis was deregulated in this model, this could be fully normalized by FGF19 administration. Taken together these data indicate that chimeric FRG-mice are a useful new model for human lipoprotein and bile-acid metabolism.

  11. Craniofacial statistical deformation models of wild-type mice and Crouzon mice

    Science.gov (United States)

    Ólafsdóttir, Hildur; Darvann, Tron A.; Ersbøll, Bjarne K.; Hermann, Nuno V.; Oubel, Estanislao; Larsen, Rasmus; Frangi, Alejandro F.; Larsen, Per; Perlyn, Chad A.; Morriss-Kay, Gillian M.; Kreiborg, Sven

    2007-03-01

    Crouzon syndrome is characterised by premature fusion of cranial sutures and synchondroses leading to craniofacial growth disturbances. The gene causing the syndrome was discovered approximately a decade ago and recently the first mouse model of the syndrome was generated. In this study, a set of Micro CT scans of the heads of wild-type (normal) mice and Crouzon mice were investigated. Statistical deformation models were built to assess the anatomical differences between the groups, as well as the within-group anatomical variation. Following the approach by Rueckert et al. we built an atlas using B-spline-based nonrigid registration and subsequently, the atlas was nonrigidly registered to the cases being modelled. The parameters of these registrations were then used as input to a PCA. Using different sets of registration parameters, different models were constructed to describe (i) the difference between the two groups in anatomical variation and (ii) the within-group variation. These models confirmed many known traits in the wild-type and Crouzon mouse craniofacial anatomy. However, they also showed some new traits.

  12. 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.

  13. Human TCR-MHC coevolution after divergence from mice includes increased nontemplate-encoded CDR3 diversity.

    Science.gov (United States)

    Chen, Xiaojing; Poncette, Lucia; Blankenstein, Thomas

    2017-11-06

    For thymic selection and responses to pathogens, T cells interact through their αβ T cell receptor (TCR) with peptide-major histocompatibility complex (MHC) molecules on antigen-presenting cells. How the diverse TCRs interact with a multitude of MHC molecules is unresolved. It is also unclear how humans generate larger TCR repertoires than mice do. We compared the TCR repertoire of CD4 T cells selected from a single mouse or human MHC class II (MHC II) in mice containing the human TCR gene loci. Human MHC II yielded greater thymic output and a more diverse TCR repertoire. The complementarity determining region 3 (CDR3) length adjusted for different inherent V-segment affinities to MHC II. Humans evolved with greater nontemplate-encoded CDR3 diversity than did mice. Our data, which demonstrate human TCR-MHC coevolution after divergence from rodents, explain the greater T cell diversity in humans and suggest a mechanism for ensuring that any V-J gene combination can be selected by a single MHC II. © 2017 Chen et al.

  14. BALANCED SCORECARDS EVALUATION MODEL THAT INCLUDES ELEMENTS OF ENVIRONMENTAL MANAGEMENT SYSTEM USING AHP MODEL

    Directory of Open Access Journals (Sweden)

    Jelena Jovanović

    2010-03-01

    Full Text Available The research is oriented on improvement of environmental management system (EMS using BSC (Balanced Scorecard model that presents strategic model of measurem ents and improvement of organisational performance. The research will present approach of objectives and environmental management me trics involvement (proposed by literature review in conventional BSC in "Ad Barska plovi dba" organisation. Further we will test creation of ECO-BSC model based on business activities of non-profit organisations in order to improve envir onmental management system in parallel with other systems of management. Using this approach we may obtain 4 models of BSC that includ es elements of environmen tal management system for AD "Barska plovidba". Taking into acc ount that implementation and evaluation need long period of time in AD "Barska plovidba", the final choice will be based on 14598 (Information technology - Software product evaluation and ISO 9126 (Software engineering - Product quality using AHP method. Those standards are usually used for evaluation of quality software product and computer programs that serve in organisation as support and factors for development. So, AHP model will be bas ed on evolution criteria based on suggestion of ISO 9126 standards and types of evaluation from two evaluation teams. Members of team & will be experts in BSC and environmental management system that are not em ployed in AD "Barska Plovidba" organisation. The members of team 2 will be managers of AD "Barska Plovidba" organisation (including manage rs from environmental department. Merging results based on previously cr eated two AHP models, one can obtain the most appropriate BSC that includes elements of environmental management system. The chosen model will present at the same time suggestion for approach choice including ecological metrics in conventional BSC model for firm that has at least one ECO strategic orientation.

  15. Resveratrol Enhances Neuroplastic Changes, Including Hippocampal Neurogenesis, and Memory in Balb/C Mice at Six Months of Age

    Science.gov (United States)

    Torres-Pérez, Mario; Tellez-Ballesteros, Ruth Ivonne; Ortiz-López, Leonardo; Ichwan, Muhammad; Vega-Rivera, Nelly Maritza; Castro-García, Mario; Gómez-Sánchez, Ariadna; Kempermann, Gerd; Ramirez-Rodriguez, Gerardo Bernabe

    2015-01-01

    Resveratrol (RVTL) is a flavonoid found in red wine and has been publicized heavily as an anti-aging compound. Indeed, basic research confirms that although there is much hype in the promotion of RVTL, flavonoids such as RVTL have a wide range of biological effects. We here investigated the effects of RVTL treatment on hippocampal plasticity and memory performance in female Balb/C mice, a strain with low baseline levels of adult neurogenesis. Two weeks of treatment with RVTL (40 mg/kg) induced the production of new neurons in vivo by increasing cell survival and possibly precursor cell proliferation. In addition, RVTL decreased the number of apoptotic cells. The number of doublecortin (DCX)-expressing intermediate cells was increased. RVTL stimulated neuronal differentiation in vitro without effects on proliferation. In the dentate gyrus, RVTL promoted the formation and maturation of spines on granule cell dendrites. RVTL also improved performance in the step down passive avoidance test. The RVTL-treated mice showed increase in the levels of two key signaling proteins, phospho-Akt and phospho-PKC, suggesting the involvement of these signaling pathways. Our results support the vision that flavonoids such as resveratrol deserve further examination as plasticity-inducing compounds in the context of successful cognitive aging. PMID:26695764

  16. Resveratrol Enhances Neuroplastic Changes, Including Hippocampal Neurogenesis, and Memory in Balb/C Mice at Six Months of Age.

    Science.gov (United States)

    Torres-Pérez, Mario; Tellez-Ballesteros, Ruth Ivonne; Ortiz-López, Leonardo; Ichwan, Muhammad; Vega-Rivera, Nelly Maritza; Castro-García, Mario; Gómez-Sánchez, Ariadna; Kempermann, Gerd; Ramirez-Rodriguez, Gerardo Bernabe

    2015-01-01

    Resveratrol (RVTL) is a flavonoid found in red wine and has been publicized heavily as an anti-aging compound. Indeed, basic research confirms that although there is much hype in the promotion of RVTL, flavonoids such as RVTL have a wide range of biological effects. We here investigated the effects of RVTL treatment on hippocampal plasticity and memory performance in female Balb/C mice, a strain with low baseline levels of adult neurogenesis. Two weeks of treatment with RVTL (40 mg/kg) induced the production of new neurons in vivo by increasing cell survival and possibly precursor cell proliferation. In addition, RVTL decreased the number of apoptotic cells. The number of doublecortin (DCX)-expressing intermediate cells was increased. RVTL stimulated neuronal differentiation in vitro without effects on proliferation. In the dentate gyrus, RVTL promoted the formation and maturation of spines on granule cell dendrites. RVTL also improved performance in the step down passive avoidance test. The RVTL-treated mice showed increase in the levels of two key signaling proteins, phospho-Akt and phospho-PKC, suggesting the involvement of these signaling pathways. Our results support the vision that flavonoids such as resveratrol deserve further examination as plasticity-inducing compounds in the context of successful cognitive aging.

  17. Resveratrol Enhances Neuroplastic Changes, Including Hippocampal Neurogenesis, and Memory in Balb/C Mice at Six Months of Age.

    Directory of Open Access Journals (Sweden)

    Mario Torres-Pérez

    Full Text Available Resveratrol (RVTL is a flavonoid found in red wine and has been publicized heavily as an anti-aging compound. Indeed, basic research confirms that although there is much hype in the promotion of RVTL, flavonoids such as RVTL have a wide range of biological effects. We here investigated the effects of RVTL treatment on hippocampal plasticity and memory performance in female Balb/C mice, a strain with low baseline levels of adult neurogenesis. Two weeks of treatment with RVTL (40 mg/kg induced the production of new neurons in vivo by increasing cell survival and possibly precursor cell proliferation. In addition, RVTL decreased the number of apoptotic cells. The number of doublecortin (DCX-expressing intermediate cells was increased. RVTL stimulated neuronal differentiation in vitro without effects on proliferation. In the dentate gyrus, RVTL promoted the formation and maturation of spines on granule cell dendrites. RVTL also improved performance in the step down passive avoidance test. The RVTL-treated mice showed increase in the levels of two key signaling proteins, phospho-Akt and phospho-PKC, suggesting the involvement of these signaling pathways. Our results support the vision that flavonoids such as resveratrol deserve further examination as plasticity-inducing compounds in the context of successful cognitive aging.

  18. Development of an Allergic Conjunctivitis Model in Mice

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    Tolga Kocatürk

    2012-12-01

    Full Text Available Pur po se: To develop an animal model that simulates human allergic conjunctivitis to understand the physiopathogenesis of allergic diseases and for developing novel therapeutic interventions. Ma te ri al and Met hod: BALB/c mice (12 males were divided into two groups each comprised of six mice. For sensitization, on the 1st and 8th days, a 0.2 ml mixed solution, adjusted to a concentration to 5mg/ml of ovalbumin (OVA and 15mg/ml of aluminium hydroxide, was administered intraperitoneally to the mice in Group 1 and 0.2 ml saline solution to the mice in Group 2. To induce experimental allergic conjunctivitis, an antigen challenge was made on days 15 and 18, using an OVA solution (5mg/ml instilled into both eyes of the mice in Group 1; while the mice in Group 2 received Human Balanced Salt Solution instead of OVA. For the clinical evaluation, the occurrence of conjunctival and palpebral oedema, conjunctival hyperaemia, and lacrimation were observed. For the histological examination, eyeballs, eyelids, and lacrimal glands were removed and prepared according to the routine processing method of the tissue laboratory. Immunohistochemical examination was made with mast cell tryptase using the labeled streptavidin–biotin amplification method and 3.3´-diaminobenzidine, in addition to hematoxylin-eosin (HE, and toluidine blue (TB staining. Re sults: Evident conjunctival oedema, palpebral oedema, conjunctival hyperaemia, and lacrimation were observed in Group 1. Mean mast cell density in cells/mm2, infiltrating the subconjunctival tissue was significantly high in Group 1 (allergy group, 23.17±7.46, p<0.0001 when compared to Group 2 (5.58±3.12. There was no increase in eosinophil and lymphocyte counts as well as vascular intensity in the subconjunctival tissue in any group. Dis cus si on: The murine model developed is similar to the human allergic conjunctivitis both clinically and histopathologically and can be used as a template for future studies

  19. Development of a model for marburgvirus based on severe-combined immunodeficiency mice

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    Kalina Warren V

    2007-10-01

    Full Text Available Abstract The filoviruses, Ebola (EBOV and Marburg (MARV, cause a lethal hemorrhagic fever. Human isolates of MARV are not lethal to immmunocompetent adult mice and, to date, there are no reports of a mouse-adapted MARV model. Previously, a uniformly lethal EBOV-Zaire mouse-adapted virus was developed by performing 9 sequential passages in progressively older mice (suckling to adult. Evaluation of this model identified many similarities between infection in mice and nonhuman primates, including viral tropism for antigen-presenting cells, high viral titers in the spleen and liver, and an equivalent mean time to death. Existence of the EBOV mouse model has increased our understanding of host responses to filovirus infections and likely has accelerated the development of countermeasures, as it is one of the only hemorrhagic fever viruses that has multiple candidate vaccines and therapeutics. Here, we demonstrate that serially passaging liver homogenates from MARV-infected severe combined immunodeficient (scid mice was highly successful in reducing the time to death in scid mice from 50–70 days to 7–10 days after MARV-Ci67, -Musoke, or -Ravn challenge. We performed serial sampling studies to characterize the pathology of these scid mouse-adapted MARV strains. These scid mouse-adapted MARV models appear to have many similar properties as the MARV models previously developed in guinea pigs and nonhuman primates. Also, as shown here, the scid-adapted MARV mouse models can be used to evaluate the efficacy of candidate antiviral therapeutic molecules, such as phosphorodiamidate morpholino oligomers or antibodies.

  20. Neuroprotective effect of geniposide on Parkinson's disease model mice

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    Yi-mei CHEN

    2015-07-01

    Full Text Available Objective  To investigate the neuroprotective effect of geniposide on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP induced Parkinson's disease (PD model mice and possible mechanism.  Methods  A total of 48 male C57BL/6 mice were randomly divided into control, model, geniposide and MPTP + geniposide groups. The behaviors of C57BL/6 mice were assessed by using open field test, the tyrosine hydroxylase (TH and Bcl-2 positive neurons in the midbrain substantia nigra of mice were detected by immunohistochemistry and the number of apoptosis neurons were observed with TdT-mediated dUTP-biotin nick end labeling (TUNEL.  Results  The number of mobile grid [(76.33 ± 8.59 times/5 min], standing [(19.58 ± 3.97 times/5 min], TH-positive neurons [(12.83 ± 2.32/HPF] and Bcl-2-positive neurons [(10.83 ± 2.23/HPF] in model group were significantly lower than those in the control group [(142.50 ± 11.65 times/5 min, (39.17 ± 4.75 times/5 min, (35.67 ± 1.75/HPF, (20.67 ± 1.75/HPF; P = 0.000, for all]. The apoptosis neurons in model group [(20.33 ± 2.58/HPF] were significantly higher than that in control group [(3.83 ± 1.67 /HPF, P = 0.000. The number of mobile grid [(97.67 ± 13.15 times/5 min, P = 0.000], standing [(29.33 ± 2.90 times/5 min, P = 0.000], TH-positive neurons [(17.50 ± 2.07/HPF, P = 0.002] and Bcl-2-positive neurons [(15.17 ± 2.79 /HPF, P = 0.003] in MPTP + geniposide group were significantly higher than those in model group. The number of apoptosis neurons [(14.67 ± 3.08 /HPF] in MPTP + geniposide group was significantly lower than that in model group (P = 0.001. Conclusions Geniposide can protect dopaminergic neurons in MPTP-induced neurodegeneration and the mechanism may be associated with the inhibition of neuronal apoptosis. DOI: 10.3969/j.issn.1672-6731.2015.06.012

  1. A novel model of human skin pressure ulcers in mice.

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    Andrés A Maldonado

    Full Text Available INTRODUCTION: Pressure ulcers are a prevalent health problem in today's society. The shortage of suitable animal models limits our understanding and our ability to develop new therapies. This study aims to report on the development of a novel and reproducible human skin pressure ulcer model in mice. MATERIAL AND METHODS: Male non-obese, diabetic, severe combined immunodeficiency mice (n = 22 were engrafted with human skin. A full-thickness skin graft was placed onto 4×3 cm wounds created on the dorsal skin of the mice. Two groups with permanent grafts were studied after 60 days. The control group (n = 6 was focused on the process of engraftment. Evaluations were conducted with photographic assessment, histological analysis and fluorescence in situ hybridization (FISH techniques. The pressure ulcer group (n = 12 was created using a compression device. A pressure of 150 mmHg for 8 h, with a total of three cycles of compression-release was exerted. Evaluations were conducted with photographic assessment and histological analysis. RESULTS: Skin grafts in the control group took successfully, as shown by visual assessment, FISH techniques and histological analysis. Pressure ulcers in the second group showed full-thickness skin loss with damage and necrosis of all the epidermal and dermal layers (ulcer stage III in all cases. Complete repair occurred after 40 days. CONCLUSIONS: An inexpensive, reproducible human skin pressure ulcer model has been developed. This novel model will facilitate the development of new clinically relevant therapeutic strategies that can be tested directly on human skin.

  2. Phenylethanoid Glycosides of Cistanche on menopausal syndrome model in mice

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    Shuo Tian

    2017-05-01

    Full Text Available Cistanche is the traditional and precious Chinese herbal, with two thousand years of use history in China. It has the effect on tonifying kidney, strong supplement to the liver and kidney, and replenishing essence and blood, known as the “desert ginseng”. Here, we explored the mechanism of Phenylethanoid Glycosides of Cistanche (PGC to the model mice of menopausal syndrome, as well as the therapeutic effect and characteristics of PGC to the menopausal syndrome. In this study, KM mice were reproduced by the complete resection of the ovaries on both sides of the back to establish the model mice of menopausal syndrome (MPS, and received distilled water or drugs, respectively. Model mice received distilled water. Mice received 200 mg/(kg day high doses of Phenylethanoid Glycosides of Cistanche (HPGC, and 100 mg/(kg day medium doses of Phenylethanoid Glycosides of Cistanche (MPGC, and 50 mg/(kg day low doses of Phenylethanoid Glycosides of Cistanche (LPGC. After 21 days, it could determine the number of independent activities and the number of standing, the latent period of first entering the dark room, and the electric number. It also calculated the viscera index of uterus, thymus, spleen, measured the levels of estradiol (E2, testosterone (T, luteinizing hormone (LH, and follicle-stimulating hormone (FSH in the serum. Furthermore, it observed the pathological changes of uterus, thymus, spleen and pituitary of mice. The results showed that behavioral indicators: Compared with the model group (MG, HPGC, MPGC, LPGC could increase the independent activities (P < 0.01; HPGC, MPGC could increase the number of standing, the latent period of first entering the dark room, and reduce the electric number (P < 0.01; LPGC could increase the number of standing (P < 0.05; Viscera index: Compared with MG, HPGC, MPGC could increase the viscera index of uterus, thymus, spleen (P < 0.01; LPGC could increase the viscera index of uterus (P < 0

  3. Rho, a Fraction From Rhodiola crenulate, Ameliorates Hepatic Steatosis in Mice Models

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    Qin Yi

    2018-03-01

    Full Text Available The prevalence of non-alcoholic fatty liver disease (NAFLD, which is developed from hepatic steatosis, is increasing worldwide. However, no specific drugs for NAFLD have been approved yet. To observe the effects of Rho, a fraction from Rhodiola crenulate, on non-alcoholic hepatic steatosis, three mouse models with characteristics of NAFLD were used including high-fat diet (HFD-induced obesity (DIO mice, KKAy mice, and HFD combined with tetracycline stimulated Model-T mice. Hepatic lipid accumulation was determined via histopathological analysis and/or hepatic TG determination. The responses to insulin were evaluated by insulin tolerance test (ITT, glucose tolerance test (GTT, and hyperinsulinemic-euglycemic clamp, respectively. The pathways involved in hepatic lipid metabolism were observed via western-blot. Furthermore, the liver microcirculation was observed by inverted microscopy. The HPLC analysis indicated that the main components of Rho were flavan polymers. The results of histopathological analysis showed that Rho could ameliorate hepatic steatosis in DIO, KKAy, and Model-T hepatic steatosis mouse models, respectively. After Rho treatment in DIO mice, insulin resistance was improved with increasing glucose infusion rate (GIR in hyperinsulinemic-euglycemic clamp, and decreasing areas under the blood glucose-time curve (AUC in both ITT and GTT; the pathways involved in fatty acid uptake and de novo lipogenesis were both down-regulated, respectively. However, the pathways involved in beta-oxidation and VLDL-export on hepatic steatosis were not changed significantly. The liver microcirculation disturbances were also improved by Rho in DIO mice. These results suggest that Rho is a lead nature product for hepatic steatosis treatment. The mechanism is related to enhancing insulin sensitivity, suppressing fatty acid uptake and inhibiting de novo lipogenesis in liver.

  4. Testing photobiomodulatory effects of laser irradiation on wound healing: development of an improved model for dressing wounds in mice.

    Science.gov (United States)

    Chung, Tzu-Yun; Peplow, Philip V; Baxter, G David

    2010-10-01

    To develop a suitable method for dressing skin wounds in BKS.Cg-m(+)/(+)Lepr(db) mice for subsequent use in laser irradiation of wounds. The healing of nonirradiated wounds (controls) was examined histologically to provide essential reference data. Dressing excisional skin wounds in mice has many advantages. However, previous studies using dressings such as Tegaderm W or OpSite, with or without adhesives, have shown that this is not easily achieved. In a pilot study, a full-thickness wound was made on the left flank in six diabetic and six nondiabetic mice, and five different methods were tried for dressing the wounds with Tegaderm HP to develop an optimized procedure. The optimized procedure was used in subsequent studies, with a total of 23 diabetic and 13 nondiabetic mice being controls for laser-irradiated mice. Measurements of healing outcomes from histologic sections of controls were statistically analyzed. The optimized procedure used Tegaderm HP with Cavilon and Fixomull Stretch strips for the first dressing, and with Mastisol for subsequent dressings. Wound closure by contraction was retarded in a large proportion of diabetic mice (approximately 80%) and a small proportion of nondiabetic mice. These wounds, described as "splinted," healed mainly by epithelial regeneration and granulation tissue formation. A simple, easy-to-perform procedure was developed for dressing wounds in diabetic and nondiabetic mice. It was found to cause splinting with wound healing mimicking that in human patients. This model is suitable for examining the effects of different therapies on wound healing, including lasers.

  5. Environmental enrichment attenuates behavioral abnormalities in valproic acid-exposed autism model mice.

    Science.gov (United States)

    Yamaguchi, Hiroshi; Hara, Yuta; Ago, Yukio; Takano, Erika; Hasebe, Shigeru; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

    2017-08-30

    We recently demonstrated that prenatal exposure to valproic acid (VPA) at embryonic day 12.5 causes autism spectrum disorder (ASD)-like phenotypes such as hypolocomotion, anxiety-like behavior, social deficits and cognitive impairment in mice and that it decreases dendritic spine density in the hippocampal CA1 region. Previous studies show that some abnormal behaviors are improved by environmental enrichment in ASD rodent models, but it is not known whether environmental enrichment improves cognitive impairment. In the present study, we examined the effects of early environmental enrichment on behavioral abnormalities and neuromorphological changes in prenatal VPA-treated mice. We also examined the role of dendritic spine formation and synaptic protein expression in the hippocampus. Mice were housed for 4 weeks from 4 weeks of age under either a standard or enriched environment. Enriched housing was found to increase hippocampal brain-derived neurotrophic factor mRNA levels in both control and VPA-exposed mice. Furthermore, in VPA-treated mice, the environmental enrichment improved anxiety-like behavior, social deficits and cognitive impairment, but not hypolocomotion. Prenatal VPA treatment caused loss of dendritic spines in the hippocampal CA1 region and decreases in mRNA levels of postsynaptic density protein-95 and SH3 and multiple ankyrin repeat domains 2 in the hippocampus. These hippocampal changes were improved by the enriched housing. These findings suggest that the environmental enrichment improved most ASD-like behaviors including cognitive impairment in the VPA-treated mice by enhancing dendritic spine function. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Modeling cognition and disease using human glial chimeric mice.

    Science.gov (United States)

    Goldman, Steven A; Nedergaard, Maiken; Windrem, Martha S

    2015-08-01

    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 that transplanted hGPCs not only engraft and expand within murine hosts, but dynamically outcompete the resident progenitors so as to ultimately dominate the host brain. The engrafted human progenitor cells proceed to generate parenchymal astrocytes, and when faced with a hypomyelinated environment, 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 cognition and information processing. In addition, the cellular humanization of these brains permits their use in studying glial infectious and inflammatory disorders unique to humans, and the effects of those disorders on the glial contributions to cognition. Perhaps most intriguingly, by pairing our ability to construct human glial chimeras with the production of patient-specific hGPCs derived from pluripotential stem cells, we may now establish mice in which a substantial proportion of resident glia are both human and disease-derived. These mice in particular may provide us new opportunities 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 neurological and neuropsychiatric disease. © 2015 Wiley Periodicals, Inc.

  7. A mathematical model for the effects of radiation to the induced cancer in mice

    Science.gov (United States)

    Wada, Takahiro; Manabe, Yuichiro; Bando, Masako

    We have been studying biological effects of radiation in terms of mathematical models. There are two main objects that we need to study: mutation and cancer. We proposed the Whack-A-Mole (WAM) model which takes account of the repair effects to study radiation induced mutations. We applied it to the mutation of several species including Drosophila and mice, and succeeded to reproduce the dose and dose-rate dependence of the mutation rates. Here, as a next step, we study the effects of low dose-rate radiation to an induced cancer in mice. In the experiment, they divided their mice in four groups and kept them under constant gamma-ray radiations with different dose rate for each group since the birth. On the 35th day, chemical carcinogen was given to each mouse and they observed the occurrence and the growth of cancer for one year. Our mathematical model consists of two stages. The first stage describes a multiple-step carcinogenesis and the second stage describes its growth. We assume that the carcinogenesis starts with the chemical carcinogen and that the rate of the following processes depends on the dose rate as it does in the WAM model. We found some irregularities in the data, however, the overall fit is satisfactory. This work was supported by JSPS KAKENHI Grant Number JP16H04637.

  8. A model of hemorrhagic cystitis induced with acrolein in mice

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    C.K.L.P. Batista

    2006-11-01

    Full Text Available Acrolein is a urinary metabolite of cyclophosphamide and ifosfamide, which has been reported to be the causative agent of hemorrhagic cystitis induced by these compounds. A direct cytotoxic effect of acrolein, however, has not yet been demonstrated. In the present study, the effects of intravesical injection of acrolein and mesna, the classical acrolein chemical inhibitor, were evaluated. Male Swiss mice weighing 25 to 35 g (N = 6 per group received saline or acrolein (25, 75, 225 µg intravesically 3, 6, 12, and 24 h before sacrifice for evaluation of bladder wet weight, macroscopic and histopathological changes by Gray's criteria, and 3 and 24 h for assessment of increase in vascular permeability. In other animals, mesna was administered intravesically (2 mg or systemically (80 mg/kg 1 h before acrolein. Intravesical administration of acrolein induced a dose- and time-dependent increase in vascular permeability and bladder wet weight (within 3 h: 2.2- and 21-fold increases in bladder wet weight and Evans blue dye exuded, respectively, at doses of 75 µg/bladder, as confirmed by Gray's criteria. Pretreatment with mesna (2-mercaptoethanesulfonic acid, which interacts with acrolein resulting in an inactive compound, inhibited all changes induced by acrolein. Our results are the first demonstration that intravesical administration of acrolein induces hemorrhagic cystitis. This model of acrolein-induced hemorrhagic cystitis in mice may be an important tool for the evaluation of the mechanism by which acrolein induces bladder lesion, as well as for investigation of new uroprotective drugs.

  9. 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...

  10. Social overcrowding as a chronic stress model that increases adiposity in mice.

    Science.gov (United States)

    Lin, En-Ju D; Sun, Meng; Choi, Eugene Y; Magee, Daniel; Stets, Colin W; During, Matthew J

    2015-01-01

    Stress is a widely recognized risk factor for psychiatric and metabolic disorders. A number of animal models utilizing various stressors have been developed to facilitate our understanding in the pathophysiology of stress-related dysfunctions. The most commonly used chronic stress paradigms include the unpredictable chronic mild stress paradigm, the social defeat paradigm and the social deprivation paradigm. Here we assess the potential of social crowding as an alternative chronic stress model to study the effects on affective behaviors and metabolic disturbances. Ten-week-old male C57BL/6 mice were housed in groups of four (control) or eight (social crowding; SC) in standard cage for 9 weeks. Exploration, anxiety- and depressive-like behaviors were assessed in the open field test, the elevated T-maze, the novelty-suppressed feeding test and the forced swim test. SC mice exhibited a modest anxiety-like phenotype without change in depressive-like behaviors. Nine weeks of social crowding did not affect the body weight, but robustly increased adiposity as determined by increased mass of fat depots. Consistent with the increased fat content, serum leptin was markedly elevated in the SC mice. Specific changes in gene expression were also observed in the hypothalamus and the white adipose tissue following SC housing. Our study demonstrates the potential of social crowding as an alternative model for the study of stress-related metabolic and behavioral dysfunctions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. A progressive compression model of thoracic spinal cord injury in mice: function assessment and pathological changes in spinal cord

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    Guo-dong Sun

    2017-01-01

    Full Text Available Non-traumatic injury accounts for approximately half of clinical spinal cord injury, including chronic spinal cord compression. However, previous rodent spinal cord compression models are mainly designed for rats, few are available for mice. Our aim is to develop a thoracic progressive compression mice model of spinal cord injury. In this study, adult wild-type C57BL/6 mice were divided into two groups: in the surgery group, a screw was inserted at T9 lamina to compress the spinal cord, and the compression was increased by turning it further into the canal (0.2 mm post-surgery every 2 weeks up to 8 weeks. In the control group, a hole was drilled into the lamina without inserting a screw. The results showed that Basso Mouse Scale scores were lower and gait worsened. In addition, the degree of hindlimb dysfunction in mice was consistent with the degree of spinal cord compression. The number of motor neurons in the anterior horn of the spinal cord was reduced in all groups of mice, whereas astrocytes and microglia were gradually activated and proliferated. In conclusion, this progressive compression of thoracic spinal cord injury in mice is a preferable model for chronic progressive spinal cord compression injury.

  12. The Lag Model, a Turbulence Model for Wall Bounded Flows Including Separation

    Science.gov (United States)

    Olsen, Michael E.; Coakley, Thomas J.; Kwak, Dochan (Technical Monitor)

    2001-01-01

    A new class of turbulence model is described for wall bounded, high Reynolds number flows. A specific turbulence model is demonstrated, with results for favorable and adverse pressure gradient flowfields. Separation predictions are as good or better than either Spalart Almaras or SST models, do not require specification of wall distance, and have similar or reduced computational effort compared with these models.

  13. Swiss bare mice: a suitable model for transcutaneous in vivo Raman spectroscopic studies of breast cancer.

    Science.gov (United States)

    Bhattacharjee, T; Kumar, Piyush; Maru, G; Ingle, A; Krishna, C Murali

    2014-01-01

    Breast cancer is the most common cancer affecting females worldwide. As early detection results in better prognosis, screening tools for breast cancer are being explored. Raman spectroscopy, a rapid, objective, and noninvasive tool, has shown promising results in the diagnosis of several cancers including breast cancer. For development as a screening tool, a study of spectral signatures associated with breast cancer progression is imperative. However, such studies are not possible in human subjects. Hence, there is a need for a suitable animal model, which is conducive to transcutaneous in vivo Raman spectroscopic measurements of breast with minimal interference from skin and hair and has contribution from functional mammary epithelium of breast. In this study, rodent models like C57, Swiss albino, Swiss bare, agouti mice, and Sprague-Dawley rats were evaluated. Among these models, transcutaneous breast spectra of hairless Swiss bare mice have the best signal-to-noise ratio and were closest to reported ex vivo as well as intraoperative in vivo human breast spectra. Principal component-linear discriminant analysis of several anatomical sites confirms minimal skin interference and suggests contribution from functional mammary epithelium of breast. Moreover, transcutaneous spectra from normal breast and breast tumors of Swiss bare mice could be classified with 99% efficiency, which is better than the previous reports. Thus, Swiss bare mice model may be better suited for transcutaneous in vivo Raman spectroscopic studies of breast physiology and pathology, especially breast cancer. Prospectively, in addition to cancer progression, breast-to-bone metastasis can also be studied, since these anatomical sites can be uniquely classified.

  14. BioModels: expanding horizons to include more modelling approaches and formats.

    Science.gov (United States)

    Glont, Mihai; Nguyen, Tung V N; Graesslin, Martin; Hälke, Robert; Ali, Raza; Schramm, Jochen; Wimalaratne, Sarala M; Kothamachu, Varun B; Rodriguez, Nicolas; Swat, Maciej J; Eils, Jurgen; Eils, Roland; Laibe, Camille; Malik-Sheriff, Rahuman S; Chelliah, Vijayalakshmi; Le Novère, Nicolas; Hermjakob, Henning

    2018-01-04

    BioModels serves as a central repository of mathematical models representing biological processes. It offers a platform to make mathematical models easily shareable across the systems modelling community, thereby supporting model reuse. To facilitate hosting a broader range of model formats derived from diverse modelling approaches and tools, a new infrastructure for BioModels has been developed that is available at http://www.ebi.ac.uk/biomodels. This new system allows submitting and sharing of a wide range of models with improved support for formats other than SBML. It also offers a version-control backed environment in which authors and curators can work collaboratively to curate models. This article summarises the features available in the current system and discusses the potential benefit they offer to the users over the previous system. In summary, the new portal broadens the scope of models accepted in BioModels and supports collaborative model curation which is crucial for model reproducibility and sharing. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating Disseminated Infection with Multi-organ Involvement Including Orchitis Effectively Treated by Recombinant Type I Interferons.

    Science.gov (United States)

    Chan, Jasper Fuk-Woo; Zhang, Anna Jinxia; Chan, Chris Chung-Sing; Yip, Cyril Chik-Yan; Mak, Winger Wing-Nga; Zhu, Houshun; Poon, Vincent Kwok-Man; Tee, Kah-Meng; Zhu, Zheng; Cai, Jian-Piao; Tsang, Jessica Oi-Ling; Chik, Kenn Ka-Heng; Yin, Feifei; Chan, Kwok-Hung; Kok, Kin-Hang; Jin, Dong-Yan; Au-Yeung, Rex Kwok-Him; Yuen, Kwok-Yung

    2016-12-01

    Disseminated or fatal Zika virus (ZIKV) infections were reported in immunosuppressed patients. Existing interferon-signaling/receptor-deficient mouse models may not be suitable for evaluating treatment effects of recombinant interferons. We developed a novel mouse model for ZIKV infection by immunosuppressing BALB/c mice with dexamethasone. Dexamethasone-immunosuppressed male mice (6-8weeks) developed disseminated infection as evidenced by the detection of ZIKV-NS1 protein expression and high viral loads in multiple organs. They had ≥10% weight loss and high clinical scores soon after dexamethasone withdrawal (10dpi), which warranted euthanasia at 12dpi. Viral loads in blood and most tissues at 5dpi were significantly higher than those at 12dpi (Pvirus dissemination, inflammation of various tissues, especially orchitis, may be potential complications of ZIKV infection with significant implications on disease transmission and male fertility. Interferon treatment should be considered in patients at high risks for ZIKV-associated complications when the potential benefits outweigh the side effects of treatment. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Spdef null mice lack conjunctival goblet cells and provide a model of dry eye.

    Science.gov (United States)

    Marko, Christina K; Menon, Balaraj B; Chen, Gang; Whitsett, Jeffrey A; Clevers, Hans; Gipson, Ilene K

    2013-07-01

    Goblet cell numbers decrease within the conjunctival epithelium in drying and cicatrizing ocular surface diseases. Factors regulating goblet cell differentiation in conjunctival epithelium are unknown. Recent data indicate that the transcription factor SAM-pointed domain epithelial-specific transcription factor (Spdef) is essential for goblet cell differentiation in tracheobronchial and gastrointestinal epithelium of mice. Using Spdef(-/-) mice, we determined that Spdef is required for conjunctival goblet cell differentiation and that Spdef(-/-) mice, which lack conjunctival goblet cells, have significantly increased corneal surface fluorescein staining and tear volume, a phenotype consistent with dry eye. Microarray analysis of conjunctival epithelium in Spdef(-/-) mice revealed down-regulation of goblet cell-specific genes (Muc5ac, Tff1, Gcnt3). Up-regulated genes included epithelial cell differentiation/keratinization genes (Sprr2h, Tgm1) and proinflammatory genes (Il1-α, Il-1β, Tnf-α), all of which are up-regulated in dry eye. Interestingly, four Wnt pathway genes were down-regulated. SPDEF expression was significantly decreased in the conjunctival epithelium of Sjögren syndrome patients with dry eye and decreased goblet cell mucin expression. These data demonstrate that Spdef is required for conjunctival goblet cell differentiation and down-regulation of SPDEF may play a role in human dry eye with goblet cell loss. Spdef(-/-) mice have an ocular surface phenotype similar to that in moderate dry eye, providing a new, more convenient model for the disease. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. Chemostat modeling of Escherichia coli persistence in conventionalized mono-associated and streptomycin-treated mice

    DEFF Research Database (Denmark)

    Rang, C.; Midtvedt, T.; Molin, Søren

    2001-01-01

    We have previously shown that Escherichia coli BJ4 has similar doubling time in mice that are mono-associated (having only the inoculated E. coli BJ4) or streptomycin-treated (having mainly gram-positive bacteria plus the inoculated E. coli BJ4). We also showed that when the mice were conventiona......We have previously shown that Escherichia coli BJ4 has similar doubling time in mice that are mono-associated (having only the inoculated E. coli BJ4) or streptomycin-treated (having mainly gram-positive bacteria plus the inoculated E. coli BJ4). We also showed that when the mice were...... the decrease in colony counts, we analyzed our previous results by a chemostat model. The analysis shows that the increasing doubling time alone is sufficient to explain the decrease in colony counts in mono- associated mice, but not in the streptomycin-treated mice. The observed decreasing rate in colony...... counts in streptomycin- treated mice is slower than predicted. Furthermore, whereas the model predicted a decrease to extinction in both mice, the E. coli persist at a frequency 10-80 times higher in streptomycin- treated mice than in mono-associated mice. Thus, while a chemostat model is able to explain...

  18. Effect of PCBs on the lactational transfer of methyl mercury in mice : PBPK modeling

    NARCIS (Netherlands)

    Lee, Sun Ku; Hamer, Dwayne; Bedwell, Cathy L.; Lohitnavy, Manupat; Yang, Raymond S. H.

    MeHg and PCB exposure to lactating mice were analyzed and a physiologically based pharmacokinetic (PBPK) model was developed to describe the lactational transfer of MeHg in mice. The influence of albumin on the lactational transfer of MeHg was incorporated into the PBPK model. Experimental results

  19. Establishment of a Novel Autoimmune Experimental Model of Bladder Pain Syndrome/Interstitial Cystitis in C57BL/6 Mice.

    Science.gov (United States)

    Jin, Xing-Wei; Liu, Bo-Ke; Zhang, Xiang; Zhao, Zhong-Hua; Shao, Yuan

    2017-06-01

    The aim of this study is to identify whether vaccinating twice with bladder homogenate can establish a new model of experimental autoimmune cystitis (EAC) in C57BL/6 strain mice. C57BL/6 mice were vaccinated with bladder homogenate in complete Freund's adjuvant (CFA) and boost immunized with bladder homogenate in incomplete Freund's adjuvant (IFA) after 2 weeks were used as the EAC model. Mice immunized with phosphate-buffered saline (PBS) in CFA or IFA were used as the control. Micturition habits and suprapubic-pelvic pain threshold were measured 4 weeks after primary immunization. Bladder to body weight ratios and expression of inflammatory cytokines and neurokinin 1 receptor (NK1R) were then examined. Histologic and immunohistochemical examination of the bladder was carried out, and IL-1β, IFN-γ, and TNF-α production by the kidneys, liver, and lungs was also tested. Double-immunized mice were extensively sensitive to pressure applied on the pelvic area (P < 0.001). Compared to single-immunized mice or controls, double-immunized mice showed more micturition frequency, lower urine output per micturition, higher bladder to body weight ratio, and significant elevation in the expression of inflammatory cytokines, including IL-1β, IL-4, IL-6, IL-10, IFN-γ, and TNF-α (all P < 0.05). NK1R gene expression was significantly increased in double-immunized mice compared to the other three groups (P < 0.001). A nonspecific immune response occurred in the liver but was much weaker than bladder inflammation. Our dual immunization EAC model in C57BL/6 mice can effectively mimic the symptoms and pathophysiologic characteristics of BPS/IC and thus can be widely used to investigate the pathogenesis and therapeutic strategies of BPS/IC.

  20. Estimation of Genetic Variance Components Including Mutation and Epistasis using Bayesian Approach in a Selection Experiment on Body Weight in Mice

    DEFF Research Database (Denmark)

    Widyas, Nuzul; Jensen, Just; Nielsen, Vivi Hunnicke

    selected downwards and three lines were kept as controls. Bayesian statistical methods are used to estimate the genetic variance components. Mixed model analysis is modified including mutation effect following the methods by Wray (1990). DIC was used to compare the model. Models including mutation effect...

  1. [Biological characteristics of an established model of ovarian cancer in mice and its homologous cell lines].

    Science.gov (United States)

    Zhang, Zheng-Mao; Zhang, Chao; Zhang, Feng-Hua; Shan, Bao-En; Nakagawa, Shinsaku

    2006-06-01

    There are no specific methods for early diagnosis of ovarian cancer, recurrence prevention and drug-resistance. The experimental mouse model of ovarian cancer could help to reveal the biological and genetic features of ovarian cancer, and provide rational basis for further intervention strategy. This study was to establish a model of ovarian cancer in mice and homologous cell line, and analyze its biological characteristics. Ovarian cancer was developed in 8-week-old female F1 (C57BL/6N x C3H/He) mice by a single whole-body neutron irradiation of 2.7 Gy from a (252)Cf source. A metastatic cell line was established through serial subcutaneous transplantation of the primary tumor for 11 generations, and then tumor cells were transferred to in vitro cultivation. These cells were cloned for more than 6 months. The biological characteristics of the tumors and the homologous cell line were determined by cellular and molecular biological techniques. The grafted tumors in mice were successively passaged for 11 generations with a successful inoculation rate of 96% during 23 months. A tumor cell line OV99 isolated from the grafted tumors was established after 6 months and grew steadily. Morphologic characters and ultrastructures of OV99 cells were accorded with those of ovarian cancer epithelia. The chromosomal analysis of OV99 cells revealed aneuploid pattern of 76 chromosomes. Flow cytometry (FCM) and reverse transcription-polymerase chain reaction (RT-PCR) showed same features between OV99 cells and positive control ovarian cancer cell line OVHM, including distribution of cell cycle, rapid growth rate and the expression of P21, P185, P53, proliferating nuclear cell antigen (PCNA) and Cyclin D proteins, and MAGE-1 and MAGE-3 mRNA. Establishment of the ovarian carcinoma animal model in mice and OV99, a cell line owns biologic characteristics of ovarian cancer cells, provides experimental materials for further investigation of ovarian carcinoma.

  2. A Model of Left Ventricular Dysfunction Complicated by CAWS Arteritis in DBA/2 Mice

    Directory of Open Access Journals (Sweden)

    Naoto Hirata

    2012-01-01

    Full Text Available It was reported previously that a Candida albicans water-soluble fraction (CAWS, including a mannoprotein and β-glucan complex, has strong potency in inducing fatal necrotizing arteritis in DBA/2 mice. In this study, histopathological changes and cardiac function were investigated in this system. One mg/day of CAWS was given to DBA/2 mice via peritoneal injection for five days. The CAWS-treated DBA/2 mice were induced aortitis and died at an incidence of 100% within several weeks. Histological findings included stenosis in the left ventricular outflow tract (LVOT and severe inflammatory changes of the aortic valve with fibrinoid necrosis. Cardiomegaly was observed and heart weight increased 1.62 fold (<0.01. Echocardiography revealed a severe reduction in contractility and dilatation of the cavity in the left ventricle (LV: LV fractional shortening (LVFS decreased from 71% to 38% (<0.01, and the LV end-diastolic diameter (LVDd increased from 2.21 mm to 3.26 mm (<0.01. The titer of BNP mRNA increased in the CAWS-treated group. Severe inflammatory changes resulting from CAWS brought about lethal LV dysfunction by aortic valve deformation with LVOT stenosis. This system is proposed as an easy and useful experimental model of heart failure because CAWS arteritis can be induced by CAWS injection alone.

  3. Gastroesophageal reflux leads to esophageal cancer in a surgical model with mice

    Directory of Open Access Journals (Sweden)

    Chen Xiaoxin

    2009-07-01

    Full Text Available Abstract Background Esophago-gastroduodenal anastomosis with rats mimics the development of human Barrett's esophagus and esophageal adenocarcinoma by introducing mixed reflux of gastric and duodenal contents into the esophagus. However, use of this rat model for mechanistic and chemopreventive studies is limited due to lack of genetically modified rat strains. Therefore, a mouse model of esophageal adenocarcinoma is needed. Methods We performed reflux surgery on wild-type, p53A135V transgenic, and INK4a/Arf+/- mice of A/J strain. Some mice were also treated with omeprazole (1,400 ppm in diet, iron (50 mg/kg/m, i.p., or gastrectomy plus iron. Mouse esophagi were harvested at 20, 40 or 80 weeks after surgery for histopathological analysis. Results At week 20, we observed metaplasia in wild-type mice (5%, 1/20 and p53A135V mice (5.3%, 1/19. At week 40, metaplasia was found in wild-type mice (16.2%, 6/37, p53A135V mice (4.8%, 2/42, and wild-type mice also receiving gastrectomy and iron (6.7%, 1/15. Esophageal squamous cell carcinoma developed in INK4a/Arf+/- mice (7.1%, 1/14, and wild-type mice receiving gastrectomy and iron (21.4%, 3/14. Among 13 wild-type mice which were given iron from week 40 to 80, twelve (92.3% developed squamous cell carcinoma at week 80. None of these mice developed esophageal adenocarcinoma. Conclusion Surgically induced gastroesophageal reflux produced esophageal squamous cell carcinoma, but not esophageal adenocarcinoma, in mice. Dominant negative p53 mutation, heterozygous loss of INK4a/Arf, antacid treatment, iron supplementation, or gastrectomy failed to promote esophageal adenocarcinoma in these mice. Further studies are needed in order to develop a mouse model of esophageal adenocarcinoma.

  4. Insulin Activates Vagal Afferent Neurons Including those Innervating Pancreas via Insulin Cascade and Ca(2+ Influx: Its Dysfunction in IRS2-KO Mice with Hyperphagic Obesity.

    Directory of Open Access Journals (Sweden)

    Yusaku Iwasaki

    Full Text Available Some of insulin's functions, including glucose/lipid metabolism, satiety and neuroprotection, involve the alteration of brain activities. Insulin could signal to the brain via penetrating through the blood-brain barrier and acting on the vagal afferents, while the latter remains unproved. This study aimed to clarify whether insulin directly regulates the nodose ganglion neurons (NGNs of vagal afferents in mice. NGs expressed insulin receptor (IR and insulin receptor substrate-2 (IRS2 mRNA, and some of NGNs were immunoreactive to IR. In patch-clamp and fura-2 microfluorometric studies, insulin (10(-12∼10(-6 M depolarized and increased cytosolic Ca(2+ concentration ([Ca(2+]i in single NGNs. The insulin-induced [Ca(2+]i increases were attenuated by L- and N-type Ca(2+ channel blockers, by phosphatidylinositol 3 kinase (PI3K inhibitor, and in NGNs from IRS2 knockout mice. Half of the insulin-responsive NGNs contained cocaine- and amphetamine-regulated transcript. Neuronal fibers expressing IRs were distributed in/around pancreatic islets. The NGNs innervating the pancreas, identified by injecting retrograde tracer into the pancreas, responded to insulin with much greater incidence than unlabeled NGNs. Insulin concentrations measured in pancreatic vein was 64-fold higher than that in circulation. Elevation of insulin to 10(-7 M recruited a remarkably greater population of NGNs to [Ca(2+]i increases. Systemic injection of glibenclamide rapidly released insulin and phosphorylated AKT in NGs. Furthermore, in IRS2 knockout mice, insulin action to suppress [Ca(2+]i in orexigenic ghrelin-responsive neurons in hypothalamic arcuate nucleus was intact while insulin action on NGN was markedly attenuated, suggesting a possible link between impaired insulin sensing by NGNs and hyperphagic obese phenotype in IRS2 knockout mice These data demonstrate that insulin directly activates NGNs via IR-IRS2-PI3K-AKT-cascade and depolarization-gated Ca(2+ influx. Pancreas

  5. Systematic analysis of a xenograft mice model for KSHV+ primary effusion lymphoma (PEL.

    Directory of Open Access Journals (Sweden)

    Lu Dai

    Full Text Available Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL, which arises preferentially in the setting of infection with human immunodeficiency virus (HIV. Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the in vivo effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV(+ PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells propagated in vivo exhibit unique biology, differing from one another or from their parental cell lines propagated through in vitro culture. Therefore, we used a KSHV(+ PEL/BCBL-1 xenograft model involving non-obese diabetic/severe-combined immunodeficient (NOD/SCID mice, and compared characteristics of effusion and solid tumors with their parent cell culture-derived counterparts. Our results indicate that although this xenograft model can be used for study of effusion and solid lymphoma observed in patients, tumor cells in vivo display unique features to those passed in vitro, including viral lytic gene expression profile, rate of solid tumor development, the host proteins and the complex of tumor microenvironment. These items should be carefully considered when the xenograft model is used for testing novel therapeutic strategies against KSHV-related lymphoma.

  6. Modelling Mediterranean agro-ecosystems by including agricultural trees in the LPJmL model

    Science.gov (United States)

    Fader, M.; von Bloh, W.; Shi, S.; Bondeau, A.; Cramer, W.

    2015-11-01

    In the Mediterranean region, climate and land use change are expected to impact on natural and agricultural ecosystems by warming, reduced rainfall, direct degradation of ecosystems and biodiversity loss. Human population growth and socioeconomic changes, notably on the eastern and southern shores, will require increases in food production and put additional pressure on agro-ecosystems and water resources. Coping with these challenges requires informed decisions that, in turn, require assessments by means of a comprehensive agro-ecosystem and hydrological model. This study presents the inclusion of 10 Mediterranean agricultural plants, mainly perennial crops, in an agro-ecosystem model (Lund-Potsdam-Jena managed Land - LPJmL): nut trees, date palms, citrus trees, orchards, olive trees, grapes, cotton, potatoes, vegetables and fodder grasses. The model was successfully tested in three model outputs: agricultural yields, irrigation requirements and soil carbon density. With the development presented in this study, LPJmL is now able to simulate in good detail and mechanistically the functioning of Mediterranean agriculture with a comprehensive representation of ecophysiological processes for all vegetation types (natural and agricultural) and in a consistent framework that produces estimates of carbon, agricultural and hydrological variables for the entire Mediterranean basin. This development paves the way for further model extensions aiming at the representation of alternative agro-ecosystems (e.g. agroforestry), and opens the door for a large number of applications in the Mediterranean region, for example assessments of the consequences of land use transitions, the influence of management practices and climate change impacts.

  7. Mathematical Model of Thyristor Inverter Including a Series-parallel Resonant Circuit

    Directory of Open Access Journals (Sweden)

    Miroslaw Luft

    2008-01-01

    Full Text Available The article presents a mathematical model of thyristor inverter including a series-parallel resonant circuit with theaid of state variable method. Maple procedures are used to compute current and voltage waveforms in the inverter.

  8. Mathematical model of thyristor inverter including a series-parallel resonant circuit

    OpenAIRE

    Luft, M.; Szychta, E.

    2008-01-01

    The article presents a mathematical model of thyristor inverter including a series-parallel resonant circuit with the aid of state variable method. Maple procedures are used to compute current and voltage waveforms in the inverter.

  9. Mathematical Model of Thyristor Inverter Including a Series-parallel Resonant Circuit

    OpenAIRE

    Miroslaw Luft; Elzbieta Szychta

    2008-01-01

    The article presents a mathematical model of thyristor inverter including a series-parallel resonant circuit with theaid of state variable method. Maple procedures are used to compute current and voltage waveforms in the inverter.

  10. Modeling of Pem Fuel Cell Systems Including Controls and Reforming Effects for Hybrid Automotive Applications

    National Research Council Canada - National Science Library

    Boettner, Daisie

    2001-01-01

    .... This study develops models for a stand-alone Proton Exchange Membrane (PEM) fuel cell stack, a direct-hydrogen fuel cell system including auxiliaries, and a methanol reforming fuel cell system for integration into a vehicle performance simulator...

  11. Modeling myocardial infarction in mice: methodology, monitoring, pathomorphology.

    Science.gov (United States)

    Ovsepyan, A A; Panchenkov, D N; Prokhortchouk, E B; Telegin, G B; Zhigalova, N A; Golubev, E P; Sviridova, T E; Matskeplishvili, S T; Skryabin, K G; Buziashvili, U I

    2011-01-01

    Myocardial infarction is one of the most serious and widespread diseases in the world. In this work, a minimally invasive method for simulating myocardial infarction in mice is described in the Russian Federation for the very first time; the procedure is carried out by ligation of the coronary heart artery or by controlled electrocoagulation. As a part of the methodology, a series of anesthetic, microsurgical and revival protocols are designed, owing to which a decrease in the postoperational mortality from the initial 94.6 to 13.6% is achieved. ECG confirms the development of large-focal or surface myocardial infarction. Postmortal histological examination confirms the presence of necrosis foci in the heart muscles of 87.5% of animals. Altogether, the medical data allow us to conclude that an adequate mouse model for myocardial infarction was generated. A further study is focused on the standardization of the experimental procedure and the use of genetically modified mouse strains, with the purpose of finding the most efficient therapeutic approaches for this disease.

  12. Modeling of the Direct Current Generator Including the Magnetic Saturation and Temperature Effects

    Directory of Open Access Journals (Sweden)

    Alfonso J. Mercado-Samur

    2013-11-01

    Full Text Available In this paper the inclusion of temperature effect on the field resistance on the direct current generator model DC1A, which is valid to stability studies is proposed. First, the linear generator model is presented, after the effect of magnetic saturation and the change in the resistance value due to temperature produced by the field current are included. The comparison of experimental results and model simulations to validate the model is used. A direct current generator model which is a better representation of the generator is obtained. Visual comparison between simulations and experimental results shows the success of the proposed model, because it presents the lowest error of the compared models. The accuracy of the proposed model is observed via Modified Normalized Sum of Squared Errors index equal to 3.8979%.

  13. Atmosphere-soil-vegetation model including CO2 exchange processes: SOLVEG2

    International Nuclear Information System (INIS)

    Nagai, Haruyasu

    2004-11-01

    A new atmosphere-soil-vegetation model named SOLVEG2 (SOLVEG version 2) was developed to study the heat, water, and CO 2 exchanges between the atmosphere and land-surface. The model consists of one-dimensional multilayer sub-models for the atmosphere, soil, and vegetation. It also includes sophisticated processes for solar and long-wave radiation transmission in vegetation canopy and CO 2 exchanges among the atmosphere, soil, and vegetation. Although the model usually simulates only vertical variation of variables in the surface-layer atmosphere, soil, and vegetation canopy by using meteorological data as top boundary conditions, it can be used by coupling with a three-dimensional atmosphere model. In this paper, details of SOLVEG2, which includes the function of coupling with atmosphere model MM5, are described. (author)

  14. Mutant Enpp1asj mice as a model for generalized arterial calcification of infancy

    Directory of Open Access Journals (Sweden)

    Qiaoli Li

    2013-09-01

    Generalized arterial calcification of infancy (GACI, an autosomal recessive disorder, is characterized by early mineralization of blood vessels, often diagnosed by prenatal ultrasound and usually resulting in demise during the first year of life. It is caused in most cases by mutations in the ENPP1 gene, encoding an enzyme that hydrolyzes ATP to AMP and inorganic pyrophosphate, the latter being a powerful anti-mineralization factor. Recently, a novel mouse phenotype was recognized as a result of ENU mutagenesis – those mice developed stiffening of the joints, hence the mutant mouse was named ‘ages with stiffened joints’ (asj. These mice harbor a missense mutation, p.V246D, in the Enpp1 gene. Here we demonstrate that the mutant ENPP1 protein is largely absent in the liver of asj mice, and the lack of enzymatic activity results in reduced inorganic pyrophosphate (PPi levels in the plasma, accompanied by extensive mineralization of a number of tissues, including arterial blood vessels. The progress of mineralization is highly dependent on the mineral composition of the diet, with significant shortening of the lifespan on a diet enriched in phosphorus and low in magnesium. These results suggest that the asj mouse can serve as an animal model for GACI.

  15. Combining prior knowledge with data driven modeling of a batch distillation column including start-up

    NARCIS (Netherlands)

    van Lith, PF; Betlem, BHL; Roffel, B

    2003-01-01

    This paper presents the development of a simple model which describes the product quality and production over time of an experimental batch distillation column, including start-up. The model structure is based on a simple physical framework, which is augmented with fuzzy logic. This provides a way

  16. Enhanced UWB Radio Channel Model for Short-Range Communication Scenarios Including User Dynamics

    DEFF Research Database (Denmark)

    Kovacs, Istvan Zsolt; Nguyen, Tuan Hung; Eggers, Patrick Claus F.

    2005-01-01

    channel model represents an enhancement of the existing IEEE 802.15.3a/4a PAN channel model, where antenna and user-proximity effects are not included. Our investigations showed that significant variations of the received wideband power and time-delay signal clustering are possible due the human body...

  17. Including operational data in QMRA model: development and impact of model inputs.

    Science.gov (United States)

    Jaidi, Kenza; Barbeau, Benoit; Carrière, Annie; Desjardins, Raymond; Prévost, Michèle

    2009-03-01

    A Monte Carlo model, based on the Quantitative Microbial Risk Analysis approach (QMRA), has been developed to assess the relative risks of infection associated with the presence of Cryptosporidium and Giardia in drinking water. The impact of various approaches for modelling the initial parameters of the model on the final risk assessments is evaluated. The Monte Carlo simulations that we performed showed that the occurrence of parasites in raw water was best described by a mixed distribution: log-Normal for concentrations > detection limit (DL), and a uniform distribution for concentrations risks significantly. The mean annual risks for conventional treatment are: 1.97E-03 (removal credit adjusted by log parasite = log spores), 1.58E-05 (log parasite = 1.7 x log spores) or 9.33E-03 (regulatory credits based on the turbidity measurement in filtered water). Using full scale validated SCADA data, the simplified calculation of CT performed at the plant was shown to largely underestimate the risk relative to a more detailed CT calculation, which takes into consideration the downtime and system failure events identified at the plant (1.46E-03 vs. 3.93E-02 for the mean risk).

  18. Mice lacking caspase-2 are protected from behavioral changes, but not pathology, in the YAC128 model of Huntington disease

    Directory of Open Access Journals (Sweden)

    Bissada Nagat

    2011-08-01

    Full Text Available Abstract Background Huntington Disease (HD is a neurodegenerative disorder in which caspase activation and cleavage of substrates, including the huntingtin protein, has been invoked as a pathological mechanism. Specific changes in caspase-2 (casp2 activity have been suggested to contribute to the pathogenesis of HD, however unique casp2 cleavage substrates have remained elusive. We thus utilized mice completely lacking casp2 (casp2-/- to examine the role played by casp2 in the progression of HD. This 'substrate agnostic' approach allows us to query the effect of casp2 on HD progression without pre-defining proteolytic substrates of interest. Results YAC128 HD model mice lacking casp2 show protection from well-validated motor and cognitive features of HD, including performance on rotarod, swimming T-maze, pre-pulse inhibition, spontaneous alternation and locomotor tasks. However, the specific pathological features of the YAC128 mice including striatal volume loss and testicular degeneration are unaltered in mice lacking casp2. The application of high-resolution magnetic resonance imaging (MRI techniques validates specific neuropathology in the YAC128 mice that is not altered by ablation of casp2. Conclusions The rescue of behavioral phenotypes in the absence of pathological improvement suggests that different pathways may be operative in the dysfunction of neural circuitry in HD leading to behavioral changes compared to the processes leading to cell death and volume loss. Inhibition of caspase-2 activity may be associated with symptomatic improvement in HD.

  19. Ectopic Mineralization and Conductive Hearing Loss in Enpp1asj Mutant Mice, a New Model for Otitis Media and Tympanosclerosis.

    Directory of Open Access Journals (Sweden)

    Cong Tian

    Full Text Available Otitis media (OM, inflammation of the middle ear, is a common cause of hearing loss in children and in patients with many different syndromic diseases. Studies of the human population and mouse models have revealed that OM is a multifactorial disease with many environmental and genetic contributing factors. Here, we report on otitis media-related hearing loss in asj (ages with stiffened joints mutant mice, which bear a point mutation in the Enpp1 gene. Auditory-evoked brainstem response (ABR measurements revealed that around 90% of the mutant mice (Enpp1asj/asj tested had moderate to severe hearing impairment in at least one ear. The ABR thresholds were variable and generally elevated with age. We found otitis media with effusion (OME in all of the hearing-impaired Enpp1asj/asj mice by anatomic and histological examinations. The volume and inflammatory cell content of the effusion varied among the asj mutant mice, but all mutants exhibited a thickened middle ear epithelium with fibrous polyps and more mucin-secreting goblet cells than controls. Other abnormalities observed in the Enpp1 mutant mice include over-ossification at the round window ridge, thickened and over-calcified stapedial artery, fusion of malleus and incus, and white patches on the inside of tympanic membrane, some of which are typical symptoms of tympanosclerosis. An excessive yellow discharge was detected in the outer ear canal of older asj mutant mice, with 100% penetrance by 5 months of age, and contributes to the progressive nature of the hearing loss. This is the first report of hearing loss and ear pathology associated with an Enpp1 mutation in mice. The Enpp1asj mutant mouse provides a new animal model for studying tympanosclerotic otitis and otitis media with effusion, and also provides a specific model for the hearing loss recently reported to be associated with human ENPP1 mutations causing generalized arterial calcification of infancy and hypophosphatemic rickets.

  20. Ectopic Mineralization and Conductive Hearing Loss in Enpp1asj Mutant Mice, a New Model for Otitis Media and Tympanosclerosis

    Science.gov (United States)

    Tian, Cong; Harris, Belinda S.; Johnson, Kenneth R.

    2016-01-01

    Otitis media (OM), inflammation of the middle ear, is a common cause of hearing loss in children and in patients with many different syndromic diseases. Studies of the human population and mouse models have revealed that OM is a multifactorial disease with many environmental and genetic contributing factors. Here, we report on otitis media-related hearing loss in asj (ages with stiffened joints) mutant mice, which bear a point mutation in the Enpp1 gene. Auditory-evoked brainstem response (ABR) measurements revealed that around 90% of the mutant mice (Enpp1asj/asj) tested had moderate to severe hearing impairment in at least one ear. The ABR thresholds were variable and generally elevated with age. We found otitis media with effusion (OME) in all of the hearing-impaired Enpp1asj/asj mice by anatomic and histological examinations. The volume and inflammatory cell content of the effusion varied among the asj mutant mice, but all mutants exhibited a thickened middle ear epithelium with fibrous polyps and more mucin-secreting goblet cells than controls. Other abnormalities observed in the Enpp1 mutant mice include over-ossification at the round window ridge, thickened and over-calcified stapedial artery, fusion of malleus and incus, and white patches on the inside of tympanic membrane, some of which are typical symptoms of tympanosclerosis. An excessive yellow discharge was detected in the outer ear canal of older asj mutant mice, with 100% penetrance by 5 months of age, and contributes to the progressive nature of the hearing loss. This is the first report of hearing loss and ear pathology associated with an Enpp1 mutation in mice. The Enpp1asj mutant mouse provides a new animal model for studying tympanosclerotic otitis and otitis media with effusion, and also provides a specific model for the hearing loss recently reported to be associated with human ENPP1 mutations causing generalized arterial calcification of infancy and hypophosphatemic rickets. PMID:27959908

  1. Ectopic Mineralization and Conductive Hearing Loss in Enpp1asj Mutant Mice, a New Model for Otitis Media and Tympanosclerosis.

    Science.gov (United States)

    Tian, Cong; Harris, Belinda S; Johnson, Kenneth R

    2016-01-01

    Otitis media (OM), inflammation of the middle ear, is a common cause of hearing loss in children and in patients with many different syndromic diseases. Studies of the human population and mouse models have revealed that OM is a multifactorial disease with many environmental and genetic contributing factors. Here, we report on otitis media-related hearing loss in asj (ages with stiffened joints) mutant mice, which bear a point mutation in the Enpp1 gene. Auditory-evoked brainstem response (ABR) measurements revealed that around 90% of the mutant mice (Enpp1asj/asj) tested had moderate to severe hearing impairment in at least one ear. The ABR thresholds were variable and generally elevated with age. We found otitis media with effusion (OME) in all of the hearing-impaired Enpp1asj/asj mice by anatomic and histological examinations. The volume and inflammatory cell content of the effusion varied among the asj mutant mice, but all mutants exhibited a thickened middle ear epithelium with fibrous polyps and more mucin-secreting goblet cells than controls. Other abnormalities observed in the Enpp1 mutant mice include over-ossification at the round window ridge, thickened and over-calcified stapedial artery, fusion of malleus and incus, and white patches on the inside of tympanic membrane, some of which are typical symptoms of tympanosclerosis. An excessive yellow discharge was detected in the outer ear canal of older asj mutant mice, with 100% penetrance by 5 months of age, and contributes to the progressive nature of the hearing loss. This is the first report of hearing loss and ear pathology associated with an Enpp1 mutation in mice. The Enpp1asj mutant mouse provides a new animal model for studying tympanosclerotic otitis and otitis media with effusion, and also provides a specific model for the hearing loss recently reported to be associated with human ENPP1 mutations causing generalized arterial calcification of infancy and hypophosphatemic rickets.

