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  1. Islamic Caring Model on Increase Patient Satisfaction

    OpenAIRE

    Abdurrouf, Muh; Nursalam, Nursalam; Purwaningsih, Purwaningsih

    2013-01-01

    Introduction: Patient satisfaction was important aspect that must be considered by health service providers, patients who were not satisfied will leave the hospital and be a competitor's customers so be able caused a decrease in sales of products/services and in turn could reduce and even loss of profit, therefore, the hospital must provided the best service so that it could increase patient satisfaction. The purpose of this study was to exams the effect of Islamic caring model on increase pa...

  2. BUSINESS MODELS FOR INCREASING TECHNOLOGICAL TRANSFER EFFECTIVENESS

    Directory of Open Access Journals (Sweden)

    Simina FULGA

    2016-05-01

    Full Text Available The present paper is devoted to analyze the appropriate recommendations to increase the effectiveness of technology transfer organizations (centers from ReNITT, by using the specific instruments of Business Model Canvas, associated to the technological transfer value chain for the value added services addressed to their clients and according to a continuously improved competitive strategy over competition analysis.

  3. ISLAMIC CARING MODEL ON INCREASE PATIENT SATISFACTION

    Directory of Open Access Journals (Sweden)

    Muh. Abdurrouf

    2017-04-01

    Full Text Available Introduction: Patient satisfaction was important aspect that must be considered by health service providers, patients who were not satisfied will leave the hospital and be a competitor's customers so be able caused a decrease in sales of products/services and in turn could reduce and even loss of profit, therefore, the hospital must provided the best service so that it could increase patient satisfaction. The purpose of this study was to exams the effect of Islamic caring model on increase patient satisfaction.. Method: This study was used pre-experimental design, the respondents were 31 patients in the treatment group assigned Islamic caring and 31 patients with a kontrol group that were not given Islamic caring Inpatient Surgical Sultan Agung Islamic Hospital Semarang by using consecutive sampling techniques, patient satisfaction data collected through questionnaires and analyzed with Mann-Whitney test, as for finding out the Islamic caring for patient satisfaction were analyzed with spearmen's rho test. Result: The results showed that there was a significant influence of Islamic caring for perceived disconfirmation (p=0,000 there was a perceived disconfirmation influence on patient satisfaction significantly (p=0,000, there was a significant influence of Islamic caring for patient satisfaction in the treatment group with a kontrol group (p=0.001. Discussion: Discussion of this study was Islamic caring model effect on the increase perceived disconfirmation and patient satisfaction, Perceived disconfirmation effect on patient satisfaction, patient satisfaction who given Islamic caring was increase, patients given Islamic caring had higher satisfaction levels than patients who not given Islamic caring. Suggestions put forward based on the results of the study of Islamic caring model could be applied in Sultan Agung Islamic Hospital as a model of nursing care, Islamic caring behavior can be learned and improved through training and commitment and

  4. Towards increased policy relevance in energy modeling

    Energy Technology Data Exchange (ETDEWEB)

    Worrell, Ernst; Ramesohl, Stephan; Boyd, Gale

    2003-07-29

    Historically, most energy models were reasonably equipped to assess the impact of a subsidy or change in taxation, but are often insufficient to assess the impact of more innovative policy instruments. We evaluate the models used to assess future energy use, focusing on industrial energy use. We explore approaches to engineering-economic analysis that could help improve the realism and policy relevance of engineering-economic modeling frameworks. We also explore solutions to strengthen the policy usefulness of engineering-economic analysis that can be built from a framework of multi-disciplinary cooperation. We focus on the so-called ''engineering-economic'' (or ''bottom-up'') models, as they include the amount of detail that is commonly needed to model policy scenarios. We identify research priorities for the modeling framework, technology representation in models, policy evaluation and modeling of decision-making behavior.

  5. Numerical Modeling of Rotary Kiln Productivity Increase

    NARCIS (Netherlands)

    Romero-Valle, M.A.; Pisaroni, M.; Van Puyvelde, D.; Lahaye, D.J.P.; Sadi, R.

    2013-01-01

    Rotary kilns are used in many industrial processes ranging from cement manufacturing to waste incineration. The operating conditions vary widely depending on the process. While there are many models available within the literature and industry, the wide range of operating conditions justifies

  6. FORUM Models for increasing the health workforce

    African Journals Online (AJOL)

    stewardship of the anticipated growth of private education and services ... The Global Health Workforce Alliance3 recognises the importance of increasing ... Action 2010 - 2014 to advance economic growth and development, to be realised by ... of the private higher education sector must be better understood and supported.

  7. A Model-Free Definition of Increasing Uncertainty

    NARCIS (Netherlands)

    Grant, S.; Quiggin, J.

    2001-01-01

    We present a definition of increasing uncertainty, independent of any notion of subjective probabilities, or of any particular model of preferences.Our notion of an elementary increase in the uncertainty of any act corresponds to the addition of an 'elementary bet' which increases consumption by a

  8. Development Parenting Model to Increase the Independence of Children

    Science.gov (United States)

    Sunarty, Kustiah; Dirawan, Gufran Darma

    2015-01-01

    This study examines parenting and the child's independence model. The research problem is whether there is a relationship between parenting and the child's independence. The purpose of research is to determine: firstly, the type of parenting in an effort to increase the independence of the child; and the relationship between parenting models and…

  9. Hybrid discrete choice models: Gained insights versus increasing effort

    International Nuclear Information System (INIS)

    Mariel, Petr; Meyerhoff, Jürgen

    2016-01-01

    Hybrid choice models expand the standard models in discrete choice modelling by incorporating psychological factors as latent variables. They could therefore provide further insights into choice processes and underlying taste heterogeneity but the costs of estimating these models often significantly increase. This paper aims at comparing the results from a hybrid choice model and a classical random parameter logit. Point of departure for this analysis is whether researchers and practitioners should add hybrid choice models to their suite of models routinely estimated. Our comparison reveals, in line with the few prior studies, that hybrid models gain in efficiency by the inclusion of additional information. The use of one of the two proposed approaches, however, depends on the objective of the analysis. If disentangling preference heterogeneity is most important, hybrid model seems to be preferable. If the focus is on predictive power, a standard random parameter logit model might be the better choice. Finally, we give recommendations for an adequate use of hybrid choice models based on known principles of elementary scientific inference. - Highlights: • The paper compares performance of a Hybrid Choice Model (HCM) and a classical Random Parameter Logit (RPL) model. • The HCM indeed provides insights regarding preference heterogeneity not gained from the RPL. • The RPL has similar predictive power as the HCM in our data. • The costs of estimating HCM seem to be justified when learning more on taste heterogeneity is a major study objective.

  10. Hybrid discrete choice models: Gained insights versus increasing effort

    Energy Technology Data Exchange (ETDEWEB)

    Mariel, Petr, E-mail: petr.mariel@ehu.es [UPV/EHU, Economía Aplicada III, Avda. Lehendakari Aguire, 83, 48015 Bilbao (Spain); Meyerhoff, Jürgen [Institute for Landscape Architecture and Environmental Planning, Technical University of Berlin, D-10623 Berlin, Germany and The Kiel Institute for the World Economy, Duesternbrooker Weg 120, 24105 Kiel (Germany)

    2016-10-15

    Hybrid choice models expand the standard models in discrete choice modelling by incorporating psychological factors as latent variables. They could therefore provide further insights into choice processes and underlying taste heterogeneity but the costs of estimating these models often significantly increase. This paper aims at comparing the results from a hybrid choice model and a classical random parameter logit. Point of departure for this analysis is whether researchers and practitioners should add hybrid choice models to their suite of models routinely estimated. Our comparison reveals, in line with the few prior studies, that hybrid models gain in efficiency by the inclusion of additional information. The use of one of the two proposed approaches, however, depends on the objective of the analysis. If disentangling preference heterogeneity is most important, hybrid model seems to be preferable. If the focus is on predictive power, a standard random parameter logit model might be the better choice. Finally, we give recommendations for an adequate use of hybrid choice models based on known principles of elementary scientific inference. - Highlights: • The paper compares performance of a Hybrid Choice Model (HCM) and a classical Random Parameter Logit (RPL) model. • The HCM indeed provides insights regarding preference heterogeneity not gained from the RPL. • The RPL has similar predictive power as the HCM in our data. • The costs of estimating HCM seem to be justified when learning more on taste heterogeneity is a major study objective.

  11. Increasing Free Throw Accuracy through Behavior Modeling and Goal Setting.

    Science.gov (United States)

    Erffmeyer, Elizabeth S.

    A two-year behavior-modeling training program focusing on attention processes, retention processes, motor reproduction, and motivation processes was implemented to increase the accuracy of free throw shooting for a varsity intercollegiate women's basketball team. The training included specific learning keys, progressive relaxation, mental…

  12. Value increasing business model for e-hospital.

    Science.gov (United States)

    Null, Robert; Wei, June

    2009-01-01

    This paper developed a business value increasing model for electronic hospital (e-hospital) based on electronic value chain analysis. From this model, 58 hospital electronic business (e-business) solutions were developed. Additionally, this paper investigated the adoption patterns of these 58 e-business solutions within six US leading hospitals. The findings show that only 36 of 58 or 62% of the e-business solutions are fully or partially implemented within the six hospitals. Ultimately, the research results will be beneficial to managers and executives for accelerating e-business adoptions for e-hospital.

  13. PHYSICS OF ECLIPSING BINARIES. II. TOWARD THE INCREASED MODEL FIDELITY

    Energy Technology Data Exchange (ETDEWEB)

    Prša, A.; Conroy, K. E.; Horvat, M.; Kochoska, A.; Hambleton, K. M. [Villanova University, Dept. of Astrophysics and Planetary Sciences, 800 E Lancaster Avenue, Villanova PA 19085 (United States); Pablo, H. [Université de Montréal, Pavillon Roger-Gaudry, 2900, boul. Édouard-Montpetit Montréal QC H3T 1J4 (Canada); Bloemen, S. [Radboud University Nijmegen, Department of Astrophysics, IMAPP, P.O. Box 9010, 6500 GL, Nijmegen (Netherlands); Giammarco, J. [Eastern University, Dept. of Astronomy and Physics, 1300 Eagle Road, St. Davids, PA 19087 (United States); Degroote, P. [KU Leuven, Instituut voor Sterrenkunde, Celestijnenlaan 200D, B-3001 Heverlee (Belgium)

    2016-12-01

    The precision of photometric and spectroscopic observations has been systematically improved in the last decade, mostly thanks to space-borne photometric missions and ground-based spectrographs dedicated to finding exoplanets. The field of eclipsing binary stars strongly benefited from this development. Eclipsing binaries serve as critical tools for determining fundamental stellar properties (masses, radii, temperatures, and luminosities), yet the models are not capable of reproducing observed data well, either because of the missing physics or because of insufficient precision. This led to a predicament where radiative and dynamical effects, insofar buried in noise, started showing up routinely in the data, but were not accounted for in the models. PHOEBE (PHysics Of Eclipsing BinariEs; http://phoebe-project.org) is an open source modeling code for computing theoretical light and radial velocity curves that addresses both problems by incorporating missing physics and by increasing the computational fidelity. In particular, we discuss triangulation as a superior surface discretization algorithm, meshing of rotating single stars, light travel time effects, advanced phase computation, volume conservation in eccentric orbits, and improved computation of local intensity across the stellar surfaces that includes the photon-weighted mode, the enhanced limb darkening treatment, the better reflection treatment, and Doppler boosting. Here we present the concepts on which PHOEBE is built and proofs of concept that demonstrate the increased model fidelity.

  14. Theoretical modeling of critical temperature increase in metamaterial superconductors

    Science.gov (United States)

    Smolyaninov, Igor; Smolyaninova, Vera

    Recent experiments have demonstrated that the metamaterial approach is capable of drastic increase of the critical temperature Tc of epsilon near zero (ENZ) metamaterial superconductors. For example, tripling of the critical temperature has been observed in Al-Al2O3 ENZ core-shell metamaterials. Here, we perform theoretical modelling of Tc increase in metamaterial superconductors based on the Maxwell-Garnett approximation of their dielectric response function. Good agreement is demonstrated between theoretical modelling and experimental results in both aluminum and tin-based metamaterials. Taking advantage of the demonstrated success of this model, the critical temperature of hypothetic niobium, MgB2 and H2S-based metamaterial superconductors is evaluated. The MgB2-based metamaterial superconductors are projected to reach the liquid nitrogen temperature range. In the case of an H2S-based metamaterial Tc appears to reach 250 K. This work was supported in part by NSF Grant DMR-1104676 and the School of Emerging Technologies at Towson University.

  15. Accounting for Business Models: Increasing the Visibility of Stakeholders

    Directory of Open Access Journals (Sweden)

    Colin Haslam

    2015-01-01

    Full Text Available Purpose: This paper conceptualises a firm’s business model employing stakeholder theory as a central organising element to help inform the purpose and objective(s of business model financial reporting and disclosure. Framework: Firms interact with a complex network of primary and secondary stakeholders to secure the value proposition of a firm’s business model. This value proposition is itself a complex amalgam of value creating, value capturing and value manipulating arrangements with stakeholders. From a financial accounting perspective the purpose of the value proposition for a firm’s business model is to sustain liquidity and solvency as a going concern. Findings: This article argues that stakeholder relations impact upon the financial viability of a firm’s business model value proposition. However current financial reporting by function of expenses and the central organising objectives of the accounting conceptual framework conceal firm-stakeholder relations and their impact on reported financials. Practical implications: The practical implication of our paper is that ‘Business Model’ financial reporting would require a reorientation in the accounting conceptual framework that defines the objectives and purpose of financial reporting. This reorientation would involve reporting about stakeholder relations and their impact on a firms financials not simply reporting financial information to ‘investors’. Social Implications: Business model financial reporting has the potential to be stakeholder inclusive because the numbers and narratives reported by firms in their annual financial statements will increase the visibility of stakeholder relations and how these are being managed. What is original/value of paper: This paper’s original perspective is that it argues that a firm’s business model is structured out of stakeholder relations. It presents the firm’s value proposition as the product of value creating, capturing and

  16. Building on crossvalidation for increasing the quality of geostatistical modeling

    Science.gov (United States)

    Olea, R.A.

    2012-01-01

    The random function is a mathematical model commonly used in the assessment of uncertainty associated with a spatially correlated attribute that has been partially sampled. There are multiple algorithms for modeling such random functions, all sharing the requirement of specifying various parameters that have critical influence on the results. The importance of finding ways to compare the methods and setting parameters to obtain results that better model uncertainty has increased as these algorithms have grown in number and complexity. Crossvalidation has been used in spatial statistics, mostly in kriging, for the analysis of mean square errors. An appeal of this approach is its ability to work with the same empirical sample available for running the algorithms. This paper goes beyond checking estimates by formulating a function sensitive to conditional bias. Under ideal conditions, such function turns into a straight line, which can be used as a reference for preparing measures of performance. Applied to kriging, deviations from the ideal line provide sensitivity to the semivariogram lacking in crossvalidation of kriging errors and are more sensitive to conditional bias than analyses of errors. In terms of stochastic simulation, in addition to finding better parameters, the deviations allow comparison of the realizations resulting from the applications of different methods. Examples show improvements of about 30% in the deviations and approximately 10% in the square root of mean square errors between reasonable starting modelling and the solutions according to the new criteria. ?? 2011 US Government.

  17. Cloud Computing Adoption Model for Universities to Increase ICT Proficiency

    Directory of Open Access Journals (Sweden)

    Safiya Okai

    2014-08-01

    Full Text Available Universities around the world especially those in developing countries are faced with the problem of delivering the level of information and communications technology (ICT needed to facilitate teaching, learning, research, and development activities ideal in a typical university, which is needed to meet educational needs in-line with advancement in technology and the growing dependence on IT. This is mainly due to the high cost involved in providing and maintaining the needed hardware and software. A technology such as cloud computing that delivers on demand provisioning of IT resources on a pay per use basis can be used to address this problem. Cloud computing promises better delivery of IT services as well as availability whenever and wherever needed at reduced costs with users paying only as much as they consume through the services of cloud service providers. The cloud technology reduces complexity while increasing speed and quality of IT services provided; however, despite these benefits the challenges that come with its adoption have left many sectors especially the higher education skeptical in committing to this technology. This article identifies the reasons for the slow rate of adoption of cloud computing at university level, discusses the challenges faced and proposes a cloud computing adoption model that contains strategic guidelines to overcome the major challenges identified and a roadmap for the successful adoption of cloud computing by universities. The model was tested in one of the universities and found to be both useful and appropriate for adopting cloud computing at university level.

  18. Increased opioid dependence in a mouse model of panic disorder

    Directory of Open Access Journals (Sweden)

    Xavier Gallego

    2010-02-01

    Full Text Available Panic disorder is a highly prevalent neuropsychiatric disorder that shows co-occurrence with substance abuse. Here, we demonstrate that TrkC, the high affinity receptor for neurotrophin-3, is a key molecule involved in panic disorder and opiate dependence, using a transgenic mouse model (TgNTRK3. Constitutive TrkC overexpression in TgNTRK3 mice dramatically alters spontaneous firing rates of locus coeruleus neurons and the response of the noradrenergic system to chronic opiate exposure, possibly related to the altered regulation of neurotrophic peptides observed. Notably, TgNTRK3 locus coeruleus neurons showed an increased firing rate in saline-treated conditions and profound abnormalities in their response to met5-enkephalin. Behaviorally, chronic morphine administration induced a significantly increased withdrawal syndrome in TgNTRK3 mice. In conclusion, we show here that the NT-3/TrkC system is an important regulator of neuronal firing in locus coeruleus and could contribute to the adaptations of the noradrenergic system in response to chronic opiate exposure. Moreover, our results indicate that TrkC is involved in the molecular and cellular changes in noradrenergic neurons underlying both panic attacks and opiate dependence and support a functional endogenous opioid deficit in panic disorder patients.

  19. Increased Statistical Efficiency in a Lognormal Mean Model

    Directory of Open Access Journals (Sweden)

    Grant H. Skrepnek

    2014-01-01

    Full Text Available Within the context of clinical and other scientific research, a substantial need exists for an accurate determination of the point estimate in a lognormal mean model, given that highly skewed data are often present. As such, logarithmic transformations are often advocated to achieve the assumptions of parametric statistical inference. Despite this, existing approaches that utilize only a sample’s mean and variance may not necessarily yield the most efficient estimator. The current investigation developed and tested an improved efficient point estimator for a lognormal mean by capturing more complete information via the sample’s coefficient of variation. Results of an empirical simulation study across varying sample sizes and population standard deviations indicated relative improvements in efficiency of up to 129.47 percent compared to the usual maximum likelihood estimator and up to 21.33 absolute percentage points above the efficient estimator presented by Shen and colleagues (2006. The relative efficiency of the proposed estimator increased particularly as a function of decreasing sample size and increasing population standard deviation.

  20. Modeled Impact of Cirrus Cloud Increases Along Aircraft Flight Paths

    Science.gov (United States)

    Rind, David; Lonergan, P.; Shah, K.

    1999-01-01

    The potential impact of contrails and alterations in the lifetime of background cirrus due to subsonic airplane water and aerosol emissions has been investigated in a set of experiments using the GISS GCM connected to a q-flux ocean. Cirrus clouds at a height of 12-15km, with an optical thickness of 0.33, were input to the model "x" percentage of clear-sky occasions along subsonic aircraft flight paths, where x is varied from .05% to 6%. Two types of experiments were performed: one with the percentage cirrus cloud increase independent of flight density, as long as a certain minimum density was exceeded; the other with the percentage related to the density of fuel expenditure. The overall climate impact was similar with the two approaches, due to the feedbacks of the climate system. Fifty years were run for eight such experiments, with the following conclusions based on the stable results from years 30-50 for each. The experiments show that adding cirrus to the upper troposphere results in a stabilization of the atmosphere, which leads to some decrease in cloud cover at levels below the insertion altitude. Considering then the total effect on upper level cloud cover (above 5 km altitude), the equilibrium global mean temperature response shows that altering high level clouds by 1% changes the global mean temperature by 0.43C. The response is highly linear (linear correlation coefficient of 0.996) for high cloud cover changes between 0. 1% and 5%. The effect is amplified in the Northern Hemisphere, more so with greater cloud cover change. The temperature effect maximizes around 10 km (at greater than 40C warming with a 4.8% increase in upper level clouds), again more so with greater warming. The high cloud cover change shows the flight path influence most clearly with the smallest warming magnitudes; with greater warming, the model feedbacks introduce a strong tropical response. Similarly, the surface temperature response is dominated by the feedbacks, and shows

  1. Increased mast cell numbers in a calcaneal tendon overuse model.

    Science.gov (United States)

    Pingel, J; Wienecke, J; Kongsgaard, M; Behzad, H; Abraham, T; Langberg, H; Scott, A

    2013-12-01

    Tendinopathy is often discovered late because the initial development of tendon pathology is asymptomatic. The aim of this study was to examine the potential role of mast cell involvement in early tendinopathy using a high-intensity uphill running (HIUR) exercise model. Twenty-four male Wistar rats were divided in two groups: running group (n = 12); sedentary control group (n = 12). The running-group was exposed to the HIUR exercise protocol for 7 weeks. The calcaneal tendons of both hind limbs were dissected. The right tendon was used for histologic analysis using Bonar score, immunohistochemistry, and second harmonic generation microscopy (SHGM). The left tendon was used for quantitative polymerase chain reaction (qPCR) analysis. An increased tendon cell density in the runners were observed compared to the controls (P = 0.05). Further, the intensity of immunostaining of protein kinase B, P = 0.03; 2.75 ± 0.54 vs 1.17 ± 0.53, was increased in the runners. The Bonar score (P = 0.05), and the number of mast cells (P = 0.02) were significantly higher in the runners compared to the controls. Furthermore, SHGM showed focal collagen disorganization in the runners, and reduced collagen density (P = 0.03). IL-3 mRNA levels were correlated with mast cell number in sedentary animals. The qPCR analysis showed no significant differences between the groups in the other analyzed targets. The current study demonstrates that 7-week HIUR causes structural changes in the calcaneal tendon, and further that these changes are associated with an increased mast cell density. © 2013 The Authors. Scand J Med Sci Sports published by John Wiley & Sons Ltd.

  2. Modeling the impact of increased adherence to asthma therapy.

    Directory of Open Access Journals (Sweden)

    Amory Schlender

    Full Text Available BACKGROUND: Nonadherence to medications occurs in up to 70% of patients with asthma. The effect of improving adherence is not well quantified. We developed a mathematical model with which to assess the population-level effects of improving medication prescribing and adherence for asthma. METHODS: A mathematical model, calibrated to clinical trial data from the U.S. NHLBI-funded SOCS trial and validated using data from the NHLBI SLIC trial, was used to model the effects of increased prescribing and adherence to asthma controllers. The simulated population consisted of 4,930 individuals with asthma, derived from a sample the National Asthma Survey. Main outcomes were controller use, reliever use, unscheduled doctor visits, emergency department (ED visits, and hospitalizations. RESULTS: For the calibration, simulated outcomes agreed closely with SOCS trial outcomes, with treatment failure hazard ratios [95% confidence interval] of 0.92 [0.58-1.26], 0.97 [0.49-1.45], and 1.01 [0-1.87] for simulation vs. trial in the in placebo, salmeterol, and triamcinolone arms, respectively. For validation, simulated outcomes predicted mid- and end-point treatment failure rates, hazard ratios 1.21 [0.08-2.34] and 0.83 [0.60-1.07], respectively, for patients treated with salmeterol/triamcinolone during the first half of the SLIC study and salmeterol monotherapy during the second half. The model performed less well for patients treated with salmeterol/triamcinolone during the entire study duration, with mid- and end-point hazard ratios 0.83 [0.00-2.12] and 0.37 [0.10-0.65], respectively. Simulation of optimal adherence and prescribing indicated that closing adherence and prescription gaps could prevent as many as nine million unscheduled doctor visits, four million emergency department visits, and one million asthma-related hospitalizations each year in the U.S. CONCLUSIONS: Improvements in medication adherence and prescribing could have a substantial impact on

  3. Increased mast cell numbers in a calcaneal tendon overuse model

    DEFF Research Database (Denmark)

    Pingel, Jessica; Wienecke, Jacob; Kongsgaard Madsen, Mads

    2013-01-01

    Tendinopathy is often discovered late because the initial development of tendon pathology is asymptomatic. The aim of this study was to examine the potential role of mast cell involvement in early tendinopathy using a high-intensity uphill running (HIUR) exercise model. Twenty-four male Wistar rats...... = 0.03; 2.75 ± 0.54 vs 1.17 ± 0.53, was increased in the runners. The Bonar score (P = 0.05), and the number of mast cells (P = 0.02) were significantly higher in the runners compared to the controls. Furthermore, SHGM showed focal collagen disorganization in the runners, and reduced collagen density...... (P = 0.03). IL-3 mRNA levels were correlated with mast cell number in sedentary animals. The qPCR analysis showed no significant differences between the groups in the other analyzed targets. The current study demonstrates that 7-week HIUR causes structural changes in the calcaneal tendon, and further...

  4. Alternative regression models to assess increase in childhood BMI

    OpenAIRE

    Beyerlein, Andreas; Fahrmeir, Ludwig; Mansmann, Ulrich; Toschke, André M

    2008-01-01

    Abstract Background Body mass index (BMI) data usually have skewed distributions, for which common statistical modeling approaches such as simple linear or logistic regression have limitations. Methods Different regression approaches to predict childhood BMI by goodness-of-fit measures and means of interpretation were compared including generalized linear models (GLMs), quantile regression and Generalized Additive Models for Location, Scale and Shape (GAMLSS). We analyzed data of 4967 childre...

  5. Bioburden Increases Heterotopic Ossification Formation in an Established Rat Model.

    Science.gov (United States)

    Pavey, Gabriel J; Qureshi, Ammar T; Hope, Donald N; Pavlicek, Rebecca L; Potter, Benjamin K; Forsberg, Jonathan A; Davis, Thomas A

    2015-09-01

    Heterotopic ossification (HO) develops in a majority of combat-related amputations wherein early bacterial colonization has been considered a potential early risk factor. Our group has recently developed a small animal model of trauma-induced HO that incorporates many of the multifaceted injury patterns of combat trauma in the absence of bacterial contamination and subsequent wound colonization. We sought to determine if (1) the presence of bioburden (Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus [MRSA]) increases the magnitude of ectopic bone formation in traumatized muscle after amputation; and (2) what persistent effects bacterial contamination has on late microbial flora within the amputation site. Using a blast-related HO model, we exposed 48 rats to blast overpressure, femur fracture, crush injury, and subsequent immediate transfemoral amputation through the zone of injury. Control injured rats (n = 8) were inoculated beneath the myodesis with phosphate-buffered saline not containing bacteria (vehicle) and treatment rats were inoculated with 1 × 10(6) colony-forming units of A baumannii (n = 20) or MRSA (n = 20). All animals formed HO. Heterotopic ossification was determined by quantitative volumetric measurements of ectopic bone at 12-weeks postinjury using micro-CT and qualitative histomorphometry for assessment of new bone formation in the residual limb. Bone marrow and muscle tissue biopsies were collected from the residual limb at 12 weeks to quantitatively measure the bioburden load and to qualitatively determine the species-level identification of the bacterial flora. At 12 weeks, we observed a greater volume of HO in rats infected with MRSA (68.9 ± 8.6 mm(3); 95% confidence interval [CI], 50.52-85.55) when compared with A baumannii (20.9 ± 3.7 mm(3); 95% CI, 13.61-28.14; p infection but were positive for other strains of bacteria (1.33 × 10(2) ± 0.89 × 10(2); 95% CI, -0.42 × 10(2)-3.08 × 10(2) and 1.25 × 10(6) ± 0

  6. Alternative regression models to assess increase in childhood BMI

    Directory of Open Access Journals (Sweden)

    Mansmann Ulrich

    2008-09-01

    Full Text Available Abstract Background Body mass index (BMI data usually have skewed distributions, for which common statistical modeling approaches such as simple linear or logistic regression have limitations. Methods Different regression approaches to predict childhood BMI by goodness-of-fit measures and means of interpretation were compared including generalized linear models (GLMs, quantile regression and Generalized Additive Models for Location, Scale and Shape (GAMLSS. We analyzed data of 4967 children participating in the school entry health examination in Bavaria, Germany, from 2001 to 2002. TV watching, meal frequency, breastfeeding, smoking in pregnancy, maternal obesity, parental social class and weight gain in the first 2 years of life were considered as risk factors for obesity. Results GAMLSS showed a much better fit regarding the estimation of risk factors effects on transformed and untransformed BMI data than common GLMs with respect to the generalized Akaike information criterion. In comparison with GAMLSS, quantile regression allowed for additional interpretation of prespecified distribution quantiles, such as quantiles referring to overweight or obesity. The variables TV watching, maternal BMI and weight gain in the first 2 years were directly, and meal frequency was inversely significantly associated with body composition in any model type examined. In contrast, smoking in pregnancy was not directly, and breastfeeding and parental social class were not inversely significantly associated with body composition in GLM models, but in GAMLSS and partly in quantile regression models. Risk factor specific BMI percentile curves could be estimated from GAMLSS and quantile regression models. Conclusion GAMLSS and quantile regression seem to be more appropriate than common GLMs for risk factor modeling of BMI data.

  7. Alternative regression models to assess increase in childhood BMI.

    Science.gov (United States)

    Beyerlein, Andreas; Fahrmeir, Ludwig; Mansmann, Ulrich; Toschke, André M

    2008-09-08

    Body mass index (BMI) data usually have skewed distributions, for which common statistical modeling approaches such as simple linear or logistic regression have limitations. Different regression approaches to predict childhood BMI by goodness-of-fit measures and means of interpretation were compared including generalized linear models (GLMs), quantile regression and Generalized Additive Models for Location, Scale and Shape (GAMLSS). We analyzed data of 4967 children participating in the school entry health examination in Bavaria, Germany, from 2001 to 2002. TV watching, meal frequency, breastfeeding, smoking in pregnancy, maternal obesity, parental social class and weight gain in the first 2 years of life were considered as risk factors for obesity. GAMLSS showed a much better fit regarding the estimation of risk factors effects on transformed and untransformed BMI data than common GLMs with respect to the generalized Akaike information criterion. In comparison with GAMLSS, quantile regression allowed for additional interpretation of prespecified distribution quantiles, such as quantiles referring to overweight or obesity. The variables TV watching, maternal BMI and weight gain in the first 2 years were directly, and meal frequency was inversely significantly associated with body composition in any model type examined. In contrast, smoking in pregnancy was not directly, and breastfeeding and parental social class were not inversely significantly associated with body composition in GLM models, but in GAMLSS and partly in quantile regression models. Risk factor specific BMI percentile curves could be estimated from GAMLSS and quantile regression models. GAMLSS and quantile regression seem to be more appropriate than common GLMs for risk factor modeling of BMI data.