  2. Experimental transmission of systemic AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice

    Science.gov (United States)

    Maeda, Mayuko; Murakami, Tomoaki; Muhammad, Naeem; Inoshima, Yasuo; Ishiguro, Naotaka

    2016-01-01

    AA amyloidosis is a protein misfolding disease characterized by extracellular deposition of amyloid A (AA) fibrils. AA amyloidosis has been identified in food animals, and it has been postulated that AA amyloidosis may be transmissible to different animal species. Since the precursor protein of AA fibrils is serum amyloid A (SAA), which is an inflammatory acute phase protein, AA amyloidosis is considered to be associated with inflammatory diseases such as rheumatoid arthritis. Chronic diseases such as autoimmune disease and type 2 diabetes mellitus could be potential factors for AA amyloidosis. In this study, to examine the relationship between the induction of AA amyloidosis and chromic abnormalities such as autoimmune disease or type 2 diabetes mellitus, amyloid fibrils from mice, cattle, or chickens were experimentally injected into disease model mice. Wild-type mice were used as controls. The concentrations of SAA, IL-6, and IL-10 in autoimmune disease model mice were higher than those of control mice. However, induction of AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice was lower than that in control mice, and the amount of amyloid deposits in the spleens of both mouse models was lower than that of control mice according to Congo red staining and immunohistochemistry. These results suggest that factors other than SAA levels, such as an inflammatory or anti-inflammatory environment in the immune response, may be involved in amyloid deposition. PMID:27321428

  3. Experimental transmission of systemic AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice.

    Science.gov (United States)

    Maeda, Mayuko; Murakami, Tomoaki; Muhammad, Naeem; Inoshima, Yasuo; Ishiguro, Naotaka

    2016-11-01

    AA amyloidosis is a protein misfolding disease characterized by extracellular deposition of amyloid A (AA) fibrils. AA amyloidosis has been identified in food animals, and it has been postulated that AA amyloidosis may be transmissible to different animal species. Since the precursor protein of AA fibrils is serum amyloid A (SAA), which is an inflammatory acute phase protein, AA amyloidosis is considered to be associated with inflammatory diseases such as rheumatoid arthritis. Chronic diseases such as autoimmune disease and type 2 diabetes mellitus could be potential factors for AA amyloidosis. In this study, to examine the relationship between the induction of AA amyloidosis and chromic abnormalities such as autoimmune disease or type 2 diabetes mellitus, amyloid fibrils from mice, cattle, or chickens were experimentally injected into disease model mice. Wild-type mice were used as controls. The concentrations of SAA, IL-6, and IL-10 in autoimmune disease model mice were higher than those of control mice. However, induction of AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice was lower than that in control mice, and the amount of amyloid deposits in the spleens of both mouse models was lower than that of control mice according to Congo red staining and immunohistochemistry. These results suggest that factors other than SAA levels, such as an inflammatory or anti-inflammatory environment in the immune response, may be involved in amyloid deposition.

  4. Mathematical modeling of the hypothalamic–pituitary–adrenal gland (HPA) axis, including hippocampal mechanisms

    DEFF Research Database (Denmark)

    Andersen, Morten; Vinther, Frank; Ottesen, Johnny T.

    2013-01-01

    This paper presents a mathematical model of the HPA axis. The HPA axis consists of the hypothalamus, the pituitary and the adrenal glands in which the three hormones CRH, ACTH and cortisol interact through receptor dynamics. Furthermore, it has been suggested that receptors in the hippocampus have...... an influence on the axis.A model is presented with three coupled, non-linear differential equations, with the hormones CRH, ACTH and cortisol as variables. The model includes the known features of the HPA axis, and includes the effects from the hippocampus through its impact on CRH in the hypothalamus...

  5. Animal models of physiologic markers of male reproduction: genetically defined infertile mice

    Energy Technology Data Exchange (ETDEWEB)

    Chubb, C.

    1987-10-01

    The present report focuses on novel animal models of male infertility: genetically defined mice bearing single-gene mutations that induce infertility. The primary goal of the investigations was to identify the reproductive defects in these mutant mice. The phenotypic effects of the gene mutations were deciphered by comparing the mutant mice to their normal siblings. Initially testicular steroidogenesis and spermatogenesis were investigated. The physiologic markers for testicular steroidogenesis were steroid secretion by testes perifused in vitro, seminal vesicle weight, and Leydig cell histology. Spermatogenesis was evaluated by the enumeration of homogenization-resistant sperm/spermatids in testes and by morphometric analyses of germ cells in the seminiferous epithelium. If testicular function appeared normal, the authors investigated the sexual behavior of the mice. The parameters of male sexual behavior that were quantified included mount patency, mount frequency, intromission latency, thrusts per intromission, ejaculation latency, and ejaculation duration. Females of pairs breeding under normal circumstances were monitored for the presence of vaginal plugs and pregnancies. The patency of the ejaculatory process was determined by quantifying sperm in the female reproductive tract after sexual behavior tests. Sperm function was studied by quantitatively determining sperm motility during videomicroscopic observation. Also, the ability of epididymal sperm to function within the uterine environment was analyzed by determining sperm capacity to initiate pregnancy after artificial insemination. Together, the experimental results permitted the grouping of the gene mutations into three general categories. They propose that the same biological markers used in the reported studies can be implemented in the assessment of the impact that environmental toxins may have on male reproduction.

  6. A new model mimicking persistent HBV e antigen-negative infection using covalently closed circular DNA in immunocompetent mice.

    Directory of Open Access Journals (Sweden)

    Lei Wang

    Full Text Available Despite the availability of an effective vaccine, hepatitis B virus (HBV infection remains a major health problem. HBV e antigen (HBeAg-negative strains have become prevalent. Previously, no animal model mimicked the clinical course of HBeAg-negative HBV infection. To establish an HBeAg-negative HBV infection model, the 3.2-kb full-length genome of HBeAg-negative HBV was cloned from a clinical sample and then circularized to form covalently closed circular (cccDNA. The resulting cccDNA was introduced into the liver of C57BL/6J mice through hydrodynamic injection. Persistence of the HBeAg-negative infection was monitored at predetermined time points using HBV-specific markers including HBV surface antigen (HBsAg, HBeAg, and HBV core antigen (HBcAg as well as DNA copies. Throughout the study, pAAV-HBV1.2 was used as a control. In mice injected with HBeAg-negative cccDNA, the HBV infection rate was 100% at the initial stage. HBsAg levels increased up to 1 week, at which point levels peaked and dropped quickly thereafter. In 60% of injected mice, HBsAg and HBcAg persisted for more than 10 weeks. High numbers of HBV DNA copies were detected in the serum and liver. Moreover, cccDNA persisted in the liver tissue of HBeAg-negative mice. In contrast to the pAAV-HBV 1.2 injected mice, no HBeAg was found in mice injected with HBeAg-negative HBV throughout the study period. These results demonstrate the first successful establishment of a model of HBeAg-negative HBV-persistent infection in immunocompetent mice. Compared to pAAV-HBV1.2-injected mice, the infection persistence and levels of serum virological and biochemical markers were approximately equal in the model mice. This model will be useful for mechanistic studies on HBeAg-negative HBV infection and will facilitate the evaluation of new antiviral drugs.

  7. Modification of TOUGH2 to Include the Dusty Gas Model for Gas Diffusion; TOPICAL

    International Nuclear Information System (INIS)

    WEBB, STEPHEN W.

    2001-01-01

    The GEO-SEQ Project is investigating methods for geological sequestration of CO(sub 2). This project, which is directed by LBNL and includes a number of other industrial, university, and national laboratory partners, is evaluating computer simulation methods including TOUGH2 for this problem. The TOUGH2 code, which is a widely used code for flow and transport in porous and fractured media, includes simplified methods for gas diffusion based on a direct application of Fick's law. As shown by Webb (1998) and others, the Dusty Gas Model (DGM) is better than Fick's Law for modeling gas-phase diffusion in porous media. In order to improve gas-phase diffusion modeling for the GEO-SEQ Project, the EOS7R module in the TOUGH2 code has been modified to include the Dusty Gas Model as documented in this report. In addition, the liquid diffusion model has been changed from a mass-based formulation to a mole-based model. Modifications for separate and coupled diffusion in the gas and liquid phases have also been completed. The results from the DGM are compared to the Fick's law behavior for TCE and PCE diffusion across a capillary fringe. The differences are small due to the relatively high permeability (k= 10(sup -11) m(sup 2)) of the problem and the small mole fraction of the gases. Additional comparisons for lower permeabilities and higher mole fractions may be useful

  8. Numerical Acoustic Models Including Viscous and Thermal losses: Review of Existing and New Methods

    DEFF Research Database (Denmark)

    Andersen, Peter Risby; Cutanda Henriquez, Vicente; Aage, Niels

    2017-01-01

    This work presents an updated overview of numerical methods including acoustic viscous and thermal losses. Numerical modelling of viscothermal losses has gradually become more important due to the general trend of making acoustic devices smaller. Not including viscothermal acoustic losses...... in such numerical computations will therefore lead to inaccurate or even wrong results. Both, Finite Element Method (FEM) and Boundary Element Method (BEM), formulations are available that incorporate these loss mechanisms. Including viscothermal losses in FEM computations can be computationally very demanding, due...... and BEM method including viscothermal dissipation are compared and investigated....

  9. Direct-phase-variable model of a synchronous reluctance motor including all slot and winding harmonics

    International Nuclear Information System (INIS)

    Obe, Emeka S.; Binder, A.

    2011-01-01

    A detailed model in direct-phase variables of a synchronous reluctance motor operating at mains voltage and frequency is presented. The model includes the stator and rotor slot openings, the actual winding layout and the reluctance rotor geometry. Hence, all mmf and permeance harmonics are taken into account. It is seen that non-negligible harmonics introduced by slots are present in the inductances computed by the winding function procedure. These harmonics are usually ignored in d-q models. The machine performance is simulated in the stator reference frame to depict the difference between this new direct-phase model including all harmonics and the conventional rotor reference frame d-q model. Saturation is included by using a polynomial fitting the variation of d-axis inductance with stator current obtained by finite-element software FEMAG DC (registered) . The detailed phase-variable model can yield torque pulsations comparable to those obtained from finite elements while the d-q model cannot.

  10. Pitx3 deficient mice as a genetic animal model of co-morbid depressive disorder and parkinsonism.

    Science.gov (United States)

    Kim, Kyoung-Shim; Kang, Young-Mi; Kang, Young; Park, Tae-Shin; Park, Hye-Yeon; Kim, Yoon-Jung; Han, Baek-Soo; Kim, Chun-Hyung; Lee, Chul-Ho; Ardayfio, Paul A; Han, Pyung-Lim; Jung, Bong-Hyun; Kim, Kwang-Soo

    2014-03-13

    Approximately 40-50% of all patients with Parkinson׳s disease (PD) show symptoms and signs of depressive disorders, for which neither pathogenic understanding nor rational treatment are available. Using Pit3x-deficient mice, a model for selective nigrostriatal dopaminergic neurodegeneration, we tested depression-related behaviors and acute stress responses to better understand how a nigrostriatal dopaminergic deficit increases the prevalence of depressive disorders in PD patients. Pitx3-deficient mice showed decreased sucrose consumption and preference in the two-bottle free-choice test of anhedonia. Acute restraint stress increased c-Fos (known as a neuronal activity marker) expression levels in various brain regions, including the prefrontal cortex, striatum, nucleus accumbens, and paraventricular nucleus of the hypothalamus (PVN), in both Pitx3+/+ and -/- mice. However, the stress-induced increases in c-Fos levels in the cortex, dorsal striatum, and PVN were significantly greater in Pitx3-/- than +/+ mice, suggesting that signs of depressive disorders in parkinsonism are related to altered stress vulnerability. Based on these results, we propose that Pitx3-/- mice may serve as a useful genetic animal model for co-morbid depressive disorder and parkinsonism. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Multi-tissue computational modeling analyzes pathophysiology of type 2 diabetes in MKR mice.

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    Full Text Available Computational models using metabolic reconstructions for in silico simulation of metabolic disorders such as type 2 diabetes mellitus (T2DM can provide a better understanding of disease pathophysiology and avoid high experimentation costs. There is a limited amount of computational work, using metabolic reconstructions, performed in this field for the better understanding of T2DM. In this study, a new algorithm for generating tissue-specific metabolic models is presented, along with the resulting multi-confidence level (MCL multi-tissue model. The effect of T2DM on liver, muscle, and fat in MKR mice was first studied by microarray analysis and subsequently the changes in gene expression of frank T2DM MKR mice versus healthy mice were applied to the multi-tissue model to test the effect. Using the first multi-tissue genome-scale model of all metabolic pathways in T2DM, we found out that branched-chain amino acids' degradation and fatty acids oxidation pathway is downregulated in T2DM MKR mice. Microarray data showed low expression of genes in MKR mice versus healthy mice in the degradation of branched-chain amino acids and fatty-acid oxidation pathways. In addition, the flux balance analysis using the MCL multi-tissue model showed that the degradation pathways of branched-chain amino acid and fatty acid oxidation were significantly downregulated in MKR mice versus healthy mice. Validation of the model was performed using data derived from the literature regarding T2DM. Microarray data was used in conjunction with the model to predict fluxes of various other metabolic pathways in the T2DM mouse model and alterations in a number of pathways were detected. The Type 2 Diabetes MCL multi-tissue model may explain the high level of branched-chain amino acids and free fatty acids in plasma of Type 2 Diabetic subjects from a metabolic fluxes perspective.

  12. Modeling of Temperature-Dependent Noise in Silicon Nanowire FETs including Self-Heating Effects

    OpenAIRE

    Anandan, P.; Malathi, N.; Mohankumar, N.

    2014-01-01

    Silicon nanowires are leading the CMOS era towards the downsizing limit and its nature will be effectively suppress the short channel effects. Accurate modeling of thermal noise in nanowires is crucial for RF applications of nano-CMOS emerging technologies. In this work, a perfect temperature-dependent model for silicon nanowires including the self-heating effects has been derived and its effects on device parameters have been observed. The power spectral density as a function of thermal resi...

  13. Dipole model analysis of highest precision HERA data, including very low Q2's

    International Nuclear Information System (INIS)

    Luszczak, A.; Kowalski, H.

    2016-12-01

    We analyse, within a dipole model, the final, inclusive HERA DIS cross section data in the low χ region, using fully correlated errors. We show, that these highest precision data are very well described within the dipole model framework starting from Q 2 values of 3.5 GeV 2 to the highest values of Q 2 =250 GeV 2 . To analyze the saturation effects we evaluated the data including also the very low 0.35including this region show a preference of the saturation ansatz.

  14. [The role of sinomenine in treatment of allergic rhinitis mice model and its mechanism].

    Science.gov (United States)

    Chen, Zhe; Tao, Zezhang; Zhang, Nana; Ren, Jie; Deng, Yuqin; Xiao, Bakui

    2013-01-01

    To explore the role of sinomenine in treatment of allergic rhinitis mice model and its possible mechanism. We used ovalbumin (OVA) to make allergic rhinitis model of BALB/c mice. Saline was used in the control group. When we challenged the mice with OVA intranasally, the mice in sinomenine treatment group were feed by the food containing sinomenine. Mice were then killed 24 h after the last OVA challenge. The noses of mice from each group were removed en bloc and fixed, then each section was stained with hematoxylin and eosin. ELISA assay was used to measure the concentration of anti-OVA IgE, IL-4 and IFN-gamma. The proteins expressive level of T-bet and GATA3 were examined. Nasal mucosa of the mice in sinomenine treatment group were not hyperplasia and without obvious infiltration of eosinophils. The concentration of anti-OVA IgE, IL-4 and IFN-gamma in the serum and T-bet and GATA3 expression levels of sinomenine treatment group were lower than those of allergic rhinitis group. The sinomenine can be used to treat allergic rhinitis mice, and the mechanism may rely on the improvements of the Th1/Th2 imbalance.

  15. The No-Core Gamow Shell Model: Including the continuum in the NCSM

    CERN Document Server

    Barrett, B R; Michel, N; Płoszajczak, M

    2015-01-01

    We are witnessing an era of intense experimental efforts that will provide information about the properties of nuclei far from the line of stability, regarding resonant and scattering states as well as (weakly) bound states. This talk describes our formalism for including these necessary ingredients into the No-Core Shell Model by using the Gamow Shell Model approach. Applications of this new approach, known as the No-Core Gamow Shell Model, both to benchmark cases as well as to unstable nuclei will be given.

  16. Conceptualizing a Dynamic Fall Risk Model Including Intrinsic Risks and Exposures.

    Science.gov (United States)

    Klenk, Jochen; Becker, Clemens; Palumbo, Pierpaolo; Schwickert, Lars; Rapp, Kilan; Helbostad, Jorunn L; Todd, Chris; Lord, Stephen R; Kerse, Ngaire

    2017-11-01

    Falls are a major cause of injury and disability in older people, leading to serious health and social consequences including fractures, poor quality of life, loss of independence, and institutionalization. To design and provide adequate prevention measures, accurate understanding and identification of person's individual fall risk is important. However, to date, the performance of fall risk models is weak compared with models estimating, for example, cardiovascular risk. This deficiency may result from 2 factors. First, current models consider risk factors to be stable for each person and not change over time, an assumption that does not reflect real-life experience. Second, current models do not consider the interplay of individual exposure including type of activity (eg, walking, undertaking transfers) and environmental risks (eg, lighting, floor conditions) in which activity is performed. Therefore, we posit a dynamic fall risk model consisting of intrinsic risk factors that vary over time and exposure (activity in context). eHealth sensor technology (eg, smartphones) begins to enable the continuous measurement of both the above factors. We illustrate our model with examples of real-world falls from the FARSEEING database. This dynamic framework for fall risk adds important aspects that may improve understanding of fall mechanisms, fall risk models, and the development of fall prevention interventions. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  17. Modeling of cylindrical surrounding gate MOSFETs including the fringing field effects

    International Nuclear Information System (INIS)

    Gupta, Santosh K.; Baishya, Srimanta

    2013-01-01

    A physically based analytical model for surface potential and threshold voltage including the fringing gate capacitances in cylindrical surround gate (CSG) MOSFETs has been developed. Based on this a subthreshold drain current model has also been derived. This model first computes the charge induced in the drain/source region due to the fringing capacitances and considers an effective charge distribution in the cylindrically extended source/drain region for the development of a simple and compact model. The fringing gate capacitances taken into account are outer fringe capacitance, inner fringe capacitance, overlap capacitance, and sidewall capacitance. The model has been verified with the data extracted from 3D TCAD simulations of CSG MOSFETs and was found to be working satisfactorily. (semiconductor devices)

  18. The Watts-Strogatz network model developed by including degree distribution: theory and computer simulation

    International Nuclear Information System (INIS)

    Chen, Y W; Zhang, L F; Huang, J P

    2007-01-01

    By using theoretical analysis and computer simulations, we develop the Watts-Strogatz network model by including degree distribution, in an attempt to improve the comparison between characteristic path lengths and clustering coefficients predicted by the original Watts-Strogatz network model and those of the real networks with the small-world property. Good agreement between the predictions of the theoretical analysis and those of the computer simulations has been shown. It is found that the developed Watts-Strogatz network model can fit the real small-world networks more satisfactorily. Some other interesting results are also reported by adjusting the parameters in a model degree-distribution function. The developed Watts-Strogatz network model is expected to help in the future analysis of various social problems as well as financial markets with the small-world property

  19. Including Effects of Water Stress on Dead Organic Matter Decay to a Forest Carbon Model

    Science.gov (United States)

    Kim, H.; Lee, J.; Han, S. H.; Kim, S.; Son, Y.

    2017-12-01

    Decay of dead organic matter is a key process of carbon (C) cycling in forest ecosystems. The change in decay rate depends on temperature sensitivity and moisture conditions. The Forest Biomass and Dead organic matter Carbon (FBDC) model includes a decay sub-model considering temperature sensitivity, yet does not consider moisture conditions as drivers of the decay rate change. This study aimed to improve the FBDC model by including a water stress function to the decay sub-model. Also, soil C sequestration under climate change with the FBDC model including the water stress function was simulated. The water stress functions were determined with data from decomposition study on Quercus variabilis forests and Pinus densiflora forests of Korea, and adjustment parameters of the functions were determined for both species. The water stress functions were based on the ratio of precipitation to potential evapotranspiration. Including the water stress function increased the explained variances of the decay rate by 19% for the Q. variabilis forests and 7% for the P. densiflora forests, respectively. The increase of the explained variances resulted from large difference in temperature range and precipitation range across the decomposition study plots. During the period of experiment, the mean annual temperature range was less than 3°C, while the annual precipitation ranged from 720mm to 1466mm. Application of the water stress functions to the FBDC model constrained increasing trend of temperature sensitivity under climate change, and thus increased the model-estimated soil C sequestration (Mg C ha-1) by 6.6 for the Q. variabilis forests and by 3.1 for the P. densiflora forests, respectively. The addition of water stress functions increased reliability of the decay rate estimation and could contribute to reducing the bias in estimating soil C sequestration under varying moisture condition. Acknowledgement: This study was supported by Korea Forest Service (2017044B10-1719-BB01)

  20. Sleep disturbances in highly stress reactive mice: Modeling endophenotypes of major depression

    Directory of Open Access Journals (Sweden)

    Landgraf Rainer

    2011-03-01

    Full Text Available Abstract Background Neuronal mechanisms underlying affective disorders such as major depression (MD are still poorly understood. By selectively breeding mice for high (HR, intermediate (IR, or low (LR reactivity of the hypothalamic-pituitary-adrenocortical (HPA axis, we recently established a new genetic animal model of extremes in stress reactivity (SR. Studies characterizing this SR mouse model on the behavioral, endocrine, and neurobiological levels revealed several similarities with key endophenotypes observed in MD patients. HR mice were shown to have changes in rhythmicity and sleep measures such as rapid eye movement sleep (REMS and non-REM sleep (NREMS as well as in slow wave activity, indicative of reduced sleep efficacy and increased REMS. In the present study we were interested in how far a detailed spectral analysis of several electroencephalogram (EEG parameters, including relevant frequency bands, could reveal further alterations of sleep architecture in this animal model. Eight adult males of each of the three breeding lines were equipped with epidural EEG and intramuscular electromyogram (EMG electrodes. After recovery, EEG and EMG recordings were performed for two days. Results Differences in the amount of REMS and wakefulness and in the number of transitions between vigilance states were found in HR mice, when compared with IR and LR animals. Increased frequencies of transitions from NREMS to REMS and from REMS to wakefulness in HR animals were robust across the light-dark cycle. Detailed statistical analyses of spectral EEG parameters showed that especially during NREMS the power of the theta (6-9 Hz, alpha (10-15 Hz and eta (16-22.75 Hz bands was significantly different between the three breeding lines. Well defined distributions of significant power differences could be assigned to different times during the light and the dark phase. Especially during NREMS, group differences were robust and could be continuously monitored

  1. Including an ocean carbon cycle model into iLOVECLIM (v1.0)

    NARCIS (Netherlands)

    Bouttes, N.; Roche, D.M.V.A.P.; Mariotti, V.; Bopp, L.

    2015-01-01

    The atmospheric carbon dioxide concentration plays a crucial role in the radiative balance and as such has a strong influence on the evolution of climate. Because of the numerous interactions between climate and the carbon cycle, it is necessary to include a model of the carbon cycle within a

  2. Analysis of mice tumor models using dynamic MRI data and a dedicated software platform

    Energy Technology Data Exchange (ETDEWEB)

    Alfke, H.; Maurer, E.; Klose, K.J. [Philipps Univ. Marburg (Germany). Dept. of Radiology; Kohle, S.; Rascher-Friesenhausen, R.; Behrens, S.; Peitgen, H.O. [MeVis - Center for Medical Diagnostic Systems and Visualization, Bremen (Germany); Celik, I. [Philipps Univ. Marburg (Germany). Inst. for Theoretical Surgery; Heverhagen, J.T. [Philipps Univ. Marburg (Germany). Dept. of Radiology; Ohio State Univ., Columbus (United States). Dept. of Radiology

    2004-09-01

    Purpose: To implement a software platform (DynaVision) dedicated to analyze data from functional imaging of tumors with different mathematical approaches, and to test the software platform in pancreatic carcinoma xenografts in mice with severe combined immunodeficiency disease (SCID). Materials and Methods: A software program was developed for extraction and visualization of tissue perfusion parameters from dynamic contrast-enhanced images. This includes regional parameter calculation from enhancement curves, parametric images (e.g., blood flow), animation, 3D visualization, two-compartment modeling a mode for comparing different datasets (e.g., therapy monitoring), and motion correction. We analyzed xenograft tumors from two pancreatic carcinoma cell lines (B x PC3 and ASPC1) implanted in 14 SCID mice after injection of Gd-DTPA into the tail vein. These data were correlated with histopathological findings. Results: Image analysis was completed in approximately 15 minutes per data set. The possibility of drawing and editing ROIs within the whole data set makes it easy to obtain quantitative data from the intensity-time curves. In one animal, motion artifacts reduced the image quality to a greater extent but data analysis was still possible after motion correction. Dynamic MRI of mice tumor models revealed a highly heterogeneous distribution of the contrast-enhancement curves and derived parameters, which correlated with differences in histopathology. ASPc1 tumors showed a more hypervascular type of curves with faster and higher signal enhancement rate (wash-in) and a faster signal decrease (wash-out). BXPC3 tumors showed a more hypovascular type with slower wash-in and wash-out. This correlated with the biological properties of the tumors. (orig.)

  3. Analysis of mice tumor models using dynamic MRI data and a dedicated software platform

    International Nuclear Information System (INIS)

    Alfke, H.; Maurer, E.; Klose, K.J.; Celik, I.; Heverhagen, J.T.; Ohio State Univ., Columbus

    2004-01-01

    Purpose: To implement a software platform (DynaVision) dedicated to analyze data from functional imaging of tumors with different mathematical approaches, and to test the software platform in pancreatic carcinoma xenografts in mice with severe combined immunodeficiency disease (SCID). Materials and Methods: A software program was developed for extraction and visualization of tissue perfusion parameters from dynamic contrast-enhanced images. This includes regional parameter calculation from enhancement curves, parametric images (e.g., blood flow), animation, 3D visualization, two-compartment modeling a mode for comparing different datasets (e.g., therapy monitoring), and motion correction. We analyzed xenograft tumors from two pancreatic carcinoma cell lines (B x PC3 and ASPC1) implanted in 14 SCID mice after injection of Gd-DTPA into the tail vein. These data were correlated with histopathological findings. Results: Image analysis was completed in approximately 15 minutes per data set. The possibility of drawing and editing ROIs within the whole data set makes it easy to obtain quantitative data from the intensity-time curves. In one animal, motion artifacts reduced the image quality to a greater extent but data analysis was still possible after motion correction. Dynamic MRI of mice tumor models revealed a highly heterogeneous distribution of the contrast-enhancement curves and derived parameters, which correlated with differences in histopathology. ASPc1 tumors showed a more hypervascular type of curves with faster and higher signal enhancement rate (wash-in) and a faster signal decrease (wash-out). BXPC3 tumors showed a more hypovascular type with slower wash-in and wash-out. This correlated with the biological properties of the tumors. (orig.)

  4. An imprecise Dirichlet model for Bayesian analysis of failure data including right-censored observations

    International Nuclear Information System (INIS)

    Coolen, F.P.A.

    1997-01-01

    This paper is intended to make researchers in reliability theory aware of a recently introduced Bayesian model with imprecise prior distributions for statistical inference on failure data, that can also be considered as a robust Bayesian model. The model consists of a multinomial distribution with Dirichlet priors, making the approach basically nonparametric. New results for the model are presented, related to right-censored observations, where estimation based on this model is closely related to the product-limit estimator, which is an important statistical method to deal with reliability or survival data including right-censored observations. As for the product-limit estimator, the model considered in this paper aims at not using any information other than that provided by observed data, but our model fits into the robust Bayesian context which has the advantage that all inferences can be based on probabilities or expectations, or bounds for probabilities or expectations. The model uses a finite partition of the time-axis, and as such it is also related to life-tables

  5. MEMLS3&a: Microwave Emission Model of Layered Snowpacks adapted to include backscattering

    Directory of Open Access Journals (Sweden)

    M. Proksch

    2015-08-01

    Full Text Available The Microwave Emission Model of Layered Snowpacks (MEMLS was originally developed for microwave emissions of snowpacks in the frequency range 5–100 GHz. It is based on six-flux theory to describe radiative transfer in snow including absorption, multiple volume scattering, radiation trapping due to internal reflection and a combination of coherent and incoherent superposition of reflections between horizontal layer interfaces. Here we introduce MEMLS3&a, an extension of MEMLS, which includes a backscatter model for active microwave remote sensing of snow. The reflectivity is decomposed into diffuse and specular components. Slight undulations of the snow surface are taken into account. The treatment of like- and cross-polarization is accomplished by an empirical splitting parameter q. MEMLS3&a (as well as MEMLS is set up in a way that snow input parameters can be derived by objective measurement methods which avoid fitting procedures of the scattering efficiency of snow, required by several other models. For the validation of the model we have used a combination of active and passive measurements from the NoSREx (Nordic Snow Radar Experiment campaign in Sodankylä, Finland. We find a reasonable agreement between the measurements and simulations, subject to uncertainties in hitherto unmeasured input parameters of the backscatter model. The model is written in Matlab and the code is publicly available for download through the following website: http://www.iapmw.unibe.ch/research/projects/snowtools/memls.html.

  6. Steady-state analysis of activated sludge processes with a settler model including sludge compression.

    Science.gov (United States)

    Diehl, S; Zambrano, J; Carlsson, B

    2016-01-01

    A reduced model of a completely stirred-tank bioreactor coupled to a settling tank with recycle is analyzed in its steady states. In the reactor, the concentrations of one dominant particulate biomass and one soluble substrate component are modelled. While the biomass decay rate is assumed to be constant, growth kinetics can depend on both substrate and biomass concentrations, and optionally model substrate inhibition. Compressive and hindered settling phenomena are included using the Bürger-Diehl settler model, which consists of a partial differential equation. Steady-state solutions of this partial differential equation are obtained from an ordinary differential equation, making steady-state analysis of the entire plant difficult. A key result showing that the ordinary differential equation can be replaced with an approximate algebraic equation simplifies model analysis. This algebraic equation takes the location of the sludge-blanket during normal operation into account, allowing for the limiting flux capacity caused by compressive settling to easily be included in the steady-state mass balance equations for the entire plant system. This novel approach grants the possibility of more realistic solutions than other previously published reduced models, comprised of yet simpler settler assumptions. The steady-state concentrations, solids residence time, and the wastage flow ratio are functions of the recycle ratio. Solutions are shown for various growth kinetics; with different values of biomass decay rate, influent volumetric flow, and substrate concentration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. TS Fuzzy Model-Based Controller Design for a Class of Nonlinear Systems Including Nonsmooth Functions

    DEFF Research Database (Denmark)

    Vafamand, Navid; Asemani, Mohammad Hassan; Khayatiyan, Alireza

    2018-01-01

    criterion, new robust controller design conditions in terms of linear matrix inequalities are derived. Three practical case studies, electric power steering system, a helicopter model and servo-mechanical system, are presented to demonstrate the importance of such class of nonlinear systems comprising......This paper proposes a novel robust controller design for a class of nonlinear systems including hard nonlinearity functions. The proposed approach is based on Takagi-Sugeno (TS) fuzzy modeling, nonquadratic Lyapunov function, and nonparallel distributed compensation scheme. In this paper, a novel...... TS modeling of the nonlinear dynamics with signum functions is proposed. This model can exactly represent the original nonlinear system with hard nonlinearity while the discontinuous signum functions are not approximated. Based on the bounded-input-bounded-output stability scheme and L₁ performance...

  8. A roller chain drive model including contact with guide-bars

    DEFF Research Database (Denmark)

    Pedersen, Sine Leergaard; Hansen, John Michael; Ambrósio, J. A. C.

    2004-01-01

    as continuous force. The model of the roller-chain drive now proposed departs from an earlier model where two contact/impact methods are proposed to describe the contact between the rollers of the chain and the teeth of the sprockets. These different formulations are based on unilateral constraints....... In the continuous force method the roller-sprocket contact, is represented by forces applied on each seated roller and in the respective sprocket teeth. These forces are functions of the pseudo penetrations between roller and sprocket, impacting velocities and a restitution coefficient. In the continuous force......A model of a roller chain drive is developed and applied to the simulation and analysis of roller chain drives of large marine diesel engines. The model includes the impact with guide-bars that are the motion delimiter components on the chain strands between the sprockets. The main components...

  9. Improving weather predictability by including land-surface model parameter uncertainty

    Science.gov (United States)

    Orth, Rene; Dutra, Emanuel; Pappenberger, Florian

    2016-04-01

    The land surface forms an important component of Earth system models and interacts nonlinearly with other parts such as ocean and atmosphere. To capture the complex and heterogenous hydrology of the land surface, land surface models include a large number of parameters impacting the coupling to other components of the Earth system model. Focusing on ECMWF's land-surface model HTESSEL we present in this study a comprehensive parameter sensitivity evaluation using multiple observational datasets in Europe. We select 6 poorly constrained effective parameters (surface runoff effective depth, skin conductivity, minimum stomatal resistance, maximum interception, soil moisture stress function shape, total soil depth) and explore their sensitivity to model outputs such as soil moisture, evapotranspiration and runoff using uncoupled simulations and coupled seasonal forecasts. Additionally we investigate the possibility to construct ensembles from the multiple land surface parameters. In the uncoupled runs we find that minimum stomatal resistance and total soil depth have the most influence on model performance. Forecast skill scores are moreover sensitive to the same parameters as HTESSEL performance in the uncoupled analysis. We demonstrate the robustness of our findings by comparing multiple best performing parameter sets and multiple randomly chosen parameter sets. We find better temperature and precipitation forecast skill with the best-performing parameter perturbations demonstrating representativeness of model performance across uncoupled (and hence less computationally demanding) and coupled settings. Finally, we construct ensemble forecasts from ensemble members derived with different best-performing parameterizations of HTESSEL. This incorporation of parameter uncertainty in the ensemble generation yields an increase in forecast skill, even beyond the skill of the default system. Orth, R., E. Dutra, and F. Pappenberger, 2016: Improving weather predictability by

  10. Global Reference Atmospheric Models, Including Thermospheres, for Mars, Venus and Earth

    Science.gov (United States)

    Justh, Hilary L.; Justus, C. G.; Keller, Vernon W.

    2006-01-01

    This document is the viewgraph slides of the presentation. Marshall Space Flight Center's Natural Environments Branch has developed Global Reference Atmospheric Models (GRAMs) for Mars, Venus, Earth, and other solar system destinations. Mars-GRAM has been widely used for engineering applications including systems design, performance analysis, and operations planning for aerobraking, entry descent and landing, and aerocapture. Preliminary results are presented, comparing Mars-GRAM with measurements from Mars Reconnaissance Orbiter (MRO) during its aerobraking in Mars thermosphere. Venus-GRAM is based on the Committee on Space Research (COSPAR) Venus International Reference Atmosphere (VIRA), and is suitable for similar engineering applications in the thermosphere or other altitude regions of the atmosphere of Venus. Until recently, the thermosphere in Earth-GRAM has been represented by the Marshall Engineering Thermosphere (MET) model. Earth-GRAM has recently been revised. In addition to including an updated version of MET, it now includes an option to use the Naval Research Laboratory Mass Spectrometer Incoherent Scatter Radar Extended Model (NRLMSISE-00) as an alternate thermospheric model. Some characteristics and results from Venus-GRAM and Earth-GRAM thermospheres are also presented.

  11. A numerical model including PID control of a multizone crystal growth furnace

    Science.gov (United States)

    Panzarella, Charles H.; Kassemi, Mohammad

    1992-01-01

    This paper presents a 2D axisymmetric combined conduction and radiation model of a multizone crystal growth furnace. The model is based on a programmable multizone furnace (PMZF) designed and built at NASA Lewis Research Center for growing high quality semiconductor crystals. A novel feature of this model is a control algorithm which automatically adjusts the power in any number of independently controlled heaters to establish the desired crystal temperatures in the furnace model. The control algorithm eliminates the need for numerous trial and error runs previously required to obtain the same results. The finite element code, FIDAP, used to develop the furnace model, was modified to directly incorporate the control algorithm. This algorithm, which presently uses PID control, and the associated heat transfer model are briefly discussed. Together, they have been used to predict the heater power distributions for a variety of furnace configurations and desired temperature profiles. Examples are included to demonstrate the effectiveness of the PID controlled model in establishing isothermal, Bridgman, and other complicated temperature profies in the sample. Finally, an example is given to show how the algorithm can be used to change the desired profile with time according to a prescribed temperature-time evolution.

  12. A New Circuit Model for Spin-Torque Oscillator Including Perpendicular Torque of Magnetic Tunnel Junction

    Directory of Open Access Journals (Sweden)

    Hyein Lim

    2013-01-01

    Full Text Available Spin-torque oscillator (STO is a promising new technology for the future RF oscillators, which is based on the spin-transfer torque (STT effect in magnetic multilayered nanostructure. It is expected to provide a larger tunability, smaller size, lower power consumption, and higher level of integration than the semiconductor-based oscillators. In our previous work, a circuit-level model of the giant magnetoresistance (GMR STO was proposed. In this paper, we present a physics-based circuit-level model of the magnetic tunnel junction (MTJ-based STO. MTJ-STO model includes the effect of perpendicular torque that has been ignored in the GMR-STO model. The variations of three major characteristics, generation frequency, mean oscillation power, and generation linewidth of an MTJ-STO with respect to the amount of perpendicular torque, are investigated, and the results are applied to our model. The operation of the model was verified by HSPICE simulation, and the results show an excellent agreement with the experimental data. The results also prove that a full circuit-level simulation with MJT-STO devices can be made with our proposed model.

  13. Including Finite Surface Span Effects in Empirical Jet-Surface Interaction Noise Models

    Science.gov (United States)

    Brown, Clifford A.

    2016-01-01

    The effect of finite span on the jet-surface interaction noise source and the jet mixing noise shielding and reflection effects is considered using recently acquired experimental data. First, the experimental setup and resulting data are presented with particular attention to the role of surface span on far-field noise. These effects are then included in existing empirical models that have previously assumed that all surfaces are semi-infinite. This extended abstract briefly describes the experimental setup and data leaving the empirical modeling aspects for the final paper.

  14. Partial Enteral Nutrition Preserves Elements of Gut Barrier Function, Including Innate Immunity, Intestinal Alkaline Phosphatase (IAP) Level, and Intestinal Microbiota in Mice

    OpenAIRE

    Wan, Xiao; Bi, Jingcheng; Gao, Xuejin; Tian, Feng; Wang, Xinying; Li, Ning; Li, Jieshou

    2015-01-01

    Lack of enteral nutrition (EN) during parenteral nutrition (PN) leads to higher incidence of infection because of gut barrier dysfunction. However, the effects of partial EN on intestina linnate immunity, intestinal alkaline phosphatase (IAP) and microbiota remain unclear. The mice were randomized into six groups to receive either standard chow or isocaloric and isonitrogenous nutritional support with variable partial EN to PN ratios. Five days later, the mice were sacrificed and tissue sampl...

  15. GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways

    Directory of Open Access Journals (Sweden)

    Laura Guerenne

    2016-01-01

    Full Text Available Abstract Background In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease. Methods We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS and acute myeloid leukemia (AML post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively. Results Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples. Conclusions These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.

  16. GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways.

    Science.gov (United States)

    Guerenne, Laura; Beurlet, Stéphanie; Said, Mohamed; Gorombei, Petra; Le Pogam, Carole; Guidez, Fabien; de la Grange, Pierre; Omidvar, Nader; Vanneaux, Valérie; Mills, Ken; Mufti, Ghulam J; Sarda-Mantel, Laure; Noguera, Maria Elena; Pla, Marika; Fenaux, Pierre; Padua, Rose Ann; Chomienne, Christine; Krief, Patricia

    2016-01-27

    In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS) patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease. We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS) and acute myeloid leukemia (AML) post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively. Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples. These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.

  17. Modeling of Temperature-Dependent Noise in Silicon Nanowire FETs including Self-Heating Effects

    Directory of Open Access Journals (Sweden)

    P. Anandan

    2014-01-01

    Full Text Available Silicon nanowires are leading the CMOS era towards the downsizing limit and its nature will be effectively suppress the short channel effects. Accurate modeling of thermal noise in nanowires is crucial for RF applications of nano-CMOS emerging technologies. In this work, a perfect temperature-dependent model for silicon nanowires including the self-heating effects has been derived and its effects on device parameters have been observed. The power spectral density as a function of thermal resistance shows significant improvement as the channel length decreases. The effects of thermal noise including self-heating of the device are explored. Moreover, significant reduction in noise with respect to channel thermal resistance, gate length, and biasing is analyzed.

  18. Ts1Cje Down syndrome model mice exhibit environmental stimuli-triggered locomotor hyperactivity and sociability concurrent with increased flux through central dopamine and serotonin metabolism.

    Science.gov (United States)

    Shimohata, Atsushi; Ishihara, Keiichi; Hattori, Satoko; Miyamoto, Hiroyuki; Morishita, Hiromasa; Ornthanalai, Guy; Raveau, Matthieu; Ebrahim, Abdul Shukkur; Amano, Kenji; Yamada, Kazuyuki; Sago, Haruhiko; Akiba, Satoshi; Mataga, Nobuko; Murphy, Niall P; Miyakawa, Tsuyoshi; Yamakawa, Kazuhiro

    2017-07-01

    Ts1Cje mice have a segmental trisomy of chromosome 16 that is orthologous to human chromosome 21 and display Down syndrome-like cognitive impairments. Despite the occurrence of affective and emotional impairments in patients with Down syndrome, these parameters are poorly documented in Down syndrome mouse models, including Ts1Cje mice. Here, we conducted comprehensive behavioral analyses, including anxiety-, sociability-, and depression-related tasks, and biochemical analyses of monoamines and their metabolites in Ts1Cje mice. Ts1Cje mice showed enhanced locomotor activity in novel environments and increased social contact with unfamiliar partners when compared with wild-type littermates, but a significantly lower activity in familiar environments. Ts1Cje mice also exhibited some signs of decreased depression like-behavior. Furthermore, Ts1Cje mice showed monoamine abnormalities, including increased extracellular dopamine and serotonin, and enhanced catabolism in the striatum and ventral forebrain. This study constitutes the first report of deviated monoamine metabolism that may help explain the basis for abnormal behaviors, including the environmental stimuli-triggered hyperactivity, increased sociability and decreased depression-like behavior in Ts1Cje mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Conditional knockdown of hyaluronidase 2 in articular cartilage stimulates osteoarthritic progression in a mice model.

    Science.gov (United States)

    Higuchi, Yoshitoshi; Nishida, Yoshihiro; Kozawa, Eiji; Zhuo, Lisheng; Arai, Eisuke; Hamada, Shunsuke; Morita, Daigo; Ikuta, Kunihiro; Kimata, Koji; Ushida, Takahiro; Ishiguro, Naoki

    2017-08-01

    The catabolism of hyaluronan in articular cartilage remains unclear. The aims of this study were to investigate the effects of hyaluronidase 2 (Hyal2) knockdown in articular cartilage on the development of osteoarthritis (OA) using genetic manipulated mice. Destabilization of the medial meniscus (DMM) model of Col2a promoter specific conditional Hyal2 knockout (Hyal -/- ) mice was established and examined. Age related and DMM induced alterations of articular cartilage of knee joint were evaluated with modified Mankin score and immunohistochemical staining of MMP-13, ADAMTS-5, KIAA11199, and biotinylated- hyaluronan binding protein staining in addition to histomorphometrical analyses. Effects of Hyal2 suppression were also analyzed using explant culture of an IL-1α induced articular cartilage degradation model. The amount and size of hyaluronan in articular cartilage were higher in Hyal2 -/- mice. Hyal2 -/- mice exhibited aggravated cartilage degradation in age-related and DMM induced mice. MMP-13 and ADAMTS-5 positive chondrocytes were significantly higher in Hyal2 -/- mice. Articular cartilage was more degraded in explant cultures obtained from Hyal2 -/- mice. Knockdown of Hyal2 in articular cartilage induced OA development and progression possibly mediated by an imbalance of HA metabolism. This suggests that Hyal2 knockdown exhibits mucopolysaccharidosis-like OA change in articular cartilage similar to Hyal1 knockdown.

  20. Producing high-accuracy lattice models from protein atomic coordinates including side chains.

    Science.gov (United States)

    Mann, Martin; Saunders, Rhodri; Smith, Cameron; Backofen, Rolf; Deane, Charlotte M

    2012-01-01

    Lattice models are a common abstraction used in the study of protein structure, folding, and refinement. They are advantageous because the discretisation of space can make extensive protein evaluations computationally feasible. Various approaches to the protein chain lattice fitting problem have been suggested but only a single backbone-only tool is available currently. We introduce LatFit, a new tool to produce high-accuracy lattice protein models. It generates both backbone-only and backbone-side-chain models in any user defined lattice. LatFit implements a new distance RMSD-optimisation fitting procedure in addition to the known coordinate RMSD method. We tested LatFit's accuracy and speed using a large nonredundant set of high resolution proteins (SCOP database) on three commonly used lattices: 3D cubic, face-centred cubic, and knight's walk. Fitting speed compared favourably to other methods and both backbone-only and backbone-side-chain models show low deviation from the original data (~1.5 Å RMSD in the FCC lattice). To our knowledge this represents the first comprehensive study of lattice quality for on-lattice protein models including side chains while LatFit is the only available tool for such models.

  1. A High-Rate, Single-Crystal Model including Phase Transformations, Plastic Slip, and Twinning

    Energy Technology Data Exchange (ETDEWEB)

    Addessio, Francis L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Bronkhorst, Curt Allan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Bolme, Cynthia Anne [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Explosive Science and Shock Physics Division; Brown, Donald William [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Materials Science and Technology Division; Cerreta, Ellen Kathleen [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Materials Science and Technology Division; Lebensohn, Ricardo A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Materials Science and Technology Division; Lookman, Turab [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Luscher, Darby Jon [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Mayeur, Jason Rhea [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Morrow, Benjamin M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Materials Science and Technology Division; Rigg, Paulo A. [Washington State Univ., Pullman, WA (United States). Dept. of Physics. Inst. for Shock Physics

    2016-08-09

    An anisotropic, rate-­dependent, single-­crystal approach for modeling materials under the conditions of high strain rates and pressures is provided. The model includes the effects of large deformations, nonlinear elasticity, phase transformations, and plastic slip and twinning. It is envisioned that the model may be used to examine these coupled effects on the local deformation of materials that are subjected to ballistic impact or explosive loading. The model is formulated using a multiplicative decomposition of the deformation gradient. A plate impact experiment on a multi-­crystal sample of titanium was conducted. The particle velocities at the back surface of three crystal orientations relative to the direction of impact were measured. Molecular dynamics simulations were conducted to investigate the details of the high-­rate deformation and pursue issues related to the phase transformation for titanium. Simulations using the single crystal model were conducted and compared to the high-­rate experimental data for the impact loaded single crystals. The model was found to capture the features of the experiments.

  2. Modeling and analysis of the affinity filtration process, including broth feeding, washing, and elution steps.

    Science.gov (United States)

    He, L Z; Dong, X Y; Sun, Y

    1998-01-01

    Affinity filtration is a developing protein purification technique that combines the high selectivity of affinity chromatography and the high processing speed of membrane filtration. In this work a lumped kinetic model was developed to describe the whole affinity filtration process, including broth feeding, contaminant washing, and elution steps. Affinity filtration experiments were conducted to evaluate the model using bovine serum albumin as a model protein and a highly substituted Blue Sepharose as an affinity adsorbent. The model with nonadjustable parameters agreed fairly to the experimental results. Thus, the performance of the affinity filtration in processing a crude broth containing contaminant proteins was analyzed by computer simulations using the lumped model. The simulation results show that there is an optimal protein loading for obtaining the maximum recovery yield of the desired protein with a constant purity at each operating condition. The concentration of a crude broth is beneficial in increasing the recovery yield of the desired protein. Using a constant amount of the affinity adsorbent, the recovery yield can be enhanced by decreasing the solution volume in the stirred tank due to the increase of the adsorbent weight fraction. It was found that the lumped kinetic model was simple and useful in analyzing the whole affinity filtration process.

  3. Model for safety reports including descriptive examples; Mall foer saekerhetsrapporter med beskrivande exempel

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-01

    Several safety reports will be produced in the process of planning and constructing the system for disposal of high-level radioactive waste in Sweden. The present report gives a model, with detailed examples, of how these reports should be organized and what steps they should include. In the near future safety reports will deal with the encapsulation plant and the repository. Later reports will treat operation of the handling systems and the repository.

  4. Collisional-radiative model including recombination processes for W27+ ion★

    Science.gov (United States)

    Murakami, Izumi; Sasaki, Akira; Kato, Daiji; Koike, Fumihiro

    2017-10-01

    We have constructed a collisional-radiative (CR) model for W27+ ions including 226 configurations with n ≤ 9 and ł ≤ 5 for spectroscopic diagnostics. We newly include recombination processes in the model and this is the first result of extreme ultraviolet spectrum calculated for recombining plasma component. Calculated spectra in 40-70 Å range in ionizing and recombining plasma components show similar 3 strong lines and 1 line weak in recombining plasma component at 45-50 Å and many weak lines at 50-65 Å for both components. Recombination processes do not contribute much to the spectrum at around 60 Å for W27+ ion. Dielectronic satellite lines are also minor contribution to the spectrum of recombining plasma component. Dielectronic recombination (DR) rate coefficient from W28+ to W27+ ions is also calculated with the same atomic data in the CR model. We found that larger set of energy levels including many autoionizing states gave larger DR rate coefficients but our rate agree within factor 6 with other works at electron temperature around 1 keV in which W27+ and W28+ ions are usually observed in plasmas. Contribution to the Topical Issue "Atomic and Molecular Data and their Applications", edited by Gordon W.F. Drake, Jung-Sik Yoon, Daiji Kato, and Grzegorz Karwasz.

  5. A 3D model of the oculomotor plant including the pulley system

    Science.gov (United States)

    Viegener, A.; Armentano, R. L.

    2007-11-01

    Early models of the oculomotor plant only considered the eye globes and the muscles that move them. Recently, connective tissue structures have been found enveloping the extraocular muscles (EOMs) and firmly anchored to the orbital wall. These structures act as pulleys; they determine the functional origin of the EOMs and, in consequence, their effective pulling direction. A three dimensional model of the oculomotor plant, including pulleys, has been developed and simulations in Simulink were performed during saccadic eye movements. Listing's law was implemented based on the supposition that there exists an eye orientation related signal. The inclusion of the pulleys in the model makes this assumption plausible and simplifies the problem of the plant noncommutativity.

  6. Protective effects of white button mushroom (Agaricus bisporus against hepatic steatosis in ovariectomized mice as a model of postmenopausal women.

    Directory of Open Access Journals (Sweden)

    Noriko Kanaya

    Full Text Available Nonalcoholic fatty liver disease (NAFLD includes various hepatic pathologies ranging from hepatic steatosis to non-alcoholic steatohepatitis (NASH, fibrosis and cirrhosis. Estrogen provides a protective effect on the development of NAFLD in women. Therefore, postmenopausal women have a higher risk of developing NAFLD. Hepatic steatosis is an early stage of fatty liver disease. Steatosis can develop to the aggressive stages (nonalcoholic steatohepatitis, fibrosis and cirrhosis. Currently, there is no specific drug to prevent/treat these liver diseases. In this study, we found that white button mushroom (WBM, Agaricus Bisporus, has protective effects against liver steatosis in ovariectomized (OVX mice (a model of postmenopausal women. OVX mice were fed a high fat diet supplemented with WBM powder. We found that dietary WBM intake significantly lowered liver weight and hepatic injury markers in OVX mice. Pathological examination of liver tissue showed less fat accumulation in the livers of mice on WBM diet; moreover, these animals had improved glucose clearance ability. Microarray analysis revealed that genes related to the fatty acid biosynthesis pathway, particularly the genes for fatty acid synthetase (Fas and fatty acid elongase 6 (Elovl6, were down-regulated in the liver of mushroom-fed mice. In vitro mechanistic studies using the HepG2 cell line showed that down-regulation of the expression of FAS and ELOVL6 by WBM extract was through inhibition of Liver X receptor (LXR signaling and its downstream transcriptional factor SREBP1c. These results suggest that WBM is protective against hepatic steatosis and NAFLD in OVX mice as a model for postmenopausal women.

  7. Persistent Coxiella burnetii infection in mice overexpressing IL-10: an efficient model for chronic Q fever pathogenesis.

    Directory of Open Access Journals (Sweden)

    Soraya Meghari

    2008-02-01

    Full Text Available Interleukin (IL-10 increases host susceptibility to microorganisms and is involved in intracellular persistence of bacterial pathogens. IL-10 is associated with chronic Q fever, an infectious disease due to the intracellular bacterium Coxiella burnetii. Nevertheless, accurate animal models of chronic C. burnetii infection are lacking. Transgenic mice constitutively expressing IL-10 in macrophages were infected with C. burnetti by intraperitoneal and intratracheal routes and infection was analyzed through real-time PCR and antibody production. Transgenic mice exhibited sustained tissue infection and strong antibody response in contrast to wild-type mice; thus, bacterial persistence was IL-10-dependent as in chronic Q fever. The number of granulomas was low in spleen and liver of transgenic mice infected through the intraperitoneal route, as in patients with chronic Q fever. Macrophages from transgenic mice were unable to kill C. burnetii. C. burnetii-stimulated macrophages were characterized by non-microbicidal transcriptional program consisting of increased expression of arginase-1, mannose receptor, and Ym1/2, in contrast to wild-type macrophages in which expression of inducible NO synthase and inflammatory cytokines was increased. In vivo results emphasized macrophage data. In spleen and liver of transgenic mice infected with C. burnetii by the intraperitoneal route, the expression of arginase-1 was increased while microbicidal pathway consisting of IL-12p40, IL-23p19, and inducible NO synthase was depressed. The overexpression of IL-10 in macrophages prevents anti-infectious competence of host, including the ability to mount granulomatous response and microbicidal pathway in tissues. To our knowledge, this is the first efficient model for chronic Q fever pathogenesis.

  8. Double-gate junctionless transistor model including short-channel effects

    International Nuclear Information System (INIS)

    Paz, B C; Pavanello, M A; Ávila-Herrera, F; Cerdeira, A

    2015-01-01

    This work presents a physically based model for double-gate junctionless transistors (JLTs), continuous in all operation regimes. To describe short-channel transistors, short-channel effects (SCEs), such as increase of the channel potential due to drain bias, carrier velocity saturation and mobility degradation due to vertical and longitudinal electric fields, are included in a previous model developed for long-channel double-gate JLTs. To validate the model, an analysis is made by using three-dimensional numerical simulations performed in a Sentaurus Device Simulator from Synopsys. Different doping concentrations, channel widths and channel lengths are considered in this work. Besides that, the series resistance influence is numerically included and validated for a wide range of source and drain extensions. In order to check if the SCEs are appropriately described, besides drain current, transconductance and output conductance characteristics, the following parameters are analyzed to demonstrate the good agreement between model and simulation and the SCEs occurrence in this technology: threshold voltage (V TH ), subthreshold slope (S) and drain induced barrier lowering. (paper)

  9. Modeling the distribution of ammonia across Europe including bi-directional surface–atmosphere exchange

    Directory of Open Access Journals (Sweden)

    R. J. Wichink Kruit

    2012-12-01

    Full Text Available A large shortcoming of current chemistry transport models (CTM for simulating the fate of ammonia in the atmosphere is the lack of a description of the bi-directional surface–atmosphere exchange. In this paper, results of an update of the surface–atmosphere exchange module DEPAC, i.e. DEPosition of Acidifying Compounds, in the chemistry transport model LOTOS-EUROS are discussed. It is shown that with the new description, which includes bi-directional surface–atmosphere exchange, the modeled ammonia concentrations increase almost everywhere, in particular in agricultural source areas. The reason is that by using a compensation point the ammonia lifetime and transport distance is increased. As a consequence, deposition of ammonia and ammonium decreases in agricultural source areas, while it increases in large nature areas and remote regions especially in southern Scandinavia. The inclusion of a compensation point for water reduces the dry deposition over sea and allows reproducing the observed marine background concentrations at coastal locations to a better extent. A comparison with measurements shows that the model results better represent the measured ammonia concentrations. The concentrations in nature areas are slightly overestimated, while the concentrations in agricultural source areas are still underestimated. Although the introduction of the compensation point improves the model performance, the modeling of ammonia remains challenging. Important aspects are emission patterns in space and time as well as a proper approach to deal with the high concentration gradients in relation to model resolution. In short, the inclusion of a bi-directional surface–atmosphere exchange is a significant step forward for modeling ammonia.

  10. Coagulation activation in an experimental pneumonia model in malnourished mice.

    Science.gov (United States)

    Zelaya, Hortensia; Haro, Cecilia; Laiño, Jonathan; Alvarez, Susana; Agüero, Graciela

    2011-01-01

    Malnutrition induces a decrease in immunity that affects the ability of the organism to deal with an infectious challenge. The clotting system is considered a branch of immunity and its activation is important in the pathogenesis of an infectious disease. This work was conducted to determine coagulation modifications in malnourished hosts before and during infection. Weaned mice were malnourished via a protein-free diet. Well-nourished control mice (WNC) consumed a balanced conventional diet. Malnourished mice (MN) and WNC were challenged intranasally with Streptococcus pneumoniae. Blood, bronchoalveolar lavages (BAL), and lung samples were taken at different times post infection. The results were that MN showed altered hemostatic tests and fibrin(ogen) deposits in the lung. Thus, an increase in thrombin-antithrombin complexes (TATc) in plasma and BAL was observed. In the MN group, infection induced a rise in TATc in plasma and BAL and increased plasma fibrinogen and fibrin(ogen) deposits in the lung. A decrease in activated protein C and antithrombin in BAL and an early decrease followed by an increase in plasma Factor VIII were also observed. Thus, malnourishment induced a procoagulant state increased by infection. This is the first work that presents results of an exhaustive study of coagulation in malnourished hosts before and during an infection.

  11. FVB/NJ Mice Are a Useful Model for Examining Cardiac Adaptations to Treadmill Exercise.

    Science.gov (United States)

    Gibb, Andrew A; McNally, Lindsey A; Riggs, Daniel W; Conklin, Daniel J; Bhatnagar, Aruni; Hill, Bradford G

    2016-01-01

    Mice are commonly used to examine the mechanisms by which exercise improves cardiometabolic health; however, exercise compliance and adaptations are often strain-dependent or are variable due to inconsistency in exercise training protocols. In this study, we examined nocturnal/diurnal behavior, treadmill exercise compliance, and systemic as well as cardiac-specific exercise adaptations in two commonly used mouse strains, C57BL/6J, and FVB/NJ mice. Metabolic cage analysis indicated a strong nocturnal nature of C57BL/6J mice, whereas FVB/NJ mice showed no circadian element to activity, food or water intake, VO 2 , or VCO 2 . Initial exercise capacity tests revealed that, compared with C57BL/6J mice, FVB/NJ mice are capable of achieving nearly 2-fold higher workloads prior to exhaustion. FVB/NJ mice tested during the day were capable of achieving significantly more work compared with their night-tested counterparts. Following 4 weeks of training, FVB/NJ mice showed significant increases in exercise capacity as well as physiologic cardiac growth characterized by enlarged myocytes and higher mitochondrial DNA content. C57BL/6J mice showed no increases in exercise capacity or cardiac growth regardless of whether they exercised during the day or the night. This lack of adaptation in C57BL/6J mice was attributable, at least in part, to their progressive loss of compliance to the treadmill training protocol. We conclude that the FVB/NJ strain is a useful and robust mouse model for examining cardiac adaptations to treadmill exercise and that treadmill training during daytime hours does not negatively affect exercise compliance or capacity.

  12. Including policy and management in socio-hydrology models: initial conceptualizations

    Science.gov (United States)

    Hermans, Leon; Korbee, Dorien

    2017-04-01

    Socio-hydrology studies the interactions in coupled human-water systems. So far, the use of dynamic models that capture the direct feedback between societal and hydrological systems has been dominant. What has not yet been included with any particular emphasis, is the policy or management layer, which is a central element in for instance integrated water resources management (IWRM) or adaptive delta management (ADM). Studying the direct interactions between human-water systems generates knowledges that eventually helps influence these interactions in ways that may ensure better outcomes - for society and for the health and sustainability of water systems. This influence sometimes occurs through spontaneous emergence, uncoordinated by societal agents - private sector, citizens, consumers, water users. However, the term 'management' in IWRM and ADM also implies an additional coordinated attempt through various public actors. This contribution is a call to include the policy and management dimension more prominently into the research focus of the socio-hydrology field, and offers first conceptual variables that should be considered in attempts to include this policy or management layer in socio-hydrology models. This is done by drawing on existing frameworks to study policy processes throughout both planning and implementation phases. These include frameworks such as the advocacy coalition framework, collective learning and policy arrangements, which all emphasis longer-term dynamics and feedbacks between actor coalitions in strategic planning and implementation processes. A case about longter-term dynamics in the management of the Haringvliet in the Netherlands is used to illustrate the paper.

  13. Modelling of Water Cooled Fuel Including Design Basis and Severe Accidents. Proceedings of a Technical Meeting

    International Nuclear Information System (INIS)

    2015-11-01

    The demands on nuclear fuel have recently been increasing, and include transient regimes, higher discharge burnup and longer fuel cycles. This has resulted in an increase of loads on fuel and core internals. In order to satisfy these demands while ensuring compliance with safety criteria, new national and international programmes have been launched and advanced modelling codes are being developed. The Fukushima Daiichi accident has particularly demonstrated the need for adequate analysis of all aspects of fuel performance to prevent a failure and also to predict fuel behaviour were an accident to occur.This publication presents the Proceedings of the Technical Meeting on Modelling of Water Cooled Fuel Including Design Basis and Severe Accidents, which was hosted by the Nuclear Power Institute of China (NPIC) in Chengdu, China, following the recommendation made in 2013 at the IAEA Technical Working Group on Fuel Performance and Technology. This recommendation was in agreement with IAEA mid-term initiatives, linked to the post-Fukushima IAEA Nuclear Safety Action Plan, as well as the forthcoming Coordinated Research Project (CRP) on Fuel Modelling in Accident Conditions. At the technical meeting in Chengdu, major areas and physical phenomena, as well as types of code and experiment to be studied and used in the CRP, were discussed. The technical meeting provided a forum for international experts to review the state of the art of code development for modelling fuel performance of nuclear fuel for water cooled reactors with regard to steady state and transient conditions, and for design basis and early phases of severe accidents, including experimental support for code validation. A round table discussion focused on the needs and perspectives on fuel modelling in accident conditions. This meeting was the ninth in a series of IAEA meetings, which reflects Member States’ continuing interest in nuclear fuel issues. The previous meetings were held in 1980 (jointly with

  14. Health Promotion Behavior of Chinese International Students in Korea Including Acculturation Factors: A Structural Equation Model.

    Science.gov (United States)

    Kim, Sun Jung; Yoo, Il Young

    2016-03-01

    The purpose of this study was to explain the health promotion behavior of Chinese international students in Korea using a structural equation model including acculturation factors. A survey using self-administered questionnaires was employed. Data were collected from 272 Chinese students who have resided in Korea for longer than 6 months. The data were analyzed using structural equation modeling. The p value of final model is .31. The fitness parameters of the final model such as goodness of fit index, adjusted goodness of fit index, normed fit index, non-normed fit index, and comparative fit index were more than .95. Root mean square of residual and root mean square error of approximation also met the criteria. Self-esteem, perceived health status, acculturative stress and acculturation level had direct effects on health promotion behavior of the participants and the model explained 30.0% of variance. The Chinese students in Korea with higher self-esteem, perceived health status, acculturation level, and lower acculturative stress reported higher health promotion behavior. The findings can be applied to develop health promotion strategies for this population. Copyright © 2016. Published by Elsevier B.V.

  15. A structural model for the in vivo human cornea including collagen-swelling interaction.

    Science.gov (United States)

    Cheng, Xi; Petsche, Steven J; Pinsky, Peter M

    2015-08-06

    A structural model of the in vivo cornea, which accounts for tissue swelling behaviour, for the three-dimensional organization of stromal fibres and for collagen-swelling interaction, is proposed. Modelled as a binary electrolyte gel in thermodynamic equilibrium, the stromal electrostatic free energy is based on the mean-field approximation. To account for active endothelial ionic transport in the in vivo cornea, which modulates osmotic pressure and hydration, stromal mobile ions are shown to satisfy a modified Boltzmann distribution. The elasticity of the stromal collagen network is modelled based on three-dimensional collagen orientation probability distributions for every point in the stroma obtained by synthesizing X-ray diffraction data for azimuthal angle distributions and second harmonic-generated image processing for inclination angle distributions. The model is implemented in a finite-element framework and employed to predict free and confined swelling of stroma in an ionic bath. For the in vivo cornea, the model is used to predict corneal swelling due to increasing intraocular pressure (IOP) and is adapted to model swelling in Fuchs' corneal dystrophy. The biomechanical response of the in vivo cornea to a typical LASIK surgery for myopia is analysed, including tissue fluid pressure and swelling responses. The model provides a new interpretation of the corneal active hydration control (pump-leak) mechanism based on osmotic pressure modulation. The results also illustrate the structural necessity of fibre inclination in stabilizing the corneal refractive surface with respect to changes in tissue hydration and IOP. © 2015 The Author(s).

  16. Secretoglobin 3A2 Exhibits Anti-Fibrotic Activity in Bleomycin-Induced Pulmonary Fibrosis Model Mice.

    Science.gov (United States)

    Cai, Yan; Kimura, Shioko

    2015-01-01

    Secretoglobin (SCGB) 3A2 is a novel lung-enriched cytokine, previously shown to exhibit anti-inflammatory, growth factor, and anti-fibrotic activities. The latter activity was demonstrated using exogenously-administered recombinant SCGB3A2 in the bleomycin (BLM)-induced pulmonary fibrosis model. Whether SCGB3A2 exhibits anti-fibrotic activity in vivo is not known. Mice null for the Scgb3a2 gene were subjected to the BLM-induced pulmonary fibrosis model, and the severity of pulmonary fibrosis determined using histological and biochemical methods. BLM treatment caused weight loss of both Scgb3a2-null and wild-type mice, however, the loss was far more pronounced in BLM-treated Scgb3a2-null than wild-type mice, and the weight of day 21 of BLM-treated Scgb3a2-null mice was about half of that of BLM-treated wild-type mice. Hematoxylin & Eosin, Masson Trichrome, and Sirius Red staining of lung sections, Ashcroft fibrosis scores, hydroxyproline contents, and the levels of mRNAs encoding various collagens demonstrated that BLM-treated Scgb3a2-null mouse lungs had more severe fibrosis than those of wild-type mouse lungs. Total and differential inflammatory cell numbers in bronchoalveolar lavage fluids, and levels of lung mRNAs including those encoding Th2 cytokines such as IL-4 and profibrotic cytokines such as TGFβ were higher in BLM-treated Scgb3a2-null mouse lungs as compared to those of wild-type mouse lungs. In contrast, mRNAs encoding surfactant proteins A, B, C, and D, and SCGB1A1 did not differ between BLM-treated Scgb3a2-null and wild-type mouse lungs. The role of SCGB3A2 in fibrosis was revisited using Scgb3a2-null mice and littermate controls in the BLM-induced pulmonary fibrosis model. The pulmonary fibrosis in the Scgb3a2-null mice was more severe than the wild-type controls, thus establishing that SCGB3A2 has anti-fibrotic activity in vivo. Importantly, surfactant proteins and SCGB1A1 appear not to be involved in the susceptibility of Scgb3a2-null mice to BLM

  17. Establishment of an orthotopic lung cancer model in nude mice and its evaluation by spiral CT.

    Science.gov (United States)

    Liu, Xiang; Liu, Jun; Guan, Yubao; Li, Huiling; Huang, Liyan; Tang, Hailing; He, Jianxing

    2012-04-01

    To establish a simple and highly efficient orthotopic animal model of lung cancer cell line A549 and evaluate the growth pattern of intrathoracic tumors by spiral CT. A549 cells (5×10(6) mL(-1)) were suspended and inoculated into the right lung of BALB/c nude mice via intrathoracic injection. Nude mice were scanned three times each week by spiral CT after inoculation of lung cancer cell line A549. The survival time and body weight of nude mice as well as tumor invasion and metastasis were examined. Tissue was collected for subsequent histological assay after autopsia of mice. The tumor-forming rate of the orthotopic lung cancer model was 90%. The median survival time was 30.7 (range, 20-41) days. The incidence of tumor metastasis was 100%. The mean tumor diameter and the average CT value gradually increased in a time-dependent manner. The method of establishing the orthotopic lung cancer model through transplanting A549 cells into the lung of nude mice is simple and highly successful. Spiral CT can be used to evaluate intrathoracic tumor growth in nude mice vividly and dynamically.

  18. A satellite relative motion model including J_2 and J_3 via Vinti's intermediary

    Science.gov (United States)

    Biria, Ashley D.; Russell, Ryan P.

    2018-03-01

    Vinti's potential is revisited for analytical propagation of the main satellite problem, this time in the context of relative motion. A particular version of Vinti's spheroidal method is chosen that is valid for arbitrary elliptical orbits, encapsulating J_2, J_3, and generally a partial J_4 in an orbit propagation theory without recourse to perturbation methods. As a child of Vinti's solution, the proposed relative motion model inherits these properties. Furthermore, the problem is solved in oblate spheroidal elements, leading to large regions of validity for the linearization approximation. After offering several enhancements to Vinti's solution, including boosts in accuracy and removal of some singularities, the proposed model is derived and subsequently reformulated so that Vinti's solution is piecewise differentiable. While the model is valid for the critical inclination and nonsingular in the element space, singularities remain in the linear transformation from Earth-centered inertial coordinates to spheroidal elements when the eccentricity is zero or for nearly equatorial orbits. The new state transition matrix is evaluated against numerical solutions including the J_2 through J_5 terms for a wide range of chief orbits and separation distances. The solution is also compared with side-by-side simulations of the original Gim-Alfriend state transition matrix, which considers the J_2 perturbation. Code for computing the resulting state transition matrix and associated reference frame and coordinate transformations is provided online as supplementary material.

  19. General hypothesis and shell model for the synthesis of semiconductor nanotubes, including carbon nanotubes

    Science.gov (United States)

    Mohammad, S. Noor

    2010-09-01

    Semiconductor nanotubes, including carbon nanotubes, have vast potential for new technology development. The fundamental physics and growth kinetics of these nanotubes are still obscured. Various models developed to elucidate the growth suffer from limited applicability. An in-depth investigation of the fundamentals of nanotube growth has, therefore, been carried out. For this investigation, various features of nanotube growth, and the role of the foreign element catalytic agent (FECA) in this growth, have been considered. Observed growth anomalies have been analyzed. Based on this analysis, a new shell model and a general hypothesis have been proposed for the growth. The essential element of the shell model is the seed generated from segregation during growth. The seed structure has been defined, and the formation of droplet from this seed has been described. A modified definition of the droplet exhibiting adhesive properties has also been presented. Various characteristics of the droplet, required for alignment and organization of atoms into tubular forms, have been discussed. Employing the shell model, plausible scenarios for the formation of carbon nanotubes, and the variation in the characteristics of these carbon nanotubes have been articulated. The experimental evidences, for example, for the formation of shell around a core, dipole characteristics of the seed, and the existence of nanopores in the seed, have been presented. They appear to justify the validity of the proposed model. The diversities of nanotube characteristics, fundamentals underlying the creation of bamboo-shaped carbon nanotubes, and the impurity generation on the surface of carbon nanotubes have been elucidated. The catalytic action of FECA on growth has been quantified. The applicability of the proposed model to the nanotube growth by a variety of mechanisms has been elaborated. These mechanisms include the vapor-liquid-solid mechanism, the oxide-assisted growth mechanism, the self

  20. A new model for including the effect of fly ash on biochemical methane potential.

    Science.gov (United States)

    Gertner, Pablo; Huiliñir, César; Pinto-Villegas, Paula; Castillo, Alejandra; Montalvo, Silvio; Guerrero, Lorna

    2017-10-01

    The modelling of the effect of trace elements on anaerobic digestion, and specifically the effect of fly ash, has been scarcely studied. Thus, the present work was aimed at the development of a new function that allows accumulated methane models to predict the effect of FA on the volume of methane accumulation. For this, purpose five fly ash concentrations (10, 25, 50, 250 and 500mg/L) using raw and pre-treated sewage sludge were used to calibrate the new function, while three fly ash concentrations were used (40, 150 and 350mg/L) for validation. Three models for accumulated methane volume (the modified Gompertz equation, the logistic function, and the transfer function) were evaluated. The results showed that methane production increased in the presence of FA when the sewage sludge was not pre-treated, while with pretreated sludge there is inhibition of methane production at FA concentrations higher than 50mg/L. In the calibration of the proposed function, it fits well with the experimental data under all the conditions, including the inhibition and stimulating zones, with the values of the parameters of the methane production models falling in the range of those reported in the literature. For validation experiments, the model succeeded in representing the behavior of new experiments in both the stimulating and inhibiting zones, with NRMSE and R 2 ranging from 0.3577 to 0.03714 and 0.2209 to 0.9911, respectively. Thus, the proposed model is robust and valid for the studied conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. A curved multi-component aerosol hygroscopicity model framework: Part 2 – Including organic compounds

    Directory of Open Access Journals (Sweden)

    D. O. Topping

    2005-01-01

    Full Text Available This paper describes the inclusion of organic particulate material within the Aerosol Diameter Dependent Equilibrium Model (ADDEM framework described in the companion paper applied to inorganic aerosol components. The performance of ADDEM is analysed in terms of its capability to reproduce the behaviour of various organic and mixed inorganic/organic systems using recently published bulk data. Within the modelling architecture already described two separate thermodynamic models are coupled in an additive approach and combined with a method for solving the Kohler equation in order to develop a tool for predicting the water content associated with an aerosol of known inorganic/organic composition and dry size. For development of the organic module, the widely used group contribution method UNIFAC is employed to explicitly deal with the non-ideality in solution. The UNIFAC predictions for components of atmospheric importance were improved considerably by using revised interaction parameters derived from electro-dynamic balance studies. Using such parameters, the model was found to adequately describe mixed systems including 5–6 dicarboxylic acids, down to low relative humidity conditions. By comparison with electrodynamic balance data, it was also found that the model was capable of capturing the behaviour of aqueous aerosols containing Suwannee River Fulvic acid, a structure previously used to represent the functionality of complex oxidised macromolecules often found in atmospheric aerosols. The additive approach for modelling mixed inorganic/organic systems worked well for a variety of mixtures. As expected, deviations between model predictions and measurements increase with increasing concentration. Available surface tension models, used in evaluating the Kelvin term, were found to reproduce measured data with varying success. Deviations from experimental data increased with increased organic compound complexity. For components only slightly

  2. A curved multi-component aerosol hygroscopicity model framework: Part 2 Including organic compounds

    Science.gov (United States)

    Topping, D. O.; McFiggans, G. B.; Coe, H.

    2005-05-01

    This paper describes the inclusion of organic particulate material within the Aerosol Diameter Dependent Equilibrium Model (ADDEM) framework described in the companion paper applied to inorganic aerosol components. The performance of ADDEM is analysed in terms of its capability to reproduce the behaviour of various organic and mixed inorganic/organic systems using recently published bulk data. Within the modelling architecture already described two separate thermodynamic models are coupled in an additive approach and combined with a method for solving the Kohler equation in order to develop a tool for predicting the water content associated with an aerosol of known inorganic/organic composition and dry size. For development of the organic module, the widely used group contribution method UNIFAC is employed to explicitly deal with the non-ideality in solution. The UNIFAC predictions for components of atmospheric importance were improved considerably by using revised interaction parameters derived from electro-dynamic balance studies. Using such parameters, the model was found to adequately describe mixed systems including 5-6 dicarboxylic acids, down to low relative humidity conditions. By comparison with electrodynamic balance data, it was also found that the model was capable of capturing the behaviour of aqueous aerosols containing Suwannee River Fulvic acid, a structure previously used to represent the functionality of complex oxidised macromolecules often found in atmospheric aerosols. The additive approach for modelling mixed inorganic/organic systems worked well for a variety of mixtures. As expected, deviations between model predictions and measurements increase with increasing concentration. Available surface tension models, used in evaluating the Kelvin term, were found to reproduce measured data with varying success. Deviations from experimental data increased with increased organic compound complexity. For components only slightly soluble in water

  3. A generalized model for optimal transport of images including dissipation and density modulation

    KAUST Repository

    Maas, Jan

    2015-11-01

    © EDP Sciences, SMAI 2015. In this paper the optimal transport and the metamorphosis perspectives are combined. For a pair of given input images geodesic paths in the space of images are defined as minimizers of a resulting path energy. To this end, the underlying Riemannian metric measures the rate of transport cost and the rate of viscous dissipation. Furthermore, the model is capable to deal with strongly varying image contrast and explicitly allows for sources and sinks in the transport equations which are incorporated in the metric related to the metamorphosis approach by Trouvé and Younes. In the non-viscous case with source term existence of geodesic paths is proven in the space of measures. The proposed model is explored on the range from merely optimal transport to strongly dissipative dynamics. For this model a robust and effective variational time discretization of geodesic paths is proposed. This requires to minimize a discrete path energy consisting of a sum of consecutive image matching functionals. These functionals are defined on corresponding pairs of intensity functions and on associated pairwise matching deformations. Existence of time discrete geodesics is demonstrated. Furthermore, a finite element implementation is proposed and applied to instructive test cases and to real images. In the non-viscous case this is compared to the algorithm proposed by Benamou and Brenier including a discretization of the source term. Finally, the model is generalized to define discrete weighted barycentres with applications to textures and objects.

  4. Empirical Validation of a Thermal Model of a Complex Roof Including Phase Change Materials

    Directory of Open Access Journals (Sweden)

    Stéphane Guichard

    2015-12-01

    Full Text Available This paper deals with the empirical validation of a building thermal model of a complex roof including a phase change material (PCM. A mathematical model dedicated to PCMs based on the heat apparent capacity method was implemented in a multi-zone building simulation code, the aim being to increase the understanding of the thermal behavior of the whole building with PCM technologies. In order to empirically validate the model, the methodology is based both on numerical and experimental studies. A parametric sensitivity analysis was performed and a set of parameters of the thermal model has been identified for optimization. The use of the generic optimization program called GenOpt® coupled to the building simulation code enabled to determine the set of adequate parameters. We first present the empirical validation methodology and main results of previous work. We then give an overview of GenOpt® and its coupling with the building simulation code. Finally, once the optimization results are obtained, comparisons of the thermal predictions with measurements are found to be acceptable and are presented.

  5. A multiscale model for glioma spread including cell-tissue interactions and proliferation.

    Science.gov (United States)

    Engwer, Christian; Knappitsch, Markus; Surulescu, Christina

    2016-04-01

    Glioma is a broad class of brain and spinal cord tumors arising from glia cells, which are the main brain cells that can develop into neoplasms. They are highly invasive and lead to irregular tumor margins which are not precisely identifiable by medical imaging, thus rendering a precise enough resection very difficult. The understanding of glioma spread patterns is hence essential for both radiological therapy as well as surgical treatment. In this paper we propose a multiscale model for glioma growth including interactions of the cells with the underlying tissue network, along with proliferative effects. Our current accounting for two subpopulations of cells to accomodate proliferation according to the go-or-grow dichtomoty is an extension of the setting in [16]. As in that paper, we assume that cancer cells use neuronal fiber tracts as invasive pathways. Hence, the individual structure of brain tissue seems to be decisive for the tumor spread. Diffusion tensor imaging (DTI) is able to provide such information, thus opening the way for patient specific modeling of glioma invasion. Starting from a multiscale model involving subcellular (microscopic) and individual (mesoscale) cell dynamics, we perform a parabolic scaling to obtain an approximating reaction-diffusion-transport equation on the macroscale of the tumor cell population. Numerical simulations based on DTI data are carried out in order to assess the performance of our modeling approach.

  6. Habitability of super-Earth planets around other suns: models including Red Giant Branch evolution.

    Science.gov (United States)

    von Bloh, W; Cuntz, M; Schröder, K-P; Bounama, C; Franck, S

    2009-01-01

    The unexpected diversity of exoplanets includes a growing number of super-Earth planets, i.e., exoplanets with masses of up to several Earth masses and a similar chemical and mineralogical composition as Earth. We present a thermal evolution model for a 10 Earth-mass planet orbiting a star like the Sun. Our model is based on the integrated system approach, which describes the photosynthetic biomass production and takes into account a variety of climatological, biogeochemical, and geodynamical processes. This allows us to identify a so-called photosynthesis-sustaining habitable zone (pHZ), as determined by the limits of biological productivity on the planetary surface. Our model considers solar evolution during the main-sequence stage and along the Red Giant Branch as described by the most recent solar model. We obtain a large set of solutions consistent with the principal possibility of life. The highest likelihood of habitability is found for "water worlds." Only mass-rich water worlds are able to realize pHZ-type habitability beyond the stellar main sequence on the Red Giant Branch.

  7. Analysis of electronic models for solar cells including energy resolved defect densities

    Energy Technology Data Exchange (ETDEWEB)

    Glitzky, Annegret

    2010-07-01

    We introduce an electronic model for solar cells including energy resolved defect densities. The resulting drift-diffusion model corresponds to a generalized van Roosbroeck system with additional source terms coupled with ODEs containing space and energy as parameters for all defect densities. The system has to be considered in heterostructures and with mixed boundary conditions from device simulation. We give a weak formulation of the problem. If the boundary data and the sources are compatible with thermodynamic equilibrium the free energy along solutions decays monotonously. In other cases it may be increasing, but we estimate its growth. We establish boundedness and uniqueness results and prove the existence of a weak solution. This is done by considering a regularized problem, showing its solvability and the boundedness of its solutions independent of the regularization level. (orig.)

  8. Effect of including decay chains on predictions of equilibrium-type terrestrial food chain models

    International Nuclear Information System (INIS)

    Kirchner, G.

    1990-01-01

    Equilibrium-type food chain models are commonly used for assessing the radiological impact to man from environmental releases of radionuclides. Usually these do not take into account build-up of radioactive decay products during environmental transport. This may be a potential source of underprediction. For estimating consequences of this simplification, the equations of an internationally recognised terrestrial food chain model have been extended to include decay chains of variable length. Example calculations show that for releases from light water reactors as expected both during routine operation and in the case of severe accidents, the build-up of decay products during environmental transport is generally of minor importance. However, a considerable number of radionuclides of potential radiological significance have been identified which show marked contributions of decay products to calculated contamination of human food and resulting radiation dose rates. (author)

  9. Effect of PCBs on the lactational transfer of methyl mercury in mice: PBPK modeling

    Science.gov (United States)

    Lee, Sun Ku; Hamer, Dwayne; Bedwell, Cathy L.; Lohitnavy, Manupat; Yang, Raymond S. H.

    2009-01-01

    MeHg and PCB exposure to lactating mice were analyzed and a physiologically-based pharmacokinetic (PBPK) model was developed to describe the lactational transfer of MeHg in mice. The influence of albumin on the lactational transfer of MeHg was incorporated into the PBPK model. Experimental results with lactating mice and their pups showed that co-exposure with PCB congeners increased the lactational transfer of MeHg to the pups, which was associated with the rise of albumin levels in maternal blood. Observed results were matched with PBPK model simulations conducted under the assumptions that (1) MeHg bound to plasma albumin is transferred to maternal milk, and (2) PCB congeners may increase the lactational transfer of MeHg by escalating albumin levels in maternal blood. Further refinement of PBPK model quantitatively described the pharmacokinetic changes of MeHg by co-exposure with PCBs in pup’s tissues. PMID:20046988

  10. Understanding Experimental LCMV Infection of Mice: The Role of Mathematical Models

    Directory of Open Access Journals (Sweden)

    Gennady Bocharov

    2015-01-01

    Full Text Available Virus infections represent complex biological systems governed by multiple-level regulatory processes of virus replication and host immune responses. Understanding of the infection means an ability to predict the systems behaviour under various conditions. Such predictions can only rely upon quantitative mathematical models. The model formulations should be tightly linked to a fundamental step called “coordinatization” (Hermann Weyl, that is, the definition of observables, parameters, and structures that enable the link with a biological phenotype. In this review, we analyse the mathematical modelling approaches to LCMV infection in mice that resulted in quantification of some fundamental parameters of the CTL-mediated virus control including the rates of T cell turnover, infected target cell elimination, and precursor frequencies. We show how the modelling approaches can be implemented to address diverse aspects of immune system functioning under normal conditions and in response to LCMV and, importantly, make quantitative predictions of the outcomes of immune system perturbations. This may highlight the notion that data-driven applications of meaningful mathematical models in infection biology remain a challenge.

  11. Including sugar cane in the agro-ecosystem model ORCHIDEE-STICS

    Science.gov (United States)

    Valade, A.; Vuichard, N.; Ciais, P.; Viovy, N.

    2010-12-01

    With 4 million ha currently grown for ethanol in Brazil only, approximately half the global bioethanol production in 2005 (Smeets 2008), and a devoted land area expected to expand globally in the years to come, sugar cane is at the heart of the biofuel debate. Indeed, ethanol made from biomass is currently the most widespread option for alternative transportation fuels. It was originally promoted as a carbon neutral energy resource that could bring energy independence to countries and local opportunities to farmers, until attention was drawn to its environmental and socio-economical drawbacks. It is still not clear to which extent it is a solution or a contributor to climate change mitigation. Dynamic Global Vegetation models can help address these issues and quantify the potential impacts of biofuels on ecosystems at scales ranging from on-site to global. The global agro-ecosystem model ORCHIDEE describes water, carbon and energy exchanges at the soil-atmosphere interface for a limited number of natural and agricultural vegetation types. In order to integrate agricultural management to the simulations and to capture more accurately the specificity of crops' phenology, ORCHIDEE has been coupled with the agronomical model STICS. The resulting crop-oriented vegetation model ORCHIDEE-STICS has been used so far to simulate temperate crops such as wheat, corn and soybean. As a generic ecosystem model, each grid cell can include several vegetation types with their own phenology and management practices, making it suitable to spatial simulations. Here, ORCHIDEE-STICS is altered to include sugar cane as a new agricultural Plant functional Type, implemented and parametrized using the STICS approach. An on-site calibration and validation is then performed based on biomass and flux chamber measurements in several sites in Australia and variables such as LAI, dry weight, heat fluxes and respiration are used to evaluate the ability of the model to simulate the specific

  12. Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice.

    Science.gov (United States)

    Oestreich, A K; Carleton, S M; Yao, X; Gentry, B A; Raw, C E; Brown, M; Pfeiffer, F M; Wang, Y; Phillips, C L

    2016-01-01

    Mice with osteogenesis imperfecta (+/oim), a disorder of bone fragility, were bred to mice with muscle over growth to test whether increasing muscle mass genetically would improve bone quality and strength. The results demonstrate that femora from mice carrying both mutations have greater mechanical integrity than their +/oim littermates. Osteogenesis imperfecta is a heritable connective tissue disorder due primarily to mutations in the type I collagen genes resulting in skeletal deformity and fragility. Currently, there is no cure, and therapeutic strategies encompass the use of antiresorptive pharmaceuticals and surgical bracing, with limited success and significant potential for adverse effects. Bone, a mechanosensing organ, can respond to high mechanical loads by increasing new bone formation and altering bone geometry to withstand increased forces. Skeletal muscle is a major source of physiological loading on bone, and bone strength is proportional to muscle mass. To test the hypothesis that congenic increases in muscle mass in the osteogenesis imperfecta murine model mouse (oim) will improve their compromised bone quality and strength, heterozygous (+/oim) mice were bred to mice deficient in myostatin (+/mstn), a negative regulator of muscle growth. The resulting adult offspring were evaluated for hindlimb muscle mass, and bone microarchitecture, physiochemistry, and biomechanical integrity. +/oim mice deficient in myostatin (+/mstn +/oim) were generated and demonstrated that myostatin deficiency increased body weight, muscle mass, and biomechanical strength in +/mstn +/oim mice as compared to +/oim mice. Additionally, myostatin deficiency altered the physiochemical properties of the +/oim bone but did not alter bone remodeling. Myostatin deficiency partially improved the reduced femoral bone biomechanical strength of adult +/oim mice by increasing muscle mass with concomitant improvements in bone microarchitecture and physiochemical properties.

  13. Development of pristane induced mice model for lupus with atherosclerosis and analysis of TLR expression.

    Science.gov (United States)

    Chen, Xiaoqing; Cui, RanRan; Li, Rongda; Lin, Huili; Huang, Ziyang; Lin, Ling

    2016-01-01

    This study was designed to establish a murine model of lupus with atherosclerosis, and to investigate the expression of Toll-like receptors (TLRs) in the aorta and kidney. The 9-week-old female ApoE-/- and C57BL/6 mice were randomly divided into a ApoE-/- pristane treated group (group A), ApoE-/- control group (group B), C57BL/6 pristane treated group (group C) and C57BL/6 control group (group D). Each mouse was given either a single intraperitoneal injection of 0.5 ml pristane or saline. We observed that group A mice specifically had poor spirit, less activity, obvious hair loss, splenomegalia and renomegaly. Levels of ANA, anti-ds-DNA and anti-Sm antibodies were significantly higher than those in other groups. The group A and B mice generally displayed intimal hyperplasia and atherosclerosis mottling in the lumen of the aorta. The kidney tissues from group A, B and C mice showed increased expression levels of TLR2, TLR4, TLR7 and TLR9 proteins in comparison to group D. However, Group A mice did not show any significant difference in TLR2 and TLR4 protein expression levels when compared to group B and C, but displayed higher TLR7 expression than group B and higher TLR9 expression than group B and C mice. In contrast, the group A and B mice apparently expressed TLR2 and TLR4. We concluded that pristane treated apoE-/- mice exhibited lupus-like phenotype and developed atherosclerosis. The pristane treatment also induced abnormally high expression of TLR2 and TLR4 in the aorta and TLR2, TLR4, TLR7 and TLR9 in the kidney of apoE-/- mice.

  14. Web-accessible molecular modeling with Rosetta: The Rosetta Online Server that Includes Everyone (ROSIE).

    Science.gov (United States)

    Moretti, Rocco; Lyskov, Sergey; Das, Rhiju; Meiler, Jens; Gray, Jeffrey J

    2018-01-01

    The Rosetta molecular modeling software package provides a large number of experimentally validated tools for modeling and designing proteins, nucleic acids, and other biopolymers, with new protocols being added continually. While freely available to academic users, external usage is limited by the need for expertise in the Unix command line environment. To make Rosetta protocols available to a wider audience, we previously created a web server called Rosetta Online Server that Includes Everyone (ROSIE), which provides a common environment for hosting web-accessible Rosetta protocols. Here we describe a simplification of the ROSIE protocol specification format, one that permits easier implementation of Rosetta protocols. Whereas the previous format required creating multiple separate files in different locations, the new format allows specification of the protocol in a single file. This new, simplified protocol specification has more than doubled the number of Rosetta protocols available under ROSIE. These new applications include pK a determination, lipid accessibility calculation, ribonucleic acid redesign, protein-protein docking, protein-small molecule docking, symmetric docking, antibody docking, cyclic toxin docking, critical binding peptide determination, and mapping small molecule binding sites. ROSIE is freely available to academic users at http://rosie.rosettacommons.org. © 2017 The Protein Society.

  15. Craniofacial Statistical Deformation Models of Wild-type mice and Crouzon mice

    DEFF Research Database (Denmark)

    Ólafsdóttir, Hildur; Darvann, Tron Andre; Ersbøll, Bjarne Kjær

    2007-01-01

    Crouzon syndrome is characterised by the premature fusion of cranial sutures and synchondroses leading to craniofacial growth disturbances. The gene causing the syndrome was discovered approximately a decade ago and recently the first mouse model of the syndrome was generated. In this study, a set...... using B-spline-based nonrigid registration and subsequently, the atlas was nonrigidly registered to the cases being modelled. The parameters of these registrations were then used as input to a PCA. Using different sets of registration parameters, different models were constructed to describe (i...

  16. A curved multi-component aerosol hygroscopicity model framework: 2 Including organics

    Science.gov (United States)

    Topping, D. O.; McFiggans, G. B.; Coe, H.

    2004-12-01

    This paper describes the inclusion of organic particulate material within the Aerosol Diameter Dependent Equilibrium Model (ADDEM) framework described in the companion paper applied to inorganic aerosol components. The performance of ADDEM is analysed in terms of its capability to reproduce the behaviour of various organic and mixed inorganic/organic systems using recently published bulk data. Within the modelling architecture already described two separate thermodynamic models are coupled in an additive approach and combined with a method for solving the Köhler equation in order to develop a tool for predicting the water content associated with an aerosol of known inorganic/organic composition and dry size. For development of the organic module, the widely used group contribution method UNIFAC is employed to explicitly deal with the non-ideality in solution. The UNIFAC predictions for components of atmospheric importance were improved considerably by using revised interaction parameters derived from electro-dynamic balance studies. Using such parameters, the model was found to adequately describe mixed systems including 5-6 dicarboxylic acids, down to low relative humidity conditions. The additive approach for modelling mixed inorganic/organic systems worked well for a variety of mixtures. As expected, deviations between predicted and measured data increase with increasing concentration. Available surface tension models, used in evaluating the Kelvin term, were found to reproduce measured data with varying success. Deviations from experimental data increased with increased organic compound complexity. For components only slightly soluble in water, significant deviations from measured surface tension depression behaviour were predicted with both model formalisms tested. A Sensitivity analysis showed that such variation is likely to lead to predicted growth factors within the measurement uncertainty for growth factor taken in the sub-saturated regime. Greater

  17. A Hydrological Concept including Lateral Water Flow Compatible with the Biogeochemical Model ForSAFE

    Directory of Open Access Journals (Sweden)

    Giuliana Zanchi

    2016-03-01

    Full Text Available The study presents a hydrology concept developed to include lateral water flow in the biogeochemical model ForSAFE. The hydrology concept was evaluated against data collected at Svartberget in the Vindeln Research Forest in Northern Sweden. The results show that the new concept allows simulation of a saturated and an unsaturated zone in the soil as well as water flow that reaches the stream comparable to measurements. The most relevant differences compared to streamflow measurements are that the model simulates a higher base flow in winter and lower flow peaks after snowmelt. These differences are mainly caused by the assumptions made to regulate the percolation at the bottom of the simulated soil columns. The capability for simulating lateral flows and a saturated zone in ForSAFE can greatly improve the simulation of chemical exchange in the soil and export of elements from the soil to watercourses. Such a model can help improve the understanding of how environmental changes in the forest landscape will influence chemical loads to surface waters.

  18. Integrated Sachs-Wolfe effect in a quintessence cosmological model: Including anisotropic stress of dark energy

    International Nuclear Information System (INIS)

    Wang, Y. T.; Xu, L. X.; Gui, Y. X.

    2010-01-01

    In this paper, we investigate the integrated Sachs-Wolfe effect in the quintessence cold dark matter model with constant equation of state and constant speed of sound in dark energy rest frame, including dark energy perturbation and its anisotropic stress. Comparing with the ΛCDM model, we find that the integrated Sachs-Wolfe (ISW)-power spectrums are affected by different background evolutions and dark energy perturbation. As we change the speed of sound from 1 to 0 in the quintessence cold dark matter model with given state parameters, it is found that the inclusion of dark energy anisotropic stress makes the variation of magnitude of the ISW source uncertain due to the anticorrelation between the speed of sound and the ratio of dark energy density perturbation contrast to dark matter density perturbation contrast in the ISW-source term. Thus, the magnitude of the ISW-source term is governed by the competition between the alterant multiple of (1+3/2xc-circumflex s 2 ) and that of δ de /δ m with the variation of c-circumflex s 2 .

  19. Expanded rock blast modeling capabilities of DMC{_}BLAST, including buffer blasting

    Energy Technology Data Exchange (ETDEWEB)

    Preece, D.S. [Sandia National Labs., Albuquerque, NM (United States); Tidman, J.P.; Chung, S.H. [ICI Explosives (Canada)

    1996-12-31

    A discrete element computer program named DMC{_}BLAST (Distinct Motion Code) has been under development since 1987 for modeling rock blasting. This program employs explicit time integration and uses spherical or cylindrical elements that are represented as circles in 2-D. DMC{_}BLAST calculations compare favorably with data from actual bench blasts. The blast modeling capabilities of DMC{_}BLAST have been expanded to include independently dipping geologic layers, top surface, bottom surface and pit floor. The pit can also now be defined using coordinates based on the toe of the bench. A method for modeling decked explosives has been developed which allows accurate treatment of the inert materials (stemming) in the explosive column and approximate treatment of different explosives in the same blasthole. A DMC{_}BLAST user can specify decking through a specific geologic layer with either inert material or a different explosive. Another new feature of DMC{_}BLAST is specification of an uplift angle which is the angle between the normal to the blasthole and a vector defining the direction of explosive loading on particles adjacent to the blasthole. A buffer (choke) blast capability has been added for situations where previously blasted material is adjacent to the free face of the bench preventing any significant lateral motion during the blast.

  20. Modelling and control of a microgrid including photovoltaic and wind generation

    Science.gov (United States)

    Hussain, Mohammed Touseef

    Extensive increase of distributed generation (DG) penetration and the existence of multiple DG units at distribution level have introduced the notion of micro-grid. This thesis develops a detailed non-linear and small-signal dynamic model of a microgrid that includes PV, wind and conventional small scale generation along with their power electronics interfaces and the filters. The models developed evaluate the amount of generation mix from various DGs for satisfactory steady state operation of the microgrid. In order to understand the interaction of the DGs on microgrid system initially two simpler configurations were considered. The first one consists of microalternator, PV and their electronics, and the second system consists of microalternator and wind system each connected to the power system grid. Nonlinear and linear state space model of each microgrid are developed. Small signal analysis showed that the large participation of PV/wind can drive the microgrid to the brink of unstable region without adequate control. Non-linear simulations are carried out to verify the results obtained through small-signal analysis. The role of the extent of generation mix of a composite microgrid consisting of wind, PV and conventional generation was investigated next. The findings of the smaller systems were verified through nonlinear and small signal modeling. A central supervisory capacitor energy storage controller interfaced through a STATCOM was proposed to monitor and enhance the microgrid operation. The potential of various control inputs to provide additional damping to the system has been evaluated through decomposition techniques. The signals identified to have damping contents were employed to design the supervisory control system. The controller gains were tuned through an optimal pole placement technique. Simulation studies demonstrate that the STATCOM voltage phase angle and PV inverter phase angle were the best inputs for enhanced stability boundaries.

  1. Alterations of in vivo CA1 network activity in Dp(16)1Yey Down syndrome model mice.

    Science.gov (United States)

    Raveau, Matthieu; Polygalov, Denis; Boehringer, Roman; Amano, Kenji; Yamakawa, Kazuhiro; McHugh, Thomas J

    2018-02-27

    Down syndrome, the leading genetic cause of intellectual disability, results from an extra-copy of chromosome 21. Mice engineered to model this aneuploidy exhibit Down syndrome-like memory deficits in spatial and contextual tasks. While abnormal neuronal function has been identified in these models, most studies have relied on in vitro measures. Here, using in vivo recording in the Dp(16)1Yey model, we find alterations in the organization of spiking of hippocampal CA1 pyramidal neurons, including deficits in the generation of complex spikes. These changes lead to poorer spatial coding during exploration and less coordinated activity during sharp-wave ripples, events involved in memory consolidation. Further, the density of CA1 inhibitory neurons expressing neuropeptide Y, a population key for the generation of pyramidal cell bursts, were significantly increased in Dp(16)1Yey mice. Our data refine the 'over-suppression' theory of Down syndrome pathophysiology and suggest specific neuronal subtypes involved in hippocampal dysfunction in these model mice. © 2018, Raveau et al.

  2. Spontaneous, Immune-Mediated Gastric Inflammation in SAMP1/YitFc Mice, a Model of Crohn’s-Like Gastritis

    Science.gov (United States)

    Reuter, Brian K.; Pastorelli, Luca; Brogi, Marco; Garg, Rekha R.; McBride, James A.; Rowlett, Robert M.; Arrieta, Marie C.; Wang, Xiao-Ming; Keller, Erik J.; Feldman, Sanford H.; Mize, James R.; Cominelli, Fabio; Meddings, Jonathan B.; Pizarro, Theresa T.

    2011-01-01

    Background & Aims Crohn’s disease (CD) can develop in any region of the gastrointestinal tract, including the stomach. The etiology and pathogenesis of Crohn’s gastritis are poorly understood, treatment approaches are limited, and there are not many suitable animal models for study. We characterized the features and mechanisms of chronic gastritis in SAMP1/YitFc (SAMP) mice, a spontaneous model of CD-like ileitis, along with possible therapeutic approaches. Methods Stomachs from specific pathogen-free and germ-free SAMP and AKR mice (controls) were evaluated histologically; the presence of Helicobacter spp. was tested in fecal pellets by PCR analysis. In vivo gastric permeability was quantified by fractional excretion of sucrose and epithelial tight junction protein expression was measured by quantitative reverse transcription PCR analysis. The effects of a proton pump inhibitor (PPI) or corticosteroids were measured and the ability of pathogenic immune cells to mediate gastritis was assessed in adoptive transfer experiments. Results SAMP mice developed Helicobacter-negative gastritis, characterized by aggregates of mononuclear cells, diffuse accumulation of neutrophils, and disruption of epithelial architecture; SAMP mice also had increased in gastric permeability compared with controls, without alterations in expression of tight junction proteins. The gastritis and associated permeability defect observed in SAMP mice were independent of bacterial colonization and reduced by administration of corticosteroids but not a PPI. CD4+ T cells isolated from draining mesenteric lymph nodes of SAMP mice were sufficient to induce gastritis in recipient SCID mice. Conclusions In SAMP mice, gastritis develops spontaneously and has many features of CD-like ileitis. These mice are a useful model to study Helicobacter-negative, immune-mediated Crohn’s gastritis. PMID:21704001

  3. The mouse as a model for understanding chronic diseases of aging: the histopathologic basis of aging in inbred mice

    Directory of Open Access Journals (Sweden)

    David Harrison

    2011-06-01

    Full Text Available Inbred mice provide a unique tool to study aging populations because of the genetic homogeneity within an inbred strain, their short life span, and the tools for analysis which are available. A large-scale longitudinal and cross-sectional aging study was conducted on 30 inbred strains to determine, using histopathology, the type and diversity of diseases mice develop as they age. These data provide tools that when linked with modern in silico genetic mapping tools, can begin to unravel the complex genetics of many of the common chronic diseases associated with aging in humans and other mammals. In addition, novel disease models were discovered in some strains, such as rhabdomyosarcoma in old A/J mice, to diseases affecting many but not all strains including pseudoxanthoma elasticum, pulmonary adenoma, alopecia areata, and many others. This extensive data set is now available online and provides a useful tool to help better understand strain-specific background diseases that can complicate interpretation of genetically engineered mice and other manipulatable mouse studies that utilize these strains.

  4. Bone invading NSCLC cells produce IL-7: mice model and human histologic data

    International Nuclear Information System (INIS)

    Roato, Ilaria; Mussa, Antonio; Ferracini, Riccardo; Caldo, Davide; Godio, Laura; D'Amico, Lucia; Giannoni, Paolo; Morello, Emanuela; Quarto, Rodolfo; Molfetta, Luigi; Buracco, Paolo

    2010-01-01

    Bone metastases are a common and dismal consequence of lung cancer that is a leading cause of death. The role of IL-7 in promoting bone metastases has been previously investigated in NSCLC, but many aspects remain to be disclosed. To further study IL-7 function in bone metastasis, we developed a human-in-mice model of bone aggression by NSCLC and analyzed human bone metastasis biopsies. We used NOD/SCID mice implanted with human bone. After bone engraftment, two groups of mice were injected subcutaneously with A549, a human NSCLC cell line, either close or at the contralateral flank to the human bone implant, while a third control group did not receive cancer cells. Tumor and bone vitality and IL-7 expression were assessed in implanted bone, affected or not by A549. Serum IL-7 levels were evaluated by ELISA. IL-7 immunohistochemistry was performed on 10 human bone NSCLC metastasis biopsies for comparison. At 12 weeks after bone implant, we observed osteogenic activity and neovascularization, confirming bone vitality. Tumor aggressive cells implanted close to human bone invaded the bone tissue. The bone-aggressive cancer cells were positive for IL-7 staining both in the mice model and in human biopsies. Higher IL-7 serum levels were found in mice injected with A549 cells close to the bone implant compared to mice injected with A549 cells in the flank opposite to the bone implant. We demonstrated that bone-invading cells express and produce IL-7, which is known to promote osteoclast activation and osteolytic lesions. Tumor-bone interaction increases IL-7 production, with an increase in IL-7 serum levels. The presented mice model of bone invasion by contiguous tumor is suitable to study bone-tumor cell interaction. IL-7 plays a role in the first steps of metastatic process

  5. Modeling the ferrochelatase c.315-48C modifier mutation for erythropoietic protoporphyria (EPP in mice

    Directory of Open Access Journals (Sweden)

    Jasmin Barman-Aksözen

    2017-03-01

    Full Text Available Erythropoietic protoporphyria (EPP is caused by deficiency of ferrochelatase (FECH, which incorporates iron into protoporphyrin IX (PPIX to form heme. Excitation of accumulated PPIX by light generates oxygen radicals that evoke excessive pain and, after longer light exposure, cause ulcerations in exposed skin areas of individuals with EPP. Moreover, ∼5% of the patients develop a liver dysfunction as a result of PPIX accumulation. Most patients (∼97% have a severe FECH mutation (Mut in trans to an intronic polymorphism (c.315-48C, which reduces ferrochelatase synthesis by stimulating the use of an aberrant 3′ splice site 63 nt upstream of the normal site for exon 4. In contrast, with the predominant c.315-48T allele, the correct splice site is mostly used, and individuals with a T/Mut genotype do not develop EPP symptoms. Thus, the C allele is a potential target for therapeutic approaches that modify this splicing decision. To provide a model for pre-clinical studies of such approaches, we engineered a mouse containing a partly humanized Fech gene with the c.315-48C polymorphism. F1 hybrids obtained by crossing these mice with another inbred line carrying a severe Fech mutation (named m1Pas show a very strong EPP phenotype that includes elevated PPIX in the blood, enlargement of liver and spleen, anemia, as well as strong pain reactions and skin lesions after a short period of light exposure. In addition to the expected use of the aberrant splice site, the mice also show a strong skipping of the partly humanized exon 3. This will limit the use of this model for certain applications and illustrates that engineering of a hybrid gene may have unforeseeable consequences on its splicing.

  6. Exergoeconomic performance optimization for a steady-flow endoreversible refrigeration model including six typical cycles

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Lingen; Kan, Xuxian; Sun, Fengrui; Wu, Feng [College of Naval Architecture and Power, Naval University of Engineering, Wuhan 430033 (China)

    2013-07-01

    The operation of a universal steady flow endoreversible refrigeration cycle model consisting of a constant thermal-capacity heating branch, two constant thermal-capacity cooling branches and two adiabatic branches is viewed as a production process with exergy as its output. The finite time exergoeconomic performance optimization of the refrigeration cycle is investigated by taking profit rate optimization criterion as the objective. The relations between the profit rate and the temperature ratio of working fluid, between the COP (coefficient of performance) and the temperature ratio of working fluid, as well as the optimal relation between profit rate and the COP of the cycle are derived. The focus of this paper is to search the compromised optimization between economics (profit rate) and the utilization factor (COP) for endoreversible refrigeration cycles, by searching the optimum COP at maximum profit, which is termed as the finite-time exergoeconomic performance bound. Moreover, performance analysis and optimization of the model are carried out in order to investigate the effect of cycle process on the performance of the cycles using numerical example. The results obtained herein include the performance characteristics of endoreversible Carnot, Diesel, Otto, Atkinson, Dual and Brayton refrigeration cycles.

  7. Intestinal bacterial overgrowth includes potential pathogens in the carbohydrate overload models of equine acute laminitis.

    Science.gov (United States)

    Onishi, Janet C; Park, Joong-Wook; Prado, Julio; Eades, Susan C; Mirza, Mustajab H; Fugaro, Michael N; Häggblom, Max M; Reinemeyer, Craig R

    2012-10-12

    Carbohydrate overload models of equine acute laminitis are used to study the development of lameness. It is hypothesized that a diet-induced shift in cecal bacterial communities contributes to the development of the pro-inflammatory state that progresses to laminar failure. It is proposed that vasoactive amines, protease activators and endotoxin, all bacterial derived bioactive metabolites, play a role in disease development. Questions regarding the oral bioavailability of many of the bacterial derived bioactive metabolites remain. This study evaluates the possibility that a carbohydrate-induced overgrowth of potentially pathogenic cecal bacteria occurs and that bacterial translocation contributes toward the development of the pro-inflammatory state. Two groups of mixed-breed horses were used, those with laminitis induced by cornstarch (n=6) or oligofructan (n=6) and non-laminitic controls (n=8). Cecal fluid and tissue homogenates of extra-intestinal sites including the laminae were used to enumerate Gram-negative and -positive bacteria. Horses that developed Obel grade2 lameness, revealed a significant overgrowth of potentially pathogenic Gram-positive and Gram-negative intestinal bacteria within the cecal fluid. Although colonization of extra-intestinal sites with potentially pathogenic bacteria was not detected, results of this study indicate that cecal/colonic lymphadenopathy and eosinophilia develop in horses progressing to lameness. It is hypothesized that the pro-inflammatory state in carbohydrate overload models of equine acute laminitis is driven by an immune response to the rapid overgrowth of Gram-positive and Gram-negative cecal bacterial communities in the gut. Further equine research is indicated to study the immunological response, involving the lymphatic system that develops in the model. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. CFD simulations and reduced order modeling of a refrigerator compartment including radiation effects

    International Nuclear Information System (INIS)

    Bayer, Ozgur; Oskay, Ruknettin; Paksoy, Akin; Aradag, Selin

    2013-01-01

    Highlights: ► Free convection in a refrigerator is simulated including radiation effects. ► Heat rates are affected drastically when radiation effects are considered. ► 95% of the flow energy can be represented by using one spatial POD mode. - Abstract: Considering the engineering problem of natural convection in domestic refrigerator applications, this study aims to simulate the fluid flow and temperature distribution in a single commercial refrigerator compartment by using the experimentally determined temperature values as the specified constant wall temperature boundary conditions. The free convection in refrigerator applications is evaluated as a three-dimensional (3D), turbulent, transient and coupled non-linear flow problem. Radiation heat transfer mode is also included in the analysis. According to the results, taking radiation effects into consideration does not change the temperature distribution inside the refrigerator significantly; however the heat rates are affected drastically. The flow inside the compartment is further analyzed with a reduced order modeling method called Proper Orthogonal Decomposition (POD) and the energy contents of several spatial and temporal modes that exist in the flow are examined. The results show that approximately 95% of all the flow energy can be represented by only using one spatial mode

  9. Knock out of S1P3 receptor signaling attenuates inflammation and fibrosis in bleomycin-induced lung injury mice model.

    Directory of Open Access Journals (Sweden)

    Ken Murakami

    Full Text Available Sphingosine-1-phosphate (S1P is a bioactive sphingolipid metabolite involved in many critical cellular processes, including proliferation, migration, and angiogenesis, through interaction with a family of five G protein-coupled receptors (S1P1-5. Some reports have implicated S1P as an important inflammatory mediator of the pathogenesis of airway inflammation, but the role of S1P3 in the pathogenesis of lung diseases is not completely understood. We used S1P3-deficient (knockout (KO mice to clarify the role of S1P3 receptor signaling in the pathogenesis of pulmonary inflammation and fibrosis using a bleomycin-induced model of lung injury. On the seventh day after bleomycin administration, S1P3 KO mice exhibited significantly less body weight loss and pulmonary inflammation than wild-type (WT mice. On the 28th day, there was less pulmonary fibrosis in S1P3 KO mice than in WT mice. S1P3 KO mice demonstrated a 56% reduction in total cell count in bronchoalveolar lavage fluid (BALF collected on the seventh day compared with WT mice; however, the differential white blood cell profiles were similar. BALF analysis on the seventh day showed that connective tissue growth factor (CTGF levels were significantly decreased in S1P3 KO mice compared with WT mice, although no differences were observed in monocyte chemotactic protein-1 (MCP-1 or transforming growth factor β1 (TGF-β1 levels. Finally, S1P levels in BALF collected on the 7th day after treatment were not significantly different between WT and S1P3 KO mice. Our results indicate that S1P3 receptor signaling plays an important role in pulmonary inflammation and fibrosis and that this signaling occurs via CTGF expression. This suggests that this pathway might be a therapeutic target for pulmonary fibrosis.

  10. The influence of stachydrine hydrochloride on the reperfusion model of mice with repetitive cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Mingsan Miao

    2017-03-01

    Full Text Available To study the influence of stachydrine hydrochloride on the inflammatory cytokines and tissue morphology of the re-perfusion model of mice with repetitive cerebral ischemia and probe into the protection mechanism of stachydrine hydrochloride for cerebral ischemia reperfusion impairment. Build a repetitive cerebral ischemia reperfusion model by first blocking the common carotid artery on both sides for 10 min, then resuming perfusion for 10 min and then blocking the common carotid artery on both sides again for 10 min. Before the operation, all the mice in the Nimodipine group, and the big, medium and small stachydrine hydrochloride dose groups were given corresponding gastric perfusion, the mice in the sham operation group and the modeled groups were at the same time given 0.5% sodium carboxymethyl cellulose for gastric perfusion of the same volume. The medicine was fed daily for 7 consecutive days. The model was built 1 h after the last feed and the perfusion continued for 24 h after the operation. Then the death rate of the mice was calculated. The mouse brains were taken out to test the ICAM-1 level and the TNF-α level, and the serum was taken out to test the NSE level and the MPO level. The tissue morphology changes were also observed. All the repetitive cerebral ischemia reperfusion models were successfully duplicated. The stachydrine hydrochloride in all the dose groups significantly reduced the death rates of big and small mice, reduced the level of ICAM-1 and the level of TNF-α in the brain tissues and the NSE level and the MPO level in the serum, significantly alleviating the pathological impairment in the hippocampus. Stachydrine hydrochloride can significantly reduce the death rate of mice, improve the pathological changes in the hippocampus, inhibit inflammatory reactions after ischemia, thus reducing the re-perfusion impairment after cerebral ischemia.

  11. [Genetic mice models of type 2 diabetes for evaluation of the effectiveness of minor biologically active food substances].

    Science.gov (United States)

    Mazo, V K; Sidorova, Yu S; Kochetkova, A A

    2015-01-01

    This report is devoted to discussion of type 2 diabetes experimental modelling on genetic mice lines. These laboratory animals, the same as genetic rats lines, are usually used in type 2 diabetes experimental modelling. The problem of using mice with genetic obesity in modeling of type 2 diabetes is discussed in details in the review. In this article the authors shortly characterize the congenic line of mice ККАУ, suffering from genetic obesity and hyperinsulinemia. The features of modelling type 2 diabetes using ob/ob and db/db mice are described closely. The phenotype of the animals comes into obesity, infertility, brakes in length growth, hyperinsulinemia and dysimmunity. Neither leptin mRNA, nor the hormone itself are synthesized in ob/ob mice, leading to ob phenotype formation. Whilst db/db mice have two mutant copies of leptin receptor gene, which leads to gradual hyperglycemia and obesity progression, followed by hyperinsulemia similar to human type 2 diabetes. C57BL/KsLeprdb/+ mice with recessive gene leptin receptoi-Lepiнlb (db) is very perspective genetic type 2 diabetes model developed in Russia. TSOD mice are used as an alternative model (Tsumura Suzuki, diabetes with obesity), showing diabetes and obesity symptoms with marked hyperinsulinemia and pancreatic gland hypertrophy. Thus, presented in this review scientific reports approve wide opportunities of effective usage of genetic lines of small laboratory animals (mice) for type 2 diabetes modelling.

  12. Expression and roles of aquaporin 1 in hippocampus of mice model with traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Bo QIU

    2014-03-01

    Full Text Available Background The "secondary brain insult" including ischemia, hypoxia and edema after primary traumatic brain injury (TBI may deteriorate the brain damages and greatly influence the prognosis. As a selective vulnerable region, the hippocampus is especially sensitive to ischemia, hypoxia or edema and yields irreversible sequelae. Aquaporin 1 (AQP1 has been reported to be related to cerebral edema, but the expression and role of AQP1 in hippocampal edema after TBI have seldomly been investigated. In this study, we established BALB/c mouse closed craniocerebral injury models and investigated the changes of AQP1 expression in hippocampus of mouse models after TBI, thereby discussing its effects on relevant pathophysiological processes.  Methods Seventy-five BALB/c mice were used to establish experimental closed TBI models with a free-falling weight drop device, and the equal numbers of mice were subject to sham operation and categorized as sham group. The neurological function of each mouse in either TBI group or sham group was scored at different time points (1, 6, 24 and 72 h after TBI or sham operation, and brain edema formation of the mice in both groups was also evaluated accordingly at 6, 24 and 72 h. The apoptotic hippocampal cells were stained in situ and detected using TdT-mediated dUTP-biotin nick end labeling (TUNEL method at different time points (6, 24 and 72 h, then AQP1 expression in hippocampus was also correspondingly detected using immunohistochemistry and Western blotting. All the data were finally compared with those in sham operation group and analyzed.  Results Experimental TBI models were successfully established and confirmed by the neurological function score and hippocampal edema evaluation. Six hours after craniocerebral injury, the apoptotic cells increased significantly in the hippocampus of mice in TBI group compared with those in sham group [(44.26 ± 15.18% vs (8.61 ± 8.25% , t = - 9.676, P = 0.002]. The apoptotic

  13. Oral administration of bepotastine besilate suppressed scratching behavior of atopic dermatitis model NC/Nga mice.

    Science.gov (United States)

    Tanizaki, Hideaki; Kambe, Naotomo; Nakamura, Yuumi; Tanaka, Akane; Matsuda, Hiroshi; Miyachi, Yoshiki

    2008-01-01

    Pruritus is the most severe problem in atopic dermatitis. Even though its mechanism is still not fully understood, antihistamines have been prescribed for atopic dermatitis. To evaluate the effect of antihistamine on atopic dermatitis, we analyzed the scratching behavior in atopic dermatitis model NC/Nga mice. BALB/c mice, in which scratching behavior was induced by intradermal injection of compound 48/80 (100 microg/100 microl/mouse), and NC/Nga mice, housed in a conventional environment and having developed spontaneous eczematous regions, were monitored with a SCLABA system after oral administration of bepotastine besilate. The number of eosinophils in the ear skin and the serum leukotriene B(4) (LTB(4)) levels were also evaluated. Bepotastine at doses of 3 and 10 mg/kg effectively inhibited the compound 48/80-induced scratching behavior of BALB/c mice 1 h after oral administration, comparable with the blood T(max), which was reached within 0.8-1.6 h in humans. Bepotastine also significantly inhibited the scratching behavior of NC/Nga mice 1 h after oral administration. Even though 10 mg/kg bepotastine could not influence the number of tissue eosinophils, it effectively suppressed the serum LTB(4) levels, just comparable with the suppression of scratch behavior of NC/Nga mice. Bepotastin effectively suppressed the scratch behavior of atopic dermatitis model mice, which may not simply be explained by the suppression of histamine but also by the suppression of other mediators like LTB(4). Bepotastine could be useful in the treatment of pruritus, especially early after oral administration. 2007 S. Karger AG, Basel

  14. Sex differences in response to activity-based anorexia model in C57Bl/6 mice.

    Science.gov (United States)

    Achamrah, Najate; Nobis, Séverine; Goichon, Alexis; Breton, Jonathan; Legrand, Romain; do Rego, Jean Luc; do Rego, Jean Claude; Déchelotte, Pierre; Fetissov, Sergueï O; Belmonte, Liliana; Coëffier, Moïse

    2017-03-01

    Anorexia nervosa is a severe eating disorder often associated with physical hyperactivity and is more frequently observed in female sex. Activity-Based Anorexia (ABA) model combines physical activity (PA) and reduced food intake and thus allows a better understanding of the mechanisms underlying anorexia nervosa. We aimed to assess sex differences in response to ABA model in C57Bl/6 mice. Twenty four male and 16 female C57BL/6 mice were studied. ABA mice were placed in individual cages with a continuously recorded activity wheel. ABA mice had a progressive limited food access from 6h/day (day 6) to 3h/day (day 9) until the end of the protocol (day 17). Body weight and food intake were daily measured. We studied physical activity during 24h, during the dark phase (D-PA) and the light phase (L-PA). We also evaluated the feeding anticipatory physical activity (A-PA), the physical activity during food intake period (FI-PA) and the post-prandial physical activity (PP-PA). We observed 16.7% of mortality in males (4 out of 24 mice) during ABA protocol while no female mice died (p=0.09). At day 17, food intake was significantly higher in females than in males (pweight loss than in females (pactivity were observed. From day 9, A-PA significantly increased over time in males (pactivities and, respectively, food intake and body weight loss showed gender differences, in particularly for L-PA and A-PA. Our results suggest a greater susceptibility of male mice to develop ABA, males and females exhibit different patterns of physical activity after limitation of food access. Underlying mechanisms should be further investigated. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. A Novel Letrozole Model Recapitulates Both the Reproductive and Metabolic Phenotypes of Polycystic Ovary Syndrome in Female Mice1

    Science.gov (United States)

    Kauffman, Alexander S.; Thackray, Varykina G.; Ryan, Genevieve E.; Tolson, Kristen P.; Glidewell-Kenney, Christine A.; Semaan, Sheila J.; Poling, Matthew C.; Iwata, Nahoko; Breen, Kellie M.; Duleba, Antoni J.; Stener-Victorin, Elisabet; Shimasaki, Shunichi; Webster, Nicholas J.; Mellon, Pamela L.

    2015-01-01

    Polycystic ovary syndrome (PCOS) pathophysiology is poorly understood, due partly to lack of PCOS animal models fully recapitulating this complex disorder. Recently, a PCOS rat model using letrozole (LET), a nonsteroidal aromatase inhibitor, mimicked multiple PCOS phenotypes, including metabolic features absent in other models. Given the advantages of using genetic and transgenic mouse models, we investigated whether LET produces a similar PCOS phenotype in mice. Pubertal female C57BL/6N mice were treated for 5 wk with LET, which resulted in increased serum testosterone and normal diestrus levels of estradiol, similar to the hyperandrogenemia and follicular phase estrogen levels of PCOS women. As in PCOS, ovaries from LET mice were larger, polycystic, and lacked corpora lutea versus controls. Most LET females were acyclic, and all were infertile. LET females displayed elevated serum LH levels and higher Lhb mRNA in the pituitary. In contrast, serum FSH and Fshb were significantly reduced in LET females, demonstrating differential effects on gonadotropins, as in PCOS. Within the ovary, LET females had higher Cyp17, Cyp19, and Fsh receptor mRNA expression. In the hypothalamus, LET females had higher kisspeptin receptor mRNA expression but lower progesterone receptor mRNA levels. LET females also gained more weight than controls, had increased abdominal adiposity and adipocyte size, elevated adipose inflammatory mRNA levels, and impaired glucose tolerance, mirroring the metabolic phenotype in PCOS women. This is the first report of a LET paradigm in mice that recapitulates both reproductive and metabolic PCOS phenotypes and will be useful to genetically probe the PCOS condition. PMID:26203175

  16. Deletion of the App-Runx1 region in mice models human partial monosomy 21

    Directory of Open Access Journals (Sweden)

    Thomas Arbogast

    2015-06-01

    Full Text Available Partial monosomy 21 (PM21 is a rare chromosomal abnormality that is characterized by the loss of a variable segment along human chromosome 21 (Hsa21. The clinical phenotypes of this loss are heterogeneous and range from mild alterations to lethal consequences, depending on the affected region of Hsa21. The most common features include intellectual disabilities, craniofacial dysmorphology, short stature, and muscular and cardiac defects. As a complement to human genetic approaches, our team has developed new monosomic mouse models that carry deletions on Hsa21 syntenic regions in order to identify the dosage-sensitive genes that are responsible for the symptoms. We focus here on the Ms5Yah mouse model, in which a 7.7-Mb region has been deleted from the App to Runx1 genes. Ms5Yah mice display high postnatal lethality, with a few surviving individuals showing growth retardation, motor coordination deficits, and spatial learning and memory impairments. Further studies confirmed a gene dosage effect in the Ms5Yah hippocampus, and pinpointed disruptions of pathways related to cell adhesion (involving App, Cntnap5b, Lgals3bp, Mag, Mcam, Npnt, Pcdhb2, Pcdhb3, Pcdhb4, Pcdhb6, Pcdhb7, Pcdhb8, Pcdhb16 and Vwf. Our PM21 mouse model is the first to display morphological abnormalities and behavioural phenotypes similar to those found in affected humans, and it therefore demonstrates the major contribution that the App-Runx1 region has in the pathophysiology of PM21.

  17. Generation and characterization of transgenic mice expressing mitochondrial targeted red fluorescent protein selectively in neurons: modeling mitochondriopathy in excitotoxicity and amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Wang Yi

    2011-11-01

    Full Text Available Abstract Background Mitochondria have roles or appear to have roles in the pathogenesis of several chronic age-related and acute neurological disorders, including Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis, Parkinson's disease, and cerebral ischemia, and could be critical targets for development of rational mechanism-based, disease-modifying therapeutics for treating these disorders effectively. A deeper understanding of neural tissue mitochondria pathobiologies as definitive mediators of neural injury, disease, and cell death merits further study, and the development of additional tools to study neural mitochondria will help achieve this unmet need. Results We created transgenic mice that express the coral (Discosoma sp. red fluorescent protein DsRed2 specifically in mitochondria of neurons using a construct engineered with a Thy1 promoter, specific for neuron expression, to drive expression of a fusion protein of DsRed2 with a mitochondrial targeting sequence. The biochemical and histological characterization of these mice shows the expression of mitochondrial-targeted DsRed2 to be specific for mitochondria and concentrated in distinct CNS regions, including cerebral cortex, hippocampus, thalamus, brainstem, and spinal cord. Red fluorescent mitochondria were visualized in cerebral cortical and hippocampal pyramidal neurons, ventrobasal thalamic neurons, subthalamic neurons, and spinal motor neurons. For the purpose of proof of principle application, these mice were used in excitotoxicity paradigms and double transgenic mice were generated by crossing Thy1-mitoDsRed2 mice with transgenic mice expressing enhanced-GFP (eGFP under the control of the Hlxb9 promoter that drives eGFP expression specifically in motor neurons and by crossing Thy1-mitoDsRed2 mice to amyotrophic lateral sclerosis (ALS mice expressing human mutant superoxide dismutase-1. Conclusions These novel transgenic mice will be a useful tool for better understanding

  18. Transcriptional profiling reveals progeroid Ercc1-/Δ mice as a model system for glomerular aging

    Science.gov (United States)

    2013-01-01

    Background Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1-/Δ progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease. Results In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1-/Δ mice showed cluster formation between young WT and Ercc1-/Δ as well as old WT and Ercc1-/Δ samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1-/Δ mice (p aging glomerulus. At the level of the transcriptome, the pattern of gene activities is similar in the progeroid Ercc1-/Δ mouse model constituting a valuable tool for future studies of aging-associated glomerular pathologies. PMID:23947592

  19. Mint3 in bone marrow-derived cells promotes lung metastasis in breast cancer model mice.

    Science.gov (United States)

    Hara, Toshiro; Murakami, Yoshinori; Seiki, Motoharu; Sakamoto, Takeharu

    2017-08-26

    Breast cancer is one of the most common cancers in women in the world. Although breast cancer is well treatable at the early stage, patients with distant metastases show a poor prognosis. Data from recent studies using transplantation models indicate that Mint3/APBA3 might promote breast cancer malignancy. However, whether Mint3 indeed contributes to tumor development, progression, or metastasis in vivo remains unclear. To address this, here we examined whether Mint3 depletion affects tumor malignancy in MMTV-PyMT breast cancer model mice. In MMTV-PyMT mice, Mint3 depletion did not affect tumor onset and tumor growth, but attenuated lung metastases. Experimental lung metastasis of breast cancer Met-1 cells derived from MMTV-PyMT mice also decreased in Mint3-depleted mice, indicating that host Mint3 expression affected lung metastasis of MMTV-PyMT-derived breast cancer cells. Further bone marrow transplant experiments revealed that Mint3 in bone marrow-derived cells promoted lung metastasis in MMTV-PyMT mice. Thus, targeting Mint3 in bone marrow-derived cells might be a good strategy for preventing metastasis and improving the prognosis of breast cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Evolution of the continental upper mantle : numerical modelling of thermo-chemical convection including partial melting

    NARCIS (Netherlands)

    de Smet, J.H.

    1999-01-01

    This thesis elaborates on the evolution of the continental upper mantle based on numerical modelling results. The descriptive and explanatory basis is formed by a numerical thermo-chemical convection model. The model evolution starts in the early Archaean about 4 billion years ago. The model follows

  1. Evolution of the continental upper mantle : numerical modelling of thermo-chemical convection including partial melting

    NARCIS (Netherlands)

    Smet, J.H. de

    1999-01-01

    This thesis elaborates on the evolution of the continental upper mantle based on numerical modelling results. The descriptive and explanatory basis is formed by a numerical thermo-chemical convection model. The model evolution starts in the early Archaean about 4 billion years ago. The model

  2. A Thermal Evolution Model of the Earth Including the Biosphere, Continental Growth and Mantle Hydration

    Science.gov (United States)

    Höning, D.; Spohn, T.

    2014-12-01

    By harvesting solar energy and converting it to chemical energy, photosynthetic life plays an important role in the energy budget of Earth [2]. This leads to alterations of chemical reservoirs eventually affecting the Earth's interior [4]. It further has been speculated [3] that the formation of continents may be a consequence of the evolution life. A steady state model [1] suggests that the Earth without its biosphere would evolve to a steady state with a smaller continent coverage and a dryer mantle than is observed today. We present a model including (i) parameterized thermal evolution, (ii) continental growth and destruction, and (iii) mantle water regassing and outgassing. The biosphere enhances the production rate of sediments which eventually are subducted. These sediments are assumed to (i) carry water to depth bound in stable mineral phases and (ii) have the potential to suppress shallow dewatering of the underlying sediments and crust due to their low permeability. We run a Monte Carlo simulation for various initial conditions and treat all those parameter combinations as success which result in the fraction of continental crust coverage observed for present day Earth. Finally, we simulate the evolution of an abiotic Earth using the same set of parameters but a reduced rate of continental weathering and erosion. Our results suggest that the origin and evolution of life could have stabilized the large continental surface area of the Earth and its wet mantle, leading to the relatively low mantle viscosity we observe at present. Without photosynthetic life on our planet, the Earth would be geodynamical less active due to a dryer mantle, and would have a smaller fraction of continental coverage than observed today. References[1] Höning, D., Hansen-Goos, H., Airo, A., Spohn, T., 2014. Biotic vs. abiotic Earth: A model for mantle hydration and continental coverage. Planetary and Space Science 98, 5-13. [2] Kleidon, A., 2010. Life, hierarchy, and the

  3. Population sensitivities of animals to chronic ionizing radiation-model predictions from mice to elephant.

    Science.gov (United States)

    Sazykina, Tatiana G

    2018-02-01

    Model predictions of population response to chronic ionizing radiation (endpoint 'morbidity') were made for 11 species of warm-blooded animals, differing in body mass and lifespan - from mice to elephant. Predictions were made also for 3 bird species (duck, pigeon, and house sparrow). Calculations were based on analytical solutions of the mathematical model, simulating a population response to low-LET ionizing radiation in an ecosystem with a limiting resource (Sazykina, Kryshev, 2016). Model parameters for different species were taken from biological and radioecological databases; allometric relationships were employed for estimating some parameter values. As a threshold of decreased health status in exposed populations ('health threshold'), a 10% reduction in self-repairing capacity of organisms was suggested, associated with a decline in ability to sustain environmental stresses. Results of the modeling demonstrate a general increase of population vulnerability to ionizing radiation in animal species of larger size and longevity. Populations of small widespread species (mice, house sparrow; body mass 20-50 g), which are characterized by intensive metabolism and short lifespan, have calculated 'health thresholds' at dose rates about 6.5-7.5 mGy day -1 . Widespread animals with body mass 200-500 g (rat, common pigeon) - demonstrate 'health threshold' values at 4-5 mGy day -1 . For populations of animals with body mass 2-5 kg (rabbit, fox, raccoon), the indicators of 10% health decrease are in the range 2-3.4 mGy day -1 . For animals with body mass 40-100 kg (wolf, sheep, wild boar), thresholds are within 0.5-0.8 mGy day -1 ; for herbivorous animals with body mass 200-300 kg (deer, horse) - 0.5-0.6 mGy day -1 . The lowest health threshold was estimated for elephant (body mass around 5000 kg) - 0.1 mGy day -1 . According to the model results, the differences in population sensitivities of warm-blooded animal species to ionizing radiation are generally

  4. Numerical modelling of seawater intrusion in Shenzhen (China) using a 3D density-dependent model including tidal effects

    Science.gov (United States)

    Lu, Wei; Yang, Qingchun; Martín, Jordi D.; Juncosa, Ricardo

    2013-04-01

    During the 1990s, groundwater overexploitation has resulted in seawater intrusion in the coastal aquifer of the Shenzhen city, China. Although water supply facilities have been improved and alleviated seawater intrusion in recent years, groundwater overexploitation is still of great concern in some local areas. In this work we present a three-dimensional density-dependent numerical model developed with the FEFLOW code, which is aimed at simulating the extent of seawater intrusion while including tidal effects and different groundwater pumping scenarios. Model calibration, using waterheads and reported chloride concentration, has been performed based on the data from 14 boreholes, which were monitored from May 2008 to December 2009. A fairly good fitness between the observed and computed values was obtained by a manual trial-and-error method. Model prediction has been carried out forward 3 years with the calibrated model taking into account high, medium and low tide levels and different groundwater exploitation schemes. The model results show that tide-induced seawater intrusion significantly affects the groundwater levels and concentrations near the estuarine of the Dasha river, which implies that an important hydraulic connection exists between this river and groundwater, even considering that some anti-seepage measures were taken in the river bed. Two pumping scenarios were considered in the calibrated model in order to predict the future changes in the water levels and chloride concentration. The numerical results reveal a decreased tendency of seawater intrusion if groundwater exploitation does not reach an upper bound of about 1.32 × 104 m3/d. The model results provide also insights for controlling seawater intrusion in such coastal aquifer systems.