  8. Electrokinetic Treatment for Model Caissons with Increasing Dimensions

    Directory of Open Access Journals (Sweden)

    Eltayeb Mohamedelhassan

    2012-01-01

    Full Text Available Electrokinetic treatment has been known in geotechnical engineering for over six decades, yet, the technique is rarely used. This stems from the absence of design guidelines and specifications for electrokinetic treatment systems. An important issue that need to be investigated and understood in order to devise guidelines from experimental results is the effect of the foundation element size on the outcome of the treatment. Also important is determining the optimum distance between the electrodes and estimating the energy consumption prior to treatment. This experimental study is a preliminary step in understanding some of the issues critical for the guidelines and specifications. Four model caissons with surface areas between 16000 and 128000 mm2 were embedded in soft clayey soil under water and treated for 168 hr with a dc voltage of 6 V. From the results, a distance between the anode (model caisson and the cathode equal 0.25 times the outside diameter of the model caisson was identified as optimum. Relationships between the surface area and axial capacity of the model caisson and the surface area and energy consumption were presented. The equations can be used to preliminary estimate the load capacity and the energy consumption for full-scale applications.

  9. Increased GABAB receptor signaling in a rat model for schizophrenia

    NARCIS (Netherlands)

    Selten, M.M.; Meyer, F.; Ba, W.; Valles, A.; Maas, D.A.; Negwer, M.J.; Eijsink, V.D.; Vugt, R.W.M. van; Hulten, J.A; Bakel, N.H.M. van; Roosen, J.; Linden, R.J. van der; Schubert, D.; Verheij, M.M.M.; Nadif Kasri, N.; Martens, G.J.M.

    2016-01-01

    Schizophrenia is a complex disorder that affects cognitive function and has been linked, both in patients and animal models, to dysfunction of the GABAergic system. However, the pathophysiological consequences of this dysfunction are not well understood. Here, we examined the GABAergic system in an

  10. Modeling the Motion of an Increasing Mass System

    Science.gov (United States)

    Kunkel, William; Harrington, Randal

    2010-01-01

    Problems on the dynamics of changing mass systems often call for the more general form of Newton's second law Fnet = dp/dt. These problems usually involve situations where the mass of the system decreases, such as in rocket propulsion. In contrast, this experiment examines a system where the mass "increases" at a constant rate and the net force…

  11. Physics Of Eclipsing Binaries. II. Towards the Increased Model Fidelity

    OpenAIRE

    Prša, Andrej; Conroy, Kyle E.; Horvat, Martin; Pablo, Herbert; Kochoska, Angela; Bloemen, Steven; Giammarco, Joseph; Hambleton, Kelly M.; Degroote, Pieter

    2016-01-01

    The precision of photometric and spectroscopic observations has been systematically improved in the last decade, mostly thanks to space-borne photometric missions and ground-based spectrographs dedicated to finding exoplanets. The field of eclipsing binary stars strongly benefited from this development. Eclipsing binaries serve as critical tools for determining fundamental stellar properties (masses, radii, temperatures and luminosities), yet the models are not capable of reproducing observed...

  12. The importance of including dynamic social networks when modeling epidemics of airborne infections: does increasing complexity increase accuracy?

    Directory of Open Access Journals (Sweden)

    Go Myong-Hyun

    2011-07-01

    Full Text Available Abstract Mathematical models are useful tools for understanding and predicting epidemics. A recent innovative modeling study by Stehle and colleagues addressed the issue of how complex models need to be to ensure accuracy. The authors collected data on face-to-face contacts during a two-day conference. They then constructed a series of dynamic social contact networks, each of which was used to model an epidemic generated by a fast-spreading airborne pathogen. Intriguingly, Stehle and colleagues found that increasing model complexity did not always increase accuracy. Specifically, the most detailed contact network and a simplified version of this network generated very similar results. These results are extremely interesting and require further exploration to determine their generalizability. Please see related article BMC Medicine, 2011, 9:87

  13. The importance of including dynamic social networks when modeling epidemics of airborne infections: does increasing complexity increase accuracy?

    Science.gov (United States)

    Blower, Sally; Go, Myong-Hyun

    2011-07-19

    Mathematical models are useful tools for understanding and predicting epidemics. A recent innovative modeling study by Stehle and colleagues addressed the issue of how complex models need to be to ensure accuracy. The authors collected data on face-to-face contacts during a two-day conference. They then constructed a series of dynamic social contact networks, each of which was used to model an epidemic generated by a fast-spreading airborne pathogen. Intriguingly, Stehle and colleagues found that increasing model complexity did not always increase accuracy. Specifically, the most detailed contact network and a simplified version of this network generated very similar results. These results are extremely interesting and require further exploration to determine their generalizability.

  14. A New Model of Clinical Education to Increase Student Placement Availability: The Capacity Development Facilitator Model

    Science.gov (United States)

    Fairbrother, Michele; Nicole, Madelyn; Blackford, Julia; Nagarajan, Srivalli Vilapakkam; McAllister, Lindy

    2016-01-01

    This paper reports on a trial of a new model of clinical education designed to increase student clinical placement availability and address workforce constraints on supervision. The University of Sydney deployed the Capacity Development Facilitators (CDF) in selected Sydney hospitals to work with staff to expand student clinical placement…

  15. Social change and increasing of bipolar disorders: an evolutionary model.

    Science.gov (United States)

    Carta, Mauro Giovanni

    2013-01-01

    The objective of this paper is to see if behaviours defined as pathological and maladjusted in certain contexts may produce adaptive effects in other contexts, especially if they occur in attenuated form. Interactions between environment and behaviour are studied from an evolutionary standpoint in an attempt to understand how new attitudes emerge in an evolving context. Narrative review. Following an historical examination of how the description of depression in Western society has changed, we examine a series of studies performed in areas where great changes have taken place as well as research on emigration from Sardinia in the 1960s and 70s and immigration to Sardinia in the 1990s. If we postulate that mood disorders are on the increase and that the epidemic began in the 17th century with the "English malady", we must suppose that at least the "light" forms have an adaptive advantage, otherwise the expansion of the disorder would have been self-limiting. "Compulsive hyper-responsabilization", as well as explorative behaviours, may represent a base for adaptation in certain conditions of social change. The social emphasis in individualism and responsibility may have changed not only the frequency, but also the phenomenology of mood disorders particularly the increases in bipolar disorders. From the sociobiological standpoint the conditions that may favour "subthreshold" bipolar or depressive features are to be considered in relation to the contextual role of gender and the different risks of the two disorders in males and females.

  16. Modeling Increased Complexity and the Reliance on Automation: FLightdeck Automation Problems (FLAP) Model

    Science.gov (United States)

    Ancel, Ersin; Shih, Ann T.

    2014-01-01

    This paper highlights the development of a model that is focused on the safety issue of increasing complexity and reliance on automation systems in transport category aircraft. Recent statistics show an increase in mishaps related to manual handling and automation errors due to pilot complacency and over-reliance on automation, loss of situational awareness, automation system failures and/or pilot deficiencies. Consequently, the aircraft can enter a state outside the flight envelope and/or air traffic safety margins which potentially can lead to loss-of-control (LOC), controlled-flight-into-terrain (CFIT), or runway excursion/confusion accidents, etc. The goal of this modeling effort is to provide NASA's Aviation Safety Program (AvSP) with a platform capable of assessing the impacts of AvSP technologies and products towards reducing the relative risk of automation related accidents and incidents. In order to do so, a generic framework, capable of mapping both latent and active causal factors leading to automation errors, is developed. Next, the framework is converted into a Bayesian Belief Network model and populated with data gathered from Subject Matter Experts (SMEs). With the insertion of technologies and products, the model provides individual and collective risk reduction acquired by technologies and methodologies developed within AvSP.

  17. Air quality models and unusually large ozone increases: Identifying model failures, understanding environmental causes, and improving modeled chemistry

    Science.gov (United States)

    Couzo, Evan A.

    Several factors combine to make ozone (O3) pollution in Houston, Texas, unique when compared to other metropolitan areas. These include complex meteorology, intense clustering of industrial activity, and significant precursor emissions from the heavily urbanized eight-county area. Decades of air pollution research have borne out two different causes, or conceptual models, of O 3 formation. One conceptual model describes a gradual region-wide increase in O3 concentrations "typical" of many large U.S. cities. The other conceptual model links episodic emissions of volatile organic compounds to spatially limited plumes of high O3, which lead to large hourly increases that have exceeded 100 parts per billion (ppb) per hour. These large hourly increases are known to lead to violations of the federal O 3 standard and impact Houston's status as a non-attainment area. There is a need to further understand and characterize the causes of peak O 3 levels in Houston and simulate them correctly so that environmental regulators can find the most cost-effective pollution controls. This work provides a detailed understanding of unusually large O 3 increases in the natural and modeled environments. First, we probe regulatory model simulations and assess their ability to reproduce the observed phenomenon. As configured for the purpose of demonstrating future attainment of the O3 standard, the model fails to predict the spatially limited O3 plumes observed in Houston. Second, we combine ambient meteorological and pollutant measurement data to identify the most likely geographic origins and preconditions of the concentrated O3 plumes. We find evidence that the O3 plumes are the result of photochemical activity accelerated by industrial emissions. And, third, we implement changes to the modeled chemistry to add missing formation mechanisms of nitrous acid, which is an important radical precursor. Radicals control the chemical reactivity of atmospheric systems, and perturbations to

  18. The importance of including dynamic social networks when modeling epidemics of airborne infections: does increasing complexity increase accuracy?

    OpenAIRE

    Blower, Sally; Go, Myong-Hyun

    2011-01-01

    Abstract Mathematical models are useful tools for understanding and predicting epidemics. A recent innovative modeling study by Stehle and colleagues addressed the issue of how complex models need to be to ensure accuracy. The authors collected data on face-to-face contacts during a two-day conference. They then constructed a series of dynamic social contact networks, each of which was used to model an epidemic generated by a fast-spreading airborne pathogen. Intriguingly, Stehle and colleagu...

  19. Examining the impacts of increased corn production on groundwater quality using a coupled modeling system

    Science.gov (United States)

    This study demonstrates the value of a coupled chemical transport modeling system for investigating groundwater nitrate contamination responses associated with nitrogen (N) fertilizer application and increased corn production. The coupled Community Multiscale Air Quality Bidirect...

  20. Increasing the reliability of ecological models using modern software engineering techniques

    Science.gov (United States)

    Robert M. Scheller; Brian R. Sturtevant; Eric J. Gustafson; Brendan C. Ward; David J. Mladenoff

    2009-01-01

    Modern software development techniques are largely unknown to ecologists. Typically, ecological models and other software tools are developed for limited research purposes, and additional capabilities are added later, usually in an ad hoc manner. Modern software engineering techniques can substantially increase scientific rigor and confidence in ecological models and...

  1. Would Outsourcing Increase or Decrease Wage Inequality? Two Models, Two Answers

    OpenAIRE

    Wenli Cheng; Dingsheng Zhang

    2005-01-01

    This paper develops two models to study the impact of outsourcing on wage inequality between skilled and unskilled labor in the developed country and the developing country. The first model assumes symmetric production technologies in both countries, and predicts that outsourcing will increase wage inequality in the developed country, but decrease wage inequality in the developing country. The second model assumes asymmetric technologies in the production of the intermediate good and predicts...

  2. Modeling of the pyrolysis of biomass under parabolic and exponential temperature increases using the Distributed Activation Energy Model

    International Nuclear Information System (INIS)

    Soria-Verdugo, Antonio; Goos, Elke; Arrieta-Sanagustín, Jorge; García-Hernando, Nestor

    2016-01-01

    Highlights: • Pyrolysis of biomass under parabolic and exponential temperature profiles is modeled. • The model is based on a simplified Distributed Activation Energy Model. • 4 biomasses are analyzed in TGA with parabolic and exponential temperature increases. • Deviations between the model prediction and TGA measurements are under 5 °C. - Abstract: A modification of the simplified Distributed Activation Energy Model is proposed to simulate the pyrolysis of biomass under parabolic and exponential temperature increases. The pyrolysis of pine wood, olive kernel, thistle flower and corncob was experimentally studied in a TGA Q500 thermogravimetric analyzer. The results of the measurements of nine different parabolic and exponential temperature increases for each sample were employed to validate the models proposed. The deviation between the experimental TGA measurements and the estimation of the reacted fraction during the pyrolysis of the four samples under parabolic and exponential temperature increases was lower than 5 °C for all the cases studied. The models derived in this work to describe the pyrolysis of biomass with parabolic and exponential temperature increases were found to be in good agreement with the experiments conducted in a thermogravimetric analyzer.

  3. Volcano and ship tracks indicate excessive aerosol-induced cloud water increases in a climate model.

    Science.gov (United States)

    Toll, Velle; Christensen, Matthew; Gassó, Santiago; Bellouin, Nicolas

    2017-12-28

    Aerosol-cloud interaction is the most uncertain mechanism of anthropogenic radiative forcing of Earth's climate, and aerosol-induced cloud water changes are particularly poorly constrained in climate models. By combining satellite retrievals of volcano and ship tracks in stratocumulus clouds, we compile a unique observational dataset and confirm that liquid water path (LWP) responses to aerosols are bidirectional, and on average the increases in LWP are closely compensated by the decreases. Moreover, the meteorological parameters controlling the LWP responses are strikingly similar between the volcano and ship tracks. In stark contrast to observations, there are substantial unidirectional increases in LWP in the Hadley Centre climate model, because the model accounts only for the decreased precipitation efficiency and not for the enhanced entrainment drying. If the LWP increases in the model were compensated by the decreases as the observations suggest, its indirect aerosol radiative forcing in stratocumulus regions would decrease by 45%.

  4. Metabolic modeling of energy balances in Mycoplasma hyopneumoniae shows that pyruvate addition increases growth rate.

    Science.gov (United States)

    Kamminga, Tjerko; Slagman, Simen-Jan; Bijlsma, Jetta J E; Martins Dos Santos, Vitor A P; Suarez-Diez, Maria; Schaap, Peter J

    2017-10-01

    Mycoplasma hyopneumoniae is cultured on large-scale to produce antigen for inactivated whole-cell vaccines against respiratory disease in pigs. However, the fastidious nutrient requirements of this minimal bacterium and the low growth rate make it challenging to reach sufficient biomass yield for antigen production. In this study, we sequenced the genome of M. hyopneumoniae strain 11 and constructed a high quality constraint-based genome-scale metabolic model of 284 chemical reactions and 298 metabolites. We validated the model with time-series data of duplicate fermentation cultures to aim for an integrated model describing the dynamic profiles measured in fermentations. The model predicted that 84% of cellular energy in a standard M. hyopneumoniae cultivation was used for non-growth associated maintenance and only 16% of cellular energy was used for growth and growth associated maintenance. Following a cycle of model-driven experimentation in dedicated fermentation experiments, we were able to increase the fraction of cellular energy used for growth through pyruvate addition to the medium. This increase in turn led to an increase in growth rate and a 2.3 times increase in the total biomass concentration reached after 3-4 days of fermentation, enhancing the productivity of the overall process. The model presented provides a solid basis to understand and further improve M. hyopneumoniae fermentation processes. Biotechnol. Bioeng. 2017;114: 2339-2347. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Using Performance Assessment Model in Physics Laboratory to Increase Students’ Critical Thinking Disposition

    Science.gov (United States)

    Emiliannur, E.; Hamidah, I.; Zainul, A.; Wulan, A. R.

    2017-09-01

    Performance Assessment Model (PAM) has been developed to represent the physics concepts which able to be devided into five experiments: 1) acceleration due to gravity; 2) Hooke’s law; 3) simple harmonic motion; 4) work-energy concepts; and 5) the law of momentum conservation. The aim of this study was to determine the contribution of PAM in physics laboratory to increase students’ Critical Thinking Disposition (CTD) at senior high school. Subject of the study were 11th grade consist 32 students of a senior high school in Lubuk Sikaping, West Sumatera. The research used one group pretest-postest design. Data was collected through essay test and questionnaire about CTD. Data was analyzed using quantitative way with N-gain value. This study concluded that performance assessmet model effectively increases the N-gain at medium category. It means students’ critical thinking disposition significant increase after implementation of performance assessment model in physics laboratory.

  6. Entrepreneurship education revisited: perceived entrepreneurial role models increase perceived behavioural control

    Science.gov (United States)

    Fellnhofer, Katharina

    2017-01-01

    Relying on Bandura’s (1986) social learning theory, Ajzen’s (1988) theory of planned behaviour (TPB), and Dyer’s (1994) model of entrepreneurial careers, this study aims to highlight the potential of entrepreneurial role models to entrepreneurship education. The results suggest that entrepreneurial courses would greatly benefit from real-life experiences, either positive or negative. The results of regression analysis based on 426 individuals, primarily from Austria, Finland, and Greece, show that role models increase learners’ entrepreneurial perceived behaviour control (PBC) by increasing their self-efficacy. This study can inform the research and business communities and governments about the importance of integrating entrepreneurs into education to stimulate entrepreneurial PBC. This study is the first of its kind using its approach, and its results warrant more in-depth studies of storytelling by entrepreneurial role models in the context of multimedia entrepreneurship education. PMID:29104604

  7. Entrepreneurship education revisited: perceived entrepreneurial role models increase perceived behavioural control.

    Science.gov (United States)

    Fellnhofer, Katharina

    2017-01-01

    Relying on Bandura's (1986) social learning theory, Ajzen's (1988) theory of planned behaviour (TPB), and Dyer's (1994) model of entrepreneurial careers, this study aims to highlight the potential of entrepreneurial role models to entrepreneurship education. The results suggest that entrepreneurial courses would greatly benefit from real-life experiences, either positive or negative. The results of regression analysis based on 426 individuals, primarily from Austria, Finland, and Greece, show that role models increase learners' entrepreneurial perceived behaviour control (PBC) by increasing their self-efficacy. This study can inform the research and business communities and governments about the importance of integrating entrepreneurs into education to stimulate entrepreneurial PBC. This study is the first of its kind using its approach, and its results warrant more in-depth studies of storytelling by entrepreneurial role models in the context of multimedia entrepreneurship education.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    to stressors, but, so far, not in models of depression. Here we report that the number of BrdU positive cells in hippocampus was (1) significantly higher in a rat model of depression, the Flinders Sensitive Line (FSL) compared to control FRL, (2) increased in both FSL and FRL following maternal separation, (3......) reduced by escitalopram treatment in maternally separated animals to the level found in non-separated animals. These results argue against the prevailing hypothesis that adult cytogenesis is reduced in depression and that the common mechanism underlying antidepressant treatments is to increase adult...

  9. Genome-enabled Modeling of Microbial Biogeochemistry using a Trait-based Approach. Does Increasing Metabolic Complexity Increase Predictive Capabilities?

    Science.gov (United States)

    King, E.; Karaoz, U.; Molins, S.; Bouskill, N.; Anantharaman, K.; Beller, H. R.; Banfield, J. F.; Steefel, C. I.; Brodie, E.

    2015-12-01

    The biogeochemical functioning of ecosystems is shaped in part by genomic information stored in the subsurface microbiome. Cultivation-independent approaches allow us to extract this information through reconstruction of thousands of genomes from a microbial community. Analysis of these genomes, in turn, gives an indication of the organisms present and their functional roles. However, metagenomic analyses can currently deliver thousands of different genomes that range in abundance/importance, requiring the identification and assimilation of key physiologies and metabolisms to be represented as traits for successful simulation of subsurface processes. Here we focus on incorporating -omics information into BioCrunch, a genome-informed trait-based model that represents the diversity of microbial functional processes within a reactive transport framework. This approach models the rate of nutrient uptake and the thermodynamics of coupled electron donors and acceptors for a range of microbial metabolisms including heterotrophs and chemolithotrophs. Metabolism of exogenous substrates fuels catabolic and anabolic processes, with the proportion of energy used for cellular maintenance, respiration, biomass development, and enzyme production based upon dynamic intracellular and environmental conditions. This internal resource partitioning represents a trade-off against biomass formation and results in microbial community emergence across a fitness landscape. Biocrunch was used here in simulations that included organisms and metabolic pathways derived from a dataset of ~1200 non-redundant genomes reflecting a microbial community in a floodplain aquifer. Metagenomic data was directly used to parameterize trait values related to growth and to identify trait linkages associated with respiration, fermentation, and key enzymatic functions such as plant polymer degradation. Simulations spanned a range of metabolic complexities and highlight benefits originating from simulations

  10. Modelling the consequences of increasing bioenergy demand on land and feed use

    NARCIS (Netherlands)

    Banse, M.A.H.; Tabeau, A.A.; Meijl, van H.; Woltjer, G.B.

    2010-01-01

    The aim of this paper is to show the consequences of a model extension towards the presentation of by-product in the production of biofuels. By-products can be used as a substitute for feed grain use in livestock production. A boost in biofuel production will also show a strong increase in the

  11. Assessing options to increase water productivity in irrigated river basins using remote sensing and modelling tools

    NARCIS (Netherlands)

    Dam, van J.C.; Singh, R.; Bessembinder, J.J.E.; Leffelaar, P.A.; Bastiaanssen, W.G.M.; Jhorar, R.K.; Kroes, J.G.; Droogers, P.

    2006-01-01

    In regions where water is more scarce than land, the water productivity concept (e.g. crop yield per unit of water utilized) provides a useful framework to analyse crop production increase or water savings in irrigated agriculture. Generic crop and soil models were applied at field and regional

  12. Cough reflex sensitivity is increased in the guinea pig model of allergic rhinitis.

    Science.gov (United States)

    Brozmanova, M; Plevkova, J; Tatar, M; Kollarik, M

    2008-12-01

    Increased cough reflex sensitivity is found in patients with allergic rhinitis and may contribute to cough caused by rhinitis. We have reported that cough to citric acid is enhanced in the guinea pig model of allergic rhinitis. Here we address the hypothesis that the cough reflex sensitivity is increased in this model. The data from our previous studies were analyzed for the cough reflex sensitivity. The allergic inflammation in the nose was induced by repeated intranasal instillations of ovalbumin in the ovalbumin-sensitized guinea pigs. Cough was induced by inhalation of doubling concentrations of citric acid (0.05-1.6 M). Cough threshold was defined as the lowest concentration of citric acid causing two coughs (C2, expressed as geometric mean [95% confidence interval]). We found that the cough threshold was reduced in animals with allergic rhinitis. C2 was 0.5 M [0.36-0.71 M] and 0.15 M [0.1-0.23 M] prior and after repeated intranasal instillations of ovalbumin, respectively, Preflex sensitivity. C2 was reduced in animals with allergic rhinitis treated orally with vehicle (0.57 M [0.28-1.1] vs. 0.09 M [0.04-0.2 M], Preflex sensitivity is increased in the guinea pig model of allergic rhinitis. Our results suggest that guinea pig is a suitable model for mechanistic studies of increased cough reflex sensitivity in rhinitis.

  13. A System Model of Increasing the Investment Potential of Technologically Unrelated Sectors

    Directory of Open Access Journals (Sweden)

    Melnyk Alexander G.

    2016-02-01

    Full Text Available The article presents a theoretical substantiation and the progress of practical application of the method for evaluating lagged effects of increasing the investment potential of interaction between industries in meso-level innovation systems on the example of the high-tech sector of Ukraine. The interaction data are considered in terms of their formation in such technologically unrelated sectors as the industrial sector and sector of education and sciences. It has been determined that the analytical basis to form the models of increasing the investment potential in innovation systems of meso-level should be presented by a comprehensive integrated assessment of all sectors involved in the reproduction process including technologically unrelated sectors of highly structured innovative systems. There has been proposed a system model of increasing the investment potential of the high-tech sector taking into account the optimization and synergy effects for system decisions concerning technologically unrelated sectors in economic systems of innovation type of reproduction.

  14. Constraints on High Northern Photosynthesis Increase Using Earth System Models and a Set of Independent Observations

    Science.gov (United States)

    Winkler, A. J.; Brovkin, V.; Myneni, R.; Alexandrov, G.

    2017-12-01

    Plant growth in the northern high latitudes benefits from increasing temperature (radiative effect) and CO2 fertilization as a consequence of rising atmospheric CO2 concentration. This enhanced gross primary production (GPP) is evident in large scale increase in summer time greening over the 36-year record of satellite observations. In this time period also various global ecosystem models simulate a greening trend in terms of increasing leaf area index (LAI). We also found a persistent greening trend analyzing historical simulations of Earth system models (ESM) participating in Phase 5 of the Coupled Model Intercomparison Project (CMIP5). However, these models span a large range in strength of the LAI trend, expressed as sensitivity to both key environmental factors, temperature and CO2 concentration. There is also a wide spread in magnitude of the associated increase of terrestrial GPP among the ESMs, which contributes to pronounced uncertainties in projections of future climate change. Here we demonstrate that there is a linear relationship across the CMIP5 model ensemble between projected GPP changes and historical LAI sensitivity, which allows using the observed LAI sensitivity as an "emerging constraint" on GPP estimation at future CO2 concentration. This constrained estimate of future GPP is substantially higher than the traditional multi-model mean suggesting that the majority of current ESMs may be significantly underestimating carbon fixation by vegetation in NHL. We provide three independent lines of evidence in analyzing observed and simulated CO2 amplitude as well as atmospheric CO2 inversion products to arrive at the same conclusion.

  15. Modeling Caspian Sea water level oscillations under different scenarios of increasing atmospheric carbon dioxide concentrations

    Directory of Open Access Journals (Sweden)

    Roshan GholamReza

    2012-12-01

    Full Text Available Abstract The rapid rise of Caspian Sea water level (about 2.25 meters since 1978 has caused much concern to all five surrounding countries, primarily because flooding has destroyed or damaged buildings and other engineering structures, roads, beaches and farm lands in the coastal zone. Given that climate, and more specifically climate change, is a primary factor influencing oscillations in Caspian Sea water levels, the effect of different climate change scenarios on future Caspian Sea levels was simulated. Variations in environmental parameters such as temperature, precipitation, evaporation, atmospheric carbon dioxide and water level oscillations of the Caspian sea and surrounding regions, are considered for both past (1951-2006 and future (2025-2100 time frames. The output of the UKHADGEM general circulation model and five alternative scenarios including A1CAI, BIASF, BIMES WRE450 and WRE750 were extracted using the MAGICC SCENGEN Model software (version 5.3. The results suggest that the mean temperature of the Caspian Sea region (Bandar-E-Anzali monitoring site has increased by ca. 0.17°C per decade under the impacts of atmospheric carbon dioxide changes (r=0.21. The Caspian Sea water level has increased by ca. +36cm per decade (r=0.82 between the years 1951-2006. Mean results from all modeled scenarios indicate that the temperature will increase by ca. 3.64°C and precipitation will decrease by ca. 10% (182 mm over the Caspian Sea, whilst in the Volga river basin, temperatures are projected to increase by ca. 4.78°C and precipitation increase by ca. 12% (58 mm by the year 2100. Finally, statistical modeling of the Caspian Sea water levels project future water level increases of between 86 cm and 163 cm by the years 2075 and 2100, respectively.

  16. Modeling Caspian Sea water level oscillations under different scenarios of increasing atmospheric carbon dioxide concentrations.

    Science.gov (United States)

    Roshan, Gholamreza; Moghbel, Masumeh; Grab, Stefan

    2012-12-12

    The rapid rise of Caspian Sea water level (about 2.25 meters since 1978) has caused much concern to all five surrounding countries, primarily because flooding has destroyed or damaged buildings and other engineering structures, roads, beaches and farm lands in the coastal zone. Given that climate, and more specifically climate change, is a primary factor influencing oscillations in Caspian Sea water levels, the effect of different climate change scenarios on future Caspian Sea levels was simulated. Variations in environmental parameters such as temperature, precipitation, evaporation, atmospheric carbon dioxide and water level oscillations of the Caspian sea and surrounding regions, are considered for both past (1951-2006) and future (2025-2100) time frames. The output of the UKHADGEM general circulation model and five alternative scenarios including A1CAI, BIASF, BIMES WRE450 and WRE750 were extracted using the MAGICC SCENGEN Model software (version 5.3). The results suggest that the mean temperature of the Caspian Sea region (Bandar-E-Anzali monitoring site) has increased by ca. 0.17°C per decade under the impacts of atmospheric carbon dioxide changes (r=0.21). The Caspian Sea water level has increased by ca. +36cm per decade (r=0.82) between the years 1951-2006. Mean results from all modeled scenarios indicate that the temperature will increase by ca. 3.64°C and precipitation will decrease by ca. 10% (182 mm) over the Caspian Sea, whilst in the Volga river basin, temperatures are projected to increase by ca. 4.78°C and precipitation increase by ca. 12% (58 mm) by the year 2100. Finally, statistical modeling of the Caspian Sea water levels project future water level increases of between 86 cm and 163 cm by the years 2075 and 2100, respectively.

  17. A Minimalistic Resource Allocation Model to Explain Ubiquitous Increase in Protein Expression with Growth Rate.

    Directory of Open Access Journals (Sweden)

    Uri Barenholz

    Full Text Available Most proteins show changes in level across growth conditions. Many of these changes seem to be coordinated with the specific growth rate rather than the growth environment or the protein function. Although cellular growth rates, gene expression levels and gene regulation have been at the center of biological research for decades, there are only a few models giving a base line prediction of the dependence of the proteome fraction occupied by a gene with the specific growth rate. We present a simple model that predicts a widely coordinated increase in the fraction of many proteins out of the proteome, proportionally with the growth rate. The model reveals how passive redistribution of resources, due to active regulation of only a few proteins, can have proteome wide effects that are quantitatively predictable. Our model provides a potential explanation for why and how such a coordinated response of a large fraction of the proteome to the specific growth rate arises under different environmental conditions. The simplicity of our model can also be useful by serving as a baseline null hypothesis in the search for active regulation. We exemplify the usage of the model by analyzing the relationship between growth rate and proteome composition for the model microorganism E.coli as reflected in recent proteomics data sets spanning various growth conditions. We find that the fraction out of the proteome of a large number of proteins, and from different cellular processes, increases proportionally with the growth rate. Notably, ribosomal proteins, which have been previously reported to increase in fraction with growth rate, are only a small part of this group of proteins. We suggest that, although the fractions of many proteins change with the growth rate, such changes may be partially driven by a global effect, not necessarily requiring specific cellular control mechanisms.

  18. Integrating linear optimization with structural modeling to increase HIV neutralization breadth.

    Directory of Open Access Journals (Sweden)

    Alexander M Sevy

    2018-02-01

    Full Text Available Computational protein design has been successful in modeling fixed backbone proteins in a single conformation. However, when modeling large ensembles of flexible proteins, current methods in protein design have been insufficient. Large barriers in the energy landscape are difficult to traverse while redesigning a protein sequence, and as a result current design methods only sample a fraction of available sequence space. We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods. We demonstrate the effectiveness of this method, which we call BROAD, by benchmarking the performance on increasing predicted breadth of anti-HIV antibodies. We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel. In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly. We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies. Finally, our approach is general and can be extended easily to other protein systems. Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.