  5. Toward an animal model for antisocial behavior : parallels between mice and humans

    NARCIS (Netherlands)

    Sluyter, F; Arseneault, L; Moffitt, TE; Veenema, AH; de Boer, S; Koolhaas, JM

    The goal of this article is to examine whether mouse lines genetically selected for short and long attack latencies are good animal models for antisocial behavior in humans. To this end, we compared male Short and Long Attack Latency mice (SAL and LAL, respectively) with the extremes of the Dunedin

  6. Optimization of an Image-Guided Laser-Induced Choroidal Neovascularization Model in Mice.

    Directory of Open Access Journals (Sweden)

    Yan Gong

    Full Text Available The mouse model of laser-induced choroidal neovascularization (CNV has been used in studies of the exudative form of age-related macular degeneration using both the conventional slit lamp and a new image-guided laser system. A standardized protocol is needed for consistent results using this model, which has been lacking. We optimized details of laser-induced CNV using the image-guided laser photocoagulation system. Four lesions with similar size were consistently applied per eye at approximately double the disc diameter away from the optic nerve, using different laser power levels, and mice of various ages and genders. After 7 days, the mice were sacrificed and retinal pigment epithelium/choroid/sclera was flat-mounted, stained with Isolectin B4, and imaged. Quantification of the area of the laser-induced lesions was performed using an established and constant threshold. Exclusion criteria are described that were necessary for reliable data analysis of the laser-induced CNV lesions. The CNV lesion area was proportional to the laser power levels. Mice at 12-16 weeks of age developed more severe CNV than those at 6-8 weeks of age, and the gender difference was only significant in mice at 12-16 weeks of age, but not in those at 6-8 weeks of age. Dietary intake of omega-3 long-chain polyunsaturated fatty acid reduced laser-induced CNV in mice. Taken together, laser-induced CNV lesions can be easily and consistently applied using the image-guided laser platform. Mice at 6-8 weeks of age are ideal for the laser-induced CNV model.

  7. Non-obese diabetic mice rapidly develop dramatic sympathetic neuritic dystrophy: a new experimental model of diabetic autonomic neuropathy.

    Science.gov (United States)

    Schmidt, Robert E; Dorsey, Denise A; Beaudet, Lucie N; Frederick, Kathy E; Parvin, Curtis A; Plurad, Santiago B; Levisetti, Matteo G

    2003-11-01

    To address the pathogenesis of diabetic autonomic neuropathy, we have examined the sympathetic nervous system in non-obese diabetic (NOD) and streptozotocin (STZ)-induced diabetic mice, two models of type 1 diabetes, and the db/db mouse, a model of type 2 diabetes. After only 3 to 5 weeks of diabetes, NOD mice developed markedly swollen axons and dendrites ("neuritic dystrophy") in the prevertebral superior mesenteric and celiac ganglia (SMG-CG), similar to the pathology described in diabetic STZ- and BBW-rat and man. Comparable changes failed to develop in the superior cervical ganglia of the NOD mouse or in the SMG-CG of non-diabetic NOD siblings. STZ-induced diabetic mice develop identical changes, although at a much slower pace and to a lesser degree than NOD mice. NOD-SCID mice, which are genetically identical to NOD mice except for the absence of T and B cells, do not develop diabetes or neuropathology comparable to diabetic NOD mice. However, STZ-treated NOD-SCID mice develop severe neuritic dystrophy, evidence against an exclusively autoimmune pathogenesis for autonomic neuropathy in this model. Chronically diabetic type 2 db/db mice fail to develop neuritic dystrophy, suggesting that hyperglycemia alone may not be the critical and sufficient element. The NOD mouse appears to be a valuable model of diabetic sympathetic autonomic neuropathy with unambiguous, rapidly developing neuropathology which corresponds closely to the characteristic pathology of other rodent models and man.

  8. PPARγ agonist pioglitazone improves cerebellar dysfunction at pre-Aβ deposition stage in APPswe/PS1dE9 Alzheimer's disease model mice

    Energy Technology Data Exchange (ETDEWEB)

    Toba, Junya; Nikkuni, Miyu [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Ishizeki, Masato [Laboratory for Neurophysiology, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Yoshii, Aya; Watamura, Naoto [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Inoue, Takafumi [Laboratory for Neurophysiology, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Ohshima, Toshio, E-mail: ohshima@waseda.jp [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan)

    2016-05-13

    Alzheimer's disease (AD) is one of the best known neurodegenerative diseases; it causes dementia and its pathological features include accumulation of amyloid β (Aβ) and neurofibrillary tangles (NFTs) in the brain. Elevated Cdk5 activity and CRMP2 phosphorylation have been reported in the brains of AD model mice at the early stage of the disease, but the significance thereof in human AD remains unelucidated. We have recently reported that Aβ accumulation in the cerebellum of AD model APPswe/PS1dE9 (APP/PS1) mice, and cerebellar dysfunctions, such as impairment of motor coordination ability and long-term depression (LTD) induction, at the pre-Aβ accumulation stage. In the present study, we found increased phosphorylation levels of CRMP2 as well as increased p35 protein levels in the cerebellum of APP/PS1 mice. Interestingly, we show that pioglitazone, an agonist of peroxisome proliferator-activated receptor γ, normalized the p35 protein and CRMP2 phosphorylation levels in the cerebellum. Impaired motor coordination ability and LTD in APP/PS1 mice were ameliorated by pioglitazone treatment at the pre-Aβ accumulation stage. These results suggest a correlation between CRMP2 phosphorylation and AD pathophysiology, and indicate the effectiveness of pioglitazone treatment at the pre-Aβ accumulation stage in AD model mice. -- Highlights: •Phosphorylation level of CRMP2 increased in the cerebellum of APP/PS1 mice. •p35 protein levels increased in the cerebellum of APP/PS1 mice. •Pioglitazone treatment improved cerebellar dysfunction of APP/PS1 mice.

  9. PPARγ agonist pioglitazone improves cerebellar dysfunction at pre-Aβ deposition stage in APPswe/PS1dE9 Alzheimer's disease model mice

    International Nuclear Information System (INIS)

    Toba, Junya; Nikkuni, Miyu; Ishizeki, Masato; Yoshii, Aya; Watamura, Naoto; Inoue, Takafumi; Ohshima, Toshio

    2016-01-01

    Alzheimer's disease (AD) is one of the best known neurodegenerative diseases; it causes dementia and its pathological features include accumulation of amyloid β (Aβ) and neurofibrillary tangles (NFTs) in the brain. Elevated Cdk5 activity and CRMP2 phosphorylation have been reported in the brains of AD model mice at the early stage of the disease, but the significance thereof in human AD remains unelucidated. We have recently reported that Aβ accumulation in the cerebellum of AD model APPswe/PS1dE9 (APP/PS1) mice, and cerebellar dysfunctions, such as impairment of motor coordination ability and long-term depression (LTD) induction, at the pre-Aβ accumulation stage. In the present study, we found increased phosphorylation levels of CRMP2 as well as increased p35 protein levels in the cerebellum of APP/PS1 mice. Interestingly, we show that pioglitazone, an agonist of peroxisome proliferator-activated receptor γ, normalized the p35 protein and CRMP2 phosphorylation levels in the cerebellum. Impaired motor coordination ability and LTD in APP/PS1 mice were ameliorated by pioglitazone treatment at the pre-Aβ accumulation stage. These results suggest a correlation between CRMP2 phosphorylation and AD pathophysiology, and indicate the effectiveness of pioglitazone treatment at the pre-Aβ accumulation stage in AD model mice. -- Highlights: •Phosphorylation level of CRMP2 increased in the cerebellum of APP/PS1 mice. •p35 protein levels increased in the cerebellum of APP/PS1 mice. •Pioglitazone treatment improved cerebellar dysfunction of APP/PS1 mice.

  10. Including Overweight or Obese Students in Physical Education: A Social Ecological Constraint Model

    Science.gov (United States)

    Li, Weidong; Rukavina, Paul

    2012-01-01

    In this review, we propose a social ecological constraint model to study inclusion of overweight or obese students in physical education by integrating key concepts and assumptions from ecological constraint theory in motor development and social ecological models in health promotion and behavior. The social ecological constraint model proposes…

  11. ETM documentation update – including modelling conventions and manual for software tools

    DEFF Research Database (Denmark)

    Grohnheit, Poul Erik

    , it summarises the work done during 2013, and it also contains presentations for promotion of fusion as a future element in the electricity generation mix and presentations for the modelling community concerning model development and model documentation – in particular for TIAM collaboration workshops....

  12. Effects of anti-cocaine vaccine and viral gene transfer of cocaine hydrolase in mice on cocaine toxicity including motor strength and liver damage.

    Science.gov (United States)

    Gao, Yang; Geng, Liyi; Orson, Frank; Kinsey, Berma; Kosten, Thomas R; Shen, Xiaoyun; Brimijoin, Stephen

    2013-03-25

    In developing an vivo drug-interception therapy to treat cocaine abuse and hinder relapse into drug seeking provoked by re-encounter with cocaine, two promising agents are: (1) a cocaine hydrolase enzyme (CocH) derived from human butyrylcholinesterase and delivered by gene transfer; (2) an anti-cocaine antibody elicited by vaccination. Recent behavioral experiments showed that antibody and enzyme work in a complementary fashion to reduce cocaine-stimulated locomotor activity in rats and mice. Our present goal was to test protection against liver damage and muscle weakness in mice challenged with massive doses of cocaine at or near the LD50 level (100-120 mg/kg, i.p.). We found that, when the interceptor proteins were combined at doses that were only modestly protective in isolation (enzyme, 1mg/kg; antibody, 8 mg/kg), they provided complete protection of liver tissue and motor function. When the enzyme levels were ~400-fold higher, after in vivo transduction by adeno-associated viral vector, similar protection was observed from CocH alone. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. Partial Enteral Nutrition Preserves Elements of Gut Barrier Function, Including Innate Immunity, Intestinal Alkaline Phosphatase (IAP) Level, and Intestinal Microbiota in Mice.

    Science.gov (United States)

    Wan, Xiao; Bi, Jingcheng; Gao, Xuejin; Tian, Feng; Wang, Xinying; Li, Ning; Li, Jieshou

    2015-08-03

    Lack of enteral nutrition (EN) during parenteral nutrition (PN) leads to higher incidence of infection because of gut barrier dysfunction. However, the effects of partial EN on intestina linnate immunity, intestinal alkaline phosphatase (IAP) and microbiota remain unclear. The mice were randomized into six groups to receive either standard chow or isocaloric and isonitrogenous nutritional support with variable partial EN to PN ratios. Five days later, the mice were sacrificed and tissue samples were collected. Bacterial translocation, the levels of lysozyme, mucin 2 (MUC2), and IAP were analyzed. The composition of intestinal microbiota was analyzed by 16S rRNA pyrosequencing. Compared with chow, total parenteral nutrition (TPN) resulted in a dysfunctional mucosal barrier, as evidenced by increased bacterial translocation (p < 0.05), loss of lysozyme, MUC2, and IAP, and changes in the gut microbiota (p < 0.001). Administration of 20% EN supplemented with PN significantly increased the concentrations of lysozyme, MUC2, IAP, and the mRNA levels of lysozyme and MUC2 (p < 0.001). The percentages of Bacteroidetes and Tenericutes were significantly lower in the 20% EN group than in the TPN group (p < 0.001). These changes were accompanied by maintained barrier function in bacterial culture (p < 0.05). Supplementation of PN with 20% EN preserves gut barrier function, by way of maintaining innate immunity, IAP and intestinal microbiota.

  14. Serverification of Molecular Modeling Applications: The Rosetta Online Server That Includes Everyone (ROSIE)

    Science.gov (United States)

    Conchúir, Shane Ó.; Der, Bryan S.; Drew, Kevin; Kuroda, Daisuke; Xu, Jianqing; Weitzner, Brian D.; Renfrew, P. Douglas; Sripakdeevong, Parin; Borgo, Benjamin; Havranek, James J.; Kuhlman, Brian; Kortemme, Tanja; Bonneau, Richard; Gray, Jeffrey J.; Das, Rhiju

    2013-01-01

    The Rosetta molecular modeling software package provides experimentally tested and rapidly evolving tools for the 3D structure prediction and high-resolution design of proteins, nucleic acids, and a growing number of non-natural polymers. Despite its free availability to academic users and improving documentation, use of Rosetta has largely remained confined to developers and their immediate collaborators due to the code’s difficulty of use, the requirement for large computational resources, and the unavailability of servers for most of the Rosetta applications. Here, we present a unified web framework for Rosetta applications called ROSIE (Rosetta Online Server that Includes Everyone). ROSIE provides (a) a common user interface for Rosetta protocols, (b) a stable application programming interface for developers to add additional protocols, (c) a flexible back-end to allow leveraging of computer cluster resources shared by RosettaCommons member institutions, and (d) centralized administration by the RosettaCommons to ensure continuous maintenance. This paper describes the ROSIE server infrastructure, a step-by-step ‘serverification’ protocol for use by Rosetta developers, and the deployment of the first nine ROSIE applications by six separate developer teams: Docking, RNA de novo, ERRASER, Antibody, Sequence Tolerance, Supercharge, Beta peptide design, NCBB design, and VIP redesign. As illustrated by the number and diversity of these applications, ROSIE offers a general and speedy paradigm for serverification of Rosetta applications that incurs negligible cost to developers and lowers barriers to Rosetta use for the broader biological community. ROSIE is available at http://rosie.rosettacommons.org. PMID:23717507

  15. Environmental Enrichment Ameliorates Behavioral Impairments Modeling Schizophrenia in Mice Lacking Metabotropic Glutamate Receptor 5.

    Science.gov (United States)

    Burrows, Emma L; McOmish, Caitlin E; Buret, Laetitia S; Van den Buuse, Maarten; Hannan, Anthony J

    2015-07-01

    Schizophrenia arises from a complex interplay between genetic and environmental factors. Abnormalities in glutamatergic signaling have been proposed to underlie the emergence of symptoms, in light of various lines of evidence, including the psychotomimetic effects of NMDA receptor antagonists. Metabotropic glutamate receptor 5 (mGlu5) has also been implicated in the disorder, and has been shown to physically interact with NMDA receptors. To clarify the role of mGlu5-dependent behavioral expression by environmental factors, we assessed mGlu5 knockout (KO) mice after exposure to environmental enrichment (EE) or reared under standard conditions. The mGlu5 KO mice showed reduced prepulse inhibition (PPI), long-term memory deficits, and spontaneous locomotor hyperactivity, which were all attenuated by EE. Examining the cellular impact of genetic and environmental manipulation, we show that EE significantly increased pyramidal cell dendritic branching and BDNF protein levels in the hippocampus of wild-type mice; however, mGlu5 KO mice were resistant to these alterations, suggesting that mGlu5 is critical to these responses. A selective effect of EE on the behavioral response to the NMDA receptor antagonist MK-801 in mGlu5 KO mice was seen. MK-801-induced hyperlocomotion was further potentiated in enriched mGlu5 KO mice and treatment with MK-801 reinstated PPI disruption in EE mGlu5 KO mice only, a response that is absent under standard housing conditions. Together, these results demonstrate an important role for mGlu5 in environmental modulation of schizophrenia-related behavioral impairments. Furthermore, this role of the mGlu5 receptor is mediated by interaction with NMDA receptor function, which may inform development of novel therapeutics.

  16. Modeling bladder cancer in mice: opportunities and challenges

    Science.gov (United States)

    Kobayashi, Takashi; Owczarek, Tomasz B.; McKiernan, James M.; Abate-Shen, Cory

    2015-01-01

    The prognosis and treatment of bladder cancer have hardly improved in the last 20 years. Bladder cancer remains a debilitating and often fatal disease, and among the most costly cancers to treat. The generation of informative mouse models has the potential to improve our understanding of bladder cancer progression, as well as impact its diagnosis and treatment. However, relatively few mouse models of bladder cancer have been described and particularly few that develop invasive cancer phenotypes. This review focuses on opportunities for improving the landscape of mouse models of bladder cancer. PMID:25533675

  17. APP transgenic mice for modelling behavioral and psychological symptoms of dementia (BPSD)

    Science.gov (United States)

    Lalonde, R.; Fukuchi, K.; Strazielle, C.

    2012-01-01

    The discovery of gene mutations responsible for autosomal dominant Alzheimer's disease has enabled researchers to reproduce in transgenic mice several hallmarks of this disorder, notably Aβ accumulation, though in most cases without neurofibrillary tangles. Mice expressing mutated and wild-type APP as well as C-terminal fragments of APP exhibit variations in exploratory activity reminiscent of behavioral and psychological symptoms of Alzeimer dementia (BPSD). In particular, open-field, spontaneous alternation, and elevated plus-maze tasks as well as aggression are modified in several APP transgenic mice relative to non-transgenic controls. However, depending on the precise murine models, changes in open-field and elevated plus-maze exploration occur in either direction, either increased or decreased relative to controls. It remains to be determined which neurotransmitter changes are responsible for this variability, in particular with respect to GABA, 5HT, and dopamine. PMID:22373961

  18. Albino mice as an animal model for infantile nystagmus syndrome

    NARCIS (Netherlands)

    D.L. Traber (Daniel); C.-C. Chen (Chien-Cheng); Y.-Y. Huang (Ying-Yu); M. Spoor (Monique); J. Roos (Jeanine); M.A. Frens (Maarten); D. Straumann (Dominik); C. Grimm (Christian)

    2012-01-01

    textabstractPURPOSE. Individuals with oculocutaneous albinism are predisposed to visual system abnormalities affecting the retina and retinofugal projections, which may lead to reduced visual acuity and Infantile Nystagmus Syndrome (INS). Due to absence of an established mammalian animal model,

  19. Human SCARB2 transgenic mice as an infectious animal model for enterovirus 71.

    Directory of Open Access Journals (Sweden)

    Yi-Wen Lin

    Full Text Available Enterovirus 71 (EV71 and coxsackievirus (CVA are the most common causative factors for hand, foot, and mouth disease (HFMD and neurological disorders in children. Lack of a reliable animal model is an issue in investigating EV71-induced disease manifestation in humans, and the current clinical therapies are symptomatic. We generated a novel EV71-infectious model with hSCARB2-transgenic mice expressing the discovered receptor human SCARB2 (hSCARB2. The challenge of hSCARB2-transgenic mice with clinical isolates of EV71 and CVA16 resulted in HFMD-like and neurological syndromes caused by E59 (B4 and N2838 (B5 strains, and lethal paralysis caused by 5746 (C2, N3340 (C4, and CVA16. EV71 viral loads were evident in the tissues and CNS accompanied the upregulated pro-inflammatory mediators (CXCL10, CCL3, TNF-α, and IL-6, correlating to recruitment of the infiltrated T lymphocytes that result in severe diseases. Transgenic mice pre-immunized with live E59 or the FI-E59 vaccine was able to resist the subsequent lethal challenge with EV71. These results indicate that hSCARB2-transgenic mice are a useful model for assessing anti-EV71 medications and for studying the pathogenesis induced by EV71.

  20. Eosinophil-induced liver injury: an experimental model using IL-5 transgenic mice.

    Science.gov (United States)

    Tsuda, K; Maeda, T; Tominaga, A; Watanabe, Y; Miyazaki, E; Enzan, H; Akisawa, N; Iwasaki, S; Saibara, T; Onishi, S

    2001-02-01

    In certain liver diseases, activated eosinophils are considered to be important effector cells in addition to T-cell-mediated cytotoxicity. No experimental model, however, has been developed for in vivo analysis of the cytotoxic mechanisms. Interleukin-5 (IL-5) transgenic mice (C3H/HeN-TgN(IL-5)Imeg), which exhibit marked eosinophilia without liver injury, were injected once with 25 microg of lipopolysaccharide (LPS) intraperitoneally. The mice were sacrificed weekly and eosinophilic injuries were assessed microscopically. To clarify the role of Kupffer cells and tumor necrosis factor-alpha (TNF-alpha) in the liver injury, gadolinium chloride (GdCl3) and anti-TNF-alpha neutralizing antibody were administrated before the LPS injection. Two weeks after injection, transgenic mice exhibited marked infiltration of eosinophils and extensive lobular necrosis. Transmigration of eosinophils through vascular endothelium and degranulation of eosinophil cytotoxic granules in inflamed areas were observed. These eosinophilic injuries were transient, but liver-specific. Pre-administration of GdCl3 and anti-TNF-alpha markedly reduced the hepatic inflammation, suggesting that LPS-activated Kupffer cells play a key role in producing the cytotoxicity of eosinophils by releasing TNF-alpha. We have established an experimental model of eosinophil-induced liver injury using IL-5 transgenic mice. Since this model is simple and highly reproducible, it will be useful for analysis of in vivo cytotoxic mechanisms of eosinophils.

  1. Development of a physiologically based pharmacokinetic model for bisphenol A in pregnant mice

    International Nuclear Information System (INIS)

    Kawamoto, Yuko; Matsuyama, Wakoto; Wada, Masahiro; Hishikawa, Junko; Chan, Melissa Pui Ling; Nakayama, Aki; Morisawa, Shinsuke

    2007-01-01

    Bisphenol A (BPA) is a weakly estrogenic monomer used to produce polymers for food contact and other applications, so there is potential for oral exposure of humans to trace amounts via ingestion. To date, no physiologically based pharmacokinetic (PBPK) model has been located for BPA in pregnant mice with or without fetuses. An estimate by a mathematical model is essential since information on humans is difficult to obtain experimentally. The PBPK model was constructed based on the pharmacokinetic data of our experiment following single oral administration of BPA to pregnant mice. The risk assessment of bisphenol A (BPA) on the development of human offspring is an important issue. There have been limited data on the exposure level of human fetuses to BPA (e.g. BPA concentration in cord blood) and no information is available on the pharmacokinetics of BPA in humans with or without fetuses. In the present study, we developed a physiologically based pharmacokinetic (PBPK) model describing the pharmacokinetics of BPA in a pregnant mouse with the prospect of future extrapolation to humans. The PBPK model was constructed based on the pharmacokinetic data of an experiment we executed on pregnant mice following single oral administration of BPA. The model could describe the rapid transfer of BPA through the placenta to the fetus and the slow disappearance from fetuses. The simulated time courses after three-time repeated oral administrations of BPA by the constructed model fitted well with the experimental data, and the simulation for the 10 times lower dose was also consistent with the experiment. This suggested that the PBPK model for BPA in pregnant mice was successfully verified and is highly promising for extrapolation to humans who are expected to be exposed more chronically to lower doses

  2. Neuropharmacological Profile of Extracts of Aerial Parts of Convolvulus pluricaulis Choisy in Mice Model

    OpenAIRE

    Siddiqui, Nasir A; Ahmad, Nihal; Musthaq, Nazia; Chattopadhyaya, Ipshita; Kumria, Rachna; Gupta, Sumeet

    2011-01-01

    The plant of Convolvulus pluricaulis Choisy was found to be used by different traditional systems and folklore for the treatment of various disorders. The aim of the present study was to investigate the neuropharmacological activity of various extracts of Convolvulus pluricaulis Choisy in albino mice. The animal behavior was evaluated by locomotor activity, tremors activity, sleep inducing model and anxiolytic activity using standard procedures in experimental animal models. The results revea...

  3. Transverse Crack Modeling and Validation in Rotor Systems, Including Thermal Effects

    Directory of Open Access Journals (Sweden)

    N. Bachschmid

    2003-01-01

    Full Text Available This article describes a model that allows the simulation of the static behavior of a transverse crack in a horizontal rotor under the action of weight and other possible static loads and the dynamic behavior of cracked rotating shaft. The crack breathes—that is, the mechanism of the crack's opening and closing is ruled by the stress on the cracked section exerted by the external loads. In a rotor, the stresses are time-dependent and have a period equal to the period of rotation; thus, the crack periodically breathes. An original, simplified model allows cracks of various shapes to be modeled and thermal stresses to be taken into account, as they may influence the opening and closing mechanism. The proposed method was validated by using two criteria. First the crack's breathing mechanism, simulated by the model, was compared with the results obtained by a nonlinear, threedimensional finite element model calculation, and a good agreement in the results was observed. Then the proposed model allowed the development of the equivalent cracked beam. The results of this model were compared with those obtained by the three-dimensional finite element model. Also in this case, there was a good agreement in the results.

  4. A model for firm-specific strategic wisdom : including illustrations and 49 guiding questions

    NARCIS (Netherlands)

    van Straten, Roeland Peter

    2017-01-01

    This PhD thesis provides an answer to the question ‘How may one think strategically’. It does so by presenting a new prescriptive ‘Model for Firm-Specific Strategic Wisdom’. This Model aims to guide any individual strategist in his or her thinking from a state of firm-specific ‘ignorance’ to a state

  5. Complete Loss and Thermal Model of Power Semiconductors Including Device Rating Information

    DEFF Research Database (Denmark)

    Ma, Ke; Bahman, Amir Sajjad; Beczkowski, Szymon

    2015-01-01

    models, only the electrical loadings are focused and treated as design variables, while the device rating is normally pre-defined by experience with limited design flexibility. Consequently, a more complete loss and thermal model is proposed in this paper, which takes into account not only the electrical...

  6. Numerical models of single- and double-negative metamaterials including viscous and thermal losses

    DEFF Research Database (Denmark)

    Cutanda Henriquez, Vicente; Sánchez-Dehesa, José

    2017-01-01

    detailed understanding on how viscous and thermal losses affect the setups at different frequencies. The modeling of a simpler single-negative metamaterial also broadens this overview. Both setups have been modeled with quadratic BEM meshes. Each sample, scaled at two different sizes, has been represented...

  7. Intestinal anti-inflammatory activity of ellagic acid in the acute and chronic dextrane sulfate sodium models of mice colitis.

    Science.gov (United States)

    Marín, Marta; María Giner, Rosa; Ríos, José-Luis; Recio, María Carmen

    2013-12-12

    Pomegranate (Punica granatum L.; Lythraceae) has traditionally been used for the treatment of various inflammatory diseases, including ulcerative colitis (UC). Because its fruits and extracts are rich in ellagitannins, which release ellagic acid when hydrolyzed, consumption of pomegranate products is currently being widely promoted for their potential health effects, including the prevention of inflammatory diseases and cancer. To evaluate the anti-inflammatory effects of ellagic acid on dextran sulfate sodium (DSS)-induced acute and chronic experimental colitis in two different strains of mice and to elucidate its possible mechanisms of action. In the acute UC model, female Balb/C mice were treated with DSS (5%) for seven days while concomitantly receiving a dietary supplement of ellagic acid (2%). In the chronic UC model, female C57BL/6 mice received four week-long cycles of DSS (1% and 2%) interspersed with week-long recovery periods along with a diet supplemented with ellagic acid (0.5%). In acute model of UC, ellagic acid ameliorated disease severity slightly as observed both macroscopically and through the profile of inflammatory mediators (IL-6, TNF-α, and IFN-γ). In the chronic UC model, ellagic acid significantly inhibited the progression of the disease, reducing intestinal inflammation and decreasing histological scores. Moreover, mediators such as COX-2 and iNOS were downregulated and the signaling pathways p38 MAPK, NF-κB, and STAT3 were blocked. Our study reinforces the hypothetical use of ellagic acid as an anti-inflammatory complement to conventional UC treatment in chronic UC patients and could be considered in the dietary prevention of intestinal inflammation and related cancer development. © 2013 Published by Elsevier Ireland Ltd.

  8. [The effect of hypertonic seawater and isotonic seawater for nasal mucosa of allergic rhinitis mice model].

    Science.gov (United States)

    Deng, Zhifeng; Xu, Yu; Ou, Jin; Xiang, Rong; Tao, Zezhang

    2014-12-01

    To study the effect of hypertonic seawater and isotonic seawater for nasal mucosa of allergic rhinitis mice model, and explore the possible mechanism of nasal irrigation with seawater in treatment of allergic rhinitis. We used Der pl to make allergic rhinitis model of BALB/c mice, and divided them into three groups randomly. Nasal irrigation with hypertonic seawater (HS) or isotonic seawater (IS) in the treatment group 1-14 days after modeling, and black control (BC) group was given no treatment after modeling. Normal control (NC) group was given no treatment, the number of rubs and sneezings in each group were counted in 30 min after the last nasal irrigation. Mice were then killed 24 h after the last therapy. The noses of mice from each group were removed and fixed, then the slices were stained with hematoxylin and eosin, the others were observed by transmission electron microscope. Mice with hypertonic seawater and isotonic seawater were significantly improved in rubs and sneezings compared to the black control group (P 0. 05); Ciliated columnar epithelium cells in mucosal tissues of HS group and IS group were arranged trimly, better than that in the black control group. Morphology and microstructure in nasal mucosal of HS group was closer to the normal group than in IS group. The injury of nasal mucosa ciliated epithelium was significantly improved by nasal irrigation with hypertonic seawater and isotonic seawater, and the former is better than the latter, the mechanism of nasal irrigation with seawater in treatment of allergic rhinitis may rely on repairing the injured nasal mucosa ciliated epithelium, thereby the symptoms of nasal was reduced.

  9. Gasification of biomass in a fixed bed downdraft gasifier--a realistic model including tar.

    Science.gov (United States)

    Barman, Niladri Sekhar; Ghosh, Sudip; De, Sudipta

    2012-03-01

    This study presents a model for fixed bed downdraft biomass gasifiers considering tar also as one of the gasification products. A representative tar composition along with its mole fractions, as available in the literature was used as an input parameter within the model. The study used an equilibrium approach for the applicable gasification reactions and also considered possible deviations from equilibrium to further upgrade the equilibrium model to validate a range of reported experimental results. Heat balance was applied to predict the gasification temperature and the predicted values were compared with reported results in literature. A comparative study was made with some reference models available in the literature and also with experimental results reported in the literature. Finally a predicted variation of performance of the gasifier by this validated model for different air-fuel ratio and moisture content was also discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Development and optimization of psychological stress model in mice using 2 level full factorial design.

    Science.gov (United States)

    Kala, Manika; Shaikh, Muhammad Vaseem; Nivsarkar, Manish

    Psychological stress has long been a silent killer, impairing normal physiological functions and leading to a variety of diseased conditions. However, the existing animal models for studying psychological stress have been marred by their inherent limitations warranting further research in their development and optimization. In this study 2 5 full factorial design was utilized for the development and optimization of psychological stress model in mice by applying different stressors viz., slanted cage(X 1 ), restraint(X 2 ), no bedding(X 3 ), dirty bedding(X 4 ) and isolation(X 5 ) at two time duration levels of 30 and 60min. The development of behavioral changes like depression, anxiety and anhedonia was taken as criteria for development of stress. These responses were analyzed using Design Expert 7.1.6. (Stat-Ease, Inc., USA). The maximum effective responses obtained were taken as a criterion for optimization. The optimized model was applied to measure the change in serum cortisol level to confirm the stress development. The statistical data showed that a quadratic model was fitted to the data obtained. All the factors were found to have a significant role in the development of stress among which restraint, slanted cage and dirty bedding were found to be more causal (pstressed mice of optimized model (ppsychological stress development in mice. The study could lay a strong platform for the use of quality by design approach in the development of robust, efficient and resourceful animal models. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Modeling of chronic radiation-induced cystitis in mice

    Directory of Open Access Journals (Sweden)

    Bernadette M.M. Zwaans, PhD

    2016-10-01

    Conclusions: We developed an RC model that mimics the human pathology and functional changes. Furthermore, radiation exposure attenuates the urothelial integrity long-term, allowing for potential continuous irritability of the bladder wall from exposure to urine. Future studies will focus on the underlying molecular changes associated with this condition and investigate novel treatment strategies.

  12. A sensitive venous bleeding model in haemophilia A mice

    DEFF Research Database (Denmark)

    Pastoft, Anne Engedahl; Lykkesfeldt, Jens; Ezban, M.

    2012-01-01

    for evaluation of pro-coagulant compounds for treatment of haemophilia. Interestingly, the vena saphena model proved to be sensitive towards FVIII in plasma levels that approach the levels preventing bleeding in haemophilia patients, and may, thus, in particular be valuable for testing of new long...

  13. A viscoplastic model including anisotropic damage for the time dependent behaviour of rock

    Science.gov (United States)

    Pellet, F.; Hajdu, A.; Deleruyelle, F.; Besnus, F.

    2005-08-01

    This paper presents a new constitutive model for the time dependent mechanical behaviour of rock which takes into account both viscoplastic behaviour and evolution of damage with respect to time. This model is built by associating a viscoplastic constitutive law to the damage theory. The main characteristics of this model are the account of a viscoplastic volumetric strain (i.e. contractancy and dilatancy) as well as the anisotropy of damage. The latter is described by a second rank tensor. Using this model, it is possible to predict delayed rupture by determining time to failure, in creep tests for example. The identification of the model parameters is based on experiments such as creep tests, relaxation tests and quasi-static tests. The physical meaning of these parameters is discussed and comparisons with lab tests are presented. The ability of the model to reproduce the delayed failure observed in tertiary creep is demonstrated as well as the sensitivity of the mechanical response to the rate of loading. The model could be used to simulate the evolution of the excavated damage zone around underground openings.

  14. Anticonvulsant properties of the novel nootropic agent nefiracetam in seizure models of mice and rats.

    Science.gov (United States)

    Kitano, Yutaka; Komiyama, Chika; Makino, Mitsuhiro; Takasuna, Kiyoshi; Takazawa, Akira; Sakurada, Shinobu

    2005-06-01

    Nefiracetam (NEF) is a novel pyrrolidone-type nootropic agent, and it has been reported to possess various pharmacologic effects as well as cognition-enhancing effects. The present study focused on the anticonvulsant effect of NEF and its potential for antiepileptic therapy. The anticonvulsant properties of NEF were investigated in experimental seizure models of mice and rats, compared with levetiracetam (LEV) and other standard antiepileptic drugs [AEDs; zonisamide (ZNS), phenytoin (PHT), carbamazepine (CBZ), valproic acid (VPA), diazepam (DZP), and ethosuximide (ESM)]. With reference to standard programs for evaluating potential AEDs, the study included the traditional maximal electroshock seizure and subcutaneous chemoconvulsant (pentylenetetrazole, bicuculline, picrotoxin, strychnine, or N-methyl-D-aspartate) seizure tests and two threshold models (the increasing-current electroshock seizure test and intravenous pentylenetetrazole seizure threshold test). Neurotoxic activities were examined with the rotarod test and traction test. NEF inhibited electroshock-induced seizures at nontoxic doses, whereas it had no effect on seizures chemically induced by pentylenetetrazole, bicuculline, picrotoxin, strychnine, or N-methyl-D-aspartate. The anticonvulsant spectrum of NEF paralleled that of ZNS, PHT, and CBZ. The anticonvulsant efficacy of NEF was comparable with that of ZNS and less potent than that of PHT, CBZ, and DZP. However, the safety margin of NEF was superior to that of ZNS, CBZ, VPA, and DZP. LEV showed only slight anticonvulsant effects in threshold models, and it was not effective in conventional screening models. These results suggest that NEF has distinct anticonvulsant spectrum and mechanisms from those of LEV. NEF is an orally active and safe AED, and it possesses a potential for antiepileptic therapy.

  15. Potential transformation of trace species including aircraft exhaust in a cloud environment. The `Chedrom model`

    Energy Technology Data Exchange (ETDEWEB)

    Ozolin, Y.E.; Karol, I.L. [Main Geophysical Observatory, St. Petersburg (Russian Federation); Ramaroson, R. [Office National d`Etudes et de Recherches Aerospatiales (ONERA), 92 - Chatillon (France)

    1997-12-31

    Box model for coupled gaseous and aqueous phases is used for sensitivity study of potential transformation of trace gases in a cloud environment. The rate of this transformation decreases with decreasing of pH in droplets, with decreasing of photodissociation rates inside the cloud and with increasing of the droplet size. Model calculations show the potential formation of H{sub 2}O{sub 2} in aqueous phase and transformation of gaseous HNO{sub 3} into NO{sub x} in a cloud. This model is applied for exploration of aircraft exhausts evolution in plume inside a cloud. (author) 10 refs.

  16. A Two-Dimensional Modeling Procedure to Estimate the Loss Equivalent Resistance Including the Saturation Effect

    Directory of Open Access Journals (Sweden)

    Rosa Ana Salas

    2013-11-01

    Full Text Available We propose a modeling procedure specifically designed for a ferrite inductor excited by a waveform in time domain. We estimate the loss resistance in the core (parameter of the electrical model of the inductor by means of a Finite Element Method in 2D which leads to significant computational advantages over the 3D model. The methodology is validated for an RM (rectangular modulus ferrite core working in the linear and the saturation regions. Excellent agreement is found between the experimental data and the computational results.

  17. A Two-Account Life Insurance Model for Scenario-Based Valuation Including Event Risk

    DEFF Research Database (Denmark)

    Jensen, Ninna Reitzel; Schomacker, Kristian Juul

    2015-01-01

    Using a two-account model with event risk, we model life insurance contracts taking into account both guaranteed and non-guaranteed payments in participating life insurance as well as in unit-linked insurance. Here, event risk is used as a generic term for life insurance events, such as death......, disability, etc. In our treatment of participating life insurance, we have special focus on the bonus schemes “consolidation” and “additional benefits”, and one goal is to formalize how these work and interact. Another goal is to describe similarities and differences between participating life insurance...... and unit-linked insurance. By use of a two-account model, we are able to illustrate general concepts without making the model too abstract. To allow for complicated financial markets without dramatically increasing the mathematical complexity, we focus on economic scenarios. We illustrate the use of our...

  18. A Lumped Thermal Model Including Thermal Coupling and Thermal Boundary Conditions for High Power IGBT Modules

    DEFF Research Database (Denmark)

    Bahman, Amir Sajjad; Ma, Ke; Blaabjerg, Frede

    2018-01-01

    Detailed thermal dynamics of high power IGBT modules are important information for the reliability analysis and thermal design of power electronic systems. However, the existing thermal models have their limits to correctly predict these complicated thermal behavior in the IGBTs: The typically used...... thermal model based on one-dimensional RC lumps have limits to provide temperature distributions inside the device, moreover some variable factors in the real-field applications like the cooling and heating conditions of the converter cannot be adapted. On the other hand, the more advanced three......-dimensional thermal models based on Finite Element Method (FEM) need massive computations, which make the long-term thermal dynamics difficult to calculate. In this paper, a new lumped three-dimensional thermal model is proposed, which can be easily characterized from FEM simulations and can acquire the critical...

  19. Advanced Modeling of Ramp Operations including Departure Status at Secondary Airports, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This project addresses three modeling elements relevant to NASA's IADS research and ATD-2 project, two related to ramp operations at primary airports and one related...

  20. Extending the Scope of the Acculturation/Pidginization Model to Include Cognition.

    Science.gov (United States)

    Schumann, John H.

    1990-01-01

    Examines five cognitive models for second-language acquisition (SLA) and assesses how each might account for the Pidginized interlanguage found in the early stages of second-language acquisition. (23 references) (JL)

  1. An integrated computable general equilibrium model including multiple types and uses of water

    OpenAIRE

    Luckmann, Jonas Jens

    2015-01-01

    Water is a scarce resource in many regions of the world and competition for water is an increasing problem. To countervail this trend policies are needed regulating supply and demand for water. As water is used in many economic activities, water related management decisions usually have complex implications. Economic simulation models have been proven useful to ex-ante assess the consequences of policy changes. Specifically, Computable General Equilibrium (CGE) models are very suitable to ana...

  2. Transverse Crack Modeling and Validation in Rotor Systems Including Thermal Effects

    Directory of Open Access Journals (Sweden)

    N. Bachschmid

    2004-01-01

    Full Text Available In this article, a model is described that allows one to simulate the static behavior of a transversal crack in a horizontal rotor, under the action of the weight and other possible static loads and the dynamical behavior of the rotating cracked shaft. The crack “breaths,” i.e., the mechanism of opening and closing of the crack, is ruled by the stress acting on the cracked section due to the external loads; in a rotor the stress is time-depending with a period equal to the period of rotation, thus the crack “periodically breaths.” An original simplified model is described that allows cracks of different shape to be modeled and thermal stresses to be taken into account, since they may influence the opening and closing mechanism. The proposed method has been validated using two criteria. Firstly, the crack “breathing” mechanism, simulated with the model, has been compared with the results obtained by a nonlinear 3-D FEM calculation and a good agreement in the results has been observed. Secondly, the proposed model allows the development of the equivalent cracked beam. The results of this model are compared with those obtained by the above-mentioned 3-D FEM. There is a good agreement in the results, of this case as well.

  3. Including sugar cane in the agro-ecosystem model ORCHIDEE-STICS: calibration and validation

    Science.gov (United States)

    Valade, A.; Vuichard, N.; Ciais, P.; Viovy, N.

    2011-12-01

    Sugarcane is currently the most efficient bioenergy crop with regards to the energy produced per hectare. With approximately half the global bioethanol production in 2005, and a devoted land area expected to expand globally in the years to come, sugar cane is at the heart of the biofuel debate. Dynamic global vegetation models coupled with agronomical models are powerful and novel tools to tackle many of the environmental issues related to biofuels if they are carefully calibrated and validated against field observations. Here we adapt the agro-terrestrial model ORCHIDEE-STICS for sugar cane simulations. Observation data of LAI are used to evaluate the sensitivity of the model to parameters of nitrogen absorption and phenology, which are calibrated in a systematic way for six sites in Australia and La Reunion. We find that the optimal set of parameters is highly dependent on the sites' characteristics and that the model can reproduce satisfactorily the evolution of LAI. This careful calibration of ORCHIDEE-STICS for sugar cane biomass production for different locations and technical itineraries provides a strong basis for further analysis of the impacts of bioenergy-related land use change on carbon cycle budgets. As a next step, a sensitivity analysis is carried out to estimate the uncertainty of the model in biomass and carbon flux simulation due to its parameterization.

  4. Simplification and Validation of a Spectral-Tensor Model for Turbulence Including Atmospheric Stability

    Science.gov (United States)

    Chougule, Abhijit; Mann, Jakob; Kelly, Mark; Larsen, Gunner C.

    2018-02-01

    A spectral-tensor model of non-neutral, atmospheric-boundary-layer turbulence is evaluated using Eulerian statistics from single-point measurements of the wind speed and temperature at heights up to 100 m, assuming constant vertical gradients of mean wind speed and temperature. The model has been previously described in terms of the dissipation rate ɛ , the length scale of energy-containing eddies L , a turbulence anisotropy parameter Γ, the Richardson number Ri, and the normalized rate of destruction of temperature variance η _θ ≡ ɛ _θ /ɛ . Here, the latter two parameters are collapsed into a single atmospheric stability parameter z / L using Monin-Obukhov similarity theory, where z is the height above the Earth's surface, and L is the Obukhov length corresponding to Ri,η _θ. Model outputs of the one-dimensional velocity spectra, as well as cospectra of the streamwise and/or vertical velocity components, and/or temperature, and cross-spectra for the spatial separation of all three velocity components and temperature, are compared with measurements. As a function of the four model parameters, spectra and cospectra are reproduced quite well, but horizontal temperature fluxes are slightly underestimated in stable conditions. In moderately unstable stratification, our model reproduces spectra only up to a scale ˜ 1 km. The model also overestimates coherences for vertical separations, but is less severe in unstable than in stable cases.

  5. A Novel Mean-Value Model of the Cardiovascular System Including a Left Ventricular Assist Device.

    Science.gov (United States)

    Ochsner, Gregor; Amacher, Raffael; Schmid Daners, Marianne

    2017-06-01

    Time-varying elastance models (TVEMs) are often used for simulation studies of the cardiovascular system with a left ventricular assist device (LVAD). Because these models are computationally expensive, they cannot be used for long-term simulation studies. In addition, their equilibria are periodic solutions, which prevent the extraction of a linear time-invariant model that could be used e.g. for the design of a physiological controller. In the current paper, we present a new type of model to overcome these problems: the mean-value model (MVM). The MVM captures the behavior of the cardiovascular system by representative mean values that do not change within the cardiac cycle. For this purpose, each time-varying element is manually converted to its mean-value counterpart. We compare the derived MVM to a similar TVEM in two simulation experiments. In both cases, the MVM is able to fully capture the inter-cycle dynamics of the TVEM. We hope that the new MVM will become a useful tool for researchers working on physiological control algorithms. This paper provides a plant model that enables for the first time the use of tools from classical control theory in the field of physiological LVAD control.

  6. Mottled Mice and Non-Mammalian Models of Menkes Disease

    DEFF Research Database (Denmark)

    Lenartowicz, Małgorzata; Krzeptowski, Wojciech; Lipiński, Paweł

    2015-01-01

    Menkes disease is a multi-systemic copper metabolism disorder caused by mutations in the X-linked ATP7A gene and characterized by progressive neurodegeneration and severe connective tissue defects. The ATP7A protein is a copper (Cu)-transporting ATPase expressed in all tissues and plays a critica......-mammalian models of Menkes disease, Drosophila melanogaster and Danio rerio mutants were used in experiments which would be technically difficult to carry out in mammals....

  7. Modeling the Cell Muscle Membrane from Normal and Desmin- or Dystrophin-null Mice as an Elastic System

    Science.gov (United States)

    García-Pelagio, Karla P.; Santamaría-Holek, Ivan; Bloch, Robert J.; Ortega, Alicia; González-Serratos, Hugo

    2010-12-01

    Two of the most important proteins linking the contractile apparatus and costameres at the sarcolemma of skeletal muscle fibers are dystrophin and desmin. We have developed an elastic model of the proteins that link the sarcolemma to the myofibrils. This is a distributed model, with an elastic constant, k, that includes the main protein components of the costameres. The distributed spring model is composed of parallel units attached in series. To test the model, we performed experiments in which we applied negative pressure, generated by an elastimeter, to a small area of the sarcolemma from single myofiber. The negative pressure formed a bleb of variable height, dependent on the pressure applied. We normalized our measurements of k in dystrophin-null (mdx) and desmin-null (des-/-) mice to the value we obtained for wild type (WT) mice, which was set at 1.0. The relative experimental value for the stiffness of myofibers from mice lacking dystrophin or desmin was 0.5 and 0.7, respectively. The theoretical k values of the individual elements were obtained using neural networks (NN), in which the input was the k value for each parallel spring component and the output was the solution of each resulting parallel system. We compare the experimental values of k in control and mutant muscles to the theoretical values obtained by NN for each protein. Computed theoretical values were 0.4 and 0.8 for dystrophin- and desmin-null muscles, respectively, and 0.9 for WT, in reasonable agreement with our experimental results. This suggests that, although it is a simplified spring model solved by NN, it provides a good approximation of the distribution of spring elements and the elastic constants of the proteins that form the costameres. Our results show that dystrophin is the protein that contributes more than any other to the strength of the connections between the sarcolemma and the contractile apparatus, the costameres.

  8. Development of an experimental model of neutrophilic pulmonary response induction in mice

    Directory of Open Access Journals (Sweden)

    Leonardo Araújo Pinto

    2003-08-01

    Full Text Available BACKGROUND: Several lung diseases are characterized by a predominantly neutrophilic inflammation. A better understanding of the mechanisms of action of some drugs on the airway inflammation of such diseases may bring advances to the treatment. OBJECTIVE: To develop a method to induce pulmonary neutrophilic response in mice, without active infection. METHODS: Eight adult Swiss mice were used. The study group (n = 4 received an intranasal challenge with 1 x 10(12 CFU/ml of Pseudomonas aeruginosa (Psa, frozen to death. The control group (n = 4 received an intranasal challenge with saline solution. Two days after the intranasal challenge, a bron­choalveolar lavage (BAL was performed with total cell and differential cellularity counts. RESULTS: The total cell count was significantly higher in the group with Psa, as compared to the control group (median of 1.17 x 10(6 and 0.08 x 10(6, respectively, p = 0.029. In addition to this, an absolute predominance of neutrophils was found in the differential cellularity of the mice that had received the Psa challenge. CONCLUSIONS: The model of inducing a neutrophilic pulmonary disease using frost-dead bacteria was successfully developed. This neutrophilic inflammatory response induction model in Swiss mice lungs may be an important tool for testing the anti-inflammatory effect of some antimicrobial drugs on the inflammation of the lower airways.

  9. Sclerostin Antibody Treatment Improves the Bone Phenotype of Crtap(-/-) Mice, a Model of Recessive Osteogenesis Imperfecta.

    Science.gov (United States)

    Grafe, Ingo; Alexander, Stefanie; Yang, Tao; Lietman, Caressa; Homan, Erica P; Munivez, Elda; Chen, Yuqing; Jiang, Ming Ming; Bertin, Terry; Dawson, Brian; Asuncion, Franklin; Ke, Hua Zhu; Ominsky, Michael S; Lee, Brendan

    2016-05-01

    Osteogenesis imperfecta (OI) is characterized by low bone mass, poor bone quality, and fractures. Standard treatment for OI patients is limited to bisphosphonates, which only incompletely correct the bone phenotype, and seem to be less effective in adults. Sclerostin-neutralizing antibodies (Scl-Ab) have been shown to be beneficial in animal models of osteoporosis, and dominant OI resulting from mutations in the genes encoding type I collagen. However, Scl-Ab treatment has not been studied in models of recessive OI. Cartilage-associated protein (CRTAP) is involved in posttranslational type I collagen modification, and its loss of function results in recessive OI. In this study, we treated 1-week-old and 6-week-old Crtap(-/-) mice with Scl-Ab for 6 weeks (25 mg/kg, s.c., twice per week), to determine the effects on the bone phenotype in models of "pediatric" and "young adult" recessive OI. Vehicle-treated Crtap(-/-) and wild-type (WT) mice served as controls. Compared with control Crtap(-/-) mice, micro-computed tomography (μCT) analyses showed significant increases in bone volume and improved trabecular microarchitecture in Scl-Ab-treated Crtap(-/-) mice in both age cohorts, in both vertebrae and femurs. Additionally, Scl-Ab improved femoral cortical parameters in both age cohorts. Biomechanical testing showed that Scl-Ab improved parameters of whole-bone strength in Crtap(-/-) mice, with more robust effects in the week 6 to 12 cohort, but did not affect the increased bone brittleness. Additionally, Scl-Ab normalized the increased osteoclast numbers, stimulated bone formation rate (week 6 to 12 cohort only), but did not affect osteocyte density. Overall, our findings suggest that Scl-Ab treatment may be beneficial in the treatment of recessive OI caused by defects in collagen posttranslational modification. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research.

  10. Functional and muscular adaptations in an experimental model for isometric strength training in mice.

    Directory of Open Access Journals (Sweden)

    Karsten Krüger

    Full Text Available Exercise training induces muscular adaptations that are highly specific to the type of exercise. For a systematic study of the differentiated exercise adaptations on a molecular level mouse models have been used successfully. The aim of the current study was to develop a suitable mouse model of isometric strength exercise training characterized by specific adaptations known from strength training. C57BL/6 mice performed an isometric strength training (ST for 10 weeks 5 days/week. Additionally, either a sedentary control group (CT or a regular endurance training group (ET groups were used as controls. Performance capacity was determined by maximum holding time (MHT and treadmill spirometry, respectively. Furthermore, muscle fiber types and diameter, muscular concentration of phosphofructokinase 1 (PFK, succinate dehydrogenase (SDHa, and glucose transporter type 4 (GLUT4 were determined. In a further approach, the effect of ST on glucose intolerance was tested in diabetic mice. In mice of the ST group we observed an increase of MHT in isometric strength tests, a type II fiber hypertrophy, and an increased GLUT4 protein content in the membrane fraction. In contrast, in mice of the ET group an increase of VO(2max, a shift to oxidative muscle fiber type and an increase of oxidative enzyme content was measured. Furthermore strength training was effective in reducing glucose intolerance in mice fed a high fat diet. An effective murine strength training model was developed and evaluated, which revealed marked differences in adaptations known from endurance training. This approach seems also suitable to test for therapeutical effects of strength training.

  11. Including crystal structure attributes in machine learning models of formation energies via Voronoi tessellations

    Science.gov (United States)

    Ward, Logan; Liu, Ruoqian; Krishna, Amar; Hegde, Vinay I.; Agrawal, Ankit; Choudhary, Alok; Wolverton, Chris

    2017-07-01

    While high-throughput density functional theory (DFT) has become a prevalent tool for materials discovery, it is limited by the relatively large computational cost. In this paper, we explore using DFT data from high-throughput calculations to create faster, surrogate models with machine learning (ML) that can be used to guide new searches. Our method works by using decision tree models to map DFT-calculated formation enthalpies to a set of attributes consisting of two distinct types: (i) composition-dependent attributes of elemental properties (as have been used in previous ML models of DFT formation energies), combined with (ii) attributes derived from the Voronoi tessellation of the compound's crystal structure. The ML models created using this method have half the cross-validation error and similar training and evaluation speeds to models created with the Coulomb matrix and partial radial distribution function methods. For a dataset of 435 000 formation energies taken from the Open Quantum Materials Database (OQMD), our model achieves a mean absolute error of 80 meV/atom in cross validation, which is lower than the approximate error between DFT-computed and experimentally measured formation enthalpies and below 15% of the mean absolute deviation of the training set. We also demonstrate that our method can accurately estimate the formation energy of materials outside of the training set and be used to identify materials with especially large formation enthalpies. We propose that our models can be used to accelerate the discovery of new materials by identifying the most promising materials to study with DFT at little additional computational cost.

  12. GH dysfunction in Engrailed-2 knockout mice, a model for autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Giovanni eProvenzano

    2014-09-01

    Full Text Available Insulin-like growth factor 1 (IGF-1 signaling promotes brain development and plasticity. Altered IGF-1 expression has been associated to autism spectrum disorders (ASD. IGF-1 levels were found increased in the blood and decreased in the cerebrospinal fluid of ASD children. Accordingly, IGF-1 treatment can rescue behavioral deficits in mouse models of ASD, and IGF-1 trials have been proposed for ASD children. IGF-1 is mainly synthesized in the liver, and its synthesis is dependent on growth hormone (GH produced in the pituitary gland. GH also modulates cognitive functions, and altered levels of GH have been detected in ASD patients.Here we analyzed the expression of GH, IGF-1, their receptors and regulatory hormones in the neuroendocrine system of adult male mice lacking the homeobox transcription factor Engrailed-2 (En2-/- mice. En2-/- mice display ASD-like behaviors (social interactions, defective spatial learning, increased seizure susceptibility accompanied by relevant neuropathological changes (loss of cerebellar and forebrain inhibitory neurons. Recent studies showed that En2 modulates IGF-1 activity during postnatal cerebellar development.We found that GH mRNA expression was markedly deregulated throughout the neuroendocrine axis in En2-/- mice, as compared to wild-type (WT controls. In mutant mice, GH mRNA levels were significantly increased in the pituitary gland, blood and liver, whereas decreased levels were detected in the hippocampus. These changes were paralleled by decreased levels of GH protein in the hippocampus but not other tissues of En2-/- mice. IGF-1 mRNA was significantly up-regulated in the liver and down-regulated in the En2-/- hippocampus, but no differences were detected in the levels of IGF-1 protein between the two genotypes. Our data strengthen the notion that altered GH levels in the hippocampus may be involved in learning disabilities associated to ASD.

  13. Mathematical modeling of left ventricular dimensional changes in mice during aging

    Directory of Open Access Journals (Sweden)

    Yang Tianyi

    2012-12-01

    Full Text Available Abstract Cardiac aging is characterized by diastolic dysfunction of the left ventricle (LV, which is due in part to increased LV wall stiffness. In the diastolic phase, myocytes are relaxed and extracellular matrix (ECM is a critical determinant to the changes of LV wall stiffness. To evaluate the effects of ECM composition on cardiac aging, we developed a mathematical model to predict LV dimension and wall stiffness changes in aging mice by integrating mechanical laws and our experimental results. We measured LV dimension, wall thickness, LV mass, and collagen content for wild type (WT C57/BL6J mice of ages ranging from 7.3 months to those of 34.0 months. The model was established using the thick wall theory and stretch-induced tissue growth to an isotropic and homogeneous elastic composite with mixed constituents. The initial conditions of the simulation were set based on the data from the young mice. Matlab simulations of this mathematical model demonstrated that the model captured the major features of LV remodeling with age and closely approximated experimental results. Specifically, the temporal progression of the LV interior and exterior dimensions demonstrated the same trend and order-of-magnitude change as our experimental results. In conclusion, we present here a validated mathematical model of cardiac aging that applies the thick-wall theory and stretch-induced tissue growth to LV remodeling with age.

  14. Including fluid shear viscosity in a structural acoustic finite element model using a scalar fluid representation

    Science.gov (United States)

    Cheng, Lei; Li, Yizeng; Grosh, Karl

    2013-01-01

    An approximate boundary condition is developed in this paper to model fluid shear viscosity at boundaries of coupled fluid-structure system. The effect of shear viscosity is approximated by a correction term to the inviscid boundary condition, written in terms of second order in-plane derivatives of pressure. Both thin and thick viscous boundary layer approximations are formulated; the latter subsumes the former. These approximations are used to develop a variational formation, upon which a viscous finite element method (FEM) model is based, requiring only minor modifications to the boundary integral contributions of an existing inviscid FEM model. Since this FEM formulation has only one degree of freedom for pressure, it holds a great computational advantage over the conventional viscous FEM formulation which requires discretization of the full set of linearized Navier-Stokes equations. The results from thick viscous boundary layer approximation are found to be in good agreement with the prediction from a Navier-Stokes model. When applicable, thin viscous boundary layer approximation also gives accurate results with computational simplicity compared to the thick boundary layer formulation. Direct comparison of simulation results using the boundary layer approximations and a full, linearized Navier-Stokes model are made and used to evaluate the accuracy of the approximate technique. Guidelines are given for the parameter ranges over which the accurate application of the thick and thin boundary approximations can be used for a fluid-structure interaction problem. PMID:23729844

  15. Kinetic modelling of anaerobic hydrolysis of solid wastes, including disintegration processes

    Energy Technology Data Exchange (ETDEWEB)

    García-Gen, Santiago [Department of Chemical Engineering, Institute of Technology, University of Santiago de Compostela, 15782 Santiago de Compostela (Spain); Sousbie, Philippe; Rangaraj, Ganesh [INRA, UR50, Laboratoire de Biotechnologie de l’Environnement, Avenue des Etangs, Narbonne F-11100 (France); Lema, Juan M. [Department of Chemical Engineering, Institute of Technology, University of Santiago de Compostela, 15782 Santiago de Compostela (Spain); Rodríguez, Jorge, E-mail: jrodriguez@masdar.ac.ae [Department of Chemical Engineering, Institute of Technology, University of Santiago de Compostela, 15782 Santiago de Compostela (Spain); Institute Centre for Water and Environment (iWater), Masdar Institute of Science and Technology, PO Box 54224 Abu Dhabi (United Arab Emirates); Steyer, Jean-Philippe; Torrijos, Michel [INRA, UR50, Laboratoire de Biotechnologie de l’Environnement, Avenue des Etangs, Narbonne F-11100 (France)

    2015-01-15

    Highlights: • Fractionation of solid wastes into readily and slowly biodegradable fractions. • Kinetic coefficients estimation from mono-digestion batch assays. • Validation of kinetic coefficients with a co-digestion continuous experiment. • Simulation of batch and continuous experiments with an ADM1-based model. - Abstract: A methodology to estimate disintegration and hydrolysis kinetic parameters of solid wastes and validate an ADM1-based anaerobic co-digestion model is presented. Kinetic parameters of the model were calibrated from batch reactor experiments treating individually fruit and vegetable wastes (among other residues) following a new protocol for batch tests. In addition, decoupled disintegration kinetics for readily and slowly biodegradable fractions of solid wastes was considered. Calibrated parameters from batch assays of individual substrates were used to validate the model for a semi-continuous co-digestion operation treating simultaneously 5 fruit and vegetable wastes. The semi-continuous experiment was carried out in a lab-scale CSTR reactor for 15 weeks at organic loading rate ranging between 2.0 and 4.7 g VS/L d. The model (built in Matlab/Simulink) fit to a large extent the experimental results in both batch and semi-continuous mode and served as a powerful tool to simulate the digestion or co-digestion of solid wastes.

  16. Results of including geometric nonlinearities in an aeroelastic model of an F/A-18

    Science.gov (United States)

    Buttrill, Carey S.

    1989-01-01

    An integrated, nonlinear simulation model suitable for aeroelastic modeling of fixed-wing aircraft has been developed. While the author realizes that the subject of modeling rotating, elastic structures is not closed, it is believed that the equations of motion developed and applied herein are correct to second order and are suitable for use with typical aircraft structures. The equations are not suitable for large elastic deformation. In addition, the modeling framework generalizes both the methods and terminology of non-linear rigid-body airplane simulation and traditional linear aeroelastic modeling. Concerning the importance of angular/elastic inertial coupling in the dynamic analysis of fixed-wing aircraft, the following may be said. The rigorous inclusion of said coupling is not without peril and must be approached with care. In keeping with the same engineering judgment that guided the development of the traditional aeroelastic equations, the effect of non-linear inertial effects for most airplane applications is expected to be small. A parameter does not tell the whole story, however, and modes flagged by the parameter as significant also need to be checked to see if the coupling is not a one-way path, i.e., the inertially affected modes can influence other modes.

  17. HIV Model Parameter Estimates from Interruption Trial Data including Drug Efficacy and Reservoir Dynamics

    Science.gov (United States)

    Luo, Rutao; Piovoso, Michael J.; Martinez-Picado, Javier; Zurakowski, Ryan

    2012-01-01

    Mathematical models based on ordinary differential equations (ODE) have had significant impact on understanding HIV disease dynamics and optimizing patient treatment. A model that characterizes the essential disease dynamics can be used for prediction only if the model parameters are identifiable from clinical data. Most previous parameter identification studies for HIV have used sparsely sampled data from the decay phase following the introduction of therapy. In this paper, model parameters are identified from frequently sampled viral-load data taken from ten patients enrolled in the previously published AutoVac HAART interruption study, providing between 69 and 114 viral load measurements from 3–5 phases of viral decay and rebound for each patient. This dataset is considerably larger than those used in previously published parameter estimation studies. Furthermore, the measurements come from two separate experimental conditions, which allows for the direct estimation of drug efficacy and reservoir contribution rates, two parameters that cannot be identified from decay-phase data alone. A Markov-Chain Monte-Carlo method is used to estimate the model parameter values, with initial estimates obtained using nonlinear least-squares methods. The posterior distributions of the parameter estimates are reported and compared for all patients. PMID:22815727

  18. Modelling of bypass transition including the pseudolaminar part of the boundary layer

    Energy Technology Data Exchange (ETDEWEB)

    Prihoda, J.; Hlava, T. [Ceska Akademie Ved, Prague (Czech Republic). Inst. of Thermomechanics; Kozel, K. [Ceske Vysoke Uceni Technicke, Prague (Czech Republic). Faculty of Mechanical Engineering

    1999-12-01

    The boundary-layer transition in turbomachinery is accelerated by a number of parameters, especially by the free-stream turbulence. This so-called bypass transition is usually modelled by means of one-equation or two-equation turbulence models based on turbulent viscosity. Using of transport equations for turbulent energy and for dissipation rate in these models is questionable before the onset of the last stage of the transition, i.e. before the formation of turbulent spots. Used approximations of production and turbulent diffusion are the weak points of turbulence models with turbulent viscosity in the pseudolaminar boundary layer, as the Boussinesq assumption on turbulent viscosity is not fulfilled in this part of the boundary layer. In order to obtain a more reliable prediction of the transitional boundary layer, Mayle and Schulz (1997) proposed for the solution of pseudolaminar boundary layer a special `laminar-kinetic-energy` equation based on the analysis of laminar boundary layer in flows with velocity fluctuations. The effect of production and turbulent diffusion on the development of turbulent energy in the pseudolaminar boundary layer was tested using a two-layer turbulence model. (orig.)

  19. Modelling of bypass transition including the pseudolaminar part of the boundary layer

    Energy Technology Data Exchange (ETDEWEB)

    Prihoda, J.; Hlava, T. (Ceska Akademie Ved, Prague (Czech Republic). Inst. of Thermomechanics); Kozel, K. (Ceske Vysoke Uceni Technicke, Prague (Czech Republic). Faculty of Mechanical Engineering)

    1999-01-01

    The boundary-layer transition in turbomachinery is accelerated by a number of parameters, especially by the free-stream turbulence. This so-called bypass transition is usually modelled by means of one-equation or two-equation turbulence models based on turbulent viscosity. Using of transport equations for turbulent energy and for dissipation rate in these models is questionable before the onset of the last stage of the transition, i.e. before the formation of turbulent spots. Used approximations of production and turbulent diffusion are the weak points of turbulence models with turbulent viscosity in the pseudolaminar boundary layer, as the Boussinesq assumption on turbulent viscosity is not fulfilled in this part of the boundary layer. In order to obtain a more reliable prediction of the transitional boundary layer, Mayle and Schulz (1997) proposed for the solution of pseudolaminar boundary layer a special 'laminar-kinetic-energy' equation based on the analysis of laminar boundary layer in flows with velocity fluctuations. The effect of production and turbulent diffusion on the development of turbulent energy in the pseudolaminar boundary layer was tested using a two-layer turbulence model. (orig.)

  20. Beam dynamics in high intensity cyclotrons including neighboring bunch effects: Model, implementation, and application

    Directory of Open Access Journals (Sweden)

    J. J. Yang (杨建俊

    2010-06-01

    Full Text Available Space-charge effects, being one of the most significant collective effects, play an important role in high intensity cyclotrons. However, for cyclotrons with small turn separation, other existing effects are of equal importance. Interactions of radially neighboring bunches are also present, but their combined effects have not yet been investigated in any great detail. In this paper, a new particle in the cell-based self-consistent numerical simulation model is presented for the first time. The model covers neighboring bunch effects and is implemented in the three-dimensional object-oriented parallel code OPAL-cycl, a flavor of the OPAL framework. We discuss this model together with its implementation and validation. Simulation results are presented from the PSI 590 MeV ring cyclotron in the context of the ongoing high intensity upgrade program, which aims to provide a beam power of 1.8 MW (CW at the target destination.

  1. Finding practical phenomenological models that include both photoresist behavior and etch process effects

    Science.gov (United States)

    Jung, Sunwook; Do, Thuy; Sturtevant, John

    2015-03-01

    For more than five decades, the semiconductor industry has overcome technology challenges with innovative ideas that have continued to enable Moore's Law. It is clear that multi-patterning lithography is vital for 20nm half pitch using 193i. Multi-patterning exposure sequences and pattern multiplication processes can create complicated tolerance accounting due to the variability associated with the component processes. It is essential to ensure good predictive accuracy of compact etch models used in multipatterning simulation. New modelforms have been developed to account for etch bias behavior at 20 nm and below. The new modeling components show good results in terms of global fitness and some improved predication capability for specific features. We've also investigated a new methodology to make the etch model aware of 3D resist profiles.

  2. A Simple Model of Fields Including the Strong or Nuclear Force and a Cosmological Speculation

    Directory of Open Access Journals (Sweden)

    David L. Spencer

    2016-10-01

    Full Text Available Reexamining the assumptions underlying the General Theory of Relativity and calling an object's gravitational field its inertia, and acceleration simply resistance to that inertia, yields a simple field model where the potential (kinetic energy of a particle at rest is its capacity to move itself when its inertial field becomes imbalanced. The model then attributes electromagnetic and strong forces to the effects of changes in basic particle shape. Following up on the model's assumption that the relative intensity of a particle's gravitational field is always inversely related to its perceived volume and assuming that all black holes spin, may create the possibility of a cosmic rebound where a final spinning black hole ends with a new Big Bang.

  3. Modeling of the dynamics of wind to power conversion including high wind speed behavior

    DEFF Research Database (Denmark)

    Litong-Palima, Marisciel; Bjerge, Martin Huus; Cutululis, Nicolaos Antonio

    2016-01-01

    This paper proposes and validates an efficient, generic and computationally simple dynamic model for the conversion of the wind speed at hub height into the electrical power by a wind turbine. This proposed wind turbine model was developed as a first step to simulate wind power time series...... speed shutdowns and restarts are represented as on–off switching rules that govern the output of the wind turbine at extreme wind speed conditions. The model uses the concept of equivalent wind speed, estimated from the single point (hub height) wind speed using a second-order dynamic filter...... measurements available from the DONG Energy offshore wind farm Horns Rev 2. Copyright © 2015 John Wiley & Sons, Ltd....

  4. Hepatic alcohol dehydrogenase deficiency induces pancreatic injury in chronic ethanol feeding model of deer mice.

    Science.gov (United States)

    Amer, Samir M; Bhopale, Kamlesh K; Kakumanu, Ramu D; Popov, Vsevolod L; Rampy, Bill A; El-Mehallawi, Inas H; Ashmawy, Magdy M; Shakeel Ansari, G A; Kaphalia, Bhupendra S

    2018-02-01

    The single most common cause of chronic pancreatitis (CP, a serious inflammatory disease) is chronic alcohol abuse, which impairs hepatic alcohol dehydrogenase (ADH, a major ethanol oxidizing enzyme). Previously, we found ~5 fold greater fatty acid ethyl esters (FAEEs), and injury in the pancreas of hepatic ADH deficient (ADH - ) vs. hepatic normal ADH (ADH + ) deer mice fed 3.5g% ethanol via liquid diet daily for two months. Therefore, progression of ethanol-induced pancreatic injury was determined in ADH - deer mice fed ethanol for four months to delineate the mechanism and metabolic basis of alcoholic chronic pancreatitis (ACP). In addition to a substantially increased blood alcohol concentration and plasma FAEEs, significant degenerative changes, including atrophy and loss of acinar cells in some areas, ultrastructural changes evident by such features as swelling and disintegration of endoplasmic reticulum (ER) cisternae and ER stress were observed in the pancreas of ethanol-fed ADH - deer mice vs. ADH + deer mice. These changes are consistent with noted increases in pancreatic injury markers (plasma lipase, pancreatic trypsinogen activation peptide, FAEE synthase and cathepsin B) in ethanol-fed ADH - deer mice. Most importantly, an increased levels of pancreatic glucose regulated protein (GRP) 78 (a prominent ER stress marker) were found to be closely associated with increased phosphorylated eukaryotic initiation factor (eIF) 2α signaling molecule in PKR-like ER kinase branch of unfolded protein response (UPR) as compared to X box binding protein 1S and activating transcription factor (ATF)6 - 50kDa protein of inositol requiring enzyme 1α and ATF6 branches of UPR, respectively, in ethanol-fed ADH - vs. ADH + deer mice. These results along with findings on plasma FAEEs, and pancreatic histology and injury markers suggest a metabolic basis of ethanol-induced pancreatic injury, and provide new avenues to understand metabolic basis and molecular mechanism of ACP

  5. An extended TRANSCAR model including ionospheric convection: simulation of EISCAT observations using inputs from AMIE

    Directory of Open Access Journals (Sweden)

    P.-L. Blelly

    2005-02-01

    Full Text Available The TRANSCAR ionospheric model was extended to account for the convection of the magnetic field lines in the auroral and polar ionosphere. A mixed Eulerian-Lagrangian 13-moment approach was used to describe the dynamics of an ionospheric plasma tube. In the present study, one focuses on large scale transports in the polar ionosphere. The model was used to simulate a 35-h period of EISCAT-UHF observations on 16-17 February 1993. The first day was magnetically quiet, and characterized by elevated electron concentrations: the diurnal F2 layer reached as much as 1012m-3, which is unusual for a winter and moderate solar activity (F10.7=130 period. An intense geomagnetic event occurred on the second day, seen in the data as a strong intensification of the ionosphere convection velocities in the early afternoon (with the northward electric field reaching 150mVm-1 and corresponding frictional heating of the ions up to 2500K. The simulation used time-dependent AMIE outputs to infer flux-tube transports in the polar region, and to provide magnetospheric particle and energy inputs to the ionosphere. The overall very good agreement, obtained between the model and the observations, demonstrates the high ability of the extended TRANSCAR model for quantitative modelling of the high-latitude ionosphere; however, some differences are found which are attributed to the precipitation of electrons with very low energy. All these results are finally discussed in the frame of modelling the auroral ionosphere with space weather applications in mind.

  6. An extended TRANSCAR model including ionospheric convection: simulation of EISCAT observations using inputs from AMIE

    Directory of Open Access Journals (Sweden)

    P.-L. Blelly

    2005-02-01

    Full Text Available The TRANSCAR ionospheric model was extended to account for the convection of the magnetic field lines in the auroral and polar ionosphere. A mixed Eulerian-Lagrangian 13-moment approach was used to describe the dynamics of an ionospheric plasma tube. In the present study, one focuses on large scale transports in the polar ionosphere. The model was used to simulate a 35-h period of EISCAT-UHF observations on 16-17 February 1993. The first day was magnetically quiet, and characterized by elevated electron concentrations: the diurnal F2 layer reached as much as 1012m-3, which is unusual for a winter and moderate solar activity (F10.7=130 period. An intense geomagnetic event occurred on the second day, seen in the data as a strong intensification of the ionosphere convection velocities in the early afternoon (with the northward electric field reaching 150mVm-1 and corresponding frictional heating of the ions up to 2500K. The simulation used time-dependent AMIE outputs to infer flux-tube transports in the polar region, and to provide magnetospheric particle and energy inputs to the ionosphere. The overall very good agreement, obtained between the model and the observations, demonstrates the high ability of the extended TRANSCAR model for quantitative modelling of the high-latitude ionosphere; however, some differences are found which are attributed to the precipitation of electrons with very low energy. All these results are finally discussed in the frame of modelling the auroral ionosphere with space weather applications in mind.

  7. Evaluation of European air quality modelled by CAMx including the volatility basis set scheme

    Directory of Open Access Journals (Sweden)

    G. Ciarelli

    2016-08-01

    Full Text Available Four periods of EMEP (European Monitoring and Evaluation Programme intensive measurement campaigns (June 2006, January 2007, September–October 2008 and February–March 2009 were modelled using the regional air quality model CAMx with VBS (volatility basis set approach for the first time in Europe within the framework of the EURODELTA-III model intercomparison exercise. More detailed analysis and sensitivity tests were performed for the period of February–March 2009 and June 2006 to investigate the uncertainties in emissions as well as to improve the modelling of organic aerosol (OA. Model performance for selected gas phase species and PM2.5 was evaluated using the European air quality database AirBase. Sulfur dioxide (SO2 and ozone (O3 were found to be overestimated for all the four periods, with O3 having the largest mean bias during June 2006 and January–February 2007 periods (8.9 pbb and 12.3 ppb mean biases respectively. In contrast, nitrogen dioxide (NO2 and carbon monoxide (CO were found to be underestimated for all the four periods. CAMx reproduced both total concentrations and monthly variations of PM2.5 for all the four periods with average biases ranging from −2.1 to 1.0 µg m−3. Comparisons with AMS (aerosol mass spectrometer measurements at different sites in Europe during February–March 2009 showed that in general the model overpredicts the inorganic aerosol fraction and underpredicts the organic one, such that the good agreement for PM2.5 is partly due to compensation of errors. The effect of the choice of VBS scheme on OA was investigated as well. Two sensitivity tests with volatility distributions based on previous chamber and ambient measurements data were performed. For February–March 2009 the chamber case reduced the total OA concentrations by about 42 % on average. In contrast, a test based on ambient measurement data increased OA concentrations by about 42 % for the same period bringing

  8. Molecular Modeling of Aerospace Polymer Matrices Including Carbon Nanotube-Enhanced Epoxy

    Science.gov (United States)

    Radue, Matthew S.

    Carbon fiber (CF) composites are increasingly replacing metals used in major structural parts of aircraft, spacecraft, and automobiles. The current limitations of carbon fiber composites are addressed through computational material design by modeling the salient aerospace matrix materials. Molecular Dynamics (MD) models of epoxies with and without carbon nanotube (CNT) reinforcement and models of pure bismaleimides (BMIs) were developed to elucidate structure-property relationships for improved selection and tailoring of matrices. The influence of monomer functionality on the mechanical properties of epoxies is studied using the Reax Force Field (ReaxFF). From deformation simulations, the Young's modulus, yield point, and Poisson's ratio are calculated and analyzed. The results demonstrate an increase in stiffness and yield strength with increasing resin functionality. Comparison between the network structures of distinct epoxies is further advanced by the Monomeric Degree Index (MDI). Experimental validation demonstrates the MD results correctly predict the relationship in Young's moduli for all epoxies modeled. Therefore, the ReaxFF is confirmed to be a useful tool for studying the mechanical behavior of epoxies. While epoxies have been well-studied using MD, there has been no concerted effort to model cured BMI polymers due to the complexity of the network-forming reactions. A novel, adaptable crosslinking framework is developed for implementing 5 distinct cure reactions of Matrimid-5292 (a BMI resin) and investigating the network structure using MD simulations. The influence of different cure reactions and extent of curing are analyzed on the several thermo-mechanical properties such as mass density, glass transition temperature, coefficient of thermal expansion, elastic moduli, and thermal conductivity. The developed crosslinked models correctly predict experimentally observed trends for various properties. Finally, the epoxies modeled (di-, tri-, and tetra

  9. Modelling of safety barriers including human and organisational factors to improve process safety

    DEFF Research Database (Denmark)

    Markert, Frank; Duijm, Nijs Jan; Thommesen, Jacob

    2013-01-01

    Assessment Methodology for IndustrieS, see Salvi et al 2006). ARAMIS employs the bow-tie approach to modelling hazardous scenarios, and it suggests the outcome of auditing safety management to be connected to a semi-quantitative assessment of the quality of safety barriers. ARAMIS discriminates a number...... of safety barrier (passive, automated, or involving human action). Such models are valuable for many purposes, but are difficult to apply to more complex situations, as the influences are to be set individually for each barrier. The approach described in this paper is trying to improve the state...

  10. The economic production lot size model extended to include more than one production rate

    DEFF Research Database (Denmark)

    Larsen, Christian

    2005-01-01

    We study an extension of the economic production lot size model, where more than one production rate can be used during a cycle. Moreover, the production rates, as well as their corresponding runtimes are decision variables. We decompose the problem into two subproblems. First, we show that all...

  11. The economic production lot size model extended to include more than one production rate

    DEFF Research Database (Denmark)

    Larsen, Christian

    2001-01-01

    We study an extension of the economic production lot size model, where more than one production rate can be used during a cycle. Moreover, the production rates, as well as their corresponding runtimes are decision variables. First, we show that all production rates should be choosen in the interval...

  12. Static aeroelastic analysis including geometric nonlinearities based on reduced order model

    Directory of Open Access Journals (Sweden)

    Changchuan Xie

    2017-04-01

    Full Text Available This paper describes a method proposed for modeling large deflection of aircraft in nonlinear aeroelastic analysis by developing reduced order model (ROM. The method is applied for solving the static aeroelastic and static aeroelastic trim problems of flexible aircraft containing geometric nonlinearities; meanwhile, the non-planar effects of aerodynamics and follower force effect have been considered. ROMs are computational inexpensive mathematical representations compared to traditional nonlinear finite element method (FEM especially in aeroelastic solutions. The approach for structure modeling presented here is on the basis of combined modal/finite element (MFE method that characterizes the stiffness nonlinearities and we apply that structure modeling method as ROM to aeroelastic analysis. Moreover, the non-planar aerodynamic force is computed by the non-planar vortex lattice method (VLM. Structure and aerodynamics can be coupled with the surface spline method. The results show that both of the static aeroelastic analysis and trim analysis of aircraft based on structure ROM can achieve a good agreement compared to analysis based on the FEM and experimental result.

  13. Dusty Plasma Modeling of the Fusion Reactor Sheath Including Collisional-Radiative Effects

    International Nuclear Information System (INIS)

    Dezairi, Aouatif; Samir, Mhamed; Eddahby, Mohamed; Saifaoui, Dennoun; Katsonis, Konstantinos; Berenguer, Chloe

    2008-01-01

    The structure and the behavior of the sheath in Tokamak collisional plasmas has been studied. The sheath is modeled taking into account the presence of the dust 2 and the effects of the charged particle collisions and radiative processes. The latter may allow for optical diagnostics of the plasma.

  14. Description of the new version 4.0 of the tritium model UFOTRI including user guide

    International Nuclear Information System (INIS)

    Raskob, W.

    1993-08-01

    In view of the future operation of fusion reactors the release of tritium may play a dominant role during normal operation as well as after accidents. Because of its physical and chemical properties which differ significantly from those of other radionuclides, the model UFOTRI for assessing the radiological consequences of accidental tritium releases has been developed. It describes the behaviour of tritium in the biosphere and calculates the radiological impact on individuals and the population due to the direct exposure and by the ingestion pathways. Processes such as the conversion of tritium gas into tritiated water (HTO) in the soil, re-emission after deposition and the conversion of HTO into organically bound tritium, are considered. The use of UFOTRI in its probabilistic mode shows the spectrum of the radiological impact together with the associated probability of occurrence. A first model version was established in 1991. As the ongoing work on investigating the main processes of the tritium behaviour in the environment shows up new results, the model has been improved in several points. The report describes the changes incorporated into the model since 1991. Additionally provides the up-dated user guide for handling the revised UFOTRI version which will be distributed to interested organizations. (orig.) [de

  15. Extending the formal model of a spatial data infrastructure to include volunteered geographical information

    CSIR Research Space (South Africa)

    Cooper, Antony K

    2011-07-01

    Full Text Available -to-date VGI, have led to the integration of VGI into some SDIs. Therefore it is necessary to rethink our formal model of an SDI to accommodate VGI. We started our rethinking process with the SDI stakeholders in an attempt to establish which changes...

  16. Loss and thermal model for power semiconductors including device rating information

    DEFF Research Database (Denmark)

    Ma, Ke; Bahman, Amir Sajjad; Beczkowski, Szymon

    2014-01-01

    pre-defined by experience with poor design flexibility. Consequently a more complete loss and thermal model is proposed in this paper, which takes into account not only the electrical loading but also the device rating as input variables. The quantified correlation between the power loss, thermal...

  17. Social Rationality as a Unified Model of Man (Including Bounded Rationality)

    NARCIS (Netherlands)

    Lindenberg, Siegwart

    2001-01-01

    In 1957, Simon published a collection of his essays under the title of “Models of Man: Social and Rational”. In the preface, he explains the choice for this title: All of the essays “are concerned with laying foundations for a science of man that will comfortably accommodate his dual nature as a

  18. Simple vibration modeling of structural fuzzy with continuous boundary by including two-dimensional spatial memory

    DEFF Research Database (Denmark)

    Friis, Lars; Ohlrich, Mogens

    2008-01-01

    is considered as one or more fuzzy substructures that are known in some statistical sense only. Experiments have shown that such fuzzy substructures often introduce a damping in the master which is much higher than the structural losses account for. A special method for modeling fuzzy substructures with a one...

  19. Situational effects of the school factors included in the dynamic model of educational effectiveness

    NARCIS (Netherlands)

    Creerners, Bert; Kyriakides, Leonidas

    We present results of a longitudinal study in which 50 schools, 113 classes and 2,542 Cypriot primary students participated. We tested the validity of the dynamic model of educational effectiveness and especially its assumption that the impact of school factors depends on the current situation of

  20. Modeling the elastic behavior of ductile cast iron including anisotropy in the graphite nodules

    DEFF Research Database (Denmark)

    Andriollo, Tito; Thorborg, Jesper; Hattel, Jesper Henri

    2016-01-01

    by means of a 3D periodic unit cell model. In this respect, an explicit procedure to enforce both periodic displacement and periodic traction boundary conditions in ABAQUS is presented, and the importance of fulfilling the traction continuity conditions at the unit cell boundaries is discussed. It is shown...

  1. A biologically inspired neural model for visual and proprioceptive integration including sensory training.

    Science.gov (United States)

    Saidi, Maryam; Towhidkhah, Farzad; Gharibzadeh, Shahriar; Lari, Abdolaziz Azizi

    2013-12-01

    Humans perceive the surrounding world by integration of information through different sensory modalities. Earlier models of multisensory integration rely mainly on traditional Bayesian and causal Bayesian inferences for single causal (source) and two causal (for two senses such as visual and auditory systems), respectively. In this paper a new recurrent neural model is presented for integration of visual and proprioceptive information. This model is based on population coding which is able to mimic multisensory integration of neural centers in the human brain. The simulation results agree with those achieved by casual Bayesian inference. The model can also simulate the sensory training process of visual and proprioceptive information in human. Training process in multisensory integration is a point with less attention in the literature before. The effect of proprioceptive training on multisensory perception was investigated through a set of experiments in our previous study. The current study, evaluates the effect of both modalities, i.e., visual and proprioceptive training and compares them with each other through a set of new experiments. In these experiments, the subject was asked to move his/her hand in a circle and estimate its position. The experiments were performed on eight subjects with proprioception training and eight subjects with visual training. Results of the experiments show three important points: (1) visual learning rate is significantly more than that of proprioception; (2) means of visual and proprioceptive errors are decreased by training but statistical analysis shows that this decrement is significant for proprioceptive error and non-significant for visual error, and (3) visual errors in training phase even in the beginning of it, is much less than errors of the main test stage because in the main test, the subject has to focus on two senses. The results of the experiments in this paper is in agreement with the results of the neural model

  2. Deletion of the App-Runx1 region in mice models human partial monosomy 21.

    Science.gov (United States)

    Arbogast, Thomas; Raveau, Matthieu; Chevalier, Claire; Nalesso, Valérie; Dembele, Doulaye; Jacobs, Hugues; Wendling, Olivia; Roux, Michel; Duchon, Arnaud; Herault, Yann

    2015-06-01

    Partial monosomy 21 (PM21) is a rare chromosomal abnormality that is characterized by the loss of a variable segment along human chromosome 21 (Hsa21). The clinical phenotypes of this loss are heterogeneous and range from mild alterations to lethal consequences, depending on the affected region of Hsa21. The most common features include intellectual disabilities, craniofacial dysmorphology, short stature, and muscular and cardiac defects. As a complement to human genetic approaches, our team has developed new monosomic mouse models that carry deletions on Hsa21 syntenic regions in order to identify the dosage-sensitive genes that are responsible for the symptoms. We focus here on the Ms5Yah mouse model, in which a 7.7-Mb region has been deleted from the App to Runx1 genes. Ms5Yah mice display high postnatal lethality, with a few surviving individuals showing growth retardation, motor coordination deficits, and spatial learning and memory impairments. Further studies confirmed a gene dosage effect in the Ms5Yah hippocampus, and pinpointed disruptions of pathways related to cell adhesion (involving App, Cntnap5b, Lgals3bp, Mag, Mcam, Npnt, Pcdhb2, Pcdhb3, Pcdhb4, Pcdhb6, Pcdhb7, Pcdhb8, Pcdhb16 and Vwf). Our PM21 mouse model is the first to display morphological abnormalities and behavioural phenotypes similar to those found in affected humans, and it therefore demonstrates the major contribution that the App-Runx1 region has in the pathophysiology of PM21. © 2015. Published by The Company of Biologists Ltd.

  3. Reduced p75NTRexpression delays disease onset only in female mice of a transgenic model of familial amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Küst, B.M.; Brouwer, N.; Mantingh, I.J.; Boddeke, H.W.G.M.; Copray, J.C.V.M.

    2003-01-01

    hSOD1 (G93A) transgenic mice develop pathological changes similar to those in patients with familial amyotrophic lateral sclerosis (FALS). In particular, the progressive degeneration of motoneurons is charactered in this mouse model. One feature of stressed motoneurons in ALS and the hSOD1 mice is

  4. A catchment-scale groundwater model including sewer pipe leakage in an urban system

    Science.gov (United States)

    Peche, Aaron; Fuchs, Lothar; Spönemann, Peter; Graf, Thomas; Neuweiler, Insa

    2016-04-01

    Keywords: pipe leakage, urban hydrogeology, catchment scale, OpenGeoSys, HYSTEM-EXTRAN Wastewater leakage from subsurface sewer pipe defects leads to contamination of the surrounding soil and groundwater (Ellis, 2002; Wolf et al., 2004). Leakage rates at pipe defects have to be known in order to quantify contaminant input. Due to inaccessibility of subsurface pipe defects, direct (in-situ) measurements of leakage rates are tedious and associated with a high degree of uncertainty (Wolf, 2006). Proposed catchment-scale models simplify leakage rates by neglecting unsaturated zone flow or by reducing spatial dimensions (Karpf & Krebs, 2013, Boukhemacha et al., 2015). In the present study, we present a physically based 3-dimensional numerical model incorporating flow in the pipe network, in the saturated zone and in the unsaturated zone to quantify leakage rates on the catchment scale. The model consists of the pipe network flow model HYSTEM-EXTAN (itwh, 2002), which is coupled to the subsurface flow model OpenGeoSys (Kolditz et al., 2012). We also present the newly developed coupling scheme between the two flow models. Leakage functions specific to a pipe defect are derived from simulations of pipe leakage using spatially refined grids around pipe defects. In order to minimize computational effort, these leakage functions are built into the presented numerical model using unrefined grids around pipe defects. The resulting coupled model is capable of efficiently simulating spatially distributed pipe leakage coupled with subsurficial water flow in a 3-dimensional environment. References: Boukhemacha, M. A., Gogu, C. R., Serpescu, I., Gaitanaru, D., & Bica, I. (2015). A hydrogeological conceptual approach to study urban groundwater flow in Bucharest city, Romania. Hydrogeology Journal, 23(3), 437-450. doi:10.1007/s10040-014-1220-3. Ellis, J. B., & Revitt, D. M. (2002). Sewer losses and interactions with groundwater quality. Water Science and Technology, 45(3), 195

  5. Impaired Maternal Behavior in Usp46 Mutant Mice: A Model for Trans-Generational Transmission of Maternal Care.

    Directory of Open Access Journals (Sweden)

    Shoya Umemura

    Full Text Available Usp46 mutant mice (congenic strain on a B6 genetic background; MT mice have a low weaning rate and display poor maternal behavior compared to C57BL/6J mice (B6 mice. Based on these observations, we examined how maternal behavior is shaped by cross-fostering and in-fostering MT and B6 mice. The experiments consisted of six groups: B6 mice fostered by their biological mother (B6-CO; MT mice fostered by their biological mother (MT-CO; B6 mice fostered by a different B6 mother (B6-IF; MT mice fostered by a different MT mother (MT-IF; B6 mice fostered by an MT mother (B6-CF; and MT mice fostered by a B6 mother (MT-CF. Maternal behavior was assessed using the pup-retrieval test in adult female offspring, and four parameters, time nursing pups in the nest, time sniffing or licking pups, rearing behavior, and latency to retrieve pups, were measured. Cross-fostering significantly reduced time spent nursing and sniffing/licking pup, and increased the number of instances of rearing in the B6-CF group, and improved three parameters of maternal behaviors (nursing, rearing and latency in the MT-CF group. These results indicate that the level of maternal care is transmitted to their pups and proper maternal behaviors can be shaped if adequate postpartum maternal care is given, even in genetically vulnerable mice. However, the offspring's genotype may also influence the development of maternal behaviors in adulthood. Thus, MT mice may prove useful as a model for trans-generational transmission of maternal care, and these findings may provide insight into the mechanisms of maltreating behaviors in human child abuse.

  6. Recovery Effect and Life Prolong Effect of Long Term Low-Dose Rate Irradiation on Type II Diabetes Model Mice

    International Nuclear Information System (INIS)

    Nomura, T.; Makino, N.; Oda, T.; Suzuki, I.; Sakai, K

    2004-01-01

    The effects of low-dose rate gamma-irradiation were investigated on model mice for type II diabetes mellitus, C57BL/KsJ-db/db. The mice develop the type II diabetes by 10 weeks of age due to obesity and are characterized by hyperinsulinemia. Female 10-week old mice, a group of 12 mice, were irradiated at 0.65 mGy/hr from 137-Cs (370 GBq). The urine glucose levels of all of the mice were strongly positive at the beginning of the irradiation. In the irradiated group, the decrease in the glucose level was observed in 3 mice. Such recovery from the diabetes was never observed in 12 mice of non-irradiated control group. There is no systematic difference in the change of body weight, food assumption, and amount of drinking water, between the irradiated group and the non-irradiated group or between the recovered mice and the non-recovered mice. The survival was better in the irradiated group: the surviving fraction at the age of 90 weeks was 75% in the irradiated group, while 40% in the non-irradiated. Marked difference was also observed in the appearance of the coat hair, skin, and tail; better condition was kept in the irradiated group. In the irradiated mice mortality was delayed and the healthy appearance was prolonged in the irradiated mice by about 20 ? 30 weeks compared with the non-irradiated mice. These results suggest that the low-dose irradiation modified the condition of the diabetic mice, which lead not only to the recovery of the diabetes, but also to the suppression of the aging process. (Author)

  7. Including Antenna Models in Microwave Imaging for Breast-Cancer Screening

    DEFF Research Database (Denmark)

    Rubæk, Tonny; Meincke, Peter

    2006-01-01

    Microwave imaging is emerging as a tool for screening for breast cancer, but the lack of methods for including the characteristics of the antennas of the imaging systems in the imaging algorithms limits their performance. In this paper, a method for incorporating the full antenna characteristics...

  8. Generation of a new bioluminescent model for visualisation of mammary tumour development in transgenic mice

    LENUS (Irish Health Repository)

    Zagozdzon, Agnieszka M

    2012-05-30

    AbstractBackgroundNumerous transgenic models have been generated to study breast cancer. However, despite many advantages, traditional transgenic models for breast cancer are also burdened with difficulties in early detection and longitudinal observation of transgene-induced tumours, which in most cases are randomly located and occur at various time points. Methods such as palpation followed by mechanical measurement of the tumours are of limited value in transgenic models. There is a crucial need for making these previously generated models suitable for modern methods of tumour visualisation and monitoring, e.g. by bioluminescence-based techniques. This approach was successfully used in the current study.ResultsA new mouse strain (MMTV-Luc2 mice) expressing Luc2 luciferase primarily in mammary tissue in females, with low-level background expression in internal organs, was generated and bred to homozygosity. After these mice were intercrossed with MMTV-PyVT mice, all double transgenic females developed mammary tumours by the age of 10 weeks, the localisation and progression of which could be effectively monitored using the luminescence-based in vivo imaging. Luminescence-based readout allowed for early visualisation of the locally overgrown mammary tissue and for longitudinal evaluation of local progression of the tumours. When sampled ex vivo at the age of 10 weeks, all tumours derived from MMTV-Luc2PyVT females displayed robust bioluminescent signal.ConclusionsWe have created a novel transgenic strain for visualisation and longitudinal monitoring of mammary tumour development in transgenic mice as an addition and\\/or a new and more advanced alternative to manual methods. Generation of this mouse strain is vital for making many of the existing mammary tumour transgenic models applicable for in vivo imaging techniques.

  9. Generation of a new bioluminescent model for visualisation of mammary tumour development in transgenic mice

    Directory of Open Access Journals (Sweden)

    Zagozdzon Agnieszka M

    2012-05-01

    Full Text Available Abstract Background Numerous transgenic models have been generated to study breast cancer. However, despite many advantages, traditional transgenic models for breast cancer are also burdened with difficulties in early detection and longitudinal observation of transgene-induced tumours, which in most cases are randomly located and occur at various time points. Methods such as palpation followed by mechanical measurement of the tumours are of limited value in transgenic models. There is a crucial need for making these previously generated models suitable for modern methods of tumour visualisation and monitoring, e.g. by bioluminescence-based techniques. This approach was successfully used in the current study. Results A new mouse strain (MMTV-Luc2 mice expressing Luc2 luciferase primarily in mammary tissue in females, with low-level background expression in internal organs, was generated and bred to homozygosity. After these mice were intercrossed with MMTV-PyVT mice, all double transgenic females developed mammary tumours by the age of 10 weeks, the localisation and progression of which could be effectively monitored using the luminescence-based in vivo imaging. Luminescence-based readout allowed for early visualisation of the locally overgrown mammary tissue and for longitudinal evaluation of local progression of the tumours. When sampled ex vivo at the age of 10 weeks, all tumours derived from MMTV-Luc2PyVT females displayed robust bioluminescent signal. Conclusions We have created a novel transgenic strain for visualisation and longitudinal monitoring of mammary tumour development in transgenic mice as an addition and/or a new and more advanced alternative to manual methods. Generation of this mouse strain is vital for making many of the existing mammary tumour transgenic models applicable for in vivo imaging techniques.

  10. Generation of a new bioluminescent model for visualisation of mammary tumour development in transgenic mice

    International Nuclear Information System (INIS)

    Zagozdzon, Agnieszka M; O’Leary, Patrick; Callanan, John J; Crown, John; Gallagher, William M; Zagozdzon, Radoslaw

    2012-01-01

    Numerous transgenic models have been generated to study breast cancer. However, despite many advantages, traditional transgenic models for breast cancer are also burdened with difficulties in early detection and longitudinal observation of transgene-induced tumours, which in most cases are randomly located and occur at various time points. Methods such as palpation followed by mechanical measurement of the tumours are of limited value in transgenic models. There is a crucial need for making these previously generated models suitable for modern methods of tumour visualisation and monitoring, e.g. by bioluminescence-based techniques. This approach was successfully used in the current study. A new mouse strain (MMTV-Luc2 mice) expressing Luc2 luciferase primarily in mammary tissue in females, with low-level background expression in internal organs, was generated and bred to homozygosity. After these mice were intercrossed with MMTV-PyVT mice, all double transgenic females developed mammary tumours by the age of 10 weeks, the localisation and progression of which could be effectively monitored using the luminescence-based in vivo imaging. Luminescence-based readout allowed for early visualisation of the locally overgrown mammary tissue and for longitudinal evaluation of local progression of the tumours. When sampled ex vivo at the age of 10 weeks, all tumours derived from MMTV-Luc2PyVT females displayed robust bioluminescent signal. We have created a novel transgenic strain for visualisation and longitudinal monitoring of mammary tumour development in transgenic mice as an addition and/or a new and more advanced alternative to manual methods. Generation of this mouse strain is vital for making many of the existing mammary tumour transgenic models applicable for in vivo imaging techniques

  11. An animal model of adult T-cell leukemia: humanized mice with HTLV-1-specific immunity.

    Science.gov (United States)

    Tezuka, Kenta; Xun, Runze; Tei, Mami; Ueno, Takaharu; Tanaka, Masakazu; Takenouchi, Norihiro; Fujisawa, Jun-ichi

    2014-01-16

    Human T-cell leukemia virus type 1 (HTLV-1) is causally associated with adult T-cell leukemia (ATL), an aggressive T-cell malignancy with a poor prognosis. To elucidate ATL pathogenesis in vivo, a variety of animal models have been established; however, the mechanisms driving this disorder remain poorly understood due to deficiencies in each of these animal models. Here, we report a novel HTLV-1-infected humanized mouse model generated by intra-bone marrow injection of human CD133(+) stem cells into NOD/Shi-scid/IL-2Rγc null (NOG) mice (IBMI-huNOG mice). Upon infection, the number of CD4(+) human T cells in the periphery increased rapidly, and atypical lymphocytes with lobulated nuclei resembling ATL-specific flower cells were observed 4 to 5 months after infection. Proliferation was seen in both CD25(-) and CD25(+) CD4 T cells with identical proviral integration sites; however, a limited number of CD25(+)-infected T-cell clones eventually dominated, indicating an association between clonal selection of infected T cells and expression of CD25. Additionally, HTLV-1-specific adaptive immune responses were induced in infected mice and might be involved in the control of HTLV-1-infected cells. Thus, the HTLV-1-infected IBMI-huNOG mouse model successfully recapitulated the development of ATL and may serve as an important tool for investigating in vivo mechanisms of ATL leukemogenesis and evaluating anti-ATL drug and vaccine candidates.

  12. [Establishment of a keloid model by transplanting human keloid onto the backs of nude mice].

    Science.gov (United States)

    Philandrianos, C; Gonnelli, D; Andrac-Meyer, L; Bruno, M; Magalon, G; Mordon, S

    2014-08-01

    Keloid scar is a proliferative healing dysfunction formed by an excessive build-up of collagen fibers on the dermis. It is responsible of aesthetic and functional disabilities. There is no ideal treatment and recurrence occurs very often. Keloid scars occur only to human, that's why animal model needs to be made to study this pathology and new treatments. Few models have been described using human keloid scars implanted into subcutaneous tissue of nude mice or rat. To allow study of topical and laser treatment we have developed a new animal model using human keloid scar fragment with epidermal and dermal tissue implanted into back of nude mice like a full thickness skin graft. Keloid fragments from five donors have been grafted onto 40 nudes mice. Macroscopic and microscopic studies have been made at day 28, 56, 84 and 112. We observed integration of the fragments in all cases. Hyalinized collagen bundles were observed in all implant biopsies confirming the stability of the keloid architecture within 112 days. This model is easily reproducible and allows the study of topical treatment and laser due to the accessibility of the keloid. Copyright © 2012. Published by Elsevier Masson SAS.

  13. Histidine decarboxylase knockout mice, a genetic model of Tourette syndrome, show repetitive grooming after induced fear.

    Science.gov (United States)

    Xu, Meiyu; Li, Lina; Ohtsu, Hiroshi; Pittenger, Christopher

    2015-05-19

    Tics, such as are seen in Tourette syndrome (TS), are common and can cause profound morbidity, but they are poorly understood. Tics are potentiated by psychostimulants, stress, and sleep deprivation. Mutations in the gene histidine decarboxylase (Hdc) have been implicated as a rare genetic cause of TS, and Hdc knockout mice have been validated as a genetic model that recapitulates phenomenological and pathophysiological aspects of the disorder. Tic-like stereotypies in this model have not been observed at baseline but emerge after acute challenge with the psychostimulant d-amphetamine. We tested the ability of an acute stressor to stimulate stereotypies in this model, using tone fear conditioning. Hdc knockout mice acquired conditioned fear normally, as manifested by freezing during the presentation of a tone 48h after it had been paired with a shock. During the 30min following tone presentation, knockout mice showed increased grooming. Heterozygotes exhibited normal freezing and intermediate grooming. These data validate a new paradigm for the examination of tic-like stereotypies in animals without pharmacological challenge and enhance the face validity of the Hdc knockout mouse as a pathophysiologically grounded model of tic disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Acinar cell apoptosis in Serpini2-deficient mice models pancreatic insufficiency.

    Directory of Open Access Journals (Sweden)

    Stacie K Loftus

    2005-09-01

    Full Text Available Pancreatic insufficiency (PI when left untreated results in a state of malnutrition due to an inability to absorb nutrients. Frequently, PI is diagnosed as part of a larger clinical presentation in cystic fibrosis or Shwachman-Diamond syndrome. In this study, a mouse model for isolated exocrine PI was identified in a mouse line generated by a transgene insertion. The trait is inherited in an autosomal recessive pattern, and homozygous animals are growth retarded, have abnormal immunity, and have reduced life span. Mice with the disease locus, named pequeño (pq, exhibit progressive apoptosis of pancreatic acinar cells with severe exocrine acinar cell loss by 8 wk of age, while the islets and ductal tissue persist. The mutation in pq/pq mice results from a random transgene insertion. Molecular characterization of the transgene insertion site by fluorescent in situ hybridization and genomic deletion mapping identified an approximately 210-kb deletion on Chromosome 3, deleting two genes. One of these genes, Serpini2, encodes a protein that is a member of the serpin family of protease inhibitors. Reintroduction of only the Serpini2 gene by bacterial artificial chromosome transgenic complementation corrected the acinar cell defect as well as body weight and immune phenotypes, showing that deletion of Serpini2 causes the pequeño phenotype. Dietary supplementation of pancreatic enzymes also corrected body size, body weight, and immunodeficiency, and increased the life span of Serpini2-deficient mice, despite continued acinar cell loss. To our knowledge, this study describes the first characterized genetic animal model for isolated PI. Genetic complementation of the transgene insertion mutant demonstrates that Serpini2 deficiency directly results in the acinar cell apoptosis, malabsorption, and malnutrition observed in pq/pq mice. The rescue of growth retardation, immunodeficiency, and mortality by either Serpini2 bacterial artificial chromosome

  15. Gelam honey attenuates ovalbumin-induced airway inflammation in a mice model of allergic asthma

    Directory of Open Access Journals (Sweden)

    Nur Salme Suhana Shamshuddin

    2018-01-01

    Full Text Available Allergic asthma is a chronic inflammatory disorder of the pulmonary airways. Gelam honey has been proven to possess anti-inflammatory property with great potential to treat an inflammatory condition. However, the effect of ingestion of Gelam honey on allergic asthma has never been studied. This study aimed to investigate the efficacy of Gelam honey on the histopathological changes in the lungs of a mice model of allergic asthma. Forty-two Balb/c mice were divided into seven groups: control, I, II, III, IV, V and VI group. All groups except the control were sensitized and challenged with ovalbumin. Mice in groups I, II, III, IV, and V were given honey at a dose of 10% (v/v, 40% (v/v and 80% (v/v, dexamethasone 3 mg/kg, and phosphate buffered saline (vehicle respectively, orally once a day for 5 days of the challenged period. Mice were sacrificed 24 h after the last OVA challenged and the lungs were evaluated for histopathological changes by light microscopy. All histopathological parameters such as epithelium thickness, the number of mast cell and mucus expression in Group III significantly improved when compared to Group VI except for subepithelial smooth muscle thickness (p < 0.05. In comparing Group III and IV, all the improvements in histopathological parameters were similar. Also, Gelam honey showed a significant (p < 0.05 reduction in inflammatory cell infiltration and beta-hexosaminidase level in bronchoalveolar lavage fluid. In conclusion, we demonstrated that administration of high concentration of Gelam honey alleviates the histopathological changes of mice model of allergic asthma.

  16. Gelam honey attenuates ovalbumin-induced airway inflammation in a mice model of allergic asthma.

    Science.gov (United States)

    Shamshuddin, Nur Salme Suhana; Mohd Zohdi, Rozaini

    2018-01-01

    Allergic asthma is a chronic inflammatory disorder of the pulmonary airways. Gelam honey has been proven to possess anti-inflammatory property with great potential to treat an inflammatory condition. However, the effect of ingestion of Gelam honey on allergic asthma has never been studied. This study aimed to investigate the efficacy of Gelam honey on the histopathological changes in the lungs of a mice model of allergic asthma. Forty-two Balb/c mice were divided into seven groups: control, I, II, III, IV, V and VI group. All groups except the control were sensitized and challenged with ovalbumin. Mice in groups I, II, III, IV, and V were given honey at a dose of 10% (v/v), 40% (v/v) and 80% (v/v), dexamethasone 3 mg/kg, and phosphate buffered saline (vehicle) respectively, orally once a day for 5 days of the challenged period. Mice were sacrificed 24 h after the last OVA challenged and the lungs were evaluated for histopathological changes by light microscopy. All histopathological parameters such as epithelium thickness, the number of mast cell and mucus expression in Group III significantly improved when compared to Group VI except for subepithelial smooth muscle thickness (p < 0.05). In comparing Group III and IV, all the improvements in histopathological parameters were similar. Also, Gelam honey showed a significant (p < 0.05) reduction in inflammatory cell infiltration and beta-hexosaminidase level in bronchoalveolar lavage fluid. In conclusion, we demonstrated that administration of high concentration of Gelam honey alleviates the histopathological changes of mice model of allergic asthma.

  17. Numerical models of single- and double-negative metamaterials including viscous and thermal losses

    DEFF Research Database (Denmark)

    Cutanda Henriquez, Vicente; Sánchez-Dehesa, José

    2017-01-01

    Negative index acoustic metamaterials are artificial structures made of subwavelength units arranged in a lattice, whose effective acoustic parameters, bulk modulus and mass density, can be negative. In these materials, sound waves propagate inside the periodic structure, assumed rigid, showing...... extraordinary properties. We are interested in two particular cases: a double-negative metamaterial, where both parameters are negative at some frequencies, and a single-negative metamaterial with negative bulk modulus within a broader frequency band. In previous research involving the double-negative...... detailed understanding on how viscous and thermal losses affect the setups at different frequencies. The modeling of a simpler single-negative metamaterial also broadens this overview. Both setups have been modeled with quadratic BEM meshes. Each sample, scaled at two different sizes, has been represented...

  18. Paint Pavement Marking Performance Prediction Model That Includes the Impacts of Snow Removal Operations

    Science.gov (United States)

    2011-03-01

    Hypothesized that snow plows wear down mountain road pavement markings. 2007 Craig et al. -Edge lines degrade slower than center/skip lines 2007...retroreflectivity to create the models. They discovered that paint pavement markings last 80% longer on Portland Cement Concrete than Asphalt Concrete at low AADT...retroreflectivity, while yellow markings lost 21%. Lu and Barter attributed the sizable degradation to snow removal, sand application, and studded

  19. An earth outgoing longwave radiation climate model. II - Radiation with clouds included

    Science.gov (United States)

    Yang, Shi-Keng; Smith, G. Louis; Bartman, Fred L.

    1988-01-01

    The model of the outgoing longwave radiation (OLWR) of Yang et al. (1987) is modified by accounting for the presence of clouds and their influence on OLWR. Cloud top temperature was adjusted so that the calculation agreed with NOAA scanning radiometer measurements. Cloudy sky cases were calculated for global average, zonal average, and worldwide distributed cases. The results were found to agree well with satellite observations.

  20. Modelling topical photodynamic therapy treatment including the continuous production of Protoporphyrin IX

    Science.gov (United States)

    Campbell, C. L.; Brown, C. T. A.; Wood, K.; Moseley, H.

    2016-11-01

    Most existing theoretical models of photodynamic therapy (PDT) assume a uniform initial distribution of the photosensitive molecule, Protoporphyrin IX (PpIX). This is an adequate assumption when the prodrug is systematically administered; however for topical PDT this is no longer a valid assumption. Topical application and subsequent diffusion of the prodrug results in an inhomogeneous distribution of PpIX, especially after short incubation times, prior to light illumination. In this work a theoretical simulation of PDT where the PpIX distribution depends on the incubation time and the treatment modality is described. Three steps of the PpIX production are considered. The first is the distribution of the topically applied prodrug, the second in the conversion from the prodrug to PpIX and the third is the light distribution which affects the PpIX distribution through photobleaching. The light distribution is modelled using a Monte Carlo radiation transfer model and indicates treatment depths of around 2 mm during daylight PDT and approximately 3 mm during conventional PDT. The results suggest that treatment depths are not only limited by the light penetration but also by the PpIX distribution.

  1. Situational effects of the school factors included in the dynamic model of educational effectiveness

    Directory of Open Access Journals (Sweden)

    Bert Creemers

    2009-08-01

    Full Text Available We present results of a longitudinal study in which 50 schools, 113 classes and 2,542 Cypriot primary students participated. We tested the validity of the dynamic model of educational effectiveness and especially its assumption that the impact of school factors depends on the current situation of the school and on the type of problems/difficulties the school is facing. Reference is made to the methods used to test this assumption of the dynamic model by measuring school effectiveness in mathematics, Greek language, and religious education over two consecutive school years. The main findings are as follows. School factors were found to have situational effects. Specifically, the development of a school policy for teaching and the school evaluation of policy for teaching were found to have stronger effects in schools where the quality of teaching at classroom level was low. Moreover, time stability in the effectiveness status of schools was identified and thereby changes in the functioning of schools were found not to have a significant impact on changes in the effectiveness status of schools. Implications of the findings for the development of the dynamic model and suggestions for further research are presented.

  2. Comparison of lead isotopes with source apportionment models, including SOM, for air particulates

    International Nuclear Information System (INIS)

    Gulson, Brian; Korsch, Michael; Dickson, Bruce; Cohen, David; Mizon, Karen; Michael Davis, J.

    2007-01-01

    We have measured high precision lead isotopes in PM 2.5 particulates from a highly-trafficked site (Mascot) and rural site (Richmond) in the Sydney Basin, New South Wales, Australia to compare with isotopic data from total suspended particulates (TSP) from other sites in the Sydney Basin and evaluate relationships with source fingerprints obtained from multi-element PM 2.5 data. The isotopic data for the period 1998 to 2004 show seasonal peaks and troughs that are more pronounced in the rural site for the PM 2.5 .samples but are consistent with the TSP. The Self Organising Map (SOM) method has been applied to the multi-element PM 2.5 data to evaluate its use in obtaining fingerprints for comparison with standard statistical procedures (ANSTO model). As seasonal effects are also significant for the multi-element data, the SOM modelling is reported as site and season dependent. At the Mascot site, the ANSTO model exhibits decreasing 206 Pb/ 204 Pb ratios with increasing contributions of fingerprints for 'secondary smoke' (industry), 'soil', 'smoke' and 'seaspray'. Similar patterns were shown by SOM winter fingerprints for both sites. At the rural site, there are large isotopic variations but for the majority of samples these are not associated with increased contributions from the main sources with the ANSTO model. For two winter sampling times, there are increased contributions from 'secondary industry', 'smoke', 'soil' and seaspray with one time having a source or sources of Pb similar to that of Mascot. The only positive relationship between increasing 206 Pb/ 204 Pb ratio and source contributions is found at the rural site using the SOM summer fingerprints, both of which show a significant contribution from sulphur. Several of the fingerprints using either model have significant contributions from black carbon (BC) and/or sulphur (S) that probably derive from diesel fuels and industrial sources. Increased contributions from sources with the SOM summer

  3. Development of a Murine Model for Aerosolized Ebolavirus Infection Using a Panel of Recombinant Inbred Mice

    Directory of Open Access Journals (Sweden)

    Malak Kotb

    2012-12-01

    Full Text Available Countering aerosolized filovirus infection is a major priority of biodefense research.  Aerosol models of filovirus infection have been developed in knock-out mice, guinea pigs and non-human primates; however, filovirus infection of immunocompetent mice by the aerosol route has not been reported.  A murine model of aerosolized filovirus infection in mice should be useful for screening vaccine candidates and therapies.  In this study, various strains of wild-type and immunocompromised mice were exposed to aerosolized wild-type (WT or mouse-adapted (MA Ebola virus (EBOV.  Upon exposure to aerosolized WT-EBOV, BALB/c, C57BL/6 (B6, and DBA/2 (D2 mice were unaffected, but 100% of severe combined immunodeficiency (SCID and 90% of signal transducers and activators of transcription (Stat1 knock-out (KO mice became moribund between 7–9 days post-exposure (dpe.  Exposure to MA-EBOV caused 15% body weight loss in BALB/c, but all mice recovered.  In contrast, 10–30% lethality was observed in B6 and D2 mice exposed to aerosolized MA-EBOV, and 100% of SCID, Stat1 KO, interferon (IFN-γ KO and Perforin KO mice became moribund between 7–14 dpe. In order to identify wild-type, inbred, mouse strains in which exposure to aerosolized MA-EBOV is uniformly lethal, 60 BXD (C57BL/6 crossed with DBA/2 recombinant inbred (RI and advanced RI (ARI mouse strains were exposed to aerosolized MA-EBOV, and monitored for disease severity. A complete spectrum of disease severity was observed. All BXD strains lost weight but many recovered. However, infection was uniformly lethal within 7 to 12 days post-exposure in five BXD strains.  Aerosol exposure of these five BXD strains to 10-fold less MA-EBOV resulted in lethality ranging from 0% in two strains to 90–100% lethality in two strains.  Analysis of post-mortem tissue from BXD strains that became moribund and were euthanized at the lower dose of MA-EBOV, showed liver damage in all mice as well as lung lesions in

  4. Development of an in vivo model of Chlamydia abortus chronic infection in mice overexpressing IL-10.

    Science.gov (United States)

    Del Río, Laura; Murcia, Antonio; Buendía, Antonio J; Álvarez, Daniel; Ortega, Nieves; Navarro, José A; Salinas, Jesús; Caro, María Rosa

    2018-01-01

    Chlamydia abortus, like other members of the family Chlamydiaceae, have a unique intracellular developmental cycle that is characterized by its chronic nature. Infection of a flock can remain undetected for months, until abortion occurs the following reproductive season but, to date, neither the location nor the mechanisms that maintain this latent phase are fully understood. Studies have shown that IL-10 produced as a response to certain micro-organisms sustains the intracellular survival of pathogens and increases host susceptibility to chlamydial infections. In order to induce a sustained infection C. abortus, transgenic mice that constitutively express IL-10 were infected and the immunological mechanisms that maintain infection in these mice were compared with the mechanisms of a resistant wild-type mouse strain. Viable bacteria could be detected in different tissues of transgenic mice up to 28 days after infection, as analysed by bacterial isolation and immunohistochemistry. Chronic infection in these mice was associated with an impaired recruitment of macrophages, decreased iNOS activity at the site of infection and a more diffuse distribution of inflammatory cells in the liver. This murine model can be of great help for understanding the immunological and bacterial mechanisms that lead to chronic chlamydial infections. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Deficient Purposeful Use of Forepaws in Female Mice Modelling Rett Syndrome

    Directory of Open Access Journals (Sweden)

    Bianca De Filippis

    2015-01-01

    Full Text Available Rett syndrome (RTT is a rare neurodevelopmental disorder, characterized by severe behavioural and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2 cause more than 95% of classic cases. Motor abnormalities represent a significant part of the spectrum of RTT symptoms. In the present study we investigated motor coordination and fine motor skill domains in MeCP2-308 female mice, a validated RTT model. This was complemented by the in vivo magnetic resonance spectroscopy (MRS analysis of metabolic profile in behaviourally relevant brain areas. MeCP2-308 heterozygous female mice (Het, 10-12 months of age were impaired in tasks validated for the assessment of purposeful and coordinated forepaw use (Morag test and Capellini handling task. A fine-grain analysis of spontaneous behaviour in the home-cage also revealed an abnormal handling pattern when interacting with the nesting material, reduced motivation to explore the environment, and increased time devoted to feeding in Het mice. The brain MRS evaluation highlighted decreased levels of bioenergetic metabolites in the striatal area in Het mice compared to controls. Present results confirm behavioural and brain alterations previously reported in MeCP2-308 males and identify novel endpoints on which the efficacy of innovative therapeutic strategies for RTT may be tested.

  6. Extending Galactic Habitable Zone Modeling to Include the Emergence of Intelligent Life.

    Science.gov (United States)

    Morrison, Ian S; Gowanlock, Michael G

    2015-08-01

    Previous studies of the galactic habitable zone have been concerned with identifying those regions of the Galaxy that may favor the emergence of complex life. A planet is deemed habitable if it meets a set of assumed criteria for supporting the emergence of such complex life. In this work, we extend the assessment of habitability to consider the potential for life to further evolve to the point of intelligence--termed the propensity for the emergence of intelligent life, φI. We assume φI is strongly influenced by the time durations available for evolutionary processes to proceed undisturbed by the sterilizing effects of nearby supernovae. The times between supernova events provide windows of opportunity for the evolution of intelligence. We developed a model that allows us to analyze these window times to generate a metric for φI, and we examine here the spatial and temporal variation of this metric. Even under the assumption that long time durations are required between sterilizations to allow for the emergence of intelligence, our model suggests that the inner Galaxy provides the greatest number of opportunities for intelligence to arise. This is due to the substantially higher number density of habitable planets in this region, which outweighs the effects of a higher supernova rate in the region. Our model also shows that φI is increasing with time. Intelligent life emerged at approximately the present time at Earth's galactocentric radius, but a similar level of evolutionary opportunity was available in the inner Galaxy more than 2 Gyr ago. Our findings suggest that the inner Galaxy should logically be a prime target region for searches for extraterrestrial intelligence and that any civilizations that may have emerged there are potentially much older than our own.

  7. porewater chemistry experiment at Mont Terri rock laboratory. Reactive transport modelling including bacterial activity

    International Nuclear Information System (INIS)

    Tournassat, Christophe; Gaucher, Eric C.; Leupin, Olivier X.; Wersin, Paul

    2010-01-01

    Document available in extended abstract form only. An in-situ test in the Opalinus Clay formation, termed pore water Chemistry (PC) experiment, was run for a period of five years. It was based on the concept of diffusive equilibration whereby traced water with a composition close to that expected in the formation was continuously circulated and monitored in a packed off borehole. The main original focus was to obtain reliable data on the pH/pCO 2 of the pore water, but because of unexpected microbially- induced redox reactions, the objective was then changed to elucidate the biogeochemical processes happening in the borehole and to understand their impact on pH/pCO 2 and pH in the low permeability clay formation. The biologically perturbed chemical evolution of the PC experiment was simulated with reactive transport models. The aim of this modelling exercise was to develop a 'minimal-' model able to reproduce the chemical evolution of the PC experiment, i.e. the chemical evolution of solute inorganic and organic compounds (organic carbon, dissolved inorganic carbon etc...) that are coupled with each other through the simultaneous occurrence of biological transformation of solute or solid compounds, in-diffusion and out-diffusion of solute species and precipitation/dissolution of minerals (in the borehole and in the formation). An accurate description of the initial chemical conditions in the surrounding formation together with simplified kinetics rule mimicking the different phases of bacterial activities allowed reproducing the evolution of all main measured parameters (e.g. pH, TOC). Analyses from the overcoring and these simulations evidence the high buffer capacity of Opalinus clay regarding chemical perturbations due to bacterial activity. This pH buffering capacity is mainly attributed to the carbonate system as well as to the clay surfaces reactivity. Glycerol leaching from the pH-electrode might be the primary organic source responsible for

  8. Coupled modeling of land hydrology–regional climate including human carbon emission and water exploitation

    Directory of Open Access Journals (Sweden)

    Zheng-Hui Xie

    2017-06-01

    Full Text Available Carbon emissions and water use are two major kinds of human activities. To reveal whether these two activities can modify the hydrological cycle and climate system in China, we conducted two sets of numerical experiments using regional climate model RegCM4. In the first experiment used to study the climatic responses to human carbon emissions, the model were configured over entire China because the impacts of carbon emissions can be detected across the whole country. Results from the first experiment revealed that near-surface air temperature may significantly increase from 2007 to 2059 at a rate exceeding 0.1 °C per decade in most areas across the country; southwestern and southeastern China also showed increasing trends in summer precipitation, with rates exceeding 10 mm per decade over the same period. In summer, only northern China showed an increasing trend of evapotranspiration, with increase rates ranging from 1 to 5 mm per decade; in winter, increase rates ranging from 1 to 5 mm per decade were observed in most regions. These effects are believed to be caused by global warming from human carbon emissions. In the second experiment used to study the effects of human water use, the model were configured over a limited region—Haihe River Basin in the northern China, because compared with the human carbon emissions, the effects of human water use are much more local and regional, and the Haihe River Basin is the most typical region in China that suffers from both intensive human groundwater exploitation and surface water diversion. We incorporated a scheme of human water regulation into RegCM4 and conducted the second experiment. Model outputs showed that the groundwater table severely declined by ∼10 m in 1971–2000 through human groundwater over-exploitation in the basin; in fact, current conditions are so extreme that even reducing the pumping rate by half cannot eliminate the groundwater depletion cones observed in the area

  9. Able but unintelligent: including positively stereotyped black subgroups in the stereotype content model.

    Science.gov (United States)

    Walzer, Amy S; Czopp, Alexander M

    2011-01-01

    The stereotype content model (SCM) posits that warmth and competence are the key components underlying judgments about social groups. Because competence can encompass different components (e.g., intelligence, talent) different group members may be perceived to be competent for different reasons. Therefore, we believe it may be important to specify the type of competence being assessed when examining perceptions of groups that are positively stereotyped (i.e., Black athletes and musical Blacks). Consistent with the SCM, these subgroups were perceived as high in competence-talent but not in competence-intelligence and low in warmth. Both the intelligence and talent frame of competence fit in the SCM's social structural hypothesis.

  10. Description and Application of A Model of Seepage under A Weir Including Mechanical Clogging

    Directory of Open Access Journals (Sweden)

    Sroka Zbigniew

    2014-07-01

    Full Text Available The paper discusses seepage flow under a damming structure (a weir in view of mechanical clogging in a thin layer at the upstream site. It was assumed that in this layer flow may be treated as one-dimensional (perpendicular to the layer, while elsewhere flow was modelled as two-dimensional. The solution in both zones was obtained in the discrete form using the finite element method and the Euler method. The effect of the clogging layer on seepage flow was modelled using the third kind boundary condition. Seepage parameters in the clogging layer were estimated based on laboratory tests conducted by Skolasińska [2006]. Typical problem was taken to provide simulation and indicate how clogging affects the seepage rate and other parameters of the flow. Results showed that clogging at the upstream site has a significant effect on the distribution of seepage velocity and hydraulic gradients. The flow underneath the structure decreases with time, but these changes are relatively slow.

  11. Modeling radiation dosimetry to predict cognitive outcomes in pediatric patients with CNS embryonal tumors including medulloblastoma

    International Nuclear Information System (INIS)

    Merchant, Thomas E.; Kiehna, Erin N.; Li Chenghong; Shukla, Hemant; Sengupta, Saikat; Xiong Xiaoping; Gajjar, Amar; Mulhern, Raymond K.

    2006-01-01

    Purpose: Model the effects of radiation dosimetry on IQ among pediatric patients with central nervous system (CNS) tumors. Methods and Materials: Pediatric patients with CNS embryonal tumors (n = 39) were prospectively evaluated with serial cognitive testing, before and after treatment with postoperative, risk-adapted craniospinal irradiation (CSI) and conformal primary-site irradiation, followed by chemotherapy. Differential dose-volume data for 5 brain volumes (total brain, supratentorial brain, infratentorial brain, and left and right temporal lobes) were correlated with IQ after surgery and at follow-up by use of linear regression. Results: When the dose distribution was partitioned into 2 levels, both had a significantly negative effect on longitudinal IQ across all 5 brain volumes. When the dose distribution was partitioned into 3 levels (low, medium, and high), exposure to the supratentorial brain appeared to have the most significant impact. For most models, each Gy of exposure had a similar effect on IQ decline, regardless of dose level. Conclusions: Our results suggest that radiation dosimetry data from 5 brain volumes can be used to predict decline in longitudinal IQ. Despite measures to reduce radiation dose and treatment volume, the volume that receives the highest dose continues to have the greatest effect, which supports current volume-reduction efforts

  12. An Improved Heat Budget Estimation Including Bottom Effects for General Ocean Circulation Models

    Science.gov (United States)

    Carder, Kendall; Warrior, Hari; Otis, Daniel; Chen, R. F.

    2001-01-01

    This paper studies the effects of the underwater light field on heat-budget calculations of general ocean circulation models for shallow waters. The presence of a bottom significantly alters the estimated heat budget in shallow waters, which affects the corresponding thermal stratification and hence modifies the circulation. Based on the data collected during the COBOP field experiment near the Bahamas, we have used a one-dimensional turbulence closure model to show the influence of the bottom reflection and absorption on the sea surface temperature field. The water depth has an almost one-to-one correlation with the temperature rise. Effects of varying the bottom albedo by replacing the sea grass bed with a coral sand bottom, also has an appreciable effect on the heat budget of the shallow regions. We believe that the differences in the heat budget for the shallow areas will have an influence on the local circulation processes and especially on the evaporative and long-wave heat losses for these areas. The ultimate effects on humidity and cloudiness of the region are expected to be significant as well.

  13. On the modelling of semi-insulating GaAs including surface tension and bulk stresses

    Energy Technology Data Exchange (ETDEWEB)

    Dreyer, W.; Duderstadt, F.

    2004-07-01

    Necessary heat treatment of single crystal semi-insulating Gallium Arsenide (GaAs), which is deployed in micro- and opto- electronic devices, generate undesirable liquid precipitates in the solid phase. The appearance of precipitates is influenced by surface tension at the liquid/solid interface and deviatoric stresses in the solid. The central quantity for the description of the various aspects of phase transitions is the chemical potential, which can be additively decomposed into a chemical and a mechanical part. In particular the calculation of the mechanical part of the chemical potential is of crucial importance. We determine the chemical potential in the framework of the St. Venant-Kirchhoff law which gives an appropriate stress/strain relation for many solids in the small strain regime. We establish criteria, which allow the correct replacement of the St. Venant-Kirchhoff law by the simpler Hooke law. The main objectives of this study are: (i) We develop a thermo-mechanical model that describes diffusion and interface motion, which both are strongly influenced by surface tension effects and deviatoric stresses. (ii) We give an overview and outlook on problems that can be posed and solved within the framework of the model. (iii) We calculate non-standard phase diagrams, i.e. those that take into account surface tension and non-deviatoric stresses, for GaAs above 786 C, and we compare the results with classical phase diagrams without these phenomena. (orig.)

  14. Effect of neurosteroids on a model lipid bilayer including cholesterol: An Atomic Force Microscopy study.

    Science.gov (United States)

    Sacchi, Mattia; Balleza, Daniel; Vena, Giulia; Puia, Giulia; Facci, Paolo; Alessandrini, Andrea

    2015-05-01

    Amphiphilic molecules which have a biological effect on specific membrane proteins, could also affect lipid bilayer properties possibly resulting in a modulation of the overall membrane behavior. In light of this consideration, it is important to study the possible effects of amphiphilic molecule of pharmacological interest on model systems which recapitulate some of the main properties of the biological plasma membranes. In this work we studied the effect of a neurosteroid, Allopregnanolone (3α,5α-tetrahydroprogesterone or Allo), on a model bilayer composed by the ternary lipid mixture DOPC/bSM/chol. We chose ternary mixtures which present, at room temperature, a phase coexistence of liquid ordered (Lo) and liquid disordered (Ld) domains and which reside near to a critical point. We found that Allo, which is able to strongly partition in the lipid bilayer, induces a marked increase in the bilayer area and modifies the relative proportion of the two phases favoring the Ld phase. We also found that the neurosteroid shifts the miscibility temperature to higher values in a way similarly to what happens when the cholesterol concentration is decreased. Interestingly, an isoform of Allo, isoAllopregnanolone (3β,5α-tetrahydroprogesterone or isoAllo), known to inhibit the effects of Allo on GABAA receptors, has an opposite effect on the bilayer properties. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer

    OpenAIRE

    Fonseca-Filho, V. C. N.; Katayama, M. L. H.; Lyra, E. C.; Maria, D. A.; Basso, R. A.; Nonogaki, S.; Guerra, J. M.; Maistro, S.; Góes, J. C. G. S.; Folgueira, M. A. A. K.

    2017-01-01

    Abstract Calcitriol antiproliferative effects were observed in xenografts of breast cancer cell lines, however they were not yet investigated in tumorgrafts, consisting of freshly collected breast cancer samples xenografted into animals. Objectives To establish a tumorgraft model, from freshly collected breast cancer samples, which were directly implanted in nude mice, to study calcitriol effects. Methods Breast cancer samples collected from 12 patients were orthotopically implanted into nu...

  16. Modeling PD pathogenesis in mice: advantages of a chronic MPTP protocol

    OpenAIRE

    Meredith, Gloria E.; Totterdell, Susan; Potashkin, Judith A.; Surmeier, D. James

    2008-01-01

    Formidable challenges for Parkinson's disease (PD) research are to understand the processes underlying nigrostriatal degeneration and how to protect the dopamine neurons. Fundamental research relies on good animal models that demonstrate the pathological hallmarks and motor deficits of PD. Using a chronic regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid (MPTP/p) in mice, dopamine cell loss exceeds 60%, extracellular glutamate is elevated, cytoplasmic inclusions are forme...

  17. Including temperature in a wavefunction description of the dynamics of the quantum Rabi model

    Science.gov (United States)

    Werther, Michael; Grossmann, Frank

    2018-01-01

    We present a wavefunction methodology to account for finite temperature initial conditions in the quantum Rabi model. The approach is based on the Davydov Ansatz together with a statistical sampling of the canonical harmonic oscillator initial density matrix. Equations of motion are gained from a variational principle and numerical results are compared to those of the thermal Hamiltonian approach. For a system consisting of a single spin and a single oscillator and for moderate coupling strength, we compare our new results with full quantum ones as well as with other Davydov-type results based on alternative sampling/summation strategies. All of these perform better than the ones based on the thermal Hamiltonian approach. The best agreement is shown by a Boltzmann weighting of individual eigenstate propagations. Extending this to a bath of many oscillators will, however, be very demanding numerically. The use of any one of the investigated stochastic sampling approaches will then be favorable.