  19. Integrating linear optimization with structural modeling to increase HIV neutralization breadth.

    Science.gov (United States)

    Sevy, Alexander M; Panda, Swetasudha; Crowe, James E; Meiler, Jens; Vorobeychik, Yevgeniy

    2018-02-01

    Computational protein design has been successful in modeling fixed backbone proteins in a single conformation. However, when modeling large ensembles of flexible proteins, current methods in protein design have been insufficient. Large barriers in the energy landscape are difficult to traverse while redesigning a protein sequence, and as a result current design methods only sample a fraction of available sequence space. We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods. We demonstrate the effectiveness of this method, which we call BROAD, by benchmarking the performance on increasing predicted breadth of anti-HIV antibodies. We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel. In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly. We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies. Finally, our approach is general and can be extended easily to other protein systems. Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.

  20. Convection links biomass burning to increased tropical ozone: However, models will tend to overpredict O3

    Science.gov (United States)

    Chatfield, Robert B.; Delany, Anthony C.

    1990-10-01

    Biomass burning throughout the inhabited portions of the tropics generates precursors which lead to significant local atmospheric ozone pollution. Several simulations show how this smog could be only an easily observed, local manifestation of a much broader increase in tropospheric ozone. We illustrate basic processes with a one-dimensional time-dependent model that is closer to true meteorological motions than commonly used eddy diffusion models. Its application to a representative region of South America gives reasonable simulations of the local pollutants measured there. Three illustrative simulations indicate the importance of dilution, principally due to vertical transport, in increasing the efficiency of ozone production, possibly enough for high ozone to be apparent on a very large, intercontinental scale. In the first, cook-then-mix, simulation the nitrogen oxides and other burning-produced pollutants are confined to a persistently subsident fair weather boundary layer for several days, and the resultant ozone is found to have only a transient influence on the whole column of tropospheric ozone. In the second, mix-then-cook, simulation the effect of typical cumulonimbus convection, which vents an actively polluted boundary layer, is to make a persistent increase in the tropical ozone column. Such a broadly increased ozone column is observed over the the populated "continental" portion of the tropics. A third simulation averages all emission, transport, and deposition parameters, representing one column in a global tropospheric model that does not simulate individual weather events. This "oversmoothing" simulation produces 60% more ozone than observed or otherwise modeled. Qualitatively similar overprediction is suggested for all models which average significantly in time or space, as all need do. Clearly, simulating these O3 levels will depend sensitively on knowledge of the timing of emissions and transport.

  1. Resource competition model predicts zonation and increasing nutrient use efficiency along a wetland salinity gradient

    Science.gov (United States)

    Schoolmaster, Donald; Stagg, Camille L.

    2018-01-01

    A trade-off between competitive ability and stress tolerance has been hypothesized and empirically supported to explain the zonation of species across stress gradients for a number of systems. Since stress often reduces plant productivity, one might expect a pattern of decreasing productivity across the zones of the stress gradient. However, this pattern is often not observed in coastal wetlands that show patterns of zonation along a salinity gradient. To address the potentially complex relationship between stress, zonation, and productivity in coastal wetlands, we developed a model of plant biomass as a function of resource competition and salinity stress. Analysis of the model confirms the conventional wisdom that a trade-off between competitive ability and stress tolerance is a necessary condition for zonation. It also suggests that a negative relationship between salinity and production can be overcome if (1) the supply of the limiting resource increases with greater salinity stress or (2) nutrient use efficiency increases with increasing salinity. We fit the equilibrium solution of the dynamic model to data from Louisiana coastal wetlands to test its ability to explain patterns of production across the landscape gradient and derive predictions that could be tested with independent data. We found support for a number of the model predictions, including patterns of decreasing competitive ability and increasing nutrient use efficiency across a gradient from freshwater to saline wetlands. In addition to providing a quantitative framework to support the mechanistic hypotheses of zonation, these results suggest that this simple model is a useful platform to further build upon, simulate and test mechanistic hypotheses of more complex patterns and phenomena in coastal wetlands.

  2. Mesenchymal stem cells enhance autophagy and increase β-amyloid clearance in Alzheimer disease models

    Science.gov (United States)

    Shin, Jin Young; Park, Hyun Jung; Kim, Ha Na; Oh, Se Hee; Bae, Jae-Sung; Ha, Hee-Jin; Lee, Phil Hyu

    2014-01-01

    Current evidence suggests a central role for autophagy in Alzheimer disease (AD), and dysfunction in the autophagic system may lead to amyloid-β (Aβ) accumulation. Using in vitro and in vivo AD models, the present study investigated whether mesenchymal stem cells (MSCs) could enhance autophagy and thus exert a neuroprotective effect through modulation of Aβ clearance In Aβ-treated neuronal cells, MSCs increased cellular viability and enhanced LC3-II expression compared with cells treated with Aβ only. Immunofluorescence revealed that MSC coculture in Aβ-treated neuronal cells increased the number of LC3-II-positive autophagosomes that were colocalized with a lysosomal marker. Ultrastructural analysis revealed that most autophagic vacuoles (AVs) in Aβ-treated cells were not fused with lysosomes, whereas a large portion of autophagosomes were conjoined with lysosomes in MSCs cocultured with Aβ-treated neuronal cells. Furthermore, MSC coculture markedly increased Aβ immunoreactivity colocalized within lysosomes and decreased intracellular Aβ levels compared with Aβ-treated cells. In Aβ-treated animals, MSC administration significantly increased autophagosome induction, final maturation of late AVs, and fusion with lysosomes. Moreover, MSC administration significantly reduced the level of Aβ in the hippocampus, which was elevated in Aβ-treated mice, concomitant with increased survival of hippocampal neurons. Finally, MSC coculture upregulated BECN1/Beclin 1 expression in AD models. These results suggest that MSCs significantly enhance autolysosome formation and clearance of Aβ in AD models, which may lead to increased neuronal survival against Aβ toxicity. Modulation of the autophagy pathway to repair the damaged AD brain using MSCs would have a significant impact on future strategies for AD treatment. PMID:24149893

  3. A modeling study of effective radiative forcing and climate response due to increased methane concentration

    Directory of Open Access Journals (Sweden)

    Bing Xie

    2016-12-01

    Full Text Available An atmospheric general circulation model BCC_AGCM2.0 and observation data from ARIS were used to calculate the effective radiative forcing (ERF due to increased methane concentration since pre-industrial times and its impacts on climate. The ERF of methane from 1750 to 2011 was 0.46 W m−2 by taking it as a well-mixed greenhouse gas, and the inhomogeneity of methane increased its ERF by about 0.02 W m−2. The change of methane concentration since pre-industrial led to an increase of 0.31 °C in global mean surface air temperature and 0.02 mm d−1 in global mean precipitation. The warming was prominent over the middle and high latitudes of the Northern Hemisphere (with a maximum increase exceeding 1.4 °C. The precipitation notably increased (maximum increase of 1.8 mm d−1 over the ocean between 10°N and 20°N and significantly decreased (maximum decrease >–0.6 mm d−1 between 10°S and 10°N. These changes caused a northward movement of precipitation cell in the Intertropical Convergence Zone (ITCZ. Cloud cover significantly increased (by approximately 4% in the high latitudes in both hemispheres, and sharply decreased (by approximately 3% in tropical areas.

  4. Increasing the Intelligence of Virtual Sales Assistants through Knowledge Modeling Techniques

    OpenAIRE

    Molina, Martin

    2001-01-01

    Shopping agents are web-based applications that help consumers to find appropriate products in the context of e-commerce. In this paper we argue about the utility of advanced model-based techniques that recently have been proposed in the fields of Artificial Intelligence and Knowledge Engineering, in order to increase the level of support provided by this type of applications. We illustrate this approach with a virtual sales assistant that dynamically configures a product according to the nee...

  5. Assessing the value of increased model resolution in forecasting fire danger

    Science.gov (United States)

    Jeanne Hoadley; Miriam Rorig; Ken Westrick; Larry Bradshaw; Sue Ferguson; Scott Goodrick; Paul Werth

    2003-01-01

    The fire season of 2000 was used as a case study to assess the value of increasing mesoscale model resolution for fire weather and fire danger forecasting. With a domain centered on Western Montana and Northern Idaho, MM5 simulations were run at 36, 12, and 4-km resolutions for a 30 day period at the height of the fire season. Verification analyses for meteorological...

  6. Does a video displaying a stair climbing model increase stair use in a worksite setting?

    Science.gov (United States)

    Van Calster, L; Van Hoecke, A-S; Octaef, A; Boen, F

    2017-08-01

    This study evaluated the effects of improving the visibility of the stairwell and of displaying a video with a stair climbing model on climbing and descending stair use in a worksite setting. Intervention study. Three consecutive one-week intervention phases were implemented: (1) the visibility of the stairs was improved by the attachment of pictograms that indicated the stairwell; (2) a video showing a stair climbing model was sent to the employees by email; and (3) the same video was displayed on a television screen at the point-of-choice (POC) between the stairs and the elevator. The interventions took place in two buildings. The implementation of the interventions varied between these buildings and the sequence was reversed. Improving the visibility of the stairs increased both stair climbing (+6%) and descending stair use (+7%) compared with baseline. Sending the video by email yielded no additional effect on stair use. By contrast, displaying the video at the POC increased stair climbing in both buildings by 12.5% on average. One week after the intervention, the positive effects on stair climbing remained in one of the buildings, but not in the other. These findings suggest that improving the visibility of the stairwell and displaying a stair climbing model on a screen at the POC can result in a short-term increase in both climbing and descending stair use. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  7. The synthetic parasite-derived peptide GK1 increases survival in a preclinical mouse melanoma model.

    Science.gov (United States)

    Pérez-Torres, Armando; Vera-Aguilera, Jesús; Hernaiz-Leonardo, Juan Carlos; Moreno-Aguilera, Eduardo; Monteverde-Suarez, Diego; Vera-Aguilera, Carlos; Estrada-Bárcenas, Daniel

    2013-11-01

    The therapeutic efficacy of a synthetic parasite-derived peptide GK1, an immune response booster, was evaluated in a mouse melanoma model. This melanoma model correlates with human stage IIb melanoma, which is treated with wide surgical excision; a parallel study employing a surgical treatment was carried out as an instructive goal. C57BL/6 mice were injected subcutaneously in the flank with 2×10(5) B16-F10 murine melanoma cells. When the tumors reached 20 mm3, mice were separated into two different groups; the GK1 group, treated weekly with peritumoral injections of GK1 (10 μg/100 μL of sterile saline solution) and the control group, treated weekly with an antiseptic peritumoral injection of 100 μL of sterile saline solution without further intervention. All mice were monitored daily for clinical appearance, tumor size, and survival. Surgical treatment was performed in parallel when the tumor size was 20 mm3 (group A), 500 mm3 (group B), and >500 mm3 (group C). The GK1 peptide effectively increased the mean survival time by 9.05 days, corresponding to an increase of 42.58%, and significantly delayed tumor growth from day 3 to 12 of treatment. In addition, tumor necrosis was significantly increased (pcancers remains to be determined, and surgical removal remains a challenge for any new experimental treatment of melanoma in mouse models.

  8. A Practitioner Model for Increasing Eye Contact in Children With Autism.

    Science.gov (United States)

    Cook, Jennifer L; Rapp, John T; Mann, Kathryn R; McHugh, Catherine; Burji, Carla; Nuta, Raluca

    2017-05-01

    Although many teaching techniques for children with autism spectrum disorder (ASD) require the instructor to gain the child's eye contact prior to delivering an instructional demand, the literature contains notably few procedures that reliably produce this outcome. To address this problem, we evaluated the effects of a sequential model for increasing eye contact in children with ASD. The model included the following phases: contingent praise only (for eye contact), contingent edibles plus praise, stimulus prompts plus contingent edibles and praise, contingent video and praise, schedule thinning, and maintenance evaluations for up to 2 years. Results indicated that the procedures increased eye contact for 20 participants (one additional participant did not require consequences). For 16 participants, praise (alone) was not sufficient to support eye contact; however, high levels of eye contact were typically maintained with these participants when therapists used combined schedules of intermittent edibles or video and continuous praise. We discuss some limitations of this model and directions for future research on increasing eye contact for children with ASD.

  9. Modeling of river bed deformation composed of frozen sediments with increasing environmental temperature

    Directory of Open Access Journals (Sweden)

    E. I. Debolskaya

    2013-01-01

    Full Text Available This paper is devoted to investigation of the influence of river flow and of the temperature rise on the deformation of the coastal slopes composed of permafrost with the inclusion of ice layer. The method of investigation is the laboratory and mathematical modeling. The laboratory experiments have shown that an increase in water and air temperature changes in a laboratory analogue of permafrost causes deformation of the channel even without wave action, i.e. at steady-state flow and non-erosive water flow velocity. The previously developed model of the bed deformation was improved to account for long-term changes of soil structure with increasing temperature. The three-dimensional mathematical model of coastal slopes thermoerosion of the rivers flowing in permafrost regions, and its verification was based on the results of laboratory experiments conducted in the hydraulic tray. Analysis of the results of mathematical and laboratory modeling showed that bed deformation of the rivers flowing in the permafrost zone, significantly different from the deformation of channels composed of soils not susceptible to the influence of the phase transition «water-ice», and can occur even under the non-erosive velocity of the water flow.

  10. Intermittent hypoxia increases kidney tumor vascularization in a murine model of sleep apnea.

    Science.gov (United States)

    Vilaseca, Antoni; Campillo, Noelia; Torres, Marta; Musquera, Mireia; Gozal, David; Montserrat, Josep M; Alcaraz, Antonio; Touijer, Karim A; Farré, Ramon; Almendros, Isaac

    2017-01-01

    We investigate the effects of intermittent hypoxia (IH), a characteristic feature of obstructive sleep apnea (OSA), on renal cancer progression in an animal and cell model. An in vivo mouse model (Balb/c, n = 50) of kidney cancer was used to assess the effect of IH on tumor growth, metastatic capacity, angiogenesis and tumor immune response. An in vitro model tested the effect of IH on RENCA cells, macrophages and endothelial cells. Tumor growth, metastatic capacity, circulating vascular endothelial growth factor (VEGF) and content of endothelial cells, tumor associated macrophages and their phenotype were assessed in the tumor. In vitro, VEGF cell expression was quantified.Although IH did not boost tumor growth, it significantly increased endothelial cells (p = 0.001) and circulating VEGF (p<0.001) in the in vivo model. Macrophages exposed to IH in vitro increased VEGF expression, whereas RENCA cells and endothelial cells did not. These findings are in keeping with previous clinical data suggesting that OSA has no effect on kidney cancer size and that the association observed between OSA and higher Fuhrman grade of renal cell carcinoma may be mediated though a proangiogenic process, with a key role of macrophages.

  11. Intermittent hypoxia increases kidney tumor vascularization in a murine model of sleep apnea.

    Directory of Open Access Journals (Sweden)

    Antoni Vilaseca

    Full Text Available We investigate the effects of intermittent hypoxia (IH, a characteristic feature of obstructive sleep apnea (OSA, on renal cancer progression in an animal and cell model. An in vivo mouse model (Balb/c, n = 50 of kidney cancer was used to assess the effect of IH on tumor growth, metastatic capacity, angiogenesis and tumor immune response. An in vitro model tested the effect of IH on RENCA cells, macrophages and endothelial cells. Tumor growth, metastatic capacity, circulating vascular endothelial growth factor (VEGF and content of endothelial cells, tumor associated macrophages and their phenotype were assessed in the tumor. In vitro, VEGF cell expression was quantified.Although IH did not boost tumor growth, it significantly increased endothelial cells (p = 0.001 and circulating VEGF (p<0.001 in the in vivo model. Macrophages exposed to IH in vitro increased VEGF expression, whereas RENCA cells and endothelial cells did not. These findings are in keeping with previous clinical data suggesting that OSA has no effect on kidney cancer size and that the association observed between OSA and higher Fuhrman grade of renal cell carcinoma may be mediated though a proangiogenic process, with a key role of macrophages.

  12. Constrained parameterisation of photosynthetic capacity causes significant increase of modelled tropical vegetation surface temperature

    Science.gov (United States)

    Kattge, J.; Knorr, W.; Raddatz, T.; Wirth, C.

    2009-04-01

    Photosynthetic capacity is one of the most sensitive parameters of terrestrial biosphere models whose representation in global scale simulations has been severely hampered by a lack of systematic analyses using a sufficiently broad database. Due to its coupling to stomatal conductance changes in the parameterisation of photosynthetic capacity may potentially influence transpiration rates and vegetation surface temperature. Here, we provide a constrained parameterisation of photosynthetic capacity for different plant functional types in the context of the photosynthesis model proposed by Farquhar et al. (1980), based on a comprehensive compilation of leaf photosynthesis rates and leaf nitrogen content. Mean values of photosynthetic capacity were implemented into the coupled climate-vegetation model ECHAM5/JSBACH and modelled gross primary production (GPP) is compared to a compilation of independent observations on stand scale. Compared to the current standard parameterisation the root-mean-squared difference between modelled and observed GPP is substantially reduced for almost all PFTs by the new parameterisation of photosynthetic capacity. We find a systematic depression of NUE (photosynthetic capacity divided by leaf nitrogen content) on certain tropical soils that are known to be deficient in phosphorus. Photosynthetic capacity of tropical trees derived by this study is substantially lower than standard estimates currently used in terrestrial biosphere models. This causes a decrease of modelled GPP while it significantly increases modelled tropical vegetation surface temperatures, up to 0.8°C. These results emphasise the importance of a constrained parameterisation of photosynthetic capacity not only for the carbon cycle, but also for the climate system.

  13. Implants delivering bisphosphonate locally increase periprosthetic bone density in an osteoporotic sheep model. A pilot study

    Directory of Open Access Journals (Sweden)

    GVA Stadelmann

    2008-07-01

    Full Text Available It is a clinical challenge to obtain a sufficient orthopaedic implant fixation in weak osteoporotic bone. When the primary implant fixation is poor, micromotions occur at the bone-implant interface, activating osteoclasts, which leads to implant loosening. Bisphosphonate can be used to prevent the osteoclastic response, but when administered systemically its bioavailability is low and the time it takes for the drug to reach the periprosthetic bone may be a limiting factor. Recent data has shown that delivering bisphosphonate locally from the implant surface could be an interesting solution. Local bisphosphonate delivery increased periprosthetic bone density, which leads to a stronger implant fixation, as demonstrated in rats by the increased implant pullout force. The aim of the present study was to verify the positive effect on periprosthetic bone remodelling of local bisphosphonate delivery in an osteoporotic sheep model. Four implants coated with zoledronate and two control implants were inserted in the femoral condyle of ovariectomized sheep for 4 weeks. The bone at the implant surface was 50% higher in the zoledronate-group compared to control group. This effect was significant up to a distance of 400µm from the implant surface. The presented results are similar to what was observed in the osteoporotic rat model, which suggest that the concept of releasing zoledronate locally from the implant to increase the implant fixation is not species specific. The results of this trial study support the claim that local zoledronate could increase the fixation of an implant in weak bone.

  14. Increased placental nutrient transport in a novel mouse model of maternal obesity with fetal overgrowth.

    Science.gov (United States)

    Rosario, Fredrick J; Kanai, Yoshikatsu; Powell, Theresa L; Jansson, Thomas

    2015-08-01

    To identify possible mechanisms linking obesity in pregnancy to increased fetal adiposity and growth, a unique mouse model of maternal obesity associated with fetal overgrowth was developed, and the hypothesis that maternal obesity causes up-regulation of placental nutrient transporter expression and activity was tested. C57BL/6J female mice were fed a control (C) or a high-fat/high-sugar (HF/HS) pelleted diet supplemented by ad libitum access to sucrose (20%) solution, mated, and studied at embryonic day 18.5. HF/HS diet increased maternal fat mass by 2.2-fold (P Maternal circulating insulin, leptin, and cholesterol were increased (P maternal obesity. © 2015 The Obesity Society.

  15. Free Base Lysine Increases Survival and Reduces Metastasis in Prostate Cancer Model.

    Science.gov (United States)

    Ibrahim-Hashim, Arig; Wojtkowiak, Jonathan W; de Lourdes Coelho Ribeiro, Maria; Estrella, Veronica; Bailey, Kate M; Cornnell, Heather H; Gatenby, Robert A; Gillies, Robert J

    2011-11-19

    Malignant tumor cells typically metabolize glucose anaerobically to lactic acid even under normal oxygen tension, a phenomenon called aerobic glycolysis or the Warburg effect. This results in increased acid production and the acidification of the extracellular microenvironment in solid tumors. H + ions tend to flow along concentration gradients into peritumoral normal tissue causing extracellular matrix degradation and increased tumor cell motility thus promoting invasion and metastasis. We have shown that reducing this acidity with sodium bicarbonate buffer decreases the metastatic fitness of circulating tumor cells in prostate cancer and other cancer models. Mathematical models of the tumor-host dynamics predicted that buffers with a pka around 7 will be more effective in reducing intra- and peri-tumoral acidosis and, thus, and possibly more effective in inhibiting tumor metastasis than sodium bicarbonate which has a pKa around 6. Here we test this prediction the efficacy of free base lysine; a non-bicarbonate/non-volatile buffer with a higher pKa (~10), on prostate tumor metastases model. Oxygen consumption and acid production rate of PC3M prostate cancer cells and normal prostate cells were determined using the Seahorse Extracellular Flux (XF-96) analyzer. In vivo effect of 200 mM lysine started four days prior to inoculation on inhibition of metastasis was examined in PC3M-LUC-C6 prostate cancer model using SCID mice. Metastases were followed by bioluminescence imaging. PC3M prostate cancer cells are highly acidic in comparison to a normal prostate cell line indicating that reduction of intra- and perit-tumoral acidosis should inhibit metastases formation. In vivo administration of 200 mM free base lysine increased survival and reduced metastasis. PC3M prostate cancer cells are highly glycolytic and produce large amounts of acid when compared to normal prostate cells. Administration of non-volatile buffer decreased growth of metastases and improved survival

  16. A Simple Model for Inducing Optimal Increase of SDF-1 with Aminoglycoside Ototoxicity

    Directory of Open Access Journals (Sweden)

    Hyun Mi Ju

    2017-01-01

    Full Text Available Objectives. As a homing factor of stem cell, stromal derived factor-1 (SDF-1 is important for the regenerative research in ototoxicity. Mice models with aminoglycoside ototoxicity have been widely used to study the regeneration capacity of MSCs in repair of cochlear injury. We developed a mouse model with maximal increase in SDF-1 levels in the inner ear, according to the “one-shot” doses of kanamycin and furosemide. Methods. C57BL/6 mice had kanamycin (420, 550, and 600 mg/kg dissolved in PBS, followed by an intraperitoneal injection of furosemide (130 mg/kg. The injuries of inner ear were measured with hearing thresholds, histology, and outer hair cell counts at 0, 3, 5, 7, 10, and 14 days before the sacrifice. The levels of SDF-1 in the inner ear were tested by real-time RT-PCR and immunohistochemistry. Results. There were a significant reduction in hearing thresholds and a maximal increase of SDF-1 levels in the furosemide 130 mg/kg + kanamycin 550 mg/kg group, but severe hearing deterioration over time was observed in the furosemide 130 mg/kg + kanamycin 600 mg/kg group and four mice were dead. SDF-1 was detected mostly in the stria vascularis and organ of Corti showing the highest increase in expression. Conclusion. We observed optimal induction of the stem cell homing factor in the newly generated aminoglycoside-induced ototoxicity mouse model using a “one-shot” protocol. This study regarding high SDF-1 levels in our mouse model of ototoxicity would play a major role in the development of therapeutic agents using MSC homing.

  17. Modelling forest growth and carbon storage in response to increasing CO2 and temperature

    Science.gov (United States)

    Kirschbaum, Miko U. F.

    1999-11-01

    The response of plant growth to increasing climate change remains one of the unresolved issues in understanding the future of the terrestrial biosphere. It was investigated here by using the comprehensive forest growth model CenW 1.0.5 which integrates routines for the fluxes of carbon and water, interception of radiation and the cycling of nutrients. It was run with water and/or nutrient limitations on a background of naturally observed climate at Canberra, Australia. It was parameterised for Pinus radiata, the commercially most important plantation species in Australia. The simulations showed that under water-limited conditions, forest growth was highly sensitive to doubling CO2,with growth increases of over 50% on average and even greater increases in dry years. In contrast, when water supply was adequate, but nutrients were limiting, growth increases were smaller, with an initial increase of about 15% during the first year after CO2 was doubled. This growth increase diminished further over subsequent years so that after 20years, there was virtually no remaining effect. This diminishing response was due to developing nutrient limitations caused by extra carbon input which immobilised nutrients in the soil. When both water and nutrients were adequate, growth was increased by about 15 20% with no decrease over time. Increasing ambient temperature had a positive effect on growth under nutrient limited conditions by stimulating nitrogen mineralisation rates, but had very little effect when nutrients were non-limiting. Responses were qualitatively similar when conditions were changed gradually. In response to increasing CO2 by 2µmol mol1year1 over 50years, growth was increased by only 1% under nutrient-limited condition but by 16% under water-limited conditions. When temperature and CO2 were both changed to emulate conditions between 1950 and 2030, growth was enhanced between 5 and 15% over the 80-year period due to the effect of CO2 on photosynthesis and water

  18. Modeling Air Temperature/Water Temperature Relations Along a Small Mountain Stream Under Increasing Urban Influence

    Science.gov (United States)

    Fedders, E. R.; Anderson, W. P., Jr.; Hengst, A. M.; Gu, C.

    2017-12-01

    Boone Creek is a headwater stream of low to moderate gradient located in Boone, North Carolina, USA. Total impervious surface coverage in the 5.2 km2 catchment drained by the 1.9 km study reach increases from 13.4% in the upstream half of the reach to 24.3% in the downstream half. Other markers of urbanization, including culverting, lack of riparian shade vegetation, and bank armoring also increase downstream. Previous studies have shown the stream to be prone to temperature surges on short timescales (minutes to hours) caused by summer runoff from the urban hardscaping. This study investigates the effects of urbanization on the stream's thermal regime at daily to yearly timescales. To do this, we developed an analytical model of daily average stream temperatures based on daily average air temperatures. We utilized a two-part model comprising annual and biannual components and a daily component consisting of a 3rd-order Markov process in order to fit the thermal dynamics of our small, gaining stream. Optimizing this model at each of our study sites in each studied year (78 total site-years of data) yielded annual thermal exchange coefficients (K) for each site. These K values quantify the strength of the relationship between stream and air temperature, or inverse thermal stability. In a uniform, pristine catchment environment, K values are expected to decrease downstream as the stream gains discharge volume and, therefore, thermal inertia. Interannual average K values for our study reach, however, show an overall increase from 0.112 furthest upstream to 0.149 furthest downstream, despite a near doubling of stream discharge between these monitoring points. K values increase only slightly in the upstream, less urban, half of the reach. A line of best fit through these points on a plot of reach distance versus K value has a slope of 2E-6. But the K values of downstream, more urbanized sites increase at a rate of 2E-5 per meter of reach distance, an order of magnitude

  19. Food Stabilizing Antioxidants Increase Nutrient Bioavailability in the in Vitro Model.

    Science.gov (United States)

    Mika, Magdalena; Wikiera, Agnieszka; Antończyk, Anna; Grabacka, Maja

    2017-01-01

    We investigated whether antioxidants may enhance bioavailability of lipids and carbohydrates and therefore increase the risk of obesity development. We tested how supplementation with antioxidants (0.01% butylated hydroxytoluene [BHT], α-tocopherol, and green tea catechins) of a diet containing butter and wheat bread affects bioavailability of fats and carbohydrates. The absorption of the in vitro digested diet was estimated in the intestinal epithelia model of the Caco-2 cells cultured in Transwell chambers. In the case of the antioxidant-supplemented diets, we observed increased bioavailability of glucose, cholesterol, and lipids, as well as elevated secretion of the main chylomicron protein apoB-48 to the basal compartment. Importantly, we did not detect any rise in the concentrations of lipid peroxidation products (malondialdehyde, MDA) in the control samples prepared without antioxidants. Addition of antioxidants (in particular BHT) to the diet increases bioavailability of lipids and carbohydrates, which consequently may increase the risk of obesity development. The dose of antioxidants is a factor of fundamental importance, particularly for catechins: low doses increase absorption of lipids, whereas high doses exert the opposite effect.

  20. Increasing operating room productivity by duration categories and a newsvendor model.

    Science.gov (United States)

    Lehtonen, Juha-Matti; Torkki, Paulus; Peltokorpi, Antti; Moilanen, Teemu

    2013-01-01

    Previous studies approach surgery scheduling mainly from the mathematical modeling perspective which is often hard to apply in a practical environment. The aim of this study is to develop a practical scheduling system that considers the advantages of both surgery categorization and newsvendor model to surgery scheduling. The research was carried out in a Finnish orthopaedic specialist centre that performs only joint replacement surgery. Four surgery categorization scenarios were defined and their productivity analyzed by simulation and newsvendor model. Detailed analyses of surgery durations and the use of more accurate case categories and their combinations in scheduling improved OR productivity 11.3 percent when compared to the base case. Planning to have one OR team to work longer led to remarkable decrease in scheduling inefficiency. In surgical services, productivity and cost-efficiency can be improved by utilizing historical data in case scheduling and by increasing flexibility in personnel management. The study increases the understanding of practical scheduling methods used to improve efficiency in surgical services.

  1. Development of the living thing transportation systems worksheet on learning cycle model to increase student understanding

    Science.gov (United States)

    Rachmawati, E.; Nurohman, S.; Widowati, A.

    2018-01-01

    This study aims to know: 1) the feasibility LKPD review of aspects of the didactic requirements, construction requirements, technical requirements and compliance with the Learning Cycle. 2) Increase understanding of learners with Learning Model Learning Cycle in SMP N 1 Wates in the form LKPD. 3) The response of learners and educators SMP N 1 Wates to quality LKPD Transportation Systems Beings. This study is an R & D with the 4D model (Define, Design, Develop and Disseminate). Data were analyzed using qualitative analysis and quantitative analysis. Qualitative analysis in the form of advice description and assessment scores from all validates that was converted to a scale of 4. While the analysis of quantitative data by calculating the percentage of materializing learning and achievement using the standard gain an increased understanding and calculation of the KKM completeness evaluation value as an indicator of the achievement of students understanding. the results of this study yield LKPD IPA model learning Cycle theme Transportation Systems Beings obtain 108.5 total scores of a maximum score of 128 including the excellent category (A). LKPD IPA developed able to demonstrate an improved understanding of learners and the response of learners was very good to this quality LKPD IPA.

  2. Joint modeling of genetically correlated diseases and functional annotations increases accuracy of polygenic risk prediction.

    Directory of Open Access Journals (Sweden)

    Yiming Hu

    2017-06-01

    Full Text Available Accurate prediction of disease risk based on genetic factors is an important goal in human genetics research and precision medicine. Advanced prediction models will lead to more effective disease prevention and treatment strategies. Despite the identification of thousands of disease-associated genetic variants through genome-wide association studies (GWAS in the past decade, accuracy of genetic risk prediction remains moderate for most diseases, which is largely due to the challenges in both identifying all the functionally relevant variants and accurately estimating their effect sizes. In this work, we introduce PleioPred, a principled framework that leverages pleiotropy and functional annotations in genetic risk prediction for complex diseases. PleioPred uses GWAS summary statistics as its input, and jointly models multiple genetically correlated diseases and a variety of external information including linkage disequilibrium and diverse functional annotations to increase the accuracy of risk prediction. Through comprehensive simulations and real data analyses on Crohn's disease, celiac disease and type-II diabetes, we demonstrate that our approach can substantially increase the accuracy of polygenic risk prediction and risk population stratification, i.e. PleioPred can significantly better separate type-II diabetes patients with early and late onset ages, illustrating its potential clinical application. Furthermore, we show that the increment in prediction accuracy is significantly correlated with the genetic correlation between the predicted and jointly modeled diseases.

  3. An EPQ Model with Increasing Demand and Demand Dependent Production Rate under Trade Credit Financing

    Directory of Open Access Journals (Sweden)

    Juanjuan QIN

    2015-05-01

    Full Text Available This paper investigates an EPQ model with the increasing demand and demand dependent production rate involving the trade credit financing policy, which is seldom reported in the literatures. The model considers the manufacturer was offered by the supplier a delayed payment time. It is assumed that the demand is a linear increasing function of the time and the production rate is proportional to the demand. That is, the production rate is also a linear function of time. This study attempts to offer a best policy for the replenishment cycle and the order quantity for the manufacturer to maximum its profit per cycle. First, the inventory model is developed under the above situation. Second, some useful theoretical results have been derived to characterize the optimal solutions for the inventory system. The Algorithm is proposed to obtain the optimal solutions of the manufacturer. Finally, the numerical examples are carried out to illustrate the theorems, and the sensitivity analysis of the optimal solutions with respect to the parameters of the inventory system is performed. Some important management insights are obtained based on the analysis.

  4. Periodontal Dressing-containing Green Tea Epigallocathechin gallate Increases Fibroblasts Number in Gingival Artifical Wound Model

    Directory of Open Access Journals (Sweden)

    Ardisa U. Pradita

    2014-04-01

    Full Text Available Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 Green tea leaf (Camellia sinensis is one of herbal plants that is used for traditional medicine. Epigallocatechin gallate (EGCG in green tea is the most potential polyphenol component and has the strongest biological activity. It is known that EGCG has potential effect on wound healing. Objective: This study aimed to determine the effect of adding green tea EGCG into periodontal dressing on the number of fibroblasts after gingival artificial wound in animal model. Methods: Gingival artifical wound model was performed using 2mm punch biopsy on 24 rabbits (Oryctolagus cuniculus. The animals were divided into two groups. Periodontal dressing with EGCG and without EGCG was applied to the experimental and control group, respectively. Decapitation period was scheduled at day 3, 5, and 7 after treatment. Histological analysis to count the number of fibroblasts was performed. Results: Number of fibroblasts was significantly increased in time over the experimental group treated with EGCG periodontal dressing compared to control (p<0.05. Conclusion: EGCG periodontal dressing could increase the number of fibroblast, therefore having role in wound healing after periodontal surgery in animal model.DOI: 10.14693/jdi.v20i3.197

  5. Increasing women's aspirations and achievement in science: The effect of role models on implicit cognitions

    Science.gov (United States)

    Phelan, Julie E.

    This research investigated the role of implicit science beliefs in the gender gap in science aspirations and achievement, with the goal of testing identification with a female role model as a potential intervention strategy for increasing women's representation in science careers. At Time 1, women's implicit science stereotyping (i.e., associating men more than women with science) was linked to more negative (implicit and explicit) attitudes towards science and less identification with science. For men, stereotypes were either non-significantly or positively related to science attitudes and identification. Time 2 examined the influence of implicit and explicit science cognitions on students' science aspirations and achievement, and found that implicit stereotyping, attitudes, and identification were all unique predictors of science aspirations, but not achievement. Of more importance, Time 2 examined the influence of science role models, and found that identification with a role model of either gender reduced women's implicit science stereotyping and increased their positive attitudes toward science. Implications for decreasing the gender gap in advanced science achievement are discussed.

  6. NEURO-FUZZY MODELING APPLIED IN PROGRAM MANAGEMENT TO INCREASE LOCAL PUBLIC ADMINISTRATION PERFORMANCE

    Directory of Open Access Journals (Sweden)

    Adrian-Mihai Zaharia-Radulescu

    2016-07-01

    Full Text Available One of the challenges in local public administration is dealing with an increasing number of competing requests coming from the communities they serve. The traditional approach would be to handle each request as a standalone project and be prioritized according to benefits and budget available. More and more nowadays program management is becoming a standard approach in managing the initiatives of local public administration. Program management approach is itself an enabler for performance in public sector organizations by allowing an organization to better coordinate its efforts and resources in managing a portfolio of projects. This paper aims to present how neuro-fuzzy modeling applied in program management can help an organization to increase its performance. Neuro-fuzzy modeling would lead organizations one step further by allowing them to simulate different scenarios and manage better the risks accompanying their initiatives. The research done by the authors is theoretical and combines knowledge from different areas and a neuro-fuzzy model is proposed and discussed.

  7. Modelling the implications of regular increases in tobacco taxation in the tobacco endgame.

    Science.gov (United States)

    Cobiac, Linda J; Ikeda, Tak; Nghiem, Nhung; Blakely, Tony; Wilson, Nick

    2015-06-01

    We examine the potential role for taxation in the tobacco endgame in New Zealand, where the goal is to become 'smokefree' (less than 5% smoking prevalence) by 2025. Modelling study using a dynamic population model. New Zealand, Māori and non-Māori men and women. Annual increases in tobacco excise tax of 5%, 10%, 15% and 20% (with 10% reflecting the annual increase recently legislated by the New Zealand Government to 2016). With a continued commitment to annual 10% increases in tobacco excise tax, in addition to on-going Quitline and cessation support, New Zealand's smoking prevalence is projected to fall from 15.1% in 2013 to 8.7% (95% uncertainty interval 8.6% to 8.9%) by 2025. This is compared to 9.9% without any further tax rises. With annual tax increases of 20%, the prevalence is projected to fall to 7.6% (7.5% to 7.7%) by 2025. The potential reductions in smoking prevalence are substantial for both Māori and non-Māori populations, although annual tax increases as high as 20% will still only see Māori smoking prevalence in 2025 approaching the non-Māori smoking levels for 2013. Scenario analyses did not suggest that growth of the illicit tobacco market would substantively undermine the impact of tobacco tax rises. Nevertheless, unknown factors such as the gradual denormalisation of smoking and changes to the 'nicotine market' may influence sensitivity to changes in tobacco prices in the future. Regular increases in tobacco taxation could play an important role in helping to achieve tobacco endgames. However, this modelling in New Zealand suggests that a wider range of tobacco endgame strategies will be needed to achieve a smoke-free goal of less than 5% prevalence for all social groups--a conclusion that could also apply in other countries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  8. Aerosol-induced thermal effects increase modelled terrestrial photosynthesis and transpiration

    International Nuclear Information System (INIS)

    Steiner, Allison L.; Chameides, W.L.

    2005-01-01

    Previous studies suggest that the radiative effects of atmospheric aerosols (reducing total radiation while increasing the diffuse fraction) can enhance terrestrial productivity. Here, simulations using a regional climate/terrestrial biosphere model suggest that atmospheric aerosols could also enhance terrestrial photosynthesis and transpiration through an interaction between solar radiation, leaf temperature and stomatal conductance. During midday, clear-sky conditions, sunlit-leaf temperatures can exceed the optimum for photosynthesis, depressing both photosynthesis and transpiration. Aerosols decrease surface solar radiation, thereby reducing leaf temperatures and enhancing sunlit-leaf photosynthesis and transpiration. This modelling study finds that, under certain conditions, this thermal response of aerosols can have a greater impact on photosynthesis and transpiration than the radiative response. This implies that a full understanding of the impact of aerosols on climate and the global carbon cycle requires consideration of the biophysical responses of terrestrial vegetation as well as atmospheric radiative and thermodynamic effects

  9. Sodium caseinate induces increased survival in leukaemic mouse J774 model.

    Science.gov (United States)

    Córdova-Galaviz, Yolanda; Ledesma-Martínez, Edgar; Aguíñiga-Sánchez, Itzen; Soldevila-Melgarejo, Gloria; Soto-Cruz, Isabel; Weiss-Steider, Benny; Santiago-Osorio, Edelmiro

    2014-01-01

    Acute myeloid leukaemia is a neoplastic disease of haematopoietic stem cells. Although there have been recent advances regarding its treatment, mortality remains high. Consequently, therapeutic alternatives continue to be explored. In the present report, we present evidence that sodium caseinate (CasNa), a salt of the principal protein in milk, may possess important anti-leukaemic properties. J774 leukaemia macrophage-like cells were cultured with CasNa and proliferation, viability and differentiation were evaluated. These cells were also inoculated into BALB/c mice as a model of leukemia. We demonstrated that CasNa inhibits the in vitro proliferation and reduces viability of J774 cells, and leads to increased survival in vivo in a leukaemic mouse model. These data indicate that CasNa may be useful in leukaemia therapy. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  10. Modelling consumer demand and household labour supply: Welfare effects of increasing carbon taxes

    International Nuclear Information System (INIS)

    Braennlund, R.; Nordstroem, J.

    2001-01-01

    The main objective of this paper is to analyse consumer response and welfare effects due to changes in energy or environmental policy. To achieve this objective we formulate and estimate an econometric model for non-durable consumer demand in Sweden that utilises micro- and macro-data. In the demand model male and female labour supply is included as conditioning goods. To account for possible changes in labour supply due to increasing carbon taxes we estimate separate labour supply functions for men and women. In the simulations we consider two revenue neutral scenarios that both imply a doubling of the CO 2 tax; one that returns the revenues in the form of a lower VAT and one that subsidise public transport. One conclusion from the simulations is that the CO 2 tax has regional distribution effects, in the sense that household living in sparsely populated areas carry a larger share of the tax burden

  11. A dual-motive model of scapegoating: displacing blame to reduce guilt or increase control.

    Science.gov (United States)

    Rothschild, Zachary K; Landau, Mark J; Sullivan, Daniel; Keefer, Lucas A

    2012-06-01

    The authors present a model that specifies 2 psychological motives underlying scapegoating, defined as attributing inordinate blame for a negative outcome to a target individual or group, (a) maintaining perceived personal moral value by minimizing feelings of guilt over one's responsibility for a negative outcome and (b) maintaining perceived personal control by obtaining a clear explanation for a negative outcome that otherwise seems inexplicable. Three studies supported hypotheses derived from this dual-motive model. Framing a negative outcome (environmental destruction or climate change) as caused by one's own harmful actions (value threat) or unknown sources (control threat) both increased scapegoating, and these effects occurred indirectly through feelings of guilt and perceived personal control, respectively (Study 1), and were differentially moderated by affirmations of moral value and personal control (Study 2). Also, scapegoating in response to value threat versus control threat produced divergent, theoretically specified effects on self-perceptions and behavioral intentions (Study 3). 2012 APA, all rights reserved

  12. Landform classification using a sub-pixel spatial attraction model to increase spatial resolution of digital elevation model (DEM

    Directory of Open Access Journals (Sweden)

    Marzieh Mokarrama

    2018-04-01

    Full Text Available The purpose of the present study is preparing a landform classification by using digital elevation model (DEM which has a high spatial resolution. To reach the mentioned aim, a sub-pixel spatial attraction model was used as a novel method for preparing DEM with a high spatial resolution in the north of Darab, Fars province, Iran. The sub-pixel attraction models convert the pixel into sub-pixels based on the neighboring pixels fraction values, which can only be attracted by a central pixel. Based on this approach, a mere maximum of eight neighboring pixels can be selected for calculating of the attraction value. In the mentioned model, other pixels are supposed to be far from the central pixel to receive any attraction. In the present study by using a sub-pixel attraction model, the spatial resolution of a DEM was increased. The design of the algorithm is accomplished by using a DEM with a spatial resolution of 30 m (the Advanced Space borne Thermal Emission and Reflection Radiometer; (ASTER and a 90 m (the Shuttle Radar Topography Mission; (SRTM. In the attraction model, scale factors of (S = 2, S = 3, and S = 4 with two neighboring methods of touching (T = 1 and quadrant (T = 2 are applied to the DEMs by using MATLAB software. The algorithm is evaluated by taking the best advantages of 487 sample points, which are measured by surveyors. The spatial attraction model with scale factor of (S = 2 gives better results compared to those scale factors which are greater than 2. Besides, the touching neighborhood method is turned to be more accurate than the quadrant method. In fact, dividing each pixel into more than two sub-pixels decreases the accuracy of the resulted DEM. On the other hand, in these cases DEM, is itself in charge of increasing the value of root-mean-square error (RMSE and shows that attraction models could not be used for S which is greater than 2. Thus considering results, the proposed model is highly capable of

  13. Increasing the Use of Earth Science Data and Models in Air Quality Management.

    Science.gov (United States)

    Milford, Jana B; Knight, Daniel

    2017-04-01

    In 2010, the U.S. National Aeronautics and Space Administration (NASA) initiated the Air Quality Applied Science Team (AQAST) as a 5-year, $17.5-million award with 19 principal investigators. AQAST aims to increase the use of Earth science products in air quality-related research and to help meet air quality managers' information needs. We conducted a Web-based survey and a limited number of follow-up interviews to investigate federal, state, tribal, and local air quality managers' perspectives on usefulness of Earth science data and models, and on the impact AQAST has had. The air quality managers we surveyed identified meeting the National Ambient Air Quality Standards for ozone and particulate matter, emissions from mobile sources, and interstate air pollution transport as top challenges in need of improved information. Most survey respondents viewed inadequate coverage or frequency of satellite observations, data uncertainty, and lack of staff time or resources as barriers to increased use of satellite data by their organizations. Managers who have been involved with AQAST indicated that the program has helped build awareness of NASA Earth science products, and assisted their organizations with retrieval and interpretation of satellite data and with application of global chemistry and climate models. AQAST has also helped build a network between researchers and air quality managers with potential for further collaborations. NASA's Air Quality Applied Science Team (AQAST) aims to increase the use of satellite data and global chemistry and climate models for air quality management purposes, by supporting research and tool development projects of interest to both groups. Our survey and interviews of air quality managers indicate they found value in many AQAST projects and particularly appreciated the connections to the research community that the program facilitated. Managers expressed interest in receiving continued support for their organizations' use of

  14. Managing structural design through integrated models and obtaining increased safety and economy

    International Nuclear Information System (INIS)

    Diaz, B.E.; Thomaz, E.C.S.

    1987-01-01

    The use of large finite element (FE) models for the design of reinforced concrete elements in nuclear power plants will be treated. For this technique a set of computer programs is necessary, since the amount of data is very large. With this design method a series of advantages is obtained such as: reduction of reinforcing steel expenditure, increase of safety through a better representation of the structures, an adequate control of the calculation due to the transparent method of design, reduction of design time due to the automatic computation and so on. (author)

  15. The flipped classroom: A learning model to increase student engagement not academic achievement

    Directory of Open Access Journals (Sweden)

    Masha Smallhorn

    2017-07-01

    Full Text Available A decrease in student attendance at lectures both nationally and internationally, has prompted educators to re-evaluate their teaching methods and investigate strategies which promote student engagement. The flipped classroom model, grounded in active learning pedagogy, transforms the face-to-face classroom. Students prepare for the flipped classroom in their own time by watching short online videos and completing readings. Face-to-face time is used to apply learning through problem-solving with peers. To improve the engagement and learning outcomes of our second year cohort, lectures were replaced with short online videos and face-to-face time was spent in a flipped classroom. The impact of the flipped classroom was analysed through surveys, attendance records, learning analytics and exam data before and after the implementation of the flipped classroom. Results suggest an increase in student engagement and a positive attitude towards the learning method. However, there were no measurable increases in student learning outcomes.

  16. Increased Plasma Colloid Osmotic Pressure Facilitates the Uptake of Therapeutic Macromolecules in a Xenograft Tumor Model

    Directory of Open Access Journals (Sweden)

    Matthias Hofmann

    2009-08-01

    Full Text Available Elevated tumor interstitial fluid pressure (TIFP is a characteristic of most solid tumors. Clinically, TIFP may hamper the uptake of chemotherapeutic drugs into the tumor tissue reducing their therapeutic efficacy. In this study, a means of modulating TIFP to increase the flux of macromolecules into tumor tissue is presented, which is based on the rationale that elevated plasma colloid osmotic pressure (COP pulls water from tumor interstitium lowering the TIFP. Concentrated human serum albumin: (20% HSA, used as an agent to enhance COP, reduced the TIFP time-dependently from 8 to 2 mm Hg in human tumor xenograft models bearing A431 epidermoid vulva carcinomas. To evaluate whether this reduction facilitates the uptake of macromolecules, the intratumoral distribution of fluorescently conjugated dextrans (2.5 mg/ml and cetuximab (2.0 mg/ml was probed using novel time domain nearinfrared fluorescence imaging. This method permitted discrimination and semiquantification of tumor-accumulated conjugate from background and unspecific probe fluorescence. The coadministration of 20% HSA together with either dextrans or cetuximab was found to lower the TIFP significantly and increase the concentration of the substances within the tumor tissue in comparison to control tumors. Furthermore, combined administration of 20%HSA plus cetuximab reduced the tumor growth significantly in comparison to standard cetuximab treatment. These data demonstrate that increased COP lowers the TIFP within hours and increases the uptake of therapeutic macromolecules into the tumor interstitium leading to reduced tumor growth. This model represents a novel approach to facilitate the delivery of therapeutics into tumor tissue, particularly monoclonal antibodies.

  17. Triiodothyronine increases calcium loss in a bed rest antigravity model for space flight.

    Science.gov (United States)

    Smith, Steven R; Lovejoy, Jennifer C; Bray, George A; Rood, Jennifer; Most, Marlene M; Ryan, Donna H

    2008-12-01

    Bed rest has been used as a model to simulate the effects of space flight on bone metabolism. Thyroid hormones accelerate bone metabolism. Thus, supraphysiologic doses of this hormone might be used as a model to accelerate bone metabolism during bed rest and potentially simulate space flight. The objective of the study was to quantitate the changes in bone turnover after low doses of triiodothyronine (T(3)) added to short-term bed rest. Nine men and 5 women were restricted to bed rest for 28 days with their heads positioned 6 degrees below their feet. Subjects were randomly assigned to receive either placebo or oral T(3) at doses of 50 to 75 microg/d in a single-blind fashion. Calcium balance was measured over 5-day periods; and T(3), thyroxine, thyroid-stimulating hormone, immunoreactive parathyroid hormone, osteocalcin, bone alkaline phosphatase, and urinary deoxypyridinoline were measured weekly. Triiodothyronine increased 2-fold in the men and 5-fold in the women during treatment, suppressing both thyroxine and thyroid-stimulating hormone. Calcium balance was negative by 300 to 400 mg/d in the T(3)-treated volunteers, primarily because of the increased fecal loss that was not present in the placebo group. Urinary deoxypyridinoline to creatinine ratio, a marker of bone resorption, increased 60% in the placebo group during bed rest, but more than doubled in the T(3)-treated subjects (P < .01), suggesting that bone resorption was enhanced by treatment with T(3). Changes in serum osteocalcin and bone-specific alkaline phosphatase, markers of bone formation, were similar in T(3)- and placebo-treated subjects. Triiodothyronine increases bone resorption and fecal calcium loss in subjects at bed rest.

  18. Using Modeling and Simulation to Complement Testing for Increased Understanding of Weapon Subassembly Response.

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Michael K. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Davidson, Megan [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-09-01

    As part of Sandia’s nuclear deterrence mission, the B61-12 Life Extension Program (LEP) aims to modernize the aging weapon system. Modernization requires requalification and Sandia is using high performance computing to perform advanced computational simulations to better understand, evaluate, and verify weapon system performance in conjunction with limited physical testing. The Nose Bomb Subassembly (NBSA) of the B61-12 is responsible for producing a fuzing signal upon ground impact. The fuzing signal is dependent upon electromechanical impact sensors producing valid electrical fuzing signals at impact. Computer generated models were used to assess the timing between the impact sensor’s response to the deceleration of impact and damage to major components and system subassemblies. The modeling and simulation team worked alongside the physical test team to design a large-scale reverse ballistic test to not only assess system performance, but to also validate their computational models. The reverse ballistic test conducted at Sandia’s sled test facility sent a rocket sled with a representative target into a stationary B61-12 (NBSA) to characterize the nose crush and functional response of NBSA components. Data obtained from data recorders and high-speed photometrics were integrated with previously generated computer models in order to refine and validate the model’s ability to reliably simulate real-world effects. Large-scale tests are impractical to conduct for every single impact scenario. By creating reliable computer models, we can perform simulations that identify trends and produce estimates of outcomes over the entire range of required impact conditions. Sandia’s HPCs enable geometric resolution that was unachievable before, allowing for more fidelity and detail, and creating simulations that can provide insight to support evaluation of requirements and performance margins. As computing resources continue to improve, researchers at Sandia are hoping

  19. Increasing the reliability of the Olkiluoto surface and near-surface hydrological model

    International Nuclear Information System (INIS)

    Karvonen, T.

    2009-05-01

    the overburden during periods when supply (rainfall or snowmelt) to overburden is low but influence of water leaking to ONKALO disappears almost totally after rainy periods. Effect of ONKALO on pressure heads in the shallow bedrock drillholes is much more pronounced than in overburden tubes. However, the effect of ONKALO is almost totally reversible in all shallow bedrock drillholes when total inflow to ONKALO is at the present measured level (17-20 l/min or 25-30 m 3 /d). The results obtained from the surface hydrological model support the earlier geochemical and isotope measurements that there has been infiltration from the Korvensuo reservoir before the construction of ONKALO started. The computed results indicate that there has been at least a slight increase in estimated outflow rate from the Korvensuo reservoir after the construction of the ONKALO. (orig.)

  20. Increased autophagy and apoptosis contribute to muscle atrophy in a myotonic dystrophy type 1 Drosophila model

    Directory of Open Access Journals (Sweden)

    Ariadna Bargiela

    2015-07-01

    Full Text Available Muscle mass wasting is one of the most debilitating symptoms of myotonic dystrophy type 1 (DM1 disease, ultimately leading to immobility, respiratory defects, dysarthria, dysphagia and death in advanced stages of the disease. In order to study the molecular mechanisms leading to the degenerative loss of adult muscle tissue in DM1, we generated an inducible Drosophila model of expanded CTG trinucleotide repeat toxicity that resembles an adult-onset form of the disease. Heat-shock induced expression of 480 CUG repeats in adult flies resulted in a reduction in the area of the indirect flight muscles. In these model flies, reduction of muscle area was concomitant with increased apoptosis and autophagy. Inhibition of apoptosis or autophagy mediated by the overexpression of DIAP1, mTOR (also known as Tor or muscleblind, or by RNA interference (RNAi-mediated silencing of autophagy regulatory genes, achieved a rescue of the muscle-loss phenotype. In fact, mTOR overexpression rescued muscle size to a size comparable to that in control flies. These results were validated in skeletal muscle biopsies from DM1 patients in which we found downregulated autophagy and apoptosis repressor genes, and also in DM1 myoblasts where we found increased autophagy. These findings provide new insights into the signaling pathways involved in DM1 disease pathogenesis.

  1. Modeling the pressure increase in liquid helium cryostats after failure of the insulating vacuum

    Energy Technology Data Exchange (ETDEWEB)

    Heidt, C.; Grohmann, S. [Karlsruhe Institute of Technology, Institute for Technical Physics, Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen, Germany and Karlsruhe Institute of Technology, Institute for Technical Thermodynamics and Refrigeration, Engler-Bunte (Germany); Süßer, M. [Karlsruhe Institute of Technology, Institute for Technical Physics, Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen (Germany)

    2014-01-29

    The pressure relief system of liquid helium cryostats requires a careful design, due to helium's low enthalpy of vaporization and due to the low operating temperature. Hazard analyses often involve the failure of the insulating vacuum in the worst-case scenario. The venting of the insulating vacuum and the implications for the pressure increase in the helium vessel, however, have not yet been fully analyzed. Therefore, the dimensioning of safety devices often requires experience and reference to very few experimental data. In order to provide a better foundation for the design of cryogenic pressure relief systems, this paper presents an analytic approach for the strongly dynamic process induced by the loss of insulating vacuum. The model is based on theoretical considerations and on differential equation modeling. It contains only few simplifying assumptions, which will be further investigated in future experiments. The numerical solutions of example calculations are presented with regard to the heat flux into the helium vessel, the helium pressure increase and the helium flow rate through the pressure relief device. Implications concerning two-phase flow and the influence of kinetic energy are discussed.

  2. Systemic EP4 Inhibition Increases Adhesion Formation in a Murine Model of Flexor Tendon Repair.

    Directory of Open Access Journals (Sweden)

    Michael B Geary

    Full Text Available Flexor tendon injuries are a common clinical problem, and repairs are frequently complicated by post-operative adhesions forming between the tendon and surrounding soft tissue. Prostaglandin E2 and the EP4 receptor have been implicated in this process following tendon injury; thus, we hypothesized that inhibiting EP4 after tendon injury would attenuate adhesion formation. A model of flexor tendon laceration and repair was utilized in C57BL/6J female mice to evaluate the effects of EP4 inhibition on adhesion formation and matrix deposition during flexor tendon repair. Systemic EP4 antagonist or vehicle control was given by intraperitoneal injection during the late proliferative phase of healing, and outcomes were analyzed for range of motion, biomechanics, histology, and genetic changes. Repairs treated with an EP4 antagonist demonstrated significant decreases in range of motion with increased resistance to gliding within the first three weeks after injury, suggesting greater adhesion formation. Histologic analysis of the repair site revealed a more robust granulation zone in the EP4 antagonist treated repairs, with early polarization for type III collagen by picrosirius red staining, findings consistent with functional outcomes. RT-PCR analysis demonstrated accelerated peaks in F4/80 and type III collagen (Col3a1 expression in the antagonist group, along with decreases in type I collagen (Col1a1. Mmp9 expression was significantly increased after discontinuing the antagonist, consistent with its role in mediating adhesion formation. Mmp2, which contributes to repair site remodeling, increases steadily between 10 and 28 days post-repair in the EP4 antagonist group, consistent with the increased matrix and granulation zones requiring remodeling in these repairs. These findings suggest that systemic EP4 antagonism leads to increased adhesion formation and matrix deposition during flexor tendon healing. Counter to our hypothesis that EP4 antagonism

  3. Increased susceptibility to cortical spreading depression in the mouse model of familial hemiplegic migraine type 2.

    Directory of Open Access Journals (Sweden)

    Loredana Leo

    2011-06-01

    Full Text Available Familial hemiplegic migraine type 2 (FHM2 is an autosomal dominant form of migraine with aura that is caused by mutations of the α2-subunit of the Na,K-ATPase, an isoform almost exclusively expressed in astrocytes in the adult brain. We generated the first FHM2 knock-in mouse model carrying the human W887R mutation in the Atp1a2 orthologous gene. Homozygous Atp1a2(R887/R887 mutants died just after birth, while heterozygous Atp1a2(+/R887 mice showed no apparent clinical phenotype. The mutant α2 Na,K-ATPase protein was barely detectable in the brain of homozygous mutants and strongly reduced in the brain of heterozygous mutants, likely as a consequence of endoplasmic reticulum retention and subsequent proteasomal degradation, as we demonstrate in transfected cells. In vivo analysis of cortical spreading depression (CSD, the phenomenon underlying migraine aura, revealed a decreased induction threshold and an increased velocity of propagation in the heterozygous FHM2 mouse. Since several lines of evidence involve a specific role of the glial α2 Na,K pump in active reuptake of glutamate from the synaptic cleft, we hypothesize that CSD facilitation in the FHM2 mouse model is sustained by inefficient glutamate clearance by astrocytes and consequent increased cortical excitatory neurotransmission. The demonstration that FHM2 and FHM1 mutations share the ability to facilitate induction and propagation of CSD in mouse models further support the role of CSD as a key migraine trigger.

  4. Overexpression of the LH receptor increases distant metastases in an endometrial cancer mouse model

    Directory of Open Access Journals (Sweden)

    Serena ePillozzi

    2013-11-01

    Full Text Available Objective. The aim of the present study was to define the role of luteinizing hormone receptor (LH-R expression in endometrial cancer (EC, using preclinical mouse models, to further transfer these data to the clinical setting. Methods. The role of LH-R over-expression was studied using EC cells (Hec1A, e.g. cells with low endogenous LH-R expression transfected with the LH-R (Hec1A-LH-R. In vitro cell proliferation was measured through the WST1 assay, whereas cell invasion was measured trough the matrigel assay. The effects of LH/hCG-R overexpresion in vivo were analyzed in an appropriately developed preclinical mouse model of EC, which mimicked postmenopausal conditions. The model consisted in an orthotopic xenograft of Hec1A cells into immunodeficient mice treated daily with recombinant LH, to assure high levels of LH. Results. In vitro data indicated that LH-R overexpression increased Hec1A invasiveness. In vivo results showed that tumors arising from Hec1A-LH-R cells injection displayed a higher local invasion and a higher number of distant metastases, mainly in the lung, compared to tumors obtained from the injection of Hec1A cells. LH withdrawl strongly inhibited local and distant metastatic spread of tumors, especially those arising from Hec1A-LH-R cells. Conclusions. The overexpression of the LH-R increases the ability of EC cells to undergo local invasion and metastatic spread. This occurs in the presence of high LH serum concentrations.

  5. Boronophenylalanine uptake in C6 glioma model is dramatically increased by L-DOPA preloading

    Energy Technology Data Exchange (ETDEWEB)

    Capuani, S. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Enrico Fermi Center, Compendio Viminale, Rome (Italy)], E-mail: silvia.capuani@roma1.infn.it; Gili, T. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Enrico Fermi Center, Compendio Viminale, Rome (Italy); Bozzali, M. [Neuroimaging Laboratory, Santa Lucia Foundation, Via Ardeatina 306, Rome (Italy); Russo, S. [Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, London (United Kingdom); Porcari, P. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Cametti, C. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Muolo, M. [Department of Biological Science, University ' Rome III' , Viale G. Marconi 446, Rome (Italy); D' Amore, E. [Serv. Qual./Sicurezza Sperim. Anim., Istituto Superiore di Sanita, Rome (Italy); Maraviglia, B. [Enrico Fermi Center, Compendio Viminale, Rome (Italy); Neuroimaging Laboratory, Santa Lucia Foundation, Via Ardeatina 306, Rome (Italy); Lazzarino, G. [Laboratory of Biochemistry, Department of Chemical Sciences, University of Catania, Viale A. Doria 6, Catania (Italy); Pastore, F.S. [Department of Neuroscience, Institute of Neurosurgery, University ' Tor Vergata' , Via Montpellier 1, Rome (Italy)

    2009-07-15

    One of the main limitations for BNCT effectiveness is the insufficient intake of {sup 10}B nuclei within tumour cells. This work was aimed at investigating the use of L-DOPA as enhancer for boronophenylalanine (BPA) uptake in the C6 glioma model. The investigation was first performed in vitro, and then extended in vivo to the animal model. BPA accumulation in C6 glioma cells was assessed, using radiowave dielectric spectroscopy (RDS), with and without L-DOPA preloading. C6 glioma cells were also implanted in the brain of 25 rats, randomly assigned to two experimental branches: (1) intra-carotid BPA infusion; (2) intra-carotid BPA infusion after pre-treatment with L-DOPA, administrated 24 h before BPA infusion. All animals were sacrificed, and assessment of BPA concentrations in tumour tissue, normal brain, and blood samples was performed using high performance liquid chromatography (HPLC). L-DOPA preloading induced a massive increase of BPA concentration either in vitro on C6 glioma cells or in vivo in the animal model tumour. Moreover, no significant difference was found in the normal brain and blood samples between the two animal groups. This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT.