  18. Dynamic Analysis of Thick Plates Including Deep Beams on Elastic Foundations Using Modified Vlasov Model

    Directory of Open Access Journals (Sweden)

    Korhan Ozgan

    2013-01-01

    Full Text Available Dynamic analysis of foundation plate-beam systems with transverse shear deformation is presented using modified Vlasov foundation model. Finite element formulation of the problem is derived by using an 8-node (PBQ8 finite element based on Mindlin plate theory for the plate and a 2-node Hughes element based on Timoshenko beam theory for the beam. Selective reduced integration technique is used to avoid shear locking problem for the evaluation of the stiffness matrices for both the elements. The effect of beam thickness, the aspect ratio of the plate and subsoil depth on the response of plate-beam-soil system is analyzed. Numerical examples show that the displacement, bending moments and shear forces are changed significantly by adding the beams.

  19. Robust and Adaptive OMR System Including Fuzzy Modeling, Fusion of Musical Rules, and Possible Error Detection

    Directory of Open Access Journals (Sweden)

    Bloch Isabelle

    2007-01-01

    Full Text Available This paper describes a system for optical music recognition (OMR in case of monophonic typeset scores. After clarifying the difficulties specific to this domain, we propose appropriate solutions at both image analysis level and high-level interpretation. Thus, a recognition and segmentation method is designed, that allows dealing with common printing defects and numerous symbol interconnections. Then, musical rules are modeled and integrated, in order to make a consistent decision. This high-level interpretation step relies on the fuzzy sets and possibility framework, since it allows dealing with symbol variability, flexibility, and imprecision of music rules, and merging all these heterogeneous pieces of information. Other innovative features are the indication of potential errors and the possibility of applying learning procedures, in order to gain in robustness. Experiments conducted on a large data base show that the proposed method constitutes an interesting contribution to OMR.

  20. Energy-based fatigue model for shape memory alloys including thermomechanical coupling

    Science.gov (United States)

    Zhang, Yahui; Zhu, Jihong; Moumni, Ziad; Van Herpen, Alain; Zhang, Weihong

    2016-03-01

    This paper is aimed at developing a low cycle fatigue criterion for pseudoelastic shape memory alloys to take into account thermomechanical coupling. To this end, fatigue tests are carried out at different loading rates under strain control at room temperature using NiTi wires. Temperature distribution on the specimen is measured using a high speed thermal camera. Specimens are tested to failure and fatigue lifetimes of specimens are measured. Test results show that the fatigue lifetime is greatly influenced by the loading rate: as the strain rate increases, the fatigue lifetime decreases. Furthermore, it is shown that the fatigue cracks initiate when the stored energy inside the material reaches a critical value. An energy-based fatigue criterion is thus proposed as a function of the irreversible hysteresis energy of the stabilized cycle and the loading rate. Fatigue life is calculated using the proposed model. The experimental and computational results compare well.

  1. Areal rainfall estimation using moving cars - computer experiments including hydrological modeling

    Science.gov (United States)

    Rabiei, Ehsan; Haberlandt, Uwe; Sester, Monika; Fitzner, Daniel; Wallner, Markus

    2016-09-01

    The need for high temporal and spatial resolution precipitation data for hydrological analyses has been discussed in several studies. Although rain gauges provide valuable information, a very dense rain gauge network is costly. As a result, several new ideas have emerged to help estimating areal rainfall with higher temporal and spatial resolution. Rabiei et al. (2013) observed that moving cars, called RainCars (RCs), can potentially be a new source of data for measuring rain rate. The optical sensors used in that study are designed for operating the windscreen wipers and showed promising results for rainfall measurement purposes. Their measurement accuracy has been quantified in laboratory experiments. Considering explicitly those errors, the main objective of this study is to investigate the benefit of using RCs for estimating areal rainfall. For that, computer experiments are carried out, where radar rainfall is considered as the reference and the other sources of data, i.e., RCs and rain gauges, are extracted from radar data. Comparing the quality of areal rainfall estimation by RCs with rain gauges and reference data helps to investigate the benefit of the RCs. The value of this additional source of data is not only assessed for areal rainfall estimation performance but also for use in hydrological modeling. Considering measurement errors derived from laboratory experiments, the result shows that the RCs provide useful additional information for areal rainfall estimation as well as for hydrological modeling. Moreover, by testing larger uncertainties for RCs, they observed to be useful up to a certain level for areal rainfall estimation and discharge simulation.

  2. ECO: a generic eutrophication model including comprehensive sediment-water interaction.

    Science.gov (United States)

    Smits, Johannes G C; van Beek, Jan K L

    2013-01-01

    The content and calibration of the comprehensive generic 3D eutrophication model ECO for water and sediment quality is presented. Based on a computational grid for water and sediment, ECO is used as a tool for water quality management to simulate concentrations and mass fluxes of nutrients (N, P, Si), phytoplankton species, detrital organic matter, electron acceptors and related substances. ECO combines integral simulation of water and sediment quality with sediment diagenesis and closed mass balances. Its advanced process formulations for substances in the water column and the bed sediment were developed to allow for a much more dynamic calculation of the sediment-water exchange fluxes of nutrients as resulting from steep concentration gradients across the sediment-water interface than is possible with other eutrophication models. ECO is to more accurately calculate the accumulation of organic matter and nutrients in the sediment, and to allow for more accurate prediction of phytoplankton biomass and water quality in response to mitigative measures such as nutrient load reduction. ECO was calibrated for shallow Lake Veluwe (The Netherlands). Due to restoration measures this lake underwent a transition from hypertrophic conditions to moderately eutrophic conditions, leading to the extensive colonization by submerged macrophytes. ECO reproduces observed water quality well for the transition period of ten years. The values of its process coefficients are in line with ranges derived from literature. ECO's calculation results underline the importance of redox processes and phosphate speciation for the nutrient return fluxes. Among other things, the results suggest that authigenic formation of a stable apatite-like mineral in the sediment can contribute significantly to oligotrophication of a lake after a phosphorus load reduction.

  3. A phantom model demonstration of tomotherapy dose painting delivery, including managed respiratory motion without motion management

    Energy Technology Data Exchange (ETDEWEB)

    Kissick, Michael W; Mo Xiaohu; McCall, Keisha C; Mackie, Thomas R [Department of Medical Physics, Wisconsin Institutes for Medical Research, 111 Highland Avenue, University of Wisconsin-Madison, Madison, WI 53705 (United States); Schubert, Leah K [Radiation Oncology Department, University of Nebraska Medical Center, Omaha, NE 68198 (United States); Westerly, David C, E-mail: mwkissick@wisc.ed [Department of Radiation Oncology, University of Colorado Denver, Aurora, CO 80045 (United States)

    2010-05-21

    The aim of the study was to demonstrate a potential alternative scenario for accurate dose-painting (non-homogeneous planned dose) delivery at 1 cm beam width with helical tomotherapy (HT) in the presence of 1 cm, three-dimensional, intra-fraction respiratory motion, but without any active motion management. A model dose-painting experiment was planned and delivered to the average position (proper phase of a 4DCT scan) with three spherical PTV levels to approximate dose painting to compensate for hypothetical hypoxia in a model lung tumor. Realistic but regular motion was produced with the Washington University 4D Motion Phantom. A small spherical Virtual Water(TM) phantom was used to simulate a moving lung tumor inside of the LUNGMAN(TM) anthropomorphic chest phantom to simulate realistic heterogeneity uncertainties. A piece of 4 cm Gafchromic EBT(TM) film was inserted into the 6 cm diameter sphere. TomoTherapy, Inc., DQA(TM) software was used to verify the delivery performed on a TomoTherapy Hi-Art II(TM) device. The dose uncertainty in the purposeful absence of motion management and in the absence of large, low frequency drifts (periods greater than the beam width divided by the couch velocity) or randomness in the breathing displacement yields very favorable results. Instead of interference effects, only small blurring is observed because of the averaging of many breathing cycles and beamlets and the avoidance of interference. Dose painting during respiration with helical tomotherapy is feasible in certain situations without motion management. A simple recommendation is to make respiration as regular as possible without low frequency drifting. The blurring is just small enough to suggest that it may be acceptable to deliver without motion management if the motion is equal to the beam width or smaller (at respiration frequencies) when registered to the average position.

  4. A phantom model demonstration of tomotherapy dose painting delivery, including managed respiratory motion without motion management

    International Nuclear Information System (INIS)

    Kissick, Michael W; Mo Xiaohu; McCall, Keisha C; Mackie, Thomas R; Schubert, Leah K; Westerly, David C

    2010-01-01

    The aim of the study was to demonstrate a potential alternative scenario for accurate dose-painting (non-homogeneous planned dose) delivery at 1 cm beam width with helical tomotherapy (HT) in the presence of 1 cm, three-dimensional, intra-fraction respiratory motion, but without any active motion management. A model dose-painting experiment was planned and delivered to the average position (proper phase of a 4DCT scan) with three spherical PTV levels to approximate dose painting to compensate for hypothetical hypoxia in a model lung tumor. Realistic but regular motion was produced with the Washington University 4D Motion Phantom. A small spherical Virtual Water(TM) phantom was used to simulate a moving lung tumor inside of the LUNGMAN(TM) anthropomorphic chest phantom to simulate realistic heterogeneity uncertainties. A piece of 4 cm Gafchromic EBT(TM) film was inserted into the 6 cm diameter sphere. TomoTherapy, Inc., DQA(TM) software was used to verify the delivery performed on a TomoTherapy Hi-Art II(TM) device. The dose uncertainty in the purposeful absence of motion management and in the absence of large, low frequency drifts (periods greater than the beam width divided by the couch velocity) or randomness in the breathing displacement yields very favorable results. Instead of interference effects, only small blurring is observed because of the averaging of many breathing cycles and beamlets and the avoidance of interference. Dose painting during respiration with helical tomotherapy is feasible in certain situations without motion management. A simple recommendation is to make respiration as regular as possible without low frequency drifting. The blurring is just small enough to suggest that it may be acceptable to deliver without motion management if the motion is equal to the beam width or smaller (at respiration frequencies) when registered to the average position.

  5. GLAST Deficiency in Mice Exacerbates Gap Detection Deficits in a Model of Salicylate-Induced Tinnitus.

    Science.gov (United States)

    Yu, Hong; Vikhe Patil, Kim; Han, Chul; Fabella, Brian; Canlon, Barbara; Someya, Shinichi; Cederroth, Christopher R

    2016-01-01

    Gap detection or gap pre-pulse inhibition of the acoustic startle (GPIAS) has been successfully used in rat and guinea pig models of tinnitus, yet this system has been proven to have low efficacy in CBA mice, with low basal GPIAS and subtle tinnitus-like effects. Here, we tested five mouse strains (CBA, BalbC, CD-1, C57BL/6 and 129sv) for pre-pulse inhibition (PPI) and gap detection with varying interstimulus intervals (ISI) and found that mice from a CBA genetic background had the poorest capacities of suppressing the startle response in the presence of a pre-pulse or a gap. CD-1 mice displayed variable responses throughout all ISI. Interestingly, C57BL/6, 129sv and BalbC showed efficient suppression with either pre-pulses or gaps with shorter ISI. The glutamate aspartate transporter (GLAST) is expressed in support cells from the cochlea and buffers the excess of glutamate. We hypothesized that loss of GLAST function could sensitize the ear to tinnitus-inducing agents, such as salicylate. Using shorter ISI to obtain a greater dynamic range to assess tinnitus-like effects, we found that disruption of gap detection by salicylate was exacerbated across various intensities of a 32-kHz narrow band noise gap carrier in GLAST knockout (KO) mice when compared to their wild-type (WT) littermates. Auditory brainstem responses (ABR) and distortion-product otoacoustic emission (DPOAE) were performed to evaluate the effects on hearing functions. Salicylate caused greater auditory threshold shifts (near 15 dB) in GLAST KO mice than in WT mice across all tested frequencies, despite similarly reduced DPOAE. Despite these changes, inhibition using broad-band gap carriers and 32 kHz pre-pulses were not affected. Our study suggests that GLAST deficiency could become a useful experimental model to decipher the mechanisms underlying drug-induced tinnitus. Future studies addressing the neurological correlates of tinnitus in this model could provide additional insights into the

  6. GLAST Deficiency in Mice Exacerbates Gap Detection Deficits in a Model of Salicylate-Induced Tinnitus

    Science.gov (United States)

    Yu, Hong; Vikhe Patil, Kim; Han, Chul; Fabella, Brian; Canlon, Barbara; Someya, Shinichi; Cederroth, Christopher R.

    2016-01-01

    Gap detection or gap pre-pulse inhibition of the acoustic startle (GPIAS) has been successfully used in rat and guinea pig models of tinnitus, yet this system has been proven to have low efficacy in CBA mice, with low basal GPIAS and subtle tinnitus-like effects. Here, we tested five mouse strains (CBA, BalbC, CD-1, C57BL/6 and 129sv) for pre-pulse inhibition (PPI) and gap detection with varying interstimulus intervals (ISI) and found that mice from a CBA genetic background had the poorest capacities of suppressing the startle response in the presence of a pre-pulse or a gap. CD-1 mice displayed variable responses throughout all ISI. Interestingly, C57BL/6, 129sv and BalbC showed efficient suppression with either pre-pulses or gaps with shorter ISI. The glutamate aspartate transporter (GLAST) is expressed in support cells from the cochlea and buffers the excess of glutamate. We hypothesized that loss of GLAST function could sensitize the ear to tinnitus-inducing agents, such as salicylate. Using shorter ISI to obtain a greater dynamic range to assess tinnitus-like effects, we found that disruption of gap detection by salicylate was exacerbated across various intensities of a 32-kHz narrow band noise gap carrier in GLAST knockout (KO) mice when compared to their wild-type (WT) littermates. Auditory brainstem responses (ABR) and distortion-product otoacoustic emission (DPOAE) were performed to evaluate the effects on hearing functions. Salicylate caused greater auditory threshold shifts (near 15 dB) in GLAST KO mice than in WT mice across all tested frequencies, despite similarly reduced DPOAE. Despite these changes, inhibition using broad-band gap carriers and 32 kHz pre-pulses were not affected. Our study suggests that GLAST deficiency could become a useful experimental model to decipher the mechanisms underlying drug-induced tinnitus. Future studies addressing the neurological correlates of tinnitus in this model could provide additional insights into the

  7. Improvement in genetic evaluation of female fertility in dairy cattle using multiple-trait models including milk production traits

    DEFF Research Database (Denmark)

    Sun, C; Madsen, P; Lund, M S

    2010-01-01

    This study investigated the improvement in genetic evaluation of fertility traits by using production traits as secondary traits (MILK = 305-d milk yield, FAT = 305-d fat yield, and PROT = 305-d protein yield). Data including 471,742 records from first lactations of Denmark Holstein cows, covering...... (DATAC1, which only contained the first crop daughters) for proven bulls. In addition, the superiority of the models was evaluated by expected reliability of EBV, calculated from the prediction error variance of EBV. Based on these criteria, the models combining milk production traits showed better model...... stability and predictive ability than single-trait models for all the fertility traits, except for nonreturn rate within 56 d after first service. The stability and predictive ability for the model including MILK or PROT were similar to the model including all 3 milk production traits and better than...

  8. Reversible control by vitamin D of granulocytes and bacteria in the lungs of mice: an ovalbumin-induced model of allergic airway disease.

    Science.gov (United States)

    Gorman, Shelley; Weeden, Clare E; Tan, Daryl H W; Scott, Naomi M; Hart, Julie; Foong, Rachel E; Mok, Danny; Stephens, Nahiid; Zosky, Graeme; Hart, Prue H

    2013-01-01

    Vitamin D may be essential for restricting the development and severity of allergic diseases and asthma, but a direct causal link between vitamin D deficiency and asthma has yet to be established. We have developed a 'low dose' model of allergic airway disease induced by intraperitoneal injection with ovalbumin (1 µg) and aluminium hydroxide (0.2 mg) in which characteristics of atopic asthma are recapitulated, including airway hyperresponsiveness, antigen-specific immunoglobulin type-E and lung inflammation. We assessed the effects of vitamin D deficiency throughout life (from conception until adulthood) on the severity of ovalbumin-induced allergic airway disease in vitamin D-replete and -deficient BALB/c mice using this model. Vitamin D had protective effects such that deficiency significantly enhanced eosinophil and neutrophil numbers in the bronchoalveolar lavage fluid of male but not female mice. Vitamin D also suppressed the proliferation and T helper cell type-2 cytokine-secreting capacity of airway-draining lymph node cells from both male and female mice. Supplementation of initially vitamin D-deficient mice with vitamin D for four weeks returned serum 25-hydroxyvitamin D to levels observed in initially vitamin D-replete mice, and also suppressed eosinophil and neutrophil numbers in the bronchoalveolar lavage fluid of male mice. Using generic 16 S rRNA primers, increased bacterial levels were detected in the lungs of initially vitamin D-deficient male mice, which were also reduced by vitamin D supplementation. These results indicate that vitamin D controls granulocyte levels in the bronchoalveolar lavage fluid in an allergen-sensitive manner, and may contribute towards the severity of asthma in a gender-specific fashion through regulation of respiratory bacteria.

  9. Regional modelling of future African climate north of 15S including greenhouse warming and land degradation

    Energy Technology Data Exchange (ETDEWEB)

    Paeth, H. [Geographical Institute, University of Wuerzburg, Am Hubland, 97074 Wuerzburg (Germany); Thamm, H.P. [Geographical Institute, University of Bonn, Bonn (Germany)

    2007-08-15

    Previous studies have highlighted the crucial role of land degradation in tropical African climate. This effect urgently has to be taken into account when predicting future African climate under enhanced greenhouse conditions. Here, we present time slice experiments of African climate until 2025, using a high-resolution regional climate model. A supposable scenario of future land use changes, involving vegetation loss and soil degradation, is prescribed simultaneously with increasing greenhouse-gas concentrations in order to detect, where the different forcings counterbalance or reinforce each other. This proceeding allows us to define the regions of highest vulnerability with respect to future freshwater availability and food security in tropical and subtropical Africa and may provide a decision basis for political measures. The model simulates a considerable reduction in precipitation amount until 2025 over most of tropical Africa, amounting to partly more than 500 mm (20-40% of the annual sum), particularly in the Congo Basin and the Sahel Zone. The change is strongest in boreal summer and basically reflects the pattern of maximum vegetation cover during the seasonal cycle. The related change in the surface energy fluxes induces a substantial near-surface warming by up to 7C. According to the modified temperature gradients over tropical Africa, the summer monsoon circulation intensifies and transports more humid air masses into the southern part of West Africa. This humidifying effect is overcompensated by a remarkable decrease in surface evaporation, leading to the overall drying tendency over most of Africa. Extreme daily rainfall events become stronger in autumn but less intense in spring. Summer and autumn appear to be characterized by more severe heat waves over Subsaharan West Africa. In addition, the Tropical Easterly Jet is weakening, leading to enhanced drought conditions in the Sahel Zone. All these results suggest that the local impact of land

  10. Immunomodulation Effects of Bryophyllum Pinnatum on Pregnant Pristane-Induced Lupus Mice Model

    Directory of Open Access Journals (Sweden)

    Nurdiana Nurdiana

    2017-03-01

    Full Text Available Objective: To determine the effect of Bryophyllum pinnatum treatment in modulating immune response and the pregnancy outcomes of pregnant pristane-induced lupus mice model. Methods: Sixteen Balb/c mice were intraperitoneally injected with single 0.5 cc pristane to induce lupus manifestations. After 12 weeks of injection, mice were mated and considered as gestational day 0 (GD0. Mice were divided into 4 groups based on the dosages of Bryophyllum pinnatum: control (no treatment, B1 (10.5 mg/kg, B2 (21 mg/kg, and B3 (42 mg/kg. The treatment was given orally every day started from GD9 until 9 days. At the end of the study, blood pressure and fetal size were measured. Serum anti-dsDNA and urine albumin levels were measured by ELISA. Spleen T helper (Th and mature B cells percentages were measured by flow cytometry. Results: Administration of Bryophyllum pinnatum reduced the percentages of Th1 (p=0.006, Th2 (p=0.005, Th17 (p=0.000, and mature B cells (p=0.007 in dose-dependent manner. B1 and B2 had significantly lower of systolic blood pressure compared to control (p=0.026 and p=0.022 respectively. Significantly lower of anti-dsDNA levels were found in B1 group compared to control (p=0.014. However, no significantly different of urine albumin levels were found between groups. Bryophyllum pinnatum also significantly increased the fetus body weight in dose-dependent manner (p=0.000. Conclusion: Treatment of Bryophyllum pinnatum could improve the pregnancy outcome and modulate the immune response in pregnant pristane-induced lupus mice. Therefore, Bryophyllum pinnatum is a potential herb which can be developed as an immunosuppressive agent in the future.

  11. Study of the involvement of allogeneic MSCs in bone formation using the model of transgenic mice.

    Science.gov (United States)

    Kuznetsova, Daria; Prodanets, Natalia; Rodimova, Svetlana; Antonov, Evgeny; Meleshina, Aleksandra; Timashev, Peter; Zagaynova, Elena

    2017-05-04

    Mesenchymal stem cells (MSCs) are thought to be the most attractive type of cells for bone repair. However, much still remains unknown about MSCs and needs to be clarified before this treatment can be widely applied in the clinical practice. The purpose of this study was to establish the involvement of allogeneic MSCs in the bone formation in vivo, using a model of transgenic mice and genetically labeled cells. Polylactide scaffolds with hydroxyapatite obtained by surface selective laser sintering were used. The scaffolds were sterilized and individually seeded with MSCs from the bone marrow of 5-week-old GFP(+) transgenic C57/Bl6 or GFP(-)C57/Bl6 mice. 4-mm-diameter critical-size defects were created on the calvarial bone of mice using a dental bur. Immediately after the generation of the cranial bone defects, the scaffolds with or without seeded cells were implanted into the injury sites. The cranial bones were harvested at either 6 or 12 weeks after the implantation. GFP(+) transgenic mice having scaffolds with unlabeled MSCs were used for the observation of the host cell migration into the scaffold. GFP(-) mice having scaffolds with GFP(+)MSCs were used to assess the functioning of the seeded MSCs. The obtained data demonstrated that allogeneic MSCs were found on the scaffolds 6 and 12 weeks post-implantation. By week 12, a newly formed bone tissue from the seeded cells was observed, without an osteogenic pre-differentiation. The host cells did not appear, and the control scaffolds without seeded cells remained empty. Besides, a possibility of vessel formation from seeded MSCs was shown, without a preliminary cell cultivation under controlled conditions.

  12. [Changes of ocular biological parameters and Lumican expression in the monocularly deprivation myopic model of mutant Lumican transgenic mice].

    Science.gov (United States)

    Sun, M S; Song, Y Z; Zhang, F J; Tao, J; Liu, Y B

    2016-11-11

    Objective: To investigate ocular changes in the monocularly deprivation myopic model of mutant Lumican transgenic mice. Comparing influences on biological parameters and sclera development between Lumican transgenic and form deprivation mice, and to prepare for further study of pathogenesis of pathological myopia (PM). Methods: Experimental research. Lumican transgenic mice and wild mice were monocularly lid-sutured at ten days after birth. All eyes were divided into 6 groups, group A(32 eyes): control eyes in transgenic mice; group B(34 eyes): sutured eyes in transgenic mice; group C(34 eyes): fellow eyes in transgenic mice; group D(28 eyes): control eyes in wild mice; group E(32 eyes): sutured eyes in wild mice; group F(32 eyes): fellow eyes in wild mice. Refraction was measured by streak retinoscopye and axial length was measured by vernier caliper at 8 weeks (56 days) after birth. Lumican expression was detected by quantitative real-time PCR in all groups. Results: The refraction in group B and group E were (-0.38±1.10) D and (0.14±1.26)D respectively, which were significantly different compared with contralateral groups and normal control groups ( F= 9.525, 10.067; Ptransgenic mice causes myopic changes in deprived eyes. The gene expression level of Lumican in sclera of transgenic mice is significantly increased compared with contralateral eyes or that of wild group. Lumican mutation may effect the development of PM, and the interaction of genetic and environmental factors may lead to development of PM. (Chin J Ophthalmol, 2016, 52: 850-855) .

  13. Landau quantized dynamics and spectra for group-VI dichalcogenides, including a model quantum wire

    Science.gov (United States)

    Horing, Norman J. M.

    2017-06-01

    This work is concerned with the derivation of the Green's function for Landau-quantized carriers in the Group-VI dichalcogenides. In the spatially homogeneous case, the Green's function is separated into a Peierls phase factor and a translationally invariant part which is determined in a closed form integral representation involving only elementary functions. The latter is expanded in an eigenfunction series of Laguerre polynomials. These results for the retarded Green's function are presented in both position and momentum representations, and yet another closed form representation is derived in circular coordinates in terms of the Bessel wave function of the second kind (not to be confused with the Bessel function). The case of a quantum wire is also addressed, representing the quantum wire in terms of a model one-dimensional δ (x ) -potential profile. This retarded Green's function for propagation directly along the wire is determined exactly in terms of the corresponding Green's function for the system without the δ (x ) -potential, and the Landau quantized eigenenergy dispersion relation is examined. The thermodynamic Green's function for the dichalcogenide carriers in a normal magnetic field is formulated here in terms of its spectral weight, and its solution is presented in a momentum/integral representation involving only elementary functions, which is subsequently expanded in Laguerre eigenfunctions and presented in both momentum and position representations.

  14. Landau quantized dynamics and spectra for group-VI dichalcogenides, including a model quantum wire

    Directory of Open Access Journals (Sweden)

    Norman J. M. Horing

    2017-06-01

    Full Text Available This work is concerned with the derivation of the Green’s function for Landau-quantized carriers in the Group-VI dichalcogenides. In the spatially homogeneous case, the Green’s function is separated into a Peierls phase factor and a translationally invariant part which is determined in a closed form integral representation involving only elementary functions. The latter is expanded in an eigenfunction series of Laguerre polynomials. These results for the retarded Green’s function are presented in both position and momentum representations, and yet another closed form representation is derived in circular coordinates in terms of the Bessel wave function of the second kind (not to be confused with the Bessel function. The case of a quantum wire is also addressed, representing the quantum wire in terms of a model one-dimensional δ(x-potential profile. This retarded Green’s function for propagation directly along the wire is determined exactly in terms of the corresponding Green’s function for the system without the δ(x-potential, and the Landau quantized eigenenergy dispersion relation is examined. The thermodynamic Green’s function for the dichalcogenide carriers in a normal magnetic field is formulated here in terms of its spectral weight, and its solution is presented in a momentum/integral representation involving only elementary functions, which is subsequently expanded in Laguerre eigenfunctions and presented in both momentum and position representations.

  15. Sh3pxd2b mice are a model for craniofacial dysmorphology and otitis media.

    Science.gov (United States)

    Yang, Bin; Tian, Cong; Zhang, Zhi-guang; Han, Feng-chan; Azem, Rami; Yu, Heping; Zheng, Ye; Jin, Ge; Arnold, James E; Zheng, Qing Y

    2011-01-01

    Craniofacial defects that occur through gene mutation during development increase vulnerability to eustachian tube dysfunction. These defects can lead to an increased incidence of otitis media. We examined the effects of a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee)) on the progression of otitis media and hearing impairment at various developmental stages. We found that all mice that had the Sh3pxd2b(nee) mutation went on to develop craniofacial dysmorphologies and subsequently otitis media, by as early as 11 days of age. We found noteworthy changes in cilia and goblet cells of the middle ear mucosa in Sh3pxd2b(nee) mutant mice using scanning electronic microscopy. By measuring craniofacial dimensions, we determined for the first time in an animal model that this mouse has altered eustachian tube morphology consistent with a more horizontal position of the eustachian tube. All mutants were found to have hearing impairment. Expression of TNF-α and TLR2, which correlates with inflammation in otitis media, was up-regulated in the ears of mutant mice when examined by immunohistochemistry and semi-quantitative RT-PCR. The mouse model with a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee)) mirrors craniofacial dysmorphology and otitis media in humans.

  16. Sh3pxd2b mice are a model for craniofacial dysmorphology and otitis media.

    Directory of Open Access Journals (Sweden)

    Bin Yang

    Full Text Available Craniofacial defects that occur through gene mutation during development increase vulnerability to eustachian tube dysfunction. These defects can lead to an increased incidence of otitis media. We examined the effects of a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee on the progression of otitis media and hearing impairment at various developmental stages. We found that all mice that had the Sh3pxd2b(nee mutation went on to develop craniofacial dysmorphologies and subsequently otitis media, by as early as 11 days of age. We found noteworthy changes in cilia and goblet cells of the middle ear mucosa in Sh3pxd2b(nee mutant mice using scanning electronic microscopy. By measuring craniofacial dimensions, we determined for the first time in an animal model that this mouse has altered eustachian tube morphology consistent with a more horizontal position of the eustachian tube. All mutants were found to have hearing impairment. Expression of TNF-α and TLR2, which correlates with inflammation in otitis media, was up-regulated in the ears of mutant mice when examined by immunohistochemistry and semi-quantitative RT-PCR. The mouse model with a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee mirrors craniofacial dysmorphology and otitis media in humans.

  17. Salivary Gland Dysplasia in Fgf10 Heterozygous Mice: A New Mouse Model of Xerostomia

    Science.gov (United States)

    May, A.J.; Chatzeli, L.; Proctor, G.B.; Tucker, A.S.

    2017-01-01

    Xerostomia, or chronic dry mouth, is a common syndrome caused by a lack of saliva that can lead to severe eating difficulties, dental caries and oral candida infections. The prevalence of xerostomia increases with age and affects approximately 30% of people aged 65 or older. Given the large numbers of sufferers, and the potential increase in incidence given our aging population, it is important to understand the complex mechanisms that drive hyposalivation and the consequences for the dentition and oral mucosa. From this study we propose the Fgf10 +/- mouse as a model to investigate xerostomia. By following embryonic salivary gland development, in vivo and in vitro, we show that a reduction in Fgf10 causes a delay in branching of salivary glands. This leads to hypoplasia of the glands, a phenotype that is not rescued postnatally or by adulthood in both male and female Fgf10 +/- mice. Histological analysis of the glands showed no obvious defect in cellular differentiation or acini/ductal arrangements, however there was a significant reduction in their size and weight. Analysis of saliva secretion showed that hypoplasia of the glands led to a significant reduction in saliva production in Fgf10 +/- adults, giving rise to a reduced saliva pellicle in the oral cavity of these mice. Mature mice were shown to drink more and in many cases had severe tooth wear. The Fgf10 +/- mouse is therefore a useful model to explore the causes and effects of xerostomia. PMID:26321752

  18. Regulatory T cell activity in immunosuppresive mice model of pseudomonas aeruginosa pneumonia.

    Science.gov (United States)

    Li, Jun-Lu; Chen, Ting-Sang; Yuan, Cong-Cong; Zhao, Guo-Qiang; Xu, Min; Li, Xiao-Yan; Cao, Jie; Xing, Li-Hua

    2017-08-01

    Pseudomonas aeruginosa (PA) pneumonia is a refractory, even lethal complication in immunosuppressive individuals and immune disturbances may promote the pathological process. We aimed to investigate the regulatory T (Treg) cell activity in an immunosuppressive mice model of PA pneumonia by estimating levels of main transcription factor and the main effector of Treg cells, i.e., Forkhead box protein 3 (FOXP3) and interleukine-10 (IL-10). Seventy-two BALB/c mice were divided into four groups randomly: control (A), PA pneumonia (B), immunosuppression (C) and immunosuppression with PA pneumonia (D). Mice were sacrificed at 4, 8 and 24 h after establishing experimental models. The pathological changes of lung tissue were graded, and the FOXP3 mRNA and serum IL-10 levels were detected. Histological analysis of lung tissues showed there were no significantly pathological changes in groups A and C, but significantly pathological changes were found in groups B and D, especially in group D at 8 h (Ppneumonia in immunosuppressive individuals worsens rapidly, which may be associated with Treg cells function disturbance. And Treg cells may be promising as adjuvant therapeutics for PA pneumonia in immunosuppressive individuals.

  19. Evaluation of bone quality in osteoporosis model mice by Raman spectroscopy

    Science.gov (United States)

    Ishimaru, Yasumitsu; Oshima, Yusuke; Imai, Yuuki; Iimura, Tadahiro; Takanezawa, Sota; Hino, Kazunori; Miura, Hiromasa

    2017-04-01

    To evaluate the bone quality in the osteoporosis, we generated sciatic nerve resection (NX) mice as an osteoporosis model and analyzed by Raman spectroscopy. Raman spectra were measured in anterior cortical surface of the proximal tibia at 5 points in each bone. After that, the samples were fixed with 70% ethanol. We then performed DXA and μCT measurement. Raman peak intensity ratios were significantly different between NX and Control. Those changes in the Raman peak intensity ratios may reflect loss of bone quality in the osteoporosis model. Raman spectroscopy is a promising technique for measuring the bone quality and bone strength.

  20. Neuropharmacological Profile of Extracts of Aerial Parts of Convolvulus pluricaulis Choisy in Mice Model.

    Science.gov (United States)

    Siddiqui, Nasir A; Ahmad, Nihal; Musthaq, Nazia; Chattopadhyaya, Ipshita; Kumria, Rachna; Gupta, Sumeet

    2014-01-01

    The plant of Convolvulus pluricaulis Choisy was found to be used by different traditional systems and folklore for the treatment of various disorders. The aim of the present study was to investigate the neuropharmacological activity of various extracts of Convolvulus pluricaulis Choisy in albino mice. The animal behavior was evaluated by locomotor activity, tremors activity, sleep inducing model and anxiolytic activity using standard procedures in experimental animal models. The results revealed that ethanolic and aqueous extract showed promising results in terms of statistical manner when compared with control group. In conclusion, this plant exhibits neuorpharmacological activity in tested animals.

  1. Clarifying the use of aggregated exposures in multilevel models: self-included vs. self-excluded measures.

    Directory of Open Access Journals (Sweden)

    Etsuji Suzuki

    Full Text Available Multilevel analyses are ideally suited to assess the effects of ecological (higher level and individual (lower level exposure variables simultaneously. In applying such analyses to measures of ecologies in epidemiological studies, individual variables are usually aggregated into the higher level unit. Typically, the aggregated measure includes responses of every individual belonging to that group (i.e. it constitutes a self-included measure. More recently, researchers have developed an aggregate measure which excludes the response of the individual to whom the aggregate measure is linked (i.e. a self-excluded measure. In this study, we clarify the substantive and technical properties of these two measures when they are used as exposures in multilevel models.Although the differences between the two aggregated measures are mathematically subtle, distinguishing between them is important in terms of the specific scientific questions to be addressed. We then show how these measures can be used in two distinct types of multilevel models-self-included model and self-excluded model-and interpret the parameters in each model by imposing hypothetical interventions. The concept is tested on empirical data of workplace social capital and employees' systolic blood pressure.Researchers assume group-level interventions when using a self-included model, and individual-level interventions when using a self-excluded model. Analytical re-parameterizations of these two models highlight their differences in parameter interpretation. Cluster-mean centered self-included models enable researchers to decompose the collective effect into its within- and between-group components. The benefit of cluster-mean centering procedure is further discussed in terms of hypothetical interventions.When investigating the potential roles of aggregated variables, researchers should carefully explore which type of model-self-included or self-excluded-is suitable for a given situation

  2. Clarifying the use of aggregated exposures in multilevel models: self-included vs. self-excluded measures.

    Science.gov (United States)

    Suzuki, Etsuji; Yamamoto, Eiji; Takao, Soshi; Kawachi, Ichiro; Subramanian, S V

    2012-01-01

    Multilevel analyses are ideally suited to assess the effects of ecological (higher level) and individual (lower level) exposure variables simultaneously. In applying such analyses to measures of ecologies in epidemiological studies, individual variables are usually aggregated into the higher level unit. Typically, the aggregated measure includes responses of every individual belonging to that group (i.e. it constitutes a self-included measure). More recently, researchers have developed an aggregate measure which excludes the response of the individual to whom the aggregate measure is linked (i.e. a self-excluded measure). In this study, we clarify the substantive and technical properties of these two measures when they are used as exposures in multilevel models. Although the differences between the two aggregated measures are mathematically subtle, distinguishing between them is important in terms of the specific scientific questions to be addressed. We then show how these measures can be used in two distinct types of multilevel models-self-included model and self-excluded model-and interpret the parameters in each model by imposing hypothetical interventions. The concept is tested on empirical data of workplace social capital and employees' systolic blood pressure. Researchers assume group-level interventions when using a self-included model, and individual-level interventions when using a self-excluded model. Analytical re-parameterizations of these two models highlight their differences in parameter interpretation. Cluster-mean centered self-included models enable researchers to decompose the collective effect into its within- and between-group components. The benefit of cluster-mean centering procedure is further discussed in terms of hypothetical interventions. When investigating the potential roles of aggregated variables, researchers should carefully explore which type of model-self-included or self-excluded-is suitable for a given situation, particularly

  3. Estimation of insulin secretion, glucose uptake by tissues, and liver handling of glucose using a mathematical model of glucose-insulin homeostasis in lean and obese mice.

    Science.gov (United States)

    Brenner, Michael; Abadi, Sakineh Esmaeili Mohsen; Balouchzadeh, Ramin; Lee, H Felix; Ko, Hoo Sang; Johns, Michael; Malik, Nehal; Lee, Joshua J; Kwon, Guim

    2017-06-01

    Destruction of the insulin-producing β-cells is the key determinant of diabetes mellitus regardless of their types. Due to their anatomical location within the islets of Langerhans scattered throughout the pancreas, it is difficult to monitor β-cell function and mass clinically. To this end, we propose to use a mathematical model of glucose-insulin homeostasis to estimate insulin secretion, glucose uptake by tissues, and hepatic handling of glucose. We applied the mathematical model by Lombarte et al. (2013) to compare various rate constants representing glucose-insulin homeostasis between lean (11% fat)- and high fat diet (HFD; 45% fat)-fed mice. Mice fed HFD (n = 12) for 3 months showed significantly higher body weights (49.97 ± 0.52 g vs. 29.86 ± 0.46 g), fasting blood glucose levels (213.08 ± 10.35 mg/dl vs. 121.91 ± 2.26 mg/dl), and glucose intolerance compared to mice fed lean diet (n = 12). Mice were injected with 1 g/kg glucose intraperitoneally and blood glucose levels were measured at various intervals for 120 min. We performed simulation using Arena™ software based on the mathematical model and estimated the rate constants (9 parameters) for various terms in the differential equations using OptQuest™. The simulated data fit accurately to the observed data for both lean and obese mice, validating the use of the mathematical model in mice at different stages of diabetes progression. Among 9 parameters, 5 parameters including basal insulin, k 2 (rate constant for insulin-dependent glucose uptake to tissues), k 3 (rate constant for insulin-independent glucose uptake to tissues), k 4 (rate constant for liver glucose transfer), and I pi (rate constant for insulin concentration where liver switches from glucose release to uptake) were significantly different between lean- and HFD-fed mice. Basal blood insulin levels, k 3 , and I pi were significantly elevated but k 2 and k 4 were reduced in mice fed a HFD compared to those fed a lean diet. Non

  4. [Effects of polydatin on ALT, AST, TNF-alpha, and COX-2 in sepsis model mice].

    Science.gov (United States)

    Li, Xiao-Hui; Wu, Meng-Jiao; Zhang, Li-Na; Zheng, Jia-Jia; Zhang, Li; Wan, Jing-Yuan

    2013-02-01

    To investigate the protective effects of polydatin on sepsis-induced acute liver injury (ALI) in mice, and to preliminarily study its mechanisms. The sepsis model was established using cecal ligation and puncture (CLP).A sham-operation control group was also set up. Polydatin (50, 100, and 300 mg/kg, respectively) was administrated to mice 1 h before CLP. The survival and liver injury were evaluated subsequently per 6 h after CLP. The survived mice were scarified 24 h later. The serum and the liver tissue sample were collected. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by colorimetric method. The content of tumor necrosis factor-alpha (TNF-alpha) was assayed by ELISA. The cyclooxygenase-2 (COX-2) expression in the liver tissue was detected by Western blot. The pathological changes of the hepatic tissue were analyzed by hematoxylin and eosin stain. The mortality of mice reached as high as 50% at 24 h after CLP. The biochemical indices and the pathological changes of the liver tissue showed obvious lesion. The success rate of modeling was 90%. Compared with the sham-operation control group, the serum ALT,AST activity, the TNF-alpha content, and the hepatic COX-2 protein expression markedly increased in the CLP group (P < 0.01). Polydatin improved the sepsis-induced mortality dose-dependently, inhibited increased ALT, AST activity and TNF-alpha, decreased the hepatic COX-2 protein expression, and attenuated the pathological injury of the liver (P < 0.05). Polydatin could effectively protect sepsis-induced ALI, which might be achieved possibly through inhibiting serum TNF-alpha production and hepatic COX-2 expression.

  5. Combining prior knowledge with data-driven modeling of a batch distillation column including start-up

    NARCIS (Netherlands)

    van Lith, P.F.; van Lith, Pascal F.; Betlem, Bernardus H.L.; Roffel, B.

    2003-01-01

    This paper presents the development of a simple model which describes the product quality and production over time of an experimental batch distillation column, including start-up. The model structure is based on a simple physical framework, which is augmented with fuzzy logic. This provides a way

  6. Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects.

    Science.gov (United States)

    Breuer, Aviva; Haj, Christeene G; Fogaça, Manoela V; Gomes, Felipe V; Silva, Nicole Rodrigues; Pedrazzi, João Francisco; Del Bel, Elaine A; Hallak, Jaime C; Crippa, José A; Zuardi, Antonio W; Mechoulam, Raphael; Guimarães, Francisco S

    2016-01-01

    Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F-CBD (HUF-101) (1), is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors.

  7. Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects.

    Directory of Open Access Journals (Sweden)

    Aviva Breuer

    Full Text Available Cannabidiol (CBD is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F-CBD (HUF-101 (1, is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors.

  8. A Novel mouse model of enhanced proteostasis: Full-length human heat shock factor 1 transgenic mice

    International Nuclear Information System (INIS)

    Pierce, Anson; Wei, Rochelle; Halade, Dipti; Yoo, Si-Eun; Ran, Qitao; Richardson, Arlan

    2010-01-01

    Research highlights: → Development of mouse overexpressing native human HSF1 in all tissues including CNS. → HSF1 overexpression enhances heat shock response at whole-animal and cellular level. → HSF1 overexpression protects from polyglutamine toxicity and favors aggresomes. → HSF1 overexpression enhances proteostasis at the whole-animal and cellular level. -- Abstract: The heat shock response (HSR) is controlled by the master transcriptional regulator heat shock factor 1 (HSF1). HSF1 maintains proteostasis and resistance to stress through production of heat shock proteins (HSPs). No transgenic model exists that overexpresses HSF1 in tissues of the central nervous system (CNS). We generated a transgenic mouse overexpressing full-length non-mutant HSF1 and observed a 2-4-fold increase in HSF1 mRNA and protein expression in all tissues studied of HSF1 transgenic (HSF1 +/0 ) mice compared to wild type (WT) littermates, including several regions of the CNS. Basal expression of HSP70 and 90 showed only mild tissue-specific changes; however, in response to forced exercise, the skeletal muscle HSR was more elevated in HSF1 +/0 mice compared to WT littermates and in fibroblasts following heat shock, as indicated by levels of inducible HSP70 mRNA and protein. HSF1 +/0 cells elicited a significantly more robust HSR in response to expression of the 82 repeat polyglutamine-YFP fusion construct (Q82YFP) and maintained proteasome-dependent processing of Q82YFP compared to WT fibroblasts. Overexpression of HSF1 was associated with fewer, but larger Q82YFP aggregates resembling aggresomes in HSF1 +/0 cells, and increased viability. Therefore, our data demonstrate that tissues and cells from mice overexpressing full-length non-mutant HSF1 exhibit enhanced proteostasis.

  9. Partial deletion of the ROCK2 protein fails to reduce renal fibrosis in a unilateral ureteral obstruction model in mice.

    Science.gov (United States)

    Baba, Itsuko; Egi, Yasuhiro; Suzuki, Kazuo

    2016-01-01

    Renal fibrosis is a well‑known cause for the progression of chronic kidney disease. Rho/Rho‑associated coiled‑coil kinase (ROCK) signaling is involved in renal fibrotic processes. Non‑selective ROCK1/2 inhibitors have been reported to reduce renal interstitial fibrosis in a rodent unilateral ureteral obstruction (UUO) model. To clarify the role and contribution of ROCK2 in renal fibrosis, the present study used ROCK2 heterozygous knockout (HKO) mice to assess collagen deposition and fibrosis‑associated gene expression in the kidney of the UUO model. In the ROCK2 HKO mice, the expression level of ROCK2 in the normal kidney was half of that in the kidney of wild‑type (WT) mice. The expression levels of ROCK1 in the ROCK2 HKO mice and WT mice were equivalent. Furthermore, in the ROCK2 HKO and the WT mice, the hydroxyproline content and the gene expression levels of collagen I and transforming growth factor‑β1 in the obstructed kidneys were augmented following UUO. By contrast, the mRNA expression of α‑smooth muscle actin decreased in the ROCK2 HKO mice, compared with that in the WT mice. The activity of ROCK in the obstructed kidneys, indicated by the phosphorylation of myosin phosphatase target subunit‑1, which is a non‑selective substrate of ROCK1 and ROCK2, was equivalent among the ROCK2 HKO and WT mice. In conclusion, no differences in renal interstitial fibrosis or UUO‑induced ROCK activity were identified between the ROCK2 HKO and WT mice, indicating that the genetic partial disruption of ROCK2 is insufficient for protecting against renal fibrosis.

  10. Acute Phase Response and Neutrophils : Lymphocyte Ratio in Response to Astaxanthin in Staphylococcal Mice Mastitis Model

    Directory of Open Access Journals (Sweden)

    Tshering Dolma

    2014-01-01

    Full Text Available The purpose of the study was to determine the immunotherapeutic effect of astaxanthin (AX on total clinical score (TCS, C-reactive protein (CRP, and neutrophil : lymphocyte ratio in mice mastitis model challenged with pathogenic Staphylococcus aureus. Twenty-four lactating mice were divided in 4 equal groups: group I mice served as normal healthy control, group II, positive control, were challenged with pathogenic S. aureus, group III mice were challenged and treated with AX, and group IV were treated with amoxicillin plus sulbactum. The TCS was higher in postchallenged mice; however it was significantly higher in group II untreated mice as compared to group III and group IV mice. The neutrophil was higher and lymphocyte count was lower in group II mice at 120 hrs post challenge (PC. The CRP was positive in all the challenged group at 24 hrs PC, but it remained positive till 120 hrs PC in group II. The parameters are related to enhancement of the mammary defense and reduction of inflammation. Hence AX may be used alone or as an adjunct therapy with antibiotic for amelioration of mastitis. Development of such therapy may be useful to reduce the antibiotic burden in management of intramammary infection.

  11. An inducible hepatocellular carcinoma model for preclinical evaluation of antiangiogenic therapy in adult mice.

    Science.gov (United States)

    Runge, Anja; Hu, Junhao; Wieland, Matthias; Bergeest, Jan-Philip; Mogler, Carolin; Neumann, André; Géraud, Cyrill; Arnold, Bernd; Rohr, Karl; Komljenovic, Dorde; Schirmacher, Peter; Goerdt, Sergij; Augustin, Hellmut G

    2014-08-01

    The limited availability of experimental tumor models that faithfully mimic the progression of human tumors and their response to therapy remains a major bottleneck to the clinical translation and application of novel therapeutic principles. To address this challenge in hepatocellular carcinoma (HCC), one of the deadliest and most common cancers in the world, we developed and validated an inducible model of hepatocarcinogenesis in adult mice. Tumorigenesis was triggered by intravenous adenoviral delivery of Cre recombinase in transgenic mice expressing the hepatocyte-specific albumin promoter, a loxP-flanked stop cassette, and the SV40 large T-antigen (iAST). Cre recombinase-mediated excision of the stop cassette led to a transient viral hepatitis and resulted in multinodular tumorigenesis within 5 to 8 weeks. Tumor nodules with histologic characteristics of human HCC established a functional vasculature by cooption, remodeling, and angiogenic expansion of the preexisting sinusoidal liver vasculature with increasing signs of vascular immaturity during tumor progression. Treatment of mice with sorafenib rapidly resulted in the induction of vascular regression, inhibition of tumor growth, and enhanced overall survival. Vascular regression was characterized by loss of endothelial cells leaving behind avascular type IV collagen-positive empty sleeves with remaining pericytes. Sorafenib treatment led to transcriptional changes of Igf1, Id1, and cMet over time, which may reflect the emergence of potential escape mechanisms. Taken together, our results established the iAST model of inducible hepatocarcinogenesis as a robust and versatile preclinical model to study HCC progression and validate novel therapies. ©2014 American Association for Cancer Research.

  12. A new model of short acceleration-based training improves exercise performance in old mice.

    Science.gov (United States)

    Niel, R; Ayachi, M; Mille-Hamard, L; Le Moyec, L; Savarin, P; Clement, M-J; Besse, S; Launay, T; Billat, V L; Momken, I

    2017-12-01

    In order to identify a more appealing exercise strategy for the elderly, we studied a mouse model to determine whether a less time-consuming training program would improve exercise performance, enzyme activities, mitochondrial respiration, and metabolomic parameters. We compared the effects of short-session (acceleration-based) training with those of long-session endurance training in 23-month-old mice. The short-session training consisted of five acceleration-based treadmill running sessions over 2 weeks (the acceleration group), whereas the endurance training consisted of five-one-hour treadmill sessions per week for 4 weeks (the endurance group). A control group of mice was also studied. In the acceleration group, the post-training maximum running speed and time to exhaustion were significantly improved, relative to pretraining values (+8% for speed, Pspeed was higher in the acceleration group than in the endurance group (by 23%; Pendurance group. Furthermore, mitochondrial respiratory activity in the gastrocnemius was higher in the acceleration group than in the control group. A metabolomic urine analysis revealed a higher mean taurine concentration and a lower mean branched amino acid concentration in the acceleration group. In old mice, acceleration-based training appears to be an efficient way of increasing performance by improving both aerobic and anaerobic metabolism, and possibly by enhancing antioxidant defenses and maintaining muscle protein balance. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Preliminary investigation of a mice model of Klebsiella pneumoniae subsp. ozaenae induced pneumonia.

    Science.gov (United States)

    Renois, Fanny; Jacques, Jérôme; Guillard, Thomas; Moret, Hélène; Pluot, Michel; Andreoletti, Laurent; de Champs, Christophe

    2011-11-01

    In the present study, we comparatively assessed the pathophysiological mechanisms developed during lung infection of BALB/C female mice infected by an original wild type Klebsiella pneumoniae subsp. ozaenae strain (CH137) or by a referent subspecies K. pneumoniae. subsp. pneumoniae strain (ATCC10031). The mice infected with 2.10⁶ CFU K. p. subsp. pneumoniae (n = 10) showed transient signs of infection and all of them recovered. All of those infected with 1.10⁶ CFU K. p. subsp. ozaenae (n = 10) developed pneumonia within 24 h and died between 48 and 72 h. Few macrophages, numerous polymorphonuclear cells and lymphocytes were observed in their lungs in opposite to K. p. subsp. pneumoniae. In bronchoalveolar lavage, a significant increase in MIP-2, IL-6, KC and MCP-1 levels was only observed in K. p. subsp. ozaenae infected mice whereas high levels of TNF-α were evidenced with the two subspecies. Our findings indicated a lethal effect of a wild type K. p. subsp. ozaenae strain by acute pneumonia reflecting an insufficient alveolar macrophage response. This model might be of a major interest to comparatively explore the pathogenicity of K. p. subsp ozaenae strains and to further explore the physiopathological mechanisms of gram-negative bacteria induced human pneumonia. Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  14. The Benefits of Including Clinical Factors in Rectal Normal Tissue Complication Probability Modeling After Radiotherapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Defraene, Gilles; Van den Bergh, Laura; Al-Mamgani, Abrahim; Haustermans, Karin; Heemsbergen, Wilma; Van den Heuvel, Frank; Lebesque, Joos V.

    2012-01-01

    Purpose: To study the impact of clinical predisposing factors on rectal normal tissue complication probability modeling using the updated results of the Dutch prostate dose-escalation trial. Methods and Materials: Toxicity data of 512 patients (conformally treated to 68 Gy [n = 284] and 78 Gy [n = 228]) with complete follow-up at 3 years after radiotherapy were studied. Scored end points were rectal bleeding, high stool frequency, and fecal incontinence. Two traditional dose-based models (Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) and a logistic model were fitted using a maximum likelihood approach. Furthermore, these model fits were improved by including the most significant clinical factors. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminating ability of all fits. Results: Including clinical factors significantly increased the predictive power of the models for all end points. In the optimal LKB, RS, and logistic models for rectal bleeding and fecal incontinence, the first significant (p = 0.011–0.013) clinical factor was “previous abdominal surgery.” As second significant (p = 0.012–0.016) factor, “cardiac history” was included in all three rectal bleeding fits, whereas including “diabetes” was significant (p = 0.039–0.048) in fecal incontinence modeling but only in the LKB and logistic models. High stool frequency fits only benefitted significantly (p = 0.003–0.006) from the inclusion of the baseline toxicity score. For all models rectal bleeding fits had the highest AUC (0.77) where it was 0.63 and 0.68 for high stool frequency and fecal incontinence, respectively. LKB and logistic model fits resulted in similar values for the volume parameter. The steepness parameter was somewhat higher in the logistic model, also resulting in a slightly lower D 50 . Anal wall DVHs were used for fecal incontinence, whereas anorectal wall dose best described the other two endpoints. Conclusions

  15. Protective Effect of Anthocyanins Extract from Blueberry on TNBS-Induced IBD Model of Mice

    Directory of Open Access Journals (Sweden)

    Lin-Hua Wu

    2011-01-01

    Full Text Available This study was carried out to evaluate the protective effect of anthocyanins extract of blueberry on trinitrobenzene sulfonic acid (TNBS-induced inflammatory bowel disease (IBD model of mice. The study employed female C57BL/6 mice (n = 50, and colitis was induced by intracolonic injection of 0.5 mg of TNBS dissolved in 50% ethanol–phosphate buffered solution. The mice were divided into five groups (n = 10: vehicle, TNBS control and anthocyanins groups that received different doses of anthocyanins extract (10, 20 and 40 mg kg-1 daily for 6 days. Both increase in body weight and diarrhea symptoms were monitored each day. After 6 days, the animals were killed, and the following parameters were assessed: colon length, morphological score, histological score and biochemical assay (NO, myeloperoxidase (MPO, interleukin (IL-12, IL-10, tumor necrosis factor (TNF-α and interferon (IFN-γ. The results showed that the anthocyanins extract of blueberry rendered strong protection against TNBS-induced colonic damage at a dosage of 40 mg kg-1. When compared with the control, anthocyanins extract significantly prevented loss of body weight and ameliorated the scores of diarrhea, morphology and histology. Treatment with anthocyanins extract restored IL-10 excretion, as well as caused reduction in the levels of NO, MPO, IL-12, TNF-α and IFN-γ. Our research revealed the protective effect of anthocyanins extract from blueberry on TNBS-induced experimental colitis in mice, as well as examined whether high levels of dietary blueberries would lower the risk or have protective effects on human IBD, which may require further investigation.

  16. Effects of candesartan on electrical remodeling in the hearts of inherited dilated cardiomyopathy model mice.

    Directory of Open Access Journals (Sweden)

    Fuminori Odagiri

    Full Text Available Inherited dilated cardiomyopathy (DCM is characterized by dilatation and dysfunction of the ventricles, and often results in sudden death or heart failure (HF. Although angiotensin receptor blockers (ARBs have been used for the treatment of HF, little is known about the effects on postulated electrical remodeling that occurs in inherited DCM. The aim of this study was to examine the effects of candesartan, one of the ARBs, on cardiac function and electrical remodeling in the hearts of inherited DCM model mice (TNNT2 ΔK210. DCM mice were treated with candesartan in drinking water for 2 months from 1 month of age. Control, non-treated DCM mice showed an enlargement of the heart with prolongation of QRS and QT intervals, and died at t1/2 of 70 days. Candesartan dramatically extended the lifespan of DCM mice, suppressed cardiac dilatation, and improved the functional parameters of the myocardium. It also greatly suppressed prolongation of QRS and QT intervals and action potential duration (APD in the left ventricular myocardium and occurrence of ventricular arrhythmia. Expression analysis revealed that down-regulation of Kv4.2 (Ito channel protein, KChIP2 (auxiliary subunit of Kv4.2, and Kv1.5 (IKur channel protein in DCM was partially reversed by candesartan administration. Interestingly, non-treated DCM heart had both normal-sized myocytes with moderately decreased Ito and IKur and enlarged cells with greatly reduced K+ currents (Ito, IKur IK1 and Iss. Treatment with candesartan completely abrogated the emergence of the enlarged cells but did not reverse the Ito, and IKur in normal-sized cells in DCM hearts. Our results indicate that candesartan treatment suppresses structural remodeling to prevent severe electrical remodeling in inherited DCM.

  17. Can a one-layer optical skin model including melanin and inhomogeneously distributed blood explain spatially resolved diffuse reflectance spectra?

    Science.gov (United States)

    Karlsson, Hanna; Pettersson, Anders; Larsson, Marcus; Strömberg, Tomas

    2011-02-01

    Model based analysis of calibrated diffuse reflectance spectroscopy can be used for determining oxygenation and concentration of skin chromophores. This study aimed at assessing the effect of including melanin in addition to hemoglobin (Hb) as chromophores and compensating for inhomogeneously distributed blood (vessel packaging), in a single-layer skin model. Spectra from four humans were collected during different provocations using a twochannel fiber optic probe with source-detector separations 0.4 and 1.2 mm. Absolute calibrated spectra using data from either a single distance or both distances were analyzed using inverse Monte Carlo for light transport and Levenberg-Marquardt for non-linear fitting. The model fitting was excellent using a single distance. However, the estimated model failed to explain spectra from the other distance. The two-distance model did not fit the data well at either distance. Model fitting was significantly improved including melanin and vessel packaging. The most prominent effect when fitting data from the larger separation compared to the smaller separation was a different light scattering decay with wavelength, while the tissue fraction of Hb and saturation were similar. For modeling spectra at both distances, we propose using either a multi-layer skin model or a more advanced model for the scattering phase function.

  18. Bofu-tsu-shosan, an oriental herbal medicine, exerts a combinatorial favorable metabolic modulation including antihypertensive effect on a mouse model of human metabolic disorders with visceral obesity.

    Directory of Open Access Journals (Sweden)

    Kengo Azushima

    Full Text Available Accumulating evidence indicates that metabolic dysfunction with visceral obesity is a major medical problem associated with the development of hypertension, type 2 diabetes (T2DM and dyslipidemia, and ultimately severe cardiovascular and renal disease. Therefore, an effective anti-obesity treatment with a concomitant improvement in metabolic profile is important for the treatment of metabolic dysfunction with visceral obesity. Bofu-tsu-shosan (BOF is one of oriental herbal medicine and is clinically available to treat obesity in Japan. Although BOF is a candidate as a novel therapeutic strategy to improve metabolic dysfunction with obesity, the mechanism of its beneficial effect is not fully elucidated. Here, we investigated mechanism of therapeutic effects of BOF on KKAy mice, a model of human metabolic disorders with obesity. Chronic treatment of KKAy mice with BOF persistently decreased food intake, body weight gain, low-density lipoprotein cholesterol and systolic blood pressure. In addition, both tissue weight and cell size of white adipose tissue (WAT were decreased, with concomitant increases in the expression of adiponectin and peroxisome proliferator-activated receptors genes in WAT as well as the circulating adiponectin level by BOF treatment. Furthermore, gene expression of uncoupling protein-1, a thermogenesis factor, in brown adipose tissue and rectal temperature were both elevated by BOF. Intriguingly, plasma acylated-ghrelin, an active form of orexigenic hormone, and short-term food intake were significantly decreased by single bolus administration of BOF. These results indicate that BOF exerts a combinatorial favorable metabolic modulation including antihypertensive effect, at least partially, via its beneficial effect on adipose tissue function and its appetite-inhibitory property through suppression on the ghrelin system.

  19. Nonlinear flow model of multiple fractured horizontal wells with stimulated reservoir volume including the quadratic gradient term

    Science.gov (United States)

    Ren, Junjie; Guo, Ping

    2017-11-01

    The real fluid flow in porous media is consistent with the mass conservation which can be described by the nonlinear governing equation including the quadratic gradient term (QGT). However, most of the flow models have been established by ignoring the QGT and little work has been conducted to incorporate the QGT into the flow model of the multiple fractured horizontal (MFH) well with stimulated reservoir volume (SRV). This paper first establishes a semi-analytical model of an MFH well with SRV including the QGT. Introducing the transformed pressure and flow-rate function, the nonlinear model of a point source in a composite system including the QGT is linearized. Then the Laplace transform, principle of superposition, numerical discrete method, Gaussian elimination method and Stehfest numerical inversion are employed to establish and solve the seepage model of the MFH well with SRV. Type curves are plotted and the effects of relevant parameters are analyzed. It is found that the nonlinear effect caused by the QGT can increase the flow capacity of fluid flow and influence the transient pressure positively. The relevant parameters not only have an effect on the type curve but also affect the error in the pressure calculated by the conventional linear model. The proposed model, which is consistent with the mass conservation, reflects the nonlinear process of the real fluid flow, and thus it can be used to obtain more accurate transient pressure of an MFH well with SRV.

  20. Compartment model predicts VEGF secretion and investigates the effects of VEGF Trap in tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    Stacey D Finley

    2013-07-01

    Full Text Available Angiogenesis, the formation of new blood vessels from existing vasculature, is important in tumor growth and metastasis. A key regulator of angiogenesis is vascular endothelial growth factor (VEGF, which has been targeted in numerous anti-angiogenic therapies aimed at inhibiting tumor angiogenesis. Systems biology approaches, including computational modeling, are useful for understanding this complex biological process and can aid in the development of novel and effective therapeutics that target the VEGF family of proteins and receptors. We have developed a computational model of VEGF transport and kinetics in the tumor-bearing mouse, which includes three compartments: normal tissue, blood, and tumor. The model simulates human tumor xenografts and includes human (VEGF121 and VEGF165 and mouse (VEGF120 and VEGF164 isoforms. The model incorporates molecular interactions between these VEGF isoforms and receptors (VEGFR1 and VEGFR2, as well as co-receptors (NRP1 and NRP2. We also include important soluble factors: soluble VEGFR1 (sFlt-1 and α-2-macroglobulin. The model accounts for transport via macromolecular transendothelial permeability, lymphatic flow, and plasma clearance. We have fit the model to available in vivo experimental data on the plasma concentration of free VEGF Trap and VEGF Trap bound to mouse and human VEGF in order to estimate the rates at which parenchymal cells (myocytes and tumor cells and endothelial cells secrete VEGF. Interestingly, the predicted tumor VEGF secretion rates are significantly lower (0.007 – 0.023 molecules/cell/s, depending on the tumor microenvironment than most reported in vitro measurements (0.03 – 2.65 molecules/cell/s. The optimized model is used to investigate the interstitial and plasma VEGF concentrations and the effect of the VEGF-neutralizing agent, VEGF Trap (aflibercept. This work complements experimental studies performed in mice and provides a framework with which to examine the effects of

  1. The effect of the administration of human gamma globulins in a model of BCG infection in mice.

    Science.gov (United States)

    Olivares, Nesty; León, Annette; López, Yamilé; Puig, Alina; Cádiz, Armando; Falero, Gustavo; Martínez, Máximo; Sarmiento, Marie E; Fariñas, Mildrey; Infante, Juan F; Sierra, Gustavo; Solís, Rosa L; Acosta, Armando

    2006-01-01

    The effect of the administration of a commercial preparation of human gamma globulins has been evaluated in a mouse model of intranasal infection with BCG. First, we demonstrated the passage of specific antibodies to saliva and lung lavage following the intranasal or intraperitoneal administration to mice of human gamma globulins. This treatment of mice inhibited BCG colonization of the lungs (p < 0.01). A similar inhibitory effect was observed after infection of mice with gamma globulin opsonized BCG organisms (p < 0.01). These results are relevant for the development of new strategies for the control and treatment of tuberculosis.

  2. Similar response in male and female B10.RIII mice in a murine model of allergic airway inflammation

    DEFF Research Database (Denmark)

    Matheu, Victor; Barrios, Ysamar; Arnau, Maria-Rosa

    2009-01-01

    BACKGROUND: Several reports have been published on the gender differences associated with allergies in mice. GOAL: In the present study we investigate the influence of gender on allergy response using a strain of mice, B10.RIII, which is commonly used in the collagen-induced arthritis murine model....... METHODS: Both male and female B10.RIII young mice were immunized with OVA and challenged four times with OVA intranasally. Samples were taken 24 h after the last challenge, and eosinophils in bronchoalveolar lavage (BAL) and parenchyma, Th-2 cytokines in BAL, total and antigen-specific IgE in sera...

  3. Enhancement of viral pathogenesis in mice maintained in an antiorthostatic suspension model - Coordination with effects on interferon production

    Science.gov (United States)

    Gould, C. L.; Sonnenfeld, G.

    1987-01-01

    Both rodents and men returning from spaceflight have exhibited alterations in immune responses and, in particular, interferon production. This work utilizes a model for antiorthostatic (20-deg head-down tilt), hypokinetic, hypodynamic suspension of mice that simulates some aspects of weightlessness. Female Swiss/Webster mice that are normally resistant to infection with the D variant of encephalomyocarditis virus showed a marked increase in susceptibility to infection when suspended. This correlated with a drop in interferom production. Control, orthostatically suspended mice (no tilt) showed no increase in susceptibility to the virus.

  4. A finite element model of the lower limb during stance phase of gait cycle including the muscle forces.

    Science.gov (United States)

    Diffo Kaze, Arnaud; Maas, Stefan; Arnoux, Pierre-Jean; Wolf, Claude; Pape, Dietrich

    2017-12-07

    Results of finite element (FE) analyses can give insight into musculoskeletal diseases if physiological boundary conditions, which include the muscle forces during specific activities of daily life, are considered in the FE modelling. So far, many simplifications of the boundary conditions are currently made. This study presents an approach for FE modelling of the lower limb for which muscle forces were included. The stance phase of normal gait was simulated. Muscle forces were calculated using a musculoskeletal rigid body (RB) model of the human body, and were subsequently applied to a FE model of the lower limb. It was shown that the inertial forces are negligible during the stance phase of normal gait. The contact surfaces between the parts within the knee were modelled as bonded. Weak springs were attached to the distal tibia for numerical reasons. Hip joint reaction forces from the RB model and those from the FE model were similar in magnitude with relative differences less than 16%. The forces of the weak spring were negligible compared to the applied muscle forces. The maximal strain was 0.23% in the proximal region of the femoral diaphysis and 1.7% in the contact zone between the tibia and the fibula. The presented approach based on FE modelling by including muscle forces from inverse dynamic analysis of musculoskeletal RB model can be used to perform analyses of the lower limb with very realistic boundary conditions. In the present form, this model can be used to better understand the loading, stresses and strains of bones in the knee area and hence to analyse osteotomy fixation devices.

  5. Global stability for infectious disease models that include immigration of infected individuals and delay in the incidence

    Directory of Open Access Journals (Sweden)

    Chelsea Uggenti

    2018-03-01

    Full Text Available We begin with a detailed study of a delayed SI model of disease transmission with immigration into both classes. The incidence function allows for a nonlinear dependence on the infected population, including mass action and saturating incidence as special cases. Due to the immigration of infectives, there is no disease-free equilibrium and hence no basic reproduction number. We show there is a unique endemic equilibrium and that this equilibrium is globally asymptotically stable for all parameter values. The results include vector-style delay and latency-style delay. Next, we show that previous global stability results for an SEI model and an SVI model that include immigration of infectives and non-linear incidence but not delay can be extended to systems with vector-style delay and latency-style delay.

  6. [The progression of applying transgenic mice as an animal model of high myopia].

    Science.gov (United States)

    Song, Yan-zheng; Zhao, Yan-yan; Zhang, Feng-ju

    2013-04-01

    Gene engineering technology provides new methods for medical research. The application of transgenic animals and knock out animals makes it possible to study the biological characteristics of genes associated with some human diseases in vivo. Transgenic mice were first achieved in the early 1980s, while they were used extensively in the field of ophthalmology doing some research a few years later after that. Therefore, it can possibly be a new path to investigate the pathogenesis by establishing transgenic mouse model of candidate gene of high myopia.

  7. Myo5b knockout mice as a model of microvillus inclusion disease

    Science.gov (United States)

    Cartón-García, Fernando; Overeem, Arend W.; Nieto, Rocio; Bazzocco, Sarah; Dopeso, Higinio; Macaya, Irati; Bilic, Josipa; Landolfi, Stefania; Hernandez-Losa, Javier; Schwartz, Simo; Ramon y Cajal, Santiago; van Ijzendoorn, Sven C. D.; Arango, Diego

    2015-01-01

    Inherited MYO5B mutations have recently been associated with microvillus inclusion disease (MVID), an autosomal recessive syndrome characterized by intractable, life-threatening, watery diarrhea appearing shortly after birth. Characterization of the molecular mechanisms underlying this disease and development of novel therapeutic approaches is hampered by the lack of animal models. In this study we describe the phenotype of a novel mouse model with targeted inactivation of Myo5b. Myo5b knockout mice show perinatal mortality, diarrhea and the characteristic mislocalization of apical and basolateral plasma membrane markers in enterocytes. Moreover, in transmission electron preparations, we observed microvillus atrophy and the presence of microvillus inclusion bodies. Importantly, Myo5b knockout embryos at day 20 of gestation already display all these structural defects, indicating that they are tissue autonomous rather than secondary to environmental cues, such as the long-term absence of nutrients in the intestine. Myo5b knockout mice closely resemble the phenotype of MVID patients and constitute a useful model to further investigate the underlying molecular mechanism of this disease and to preclinically assess the efficacy of novel therapeutic approaches. PMID:26201991

  8. Complex restitution behavior and reentry in a cardiac tissue model for neonatal mice.

    Science.gov (United States)

    Mayer, Andreas; Bittihn, Philip; Luther, Stefan

    2017-10-01

    Spatiotemporal dynamics in cardiac tissue emerging from the coupling of individual cardiomyocytes underlie the heart's normal rhythm as well as undesired and possibly life-threatening arrhythmias. While single cells and their transmembrane currents have been studied extensively, systematically investigating spatiotemporal dynamics is complicated by the nontrivial relationship between single-cell and emergent tissue properties. Mathematical models have been employed to bridge this gap and contribute to a deepened understanding of the onset, development, and termination of arrhythmias. However, no such tissue-level model currently exists for neonatal mice. Here, we build on a recent single-cell model of neonatal mouse cardiomyocytes by Wang and Sobie ( Am. J. Physiol. Heart Circ. Physiol 294:H2565) to predict properties that are commonly used to gauge arrhythmogenicity of cardiac substrates. We modify the model to yield well-defined behavior for common experimental protocols and construct a spatially extended version to study emergent tissue dynamics. We find a complex action potential duration (APD) restitution behavior characterized by a nonmonotonic dependence on pacing frequency. Electrotonic coupling in tissue leads not only to changes in action potential morphology but can also induce spatially concordant and discordant alternans not observed in the single-cell model. In two-dimensional tissue, our results show that the model supports stable functional reentry, whose frequency is in good agreement with that observed in adult mice. Our results can be used to further constrain and validate the mathematical model of neonatal mouse cardiomyocytes with future experiments. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  9. Discovery of p1736, a novel antidiabetic compound that improves peripheral insulin sensitivity in mice models.

    Directory of Open Access Journals (Sweden)

    Jessy Anthony

    Full Text Available Insulin resistance is a characteristic feature of Type 2 diabetes. Insulin resistance has also been implicated in the pathogenesis of cardiovascular disease. Currently used thiazolidinedione (TZD insulin sensitizers although effective, have adverse side effects of weight gain, fluid retention and heart failure. Using fat cell-based phenotypic drug discovery approach we identified P1736, a novel antidiabetic molecule that has completed Phase II clinical trials. The present study evaluated the in vitro and in vivo pharmacological properties of P1736. P1736 is a non-TZD and it did not activate human PPAR(Peroxisome Proliferator Activated Receptor Gamma receptors. P1736 caused dose dependent increase in glucose uptake (EC50-400 nM in the insulin resistant 3T3 adipocytes. The compound (10 µM induced translocation of GLUT-4 (Glucose Transporter type 4 transporters in these adipocytes while metformin (1.0mM was inactive. In diabetic db/db mice, P1736 (150 mg/kg was more efficacious than metformin in lowering plasma glucose (35% vs 25% and triglyceride levels (38% vs 31%. P1736 tested at 5mg/kg, twice daily doses, reduced glucose by 41% and triglycerides by 32%, in db/db mice. These effects were not associated with adverse effects on body weight or liver function. Rosiglitazone (5mg/kg, twice daily caused 60% and 40 % decreases in glucose and triglyceride levels, respectively. However, rosiglitazone induced 13% weight gain (p<0.05 in db/db mice. P1736 was also efficacious in ob/ob mice wherein 30-35% decrease in glucose and significant improvement in hyperinsulinemia were observed. Administration of P1736 to ob/ob mice resulted in 70% increase in glucose uptake in soleus muscles while metformin caused 38% increase. P1736 exhibited excellent safety profile and was weight neutral in all preclinical models of diabetes. Thus, P1736 with its unique pharmacology coupled with PPAR- independent mode of action could represent an alternative option in the

  10. Discovery of p1736, a novel antidiabetic compound that improves peripheral insulin sensitivity in mice models.

    Science.gov (United States)

    Anthony, Jessy; Kelkar, Aditya; Wilankar, Chandan; Ranjith, Vijayalakshmi; Bhumra, Sujit Kaur; Mutt, Shivaprakash Jagalur; Mutt, Shivaprakash; Deka, Nabajyoti; Sivaramakrishnan, Hariharan; Sharma, Somesh; Marita, Adaikalasamy Rosalind

    2013-01-01

    Insulin resistance is a characteristic feature of Type 2 diabetes. Insulin resistance has also been implicated in the pathogenesis of cardiovascular disease. Currently used thiazolidinedione (TZD) insulin sensitizers although effective, have adverse side effects of weight gain, fluid retention and heart failure. Using fat cell-based phenotypic drug discovery approach we identified P1736, a novel antidiabetic molecule that has completed Phase II clinical trials. The present study evaluated the in vitro and in vivo pharmacological properties of P1736. P1736 is a non-TZD and it did not activate human PPAR(Peroxisome Proliferator Activated Receptor Gamma )receptors. P1736 caused dose dependent increase in glucose uptake (EC50-400 nM) in the insulin resistant 3T3 adipocytes. The compound (10 µM) induced translocation of GLUT-4 (Glucose Transporter type 4) transporters in these adipocytes while metformin (1.0mM) was inactive. In diabetic db/db mice, P1736 (150 mg/kg) was more efficacious than metformin in lowering plasma glucose (35% vs 25%) and triglyceride levels (38% vs 31%). P1736 tested at 5mg/kg, twice daily doses, reduced glucose by 41% and triglycerides by 32%, in db/db mice. These effects were not associated with adverse effects on body weight or liver function. Rosiglitazone (5mg/kg, twice daily) caused 60% and 40 % decreases in glucose and triglyceride levels, respectively. However, rosiglitazone induced 13% weight gain (p<0.05) in db/db mice. P1736 was also efficacious in ob/ob mice wherein 30-35% decrease in glucose and significant improvement in hyperinsulinemia were observed. Administration of P1736 to ob/ob mice resulted in 70% increase in glucose uptake in soleus muscles while metformin caused 38% increase. P1736 exhibited excellent safety profile and was weight neutral in all preclinical models of diabetes. Thus, P1736 with its unique pharmacology coupled with PPAR- independent mode of action could represent an alternative option in the management of

  11. Surface potential based modeling of charge, current, and capacitances in DGTFET including mobile channel charge and ambipolar behaviour

    Science.gov (United States)

    Jain, Prateek; Yadav, Chandan; Agarwal, Amit; Chauhan, Yogesh Singh

    2017-08-01

    We present a surface potential based analytical model for double gate tunnel field effect transistor (DGTFET) for the current, terminal charges, and terminal capacitances. The model accounts for the effect of the mobile charge in the channel and captures the device physics in depletion as well as in the strong inversion regime. The narrowing of the tunnel barrier in the presence of mobile charges in the channel is incorporated via modeling of the inverse decay length, which is constant under channel depletion condition and bias dependent under inversion condition. To capture the ambipolar current behavior in the model, tunneling at the drain junction is also included. The proposed model is validated against TCAD simulation data and it shows close match with the simulation data.

  12. Model Selection and Evaluation Based on Emerging Infectious Disease Data Sets including A/H1N1 and Ebola

    Directory of Open Access Journals (Sweden)

    Wendi Liu

    2015-01-01

    Full Text Available The aim of the present study is to apply simple ODE models in the area of modeling the spread of emerging infectious diseases and show the importance of model selection in estimating parameters, the basic reproduction number, turning point, and final size. To quantify the plausibility of each model, given the data and the set of four models including Logistic, Gompertz, Rosenzweg, and Richards models, the Bayes factors are calculated and the precise estimates of the best fitted model parameters and key epidemic characteristics have been obtained. In particular, for Ebola the basic reproduction numbers are 1.3522 (95% CI (1.3506, 1.3537, 1.2101 (95% CI (1.2084, 1.2119, 3.0234 (95% CI (2.6063, 3.4881, and 1.9018 (95% CI (1.8565, 1.9478, the turning points are November 7,November 17, October 2, and November 3, 2014, and the final sizes until December 2015 are 25794 (95% CI (25630, 25958, 3916 (95% CI (3865, 3967, 9886 (95% CI (9740, 10031, and 12633 (95% CI (12515, 12750 for West Africa, Guinea, Liberia, and Sierra Leone, respectively. The main results confirm that model selection is crucial in evaluating and predicting the important quantities describing the emerging infectious diseases, and arbitrarily picking a model without any consideration of alternatives is problematic.

  13. Mathematical multi-scale model of the cardiovascular system including mitral valve dynamics. Application to ischemic mitral insufficiency

    Science.gov (United States)

    2011-01-01

    Background Valve dysfunction is a common cardiovascular pathology. Despite significant clinical research, there is little formal study of how valve dysfunction affects overall circulatory dynamics. Validated models would offer the ability to better understand these dynamics and thus optimize diagnosis, as well as surgical and other interventions. Methods A cardiovascular and circulatory system (CVS) model has already been validated in silico, and in several animal model studies. It accounts for valve dynamics using Heaviside functions to simulate a physiologically accurate "open on pressure, close on flow" law. However, it does not consider real-time valve opening dynamics and therefore does not fully capture valve dysfunction, particularly where the dysfunction involves partial closure. This research describes an updated version of this previous closed-loop CVS model that includes the progressive opening of the mitral valve, and is defined over the full cardiac cycle. Results Simulations of the cardiovascular system with healthy mitral valve are performed, and, the global hemodynamic behaviour is studied compared with previously validated results. The error between resulting pressure-volume (PV) loops of already validated CVS model and the new CVS model that includes the progressive opening of the mitral valve is assessed and remains within typical measurement error and variability. Simulations of ischemic mitral insufficiency are also performed. Pressure-Volume loops, transmitral flow evolution and mitral valve aperture area evolution follow reported measurements in shape, amplitude and trends. Conclusions The resulting cardiovascular system model including mitral valve dynamics provides a foundation for clinical validation and the study of valvular dysfunction in vivo. The overall models and results could readily be generalised to other cardiac valves. PMID:21942971

  14. Mathematical multi-scale model of the cardiovascular system including mitral valve dynamics. Application to ischemic mitral insufficiency

    Directory of Open Access Journals (Sweden)

    Moonen Marie

    2011-09-01

    Full Text Available Abstract Background Valve dysfunction is a common cardiovascular pathology. Despite significant clinical research, there is little formal study of how valve dysfunction affects overall circulatory dynamics. Validated models would offer the ability to better understand these dynamics and thus optimize diagnosis, as well as surgical and other interventions. Methods A cardiovascular and circulatory system (CVS model has already been validated in silico, and in several animal model studies. It accounts for valve dynamics using Heaviside functions to simulate a physiologically accurate "open on pressure, close on flow" law. However, it does not consider real-time valve opening dynamics and therefore does not fully capture valve dysfunction, particularly where the dysfunction involves partial closure. This research describes an updated version of this previous closed-loop CVS model that includes the progressive opening of the mitral valve, and is defined over the full cardiac cycle. Results Simulations of the cardiovascular system with healthy mitral valve are performed, and, the global hemodynamic behaviour is studied compared with previously validated results. The error between resulting pressure-volume (PV loops of already validated CVS model and the new CVS model that includes the progressive opening of the mitral valve is assessed and remains within typical measurement error and variability. Simulations of ischemic mitral insufficiency are also performed. Pressure-Volume loops, transmitral flow evolution and mitral valve aperture area evolution follow reported measurements in shape, amplitude and trends. Conclusions The resulting cardiovascular system model including mitral valve dynamics provides a foundation for clinical validation and the study of valvular dysfunction in vivo. The overall models and results could readily be generalised to other cardiac valves.

  15. Physiological and functional changes in the stratum corneum restored by oestrogen in an ovariectomized mice model of climacterium.

    Science.gov (United States)

    Chen, Yue; Yokozeki, Hiroo; Katagiri, Kazumoto

    2017-05-01

    Significant decreases in hormonal levels at menopause induce physiological and functional discomfort in the skin. Representative changes at menopause are based on so-called dry skin. However, there is no evidence to explain the mechanism, even though hydration of the stratum corneum (SC) in women at menopause is comparable with that at premenopause but is enhanced by hormone replacement therapy. This study objective was to evaluate structural and functional changes in the SC in ovariectomized mice model of menopause. Hydration of the SC, recovery of the permeability barrier function, integrity and cohesion of the SC, and irritant dermatitis were analysed in mice that underwent ovariectomy with or without replacement of 17ß-estradiol. In ovariectomized mice, hydration of the SC was reduced, recovery of permeability barrier function after acute disruption was impaired, and integrity of the SC was weakened and was associated with increased cohesion and increased levels of irritant dermatitis. Oestrogen replacement treatment restored all changes. Immunohistochemistry revealed reduced levels of expression of desmoglein-1 and differentiation markers of epidermis in ovariectomized mice compared with control mice and mice with oestrogen replacement treatment. These changes might be directly associated with weakened integrity and impaired permeability barrier function of the SC in ovariectomized mice. This study results reveal that so-called dry skin at menopause is caused by not only lower hydration of the SC but also complicated structural and functional changes in the SC and skin. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Progressive Depletion of Rough Endoplasmic Reticulum in Epithelial Cells of the Small Intestine in Monosodium Glutamate Mice Model of Obesity

    Directory of Open Access Journals (Sweden)

    Kazuhiko Nakadate

    2016-01-01

    Full Text Available Chronic obesity is a known risk factor for metabolic syndrome. However, little is known about pathological changes in the small intestine associated with chronic obesity. This study investigated cellular and subcellular level changes in the small intestine of obese mice. In this study, a mouse model of obesity was established by early postnatal administration of monosodium glutamate. Changes in body weight were monitored, and pathological changes in the small intestine were evaluated using hematoxylin-eosin and Nissl staining and light and electron microscopy. Consequently, obese mice were significantly heavier compared with controls from 9 weeks of age. Villi in the small intestine of obese mice were elongated and thinned. There was reduced hematoxylin staining in the epithelium of the small intestine of obese mice. Electron microscopy revealed a significant decrease in and shortening of rough endoplasmic reticulum in epithelial cells of the small intestine of obese mice compared with normal mice. The decrease in rough endoplasmic reticulum in the small intestine epithelial cells of obese mice indicates that obesity starting in childhood influences various functions of the small intestine, such as protein synthesis, and could impair both the defense mechanism against invasion of pathogenic microbes and nutritional absorption.

  17. NASTRAN thermal analyzer: Theory and application including a guide to modeling engineering problems, volume 2. [sample problem library guide

    Science.gov (United States)

    Jackson, C. E., Jr.

    1977-01-01

    A sample problem library containing 20 problems covering most facets of Nastran Thermal Analyzer modeling is presented. Areas discussed include radiative interchange, arbitrary nonlinear loads, transient temperature and steady-state structural plots, temperature-dependent conductivities, simulated multi-layer insulation, and constraint techniques. The use of the major control options and important DMAP alters is demonstrated.

  18. [Establishment and comparison of stoma and stoma-free heterotopic small intestine transplantation models in mice].

    Science.gov (United States)

    Meng, Ning; Pan, Zhijian; Liu, Yadong; Xu, Xin; Shen, Jiliang; Shen, Bo

    2016-03-01

    To establish stoma and stoma-free murine models of heterotopic small intestine transplantation in order to choose a more effective and reliable model. A total of 140 male 8-10 weeks age C57BL/6(B6) mice weighted 25-30 g were enrolled in the experiment. Syngeneic heterotopic small intestine transplantation was performed between C57BL/6 mice, and recipient mice were divided into either stoma or stoma-free group. Heterotopic small intestine transplantation was performed in 70 mice, with 35 mice in each group. After closing the proximal end of the graft by ligation, the distal end of graft was exteriorized as a stoma then secured to the skin of the abdominal wall in stoma group. In stoma-free group, the distal end of graft was anastomosed end-to-side to the recipient ileum. Successful rate of operation, two-week survival rate, operation time, associated complications, postoperative care time and body weight change were recorded and compared between two groups. The successful rate of stoma group was 65.7%, while it was 80.0% of stoma-free group (χ(2)=1.806, P=0.179). The operation time of donor in stoma group was (48.1±6.6) minutes, while it was (47.2±5.9) minutes in stoma-free group (t=0.598, P=0.552). The operation time of recipient in stoma group was (77.9±9.1) minutes, while it was (76.4±8.3) minutes in stoma-free group (t=0.683, P=0.497). The cold ischemic time of graft in stoma group was (34.7±4.0) minutes, while it was (33.9±4.6) minutes in stoma-free group(t=0.667, P=0.507). The two-week survival rate of stoma group was 45.7%, and it was 77.1% of stoma-free group(χ(2)=7.295, P=0.007). The stoma group had more complications[54.3%(19/35) vs. 22.9%(8/35), χ(2)=7.295, P=0.007], which needed more postoperative care time(191 min vs. 35 min). The weight loss in stoma group in the third day after operation was more significant [(81.52±5.20)% vs. (85.46±4.65)%, t=2.856, P=0.006]. By 2 weeks after operation, the weight of mice in both groups retruned to 95% of

  19. Recent Progress on Labfit: a Multispectrum Analysis Program for Fitting Lineshapes Including the Htp Model and Temperature Dependence

    Science.gov (United States)

    Cich, Matthew J.; Guillaume, Alexandre; Drouin, Brian; Benner, D. Chris

    2017-06-01

    Multispectrum analysis can be a challenge for a variety of reasons. It can be computationally intensive to fit a proper line shape model especially for high resolution experimental data. Band-wide analyses including many transitions along with interactions, across many pressures and temperatures are essential to accurately model, for example, atmospherically relevant systems. Labfit is a fast multispectrum analysis program originally developed by D. Chris Benner with a text-based interface. More recently at JPL a graphical user interface was developed with the goal of increasing the ease of use but also the number of potential users. The HTP lineshape model has been added to Labfit keeping it up-to-date with community standards. Recent analyses using labfit will be shown to demonstrate its ability to competently handle large experimental datasets, including high order lineshape effects, that are otherwise unmanageable.

  20. Application of a new combined model including radiological indicators to predict difficult airway in patients undergoing surgery for cervical spondylosis.

    Science.gov (United States)

    Xu, Mao; Li, Xiaoxi; Wang, Jun; Guo, Xiangyang

    2014-01-01

    Airway management is crucial in clinical anesthesia. Many complications associated with airway management result from unexpected difficult airway, but predicting a difficult airway is a major challenge. We investigated the efficacy of a new combined model including radiological indicators to predict difficult airway in patients undergoing surgery for cervical spondylosis, a population with a high incidence of difficult airway. We randomly enrolled 303 patients scheduled for elective surgery for cervical spondylosis at Peking University Third Hospital between August 2012 and March 2013. Preoperatively, patients were evaluated for difficult airway according to a clinical index and parameters on lateral cervical radiographs and magnetic resonance images. Difficult airway was defined as Cormack-Lehane grades III-IV. Logistic regression was used to identify a combined (clinical and radiological) model for difficult airway. A receiver operating characteristic (ROC) curve was used to describe the effectiveness of prediction. We identified three clinical predictive factors using the ROC curve: mouth opening, sternomental distance, and neck mobility. We created a clinical model using three factors: gender, age, and mouth opening, with odds ratios (OR) of 0.370, 1.034, and 0.358, respectively. Using the clinical and radiological parameters, we formulated a combined model with five risk factors: gender, mouth opening, atlanto-occipital gap, the angle from the second to sixth cervical vertebraes in the neutral position, and the angle difference of d (the angle between the laryngeal axis and the epiglottic axis) from the neutral position to extension (OR: 0.107, 0.355, 0.846, 1.057, and 0.952, respectively). The sensitivity and specificity of the combined model were 80.0% and 65.7%, respectively, and the ROC curve confirmed that the combined model was better than any single clinical predictor and the clinical model. The efficacy of the combined model including both clinical and

  1. Haemophilus influenzae LicB contributes to lung damage in an aged mice co-infection model.

    Science.gov (United States)

    Bondy, Jessica; Osharovich, Sofya; Storm, Julie; Durning, Graham; McAuliffe, Timothy; Fan, Xin

    2016-01-01

    Phosphorylcholine (ChoP) decoration of lipopolysaccharides is an important virulence strategy adopted by Haemophilus influenzae to establish a niche on the mucosal surface and to promote adherence to the host cells. The incorporation of ChoP on the LPS surface involves the lic1 operon, which consists of the licA, licB, licC, and licD genes. Among which, licB is a choline transporter gene required for acquisition of choline from environmental sources. In this study, we investigated the pathogenesis of the licB gene in an aged mice infection model. Due to immediate clearance of H. influenzae upon infection in mice, we employed influenza A virus and H. influenzae co-infection model. Our data showed that in the co-infection model, the secondary bacterial infection with a very low H. influenzae concentration of 100 colony forming unit is lethal to the aged mice. Although we did not observe any differences in weight loss between parent and licB mutant strains during the course of infection, a significant reduction of lung tissue damage was observed in the licB mutant infected aged mice. These results suggest that the licB gene is a virulence factor during H. influenzae infection in the lung in aged mice, possibly due to the increased binding to the host cell receptor via ChoP expression on the bacterial surface. In addition, when aged mice and mature mice were compared in the challenge experiments, we did not observe any protective immunity in the co-infection model suggesting the detrimental effects of the secondary bacterial infection on the aged mice in contrast to obvious immune-protections observed in the mature mice. The results of our experiments also implied that the co-infection model with influenza A virus and H. influenzae may be employed as a model system to study H. influenzae pathogenesis in vivo in aged mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer

    Directory of Open Access Journals (Sweden)

    V. C. N. Fonseca-Filho

    2017-05-01

    Full Text Available Abstract Calcitriol antiproliferative effects were observed in xenografts of breast cancer cell lines, however they were not yet investigated in tumorgrafts, consisting of freshly collected breast cancer samples xenografted into animals. Objectives To establish a tumorgraft model, from freshly collected breast cancer samples, which were directly implanted in nude mice, to study calcitriol effects. Methods Breast cancer samples collected from 12 patients were orthotopically implanted into nude mice. Animals were treated with weekly intratumoral injections of calcitriol 3 μg/Kg, which was previously shown to induce peak serum calcitriol levels in the predicted therapeutic range. Results Success engraftment rate was 25%. Tumorgrafts were established from aggressive (HER2 positive or histological grade 3 highly proliferative samples and original tumor characteristics were preserved. Calcitriol highly induced its target gene, CYP24A1, indicating that the genomic vitamin D pathway is active in tumorgrafts. However, no differences in the expression of proliferation and apoptosis markers (BrdU incorporation, Ki67, CDKN1A, CDKN1B, BCL2 expression were observed in these highly proliferative tumor samples. Conclusions Tumorgrafts seem a promising model to explore other calcitriol doses and regimens, considering the heterogeneity of the disease and microenvironment interactions.

  3. Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer.

    Science.gov (United States)

    Fonseca-Filho, V C N; Katayama, M L H; Lyra, E C; Maria, D A; Basso, R A; Nonogaki, S; Guerra, J M; Maistro, S; Góes, J C G S; Folgueira, M A A K

    2017-11-01

    Calcitriol antiproliferative effects were observed in xenografts of breast cancer cell lines, however they were not yet investigated in tumorgrafts, consisting of freshly collected breast cancer samples xenografted into animals. To establish a tumorgraft model, from freshly collected breast cancer samples, which were directly implanted in nude mice, to study calcitriol effects. Breast cancer samples collected from 12 patients were orthotopically implanted into nude mice. Animals were treated with weekly intratumoral injections of calcitriol 3 μg/Kg, which was previously shown to induce peak serum calcitriol levels in the predicted therapeutic range. Success engraftment rate was 25%. Tumorgrafts were established from aggressive (HER2 positive or histological grade 3) highly proliferative samples and original tumor characteristics were preserved. Calcitriol highly induced its target gene, CYP24A1, indicating that the genomic vitamin D pathway is active in tumorgrafts. However, no differences in the expression of proliferation and apoptosis markers (BrdU incorporation, Ki67, CDKN1A, CDKN1B, BCL2 expression) were observed in these highly proliferative tumor samples. Tumorgrafts seem a promising model to explore other calcitriol doses and regimens, considering the heterogeneity of the disease and microenvironment interactions.

  4. ASIC1a Deficient Mice Show Unaltered Neurodegeneration in the Subacute MPTP Model of Parkinson Disease.

    Science.gov (United States)

    Komnig, Daniel; Imgrund, Silke; Reich, Arno; Gründer, Stefan; Falkenburger, Björn H

    2016-01-01

    Inflammation contributes to the death of dopaminergic neurons in Parkinson disease and can be accompanied by acidification of extracellular pH, which may activate acid-sensing ion channels (ASIC). Accordingly, amiloride, a non-selective inhibitor of ASIC, was protective in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson disease. To complement these findings we determined MPTP toxicity in mice deficient for ASIC1a, the most common ASIC isoform in neurons. MPTP was applied i.p. in doses of 30 mg per kg on five consecutive days. We determined the number of dopaminergic neurons in the substantia nigra, assayed by stereological counting 14 days after the last MPTP injection, the number of Nissl positive neurons in the substantia nigra, and the concentration of catecholamines in the striatum. There was no difference between ASIC1a-deficient mice and wildtype controls. We are therefore not able to confirm that ASIC1a are involved in MPTP toxicity. The difference might relate to the subacute MPTP model we used, which more closely resembles the pathogenesis of Parkinson disease, or to further targets of amiloride.

  5. Korean red ginseng extract ameliorates skin lesions in NC/Nga mice: an atopic dermatitis model.

    Science.gov (United States)

    Lee, Ji Hyun; Cho, Sang Hyun

    2011-01-27

    Korean red ginseng (KRG, Panax ginseng C.A. Meyer) has traditionally been considered to harbor anti-allergic effects, however its action on atopic dermatitis (AD) is unclear. Therefore, we investigated the effect of KRG on AD using NC/Nga mice as an AD model. In addition, we examined the effect of aprepitant (substance P specific neurokinin receptor antagonist) on AD. The KRG extract and aprepitant were administered orally to NC/Nga mice. The efficacy of KRG and aprepitant was evaluated by assessing total clinical severity score, ear thickness, serum IgE level and histology. In addition, mRNA and protein expression were measured by real-time RT-PCR and immunohistochemistry, respectively. The KRG extract significantly reduced the total clinical severity score, ear thickness and the level of serum IgE in AD mouse model, whereas aprepitant reduced only the serum IgE level. KRG not only decreased TNF-α, IFN-γ and substance P but also reduced the infiltration of FOXP3+ regulatory T (Treg) cells and CD1a+ Langerhans cells in the lesions, whereas aprepitant decreased only substance P and the infiltration of Treg cells. These results suggest that KRG extract may be a potential therapeutic modality for AD and aprepitant could be used as adjunctive agent to control pruritus in AD. Crown Copyright © 2010. Published by Elsevier Ireland Ltd. All rights reserved.

  6. Steroid Tumor Environment in Male and Female Mice Model of Canine and Human Inflammatory Breast Cancer

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    Sara Caceres

    2016-01-01

    Full Text Available Canine inflammatory mammary cancer (IMC shares clinical and histopathological characteristics with human inflammatory breast cancer (IBC and has been proposed as a good model for studying the human disease. The aim of this study was to evaluate the capacity of female and male mice to reproduce IMC and IBC tumors and identify the hormonal tumor environment. To perform the study sixty 6–8-week-old male and female mice were inoculated subcutaneously with a suspension of 106 IPC-366 and SUM149 cells. Tumors and serum were collected and used for hormonal analysis. Results revealed that IPC-366 reproduced tumors in 90% of males inoculated after 2 weeks compared with 100% of females that reproduced tumor at the same time. SUM149 reproduced tumors in 40% of males instead of 80% of females that reproduced tumors after 4 weeks. Both cell lines produce distant metastasis in lungs being higher than the metastatic rates in females. EIA analysis revealed that male tumors had higher T and SO4E1 concentrations compared to female tumors. Serum steroid levels were lower than those found in tumors. In conclusion, IBC and IMC male mouse model is useful as a tool for IBC research and those circulating estrogens and intratumoral hormonal levels are crucial in the development and progression of tumors.

  7. ASIC1a Deficient Mice Show Unaltered Neurodegeneration in the Subacute MPTP Model of Parkinson Disease.

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    Daniel Komnig

    Full Text Available Inflammation contributes to the death of dopaminergic neurons in Parkinson disease and can be accompanied by acidification of extracellular pH, which may activate acid-sensing ion channels (ASIC. Accordingly, amiloride, a non-selective inhibitor of ASIC, was protective in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP mouse model of Parkinson disease. To complement these findings we determined MPTP toxicity in mice deficient for ASIC1a, the most common ASIC isoform in neurons. MPTP was applied i.p. in doses of 30 mg per kg on five consecutive days. We determined the number of dopaminergic neurons in the substantia nigra, assayed by stereological counting 14 days after the last MPTP injection, the number of Nissl positive neurons in the substantia nigra, and the concentration of catecholamines in the striatum. There was no difference between ASIC1a-deficient mice and wildtype controls. We are therefore not able to confirm that ASIC1a are involved in MPTP toxicity. The difference might relate to the subacute MPTP model we used, which more closely resembles the pathogenesis of Parkinson disease, or to further targets of amiloride.

  8. Morphological studies in a model for dengue-2 virus infection in mice

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    Ortrud Monika Barth

    2006-12-01

    Full Text Available One of the main difficulties in studying dengue virus infection in humans and in developing a vaccine is the absence of a suitable animal model which develops the full spectrum of dengue fever, dengue haemorrhagic fever, and dengue shock syndrome. It is our proposal to present morphological aspects of an animal model which shows many similarities with the dengue infection in humans. BALB/c mice were intraperitoneally infected with non-neuroadapted dengue virus serotype 2 (DENV-2. Histopathological and morphometrical analyses of liver tissue revealed focal alterations along the infection, reaching wide-ranging portal and centrolobular veins congestion and sinusoidal cell death. Additional ultrastructural observations demonstrated multifocal endothelial injury, platelet recruitment, and alterated hepatocytes. Dengue virus antigen was detected in hepatocytes and in the capillar endothelium of the central lobular vein area. Liver function tests showed high levels of aspartate transaminase and alanine transaminase enzyme activity. Lung tissue showed interstitial pneumonia and mononuclear cells, interseptal oedema, hyperplasia, and hypertrophy of the bronchiolar epithelial cells. DENV-2 led to a transient inflammatory process, but caused focal alterations of the blood-exchange barrier. Viremia was observed from 2nd to 11th day p.i. by isolation of DENV-2 in C6/36 mosquito cell line inoculated with the supernatant of macerated liver, lung, kidney, and cerebellum tissues of the infected mice.

  9. Experimental Model of Progressive Disseminated Trichosporonosis in Mice with Latent Trichosporonemia

    Science.gov (United States)

    Yamagata, Eiji; Kamberi, Perparim; Yamakami, Yuriko; Hashimoto, Atsuro; Nasu, Masaru

    2000-01-01

    Trichosporon asahii and Trichosporon mucoides are the most common strains of fungi that cause disseminated trichosporonosis, a severe opportunistic infection in immunocompromised hosts. We have previously established a nested PCR assay using serum samples for detection of both strains. Here we describe a new experimental animal model for investigating the underlying mechanisms of disseminated trichosporonosis. T. asahii (OMU239, a clinical isolate from a patient with acute myelogenous leukemia) and 8-week-old ICR male mice were used in all experiments. A suspension of T. asahii (3 × 106 CFU/animal) was injected into the caudal vein of each mouse after immunosuppression with cyclophosphamide (200 mg/kg of body weight/day for 2 days) and prednisolone (30 mg/kg/day for 1 day). Mice were then divided into four subgroups (R0, R1, R2, and R3) based on the time of reimmunosuppression. The latter was performed using the same drugs 1 week (group R1), 2 weeks (group R2), and 3 weeks (group R3) after fungal infection. Reimmunosuppression was not performed in group R0. The 5-week-survival rates of mice after T. asahii infection were 0% for group R1, 50% for group R2, 80% for group R3, and 80% for group R0. There was a significant difference in the survival rates between group R1 and either group R0 or R3 (P < 0.05). Fungal clearance in peripheral blood and various organs of group R1 and R2 was delayed relative to that of group R0 but was similar to the control in group R3 in spite of reimmunosuppression. Our results suggest that the critical period for the development of disseminated trichosporonosis in our model is shorter than 3 weeks after T. asahii infection. We concluded that mice during this critical period were in a state of latent trichosporonemia. Comparison of the survival rates suggests that the nested PCR assay was more useful than blood culture and glucuronoxylomannan antigen assay in the detection of this latent trichosporonemia. PMID:10970368

  10. Tracer experiment data sets for the verification of local and meso-scale atmospheric dispersion models including topographic effects

    International Nuclear Information System (INIS)

    Sartori, E.; Schuler, W.

    1992-01-01

    Software and data for nuclear energy applications are acquired, tested and distributed by several information centres; in particular, relevant computer codes are distributed internationally by the OECD/NEA Data Bank (France) and by ESTSC and EPIC/RSIC (United States). This activity is coordinated among the centres and is extended outside the OECD area through an arrangement with the IAEA. This article proposes more specifically a scheme for acquiring, storing and distributing atmospheric tracer experiment data (ATE) required for verification of atmospheric dispersion models especially the most advanced ones including topographic effects and specific to the local and meso-scale. These well documented data sets will form a valuable complement to the set of atmospheric dispersion computer codes distributed internationally. Modellers will be able to gain confidence in the predictive power of their models or to verify their modelling skills. (au)

  11. Repetitive behavior and increased activity in mice with Purkinje cell loss: a model for understanding the role of cerebellar pathology in autism.

    Science.gov (United States)

    Martin, Loren A; Goldowitz, Dan; Mittleman, Guy

    2010-02-01

    Repetitive behaviors and hyperactivity are common features of developmental disorders, including autism. Neuropathology of the cerebellum is also a frequent occurrence in autism and other developmental disorders. Recent studies have indicated that cerebellar pathology may play a causal role in the generation of repetitive and hyperactive behaviors. In this study, we examined the relationship between cerebellar pathology and these behaviors in a mouse model of Purkinje cell loss. Specifically, we made aggregation chimeras between Lc/+ mutant embryos and +/+ embryos. Lc/+ mice lose 100% of their Purkinje cells postnatally due to a cell-intrinsic gain-of-function mutation. Through our histological examination, we demonstrated that Lc/++/+ chimeric mice have Purkinje cells ranging from zero to normal numbers. Our analysis of these chimeric cerebella confirmed previous studies on Purkinje cell lineage. The results of both open-field activity and hole-board exploration testing indicated negative relationships between Purkinje cell number and measures of activity and investigatory nose-poking. Additionally, in a progressive-ratio operant paradigm, we found that Lc/+ mice lever-pressed significantly less than +/+ controls, which led to significantly lower breakpoints in this group. In contrast, chimeric mice lever-pressed significantly more than controls and this repetitive lever-pressing behavior was significantly and negatively correlated with total Purkinje cell numbers. Although the performance of Lc/+ mice is probably related to their motor deficits, the significant relationships between Purkinje cell number and repetitive lever-pressing behavior as well as open-field activity measures provide support for a role of cerebellar pathology in generating repetitive behavior and increased activity in chimeric mice.

  12. Analytical linear energy transfer model including secondary particles: calculations along the central axis of the proton pencil beam

    International Nuclear Information System (INIS)

    Marsolat, F; De Marzi, L; Mazal, A; Pouzoulet, F

    2016-01-01

    In proton therapy, the relative biological effectiveness (RBE) depends on various types of parameters such as linear energy transfer (LET). An analytical model for LET calculation exists (Wilkens’ model), but secondary particles are not included in this model. In the present study, we propose a correction factor, L sec , for Wilkens’ model in order to take into account the LET contributions of certain secondary particles. This study includes secondary protons and deuterons, since the effects of these two types of particles can be described by the same RBE-LET relationship. L sec was evaluated by Monte Carlo (MC) simulations using the GATE/GEANT4 platform and was defined by the ratio of the LET d distributions of all protons and deuterons and only primary protons. This method was applied to the innovative Pencil Beam Scanning (PBS) delivery systems and L sec was evaluated along the beam axis. This correction factor indicates the high contribution of secondary particles in the entrance region, with L sec values higher than 1.6 for a 220 MeV clinical pencil beam. MC simulations showed the impact of pencil beam parameters, such as mean initial energy, spot size, and depth in water, on L sec . The variation of L sec with these different parameters was integrated in a polynomial function of the L sec factor in order to obtain a model universally applicable to all PBS delivery systems. The validity of this correction factor applied to Wilkens’ model was verified along the beam axis of various pencil beams in comparison with MC simulations. A good agreement was obtained between the corrected analytical model and the MC calculations, with mean-LET deviations along the beam axis less than 0.05 keV μm −1 . These results demonstrate the efficacy of our new correction of the existing LET model in order to take into account secondary protons and deuterons along the pencil beam axis. (paper)

  13. Degeneration of retinal on bipolar cells induced by serum including autoantibody against TRPM1 in mouse model of paraneoplastic retinopathy.

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    Shinji Ueno

    Full Text Available The paraneoplastic retinopathies (PRs are a group of eye diseases characterized by a sudden and progressive dysfunction of the retina caused by an antibody against a protein in a neoplasm. Evidence has been obtained that the transient receptor potential melastatin 1 (TRPM1 protein was one of the antigens for the autoantibody against the ON bipolar cells in PR patients. However, it has not been determined how the autoantibody causes the dysfunction of the ON bipolar cells. We hypothesized that the antibody against TRPM1 in the serum of patients with PR causes a degeneration of retinal ON bipolar cells. To test this hypothesis, we injected the serum from the PR patient, previously shown to contain anti-TRPM1 antibodies by westerblot, intravitreally into mice and examined the effects on the retina. We found that the electroretinograms (ERGs of the mice were altered acutely after the injection, and the shape of the ERGs resembled that of the patient with PR. Immunohistochemical analysis of the eyes injected with the serum showed immunoreactivity against bipolar cells only in wild-type animals and not in TRPM1 knockout mice,consistent with the serum containing anti-TRPM1 antibodies. Histology also showed that some of the bipolar cells were apoptotic by 5 hours after the injection in wild type mice, but no bipolar cell death was found in TRPM1 knockout mice, . At 3 months, the inner nuclear layer was thinner and the amplitudes of the ERGs were still reduced. These results indicate that the serum of a patient with PR contained an antibody against TRPM1 caused an acute death of retinal ON bipolar cells of mice.

  14. Finite Element Modeling and Analysis of Nonlinear Impact and Frictional Motion Responses Including Fluid—Structure Coupling Effects

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    Yong Zhao

    1997-01-01

    Full Text Available A nonlinear three dimensional (3D single rack model and a nonlinear 3D whole pool multi-rack model are developed for the spent fuel storage racks of a nuclear power plant (NPP to determine impacts and frictional motion responses when subjected to 3D excitations from the supporting building floor. The submerged free standing rack system and surrounding water are coupled due to hydrodynamic fluid-structure interaction (FSI using potential theory. The models developed have features that allow consideration of geometric and material nonlinearities including (1 the impacts of fuel assemblies to rack cells, a rack to adjacent racks or pool walls, and rack support legs to the pool floor; (2 the hydrodynamic coupling of fuel assemblies with their storing racks, and of a rack with adjacent racks, pool walls, and the pool floor; and (3 the dynamic motion behavior of rocking, twisting, and frictional sliding of rack modules. Using these models 3D nonlinear time history dynamic analyses are performed per the U.S. Nuclear Regulatory Commission (USNRC criteria. Since few such modeling, analyses, and results using both the 3D single and whole pool multiple rack models are available in the literature, this paper emphasizes description of modeling and analysis techniques using the SOLVIA general purpose nonlinear finite element code. Typical response results with different Coulomb friction coefficients are presented and discussed.

  15. The use of mice and rats as animal models for cardiopulmonary resuscitation research.

    Science.gov (United States)

    Papadimitriou, D; Xanthos, T; Dontas, I; Lelovas, P; Perrea, D

    2008-07-01

    Cardiopulmonary resuscitation (CPR) after the induction of cardiac arrest (CA) has been studied in mice and rats. The anatomical and physiological parameters of the cardiopulmonary system of these two species have been defined during experimental studies and are comparable with those of humans. Moreover, these animal models are more ethical to establish and are easier to manipulate, when compared with larger experimental animals. Accordingly, the effects of successful CPR on the function of vital organs, such as the brain, have been investigated because damage to these vital organs is of concern in CA survivors. Furthermore, the efficacy of several drugs, such as adrenaline (epinephrine), vasopressin and nitroglycerin, has been evaluated for use in CA in these small animal models. The purpose of these studies is not only to increase the rate of survival of CA victims, but also to improve their quality of life by reducing damage to their vital organs after CA and during CPR.

  16. Effect of pioglitazone on metabolic features in endotoxemia model in obese diabetic db/db mice.

    Science.gov (United States)

    Sharma, Manoranjan; Mohapatra, Jogeswar; Malik, Umar; Nagar, Jignesh; Chatterjee, Abhijit; Ramachandran, Balaraman; Jain, Mukul R

    2017-06-01

    Infectious diseases are more frequent in diabetic patients, leading to increased morbidity and mortality. Endotoxemia affects glucose metabolism and lipolytic capacity. The aims of the present study were to determine whether endotoxemia exacerbates metabolic features (adipose inflammation, adipogenesis, and insulin resistance [IR]) in an animal model of diabetes (i.e. db/db mice) after acute infection and the effects of pioglitazone. Female db/db mice treated with pioglitazone (3 and 30 mg/kg, p.o.) for 14 days were challenged with lipopolysaccharide (LPS; 200 μg/kg), followed by an oral glucose tolerance test (OGTT). Quantitative real-time polymerase chain reaction (PCR) was used to evaluate the expression of genes in white adipose tissue (WAT) involved in: (i) adipogenesis (lipoprotein lipase [Lpl], fatty acid binding protein-4 [Ap2] and adiponectin [Adipoq]); (ii) insulin signaling (peroxisome proliferator-activated receptor gamma [Pparg], suppressor of cytokine signaling 3 [Socs3], solute carrier family 2 [facilitated glucose transporter], member 4 [Slc2a4]); and (iii) inflammation (tumor necrosis factor [Tnf], interleukin-6 [Il6], monocyte chemoattractant protein-1 [Ccl2], cyclo-oxygenase-2 [prostaglandin-endoperoxide synthase 2; Ptgs2]). Experimental endotoxemia downregulated mRNA expression of Pparg, Slc2a4, Adipoq, Lpl, and Ap2, which coincided with upregulation of Il6, Tnf, Ccl2, Ptgs2, and Socs3 expression. Pioglitazone dose-dependently decreased Tnf, Il6, Ccl2, Ptgs2, and Socs3 expression in WAT, in association with upregulation of Lpl, Ap2, Slc2a4, and Adipoq expression, indicating improvement in endotoxin-induced IR. The findings suggest that LPS challenge exacerbates IR in db/db mice by altering the expression of genes in WAT involved in adipogenesis and inflammation, which is effectively controlled by pioglitazone treatment. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  17. Hypericum perforatum treatment: effect on behaviour and neurogenesis in a chronic stress model in mice

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    Cuzzocrea Salvatore

    2011-01-01

    Full Text Available Abstract Background Extracts of Hypericum perforatum (St. John's wort have been traditionally recommended for a wide range of medical conditions, in particular mild-to-moderate depression. The present study was designed to investigate the effect of Hypericum perforatum treatment in a mouse model of anxiety/depressive-like behavior, induced by chronic corticosterone administration. Methods CD1 mice were submitted to 7 weeks corticosterone administration and then behavioral tests as Open Field (OF, Novelty-Suppressed Feeding (NSF, Forced Swim Test (FST were performed. Cell proliferation in hippocampal dentate gyrus (DG was investigated by both 5-bromo-2'-deoxyuridine (BrdU and doublecortin (DCX immunohistochemistry techniques and stereological procedure was used to quantify labeled cells. Golgi-impregnation method was used to evaluate changes in dendritic spines in DG. Hypericum perforatum (30 mg/Kg has been administered for 3 weeks and then neural development in the adult hippocampus and behavioral changes have been examined. Results The anxiety/depressive-like state due to chronic corticosterone treatment was reversed by exogenous administration of Hypericum perforatum; the proliferation of progenitor cells in mice hippocampus was significantly reduced under chronic corticosterone treatment, whereas a long term treatment with Hypericum perforatum prevented the corticosterone-induced decrease in hippocampal cell proliferation. Corticosterone-treated mice exhibited a reduced spine density that was ameliorated by Hypericum perforatum administration. Conclusion These results provide evidence of morphological adaptations occurring in mature hippocampal neurons that might underlie resilient responses to chronic stress and contribute to the therapeutic effects of chronic Hypericum perforatum treatment.

  18. Studies on the correlation with olfactory dysfunction in a transgenic mice model of Alzheimer's disease

    Science.gov (United States)

    Rasheed, Ameer; Lee, Ji Hye; Suh, Yoo-Hun; Moon, Cheil

    2013-05-01

    Alzheimer's disease (AD) is a progressively debilitating neurodegenerative disorder characterized by the presence of proteinaceous deposits in the brain. AD often results in olfactory dysfunction and impaired olfactory perceptual acuity may be a potential biomarker for early diagnosis of AD. Until recently, there is no Alzheimer's nanoscope or any other high-end microscope developed to be capable of seeing buried feature of AD clearly. Modern neuroimaging techniques are more effective only after the occurrence of cognitive impairment. Therefore, early detection of Alzheimer's disease is critical in developing effective treatment of AD. H and E (Haematoxyline and Eosin) staining is performed for examining gross morphological changes, while TUNEL (transferase (TdT)-mediated dUTP nick end labeling) staining for monitoring neuronal death in the olfactory epithelium (OE). Furthermore, immunohistochemistry and western blot are performed to examine β-amyloid protein expression. AD model animals were Tg2576 (transgenic mice that overexpress a mutated form of the Aβ precursor protein), and 6 month (before onset of AD symptoms) and 14 month (after onset of AD symptoms) old WT (wild type) and transgenic mice were compared in their olfactory system. We found that in OE of Tg2576 mice, thickness and total number of cells were decreased, while the numbers of TUNEL-positive neurons, caspase-3 activation were significantly increased compared with age-matched WT. Our results demonstrate that the olfactory system may get deteriorated before onset of AD symptoms. Our findings imply that an olfactory biopsy could be served as an early and relatively simple diagnostic tool for potential AD patients.

  19. Effects of low dose rate irradiation on life span prolongation of human premature-aging syndrome model mice

    International Nuclear Information System (INIS)

    Nomura, Takaharu

    2006-01-01

    We previously showed that Type II diabetes model mice prolonged of their life span by life long low dose rate irradiation. We also found that antioxidant function in variety tissues of some strain of mice were enhancement after low dose/low dose rate irradiation. The prolongation of life span might depend on certain damaged level of reactive oxygen species. We thought the effect of the prolongation was due to the enhancement of the antioxidant activities after irradiation. We investigated whether the enhancement of antioxidant activities after low dose rate irradiation had an effect on life span prolongation. Four-week-old female human premature-aging syndrome model mice, kl/kl (klotho) mice, which the life span of this model mouse is about 65 days, were irradiated with gamma rays at 0.35, 0.70 or 1.2 mGy/hr. The 0.70 mGy/hr-irradiated group remarkably effected on the prolongation of their life span. Some mice of the group were extremely survived for about and more 100 days. Antioxidant activities in the irradiated groups were enhancement by low dose rate irradiation, however the dependence of the dose rates were not clearly difference. These results suggest that the antioxidant activities in this model mouse were enhanced by the low dose rate irradiation, and may make it possible to prolong the life span of this mouse. (author)

  20. Extensions of the Rosner-Colditz breast cancer prediction model to include older women and type-specific predicted risk.

    Science.gov (United States)

    Glynn, Robert J; Colditz, Graham A; Tamimi, Rulla M; Chen, Wendy Y; Hankinson, Susan E; Willett, Walter W; Rosner, Bernard

    2017-08-01

    A breast cancer risk prediction rule previously developed by Rosner and Colditz has reasonable predictive ability. We developed a re-fitted version of this model, based on more than twice as many cases now including women up to age 85, and further extended it to a model that distinguished risk factor prediction of tumors with different estrogen/progesterone receptor status. We compared the calibration and discriminatory ability of the original, the re-fitted, and the type-specific models. Evaluation used data from the Nurses' Health Study during the period 1980-2008, when 4384 incident invasive breast cancers occurred over 1.5 million person-years. Model development used two-thirds of study subjects and validation used one-third. Predicted risks in the validation sample from the original and re-fitted models were highly correlated (ρ = 0.93), but several parameters, notably those related to use of menopausal hormone therapy and age, had different estimates. The re-fitted model was well-calibrated and had an overall C-statistic of 0.65. The extended, type-specific model identified several risk factors with varying associations with occurrence of tumors of different receptor status. However, this extended model relative to the prediction of any breast cancer did not meaningfully reclassify women who developed breast cancer to higher risk categories, nor women remaining cancer free to lower risk categories. The re-fitted Rosner-Colditz model has applicability to risk prediction in women up to age 85, and its discrimination is not improved by consideration of varying associations across tumor subtypes.

  1. Method for widespread microRNA-155 inhibition prolongs survival in ALS-model mice

    Science.gov (United States)

    Koval, Erica D.; Shaner, Carey; Zhang, Peter; du Maine, Xavier; Fischer, Kimberlee; Tay, Jia; Chau, B. Nelson; Wu, Gregory F.; Miller, Timothy M.

    2013-01-01

    microRNAs (miRNAs) are dysregulated in a variety of disease states, suggesting that this newly discovered class of gene expression repressors may be viable therapeutic targets. A microarray of miRNA changes in ALS-model superoxide dismutase 1 (SOD1)G93A rodents identified 12 miRNAs as significantly changed. Six miRNAs tested in human ALS tissues were confirmed increased. Specifically, miR-155 was increased 5-fold in mice and 2-fold in human spinal cords. To test miRNA inhibition in the central nervous system (CNS) as a potential novel therapeutic, we developed oligonucleotide-based miRNA inhibitors (anti-miRs) that could inhibit miRNAs throughout the CNS and in the periphery. Anti-miR-155 caused global derepression of targets in peritoneal macrophages and, following intraventricular delivery, demonstrated widespread functional distribution in the brain and spinal cord. After treating SOD1G93A mice with anti-miR-155, we significantly extended survival by 10 days and disease duration by 15 days (38%) while a scrambled control anti-miR did not significantly improve survival or disease duration. Therefore, antisense oligonucleotides may be used to successfully inhibit miRNAs throughout the brain and spinal cord, and miR-155 is a promising new therapeutic target for human ALS. PMID:23740943

  2. Vaping Synthetic Cannabinoids: A Novel Preclinical Model of E-Cigarette Use in Mice.

    Science.gov (United States)

    Lefever, Timothy W; Marusich, Julie A; Thomas, Brian F; Barrus, Daniel G; Peiper, Nicholas C; Kevin, Richard C; Wiley, Jenny L

    2017-01-01

    Smoking is the most common route of administration for cannabis; however, vaping cannabis extracts and synthetic cannabinoids ("fake marijuana") in electronic cigarette devices has become increasingly popular. Yet, most animal models used to investigate biological mechanisms underlying cannabis use employ injection as the route of administration. This study evaluated a novel e-cigarette device that delivers aerosolized cannabinoids to mice. The effects of aerosolized and injected synthetic cannabinoids (CP 55,940, AB-CHMINACA, XLR-11, and JWH-018) in mice were compared in a battery of bioassays in which psychoactive cannabinoids produce characteristic effects. The most potent cannabinoids (CP 55,940 and AB-CHMINACA) produced the full cannabinoid profile (ie, hypothermia, hypolocomotion, and analgesia), regardless of the route of administration. In contrast, aerosolized JWH-018 and XLR-11 did not produce the full profile of cannabimimetic effects. Results of time course analysis for hypothermia showed that aerosol exposure to CP 55,940 and AB-CHMINACA produced faster onset of effects and shorter duration of action than injection. The ability to administer cannabinoids to rodents using the most common route of administration among humans provides a method for collecting preclinical data with enhanced translational relevance.

  3. Vaping Synthetic Cannabinoids: A Novel Preclinical Model of E-Cigarette Use in Mice

    Directory of Open Access Journals (Sweden)

    Timothy W Lefever

    2017-03-01

    Full Text Available Smoking is the most common route of administration for cannabis; however, vaping cannabis extracts and synthetic cannabinoids (“fake marijuana” in electronic cigarette devices has become increasingly popular. Yet, most animal models used to investigate biological mechanisms underlying cannabis use employ injection as the route of administration. This study evaluated a novel e-cigarette device that delivers aerosolized cannabinoids to mice. The effects of aerosolized and injected synthetic cannabinoids (CP 55,940, AB-CHMINACA, XLR-11, and JWH-018 in mice were compared in a battery of bioassays in which psychoactive cannabinoids produce characteristic effects. The most potent cannabinoids (CP 55,940 and AB-CHMINACA produced the full cannabinoid profile (ie, hypothermia, hypolocomotion, and analgesia, regardless of the route of administration. In contrast, aerosolized JWH-018 and XLR-11 did not produce the full profile of cannabimimetic effects. Results of time course analysis for hypothermia showed that aerosol exposure to CP 55,940 and AB-CHMINACA produced faster onset of effects and shorter duration of action than injection. The ability to administer cannabinoids to rodents using the most common route of administration among humans provides a method for collecting preclinical data with enhanced translational relevance.

  4. Antinociceptive Effect of Ondansetron in Albino Mice Using Acetic Acid Induced Writhing Model

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    Abhay Purohit

    2016-10-01

    Full Text Available Background: Pain is an unpleasant sensory and emotional experience. Pain is a protective mechanism. Pain occurs whenever any tissues are being damaged, and it causes the individual to react and to remove the pain stimulus. Aim and Objectives: To evaluate the antinociceptive effect of ondansetron in comparison with the standard diclofenac. Material and Methods: The antinociceptive effect was tested by using the acetic acid induced writhing model in Swiss Albino mice. Animals were divided into 4 groups of 6 animals each. Animals were received distilled water (control, diclofenac (standard, ondansetron 0.5mg/kg (test I and ondansetron 1mg/kg (test II. After 30 minutes of drug administration, 0.1 ml of 1% acetic acid was injected. Mice were placed individually into glass beakers and five minutes were allowed to elapse. They were then observed for a period of ten minutes and the numbers of writhes were recorded in each animal. The results were expressed as mean ± SEM. One way ANOVA with post-test was used for statistical calculation. Results: The numbers of writhes were 1.33±0.494 for diclofenac; 6.33±1.872 and 9.33±1.706 for ondansetron 0.5 and 1mg/kg respectively. Conclusion: Ondansetron demonstrated statistical significant antinociceptive activity at both doses (0.5mg/kg and 1mg/kg and statistically similar effect as diclofenac

  5. Repeated hapten exposure induces persistent tactile sensitivity in mice modeling localized provoked vulvodynia.

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    Jasmine Landry

    Full Text Available Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology. Epidemiologic studies associate the risk of vulvodynia with a history of atopic disease. We used an established model of hapten-driven contact hypersensitivity to investigate the underlying mechanisms of allergy-provoked prolonged sensitivity to pressure.We sensitized female ND4 Swiss mice to the hapten oxazolone on their flanks, and subsequently challenged them four days later with oxazolone or vehicle for ten consecutive days on the labia. We evaluated labiar sensitivity to touch, local mast cell accumulation, and hyperinnervation after ten challenges.Oxazolone-challenged mice developed significant tactile sensitivity that persisted for over three weeks after labiar allergen exposures ceased. Allergic sites were characterized by mast cell accumulation, sensory hyper-innervation and infiltration of regulatory CD4+CD25+FoxP3+ T cells as well as localized early increases in transcripts encoding Nerve Growth Factor and nerve-mast cell synapse marker Cell Adhesion Molecule 1. Local depletion of mast cells by intra-labiar administration of secretagogue compound 48/80 led to a reduction in both nerve density and tactile sensitivity.Mast cells regulate allergy-provoked persistent sensitivity to touch. Mast cell-targeted therapeutic strategies may provide novel means to manage and limit chronic pain conditions associated with atopic disease.

  6. Inhibition of Asthma in OVA Sensitized Mice Model by a Traditional Uygur Herb Nepeta bracteata Benth.

    Directory of Open Access Journals (Sweden)

    Jing Wang

    2016-01-01

    Full Text Available Asthma is a chronic lung inflammation which affects many people. As current therapies for asthma mainly rely on administration of glucocorticoids and have many side effects, new therapy is needed. In this study, we investigated Nepeta bracteata Benth., a traditional Uygur Herb, for its therapeutics effect in OVA induced asthmatic mice model. Treatment of OVA sensitized asthma mice with extract from Nepeta bracteata Benth. demonstrated improved lung pathology, as well as reduced infiltration of eosinophil and neutrophil. Nepeta bracteata Benth. extract also contributed to the rebalance of Th17/Treg cell via decreasing the Th17 cell and increasing the Treg, which was corresponding with the inhibited Th17 cytokine response and increased IL-10 level. Moreover, the reduced TGF-β level and Smad2/3 protein level also suggested that Nepeta bracteata Benth. extract could inhibit TGF-β mediated airway remodelling as well. Taken together, these data suggested that Nepeta bracteata Benth. may be a novel candidate for future antiasthma drug development.

  7. Nonlocal continuum-based modeling of breathing mode of nanowires including surface stress and surface inertia effects

    International Nuclear Information System (INIS)

    Ghavanloo, Esmaeal; Fazelzadeh, S. Ahmad; Rafii-Tabar, Hashem

    2014-01-01

    Nonlocal and surface effects significantly influence the mechanical response of nanomaterials and nanostructures. In this work, the breathing mode of a circular nanowire is studied on the basis of the nonlocal continuum model. Both the surface elastic properties and surface inertia effect are included. Nanowires can be modeled as long cylindrical solid objects. The classical model is reformulated using the nonlocal differential constitutive relations of Eringen and Gurtin–Murdoch surface continuum elasticity formalism. A new frequency equation for the breathing mode of nanowires, including small scale effect, surface stress and surface inertia is presented by employing the Bessel functions. Numerical results are computed, and are compared to confirm the validity and accuracy of the proposed method. Furthermore, the model is used to elucidate the effect of nonlocal parameter, the surface stress, the surface inertia and the nanowire orientation on the breathing mode of several types of nanowires with size ranging from 0.5 to 4 nm. Our results reveal that the combined surface and small scale effects are significant for nanowires with diameter smaller than 4 nm.

  8. Nonlocal continuum-based modeling of breathing mode of nanowires including surface stress and surface inertia effects

    Science.gov (United States)

    Ghavanloo, Esmaeal; Fazelzadeh, S. Ahmad; Rafii-Tabar, Hashem

    2014-05-01

    Nonlocal and surface effects significantly influence the mechanical response of nanomaterials and nanostructures. In this work, the breathing mode of a circular nanowire is studied on the basis of the nonlocal continuum model. Both the surface elastic properties and surface inertia effect are included. Nanowires can be modeled as long cylindrical solid objects. The classical model is reformulated using the nonlocal differential constitutive relations of Eringen and Gurtin-Murdoch surface continuum elasticity formalism. A new frequency equation for the breathing mode of nanowires, including small scale effect, surface stress and surface inertia is presented by employing the Bessel functions. Numerical results are computed, and are compared to confirm the validity and accuracy of the proposed method. Furthermore, the model is used to elucidate the effect of nonlocal parameter, the surface stress, the surface inertia and the nanowire orientation on the breathing mode of several types of nanowires with size ranging from 0.5 to 4 nm. Our results reveal that the combined surface and small scale effects are significant for nanowires with diameter smaller than 4 nm.

  9. One Dimensional Analysis Model of a Condensing Spray Chamber Including Rocket Exhaust Using SINDA/FLUINT and CEA

    Science.gov (United States)

    Sakowski, Barbara; Edwards, Daryl; Dickens, Kevin

    2014-01-01

    Modeling droplet condensation via CFD codes can be very tedious, time consuming, and inaccurate. CFD codes may be tedious and time consuming in terms of using Lagrangian particle tracking approaches or particle sizing bins. Also since many codes ignore conduction through the droplet and or the degradating effect of heat and mass transfer if noncondensible species are present, the solutions may be inaccurate. The modeling of a condensing spray chamber where the significant size of the water droplets and the time and distance these droplets take to fall, can make the effect of droplet conduction a physical factor that needs to be considered in the model. Furthermore the presence of even a relatively small amount of noncondensible has been shown to reduce the amount of condensation [Ref 1]. It is desirable then to create a modeling tool that addresses these issues. The path taken to create such a tool is illustrated. The application of this tool and subsequent results are based on the spray chamber in the Spacecraft Propulsion Research Facility (B2) located at NASA's Plum Brook Station that tested an RL-10 engine. The platform upon which the condensation physics is modeled is SINDAFLUINT. The use of SINDAFLUINT enables the ability to model various aspects of the entire testing facility, including the rocket exhaust duct flow and heat transfer to the exhaust duct wall. The ejector pumping system of the spray chamber is also easily implemented via SINDAFLUINT. The goal is to create a transient one dimensional flow and heat transfer model beginning at the rocket, continuing through the condensing spray chamber, and finally ending with the ejector pumping system. However the model of the condensing spray chamber may be run independently of the rocket and ejector systems detail, with only appropriate mass flow boundary conditions placed at the entrance and exit of the condensing spray chamber model. The model of the condensing spray chamber takes into account droplet

  10. Early immunopathological events in acute model of mycobacterial hypersensitivity pneumonitis in mice.

    Science.gov (United States)

    Johansson, Elisabet; Boivin, Gregory P; Yadav, Jagjit S

    2017-12-01

    Prolonged exposure to antigens of non-tuberculous mycobacteria species colonizing industrial metalworking fluid (MWF), particularly Mycobacterium immunogenum (MI), has been implicated in chronic forms of hypersensitivity pneumonitis (HP) in machinists based on epidemiology studies and long-term exposure of mouse models. However, a role of short-term acute exposure to these antigens has not been described in the context of acute forms of HP. This study investigated short-term acute exposure of mice to MI cell lysate (or live cell suspension) via oropharyngeal aspiration. The results showed there was a dose- and time-dependent increase (peaking at 2 h post-instillation) in lung immunological responses in terms of the pro- (TNFα, IL-6, IL-1β) and anti-inflammatory (IL-10) cytokines. Bronchoalveolar lavage and histology showed neutrophils as the predominant infiltrating cell type, with lymphocytes mice led to a transient early immunopathologic response, with little adaptive immunity, which is consistent with events associated with human acute forms of HP. Screening of MWF-originated mycobacterial genotypes/variants (six of MI, four of M. chelonae, two of M. abscessus) showed both inter- and intra-species differences, with MI genotype MJY10 being the most immunogenic. In conclusion, this study characterized the first short-term mycobacterial exposure mouse model that mimics acute HP in machinists; this could serve as a potentially useful model for rapid screening of field MWF-associated mycobacteria for routine and timely occupational risk assessment and for investigating early biomarkers and mechanisms of this understudied immune lung disease.