  6. Effect of increasing greenhouse gases on Indian monsoon rainfall as downscaled from the ECHAM coupled model

    International Nuclear Information System (INIS)

    Singh, S.V.; Storch, H.V.

    1994-01-01

    It is more or less accepted that the increasing anthropogenic gases will result in global warming through the greenhouse effect. The major influence of this will be felt in the form of ice melts and rising sea levels. The influence on regional climates like monsoons is not very clear. Since the monsoons arise due to surface heating, one would expect that global warming will lead to more vigorous monsoons. The expected change in a climate parameter can be studied by analyzing the historical data and then extrapolating in time. Alternatively, one can use the state-of-the-art coupled GCMs which are able to simulate the earth's climate with reasonable accuracy. Both methods have some limitations. The first method cannot adequately consider the nonlinearity, and the second method may not be efficient for regional scales. So that the projections can be trusted, the regional features should be well simulated. None of the current models are able to simulate the Indian monsoon satisfactorily. Therefore it is desirable to infer the expected change in monsoons from other large and near global scale features which are better simulated. This approach, which depends on the concurrent association between a large-scale modeled feature and a regional scale, is known as downscaling, after Storch et al., and is adopted here to project the Indian monsoon rainfall for the next 100 years from the ECHAM T21 coupled model

  7. Boronophenylalanine uptake in C6 glioma model is dramatically increased by L-DOPA preloading

    International Nuclear Information System (INIS)

    Capuani, S.; Gili, T.; Bozzali, M.; Russo, S.; Porcari, P.; Cametti, C.; Muolo, M.; D'Amore, E.; Maraviglia, B.; Lazzarino, G.; Pastore, F.S.

    2009-01-01

    One of the main limitations for BNCT effectiveness is the insufficient intake of 10 B nuclei within tumour cells. This work was aimed at investigating the use of L-DOPA as enhancer for boronophenylalanine (BPA) uptake in the C6 glioma model. The investigation was first performed in vitro, and then extended in vivo to the animal model. BPA accumulation in C6 glioma cells was assessed, using radiowave dielectric spectroscopy (RDS), with and without L-DOPA preloading. C6 glioma cells were also implanted in the brain of 25 rats, randomly assigned to two experimental branches: (1) intra-carotid BPA infusion; (2) intra-carotid BPA infusion after pre-treatment with L-DOPA, administrated 24 h before BPA infusion. All animals were sacrificed, and assessment of BPA concentrations in tumour tissue, normal brain, and blood samples was performed using high performance liquid chromatography (HPLC). L-DOPA preloading induced a massive increase of BPA concentration either in vitro on C6 glioma cells or in vivo in the animal model tumour. Moreover, no significant difference was found in the normal brain and blood samples between the two animal groups. This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT.

  8. A mouse model for chronic pain-induced increase in ethanol consumption.

    Science.gov (United States)

    Butler, Ryan K; Knapp, Darin J; Ulici, Veronica; Longobardi, Lara; Loeser, Richard F; Breese, George R

    2017-03-01

    Chronic pain conditions are often comorbid with alcohol abuse. "Self-medication" with alcohol introduces a host of problems associated with the abuse of alcohol which over time has the potential of exacerbating the painful condition. Despite the prevalence of chronic pain being associated with alcohol abuse, rodent models which mimic the comorbid conditions are lacking. In this study, we model osteoarthritis (OA) in C57BL/6J mice by surgically destabilizing the medial meniscus (DMM). Sham-operated mice served as controls. Thirteen weeks after surgery, DMM but not sham-operated mice exhibited pronounced incapacitance of the surgically manipulated hind limb compared with the nonsurgically manipulated hind limb. At this time, the mice were exposed to the 2-bottle ethanol choice, beginning with 2.5% with a gradual increasing to 20%. Compared with sham controls, DMM mice consumed more EtOH and preferred EtOH over water at the 20% EtOH concentration. Histological analysis verified that the DMM mice exhibited significant damage to the articular cartilage and osteophyte growth compared with sham controls and these measures of the severity of OA correlated with the amount of ethanol intake. Thus, the combination of the DMM model of OA with the enhanced two-bottle ethanol choice is a potential preclinical approach in mice by which the basis of the comorbid association of alcohol abuse and chronic pain conditions can be explored.

  9. N-acetylglucosamine increases symptoms and fungal burden in a murine model of oral candidiasis.

    Science.gov (United States)

    Ishijima, Sanae A; Hayama, Kazumi; Takahashi, Miki; Holmes, Ann R; Cannon, Richard D; Abe, Shigeru

    2012-04-01

    The amino sugar N-acetylglucosamine (GlcNAc) is an in vitro inducer of the hyphal mode of growth of the opportunistic pathogen Candida albicans. The development of hyphae by C. albicans is considered to contribute to the pathogenesis of mucosal oral candidiasis. GlcNAc is also a commonly used nutritional supplement for the self-treatment of conditions such as arthritis. To date, no study has investigated whether ingestion of GlcNAc has an effect on the in vivo growth of C. albicans or the pathogenesis of a C. albicans infection. Using a murine model of oral candidiasis, we have found that administration of GlcNAc, but not glucose, increased oral symptoms of candidiasis and fungal burden. Groups of mice were given GlcNAc in either water or in a viscous carrier, i.e., 1% methylcellulose. There was a dose-dependent relationship between GlcNAc concentration and the severity of oral symptoms. Mice given the highest dose of GlcNAc, 45.2 mM, also showed a significant increase in fungal burden, and increased histological evidence of infection compared to controls given water alone. We propose that ingestion of GlcNAc, as a nutritional supplement, may have an impact on oral health in people susceptible to oral candidiasis.

  10. Modelling the impact of increasing soil sealing on runoff coefficients at regional scale: a hydropedological approach

    Directory of Open Access Journals (Sweden)

    Ungaro Fabrizio

    2014-03-01

    Full Text Available Soil sealing is the permanent covering of the land surface by buildings, infrastructures or any impermeable artificial material. Beside the loss of fertile soils with a direct impact on food security, soil sealing modifies the hydrological cycle. This can cause an increased flooding risk, due to urban development in potential risk areas and to the increased volumes of runoff. This work estimates the increase of runoff due to sealing following urbanization and land take in the plain of Emilia Romagna (Italy, using the Green and Ampt infiltration model for two rainfall return periods (20 and 200 years in two different years, 1976 and 2008. To this goal a hydropedological approach was adopted in order to characterize soil hydraulic properties via locally calibrated pedotransfer functions (PTF. PTF inputs were estimated via sequential Gaussian simulations coupled with a simple kriging with varying local means, taking into account soil type and dominant land use. Results show that in the study area an average increment of 8.4% in sealed areas due to urbanization and sprawl induces an average increment in surface runoff equal to 3.5 and 2.7% respectively for 20 and 200-years return periods, with a maximum > 20% for highly sealed coast areas.

  11. Pregnant women models analyzed for RF exposure and temperature increase in 3T RF shimmed birdcages.

    Science.gov (United States)

    Murbach, Manuel; Neufeld, Esra; Samaras, Theodoros; Córcoles, Juan; Robb, Fraser J; Kainz, Wolfgang; Kuster, Niels

    2017-05-01

    MRI is increasingly used to scan pregnant patients. We investigated the effect of 3 Tesla (T) two-port radiofrequency (RF) shimming in anatomical pregnant women models. RF shimming improves B 1 + uniformity, but may at the same time significantly alter the induced current distribution and result in large changes in both the level and location of the absorbed RF energy. In this study, we evaluated the electrothermal exposure of pregnant women in the third, seventh, and ninth month of gestation at various imaging landmarks in RF body coils, including modes with RF shimming. Although RF shimmed configurations may lower the local RF exposure for the mother, they can increase the thermal load on the fetus. In worst-case configurations, whole-body exposure and local peak temperatures-up to 40.8°C-are equal in fetus and mother. Two-port RF shimming can significantly increase the fetal exposure in pregnant women, requiring further research to derive a very robust safety management. For the time being, restriction to the CP mode, which reduces fetal SAR exposure compared with linear-horizontal polarization modes, may be advisable. Results from this study do not support scanning pregnant patients above the normal operating mode. Magn Reson Med 77:2048-2056, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  12. An evaluation of in vivo desensitization and video modeling to increase compliance with dental procedures in persons with mental retardation.

    Science.gov (United States)

    Conyers, Carole; Miltenberger, Raymond G; Peterson, Blake; Gubin, Amber; Jurgens, Mandy; Selders, Andrew; Dickinson, Jessica; Barenz, Rebecca

    2004-01-01

    Fear of dental procedures deters many individuals with mental retardation from accepting dental treatment. This study was conducted to assess the effectiveness of two procedures, in vivo desensitization and video modeling, for increasing compliance with dental procedures in participants with severe or profound mental retardation. Desensitization increased compliance for all 5 participants, whereas video modeling increased compliance for only 1 of 3 participants.

  13. Mesoscale modelling methodology based on nudging to increase accuracy in WRA

    Science.gov (United States)

    Mylonas Dirdiris, Markos; Barbouchi, Sami; Hermmann, Hugo

    2016-04-01

    The offshore wind energy has recently become a rapidly growing renewable energy resource worldwide, with several offshore wind projects in development in different planning stages. Despite of this, a better understanding of the atmospheric interaction within the marine atmospheric boundary layer (MABL) is needed in order to contribute to a better energy capture and cost-effectiveness. Light has been thrown in observational nudging as it has recently become an innovative method to increase the accuracy of wind flow modelling. This particular study focuses on the observational nudging capability of Weather Research and Forecasting (WRF) and ways the uncertainty of wind flow modelling in the wind resource assessment (WRA) can be reduced. Finally, an alternative way to calculate the model uncertainty is pinpointed. Approach WRF mesoscale model will be nudged with observations from FINO3 at three different heights. The model simulations with and without applying observational nudging will be verified against FINO1 measurement data at 100m. In order to evaluate the observational nudging capability of WRF two ways to derive the model uncertainty will be described: one global uncertainty and an uncertainty per wind speed bin derived using the recommended practice of the IEA in order to link the model uncertainty to a wind energy production uncertainty. This study assesses the observational data assimilation capability of WRF model within the same vertical gridded atmospheric column. The principal aim is to investigate whether having observations up to one height could improve the simulation at a higher vertical level. The study will use objective analysis implementing a Cress-man scheme interpolation to interpolate the observation in time and in sp ace (keeping the horizontal component constant) to the gridded analysis. Then the WRF model core will incorporate the interpolated variables to the "first guess" to develop a nudged simulation. Consequently, WRF with and without

  14. Online decision support based on modeling with the aim of increased irrigation efficiency

    Science.gov (United States)

    Dövényi-Nagy, Tamás; Bakó, Károly; Molnár, Krisztina; Rácz, Csaba; Vasvári, Gyula; Nagy, János; Dobos, Attila

    2015-04-01

    The significant changes in the structure of ownership and control of irrigation infrastructure in the past decades resultted in the decrease of total irrigable and irrigated area (Szilárd, 1999). In this paper, the development of a model-based online service is described whose aim is to aid reasonable irrigation practice and increase water use efficiency. In order to establish a scientific background for irrigation, an agrometeorological station network has been built up by the Agrometeorological and Agroecological Monitoring Centre. A website has been launched in order to provide direct access for local agricultural producers to both the measured weather parameters and results of model based calculations. The public site provides information for general use, registered partners get a handy model based toolkit for decision support at the plot level concerning irrigation, plant protection or frost forecast. The agrometeorological reference station network was established in the recent years by the Agrometeorological and Agroecological Monitoring Centre and is distributed to cover most of the irrigated cropland areas of Hungary. From the spatial aspect, the stations have been deployed mainly in Eastern Hungary with concentrated irrigation infrastructure. The meteorological stations' locations have been carefully chosen to represent their environment in terms of soil, climatic and topographic factors, thereby assuring relevant and up-to-date input data for the models. The measured parameters range from classic meteorological data (air temperature, relative humidity, solar irradiation, wind speed etc.) to specific data which are not available from other services in the region, such as soil temperature, soil water content in multiple depths and leaf wetness. In addition to the basic grid of reference stations, specific stations under irrigated conditions have been deployed to calibrate and validate the models. A specific modeling framework (MetAgro) has been developed

  15. A new modelling framework and mitigation measures for increased resilience to flooding

    Science.gov (United States)

    Valyrakis, Manousos; Alexakis, Athanasios; Solley, Mark

    2015-04-01

    Flooding in rivers and estuaries is amongst the most significant challenges our society has yet to tackle effectively. Use of floodwall systems is one of the potential measures that can be used to mitigate the detrimental socio-economical and ecological impacts and alleviate the associated costs of flooding. This work demonstrates the utility of such systems for a case study via appropriate numerical simulations, in addition to conducting scaled flume experiments towards obtaining a better understanding of the performance and efficiency of the flood-wall systems. At first, the results of several characteristic inundation modeling scenarios and flood mitigation options, for a flood-prone region in Scotland. In particular, the history and hydrology of the area are discussed and the assumptions and hydraulic model input (model geometry including instream hydraulic structures -such as bridges and weirs- river and floodplain roughness, initial and boundary conditions) are presented, followed by the model results. Emphasis is given on the potential improvements brought about by mitigating flood risk using flood-wall systems. Further, the implementation of the floodwall in mitigating flood risk is demonstrated via appropriate numerical modeling, utilizing HEC-RAS to simulate the effect of a river's rising stage during a flood event, for a specific area. The later part of this work involves the design, building and utilization of a scaled physical model of a flood-wall system. These experiments are carried out at one of the research flumes in the Water Engineering laboratory of the University of Glasgow. These involve an experimental investigation where the increase of force applied on the floodwall is measured for different degrees of deflection of the water in the stream, under the maximum flow discharge that can be carried through without exceeding the floodwall height (and accounting for the effect of super-elevation). These results can be considered upon the

  16. Study of the Deformation/Interaction Model: How Interactions Increase the Reaction Barrier

    Directory of Open Access Journals (Sweden)

    Zhiling Liang

    2018-01-01

    Full Text Available The interactions (including weak interactions between dienophiles and dienes play an important role in the Diels-Alder reaction. To elucidate the influence of these interactions on the reactivity, a popular DFT functional and a variational DFT functional corrected with dispersion terms are used to investigate different substituent groups incorporated on the dienophiles and dienes. The bond order is used to track the trajectory of the cycloaddition reaction. The deformation/interaction model is used to obtain the interaction energy from the reactant complex to the inflection point until reaching the saddle point. The interaction energy initially increases with a decrease in the interatomic distance, reaching a maximum value, but then decreases when the dienophiles and dienes come closer. Reduced density gradient and chemical energy component analysis are used to analyse the interaction. Traditional transition state theory and variational transition state theory are used to obtain the reaction rates. The influence of tunneling on the reaction rate is also discussed.

  17. Increased numbers of orexin/hypocretin neurons in a genetic rat depression model

    DEFF Research Database (Denmark)

    Mikrouli, Elli; Wörtwein, Gitta; Soylu, Rana

    2011-01-01

    The Flinders Sensitive Line (FSL) rat is a genetic animal model of depression that displays characteristics similar to those of depressed patients including lower body weight, decreased appetite and reduced REM sleep latency. Hypothalamic neuropeptides such as orexin/hypocretin, melanin......-concentrating hormone (MCH) and cocaine and amphetamine regulated transcript (CART), that are involved in the regulation of both energy metabolism and sleep, have recently been implicated also in depression. We therefore hypothesized that alterations in these neuropeptide systems may play a role in the development...... of the FSL phenotype with both depressive like behavior, metabolic abnormalities and sleep disturbances. In this study, we first confirmed that the FSL rats displayed increased immobility in the Porsolt forced swim test compared to their control strain, the Flinders Resistant Line (FRL), which is indicative...

  18. Etoposide Incorporated into Camel Milk Phospholipids Liposomes Shows Increased Activity against Fibrosarcoma in a Mouse Model

    Directory of Open Access Journals (Sweden)

    Hamzah M. Maswadeh

    2015-01-01

    Full Text Available Phospholipids were isolated from camel milk and identified by using high performance liquid chromatography and gas chromatography-mass spectrometry (GC/MS. Anticancer drug etoposide (ETP was entrapped in liposomes, prepared from camel milk phospholipids, to determine its activity against fibrosarcoma in a murine model. Fibrosarcoma was induced in mice by injecting benzopyrene (BAP and tumor-bearing mice were treated with various formulations of etoposide, including etoposide entrapped camel milk phospholipids liposomes (ETP-Cam-liposomes and etoposide-loaded DPPC-liposomes (ETP-DPPC-liposomes. The tumor-bearing mice treated with ETP-Cam-liposomes showed slow progression of tumors and increased survival compared to free ETP or ETP-DPPC-liposomes. These results suggest that ETP-Cam-liposomes may prove to be a better drug delivery system for anticancer drugs.

  19. Development of E-Book Multimedia Model to Increase Critical Thinking of Senior High School Students

    Directory of Open Access Journals (Sweden)

    Suparno Suparno

    2018-03-01

    Full Text Available This study aims to develop the interactive e-book multimedia model to improve the students' critical thinking ability (KBK. Critical thinking is very important to develop because it provides a high level of reasoning thinking that provides permanent experience to students through conscious and controlled decision making in a rational, reflective, responsible manner with the optimization of potential. Flash-based e-book media is capable of interactively loading videos, pictures, practice questions and learning with directed directions from the teacher. The research method developed is research and development. The output products are learning plan, KBK evaluation question, flash-based interactive e-book multimedia, and quasi experiment to see media effectiveness to KBK. The results showed that e-book multimedia is able to significantly increase the KBK of high school students in economic learning.

  20. Reducing sexual violence by increasing the supply of toilets in Khayelitsha, South Africa: a mathematical model.

    Directory of Open Access Journals (Sweden)

    Gregg S Gonsalves

    Full Text Available Sexual violence is a major public health issue, affecting 35% of women worldwide. Major risk factors for sexual assault include inadequate indoor sanitation and the need to travel to outdoor toilet facilities. We estimated how increasing the number of toilets in an urban township (Khayelitsha, South Africa might reduce both economic costs and the incidence and social burden of sexual assault.We developed a mathematical model that links risk of sexual assault to the number of sanitation facilities and the time a woman must spend walking to a toilet. We defined a composite societal cost function, comprising both the burden of sexual assault and the costs of installing and maintaining public chemical toilets. By expressing total social costs as a function of the number of available toilets, we were able to identify an optimal (i.e., cost-minimizing social investment in toilet facilities.There are currently an estimated 5600 toilets in Khayelitsha. This results in 635 sexual assaults and US$40 million in combined social costs each year. Increasing the number of toilets to 11300 would minimize total costs ($35 million and reduce sexual assaults to 446. Higher toilet installation and maintenance costs would be more than offset by lower sexual assault costs. Probabilistic sensitivity analysis shows that the optimal number of toilets exceeds the original allocation of toilets in the township in over 80% of the 5000 iterations of the model.Improving access to sanitation facilities in urban settlements will simultaneously reduce the incidence of sexual assaults and overall cost to society. Since our analysis ignores the many additional health benefits of improving sanitation in resource-constrained urban areas (e.g., potential reductions in waterborne infectious diseases, the optimal number of toilets identified here should be interpreted as conservative.

  1. New Careers in Nursing: An Effective Model for Increasing Nursing Workforce Diversity.

    Science.gov (United States)

    Craft-Blacksheare, Melva

    2018-03-01

    The Robert Wood Johnson Foundation and the American Association of Colleges of Nursing developed the New Careers in Nursing (NCIN) program to address the nursing shortage, increase workforce diversity, and raise the profession's educational level. The program provided scholarships to second-degree underrepresented or economically disadvantaged (UED) students attending an accelerated nursing program to earn a Bachelor of Science in Nursing degree. A midwestern university received three academic-year cycles of NCIN funding. The program's model, resources, and functioning are described. The NCIN provided exceptional financial and program support that received high marks from participants. During the three award cycles, 20 UED scholars graduated with a Bachelor of Science in Nursing degree. Nineteen of the 20 scholars passed the NCLEX-RN on the first attempt. While the NCIN program has ended, nursing school administrators and faculty wishing to promote UED student success should consider using the program's model and resources as the basis for their own program. [J Nurs Educ. 2018;57(3):178-183.]. Copyright 2018, SLACK Incorporated.

  2. The implementation of discovery learning model based on lesson study to increase student's achievement in colloid

    Science.gov (United States)

    Suyanti, Retno Dwi; Purba, Deby Monika

    2017-03-01

    The objectives of this research are to get the increase student's achievement on the discovery learning model based on lesson study. Beside of that, this research also conducted to know the cognitive aspect. This research was done in three school that are SMA N 3 Medan. Population is all the students in SMA N 11 Medan which taken by purposive random sampling. The research instruments are achievement test instruments that have been validated. The research data analyzed by statistic using Ms Excell. The result data shows that the student's achievement taught by discovery learning model based on Lesson study higher than the student's achievement taught by direct instructional method. It can be seen from the average of gain and also proved with t-test, the normalized gain in experimental class of SMA N 11 is (0.74±0.12) and control class (0.45±0.12), at significant level α = 0.05, Ha is received and Ho is refused where tcount>ttable in SMA N 11 (9.81>1,66). Then get the improvement cognitive aspect from three of school is C2 where SMA N 11 is 0.84(high). Then the observation sheet result of lesson study from SMA N 11 92 % of student working together while 67% less in active using media.

  3. Modeling The Economic And Health Impact Of Increasing Children's Physical Activity In The United States.

    Science.gov (United States)

    Lee, Bruce Y; Adam, Atif; Zenkov, Eli; Hertenstein, Daniel; Ferguson, Marie C; Wang, Peggy I; Wong, Michelle S; Wedlock, Patrick; Nyathi, Sindiso; Gittelsohn, Joel; Falah-Fini, Saeideh; Bartsch, Sarah M; Cheskin, Lawrence J; Brown, Shawn T

    2017-05-01

    Increasing physical activity among children is a potentially important public health intervention. Quantifying the economic and health effects of the intervention would help decision makers understand its impact and priority. Using a computational simulation model that we developed to represent all US children ages 8-11 years, we estimated that maintaining the current physical activity levels (only 31.9 percent of children get twenty-five minutes of high-calorie-burning physical activity three times a week) would result each year in a net present value of $1.1 trillion in direct medical costs and $1.7 trillion in lost productivity over the course of their lifetimes. If 50 percent of children would exercise, the number of obese and overweight youth would decrease by 4.18 percent, averting $8.1 billion in direct medical costs and $13.8 billion in lost productivity. Increasing the proportion of children who exercised to 75 percent would avert $16.6 billion and $23.6 billion, respectively. Project HOPE—The People-to-People Health Foundation, Inc.

  4. ATM-deficiency increases genomic instability and metastatic potential in a mouse model of pancreatic cancer.

    Science.gov (United States)

    Drosos, Yiannis; Escobar, David; Chiang, Ming-Yi; Roys, Kathryn; Valentine, Virginia; Valentine, Marc B; Rehg, Jerold E; Sahai, Vaibhav; Begley, Lesa A; Ye, Jianming; Paul, Leena; McKinnon, Peter J; Sosa-Pineda, Beatriz

    2017-09-11

    Germline mutations in ATM (encoding the DNA-damage signaling kinase, ataxia-telangiectasia-mutated) increase Familial Pancreatic Cancer (FPC) susceptibility, and ATM somatic mutations have been identified in resected human pancreatic tumors. Here we investigated how Atm contributes to pancreatic cancer by deleting this gene in a murine model of the disease expressing oncogenic Kras (Kras G12D ). We show that partial or total ATM deficiency cooperates with Kras G12D to promote highly metastatic pancreatic cancer. We also reveal that ATM is activated in pancreatic precancerous lesions in the context of DNA damage and cell proliferation, and demonstrate that ATM deficiency leads to persistent DNA damage in both precancerous lesions and primary tumors. Using low passage cultures from primary tumors and liver metastases we show that ATM loss accelerates Kras-induced carcinogenesis without conferring a specific phenotype to pancreatic tumors or changing the status of the tumor suppressors p53, p16 Ink4a and p19 Arf . However, ATM deficiency markedly increases the proportion of chromosomal alterations in pancreatic primary tumors and liver metastases. More importantly, ATM deficiency also renders murine pancreatic tumors highly sensitive to radiation. These and other findings in our study conclusively establish that ATM activity poses a major barrier to oncogenic transformation in the pancreas via maintaining genomic stability.

  5. Intermittent hypoxia increases melanoma metastasis to the lung in a mouse model of sleep apnea.

    Science.gov (United States)

    Almendros, Isaac; Montserrat, Josep M; Torres, Marta; Dalmases, Mireia; Cabañas, Maria L; Campos-Rodríguez, Francisco; Navajas, Daniel; Farré, Ramon

    2013-05-01

    Obstructive sleep apnea (OSA) has recently been associated with an increased risk of cancer incidence and mortality in humans. Experimental data in mice have also shown that intermittent hypoxia similar to that observed in OSA patients enhances tumor growth. The aim of this study was to test the hypothesis that intermittent hypoxia mimicking OSA enhances lung metastasis. A total of 75 C57BL/6J male mice (10-week-old) were subjected to either spontaneous or induced melanoma lung metastasis. Normoxic animals breathed room air and intermittent hypoxic animals were subjected to cycles of 20s of 5% O2 followed by 40s of room air for 6h/day. Spontaneous and induced lung metastases were studied after subcutaneous and intravenous injection of B16F10 melanoma cells, respectively. Compared with normoxia, intermittent hypoxia induced a significant increase in melanoma lung metastasis. These animal model results suggest that intermittent hypoxia could contribute to cancer metastasis in patients with OSA. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Increased airway reactivity in a neonatal mouse model of Continuous Positive Airway Pressure (CPAP)

    Science.gov (United States)

    Mayer, Catherine A.; Martin, Richard J.; MacFarlane, Peter M.

    2015-01-01

    Background Continuous positive airway pressure (CPAP) is a primary form of respiratory support used in the intensive care of preterm infants, but its long-term effects on airway (AW) function are unknown. Methods We developed a neonatal mouse model of CPAP treatment to determine whether it modifies later AW reactivity. Un-anesthetized spontaneously breathing mice were fitted with a mask to deliver CPAP (6cmH2O, 3hrs/day) for 7 consecutive days starting at postnatal day 1. Airway reactivity to methacholine was assessed using the in vitro living lung slice preparation. Results One week of CPAP increased AW responsiveness to methacholine in male, but not female mice, compared to untreated control animals. The AW hyper-reactivity of male mice persisted for 2 weeks (at P21) after CPAP treatment ended. 4 days of CPAP, however, did not significantly increase AW reactivity. Females also exhibited AW hyper-reactivity at P21, suggesting a delayed response to early (7 days) CPAP treatment. The effects of 7 days of CPAP on hyper-reactivity to methacholine were unique to smaller AWs whereas larger ones were relatively unaffected. Conclusion These data may be important to our understanding of the potential long-term consequences of neonatal CPAP therapy used in the intensive care of preterm infants. PMID:25950451

  7. Curcumin increases the pathogenicity of Salmonella enterica serovar Typhimurium in murine model.

    Directory of Open Access Journals (Sweden)

    Sandhya A Marathe

    Full Text Available Curcumin has gained immense importance for its vast therapeutic and prophylactic applications. Contrary to this, our study reveals that it regulates the defense pathways of Salmonella enterica serovar Typhimurium (S. Typhimurium to enhance its pathogenicity. In a murine model of typhoid fever, we observed higher bacterial load in Peyer's patches, mesenteric lymph node, spleen and liver, when infected with curcumin-treated Salmonella. Curcumin increased the resistance of S. Typhimurium against antimicrobial agents like antimicrobial peptides, reactive oxygen and nitrogen species. This increased tolerance might be attributed to the up-regulation of genes involved in resistance against antimicrobial peptides--pmrD and pmrHFIJKLM and genes with antioxidant function--mntH, sodA and sitA. We implicate that iron chelation property of curcumin have a role in regulating mntH and sitA. Interestingly, we see that the curcumin-mediated modulation of pmr genes is through the PhoPQ regulatory system. Curcumin downregulates SPI1 genes, required for entry into epithelial cells and upregulates SPI2 genes required to intracellular survival. Since it is known that the SPI1 and SPI2 system can be regulated by the PhoPQ system, this common regulator could explain curcumin's mode of action. This data urges us to rethink the indiscriminate use of curcumin especially during Salmonella outbreaks.

  8. Increased susceptibility to structural acute kidney injury in a mouse model of presymptomatic cardiomyopathy.

    Science.gov (United States)

    Pleasant, LaTawnya; Ma, Qing; Devarajan, Mahima; Parameswaran, Priyanka; Drake, Keri; Siroky, Brian; Shay-Winkler, Kritton; Robbins, Jeffrey; Devarajan, Prasad

    2017-09-01

    The early events that signal renal dysfunction in presymptomatic heart failure are unclear. We tested the hypothesis that functional and mechanistic changes occur in the kidney that precede the development of symptomatic heart failure. We employed a transgenic mouse model with cardiomyocyte-specific overexpression of mutant α-B-crystallin that develops slowly progressive cardiomyopathy. Presymptomatic transgenic mice displayed an increase in serum creatinine (1.17 ± 0.34 vs. wild type 0.65 ± 0.16 mg/dl, P kidneys exhibited a twofold upregulation of the Ren1 gene, marked overexpression of renin protein in the tubules, and a worsened response to ischemia-reperfusion injury based on serum creatinine (2.77 ± 0.66 in transgenic mice vs. 2.01 ± 0.58 mg/dl in wild type, P kidney that occur in early presymptomatic heart failure, which increase the susceptibility to subsequent acute kidney injury. Copyright © 2017 the American Physiological Society.

  9. Increased lipolysis and energy expenditure in a mouse model with severely impaired glucagon secretion.

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    Phing-How Lou

    Full Text Available BACKGROUND: Secretion of insulin and glucagon is triggered by elevated intracellular calcium levels. Although the precise mechanism by which the calcium signal is coupled to insulin and glucagon granule exocytosis is unclear, synaptotagmin-7 has been shown to be a positive regulator of calcium-dependent insulin and glucagon secretion, and may function as a calcium sensor for insulin and glucagon granule exocytosis. Deletion of synaptotagmin-7 leads to impaired glucose-stimulated insulin secretion and nearly abolished Ca(2+-dependent glucagon secretion in mice. Under non-stressed resting state, however, synaptotagmin-7 KO mice exhibit normal insulin level but severely reduced glucagon level. METHODOLOGY/PRINCIPAL FINDINGS: We studied energy expenditure and metabolism in synaptotagmin-7 KO and control mice using indirect calorimetry and biochemical techniques. Synaptotagmin-7 KO mice had lower body weight and body fat content, and exhibited higher oxygen consumption and basal metabolic rate. Respiratory exchange ratio (RER was lower in synaptotagmin-7 KO mice, suggesting an increased use of lipid in their energy production. Consistent with lower RER, gene expression profiles suggest enhanced lipolysis and increased capacity for fatty acid transport and oxidation in synaptotagmin-7 KO mice. Furthermore, expression of uncoupling protein 3 (UCP3 in skeletal muscle was approximately doubled in the KO mice compared with control mice. CONCLUSIONS: These results show that the lean phenotype in synaptotagmin-7 KO mice was mostly attributed to increased lipolysis and energy expenditure, and suggest that reduced glucagon level may have broad influence on the overall metabolism in the mouse model.

  10. Fluvastatin increases insulin-like growth factor-1 gene expression in rat model of metabolic syndrome

    International Nuclear Information System (INIS)

    Mansy, Wael H.; Sourour, Doaa A.; Shaker, Olfat G.; Mahfouz, Mahmoud M.

    2008-01-01

    Insulin-like growth factor-1 (IGF-1) was found to have a role in both glucose homeostasis and cardiovascular diseases. The present study was designed to compare the effects of fluvastatin and metformin on IGF-1 mRNA expression within the liver and other individual components of the metabolic syndrome induced in rats by high fructose feeding. Rats fed 60% fructose in diet for 6 weeks were treated daily with fluvastatin (3.75 mg/kg/day) during the last two weeks and were compared with untreated fructose fed group. Fasting levels of plasma cholesterol, triglyceride, glucose, insulin, nitric oxide products, IGF-1 mRNA within the liver as well as systolic blood pressure and body weight were determined. Compared to control rats, the fructose fed group developed hypertension, hyperlipidemia, hyperinsulinemia, hyperglycemia and endothelial dysfunction as well as decreased levels of plasma IGF-1 and its mRNA within the liver. Fructose fed rats treated with fluvastatin or metformin for 2 weeks showed significant decrease in plasma cholesterol, triglyceride, insulin and glucose levels compared to untreated fructose fed group. Also, both drugs increased significantly plasma levels of nitric oxide products and IGF-1 together with significant increase in IGF-1 mRNA within the liver. However, only metformin treated rats showed significant decrease in systolic blood pressure compared to fructose fed group. This study showed that in a rat model of insulin resistance, fluvastatin improves the metabolic profile and increases plasma level of IGF-1 and its gene expression as effective as metformin. (author)

  11. Increased plasma lipid levels exacerbate muscle pathology in the mdx mouse model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Milad, Nadia; White, Zoe; Tehrani, Arash Y; Sellers, Stephanie; Rossi, Fabio M V; Bernatchez, Pascal

    2017-09-12

    Duchenne muscular dystrophy (DMD) is caused by loss of dystrophin expression and leads to severe ambulatory and cardiac function decline. However, the dystrophin-deficient mdx murine model of DMD only develops a very mild form of the disease. Our group and others have shown vascular abnormalities in animal models of MD, a likely consequence of the fact that blood vessels express the same dystrophin-associated glycoprotein complex (DGC) proteins as skeletal muscles. To test the blood vessel contribution to muscle damage in DMD, mdx 4cv mice were given elevated lipid levels via apolipoprotein E (ApoE) gene knockout combined with normal chow or lipid-rich Western diets. Ambulatory function and heart function (via echocardiogram) were assessed at 4 and 7 months of age. After sacrifice, muscle histology and aortic staining were used to assess muscle pathology and atherosclerosis development, respectively. Plasma levels of total cholesterol, high-density lipoprotein (HDL), triglycerides, and creatine kinase (CK) were also measured. Although there was an increase in left ventricular heart volume in mdx-ApoE mice compared to that in mdx mice, parameters of heart function were not affected. Compared with wild-type and ApoE-null, only mdx-ApoE KO mice showed significant ambulatory dysfunction. Despite no significant difference in plasma CK, histological analyses revealed that elevated plasma lipids in chow- and Western diet-fed mdx-ApoE mice was associated with severe exacerbation of muscle pathology compared to mdx mice: significant increase in myofiber damage and fibrofatty replacement in the gastrocnemius and triceps brachii muscles, more reminiscent of human DMD pathology. Finally, although both ApoE and mdx-ApoE groups displayed increased plasma lipids, mdx-ApoE exhibited atherosclerotic plaque deposition equal to or less than that of ApoE mice. Since others have shown that lipid abnormalities correlate with DMD severity, our data suggest that plasma lipids could be

  12. Sleep disruption increases seizure susceptibility: Behavioral and EEG evaluation of an experimental model of sleep apnea.

    Science.gov (United States)

    Hrnčić, Dragan; Grubač, Željko; Rašić-Marković, Aleksandra; Šutulović, Nikola; Šušić, Veselinka; Bjekić-Macut, Jelica; Stanojlović, Olivera

    2016-03-01

    Sleep disruption accompanies sleep apnea as one of its major symptoms. Obstructive sleep apnea is particularly common in patients with refractory epilepsy, but causing factors underlying this are far from being resolved. Therefore, translational studies regarding this issue are important. Our aim was to investigate the effects of sleep disruption on seizure susceptibility of rats using experimental model of lindane-induced refractory seizures. Sleep disruption in male Wistar rats with implanted EEG electrodes was achieved by treadmill method (belt speed set on 0.02 m/s for working and 0.00 m/s for stop mode, respectively). Animals were assigned to experimental conditions lasting 6h: 1) sleep disruption (sleep interrupted, SI; 30s working and 90 s stop mode every 2 min; 180 cycles in total); 2) activity control (AC, 10 min working and 30 min stop mode, 9 cycles in total); 3) treadmill chamber control (TC, only stop mode). Afterwards, the animals were intraperitoneally treated with lindane (L, 4 mg/kg, SI+L, AC+L and TC+L groups) or dimethylsulfoxide (DMSO, SIc, ACc and TCc groups). Convulsive behavior was assessed by seizure incidence, latency time to first seizure, and its severity during 30 min after drug administration. Number and duration of ictal periods were determined in recorded EEGs. Incidence and severity of lindane-induced seizures were significantly increased, latency time significantly decreased in animals undergoing sleep disruption (SI+L group) compared with the animals from TC+L. Seizure latency was also significantly decreased in SI+L compared to AC+L groups. Number of ictal periods were increased and duration of it presented tendency to increase in SI+L comparing to AC+L. No convulsive signs were observed in TCc, ACc and SIc groups, as well as no ictal periods in EEG. These results indicate sleep disruption facilitates induction of epileptic activity in rodent model of lindane-epilepsy enabling translational research of this phenomenon. Copyright

  13. A Nursing Management Model to Increase Medication Adherence and Nutritional Status of Patients with Pulmonary TB

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    Eka Mishbahatul Mar’ah Has

    2015-04-01

    Full Text Available Introduction: High dropout rate, inadequate treatment, and resistance to medication, still become an obstacle in the treatment of pulmonary TB. Pulmonary TB patient care management at home can be done actively through telenursing. N-SMSI (Ners-Short Message Service Intervention is one of community nursing intervention, in which community nurses send short messages to remind patients to take medication and nutrition. The aim of this study was to analyze the effect of nursing management model N-SMSI to increased medication adherence and nutritional status of patients with pulmonary TB. Method: This study was used prospective design. The populations were new pulmonary TB patient at intensive phase, at Puskesmas Pegirian Surabaya. Samples were taken by purposive sampling technique; consist of 30 people, divided into treatment and control groups. The independent variable was N-SMSI. The dependent variables were medication adherence collected by using questionnaire and nutritional status by using measurement of body weight (kg. The data were then analyzed by using Wilcoxon Signed Rank Test, Mann Whitney, and Independent t-test with α ≤ 0.05 Result: The results of wilcoxon signed rank test had showed difference in the nutritional status of the treatment group before and after intervention, with p = 0.001. It’s similar with the control group, with p = 0.002. Mann whitney test results had showed no signifi cant difference in nutritional status between treatment and control group, as indicated by the value of p=0.589. While independent t-test had showed difference in compliance between treatment and control group, with p=0.031. Conslusion: N-SMSI can improve medication adherence of patient with Pulmonary TB. This model can be developed by nurse as alternative methods to improve medication adherence in patients with Pulmonary TB. Further research should modify nursing management model which can improve the nutritional status of patient with Pulmonary

  14. Conditionally replicating adenovirus expressing TIMP2 increases survival in a mouse model of disseminated ovarian cancer.

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    Sherry W Yang

    Full Text Available Ovarian cancer remains difficult to treat mainly due to presentation of the disease at an advanced stage. Conditionally-replicating adenoviruses (CRAds are promising anti-cancer agents that selectively kill the tumor cells. The present study evaluated the efficacy of a novel CRAd (Ad5/3-CXCR4-TIMP2 containing the CXCR4 promoter for selective viral replication in cancer cells together with TIMP2 as a therapeutic transgene, targeting the matrix metalloproteases (MMPs in a murine orthotopic model of disseminated ovarian cancer. An orthotopic model of ovarian cancer was established in athymic nude mice by intraperitonal injection of the human ovarian cancer cell line, SKOV3-Luc, expressing luciferase. Upon confirmation of peritoneal dissemination of the cells by non-invasive imaging, mice were randomly divided into four treatment groups: PBS, Ad-ΔE1-TIMP2, Ad5/3-CXCR4, and Ad5/3-CXCR4-TIMP2. All mice were imaged weekly to monitor tumor growth and were sacrificed upon reaching any of the predefined endpoints, including high tumor burden and significant weight loss along with clinical evidence of pain and distress. Survival analysis was performed using the Log-rank test. The median survival for the PBS cohort was 33 days; for Ad-ΔE1-TIMP2, 39 days; for Ad5/3-CXCR4, 52.5 days; and for Ad5/3-CXCR4-TIMP2, 63 days. The TIMP2-armed CRAd delayed tumor growth and significantly increased survival when compared to the unarmed CRAd. This therapeutic effect was confirmed to be mediated through inhibition of MMP9. Results of the in vivo study support the translational potential of Ad5/3-CXCR4-TIMP2 for treatment of human patients with advanced ovarian cancer.

  15. Attention increases the temporal precision of conscious perception: verifying the Neural-ST Model.

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    Srivas Chennu

    2009-11-01

    Full Text Available What role does attention play in ensuring the temporal precision of visual perception? Behavioural studies have investigated feature selection and binding in time using fleeting sequences of stimuli in the Rapid Serial Visual Presentation (RSVP paradigm, and found that temporal accuracy is reduced when attentional control is diminished. To reduce the efficacy of attentional deployment, these studies have employed the Attentional Blink (AB phenomenon. In this article, we use electroencephalography (EEG to directly investigate the temporal dynamics of conscious perception. Specifically, employing a combination of experimental analysis and neural network modelling, we test the hypothesis that the availability of attention reduces temporal jitter in the latency between a target's visual onset and its consolidation into working memory. We perform time-frequency analysis on data from an AB study to compare the EEG trials underlying the P3 ERPs (Event-related Potential evoked by targets seen outside vs. inside the AB time window. We find visual differences in phase-sorted ERPimages and statistical differences in the variance of the P3 phase distributions. These results argue for increased variation in the latency of conscious perception during the AB. This experimental analysis is complemented by a theoretical exploration of temporal attention and target processing. Using activation traces from the Neural-ST(2 model, we generate virtual ERPs and virtual ERPimages. These are compared to their human counterparts to propose an explanation of how target consolidation in the context of the AB influences the temporal variability of selective attention. The AB provides us with a suitable phenomenon with which to investigate the interplay between attention and perception. The combination of experimental and theoretical elucidation in this article contributes to converging evidence for the notion that the AB reflects a reduction in the temporal acuity of

  16. Mycobacterium tuberculosis PPE18 Protein Reduces Inflammation and Increases Survival in Animal Model of Sepsis.

    Science.gov (United States)

    Ahmed, Asma; Dolasia, Komal; Mukhopadhyay, Sangita

    2018-04-18

    Mycobacterium tuberculosis PPE18 is a member of the PPE family. Previous studies have shown that recombinant PPE18 (rPPE18) protein binds to TLR2 and triggers a signaling cascade which reduces levels of TNF-α and IL-12, and increases IL-10 in macrophages. Because TNF-α is a major mediator of the pathophysiology of sepsis and blocking inflammation is a possible line of therapy in such circumstances, we tested the efficacy of rPPE18 in reducing symptoms of sepsis in a mouse model of Escherichia coli- induced septic peritonitis. rPPE18 significantly decreased levels of serum TNF-α, IL-1β, IL-6, and IL-12 and reduced organ damage in mice injected i.p. with high doses of E. coli Peritoneal cells isolated from rPPE18-treated mice had characteristics of M2 macrophages which are protective in excessive inflammation. Additionally, rPPE18 inhibited disseminated intravascular coagulation, which can cause organ damage resulting in death. rPPE18 was able to reduce sepsis-induced mortality when given prophylactically or therapeutically. Additionally, in a mouse model of cecal ligation and puncture-induced sepsis, rPPE18 reduced TNF-α, alanine transaminase, and creatinine, attenuated organ damage, prevented depletion of monocytes and lymphocytes, and improved survival. Our studies show that rPPE18 has potent anti-inflammatory properties and can serve as a novel therapeutic to control sepsis. Copyright © 2018 by The American Association of Immunologists, Inc.

  17. Increased Foraging in Outdoor Organic Pig Production—Modeling Environmental Consequences

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    Malene Jakobsen

    2015-11-01

    Full Text Available Consumers’ motivations for buying organic products include a wish of acquiring healthy, environmentally friendly products from production systems that also ensure a high level of animal welfare. However, the current Danish organic pig production faces important challenges regarding environmental impact of the system. High ammonia emissions arise from outdoor concrete areas with growing pigs and sows on pasture possess an increased risk of nitrogen (N leaching. Direct foraging in the range area is suggested as a way to improve the nutrient efficiency at farm level and to support a more natural behavior of the pig. Thus, by modeling, we investigated the environmental consequences of two alternative scenarios with growing pigs foraging in the range area and different levels of crops available for foraging—grass–clover or a combination of Jerusalem artichokes and lucerne. It was possible to have growing pigs on free-range without increasing N leaching compared to the current practice. The alternative system with Jerusalem artichokes and lucerne (high integration of forage showed the lowest carbon foot print with 3.12 CO2 eq kg−1 live weight pig compared to the current Danish pasture based system with 3.69 kg CO2 eq kg−1 live weight pig. Due to positive impact on soil carbon sequestration, the second alternative system based on grass-clover (low integration of forage showed a similar carbon foot print compared to current practice with 3.68 kg CO2 eq kg−1 live weight pig. It is concluded that in practice there is room for development of organic farming systems where direct foraging plays a central role.

  18. Increasing reach by offering choices: Results from an innovative model for statewide services for smoking cessation.

    Science.gov (United States)

    Keller, Paula A; Schillo, Barbara A; Kerr, Amy N; Lien, Rebecca K; Saul, Jessie; Dreher, Marietta; Lachter, Randi B

    2016-10-01

    Although state quitlines provide free telephone counseling and often include nicotine replacement therapy (NRT), reach remains limited (1-2% in most states). More needs to be done to engage all smokers in the quitting process. A possible strategy is to offer choices of cessation services through quitlines and to reduce registration barriers. In March 2014, ClearWay Minnesota SM implemented a new model for QUITPLAN® Services, the state's population-wide cessation services. Tobacco users could choose the QUITPLAN® Helpline or one or more Individual QUITPLAN® Services (NRT starter kit, text messaging, email program, or quit guide). The program website was redesigned, online enrollment was added, and a new advertising campaign was created and launched. In 2014-2015, we evaluated whether these changes increased reach. We also assessed quit attempts, quit outcomes, predictors of 30-day abstinence, and average cost per quit via a seven-month follow-up survey. Between March 2014-February 2015, 15,861 unique tobacco users registered, which was a 169% increase over calendar year 2013. The majority of participants made a quit attempt (83.7%). Thirty-day point prevalence abstinence rates (responder rates) were 26.1% for QUITPLAN Services overall, 29.6% for the QUITPLAN Helpline, and 25.5% for Individual QUITPLAN Services. Several variables predicted quit outcomes, including receiving only one call from the Helpline and using both the Helpline and the NRT starter kit. Providing greater choice of cessation services and reducing registration barriers have the potential to engage more tobacco users, foster more quit attempts, and ultimately lead to long-term cessation and reductions in prevalence. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Cellular retention of radioactivity and increased radiation dose. Model experiments with EGF-dextran

    International Nuclear Information System (INIS)

    Sundberg, Aasa Liljegren; Blomquist, Erik; Carlsson, Joergen; Steffen, Ann-Charlott; Gedda, Lars

    2003-01-01

    Targeting of tumor cells with radiolabeled biomolecules is a possible approach to inactivate disseminated tumor cells. However, rapid degradation of the biomolecules after cellular internalization and subsequent excretion of the radioactivity is a problem. We studied the possibility of using dextran as a carrier of radionuclides to improve the intracellular retention. An EGF-dextran conjugate, aimed for targeting of tumor cells overexpressing the EGF-receptor, was used as model. Retention tests were performed with 125 I on different parts: [ 125 I]-EGF-dextran-[ 125 I], [ 125 I]-EGF-dextran and EGF-dextran-[ 125 I]. Comparisons were made with [ 125 I]-EGF. The radiolabeled compounds were incubated with cultured glioma cells for different times. The cellular retention of radioactivity was then measured for up to 24 h. Expected radiation doses at the cellular level were calculated assuming that 131 I, instead of 125 I, was coupled to EGF and EGF-dextran. The results indicated that the EGF-part of the conjugate was degraded and the EGF-attached radioactivity was rapidly excreted, whereas radioactivity on dextran was retained intracellularly to a high degree, i.e. 70-80% of the radioactivity bound to dextran was still cell-associated after 24 h. The retention after 24 h was significantly higher (p < 0.001) when the radioactivity was on the dextran instead of the EGF-part. The radiolabeled EGF-dextran had a notably high specific radioactivity; up to 11 MBq/μg. There was potential for at least hundred times increased radiation dose per receptor interaction when the radioactivity was on the dextran part. The advantage with radioactivity on the dextran part was the high cellular retention and the high specific radioactivity (higher than previously reported for other residualizing labels) without severe loss of receptor specific binding. Thus, dextran seems suitable as a carrier of radionuclides aimed for therapy and gives potential for a highly increased radiation dose

  20. Cement/clay interactions: feedback on the increasing complexity of modeling assumptions

    International Nuclear Information System (INIS)

    Marty, Nicolas C.M.; Gaucher, Eric C.; Tournassat, Christophe; Gaboreau, Stephane; Vong, Chan Quang; Claret, F.; Munier, Isabelle; Cochepin, Benoit

    2012-01-01

    Document available in extended abstract form only. Cementitious materials will be widely used in French concept of radioactive waste repositories. During their degradation over time, in contact with geological pore water, they will release hyper-alkaline fluids rich in calcium and alkaline cations. This chemical gradient likely to develop at the cement/clay interfaces will induce geochemical transformations. The first simplified calculations based mainly on simple mass balance calculation led to a very pessimistic understanding of the real expansion mechanism of the alkaline plume. However, geochemical and migration processes are much more complex because of the dissolution of the barrier's accessory phases and the precipitation of secondary minerals. To describe and to understand this complexity, coupled geochemistry and transport calculations are a useful and a mandatory tool. Furthermore, such sets of modeling when properly calibrated on experimental results are able to give insights on larger time scale unreachable with experiments. Since approximately 20 years, numerous papers have described the results of reactive transport modeling of cement/clay interactions with various numerical assumptions. For example, some authors selected a purely thermodynamic approach while others preferred a coupled thermodynamic/kinetic approach. Unfortunately, most of these studies used different and not comparable parameters as space discretization, initial and boundary conditions, thermodynamic databases, clayey and cementitious materials, etc... This study revisits the types of simulations proposed in the past to represent the effect of an alkaline perturbation with regard to the degree of complexity that was considered. The main goal of the study is to perform simulations with a consistent set of data and an increasing complexity. In doing so, the analysis of numerical results will give a clear vision of key parameters driving the expansion of alteration fronts and

  1. Increased risk of neuropsychological disorders in children born preterm without major disabilities: a neurodevelopmental model

    Directory of Open Access Journals (Sweden)

    Dipasquale Filippo

    2009-06-01

    Full Text Available Over the past 30 years, preterm births have drastically increased and today represent 12.5% of total births. About 1.2% of preterm births characterize very preterm births (GA<32weeks that, with very low birth weight (BW<1500grams, are constantly found as risk factors of unfavourable neurological outcomes in longitudinal follow up studies. Actually, also “late preterm” children (preterm born from 33 to 36 weeks of gestational age, normally considered at low risk for neurodevelopmental disabilities, are supposed to represent a population of children to be monitored. Previous findings of a general cognitive impairment in children born preterm have gradually addressed the assessment of more specific neuropsychological skills and pointed out the importance to follow these children up to adolescent age. The neuroanatomical prerequisite of an abnormality in frontal lobe development and the correlation with various neuropsychological dysfunctions (fine and gross motor disabilities, executive function and working memory deficits, visual-constructional and attentional dysfunctions underline the interference of preterm birth with normal brain maturational phases. Though showing more demanding neurodevelopmental pathways than term peers, a large number of preterm children tend to functionally normalize in adolescence. The review supports the hypothesis of a neurodevelopmental model that can be at risk to influence dysfunctional neuropsychological outcome.

  2. Increased susceptibility to otitis media in a Splunc1-deficient mouse model

    Science.gov (United States)

    Bartlett, Jennifer A.; Meyerholz, David K.; Wohlford-Lenane, Christine L.; Naumann, Paul W.; Salzman, Nita H.; McCray, Paul B.

    2015-01-01

    ABSTRACT Otitis media (inflammation of the middle ear) is one of the most common diseases of early childhood. Susceptibility to otitis is influenced by a number of factors, including the actions of innate immune molecules secreted by the epithelia lining the nasopharynx, middle ear and Eustachian tube. The SPLUNC1 (short palate, lung, nasal epithelial clone 1) protein is a highly abundant secretory product of the mammalian nasal, oral and respiratory mucosa that is thought to play a multifunctional role in host defense. In this study we investigated Splunc1 expression in the ear of the mouse, and examined whether this protein contributes to overall host defense in the middle ear and/or Eustachian tube. We found that Splunc1 is highly expressed in both the surface epithelium and in submucosal glands in these regions in wild-type mice. In mice lacking Splunc1, we noted histologically an increased frequency of otitis media, characterized by the accumulation of leukocytes (neutrophils with scattered macrophages), proteinaceous fluid and mucus in the middle ear lumens. Furthermore, many of these mice had extensive remodeling of the middle ear wall, suggesting a chronic course of disease. From these observations, we conclude that loss of Splunc1 predisposes mice to the development of otitis media. The Splunc1−/− mouse model should help investigators to better understand both the biological role of Splunc1 as well as host defense mechanisms in the middle ear. PMID:25765466

  3. Prowashonupana barley dietary fibre reduces body fat and increases insulin sensitivity in Caenorhabditis elegans model

    Science.gov (United States)

    Gao, Chenfei; King, Michael L.; Fitzpatrick, Zachary L.; Wei, Wenqian; King, Jason F.; Wang, Mingming; Greenway, Frank L.; Finley, John W.; Burton, Jeffrey H.; Johnson, William D.; Keenan, Michael J.; Enright, Frederick M.; Martin, Roy J.; Zheng, Jolene

    2016-01-01

    Prowashonupana barley (PWB) is high in β-glucan with moderate content of resistant starch. PWB reduced intestinal fat deposition (IFD) in wild type Caenorhabditis elegans (C. elegans, N2), and in sir-2.1 or daf-16 null mutants, and sustained a surrogate marker of lifespan, pharyngeal pumping rate (PPR), in N2, sir-2.1, daf-16, or daf-16/daf-2 mutants. Hyperglycaemia (2% glucose) reversed or reduced the PWB effect on IFD in N2 or daf-16/daf-2 mutants with a sustained PPR. mRNA expression of cpt-1, cpt-2, ckr-1, and gcy-8 were dose-dependently reduced in N2 or daf-16 mutants, elevated in daf-16/daf-2 mutants with reduction in cpt-1, and unchanged in sir-2.1 mutants. mRNA expressions were increased by hyperglycaemia in N2 or daf-16/daf-2 mutants, while reduced in sir-2.1 or daf-16 mutants. The effects of PWB in the C. elegans model appeared to be primarily mediated via sir-2.1, daf-16, and daf-16/daf-2. These data suggest that PWB and β-glucans may benefit hyperglycaemia-impaired lipid metabolism. PMID:27721901

  4. A Novel Trp-rich Model Antimicrobial Peptoid with Increased Protease Stability

    International Nuclear Information System (INIS)

    Bang, Jeong Kyu; Nan, Yong Hai; Lee, Eun Kyu; Shin, Song Yub

    2010-01-01

    In order to increase protease stability of a novel Trp-rich model antimicrobial peptide, K 6 L 2 W 3 (KLWKKWKKWLKNH 2 ) and investigate the effect of L-amino acid to peptoid residue conversion on biological functions, we synthesized its antimicrobial peptoid, k 6 l 2 w 3 . Peptoid k 6 l 2 w 3 had similar bacterial selectivity compared to peptide K 6 L 2 W 3 . The bactericidal rate of k 6 l 2 w 3 was somewhat slower than that of K 6 L 2 W 3 . Peptoid k 6 l 2 w 3 exhibited very little dye leakage from bacterial outer-membrane mimicking PE/PG liposomes, as observed in K 6 L 2 W 3 , indicating that the major target site of K 6 L 2 W 3 and k 6 l 2 w 3 may be not the cell membrane but the cytoplasm of bacteria. Trypsin treatment of K 6 L 2 W 3 completely abolished antimicrobial activities against Escherichia coli and Staphylococcus aureus. In contrast, the antimicrobial activity of k 6 l 2 w 3 was completely preserved after trypsin treatment. Taken together, our results suggested that antimicrobial peptoid k 6 l 2 w 3 can potentially serves as a promising therapeutic agent for the treatment of microbial infection

  5. The bile sequestrant cholestyramine increases survival in a rabbit model of brodifacoum poisoning.

    Science.gov (United States)

    Lindeblad, Matthew; Lyubimov, Alexander; van Breemen, Richard; Gierszal, Kamil; Weinberg, Guy; Rubinstein, Israel; Feinstein, Douglas L

    2018-06-12

    Patients exposed to long acting anticoagulant rodenticides (LAARs) are typically administered large amounts of oral vitamin K1 (VK1) to counteract life-threatening anti-coagulant effects. While VK1 treatment effectively prevents mortality, additional methods are needed to reduce the long duration of VK1 treatment which can last for months at high expense. We developed a model of brodifacoum (BDF) poisoning, one of the most potent LAARs, in adult male New Zealand White (NZW) rabbits. The LD50 for oral BDF was determined to be 192 μg/kg, similar to that calculated for adult rats. However, in contrast to rats, NZW rabbits exhibited severe internal hemorrhage including in the brain, symptoms which mimic what occurs in cases of human poisoning. Similar to warfarin, BDF and other LAARs undergo enterohepatic recirculation which contributes to their long half-lives. We therefore tested effects of cholestyramine (CSA), an FDA-approved bile sequestrant, on BDF-induced mortality. When given daily (0.67 gm/kg, oral) starting the day of BDF administration, CSA reduced mortality from 67% to 11%. At the same CSA prevented the increase in clotting time, and reduced the decrease in core body temperature due to BDF. Given its excellent safety record and that it is approved for children older than 6 years, these findings suggest CSA could be considered as an adjunct to VK1 for treatment of LAAR poisoning.

  6. Prior stress exposure increases pain behaviors in a rat model of full thickness thermal injury.

    Science.gov (United States)

    Nyland, Jennifer E; McLean, Samuel A; Averitt, Dayna L

    2015-12-01

    Thermal burns among individuals working in highly stressful environments, such as firefighters and military Service Members, are common. Evidence suggests that pre-injury stress may exaggerate pain following thermal injury; however current animal models of burn have not evaluated the potential influence of pre-burn stress. This sham-controlled study evaluated the influence of prior stress exposure on post-burn thermal and mechanical sensitivity in male Sprague-Dawley rats. Rats were exposed to 20 min of inescapable swim stress or sham stress once per day for three days. Exposure to inescapable swim stress (1) increased the intensity and duration of thermal hyperalgesia after subsequent burn and (2) accelerated the onset of thermal hyperalgesia and mechanical allodynia after subsequent burn. This stress-induced exacerbation of pain sensitivity was reversed by pretreatment and concurrent treatment with the serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine. These data suggest a better understanding of mechanisms by which prior stress augments pain after thermal burn may lead to improved pain treatments for burn survivors. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

  7. Ceres model application for increasing preparedness to climate variability in agricultural planning

    Science.gov (United States)

    Popova, Z.; Kercheva, M.

    2003-04-01

    The paper should demonstrate how knowledge of climate variability and simulation analyses over 30 years could be used to study the vulnerability of maize and wheat ecosystems in the region of Sofia. The procedure of stepwise calibration and validation of agricultural simulation CERES-maize and CERES-wheat models was used at two fields of contrastive soil conditions (Chromic Luvisol and Vertisol). Lysimeters observations under "Chromic Luvisol-maize" combination enabled to test integrally the prediction capacity of CERES-maize, including water and nitrogen fluxes at the boundaries of this vulnerable system over "1.05.1997-1.10.1999" period. The role of soil, crop, climate and irrigation scheduling (under maize only) on drought consequences and groundwater pollution was quantified for four "soil-crop" combinations by CERES models. Four water supply treatments of maize were considered on both soils: one under rainfed conditions and three with varied irrigation application. Water application in initial, development, and mid season growth stages was scheduled by CROPWAT model at any day that soil matrix suction fell to 3.0-3.2 pF with one irrigation scenario and 2.4-2.6 pF with another one. The third drainage-controlling scenario was developed on the basis of 50-75% of the required irrigation depth by satisfying most sensible phases of maize. It was established that "Chromic Luvisol -maize - dry land" combination was associated with the greatest coefficient of variability of yields (Cv=42%) and drought frequency (75% of the years with yield losses more than 20%). Average yield losses in dry vegetation seasons were 60% of the productivity potential under sufficient soil moisture. As a consequence maize cultivation under these conditions was inefficient in 20% of the years when production expenses were greater than losses. Any irrigation practice, even the drainage controlling scenario, mitigated drought consequences on risky soils as Chromic Luvisol by reducing year

  8. Increasing canopy photosynthesis in rice can be achieved without a large increase in water use-A model based on free-air CO2 enrichment.