  11. A comparison of different ways of including baseline counts in negative binomial models for data from falls prevention trials.

    Science.gov (United States)

    Zheng, Han; Kimber, Alan; Goodwin, Victoria A; Pickering, Ruth M

    2018-01-01

    A common design for a falls prevention trial is to assess falling at baseline, randomize participants into an intervention or control group, and ask them to record the number of falls they experience during a follow-up period of time. This paper addresses how best to include the baseline count in the analysis of the follow-up count of falls in negative binomial (NB) regression. We examine the performance of various approaches in simulated datasets where both counts are generated from a mixed Poisson distribution with shared random subject effect. Including the baseline count after log-transformation as a regressor in NB regression (NB-logged) or as an offset (NB-offset) resulted in greater power than including the untransformed baseline count (NB-unlogged). Cook and Wei's conditional negative binomial (CNB) model replicates the underlying process generating the data. In our motivating dataset, a statistically significant intervention effect resulted from the NB-logged, NB-offset, and CNB models, but not from NB-unlogged, and large, outlying baseline counts were overly influential in NB-unlogged but not in NB-logged. We conclude that there is little to lose by including the log-transformed baseline count in standard NB regression compared to CNB for moderate to larger sized datasets. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Structure modeling and antidiabetic activity of a seed protein of Momordica charantia in non-obese diabetic (NOD) mice.

    Science.gov (United States)

    Chhabra, Gagan; Dixit, Aparna

    2013-01-01

    Momordica charantia is a well known medicinal plant used in the traditional medicinal system for the treatment of various diseases including diabetes mellitus. Recently, a novel protein termed as ADMc1 from the seed extract of M. charantia has been identified and isolated showing significant antihyperglycemic activity in type 1 diabetic rats in which diabetes was induced. However, the structure of this protein has not yet been analyzed. Homology modeling approach was used to generate a high quality protein 3D structure for the amino acid sequence of the ADMc1 protein in this study. The comparative assessment of secondary structures revealed ADMc1 as an all-alpha helix protein with random coils. Tertiary structure predicted on the template structure of Napin of B. Napus (PDB ID: 1SM7) with which the ADMc1 showed significant sequence similarity, was validated using protein structure validation tools like PROCHECK, WHAT_CHECK, VERIFY3D and ProSA. Arrangement of disulfide bridges formed by cysteine residues were predicted by the Dianna 1.1 server. The presence of multiple disulfide bond confers the stable nature of the ADMc1 protein. Further, the biological activity of the ADMc1 was assessed in non-obese diabetic (NOD) mice which are spontaneous model of type 1 diabetes. Significant reduction in the blood glucose levels of NOD mice was observed up to 8 h post administration of the rADMc1 protein. Overall, the structural characterizations with antihyperglycemic activity of this seed protein of Momordica charantia demonstrate its potential as an antidiabetic agent.

  13. Enhanced Expression of Contractile-Associated Proteins and Ion Channels in Preterm Delivery Model Mice With Chronic Odontogenic Porphyromonas Gingivalis Infection.

    Science.gov (United States)

    Miyoshi, Hiroshi; Konishi, Haruhisa; Teraoka, Yuko; Urabe, Satoshi; Furusho, Hisako; Miyauchi, Mutsumi; Takata, Takashi; Kudo, Yoshiki

    2016-07-01

    Inflammation and infection have been reported to induce preterm delivery. We have studied the relationship between inflammation and various ion channels, including the L-type Ca(2+) channel and P2X7 receptor, during acute inflammation of the pregnant rat uterus induced by lipopolysaccharides. Recently, we found that mice with odontogenic Porphyromonas gingivalis (P.g, an important odontogenic pathogen) infection delivered at day 18.3 of gestation (vs. day 20.5 in normal mice). The purpose of this study was to investigate the expression of myometrial contractile-associated proteins inducing contractions and confirm that these mice are useful as a model for preterm delivery induced by chronic inflammation. We examined the expression of the oxytocin receptor, connexin 43, prostaglandin F receptors, L-type Ca(2+) channel, and P2X7 receptor in the myometrium at day 18 of gestation by real-time PCR and western blot analyses. We also measured TNF-α and IL-1β levels in the blood serum, placenta, fetal membrane and myometrium on the same day. mRNA expression of the oxytocin receptor, connexin 43, prostaglandin F receptors, L-type Ca(2+) channel, and P2X7 receptor was elevated by 5.4, 3.2, 2.4, 2.5, and 1.7 fold, respectively, in the P.g-infected mice. Protein levels of the oxytocin receptor and connexin 43 also increased. Serum levels of TNF-α and IL-1β were elevated, showing that systemic inflammation continued during pregnancy. IL-1β levels in the placenta and fetal membrane also increased, suggesting inflammatory reactions were induced. Thus, mice with odontogenic infection may be useful as a model of chronic inflammation-induced preterm delivery. © The Author(s) 2015.

  14. Neoplastic and nonneoplastic lesions in aging mice of unique and common inbred strains contribution to modeling of human neoplastic diseases.

    Science.gov (United States)

    Szymanska, H; Lechowska-Piskorowska, J; Krysiak, E; Strzalkowska, A; Unrug-Bielawska, K; Grygalewicz, B; Skurzak, H M; Pienkowska-Grela, B; Gajewska, M

    2014-05-01

    The evaluation of spontaneous lesions in classical inbred strains of mice has become increasingly important because genetically engineered mice (GEMs) are created on these backgrounds. Novel inbred strains-genetically diverse from classic strains-are valuable both as a new background for GEM mice and to increase the genetic variation found in laboratory mice. Newly arising spontaneous genetic alterations in commonly used strains may also lead to new and valuable mouse models of disease. This report evaluates gross and histological lesions in relatively new, classic, and rarely explored mouse inbred strains. Pathological lesions of 1273 mice from 12 inbred strains (129S1/SvW, A.CA-H2(f) /W, AKR/W, BALB/cW, BN/aW, C57BL/6 W, C57BL/10 W, C3H/W, C3H (wad) /W, CBA/W, DBA/2 W, and WOM/W) are reported. BN/aW, WOM/W, and C3H (wad) /W are novel inbred strains produced and maintained in the Department of Genetics and Laboratory Animal Breeding at the Center of Oncology, Warsaw, Poland. Both neoplastic and nonneoplastic lesions were examined. The prevalence of lung neoplasms was significantly higher in A.CA-H2(f) /W (33.3%) and BALB/cW (33.8%) mice (P WOM/W mice developed T-cell lymphoblastic lymphoma with high frequency (110/121 [90.9%] and 159/175 [90.9%], respectively) before 1 year of age. The occurrence of nonneoplastic lesions in the kidneys of BN/aW mice was increased (P < .01).

  15. Assessment of intensive care unit-acquired weakness in young and old mice: An E. coli septic peritonitis model.

    Science.gov (United States)

    Witteveen, Esther; Hoogland, Inge C M; Wieske, Luuk; Weber, Nina C; Verhamme, Camiel; Schultz, Marcus J; van Schaik, Ivo N; Horn, Janneke

    2016-01-01

    There are few reports of in vivo muscle strength measurements in animal models of ICU-acquired weakness (ICU-AW). In this study we investigated whether the Escherichia coli (E. coli) septic peritonitis mouse model may serve as an ICU-AW model using in vivo strength measurements and myosin/actin assays, and whether development of ICU-AW is age-dependent in this model. Young and old mice were injected intraperitoneally with E. coli and treated with ceftriaxone. Forelimb grip strength was measured at multiple time points, and the myosin/actin ratio in muscle was determined. E. coli administration was not associated with grip strength decrease, neither in young nor in old mice. In old mice, the myosin/actin ratio was lower in E. coli mice at t = 48 h and higher at t = 72 h compared with controls. This E. coli septic peritonitis mouse model did not induce decreased grip strength. In its current form, it seems unsuitable as a model for ICU-AW. © 2015 The Authors. Muscle & Nerve Published by Wiley Periodicals, Inc.

  16. Analysis of Two Stroke Marine Diesel Engine Operation Including Turbocharger Cut-Out by Using a Zero-Dimensional Model

    Directory of Open Access Journals (Sweden)

    Cong Guan

    2015-06-01

    Full Text Available In this article, the operation of a large two-stroke marine diesel engine including various cases with turbocharger cut-out was thoroughly investigated by using a modular zero-dimensional engine model built in MATLAB/Simulink environment. The model was developed by using as a basis an in-house modular mean value engine model, in which the existing cylinder block was replaced by a more detailed one that is capable of representing the scavenging ports-cylinder-exhaust valve processes. Simulation of the engine operation at steady state conditions was performed and the derived engine performance parameters were compared with the respective values obtained by the engine shop trials. The investigation of engine operation under turbocharger cut-out conditions in the region from 10% to 50% load was carried out and the influence of turbocharger cut-out on engine performance including the in-cylinder parameters was comprehensively studied. The recommended schedule for the combination of the turbocharger cut-out and blower activation was discussed for the engine operation under part load conditions. Finally, the influence of engine operating strategies on the annual fuel savings, CO2 emissions reduction and blower operating hours for a Panamax container ship operating at slow steaming conditions is presented and discussed.

  17. Adaptive fuzzy neural network control design via a T-S fuzzy model for a robot manipulator including actuator dynamics.

    Science.gov (United States)

    Wai, Rong-Jong; Yang, Zhi-Wei

    2008-10-01

    This paper focuses on the development of adaptive fuzzy neural network control (AFNNC), including indirect and direct frameworks for an n-link robot manipulator, to achieve high-precision position tracking. In general, it is difficult to adopt a model-based design to achieve this control objective due to the uncertainties in practical applications, such as friction forces, external disturbances, and parameter variations. In order to cope with this problem, an indirect AFNNC (IAFNNC) scheme and a direct AFNNC (DAFNNC) strategy are investigated without the requirement of prior system information. In these model-free control topologies, a continuous-time Takagi-Sugeno (T-S) dynamic fuzzy model with online learning ability is constructed to represent the system dynamics of an n-link robot manipulator. In the IAFNNC, an FNN estimator is designed to tune the nonlinear dynamic function vector in fuzzy local models, and then, the estimative vector is used to indirectly develop a stable IAFNNC law. In the DAFNNC, an FNN controller is directly designed to imitate a predetermined model-based stabilizing control law, and then, the stable control performance can be achieved by only using joint position information. All the IAFNNC and DAFNNC laws and the corresponding adaptive tuning algorithms for FNN weights are established in the sense of Lyapunov stability analyses to ensure the stable control performance. Numerical simulations and experimental results of a two-link robot manipulator actuated by dc servomotors are given to verify the effectiveness and robustness of the proposed methodologies. In addition, the superiority of the proposed control schemes is indicated in comparison with proportional-differential control, fuzzy-model-based control, T-S-type FNN control, and robust neural fuzzy network control systems.

  18. Statistical methodology for discrete fracture model - including fracture size, orientation uncertainty together with intensity uncertainty and variability

    International Nuclear Information System (INIS)

    Darcel, C.; Davy, P.; Le Goc, R.; Dreuzy, J.R. de; Bour, O.

    2009-11-01

    the other, addresses the issue of the nature of the transition. We develop a new 'mechanistic' model that could help in modeling why and where this transition can occur. The transition between both regimes would occur for a fracture length of 1-10 m and even at a smaller scale for the few outcrops that follow the self-similar density model. A consequence for the disposal issue is that the model that is likely to apply in the 'blind' scale window between 10-100 m is the self-similar model as it is defined for large-scale lineaments. The self-similar model, as it is measured for some outcrops and most lineament maps, is definitely worth being investigated as a reference for scales above 1-10 m. In the rest of the report, we develop a methodology for incorporating uncertainty and variability into the DFN modeling. Fracturing properties arise from complex processes which produce an intrinsic variability; characterizing this variability as an admissible variation of model parameter or as the division of the site into subdomains with distinct DFN models is a critical point of the modeling effort. Moreover, the DFN model encompasses a part of uncertainty, due to data inherent uncertainties and sampling limits. Both effects must be quantified and incorporated into the DFN site model definition process. In that context, all available borehole data including recording of fracture intercept positions, pole orientation and relative uncertainties are used as the basis for the methodological development and further site model assessment. An elementary dataset contains a set of discrete fracture intercepts from which a parent orientation/density distribution can be computed. The elementary bricks of the site, from which these initial parent density distributions are computed, rely on the former Single Hole Interpretation division of the boreholes into sections whose local boundaries are expected to reflect - locally - geology and fracturing properties main characteristics. From that

  19. Anticonvulsant activity of Aloe vera leaf extract in acute and chronic models of epilepsy in mice.

    Science.gov (United States)

    Rathor, Naveen; Arora, Tarun; Manocha, Sachin; Patil, Amol N; Mediratta, Pramod K; Sharma, Krishna K

    2014-03-01

    The effect of Aloe vera in epilepsy has not yet been explored. This study was done to explore the effect of aqueous extract of Aloe vera leaf powder on three acute and one chronic model of epilepsy. In acute study, aqueous extract of Aloe vera leaf (extract) powder was administered in doses 100, 200 and 400 mg/kg p.o. Dose of 400 mg/kg of Aloe vera leaf extract was chosen for chronic administration. Oxidative stress parameters viz. malondialdehyde (MDA) and reduced glutathione (GSH) were also estimated in brain of kindled animals. In acute study, Aloe vera leaf (extract) powder in a dose-dependent manner significantly decreased duration of tonic hind limb extension in maximal electroshock seizure model, increased seizure threshold current in increasing current electroshock seizure model, and increased latency to onset and decreased duration of clonic convulsion in pentylenetetrazole (PTZ) model as compared with control group. In chronic study, Aloe vera leaf (extract) powder prevented progression of kindling in PTZ-kindled mice. Aloe vera leaf (extract) powder 400 mg/kg p.o. also reduced brain levels of MDA and increased GSH levels as compared to the PTZ-kindled non-treated group. The results of study showed that Aloe vera leaf (extract) powder possessed significant anticonvulsant and anti-oxidant activity. © 2013 Royal Pharmaceutical Society.

  20. Evaluation of analgesic activity of allopurinol and febuxostat in experimental analgesic models in mice

    Directory of Open Access Journals (Sweden)

    Promod D Shankpal

    2015-01-01

    Full Text Available Background: Allopurinol and febuxostat are xanthine oxidase inhibitors which are used in the treatment of hyperuricemia and gout. Pain is one of the important symptoms in gout patients. The present study was to evaluate the analgesic activity of allopurinol and febuxostat in two analgesic models in mice. Materials and Methods: The analgesic activity of allopurinol (39 mg/kg and febuxostat (15.6 mg/kg was evaluated using central analgesic model of Eddy′s hot plate and peripheral analgesic model of acetic acid induced writhing. Both drugs were compared with the positive control, pentazocine for a hot plate method and aspirin for the writhing method. Furthermore, both allopurinol and febuxostat were compared with each other. Results: Both allopurinol and febuxostat showed significant increase in reaction time at various time periods in hot plate method and also showed significant delay in onset of writhing as well as decrease in number of writhes in writhing method. As compared to positive control result, allopurinol and febuxostat result were lower. Febuxostat shows better analgesic activity as compared to that of allopurinol. Conclusion: Allopurinol and febuxostat exhibited analgesic activity in both central and peripheral models of pain.

  1. Laboratory Studies of the Reactive Chemistry and Changing CCN Properties of Secondary Organic Aerosol, Including Model Development

    Energy Technology Data Exchange (ETDEWEB)

    Scot Martin

    2013-01-31

    The chemical evolution of secondary-organic-aerosol (SOA) particles and how this evolution alters their cloud-nucleating properties were studied. Simplified forms of full Koehler theory were targeted, specifically forms that contain only those aspects essential to describing the laboratory observations, because of the requirement to minimize computational burden for use in integrated climate and chemistry models. The associated data analysis and interpretation have therefore focused on model development in the framework of modified kappa-Koehler theory. Kappa is a single parameter describing effective hygroscopicity, grouping together several separate physicochemical parameters (e.g., molar volume, surface tension, and van't Hoff factor) that otherwise must be tracked and evaluated in an iterative full-Koehler equation in a large-scale model. A major finding of the project was that secondary organic materials produced by the oxidation of a range of biogenic volatile organic compounds for diverse conditions have kappa values bracketed in the range of 0.10 +/- 0.05. In these same experiments, somewhat incongruently there was significant chemical variation in the secondary organic material, especially oxidation state, as was indicated by changes in the particle mass spectra. Taken together, these findings then support the use of kappa as a simplified yet accurate general parameter to represent the CCN activation of secondary organic material in large-scale atmospheric and climate models, thereby greatly reducing the computational burden while simultaneously including the most recent mechanistic findings of laboratory studies.

  2. Modelling the effect of acoustic waves on the thermodynamics and kinetics of phase transformation in a solution: Including mass transportation

    Science.gov (United States)

    Haqshenas, S. R.; Ford, I. J.; Saffari, N.

    2018-01-01

    Effects of acoustic waves on a phase transformation in a metastable phase were investigated in our previous work [S. R. Haqshenas, I. J. Ford, and N. Saffari, "Modelling the effect of acoustic waves on nucleation," J. Chem. Phys. 145, 024315 (2016)]. We developed a non-equimolar dividing surface cluster model and employed it to determine the thermodynamics and kinetics of crystallisation induced by an acoustic field in a mass-conserved system. In the present work, we developed a master equation based on a hybrid Szilard-Fokker-Planck model, which accounts for mass transportation due to acoustic waves. This model can determine the kinetics of nucleation and the early stage of growth of clusters including the Ostwald ripening phenomenon. It was solved numerically to calculate the kinetics of an isothermal sonocrystallisation process in a system with mass transportation. The simulation results show that the effect of mass transportation for different excitations depends on the waveform as well as the imposed boundary conditions and tends to be noticeable in the case of shock waves. The derivations are generic and can be used with any acoustic source and waveform.

  3. Design and modeling of an advanced marine machinery system including waste heat recovery and removal of sulphur oxides

    DEFF Research Database (Denmark)

    Frimann Nielsen, Rasmus; Haglind, Fredrik; Larsen, Ulrik

    2014-01-01

    the efficiency of machinery systems. The wet sulphuric acid process is an effective way of removing flue gas sulphur oxides from land-based coal-fired power plants. Moreover, organic Rankine cycles (ORC) are suitable for heat to power conversion for low temperature heat sources. This paper describes the design...... and modeling of a highly efficient machinery system which includes the removal of exhaust gas sulphur oxides. The system consists of a two-stroke diesel engine, the wet sulphuric process for sulphur removal, a conventional steam Rankine cycle and an ORC. Results of numerical modeling efforts suggest...... that an ORC placed after the conventional waste heat recovery system is able to extract the sulphuric acid from the exhaust gas, while at the same time increase the combined cycle thermal efficiency by 2.6%. The findings indicate that the technology has potential in marine applications regarding both energy...

  4. Chronic subordination stress induces hyperphagia and disrupts eating behavior in mice modeling binge-eating-like disorder

    Directory of Open Access Journals (Sweden)

    Maria eRazzoli

    2015-01-01

    Full Text Available Background: Eating disorders are associated with physical morbidity and appear to have causal factors like stressful life events and negative affect. Binge eating disorder (BED is characterized by eating in a discrete period of time a larger than normal amount of food, a sense of lack of control over eating, and marked distress. There are still unmet needs for the identification of mechanisms regulating excessive eating, which is in part due to the lack of appropriate animal models. We developed a naturalistic murine model of subordination stress induced hyperphagia associated with the development of obesity. Here we tested the hypotheses that the eating responses of subordinate mice recapitulate the BED and that limiting hyperphagia could prevent stress-associated metabolic changes. Methods: Adult male mice were exposed to a model of chronic subordination stress associated with the automated acquisition of food intake and we performed a detailed meal pattern analysis. Additionally, using a pair-feeding protocol was test the hypothesis that the manifestation of obesity and the metabolic syndrome could be prevented by limiting hyperphagia. Results: The architecture of feeding of subordinate mice was disrupted during the stress protocol due to disproportionate amount of food ingested at higher rate and with shorter satiety ratio than control mice. Subordinate mice hyperphagia was further exacerbated in response to either hunger or to the acute application of a social defeat. Notably, the obese phenotype but not the fasting hyperglycemia of subordinate mice was abrogated by preventing hyperphagia in a pair feeding paradigm. Conclusion: Overall these results support the validity of our chronic subordination stress to model binge eating disorder allowing for the determination of the underlying molecular mechanisms and the generation of testable predictions for innovative therapies, based on the understanding of the regulation and the control of food

  5. Systematic investigation on the turning point of over-inflammation to immunosuppression in CLP mice model and their characteristics.

    Science.gov (United States)

    Deng, Dongmei; Li, Xiaoli; Liu, Chao; Zhai, Zhaoxia; Li, Bin; Kuang, Mei; Li, Pan; Shang, Shenglan; Song, Yi; Cen, Yanyan; Qin, Rongxin; Lu, Yonglin; Zhao, Yibo; Cheng, Hao; Zheng, Jiang; Zhou, Hong

    2017-01-01

    Immunosuppression is involved in refractory innate and adaptive immune responses and is considered to be the predominant driving force for mortality in sepsis. The cecal ligation and puncture (CLP) model is regarded as a golden standard model for sepsis study, but the turning point of over-inflammation to immunosuppression was reported differently. Herein, systematic investigation on the turning point of over-inflammation to immunosuppression in CLP mice model was carried out. The results showed only the mortality of mice challenged with of Pseudomonas aeruginosa on Day 1 not other days after the surgery was higher than that of other mice with Sham surgery, suggesting Day 1 after the CLP surgery might be the turning point. There was very low mortality even without death in Sham mice but the mortality was 80% after mice were challenged with 2.5×10 7 , 5.0×10 6 and 1.0×10 6 CFU/10g of Pseudomonas aeruginosa, further demonstrating Day 1 after the CLP surgery was the turning point. And, CLP mice presented low levels of pro-inflammatory and anti-inflammatory cytokines, and high bacterial loads on Day 1. Additionally, the amounts and proportion of blood cells and monocytes significantly changed, too. In conclusion, Day 1 after the CLP surgery was the turning point of over-inflammation to immunosuppression, and low levels of cytokines and high bacterial loads were the characteristics of this model on Day 1, which is significant for pharmacological investigation on sepsis. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Chronic subordination stress induces hyperphagia and disrupts eating behavior in mice modeling binge-eating-like disorder.

    Science.gov (United States)

    Razzoli, Maria; Sanghez, Valentina; Bartolomucci, Alessandro

    Eating disorders are associated with physical morbidity and appear to have causal factors like stressful life events and negative affect. Binge eating disorder (BED) is characterized by eating in a discrete period of time a larger than normal amount of food, a sense of lack of control over eating, and marked distress. There are still unmet needs for the identification of mechanisms regulating excessive eating, which is in part due to the lack of appropriate animal models. We developed a naturalistic murine model of subordination stress induced hyperphagia associated with the development of obesity. Here we tested the hypotheses that the eating responses of subordinate mice recapitulate the BED and that limiting hyperphagia could prevent stress-associated metabolic changes. Adult male mice were exposed to a model of chronic subordination stress associated with the automated acquisition of food intake and we performed a detailed meal pattern analysis. Additionally, using a pair-feeding protocol was test the hypothesis that the manifestation of obesity and the metabolic syndrome could be prevented by limiting hyperphagia. The architecture of feeding of subordinate mice was disrupted during the stress protocol due to disproportionate amount of food ingested at higher rate and with shorter satiety ratio than control mice. Subordinate mice hyperphagia was further exacerbated in response to either hunger or to the acute application of a social defeat. Notably, the obese phenotype but not the fasting hyperglycemia of subordinate mice was abrogated by preventing hyperphagia in a pair feeding paradigm. Overall these results support the validity of our chronic subordination stress to model binge eating disorder allowing for the determination of the underlying molecular mechanisms and the generation of testable predictions for innovative therapies, based on the understanding of the regulation and the control of food intake.

  7. DETERMINATION OF AGE AND GENDER DIFFERENCES IN BIOCHEMICAL PROCESSES AFFECTING THE DISPOSITION OF 2-BUTOXYETHANOL AND ITS METABOLITES IN MICE AND RATS TO IMPROVE PBPK MODELING

    Energy Technology Data Exchange (ETDEWEB)

    Corley, Rick A.; Grant, Donna M.; Farris, Elizabeth; Weitz, Karl K.; Soelberg, Jolen J.; Thrall, K D.; Poet, Torka S.

    2005-03-28

    2-Butoxyethanol (BE) is the most widely used glycol ether solvent. BE's major metabolite, butoxyacetic acid (BAA), causes hemolysis with significant species differences in sensitivity. Several PBPK models have been developed over the past two decades to describe the disposition of BE and BAA in male rats and humans to refine health risk assessments. More recent efforts by Lee et al. (1998) to describe the kinetics of BE and BAA in the National Toxicology Program (NTP) chronic inhalation studies required the use of several assumptions to extrapolate model parameters from earlier PBPK models developed for young male rats to include female F344 and both sexes of B6C3F1 mice and the effects of aging. To replace these assumptions, studies were conducted to determine the impact of age, gender and species on the metabolism of BE, and the tissue partitioning, renal acid transport and plasma protein binding of BAA. In the current study, the Lee et al. PBPK model was updated and expanded to include the further metabolism of BAA and the salivary excretion of BE and BAA which may contribute to the forestomach irritation observed in mice in the NTP study. The revised model predicted that peak blood concentrations of BAA achieved following 6-hr inhalation exposures are greatest in young adult female rats at concentrations up to 300 ppm. This is not the case predicted for old (>18 months) animals, where peak blood concentrations of BAA in male and female mice were similar to or greater than female rats. The revised model serves as a quantitative tool for integrating an extensive pharmacokinetic and mechanistic database into a format that can readily be used to compare internal dosimetry across dose, route of exposure and species.

  8. Statistical methodology for discrete fracture model - including fracture size, orientation uncertainty together with intensity uncertainty and variability

    Energy Technology Data Exchange (ETDEWEB)

    Darcel, C. (Itasca Consultants SAS (France)); Davy, P.; Le Goc, R.; Dreuzy, J.R. de; Bour, O. (Geosciences Rennes, UMR 6118 CNRS, Univ. def Rennes, Rennes (France))

    2009-11-15

    the lineament scale (k{sub t} = 2) on the other, addresses the issue of the nature of the transition. We develop a new 'mechanistic' model that could help in modeling why and where this transition can occur. The transition between both regimes would occur for a fracture length of 1-10 m and even at a smaller scale for the few outcrops that follow the self-similar density model. A consequence for the disposal issue is that the model that is likely to apply in the 'blind' scale window between 10-100 m is the self-similar model as it is defined for large-scale lineaments. The self-similar model, as it is measured for some outcrops and most lineament maps, is definitely worth being investigated as a reference for scales above 1-10 m. In the rest of the report, we develop a methodology for incorporating uncertainty and variability into the DFN modeling. Fracturing properties arise from complex processes which produce an intrinsic variability; characterizing this variability as an admissible variation of model parameter or as the division of the site into subdomains with distinct DFN models is a critical point of the modeling effort. Moreover, the DFN model encompasses a part of uncertainty, due to data inherent uncertainties and sampling limits. Both effects must be quantified and incorporated into the DFN site model definition process. In that context, all available borehole data including recording of fracture intercept positions, pole orientation and relative uncertainties are used as the basis for the methodological development and further site model assessment. An elementary dataset contains a set of discrete fracture intercepts from which a parent orientation/density distribution can be computed. The elementary bricks of the site, from which these initial parent density distributions are computed, rely on the former Single Hole Interpretation division of the boreholes into sections whose local boundaries are expected to reflect - locally - geology

  9. Development of a mechanism-based pharmacokinetic/pharmacodynamic model to characterize the thermoregulatory effects of serotonergic drugs in mice.

    Science.gov (United States)

    Jiang, Xi-Ling; Shen, Hong-Wu; Mager, Donald E; Schmidt, Stephan; Yu, Ai-Ming

    2016-09-01

    We have shown recently that concurrent harmaline, a monoamine oxidase-A inhibitor (MAOI), potentiates serotonin (5-HT) receptor agonist 5-methoxy- N,N -dimethyltryptamine (5-MeO-DMT)-induced hyperthermia. The objective of this study was to develop an integrated pharmacokinetic/pharmacodynamic (PK/PD) model to characterize and predict the thermoregulatory effects of such serotonergic drugs in mice. Physiological thermoregulation was described by a mechanism-based indirect-response model with adaptive feedback control. Harmaline-induced hypothermia and 5-MeO-DMT-elicited hyperthermia were attributable to the loss of heat through the activation of 5-HT 1A receptor and thermogenesis via the stimulation of 5-HT 2A receptor, respectively. Thus serotonergic 5-MeO-DMT-induced hyperthermia was readily distinguished from handling/injection stress-provoked hyperthermic effects. This PK/PD model was able to simultaneously describe all experimental data including the impact of drug-metabolizing enzyme status on 5-MeO-DMT and harmaline PK properties, and drug- and stress-induced simple hypo/hyperthermic and complex biphasic effects. Furthermore, the modeling results revealed a 4-fold decrease of apparent SC 50 value (1.88-0.496 µmol/L) for 5-MeO-DMT when harmaline was co-administered, providing a quantitative assessment for the impact of concurrent MAOI harmaline on 5-MeO-DMT-induced hyperthermia. In addition, the hyperpyrexia caused by toxic dose combinations of harmaline and 5-MeO-DMT were linked to the increased systemic exposure to harmaline rather than 5-MeO-DMT, although the body temperature profiles were mispredicted by the model. The results indicate that current PK/PD model may be used as a new conceptual framework to define the impact of serotonergic agents and stress factors on thermoregulation.

  10. Development of a mechanism-based pharmacokinetic/pharmacodynamic model to characterize the thermoregulatory effects of serotonergic drugs in mice

    Directory of Open Access Journals (Sweden)

    Xi-Ling Jiang

    2016-09-01

    Full Text Available We have shown recently that concurrent harmaline, a monoamine oxidase-A inhibitor (MAOI, potentiates serotonin (5-HT receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT-induced hyperthermia. The objective of this study was to develop an integrated pharmacokinetic/pharmacodynamic (PK/PD model to characterize and predict the thermoregulatory effects of such serotonergic drugs in mice. Physiological thermoregulation was described by a mechanism-based indirect-response model with adaptive feedback control. Harmaline-induced hypothermia and 5-MeO-DMT–elicited hyperthermia were attributable to the loss of heat through the activation of 5-HT1A receptor and thermogenesis via the stimulation of 5-HT2A receptor, respectively. Thus serotonergic 5-MeO-DMT–induced hyperthermia was readily distinguished from handling/injection stress-provoked hyperthermic effects. This PK/PD model was able to simultaneously describe all experimental data including the impact of drug-metabolizing enzyme status on 5-MeO-DMT and harmaline PK properties, and drug- and stress-induced simple hypo/hyperthermic and complex biphasic effects. Furthermore, the modeling results revealed a 4-fold decrease of apparent SC50 value (1.88–0.496 µmol/L for 5-MeO-DMT when harmaline was co-administered, providing a quantitative assessment for the impact of concurrent MAOI harmaline on 5-MeO-DMT–induced hyperthermia. In addition, the hyperpyrexia caused by toxic dose combinations of harmaline and 5-MeO-DMT were linked to the increased systemic exposure to harmaline rather than 5-MeO-DMT, although the body temperature profiles were mispredicted by the model. The results indicate that current PK/PD model may be used as a new conceptual framework to define the impact of serotonergic agents and stress factors on thermoregulation.

  11. Mathematical modeling of HIV prevention measures including pre-exposure prophylaxis on HIV incidence in South Korea.

    Science.gov (United States)

    Kim, Sun Bean; Yoon, Myoungho; Ku, Nam Su; Kim, Min Hyung; Song, Je Eun; Ahn, Jin Young; Jeong, Su Jin; Kim, Changsoo; Kwon, Hee-Dae; Lee, Jeehyun; Smith, Davey M; Choi, Jun Yong

    2014-01-01

    Multiple prevention measures have the possibility of impacting HIV incidence in South Korea, including early diagnosis, early treatment, and pre-exposure prophylaxis (PrEP). We investigated how each of these interventions could impact the local HIV epidemic, especially among men who have sex with men (MSM), who have become the major risk group in South Korea. A mathematical model was used to estimate the effects of each these interventions on the HIV epidemic in South Korea over the next 40 years, as compared to the current situation. We constructed a mathematical model of HIV infection among MSM in South Korea, dividing the MSM population into seven groups, and simulated the effects of early antiretroviral therapy (ART), early diagnosis, PrEP, and combination interventions on the incidence and prevalence of HIV infection, as compared to the current situation that would be expected without any new prevention measures. Overall, the model suggested that the most effective prevention measure would be PrEP. Even though PrEP effectiveness could be lessened by increased unsafe sex behavior, PrEP use was still more beneficial than the current situation. In the model, early diagnosis of HIV infection was also effectively decreased HIV incidence. However, early ART did not show considerable effectiveness. As expected, it would be most effective if all interventions (PrEP, early diagnosis and early treatment) were implemented together. This model suggests that PrEP and early diagnosis could be a very effective way to reduce HIV incidence in South Korea among MSM.

  12. Genomic Methylation Inhibits Expression of Hepatitis B Virus Envelope Protein in Transgenic Mice: A Non-Infectious Mouse Model to Study Silencing of HBV Surface Antigen Genes.

    Science.gov (United States)

    Graumann, Franziska; Churin, Yuri; Tschuschner, Annette; Reifenberg, Kurt; Glebe, Dieter; Roderfeld, Martin; Roeb, Elke

    2015-01-01

    The Hepatitis B virus genome persists in the nucleus of virus infected hepatocytes where it serves as template for viral mRNA synthesis. Epigenetic modifications, including methylation of the CpG islands contribute to the regulation of viral gene expression. The present study investigates the effects of spontaneous age dependent loss of hepatitis B surface protein- (HBs) expression due to HBV-genome specific methylation as well as its proximate positive effects in HBs transgenic mice. Liver and serum of HBs transgenic mice aged 5-33 weeks were analyzed by Western blot, immunohistochemistry, serum analysis, PCR, and qRT-PCR. From the third month of age hepatic loss of HBs was observed in 20% of transgenic mice. The size of HBs-free area and the relative number of animals with these effects increased with age and struck about 55% of animals aged 33 weeks. Loss of HBs-expression was strongly correlated with amelioration of serum parameters ALT and AST. In addition lower HBs-expression went on with decreased ER-stress. The loss of surface protein expression started on transcriptional level and appeared to be regulated epigenetically by DNA methylation. The amount of the HBs-expression correlated negatively with methylation of HBV DNA in the mouse genome. Our data suggest that methylation of specific CpG sites controls gene expression even in HBs-transgenic mice with truncated HBV genome. More important, the loss of HBs expression and intracellular aggregation ameliorated cell stress and liver integrity. Thus, targeted modulation of HBs expression may offer new therapeutic approaches. Furthermore, HBs-transgenic mice depict a non-infectious mouse model to study one possible mechanism of HBs gene silencing by hypermethylation.

  13. Effects of Chimonanthus nitens Oliv. Leaf Extract on Glycolipid Metabolism and Antioxidant Capacity in Diabetic Model Mice

    Directory of Open Access Journals (Sweden)

    Hui Chen

    2017-01-01

    Full Text Available The paper investigated the antihyperglycemic and antihyperlipidemic efficacy and antioxidant capacity of Chimonanthus nitens Oliv. leaf extract (COE in combination of high-glucose-fat diet-fed and streptozotocin-induced diabetic model mice. Various physiological indexes in diabetic model mice were well improved especially by oral administration of high dose of COE; the results were listed as follows. Fast blood glucose (FBG level and serum triglyceride (TC, total cholesterol (TG, low-density lipoprotein cholesterol (LDLC, and malondialdehyde (MDA as well as MDA in liver were significantly reduced; fasting serum insulin (FINS and insulin sensitivity index (ISI were both increased; high-density lipoprotein cholesterol (HDLC in serum was significantly increased; total antioxidant capacity (T-AOC, activities of superoxide dismutase (SOD, glutathione peroxidase (GSH-Px, and catalase (CAT in serum and liver were apparently enhanced; liver coefficient (LC, liver transaminase, and alkaline phosphatase (ALP were decreased. Furthermore, pancreas islets and liver in diabetic model mice showed some extend of improvement in morphology and function after 4 weeks of COE treatment. In consequence, COE was advantageous to regulate glycolipid metabolism and elevate antioxidant capacity in diabetic model mice. Thus, the present study will provide a scientific evidence for the use of COE in the management of diabetes and its related complications.

  14. Neuropsychiatric Symptom Modeling in Male and Female C57BL/6J Mice after Experimental Traumatic Brain Injury

    Science.gov (United States)

    Tucker, Laura B.; Burke, John F.; Fu, Amanda H.

    2017-01-01

    Abstract Psychiatric symptoms such as anxiety and depression are frequent and persistent complaints following traumatic brain injury (TBI). Modeling these symptoms in animal models of TBI affords the opportunity to determine mechanisms underlying behavioral pathologies and to test potential therapeutic agents. However, testing these symptoms in animal models of TBI has yielded inconsistent results. The goal of the current study was to employ a battery of tests to measure multiple anxiety- and depressive-like symptoms following TBI in C57BL/6J mice, and to determine if male and female mice are differentially affected by the injury. Following controlled cortical impact (CCI) at a parietal location, neither male nor female mice showed depressive-like symptoms as measured by the Porsolt forced-swim test and sucrose preference test. Conclusions regarding anxiety-like behaviors were dependent upon the assay employed; CCI-induced thigmotaxis in the open field suggested an anxiogenic effect of the injury; however, results from the elevated zero maze, light-dark box, and marble-burying tests indicated that CCI reduced anxiety-like behaviors. Fewer anxiety-like behaviors were also associated with the female sex. Increased levels of activity were also measured in female mice and injured mice in these tests, and conclusions regarding anxiety should be taken with caution when experimental manipulations induce changes in baseline activity. These results underscore the irreconcilability of results from studies attempting to model TBI-induced neuropsychiatric symptoms. Changes in injury models or better attempts to replicate the clinical syndrome may improve the translational applicability of rodent models of TBI-induced anxiety and depression. PMID:27149139

  15. A quantitative model for dermal infection and oedema in BALB/c mice pinna.

    Science.gov (United States)

    Marino-Marmolejo, Erika Nahomy; Flores-Hernández, Flor Yohana; Flores-Valdez, Mario Alberto; García-Morales, Luis Felipe; González-Villegas, Ana Cecilia; Bravo-Madrigal, Jorge

    2016-12-12

    Pharmaceutical industry demands innovation for developing new molecules to improve effectiveness and safety of therapeutic medicines. Preclinical assays are the first tests performed to evaluate new therapeutic molecules using animal models. Currently, there are several models for evaluation of treatments, for dermal oedema or infection. However, the most common or usual way is to induce the inflammation with chemical substances instead of infectious agents. On the other hand, this kind of models require the implementation of histological techniques and the interpretation of pathologies to verify the effectiveness of the therapy under assessment. This work was focused on developing a quantitative model of infection and oedema in mouse pinna. The infection was achieved with a strain of Streptococcus pyogenes that was inoculated in an injury induced at the auricle of BALB/c mice, the induced oedema was recorded by measuring the ear thickness with a digital micrometer and histopathological analysis was performed to verify the damage. The presence of S. pyogenes at the infection site was determined every day by culture. Our results showed that S. pyogenes can infect the mouse pinna and that it can be recovered at least for up to 4 days from the infected site; we also found that S. pyogenes can induce a bigger oedema than the PBS-treated control for at least 7 days; our results were validated with an antibacterial and anti-inflammatory formulation made with ciprofloxacin and hydrocortisone. The model we developed led us to emulate a dermal infection and allowed us to objectively evaluate the increase or decrease of the oedema by measuring the thickness of the ear pinna, and to determine the presence of the pathogen in the infection site. We consider that the model could be useful for assessment of new anti-inflammatory or antibacterial therapies for dermal infections.

  16. Ameliorative Effect and Its Mechanism of Forsythiaside on Learning and Memory of Composite Alzheimer's Disease Model Mice

    Directory of Open Access Journals (Sweden)

    Yu-ping XIONG

    2016-03-01

    Full Text Available Objective: To explore the ameliorative effect of forsythiaside and its mechanism on learning and memory of composite Alzheimer’s disease (AD model mice. Methods: Fifty SAMP8 mice of 8 months old were randomly divided into negative control group (gavage of distilled water, positive control group (gavage of donepezil, low-, middle-, and high-dose groups (gavage of forsythiaside 60, 120, and 240 mg/kg, respectively, 10 cases for each group. Another 10 SAMR1 male mice of 8-month old were designed as blank control group (gavage of distilled water. After gavage for 30 consecutive days, Morris water maze test was used to conduct behavioral test 1 h after gavage everyday. 24 h after completing behavior test, the vitality of superoxide dismutase (SOD, acetylcholine esterase (AchE, choline acetyl transferase (ChAT, monoamine oxidase (MAO, and glutathion peroxidase (GSH-PX as well as the content of malondialdehyde (MDA and nitric oxide (NO in brain tissue of mice in each group were tested. Results: In water maze test, forsythiaside could improve the learning and memory ability of composite AD model mice. After being given different doses of forsythiaside for a long term, the activity of SOD, ChAT, and GSH-PX increased inordinately and the content of MDA and NO reduced in varying degrees in a dose-dependent manner. Of all, the high-dose forsythiaside group was the best in therapeutic effect. Conclusion: Forsythiaside has a therapeutic effect on the learning and memory impairment of composite AD model mice probably by regulating the mechanism of the cholinergic system and antioxygenation.

  17. Activating brown adipose tissue for weight loss and lowering of blood glucose levels: a microPET study using obese and diabetic model mice.

    Directory of Open Access Journals (Sweden)

    Chenxi Wu

    Full Text Available PURPOSE: This study aims at using 18F-FDG microPET to monitor the brown adipose tissue (BAT glucose metabolism in obese and diabetic mouse models under different interventions, and study the therapeutic potential of BAT activation for weight loss and lowering of blood glucose in these models. METHODS: Obese mice were established by a high-fat diet for eight weeks, and diabetes mellitus(DM models were induced with Streptozocin in obese mice. 18F-FDG microPET was used to monitor BAT function during obese and DM modeling, and also after BRL37344 (a β3-adrenergic receptor agonist or levothyroxine treatment. The BAT function was correlated with the body weight and blood glucose levels. RESULTS: Compared with the controls, the obese mice and DM mice showed successively lower 18F-FDG uptake in the interscapular BAT (P = 0.036 and < 0.001, respectively. After two-week BRL37344 treatment, the BAT uptake was significantly elevated in both obese mice (P = 0.010 and DM mice (P = 0.004, accompanied with significantly decreased blood glucose levels (P = 0.023 and 0.036, respectively. The BAT uptake was negatively correlated with the blood glucose levels in both obese mice (r = -0.71, P = 0.003 and DM mice (r = -0.74, P = 0.010. BRL37344 treatment also caused significant weight loss in the obese mice (P = 0.001. Levothyroxine treatment increased the BAT uptake in the control mice (P = 0.025 and obese mice (P = 0.013, but not in the DM mice (P = 0.45. CONCLUSION: The inhibited BAT function in obese and DM mice can be re-activated by β3-adrenergic receptor agonist or thyroid hormone, and effective BAT activation may lead to weight loss and blood glucose lowering. Activating BAT can provide a new treatment strategy for obesity and DM.

  18. Modelled hydraulic redistribution by sunflower (Helianthus annuus L.) matches observed data only after including night-time transpiration.

    Science.gov (United States)

    Neumann, Rebecca B; Cardon, Zoe G; Teshera-Levye, Jennifer; Rockwell, Fulton E; Zwieniecki, Maciej A; Holbrook, N Michele

    2014-04-01

    The movement of water from moist to dry soil layers through the root systems of plants, referred to as hydraulic redistribution (HR), occurs throughout the world and is thought to influence carbon and water budgets and ecosystem functioning. The realized hydrologic, biogeochemical and ecological consequences of HR depend on the amount of redistributed water, whereas the ability to assess these impacts requires models that correctly capture HR magnitude and timing. Using several soil types and two ecotypes of sunflower (Helianthus annuus L.) in split-pot experiments, we examined how well the widely used HR modelling formulation developed by Ryel et al. matched experimental determination of HR across a range of water potential driving gradients. H. annuus carries out extensive night-time transpiration, and although over the last decade it has become more widely recognized that night-time transpiration occurs in multiple species and many ecosystems, the original Ryel et al. formulation does not include the effect of night-time transpiration on HR. We developed and added a representation of night-time transpiration into the formulation, and only then was the model able to capture the dynamics and magnitude of HR we observed as soils dried and night-time stomatal behaviour changed, both influencing HR. © 2013 John Wiley & Sons Ltd.

  19. Effects of low-dose rate irradiation on two types of type II diabetes model mice

    International Nuclear Information System (INIS)

    Nomura, Takaji; Sakai, Kazuo

    2004-01-01

    The effects of low-dose rate gamma-irradiation were investigated in two mouse strains - C57BL/KsJ-db/db (db mouse) and AKITA (AKITA mouse)-for type II diabetes mellitus. Both strains develop the developed type II diabetes by about 8 weeks of age due to dysfunction of the insulin/insulin receptor. The db Mouse' shows obese and exhibits hyperinsulinism, and the onset of Type II diabetes like resembles that for Westerners. On the other hand, the AKITA mouse has exhibits disordered insulin secretion, and the diabetes such as resembles that of Asians. Ten-week old female mice, in groups of 8 or 12, were irradiated at 0.65 mGy/hr in the low-dose rate irradiation facility in the Low Dose Radiation Research Center. The level of urine glucose was measured with test slips. The urine glucose levels of all of the mice were highly elevated the beginning of the irradiation. In the irradiated group of db mice, three mice showed decrease in glucose level compare to the level of non-irradiated diabetes mice after 35, 52 or 80 weeks of irradiation. All had maintained a normal level thereafter. No such improvement in diabetes was ever observed in the 12 mice of in the non-irradiated control group. The AKITA mice, however, did not decrease the glucose level regardless of the irradiation. Both the db mice and AKITA mice had their lives prolonged their life by the irradiation. The survival rate of db mice at the age of 90 weeks was 75% in the irradiated group, but 50% in the non-irradiated group. The average life span was 104 weeks in the irradiated group and 87 weeks in the control group. Furthermore, a marked difference was furthermore observed in the appearance of the coat hair, skin, and tail; appearances were well preserved in the irradiated group. The average life span in the irradiated AKITA mice was also longer than that for the non-irradiated mice, 51 weeks and 41 weeks in the irradiated and non-irradiated group respectively. These results suggest that the low-dose irradiation

  20. New operant model of reinstatement of food-seeking behavior in mice.

    Science.gov (United States)

    Martín-García, Elena; Burokas, Aurelijus; Kostrzewa, Elzbieta; Gieryk, Agnieszka; Korostynski, Michal; Ziolkowska, Barbara; Przewlocka, Barbara; Przewlocki, Ryszard; Maldonado, Rafael

    2011-05-01

    A major problem in treating obesity is the high rate of relapse to abnormal food-taking behavior when maintaining diet. The present study evaluates the reinstatement of extinguished palatable food-seeking behavior induced by cues previously associated with the palatable food, re-exposure to this food, or stress. The participation of the opioid and dopamine mechanisms in the acquisition, extinction, and cue-induced reinstatement was also investigated. C57BL/6 mice were first trained on a fixed-ratio-1 schedule of reinforcement to obtain chocolate-flavored pellets during 20 days, which was associated to a stimulus light. Operant behavior was then extinguished during 20 daily sessions. mRNA levels of opioid peptide precursors and dopamine receptors were evaluated in the brain by in situ hybridization and RT-PCR techniques. A reinstatement of food-seeking behavior was only obtained after exposure to the food-associated cue. A down-regulation of prodynorphin mRNA was found in the dorsal striatum and nucleus accumbens after the acquisition, extinction, and reinstatement of the operant behavior. Extinction and reinstatement of this operant response enhanced proenkephalin mRNA in the dorsal striatum and/or the nucleus accumbens core. Down-regulation of D2 receptor expression was observed in the dorsal striatum and nucleus accumbens after reinstatement. An up-regulation of PDYN mRNA expression was found in the hypothalamus after extinction and reinstatement. This study provides a new operant model in mice for the evaluation of food-taking behavior and reveals specific changes in the dopamine and opioid system associated to the behavioral responses directed to obtain a natural reward.

  1. Recombinant lambda-phage nanobioparticles for tumor therapy in mice models.

    Science.gov (United States)

    Ghaemi, Amir; Soleimanjahi, Hoorieh; Gill, Pooria; Hassan, Zuhair; Jahromi, Soodeh Razeghi M; Roohvand, Farzin

    2010-05-12

    Lambda phages have considerable potential as gene delivery vehicles due to their genetic tractability, low cost, safety and physical characteristics in comparison to other nanocarriers and gene porters. Little is known concerning lambda phage-mediated gene transfer and expression in mammalian hosts. We therefore performed experiments to evaluate lambda-ZAP bacteriophage-mediated gene transfer and expression in vitro. For this purpose, we constructed recombinant lambda-phage nanobioparticles containing a mammalian expression cassette encoding enhanced green fluorescent protein (EGFP) and E7 gene of human papillomavirus type 16 (lambda-HPV-16 E7) using Lambda ZAP- CMV XR vector. Four cell lines (COS-7, CHO, TC-1 and HEK-239) were transduced with the nanobioparticles. We also characterized the therapeutic anti-tumor effects of the recombinant lambda-HPV-16 E7 phage in C57BL/6 tumor mice model as a cancer vaccine. Obtained results showed that delivery and expression of these genes in fibroblastic cells (COS-7 and CHO) are more efficient than epithelial cells (TC-1 and HEK-239) using these nanobioparticles. Despite the same phage M.O.I entry, the internalizing titers of COS-7 and CHO cells were more than TC-1 and HEK-293 cells, respectively. Mice vaccinated with lambda-HPV-16 E7 are able to generate potent therapeutic antitumor effects against challenge with E7- expressing tumor cell line, TC-1 compared to group treated with the wild phage. The results demonstrated that the recombinant lambda-phages, due to their capabilities in transducing mammalian cells, can also be considered in design and construction of novel and safe phage-based nanomedicines.

  2. Including the effects of elastic compressibility and volume changes in geodynamical modeling of crust-lithosphere-mantle deformation

    Science.gov (United States)

    de Monserrat, Albert; Morgan, Jason P.

    2016-04-01

    Materials in Earth's interior are exposed to thermomechanical (e.g. variations in stress/pressure and temperature) and chemical (e.g. phase changes, serpentinization, melting) processes that are associated with volume changes. Most geodynamical codes assume the incompressible Boussinesq approximation, where changes in density due to temperature or phase change effect buoyancy, yet volumetric changes are not allowed, and mass is not locally conserved. Elastic stresses induced by volume changes due to thermal expansion, serpentinization, and melt intrusion should cause 'cold' rocks to brittlely fail at ~1% strain. When failure/yielding is an important rheological feature, we think it plausible that volume-change-linked stresses may have a significant influence on the localization of deformation. Here we discuss a new Lagrangian formulation for "elasto-compressible -visco-plastic" flow. In this formulation, the continuity equation has been generalised from a Boussinesq incompressible formulation to include recoverable, elastic, volumetric deformations linked to the local state of mean compressive stress. This formulation differs from the 'anelastic approximation' used in compressible viscous flow in that pressure- and temperature- dependent volume changes are treated as elastic deformation for a given pressure, temperature, and composition/phase. This leads to a visco-elasto-plastic formulation that can model the effects of thermal stresses, pressure-dependent volume changes, and local phase changes. We use a modified version of the (Miliman-based) FEM code M2TRI to run a set of numerical experiments for benchmarking purposes. Three benchmarks are being used to assess the accuracy of this formulation: (1) model the effects on density of a compressible mantle under the influence of gravity; (2) model the deflection of a visco-elastic beam under the influence of gravity, and its recovery when gravitational loading is artificially removed; (3) Modelling the stresses

  3. Spectral element modelling of seismic wave propagation in visco-elastoplastic media including excess-pore pressure development

    Science.gov (United States)

    Oral, Elif; Gélis, Céline; Bonilla, Luis Fabián; Delavaud, Elise

    2017-12-01

    Numerical modelling of seismic wave propagation, considering soil nonlinearity, has become a major topic in seismic hazard studies when strong shaking is involved under particular soil conditions. Indeed, when strong ground motion propagates in saturated soils, pore pressure is another important parameter to take into account when successive phases of contractive and dilatant soil behaviour are expected. Here, we model 1-D seismic wave propagation in linear and nonlinear media using the spectral element numerical method. The study uses a three-component (3C) nonlinear rheology and includes pore-pressure excess. The 1-D-3C model is used to study the 1987 Superstition Hills earthquake (ML 6.6), which was recorded at the Wildlife Refuge Liquefaction Array, USA. The data of this event present strong soil nonlinearity involving pore-pressure effects. The ground motion is numerically modelled for different assumptions on soil rheology and input motion (1C versus 3C), using the recorded borehole signals as input motion. The computed acceleration-time histories show low-frequency amplification and strong high-frequency damping due to the development of pore pressure in one of the soil layers. Furthermore, the soil is found to be more nonlinear and more dilatant under triaxial loading compared to the classical 1C analysis, and significant differences in surface displacements are observed between the 1C and 3C approaches. This study contributes to identify and understand the dominant phenomena occurring in superficial layers, depending on local soil properties and input motions, conditions relevant for site-specific studies.

  4. Effect of Alnus japonica extract on a model of atopic dermatitis in NC/Nga mice.

    Science.gov (United States)

    Choi, Sun Eun; Park, Kwan Hee; Jeong, Mi Sook; Kim, Han Hyuk; Lee, Do Ik; Joo, Seong Soo; Lee, Chung Soo; Bang, Hyoweon; Choi, Young Wook; Lee, Mi-Kyung; Seo, Seong Jun; Lee, Min Won

    2011-07-14

    The bark of Alnus species has long been used in traditional oriental medicine in the treatment of many pathological conditions, including fever, hemorrhage, diarrhea, alcoholism, various skin diseases (e.g. chronic herpes, eczema and prurigo), and inflammation. In order to assess the immunomodulatory efficacy of a novel herbal medicine in treating atopic dermatitis, we measured serum levels of several allergic and inflammatory biomarkers in NC/Nga mice before and after treatment with this experimental agent. Gene and protein expression analyses of iNOS and COX-2 were quantified by real time PCR and Western blot analysis and serum levels of IL-4, -5 and -13 were also measured by ELISA, all of which were reduced after treatment with the experimental agent. Additionally, serum concentrations of IgE and blood eosinophil counts were reduced in treated mice. The topical application of leaf and bark extract from Alnus japonica suppressed the development of AD-like skin lesions. The percent of blood eosinophils was decreased after treatment with leaf and bark extract from Alnus japonica. The serum IgE and Th2-related cytokine levels were decreased after treatment with leaf and bark extract from Alnus japonica compared with those treated with base cream (vehicle treated AD group). The IL-4, IL-5 and IL-13 were lower than those of vehicle treated AD group. We contend that leaf and bark extract from Alnus japonica may prove useful in the treatment of atopic dermatitis and other allergic skin diseases, although more in-depth clinical studies are necessary before clinical implementation. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  5. Modeling environmental risk factors of autism in mice induces IBD-related gut microbial dysbiosis and hyperserotonemia.

    Science.gov (United States)

    Lim, Joon Seo; Lim, Mi Young; Choi, Yongbin; Ko, GwangPyo

    2017-04-20

    Autism spectrum disorder (ASD) is a range of neurodevelopmental conditions that are sharply increasing in prevalence worldwide. Intriguingly, ASD is often accompanied by an array of systemic aberrations including (1) increased serotonin, (2) various modes of gastrointestinal disorders, and (3) inflammatory bowel disease (IBD), albeit the underlying cause for such comorbidities remains uncertain. Also, accumulating number of studies report that the gut microbial composition is significantly altered in children with ASD or patients with IBD. Surprisingly, when we analyzed the gut microbiota of poly I:C and VPA-induced mouse models of ASD, we found a distinct pattern of microbial dysbiosis that highly recapitulated those reported in clinical cases of ASD and IBD. Moreover, we report that such microbial dysbiosis led to notable perturbations in microbial metabolic pathways that are known to negatively affect the host, especially with regards to the pathogenesis of ASD and IBD. Lastly, we found that serum level of serotonin is significantly increased in both poly I:C and VPA mice, and that it correlates with increases of a bacterial genus and a metabolic pathway that are implicated in stimulation of host serotonin production. Our results using animal model identify prenatal environmental risk factors of autism as possible causative agents of IBD-related gut microbial dysbiosis in ASD, and suggest a multifaceted role of gut microbiota in the systemic pathogenesis of ASD and hyperserotonemia.

  6. Kaempferol attenuates acute lung injury in caecal ligation and puncture model of sepsis in mice.

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    Rabha, Dipankar Jyoti; Singh, Thakur Uttam; Rungsung, Soya; Kumar, Tarun; Parida, Subhashree; Lingaraju, Madhu Cholenahalli; Paul, Avishek; Sahoo, Monalisa; Kumar, Dinesh

    2018-03-01

    Kaempferol is a flavonoid and important part of the diet. Kaempferol has shown antioxidant, antiinflammatory and antidiabetic activities in various studies. However, protective potential of kaempferol in acute lung injury induced by sepsis and its mechanism remains unclear. The present study was undertaken to evaluate the effect of kaempferol in sepsis-induced acute lung injury in mice and its possible mechanism of action. Acute lung injury was induced by CLP surgery in mice. Kaempferol (100 mg/kg bw) was administered orally one hour before caecal ligation and puncture surgery in mice. Mice were divided into four groups sham, KEM+sham, sepsis (CLP), and KEM+sepsis. Assessment of lung injury was done by estimation of protein content in lung tissue, lung edema, proinflammatory cytokines in plasma and lung tissue, oxidative stress, antioxidant enzymes, nitrite production, and histopathology. Kaempferol pretreated mice showed significant (P Kaempferol pretreatment showed reduction in cytokines IL-6, IL-1β, and TNF-α in plasma as well as in lung tissue in comparison with septic mice without pretreatment. Pretreatment with kaempferol did not show any reduction in MDA level in comparison with septic mice. Antioxidant enzymes SOD and catalase and nonenzymatic antioxidant GSH activities were also increased with kaempferol pretreatment in septic mice. Further, kaempferol pretreatment reduced the lung tissue nitrite level (P Kaempferol pretreatment did not decrease bacterial load in septic mice. Mice pretreated with kaempferol followed by sepsis showed lesser infiltration of cells and more arranged alveolar structure in histopathological analysis. The study suggests that kaempferol showed attenuation in sepsis-induced acute lung injury in mice through suppression of oxidative stress, iNOS, and ICAM-1 pathways.

  7. Subchronic infusion of the product of inflammation prostaglandin J2 models sporadic Parkinson's disease in mice

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    Figueiredo-Pereira Maria E

    2009-07-01

    Full Text Available Abstract Background Chronic neuroinflammation is implicated in Parkinson's disease (PD. Inflammation involves the activation of microglia and astrocytes that release high levels of prostaglandins. There is a profound gap in our understanding of how cyclooxygenases and their prostaglandin products redirect cellular events to promote PD neurodegeneration. The major prostaglandin in the mammalian brain is prostaglandin D2, which readily undergoes spontaneous dehydration to generate the bioactive cyclopentenone prostaglandins of the J2 series. These J2 prostaglandins are highly reactive and neurotoxic products of inflammation shown in cellular models to impair the ubiquitin/proteasome pathway and cause the accumulation of ubiquitinated proteins. PD is a disorder that exhibits accumulation of ubiquitinated proteins in neuronal inclusions (Lewy bodies. The role of J2 prostaglandins in promoting PD neurodegeneration has not been investigated under in vivo conditions. Methods We addressed the neurodegenerative and behavioral effects of the administration of prostaglandin J2 (PGJ2 simultaneously into the substantia nigra/striatum of adult male FVB mice by subchronic microinjections. One group received unilateral injections of DMSO (vehicle, n = 6 and three groups received PGJ2 [3.4 μg or 6.7 μg (n = 6 per group or 16.7 μg (n = 5] per injection. Immunohistochemical and behavioral analyses were applied to assess the effects of the subchronic PGJ2 microinfusions. Results Immunohistochemical analysis demonstrated a PGJ2 dose-dependent significant and selective loss of dopaminergic neurons in the substantia nigra while the GABAergic neurons were spared. PGJ2 also triggered formation of aggregates immunoreactive for ubiquitin and α-synuclein in the spared dopaminergic neurons. Moreover, PGJ2 infusion caused a massive microglia and astrocyte activation that could initiate a deleterious cascade leading to self-sustained progressive neurodegeneration. The PGJ

  8. Including cetaceans in multi-species assessment models using strandings data: why, how and what can we do about it?

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    Camilo Saavedra

    2014-07-01

    Full Text Available Single-species models have been commonly used to assess fish stocks in the past. Since these models have relatively simple data requirements, they sometimes provide the only tool available to assess the status of a stock when data are not enough to develop more complex models. However, these models have been criticized for several reasons since they provide reference points independently for each species assessed ignoring their interactions. For example, several studies suggest that even more substantial reductions in fishing mortality may be necessary to ensure MSY is reached when taking into consideration multiespecies interactions. Therefore, and as Pauly et al. (1998 stated, single-species analysis may mislead researchers and managers into neglecting the gear and trophic interactions which ultimately determine stocks long-term yields and ecosystem health. Ecosystem or multispecies models offer a number of advantages over single-species models. As stated in the workshop “Incorporating ecosystem considerations into stock assessments and management advice” (Mace, 2000 two general improvements are: a better appreciation of the fishing on ecosystem structure and function, and a better appreciation of the need to consider de value of marine ecosystems for functions other than harvesting fish. As disadvantages, multispecies models are statistically complex and include trophic relationships requiring more information (e.g. good estimations of biological parameters of each species and generally a full quantification of the diet sometimes available though the analysis of stomach contents. To reduce the number of species and therefore the amount of information needed, Minimum Realistic Models (MRMs represent an intermediate level of complexity, where only the subset of the ecosystem, important for the issue under consideration, is modeled. This approach offers the advantage of allowing a refinement of our estimates and can help answer more targeted

  9. A model of Salmonella colitis with features of diarrhea in SLC11A1 wild-type mice.

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    Heungjeong Woo

    Full Text Available BACKGROUND: Mice do not get diarrhea when orally infected with S. enterica, but pre-treatment with oral aminoglycosides makes them susceptible to Salmonella colitis. However, genetically susceptible ItyS mice (Nramp1(G169D allele die from systemic infection before they develop diarrhea, so a new model is needed to study the pathogenesis of diarrhea. We pretreated ItyR mice (Nramp1(G169 with oral kanamycin prior to infecting them with virulent S. Typhimurium strain 14028s in order to study Salmonella-induced diarrhea. We used both a visual scoring system and the measurement of fecal water content to measure diarrhea. BALB/c.D2(Nramp1 congenic started losing weight 5 days post-infection and they began to die from colitis 10-14 days after infection. A SPI-1 (invA mutant caused cecal, but not colonic inflammation and did not cause diarrhea. A phoP- mutant did not cause manifestations of diarrhea in either normal or NADPH-deficient (gp91(phox mice. However, strain 14028s caused severe colitis and diarrhea in gp91(phox-deficient mice on an ItyR background. pmr A and F mutants, which are less virulent in orally infected BALB/c mice, were fully virulent in this model of colitis. CONCLUSIONS: S. enterica must be able to invade the colonic epithelium and to persist in the colon in order to cause colitis with manifestations of diarrhea. The NADPH oxidase is not required for diarrhea in Salmonella colitis. Furthermore, a Salmonella phoP mutant can be cleared from the colon by non-oxidative host defenses.

  10. Effects of the hindlimb-unloading model of spaceflight conditions on resistance of mice to infection with Klebsiella pneumoniae

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    Belay, Tesfaye; Aviles, Hernan; Vance, Monique; Fountain, Kimberly; Sonnenfeld, Gerald

    2002-01-01

    BACKGROUND: It has been well documented in several studies that many immunologic parameters are altered in experimental animals and human subjects who have flown in space. However, it is not fully known whether these immunologic changes could result in increased susceptibility to infection. Hindlimb (antiorthostatic) unloading of rodents has been used successfully to simulate some of the effects of spaceflight on physiologic systems. OBJECTIVE: The objective of this study was to determine the effect of hindlimb unloading on the outcome of Klebsiella pneumoniae infection in mice. METHODS: Hindlimb-unloaded, hindlimb-restrained, and control mice were intraperitoneally infected with one 50% lethal dose of K pneumoniae 2 days after suspension. Mortality and bacterial load in several organs were compared among the groups. RESULTS: Unloaded mice showed significantly increased mortality and reduced mean time to death compared with that seen in the control groups. Kinetics of bacterial growth with smaller infective doses revealed that control mice were able to clear bacteria from the organs after 30 hours. In contrast, unloaded mice had continued bacterial growth at the same time point. CONCLUSION: The results of this study suggest that hindlimb unloading might enhance the dissemination of K pneumoniae, leading to increased mortality. The complex physiologic changes observed during hindlimb unloading, including stress, have a key role in the pathophysiology of this infection.

  11. Compensatory mechanisms in genetic models of neurodegeneration: are the mice better than humans?

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    Grzegorz eKreiner

    2015-03-01

    Full Text Available Neurodegenerative diseases are one of the main causes of mental and physical disabilities. Neurodegeneration has been estimated to begin many years before the first clinical symptoms manifest, and even a prompt diagnosis at this stage provides very little advantage for a more effective treatment as the currently available pharmacotherapies are based on disease symptomatology. The etiology of the majorit