    Science.gov (United States)

    Ikawa, Hiroki; Chen, Charles P; Sikma, Martin; Yoshimoto, Mayumi; Sakai, Hidemitsu; Tokida, Takeshi; Usui, Yasuhiro; Nakamura, Hirofumi; Ono, Keisuke; Maruyama, Atsushi; Watanabe, Tsutomu; Kuwagata, Tsuneo; Hasegawa, Toshihiro

    2018-03-01

    Achieving higher canopy photosynthesis rates is one of the keys to increasing future crop production; however, this typically requires additional water inputs because of increased water loss through the stomata. Lowland rice canopies presently consume a large amount of water, and any further increase in water usage may significantly impact local water resources. This situation is further complicated by changing the environmental conditions such as rising atmospheric CO 2 concentration ([CO 2 ]). Here, we modeled and compared evapotranspiration of fully developed rice canopies of a high-yielding rice cultivar (Oryza sativa L. cv. Takanari) with a common cultivar (cv. Koshihikari) under ambient and elevated [CO 2 ] (A-CO 2 and E-CO 2 , respectively) via leaf ecophysiological parameters derived from a free-air CO 2 enrichment (FACE) experiment. Takanari had 4%-5% higher evapotranspiration than Koshihikari under both A-CO 2 and E-CO 2 , and E-CO 2 decreased evapotranspiration of both varieties by 4%-6%. Therefore, if Takanari was cultivated under future [CO 2 ] conditions, the cost for water could be maintained at the same level as for cultivating Koshihikari at current [CO 2 ] with an increase in canopy photosynthesis by 36%. Sensitivity analyses determined that stomatal conductance was a significant physiological factor responsible for the greater canopy photosynthesis in Takanari over Koshihikari. Takanari had 30%-40% higher stomatal conductance than Koshihikari; however, the presence of high aerodynamic resistance in the natural field and lower canopy temperature of Takanari than Koshihikari resulted in the small difference in evapotranspiration. Despite the small difference in evapotranspiration between varieties, the model simulations showed that Takanari clearly decreased canopy and air temperatures within the planetary boundary layer compared to Koshihikari. Our results indicate that lowland rice varieties characterized by high-stomatal conductance can play a

  9. LEARNING CYCLE-7E MODEL TO INCREASE STUDENT’S CRITICAL THINKING ON SCIENCE

    Directory of Open Access Journals (Sweden)

    Hartono -

    2013-01-01

    Full Text Available Penelitian ini bertujuan untuk memperoleh model pembelajaran Learning Cycle-7E  yang dapat meningkatkan kemampuan berpikir kritis siswa dan menuntaskan hasil belajar siswa SMPN 21 Semarang terhadap matapelajaran IPA. Penelitian PTK ini dilaksanakan dalam dua siklus. Siklus pertama belum menunjukkan peningkatan yang maksimum. Aktivitas bertanya kepada guru, keseriusan melaksanakan tugas, dan persiapan dalam mengikuti pelajaran masih pada kategori sedang. Ketuntasan belajar secara individual dan klasikal belum memenuhi kriteria yang ditetapkan. Oleh sebab itu, aktivitas ini menjadi fokus perbaikan pada siklus berikutnya. Hasil pada siklus ke-dua menunjukkan peningkatan yang signifikan. Kemampuan berpikir kritis telah tumbuh, aktivitas bertanya pada guru dan keseriusan dalam melaksanakan tugas meningkat pada kategori tinggi. Ketuntasan belajar klasikal sebesar 79%, melebihi kriteria keberhasilan tindakan yang ditetapkan pada penelitian ini yaitu sebesar 75%. Hal ini berarti bahwa model pembelajaran Learning Cycle-7E dapat meningkatkan kemampuan berpikir kritis siswa, tanpa mengganggu hasil belajar kognitifnya. This research aimed to increase the students’ critical thinking by designing Learning Cycle- 7E which is suitable with the criteria set out in SJHS 21 Semarang. Thisclassroom action research was carried out in two cycles. In cycle-I, the students’ critical thinking was growing but not maximum, their activity during learning process was in medium category. That is why there were several aspects of students’ activity that need to be investigated. They were the students’courage to ask the teacher, their seriousness to do the assignments, and their readiness to learn as well as to prepare a question prior learning. The students’ average cognitive learning outcomes and the classical learning outcomes were not very satisfied. The result of the cycle-II showed a significant improvements. The students

  10. Increased thrombin generation in a mouse model of cancer cachexia is partially interleukin-6 dependent.

    Science.gov (United States)

    Reddel, C J; Allen, J D; Ehteda, A; Taylor, R; Chen, V M Y; Curnow, J L; Kritharides, L; Robertson, G

    2017-03-01

    Essentials Cancer cachexia and cancer-associated thrombosis have not previously been mechanistically linked. We assessed thrombin generation and coagulation parameters in cachectic C26 tumor-bearing mice. C26 mice are hypercoagulable, partially corrected by blocking tumor derived interleukin-6. Coagulability and anti-inflammatory interventions may be clinically important in cancer cachexia. Background Cancer cachexia and cancer-associated thrombosis are potentially fatal outcomes of advanced cancer, which have not previously been mechanistically linked. The colon 26 (C26) carcinoma is a well-established mouse model of complications of advanced cancer cachexia, partially dependent on high levels of interleukin-6 (IL-6) produced by the tumor. Objectives To assess if cancer cachexia altered the coagulation state and if this was attributable to tumor IL-6 production. Methods In male BALB/c*DBA2 (F1 hybrid) mice with a C26 tumor we used modified calibrated automated thrombogram and fibrin generation (based on overall hemostatic potential) assays to assess the functional coagulation state, and also examined fibrinogen, erythrocyte sedimentation rate (ESR), platelet count, tissue factor pathway inhibitor (TFPI) and hepatic expression of coagulation factors by microarray. C26 mice were compared with non-cachectic NC26, pair-fed and sham control mice. IL-6 expression in C26 cells was knocked down by lentiviral shRNA constructs. Results C26 mice with significant weight loss and highly elevated IL-6 had elevated thrombin generation, fibrinogen, ESR, platelets and TFPI compared with all control groups. Fibrin generation was elevated compared with pair-fed and sham controls but not compared with NC26 tumor mice. Hepatic expression of coagulation factors and fibrinolytic inhibitors was increased. Silencing IL-6 in the tumor significantly, but incompletely, attenuated the increased thrombin generation, fibrinogen and TFPI. Conclusions Cachectic C26 tumor-bearing mice are in a

  11. Dystropathology Increases Energy Expenditure and Protein Turnover in the Mdx Mouse Model of Duchenne Muscular Dystrophy

    Science.gov (United States)

    Radley-Crabb, Hannah G.; Marini, Juan C.; Sosa, Horacio A.; Castillo, Liliana I.; Grounds, Miranda D.; Fiorotto, Marta L.

    2014-01-01

    The skeletal muscles in Duchenne muscular dystrophy and the mdx mouse model lack functional dystrophin and undergo repeated bouts of necrosis, regeneration, and growth. These processes have a high metabolic cost. However, the consequences for whole body energy and protein metabolism, and on the dietary requirements for these macronutrients at different stages of the disease, are not well-understood. This study used juvenile (4- to 5- wk-old) and adult (12- to 14-wk-old) male dystrophic C57BL/10ScSn-mdx/J and age-matched C57BL/10ScSn/J control male mice to measure total and resting energy expenditure, food intake, spontaneous activity, body composition, whole body protein turnover, and muscle protein synthesis rates. In juvenile mdx mice that have extensive muscle damage, energy expenditure, muscle protein synthesis, and whole body protein turnover rates were higher than in age-matched controls. Adaptations in food intake and decreased activity were insufficient to meet the increased energy and protein needs of juvenile mdx mice and resulted in stunted growth. In (non-growing) adult mdx mice with less severe dystropathology, energy expenditure, muscle protein synthesis, and whole body protein turnover rates were also higher than in age-matched controls. Food intake was sufficient to meet their protein and energy needs, but insufficient to result in fat deposition. These data show that dystropathology impacts the protein and energy needs of mdx mice and that tailored dietary interventions are necessary to redress this imbalance. If not met, the resultant imbalance blunts growth, and may limit the benefits of therapies designed to protect and repair dystrophic muscles. PMID:24586653

  12. An advection-based model to increase the temporal resolution of PIV time series.

    Science.gov (United States)

    Scarano, Fulvio; Moore, Peter

    A numerical implementation of the advection equation is proposed to increase the temporal resolution of PIV time series. The method is based on the principle that velocity fluctuations are transported passively, similar to Taylor's hypothesis of frozen turbulence . In the present work, the advection model is extended to unsteady three-dimensional flows. The main objective of the method is that of lowering the requirement on the PIV repetition rate from the Eulerian frequency toward the Lagrangian one. The local trajectory of the fluid parcel is obtained by forward projection of the instantaneous velocity at the preceding time instant and backward projection from the subsequent time step. The trajectories are approximated by the instantaneous streamlines, which yields accurate results when the amplitude of velocity fluctuations is small with respect to the convective motion. The verification is performed with two experiments conducted at temporal resolutions significantly higher than that dictated by Nyquist criterion. The flow past the trailing edge of a NACA0012 airfoil closely approximates frozen turbulence , where the largest ratio between the Lagrangian and Eulerian temporal scales is expected. An order of magnitude reduction of the needed acquisition frequency is demonstrated by the velocity spectra of super-sampled series. The application to three-dimensional data is made with time-resolved tomographic PIV measurements of a transitional jet. Here, the 3D advection equation is implemented to estimate the fluid trajectories. The reduction in the minimum sampling rate by the use of super-sampling in this case is less, due to the fact that vortices occurring in the jet shear layer are not well approximated by sole advection at large time separation. Both cases reveal that the current requirements for time-resolved PIV experiments can be revised when information is poured from space to time . An additional favorable effect is observed by the analysis in the

  13. Can a model of study activity increase didactic dialogue and students' understanding of learning in IPE?

    DEFF Research Database (Denmark)

    Hansen, Bodil Winther; Hatt, Camusa

    at Metropolitan University College. Since 2013 all UCS have worked with a nationally decided study activity model. The model outlines four different types of learning activities. Students are introduced to courses via the model to heighten their understanding of course design and the expectations...... combining quantitative surveys, interviews, observation and focus groups. Comparisonldiscussion: The presentation will discuss the ambition to optimize dialogue about learning between lecturers and students by using a model of study activity. Results related to the value and potential of the model as seen...... by both lecturers and students will be presented. Findings/results/outcomes/effects: Students point out that the model can be a useful tool to gain an overview of learning activities and the amount of time they are expected to spend in courses. When lecturers introduce courses via the model it deepens...

  14. Increase of carbon cycle feedback with climate sensitivity: results from a coupled climate and carbon cycle model

    International Nuclear Information System (INIS)

    Govindasamy, B.; Thompson, S.; Mirin, A.; Wickett, M.; Caldeira, K.; Delire, C.

    2005-01-01

    Coupled climate and carbon cycle modelling studies have shown that the feedback between global warming and the carbon cycle, in particular the terrestrial carbon cycle, could accelerate climate change and result in greater warming. In this paper we investigate the sensitivity of this feedback for year 2100 global warming in the range of 0 to 8 K. Differing climate sensitivities to increased CO 2 content are imposed on the carbon cycle models for the same emissions. Emissions from the SRES A2 scenario are used. We use a fully coupled climate and carbon cycle model, the INtegrated Climate and CArbon model (INCCA), the NCAR/DOE Parallel Climate Model coupled to the IBIS terrestrial biosphere model and a modified OCMIP ocean biogeochemistry model. In our integrated model, for scenarios with year 2100 global warming increasing from 0 to 8 K, land uptake decreases from 47% to 29% of total CO 2 emissions. Due to competing effects, ocean uptake (16%) shows almost no change at all. Atmospheric CO 2 concentration increases are 48% higher in the run with 8 K global climate warming than in the case with no warming. Our results indicate that carbon cycle amplification of climate warming will be greater if there is higher climate sensitivity to increased atmospheric CO 2 content; the carbon cycle feedback factor increases from 1.13 to 1.48 when global warming increases from 3.2 to 8 K

  15. Fighter Pilot Inventory and Requirements Model; A Ten Year Look with Impact of UAV Increase

    National Research Council Canada - National Science Library

    Garner, Russell S; Villem, Paul A

    2005-01-01

    .... In recent years, Unmanned Aerial Vehicles have become a highly sought after commodity, and the number of UAV billets have increased, with more increases expected in the near future. Currently 45...

  16. A Conceptual Model for Increasing Use of Electronic Medical Records by Primary Care Physicians Through End-User Support.

    Science.gov (United States)

    Randhawa, Gurprit K

    2017-01-01

    A conceptual model for exploring the relationship between end-user support (EUS) and electronic medical record (EMR) use by primary care physicians is presented. The model was developed following a review of conceptual and theoretical frameworks related to technology adoption/use and EUS. The model includes (a) one core construct (facilitating conditions), (b) four antecedents and one postcedent of facilitating conditions, and (c) four moderators. EMR use behaviour is the key outcome of the model. The proposed conceptual model should be tested. The model may be used to inform planning and decision-making for EMR implementations to increase EMR use for benefits realization.

  17. Increased Cortical Gamma-Aminobutyric Acid Precedes Incomplete Extinction of Conditioned Fear and Increased Hippocampal Excitatory Tone in a Mouse Model of Mild Traumatic Brain Injury.

    Science.gov (United States)

    Schneider, Brandy L; Ghoddoussi, Farhad; Charlton, Jennifer L; Kohler, Robert J; Galloway, Matthew P; Perrine, Shane A; Conti, Alana C

    2016-09-01

    Mild traumatic brain injury (mTBI) contributes to development of affective disorders, including post-traumatic stress disorder (PTSD). Psychiatric symptoms typically emerge in a tardive fashion post-TBI, with negative effects on recovery. Patients with PTSD, as well as rodent models of PTSD, demonstrate structural and functional changes in brain regions mediating fear learning, including prefrontal cortex (PFC), amygdala (AMYG), and hippocampus (HC). These changes may reflect loss of top-down control by which PFC normally exhibits inhibitory influence over AMYG reactivity to fearful stimuli, with HC contribution. Considering the susceptibility of these regions to injury, we examined fear conditioning (FC) in the delayed post-injury period, using a mouse model of mTBI. Mice with mTBI displayed enhanced acquisition and delayed extinction of FC. Using proton magnetic resonance spectroscopy ex vivo, we examined PFC, AMYG, and HC levels of gamma-aminobutyric acid (GABA) and glutamate as surrogate measures of inhibitory and excitatory neurotransmission, respectively. Eight days post-injury, GABA was increased in PFC, with no significant changes in AMYG. In animals receiving FC and mTBI, glutamate trended toward an increase and the GABA/glutamate ratio decreased in ventral HC at 25 days post-injury, whereas GABA decreased and GABA/glutamate decreased in dorsal HC. These neurochemical changes are consistent with early TBI-induced PFC hypoactivation facilitating the fear learning circuit and exacerbating behavioral fear responses. The latent emergence of overall increased excitatory tone in the HC, despite distinct plasticity in dorsal and ventral HC fields, may be associated with disordered memory function, manifested as incomplete extinction and enhanced FC recall.

  18. Effects of increasing aerosol on regional climate change in China: Observation and modeling

    Science.gov (United States)

    Qian, Y.; Leung, L.; Ghan, S. J.

    2002-12-01

    We present regional simulations of climate, aerosol properties, and direct radiative forcing and climatic effects of aerosol and analyze the pollutant emissions and observed climatic data during the latter decades of last century in China. The regional model generally captures the spatial distributions and seasonal pattern of temperature and precipitation. Aerosol extinction coefficient and aerosol optical depth are generally well simulated in both magnitude and spatial distribution, which provides a reliable foundation for estimating the radiative forcing and climatic effects of aerosol. The radiative forcing of aerosol is in the range of -1 to -14 W m-2 in autumn and summer and -1 to -9 W m-2 in spring and winter, with substantial spatial variability at the sub-regional scale. A strong maximum in negative radiative forcing corresponding to the maximum optical depth is found over the Sichuan Basin, where emission as well as relative humidity are high, and stagnant atmospheric conditions inhibit pollutants dispersion. Negative radiative forcing of aerosol induces a surface cooling, which is stronger in the range of -0.6 to -1.2oC in autumn and winter than in spring (-0.3 to -0.6oC) and summer (0.0 to -0.9oC) over the Sichuan Basin and East China due to more significant effects of cloud and precipitation in the summer and spring. Aerosol-induced cooling is mainly contributed by cooling in the daytime temperature. The cooling reaches a maximum and is statistically significant in the Sichuan Basin. The effect of aerosol on precipitation is not evident in our simulations. The temporal and spatial patterns of temperature trends observed in the second half of the twentieth century, including the asymmetric daily maximum and minimum temperature trends, are at least qualitatively consistent with the simulated aerosol-induced cooling over the Sichuan Basin and East China. It supports the hypothesis that the observed temperature trends during the latter decades of the

  19. Towards Increased Relevance: Context-Adapted Models of the Learning Organization

    Science.gov (United States)

    Örtenblad, Anders

    2015-01-01

    Purpose: The purposes of this paper are to take a closer look at the relevance of the idea of the learning organization for organizations in different generalized organizational contexts; to open up for the existence of multiple, context-adapted models of the learning organization; and to suggest a number of such models.…

  20. Entrepreneurship Education Revisited: Perceived Entrepreneurial Role Models Increase Perceived Behavioural Control

    Science.gov (United States)

    Fellnhofer, Katharina

    2017-01-01

    Relying on Bandura's (1986) social learning theory, Ajzen's (1988) theory of planned behaviour (TPB), and Dyer's (1994) model of entrepreneurial careers, this study aims to highlight the potential of entrepreneurial role models to entrepreneurship education. The results suggest that entrepreneurial courses would greatly benefit from real-life…

  1. Increased prediction accuracy in wheat breeding trials using a marker × environment interaction genomic selection model.

    Science.gov (United States)

    Lopez-Cruz, Marco; Crossa, Jose; Bonnett, David; Dreisigacker, Susanne; Poland, Jesse; Jannink, Jean-Luc; Singh, Ravi P; Autrique, Enrique; de los Campos, Gustavo

    2015-02-06

    Genomic selection (GS) models use genome-wide genetic information to predict genetic values of candidates of selection. Originally, these models were developed without considering genotype × environment interaction(G×E). Several authors have proposed extensions of the single-environment GS model that accommodate G×E using either covariance functions or environmental covariates. In this study, we model G×E using a marker × environment interaction (M×E) GS model; the approach is conceptually simple and can be implemented with existing GS software. We discuss how the model can be implemented by using an explicit regression of phenotypes on markers or using co-variance structures (a genomic best linear unbiased prediction-type model). We used the M×E model to analyze three CIMMYT wheat data sets (W1, W2, and W3), where more than 1000 lines were genotyped using genotyping-by-sequencing and evaluated at CIMMYT's research station in Ciudad Obregon, Mexico, under simulated environmental conditions that covered different irrigation levels, sowing dates and planting systems. We compared the M×E model with a stratified (i.e., within-environment) analysis and with a standard (across-environment) GS model that assumes that effects are constant across environments (i.e., ignoring G×E). The prediction accuracy of the M×E model was substantially greater of that of an across-environment analysis that ignores G×E. Depending on the prediction problem, the M×E model had either similar or greater levels of prediction accuracy than the stratified analyses. The M×E model decomposes marker effects and genomic values into components that are stable across environments (main effects) and others that are environment-specific (interactions). Therefore, in principle, the interaction model could shed light over which variants have effects that are stable across environments and which ones are responsible for G×E. The data set and the scripts required to reproduce the analysis are

  2. Intravenous infusion of docosahexaenoic acid increases serum concentrations in a dose-dependent manner and increases seizure latency in the maximal PTZ model.

    Science.gov (United States)

    Trépanier, Marc-Olivier; Kwong, Kei-Man; Domenichiello, Anthony F; Chen, Chuck T; Bazinet, Richard P; Burnham, W M

    2015-09-01

    Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) that has been shown to raise seizure thresholds in the maximal pentylenetetrazole model following acute subcutaneous (s.c.) administration in rats. Following s.c. administration, however, the dose-response relationship for DHA has shown an inverted U-pattern. The purposes of the present experiment were as follows: (1) to determine the pattern of serum unesterified concentrations resulting from the intravenous (i.v.) infusions of various doses of DHA, (2) to determine the time course of these concentrations following the discontinuation of the infusions, and (3) to determine whether seizure protection in the maximal PTZ model would correlate with serum unesterified DHA levels. Animals received 5-minute i.v. infusions of saline or 25, 50, 100, or 200mg/kg of DHA via a cannula inserted into one of the tail veins. Blood was collected during and after the infusions by means of a second cannula inserted into the other tail vein (Experiment 1). A separate group of animals received saline or 12.5-, 25-, 50-, 100-, or 200 mg/kg DHA i.v. via a cannula inserted into one of the tail veins and were then seizure-tested in the maximal PTZ model either during infusion or after the discontinuation of the infusions. Slow infusions of DHA increased serum unesterified DHA concentrations in a dose-dependent manner, with the 200-mg/kg dose increasing the concentration approximately 260-fold compared with saline-infused animals. Following discontinuation of the infusions, serum concentrations rapidly dropped toward baseline, with half-lives of approximately 40 and 11s for the 25-mg/kg dose and 100-mg/kg dose, respectively. In the seizure-tested animals, DHA significantly increased latency to seizure onset in a dose-dependent manner. Following the discontinuation of infusion, seizure latency rapidly decreased toward baseline. Overall, our study suggests that i.v. infusion of unesterified DHA results in

  3. Pedicle distraction increases intervertebral and spinal canal area in a cadaver and bone model

    Directory of Open Access Journals (Sweden)

    Hughes Matthew

    2018-01-01

    Discussion: For each increase in pedicle distraction the area of the spinal and vertebral foramen increases. Pedicle distraction could potentially be used to alleviate spinal stenosis and root impingement. A potential osteotomy plane could be at the midpoint of the pedicle with minimal risk to nerve roots and soft tissue restrictions to prevent distraction.

  4. A Model Based Approach to Increase the Part Accuracy in Robot Based Incremental Sheet Metal Forming

    International Nuclear Information System (INIS)

    Meier, Horst; Laurischkat, Roman; Zhu Junhong

    2011-01-01

    One main influence on the dimensional accuracy in robot based incremental sheet metal forming results from the compliance of the involved robot structures. Compared to conventional machine tools the low stiffness of the robot's kinematic results in a significant deviation of the planned tool path and therefore in a shape of insufficient quality. To predict and compensate these deviations offline, a model based approach, consisting of a finite element approach, to simulate the sheet forming, and a multi body system, modeling the compliant robot structure, has been developed. This paper describes the implementation and experimental verification of the multi body system model and its included compensation method.

  5. Overall models and experimental database for UO2 and MOX fuel increasing performance

    International Nuclear Information System (INIS)

    Bernard, L.C.; Blanpain, P.

    2001-01-01

    COPERNIC is an advanced fuel rod performance code developed by Framatome. It is based on the TRANSURANUS code that contains a clear and flexible architecture, and offers many modeling possibilities. The main objectives of COPERNIC are to accurately predict steady-state and transient fuel operations at high burnups and to incorporate advanced materials such as the Framatome M5-alloy cladding. An extensive development program was undertaken to benchmark the code to very high burnups and to new M5-alloy cladding data. New models were developed for the M5-alloy cladding and the COPERNIC thermal models were upgraded and improved to extend the predictions to burnups over 100 GWd/tM. Since key phenomena, like fission gas release, are strongly temperature dependent, many other models were upgraded also. The COPERNIC qualification range extends to 67, 55, 53 GWd/tM respectively for UO 2 , UO 2 -Gd 2 O 3 , and MOX fuels with Zircaloy-4 claddings. The range extends to 63 GWd/tM with UO 2 fuel and the advanced M5-alloy cladding. The paper focuses on thermal and fission gas release models, and on MOX fuel modeling. The COPERNIC thermal model consists of several submodels: gap conductance, gap closure, fuel thermal conductivity, radial power profile, and fuel rim. The fuel thermal conductivity and the gap closure models, in particular, have been significantly improved. The model was benchmarked with 3400 fuel centerline temperature data from many French and international programs. There are no measured to predicted statistical biases with respect to linear heat generation rate or burnup. The overall quality of the model is state-of-the-art as the model uncertainty is below 10 %. The fission gas release takes into account athermal and thermally activated mechanisms. The model was adapted to MOX and Gadolinia fuels. For the heterogeneous MOX MIMAS fuels, an effective burnup is used for the incubation threshold. For gadolinia fuels, a scaled temperature effect is used. The

  6. Using the mouse to model human disease: increasing validity and reproducibility

    Directory of Open Access Journals (Sweden)

    Monica J. Justice

    2016-02-01

    Full Text Available Experiments that use the mouse as a model for disease have recently come under scrutiny because of the repeated failure of data, particularly derived from preclinical studies, to be replicated or translated to humans. The usefulness of mouse models has been questioned because of irreproducibility and poor recapitulation of human conditions. Newer studies, however, point to bias in reporting results and improper data analysis as key factors that limit reproducibility and validity of preclinical mouse research. Inaccurate and incomplete descriptions of experimental conditions also contribute. Here, we provide guidance on best practice in mouse experimentation, focusing on appropriate selection and validation of the model, sources of variation and their influence on phenotypic outcomes, minimum requirements for control sets, and the importance of rigorous statistics. Our goal is to raise the standards in mouse disease modeling to enhance reproducibility, reliability and clinical translation of findings.

  7. Increasing biological diversity in a dynamic vegetation model and consequences for simulated response to climate change

    Science.gov (United States)

    Keribin, R. M.; Friend, A. D.; Purves, D.; Smith, M. J.

    2013-12-01

    Vegetation, from tropical rainforests to the tundra, is the basis of the world food chain but is also a key component of the Earth system, with biophysical and biogeochemical impacts on the global climate, and Dynamic Global Vegetation Models (DGVMs) are an important integrative tool for understanding its responses to climate change. DGVMs up to now have treated only a small number of plant types representing broad divisions in vegetation worldwide (e.g. trees and grasses, broadleaf and needleleaf, deciduousness), but these categories ignore most of the variation that exists between plant species and between individuals within a species. Research in community ecology makes it clear however that these variations can affect large-scale ecosystem properties such as productivity and resilience to environmental changes. The current challenge is for DGVMs to account for fine-grained variations between plants and a few such models are being developed using newly-available plant trait databases such as the TRY database and insights from community ecology such as habitat filtering. Hybrid is an individual-based DGVM, first published in 1993, that models plant physiology in a mechanistic way. We modified Hybrid 8, the latest version of the model which uses surface physics taken from the GISS ModelE GCM, to include a mechanistic gap-model component with individual-based variation in tree wood density. This key plant trait is known to be strongly correlated with a trade-off between growth and mortality in the majority of forests worldwide, which allows for otherwise-similar individuals to have different life-history strategies. We investigate how the inclusion of continuous variation in wood density into the model affects the ecosystem's transient dynamics under climate change.

  8. Tests of the validity of a model relating frequency of contaminated items and increasing radiation dose

    International Nuclear Information System (INIS)

    Tallentire, A.; Khan, A.A.

    1975-01-01

    The 60 Co radiation response of Bacillus pumilus E601 spores has been characterized when present in a laboratory test system. The suitability of test vessels to act as both containers for irradiation and culture vessels in sterility testing has been checked. Tests have been done with these spores to verify assumptions basic to the general model described in a previous paper. First measurements indicate that the model holds with this laboratory test system. (author)

  9. Further Evaluation of a Practitioner Model for Increasing Eye Contact in Children With Autism.

    Science.gov (United States)

    Rapp, John T; Cook, Jennifer L; Nuta, Raluca; Balagot, Carissa; Crouchman, Kayla; Jenkins, Claire; Karim, Sidrah; Watters-Wybrow, Chelsea

    2018-02-01

    Cook et al. recently described a progressive model for teaching children with autism spectrum disorder (ASD) to provide eye contact with an instructor following a name call. The model included the following phases: contingent praise only, contingent edibles plus praise, stimulus prompts plus contingent edibles and praise, contingent video and praise, schedule thinning, generalization assessments, and maintenance evaluations. In the present study, we evaluated the extent to which modifications to the model were needed to train 15 children with ASD to engage in eye contact. Results show that 11 of 15 participants acquired eye contact with the progressive model; however, eight participants required one or more procedural modifications to the model to acquire eye contact. In addition, the four participants who did not acquire eye contact received one or more modifications. Results also show that participants who acquired eye contact with or without modifications continued to display high levels of the behavior during follow-up probes. We discuss directions for future research with and limitations of this progressive model.

  10. Islamic Counselling Model to Increase Religious Commitment (Study of Students at the University UIN Bandung

    Directory of Open Access Journals (Sweden)

    Fenti Hikmawati

    2014-06-01

    Full Text Available The study aims to test the effectiveness of Islamic counseling model for helping the students to tight their religious commitment. The religious commitment is covered in three major Islamic teachings: Iman (faith, Islam (surrender to Allah, and lhsan (state of being observed by Allah. The model of Islamic counseling aims to tight students' religious commitment must to be applied immediately because the preface study reveals some students' religious commitment were not strong enough, their behavior and thinking symptoms tend to not appropriate yet with Islam norm among their association and conception toward the truth of God. To achieve the aim, the study was carried out with three steps: (1 designing a model of counseling; (2 trying out field study, using pretest-post test control group experimental design with 140 students of Islamic Religion Education, the Faculty of Tarbiyah and Teaching, State Islamic University, Sunan Gunung Djati, Bandung. Of 140 students, 70 students are from the classes: A (32 people, B (38 people, involved in control group and the test; 37 people from class C, and 33 students from class D involved in the experiment group, and; (3 designing a final model by revising the model tried-out. The variable involved three major Islamic dimensions: the iman, Islam, and ihsan of the students. The model was designed based on the theory put forward by Musfir bin Said Az-Zalmmi, that is, an integrated counseling model. The model combines and employs the ideas from other concepts into a tightly united concept, called Islamic concept. Upon completing analysis, it was found that the new concept is significantly effective to enhance students' religious commitment. A Model of Islamic Counseling (MIC is an alternative-counseling model that can be employed for teenagers/ students to enhance their religious commitment. The study recommends that: (1 MIC can be applied to fifth semester students in the Faculty of Tarbiyah State Islamic

  11. Increasingly, Data Availability Limits Model Predictive Capacity: the Western Lake Erie Basin, a Case Study

    Science.gov (United States)

    Behrman, K. D.; Johnson, M. V. V.; Atwood, J. D.; Norfleet, M. L.

    2016-12-01

    Recent algal blooms in Western Lake Erie Basin (WLEB) have renewed scientific community's interest in developing process based models to better understand and predict the drivers of eutrophic conditions in the lake. At the same time, in order to prevent future blooms, farmers, local communities and policy makers are interested in developing spatially explicit nutrient and sediment management plans at various scales, from field to watershed. These interests have fueled several modeling exercises intended to locate "hotspots" in the basin where targeted adoption of additional agricultural conservation practices could provide the most benefit to water quality. The models have also been used to simulate various scenarios representing potential agricultural solutions. The Soil and Water Assessment Tool (SWAT) and its sister model, the Agricultural Policy Environmental eXtender (APEX), have been used to simulate hydrology of interacting land uses in thousands of scientific studies around the world. High performance computing allows SWAT and APEX users to continue to improve and refine the model specificity to make predictions at small-spatial scales. Consequently, data inputs and calibration/validation data are now becoming the limiting factor to model performance. Water quality data for the tributaries and rivers that flow through WLEB is spatially and temporally limited. Land management data, including conservation practice and nutrient management data, are not publicly available at fine spatial and temporal scales. Here we show the data uncertainties associated with modeling WLEB croplands at a relatively large spatial scale (HUC-4) using site management data from over 1,000 farms collected by the Conservation Effects Assessment Project (CEAP). The error associated with downscaling this data to the HUC-8 and HUC-12 scale is shown. Simulations of spatially explicit dynamics can be very informative, but care must be taken when policy decisions are made based on models

  12. Evolutionary Modeling Predicts a Decrease in Postcopulatory Sperm Viability as a Response to Increasing Levels of Sperm Competition

    NARCIS (Netherlands)

    Engqvist, Leif

    Sperm competition has been found to have a strong influence on the evolution of many male and female reproductive traits. Theoretical models have shown that, with increasing levels of sperm competition, males are predicted to increase ejaculate investment, and there is ample empirical evidence

  13. Examining the impacts of increased corn production on groundwater quality using a coupled modeling system

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset was used to create graphics associated with manuscript: Garcia et al., Examining the impacts of increased corn production on groundwater quality using a...

  14. High-anxious individuals show increased chronic stress burden, decreased protective immunity, and increased cancer progression in a mouse model of squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Firdaus S Dhabhar

    Full Text Available In spite of widespread anecdotal and scientific evidence much remains to be understood about the long-suspected connection between psychological factors and susceptibility to cancer. The skin is the most common site of cancer, accounting for nearly half of all cancers in the US, with approximately 2-3 million cases of non-melanoma cancers occurring each year worldwide. We hypothesized that a high-anxious, stress-prone behavioral phenotype would result in a higher chronic stress burden, lower protective-immunity, and increased progression of the immuno-responsive skin cancer, squamous cell carcinoma. SKH1 mice were phenotyped as high- or low-anxious at baseline, and subsequently exposed to ultraviolet-B light (1 minimal erythemal dose (MED, 3 times/week, 10-weeks. The significant strengths of this cancer model are that it uses a normal, immunocompetent, outbred strain, without surgery/injection of exogenous tumor cells/cell lines, and produces lesions that resemble human tumors. Tumors were counted weekly (primary outcome, and tissues collected during early and late phases of tumor development. Chemokine/cytokine gene-expression was quantified by PCR, tumor-infiltrating helper (Th, cytolytic (CTL, and regulatory (Treg T cells by immunohistochemistry, lymph node T and B cells by flow cytometry, adrenal and plasma corticosterone and tissue vascular-endothelial-growth-factor (VEGF by ELISA. High-anxious mice showed a higher tumor burden during all phases of tumor development. They also showed: higher corticosterone levels (indicating greater chronic stress burden, increased CCL22 expression and Treg infiltration (increased tumor-recruited immuno-suppression, lower CTACK/CCL27, IL-12, and IFN-γ gene-expression and lower numbers of tumor infiltrating Th and CTLs (suppressed protective immunity, and higher VEGF concentrations (increased tumor angiogenesis/invasion/metastasis. These results suggest that the deleterious effects of high trait anxiety

  15. A model for increasing appreciation, accessibility and application of research in nursing.

    Science.gov (United States)

    Edward, Karen-Leigh

    2015-01-01

    The confidence and engagement of nurses (and midwives) in research are an area for continued development. The Research Appreciation, Accessibility, and Application Model (RAAAM), developed in 2011, provides a framework for enhancing research activities by nurses within the clinical setting. Unlike other models, the RAAAM does not assume a preexisting capacity or knowledge of research; however, the model incorporates the multiple research activities that comprise a research culture. Although it is acknowledged that undertaking a research project is not for everyone, using evidence-based knowledge for practice development is essential and relates to all clinical staff. The RAAAM model presents four domains-research appreciation, research accessibility, research application, and research sustainability. Research appreciation is a first step in realizing the potential beneficial impact of research in practice. Relating these activities to identified key result areas that are drawn from key stakeholders completes the loop, ensuring sustainability of research activities and processes. The model presented here offers a practical and user-friendly approach for research enhancement in nursing using the platform of a clinical and academic partnership. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. An auto-focusing heuristic model to increase the reliability of a scientific mission

    International Nuclear Information System (INIS)

    Gualdesi, Lavinio

    2006-01-01

    Researchers invest a lot of time and effort on the design and development of components used in a scientific mission. To capitalize on this investment and on the operational experience of the researchers, it is useful to adopt a quantitative data base to monitor the history and usage of the components. This work describes a model to monitor the reliability level of components. The model is very flexible and allows users to compose systems using the same components in different configurations as required by each mission. This tool provides availability and reliability figures for the configuration requested, derived from historical data of the components' previous performance. The system is based on preliminary checklists to establish standard operating procedures (SOP) for all components life phases. When an infringement to the SOP occurs, a quantitative ranking is provided in order to quantify the risk associated with this deviation. The final agreement between field data and expected performance of the component makes the model converge onto a heuristic monitoring system. The model automatically focuses on points of failure at the detailed component element level, calculates risks, provides alerts when a demonstrated risk to safety is encountered, and advises when there is a mismatch between component performance and mission requirements. This model also helps the mission to focus resources on critical tasks where they are most needed

  17. Using a High-Performance Planning Model to Increase Levels of Functional Effectiveness Within Professional Development.

    Science.gov (United States)

    Winter, Peggi

    2016-01-01

    Nursing professional practice models continue to shape how we practice nursing by putting families and members at the heart of everything we do. Faced with enormous challenges around healthcare reform, models create frameworks for practice by unifying, uniting, and guiding our nurses. The Kaiser Permanente Practice model was developed to ensure consistency for nursing practice across the continuum. Four key pillars support this practice model and the work of nursing: quality and safety, leadership, professional development, and research/evidence-based practice. These four pillars form the foundation that makes transformational practice possible and aligns nursing with Kaiser Permanente's mission. The purpose of this article is to discuss the pillar of professional development and the components of the Nursing Professional Development: Scope and Standards of Practice model (American Nurses Association & National Nursing Staff Development Organization, 2010) and place them in a five-level development framework. This process allowed us to identify the current organizational level of practice, prioritize each nursing professional development component, and design an operational strategy to move nursing professional development toward a level of high performance. This process is suggested for nursing professional development specialists.

  18. Pedicle distraction increases intervertebral and spinal canal area in a cadaver and bone model.

    Science.gov (United States)

    Hughes, Matthew; Papadakos, Nikolaos; Bishop, Tim; Bernard, Jason

    2018-01-01

    Lumbar spinal stenosis is degenerative narrowing of the spinal canal and/or intervertebral foramen causing compression of the spinal cord and nerve roots. Traditional decompression techniques can often cause significant trauma and vertebral instability. This paper evaluates a method of increasing pedicle length to decompress the spinal and intervertebral foramen, which could be done minimally invasive. Three Sawbone (Sawbones Europe, Sweden) and 1 cadaveric lumbar spine underwent bilateral pedicle distraction at L4. A pedicle channel was drilled between the superior articular process and transverse process into the vertebral body. The pedicles underwent osteotomy at the midpoint. Screws were inserted bilaterally and fixated distraction of 0 mm, 2 mm, 4 mm and 6 mm. CT images were taken at each level of distraction. Foramen area was measured in the sagittal plane at L3/4. Spinal canal area was measured at L4 in the axial images. The cadaver was used to evaluate safety of osteotomy and soft tissue interactions preventing distraction. Statistical analysis was by student paired t-test and Pearson rank test. Increasing distraction led to greater Spinal canal area. From 4.27 cm 2 to 5.72 cm 2 (p = 0.002) with 6 mm distraction. A Maximal increase of 34.1%. Vertebral foramen area also increased with increasing pedicle distraction. From 2.43 cm 2 to 3.22 cm 2 (p = 0.022) with 6 mm distraction. A maximal increase of 32.3%. The cadaver spinal canal increased in area by 21.7%. The vertebral foramen increased in area by 36.2% (left) and 22.6% (right). For each increase in pedicle distraction the area of the spinal and vertebral foramen increases. Pedicle distraction could potentially be used to alleviate spinal stenosis and root impingement. A potential osteotomy plane could be at the midpoint of the pedicle with minimal risk to nerve roots and soft tissue restrictions to prevent distraction. © The Authors, published by EDP Sciences, 2018.

  19. A predictive modeling approach to increasing the economic effectiveness of disease management programs.

    Science.gov (United States)

    Bayerstadler, Andreas; Benstetter, Franz; Heumann, Christian; Winter, Fabian

    2014-09-01

    Predictive Modeling (PM) techniques are gaining importance in the worldwide health insurance business. Modern PM methods are used for customer relationship management, risk evaluation or medical management. This article illustrates a PM approach that enables the economic potential of (cost-) effective disease management programs (DMPs) to be fully exploited by optimized candidate selection as an example of successful data-driven business management. The approach is based on a Generalized Linear Model (GLM) that is easy to apply for health insurance companies. By means of a small portfolio from an emerging country, we show that our GLM approach is stable compared to more sophisticated regression techniques in spite of the difficult data environment. Additionally, we demonstrate for this example of a setting that our model can compete with the expensive solutions offered by professional PM vendors and outperforms non-predictive standard approaches for DMP selection commonly used in the market.

  20. Accounting for Local Dependence with the Rasch Model: The Paradox of Information Increase.

    Science.gov (United States)

    Andrich, David

    Test theories imply statistical, local independence. Where local independence is violated, models of modern test theory that account for it have been proposed. One violation of local independence occurs when the response to one item governs the response to a subsequent item. Expanding on a formulation of this kind of violation between two items in the dichotomous Rasch model, this paper derives three related implications. First, it formalises how the polytomous Rasch model for an item constituted by summing the scores of the dependent items absorbs the dependence in its threshold structure. Second, it shows that as a consequence the unit when the dependence is accounted for is not the same as if the items had no response dependence. Third, it explains the paradox, known, but not explained in the literature, that the greater the dependence of the constituent items the greater the apparent information in the constituted polytomous item when it should provide less information.

  1. UNIRAM modeling for increased nuclear-plant availability and life extension

    International Nuclear Information System (INIS)

    O'Mara, R.L.

    1988-01-01

    At the start of a nuclear-power plant's design life of 40 years, most parts of the plant are effectively brand new, but some subcomponents have already experienced significant wear and aging effects. In short, the spectrum of where each component is in its life cycle at any time is quite broad, and this makes the prediction of the future availability of the plant a complex issue. Predictive models that account for the differential effects of aging, wear, and functional failure on the plant are desirable as a means to represent this complex behavior. This paper addresses the task of using a computer model to account for the relationships between components, systems, and plant availability, in the context of current and future needs, including eventual life extension. The computer model is based on the Electric Power Research Institute's (EPRI) code, UNIRAM, which has a large and growing user base among utilities

  2. Increased Tidal Dissipation Using Advanced Rheological Models: Implications for Io and Tidally Active Exoplanets

    Science.gov (United States)

    Renaud, Joe P.; Henning, Wade G.

    2018-04-01

    The advanced rheological models of Andrade and Sundberg & Cooper are compared to the traditional Maxwell model to understand how each affects the tidal dissipation of heat within rocky bodies. We find both Andrade and Sundberg–Cooper rheologies can produce at least 10× the tidal heating compared to a traditional Maxwell model for a warm (1400–1600 K) Io-like satellite. Sundberg–Cooper can cause even larger dissipation around a critical temperature and frequency. These models allow cooler planets to stay tidally active in the face of orbital perturbations—a condition we term “tidal resilience.” This has implications for the time evolution of tidally active worlds and the long-term equilibria they fall into. For instance, if Io’s interior is better modeled by the Andrade or Sundberg–Cooper rheologies, the number of possible resonance-forming scenarios that still produce a hot, modern Io is expanded, and these scenarios do not require an early formation of the Laplace resonance. The two primary empirical parameters that define the Andrade anelasticity are examined in several phase spaces to provide guidance on how their uncertainties impact tidal outcomes, as laboratory studies continue to constrain their real values. We provide detailed reference tables on the fully general equations required for others to insert the models of Andrade and Sundberg–Cooper into standard tidal formulae. Lastly, we show that advanced rheologies can greatly impact the heating of short-period exoplanets and exomoons, while the properties of tidal resilience could mean a greater number of tidally active worlds among all extrasolar systems.

  3. A model to obtain an optimum erbium desity for gain increasing in EDFA

    Directory of Open Access Journals (Sweden)

    E. Arzi

    2003-12-01

    Full Text Available   In this paper, we suggest a novel model, based on input pump power and wave guidestructure, to calculate the Er-density profile in Erbium doped fiber amplifiers. This optimization is carried out for both SMF and DSF fibers. These optimized profiles have a Gaussian-like shape. Using the SMF optimized Er-density profile, high gain enhancement is obtained in a relatively short length of fibers. On the other hand, the DSF optimized profile shows small changes in the gain, which agrees with the previously report on other method of gain enhancement. This model is applicable to all active waveguides and any other dopant as well .

  4. Higher measured than modeled ozone production at increased NOx levels in the Colorado Front Range

    Directory of Open Access Journals (Sweden)

    B. C. Baier

    2017-09-01

    Full Text Available Chemical models must correctly calculate the ozone formation rate, P(O3, to accurately predict ozone levels and to test mitigation strategies. However, air quality models can have large uncertainties in P(O3 calculations, which can create uncertainties in ozone forecasts, especially during the summertime when P(O3 is high. One way to test mechanisms is to compare modeled P(O3 to direct measurements. During summer 2014, the Measurement of Ozone Production Sensor (MOPS directly measured net P(O3 in Golden, CO, approximately 25 km west of Denver along the Colorado Front Range. Net P(O3 was compared to rates calculated by a photochemical box model that was constrained by measurements of other chemical species and that used a lumped chemical mechanism and a more explicit one. Median observed P(O3 was up to a factor of 2 higher than that modeled during early morning hours when nitric oxide (NO levels were high and was similar to modeled P(O3 for the rest of the day. While all interferences and offsets in this new method are not fully understood, simulations of these possible uncertainties cannot explain the observed P(O3 behavior. Modeled and measured P(O3 and peroxy radical (HO2 and RO2 discrepancies observed here are similar to those presented in prior studies. While a missing atmospheric organic peroxy radical source from volatile organic compounds co-emitted with NO could be one plausible solution to the P(O3 discrepancy, such a source has not been identified and does not fully explain the peroxy radical model–data mismatch. If the MOPS accurately depicts atmospheric P(O3, then these results would imply that P(O3 in Golden, CO, would be NOx-sensitive for more of the day than what is calculated by models, extending the NOx-sensitive P(O3 regime from the afternoon further into the morning. These results could affect ozone reduction strategies for the region surrounding Golden and possibly other areas that do not comply with national ozone

  5. Modeling of the climate system and of its response to a greenhouse effect increase

    International Nuclear Information System (INIS)

    Li, L.

    2005-01-01

    The anthropic disturbance of the Earth's greenhouse effect is already visible and will enhance in the coming years or decades. In front of the rapidity and importance of the global warming effect, the socio-economical management of this change will rise problems and must be studied by the scientific community. At the modeling level, finding a direct strategy for the validation of climate models is not easy: many uncertainties exist because energy transformations take place at a low level and several processes take place at the same time. The variability observed at the seasonal, inter-annual or paleo- scales allows to validate the models at the process level but not the evolution of the whole system. The management of these uncertainties is an integral part of the global warming problem. Thus, several scenarios can be proposed and their risk of occurrence must be estimated. This paper presents first the greenhouse effect, the climatic changes during geologic times, the anthropic disturbance of the greenhouse effect, the modeling of climate and the forecasting of its evolution. (J.S.)

  6. Time series modelling of increased soil temperature anomalies during long period

    Science.gov (United States)

    Shirvani, Amin; Moradi, Farzad; Moosavi, Ali Akbar

    2015-10-01

    Soil temperature just beneath the soil surface is highly dynamic and has a direct impact on plant seed germination and is probably the most distinct and recognisable factor governing emergence. Autoregressive integrated moving average as a stochastic model was developed to predict the weekly soil temperature anomalies at 10 cm depth, one of the most important soil parameters. The weekly soil temperature anomalies for the periods of January1986-December 2011 and January 2012-December 2013 were taken into consideration to construct and test autoregressive integrated moving average models. The proposed model autoregressive integrated moving average (2,1,1) had a minimum value of Akaike information criterion and its estimated coefficients were different from zero at 5% significance level. The prediction of the weekly soil temperature anomalies during the test period using this proposed model indicated a high correlation coefficient between the observed and predicted data - that was 0.99 for lead time 1 week. Linear trend analysis indicated that the soil temperature anomalies warmed up significantly by 1.8°C during the period of 1986-2011.

  7. Dystropathology increases energy expenditure and protein turnover in the Mdx mouse model of Duchenne muscular dystrophy

    Science.gov (United States)

    The skeletal muscles in Duchenne muscular dystrophy and the mdx mouse model lack functional dystrophin and undergo repeated bouts of necrosis, regeneration, and growth. These processes have a high metabolic cost. However, the consequences for whole body energy and protein metabolism, and on the diet...

  8. Modeling Method for Increased Precision and Scope of Directly Measurable Fluxes at a Genome-Scale

    DEFF Research Database (Denmark)

    McCloskey, Douglas; Young, Jamey D.; Xu, Sibei

    2016-01-01

    pathways of traditional MFA models and also covers the additional pathways of purine, pyrimidine, isoprenoid, methionine, riboflavin, coenzyme A, and folate, as well as other biosynthetic pathways. When evaluating the iDM2014 using a set of measured intracellular intermediate and cofactor mass isotopomer...

  9. Increasing Energy Access in Sub-Saharan Africa: Exploring Public-Private Models for Intervention

    Energy Technology Data Exchange (ETDEWEB)

    Bazilian, Morgan; Pless, Jacquelyn

    2014-01-16

    This report, by Morgan Bazilian and Jacquelyn Pless, examines ways that Energy+ could make a large impact in providing energy access to the poor, focusing on four promising models. While there remains a focus on a technology (PV), and a region (SSA) in this report, the models the authors explore are amenable to other specifications as well. Thus, the models presented provide an opportunity for stakeholders and the international community to collaborate and leverage capacities, resources, and networks. Of course, these models are only a few of the very wide range of possible mechanisms. They also are somewhat focused on engaging the private sector. The report does not provide a full context for the complex landscape of energy access and energy poverty. Rather, the paper is focused around the specifics of the interventions. It remains the case that the fundamental building blocks of capacity building, good governance and planning, and the ability to find funding for 'upfront' due diligence and analysis remain critical. Those items are, however, largely outside the scope of this short report.

  10. Integrating quality improvement and translational research models to increase exclusive breastfeeding.

    Science.gov (United States)

    Brown, Peggy A; Kaiser, Katherine Laux; Nailon, Regina E

    2014-01-01

    Exclusive breastfeeding (EBF), a perinatal core measure, is associated with a longer duration of breastfeeding. The purpose of this quality improvement project was to increase the percent of healthy term singleton newborns who were exclusively breastfed at an academic medical center in the Midwest. Implementation of skin-to-skin contact between mother and newborn immediately following birth resulted in an increase in the percent of healthy term singleton newborns who were EBF from 55% to 64%. © 2014 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

  11. Bullying in an Increasingly Diverse School Population: A Socio-Ecological Model Analysis

    Science.gov (United States)

    Lim, Seok Jeng Jane; Hoot, James L.

    2015-01-01

    Systematic research into bullying has a short history spanning about 40 years. However, investigations into school bullying from a multicultural context are especially limited. As schools in the 21st century become increasingly diverse due to rapid globalization and immigration, there is a need to consider bullying within changing populations. The…

  12. Increase of hepatic nitric oxide levels in a nutritional model of fatty ...

    African Journals Online (AJOL)

    Fatty liver hemorrhagic syndrome (FLHS) is a metabolic condition of laying hens characterized by the accumulation of excess fat in the liver and liver hemorrhage. It suggested that oxidative damage to the cellular and organelle membranes of the liver increases the susceptibility of the liver to hemorrhage. However, a local ...

  13. Increased lipolysis and energy expenditure in a mouse model with severely impaired glucagon secretion

    DEFF Research Database (Denmark)

    Lou, Phing-How; Gustavsson, Natalia; Wang, Yue

    2011-01-01

    and increased capacity for fatty acid transport and oxidation in synaptotagmin-7 KO mice. Furthermore, expression of uncoupling protein 3 (UCP3) in skeletal muscle was approximately doubled in the KO mice compared with control mice. CONCLUSIONS: These results show that the lean phenotype in synaptotagmin-7 KO...

  14. Modeling Effectiveness of Gradual Increases in Source Level to Mitigate Effects of Sonar on Marine Mammals

    NARCIS (Netherlands)

    Benda-Beckmann, A.M. von; Wensveen, P.J.; Kvadsheim, P.H.; Lam, F.P.A.; Miller, P.J.O.; Tyack, P.L.; Ainslie, M.A.

    2013-01-01

    Ramp-up or soft-start procedures (i.e., gradual increase in the source level) are used to mitigate the effect of sonar sound on marine mammals, although no one to date has tested whether ramp-up procedures are effective at reducing the effect of sound on marine mammals. We investigated the

  15. Increasing part-time working hours in the Netherlands. Identifying policy recommendations through Group Model Building

    NARCIS (Netherlands)

    Bleijenbergh, I.L.; Fokkinga, B.L.A.

    2013-01-01

    With 73% of women and 19% of men working part-time,the Netherlands is known as the champion of part-time work. In order to increase especially the working hours of women with small part-time jobs (less than 20 hours per week) the Dutch government installed a thinktank of employers, employees

  16. Ureteral growth in animal models with increased renal excretion of urine

    DEFF Research Database (Denmark)

    Thulesen, J; Poulsen, Steen Seier; Nexø, Ebba

    1999-01-01

    The influence of increased functional load on the macroscopical and histological appearance of the ureter was investigated. Sixty rats were divided into five groups: (1) sucrose-fed rats with non-osmotic polyuria; (2) diabetic rats with osmotic polyuria; (3) uninephrectomized rats; (4) sham-opera...

  17. N-acetylcysteine manipulation fails to elicit an increase in glutathione in a teleost model

    DEFF Research Database (Denmark)

    Birnie-Gauvin, Kim; Larsen, Martin Hage; Aarestrup, Kim

    2018-01-01

    and vegetable shortening, at two different concentrations (100 and 400 mg/kg), with the appropriate controls and shams, under controlled laboratory settings. We found that NAC failed to elicit an increase in GSH over three time periods and concluded that NAC is not an effective method to enhance GSH levels...

  18. Breast-cancer-associated metastasis is significantly increased in a model of autoimmune arthritis.

    Science.gov (United States)

    Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

    2009-01-01

    Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor-alpha (TNF-alpha) may contribute

  19. Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis

    Science.gov (United States)

    Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

    2009-01-01

    Introduction Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. Methods To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. Results We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor

  20. Vorinostat increases expression of functional norepinephrine transporter in neuroblastoma in vitro and in vivo model systems

    Science.gov (United States)

    More, Swati S.; Itsara, Melissa; Yang, Xiaodong; Geier, Ethan G.; Tadano, Michelle K.; Seo, Youngho; VanBrocklin, Henry F.; Weiss, William A.; Mueller, Sabine; Haas-Kogan, Daphne A.; DuBois, Steven G.; Matthay, Katherine K.; Giacomini, Kathleen M.

    2011-01-01

    Purpose Histone deacetylase (HDAC) inhibition causes transcriptional activation or repression of several genes that in turn can influence the biodistribution of other chemotherapeutic agents. Here, we hypothesize that the combination of vorinostat, a HDAC inhibitor, with 131I-metaiodobenzylguanidine (MIBG) would lead to preferential accumulation of the latter in neuroblastoma (NB) tumors via increased expression of the human norepinephrine transporter (NET). Experimental Design In vitro and in vivo experiments examined the effect of vorinostat on the expression of NET, an uptake transporter for 131I-MIBG. Human NB cell lines (Kelly and SH-SY-5Y) and NB1691luc mouse xenografts were employed. The upregulated NET protein was characterized for its effect on 123I-MIBG biodistribution. Results Preincubation of NB cell lines, Kelly and SH-SY-5Y, with vorinostat caused dose-dependent increases in NET mRNA and protein levels. Accompanying this was a corresponding dose-dependent increase in MIBG uptake in NB cell lines. Four-fold and 2.5 fold increases were observed in Kelly and SH-SY-5Y cells, respectively, pre-treated with vorinostat in comparison to untreated cells. Similarly, NB xenografts, created by intravenous tail vein injection of NB1691-luc, and harvested from nude mice livers treated with vorinostat (150 mg/kg i.p.) showed substantial increases in NET protein expression. Maximal effect of vorinostat pretreatment in NB xenografts on 123I-MIBG biodistribution was observed in tumors that exhibited enhanced uptake in vorinostat treated (0.062 ± 0.011 μCi/(mg tissue-dose injected)) versus untreated mice (0.022 ± 0.003 μCi/(mg tissue-dose injected); p vorinostat treatment can enhance NB therapy with 131I-MIBG. PMID:21421857

  1. Increasing economic stability of the industrial enterprise as a result of its market value modeling

    Directory of Open Access Journals (Sweden)

    Efimova M.G.

    2017-01-01

    Full Text Available The article deals with an urgent problem of the Russian and global economic stability. The issues of management of the modern industrial enterprise in the conditions of variable economy are considered in this research. Also the article highlights the importance of evaluation of industrial enterprises in Russia nowadays. The management model of the industrial enterprise cost based on sustainability criteria is constructed. The author focuses on new approaches to mathematic modeling of business evaluation. The article contains graphs and charts related to performance of enterprise system and different business strategies based on economic sustainability. Relevant problems of management by means of business assessment for enterprises owners and top managers are defined. The aim of the article is to suggest measures for the Russian industry to manage the cost of enterprises and consequently, to make national economy management more effective.

  2. The flipped classroom: A learning model to increase student engagement not academic achievement

    OpenAIRE

    Masha Smallhorn

    2017-01-01

    A decrease in student attendance at lectures both nationally and internationally, has prompted educators to re-evaluate their teaching methods and investigate strategies which promote student engagement. The flipped classroom model, grounded in active learning pedagogy, transforms the face-to-face classroom. Students prepare for the flipped classroom in their own time by watching short online videos and completing readings. Face-to-face time is used to apply learning through problem-solving w...

  3. Development of E-Book Multimedia Model to Increase Critical Thinking of Senior High School Students

    OpenAIRE

    Suparno Suparno

    2018-01-01

    This study aims to develop the interactive e-book multimedia model to improve the students' critical thinking ability (KBK). Critical thinking is very important to develop because it provides a high level of reasoning thinking that provides permanent experience to students through conscious and controlled decision making in a rational, reflective, responsible manner with the optimization of potential. Flash-based e-book media is capable of interactively loading videos, pictures, practice ques...

  4. Recalibrating disease parameters for increasing realism in modeling epidemics in closed settings

    Directory of Open Access Journals (Sweden)

    Livio Bioglio

    2016-11-01

    Full Text Available Abstract Background The homogeneous mixing assumption is widely adopted in epidemic modelling for its parsimony and represents the building block of more complex approaches, including very detailed agent-based models. The latter assume homogeneous mixing within schools, workplaces and households, mostly for the lack of detailed information on human contact behaviour within these settings. The recent data availability on high-resolution face-to-face interactions makes it now possible to assess the goodness of this simplified scheme in reproducing relevant aspects of the infection dynamics. Methods We consider empirical contact networks gathered in different contexts, as well as synthetic data obtained through realistic models of contacts in structured populations. We perform stochastic spreading simulations on these contact networks and in populations of the same size under a homogeneous mixing hypothesis. We adjust the epidemiological parameters of the latter in order to fit the prevalence curve of the contact epidemic model. We quantify the agreement by comparing epidemic peak times, peak values, and epidemic sizes. Results Good approximations of the peak times and peak values are obtained with the homogeneous mixing approach, with a median relative difference smaller than 20 % in all cases investigated. Accuracy in reproducing the peak time depends on the setting under study, while for the peak value it is independent of the setting. Recalibration is found to be linear in the epidemic parameters used in the contact data simulations, showing changes across empirical settings but robustness across groups and population sizes. Conclusions An adequate rescaling of the epidemiological parameters can yield a good agreement between the epidemic curves obtained with a real contact network and a homogeneous mixing approach in a population of the same size. The use of such recalibrated homogeneous mixing approximations would enhance the accuracy and

  5. Recalibrating disease parameters for increasing realism in modeling epidemics in closed settings.

    Science.gov (United States)

    Bioglio, Livio; Génois, Mathieu; Vestergaard, Christian L; Poletto, Chiara; Barrat, Alain; Colizza, Vittoria

    2016-11-14

    The homogeneous mixing assumption is widely adopted in epidemic modelling for its parsimony and represents the building block of more complex approaches, including very detailed agent-based models. The latter assume homogeneous mixing within schools, workplaces and households, mostly for the lack of detailed information on human contact behaviour within these settings. The recent data availability on high-resolution face-to-face interactions makes it now possible to assess the goodness of this simplified scheme in reproducing relevant aspects of the infection dynamics. We consider empirical contact networks gathered in different contexts, as well as synthetic data obtained through realistic models of contacts in structured populations. We perform stochastic spreading simulations on these contact networks and in populations of the same size under a homogeneous mixing hypothesis. We adjust the epidemiological parameters of the latter in order to fit the prevalence curve of the contact epidemic model. We quantify the agreement by comparing epidemic peak times, peak values, and epidemic sizes. Good approximations of the peak times and peak values are obtained with the homogeneous mixing approach, with a median relative difference smaller than 20 % in all cases investigated. Accuracy in reproducing the peak time depends on the setting under study, while for the peak value it is independent of the setting. Recalibration is found to be linear in the epidemic parameters used in the contact data simulations, showing changes across empirical settings but robustness across groups and population sizes. An adequate rescaling of the epidemiological parameters can yield a good agreement between the epidemic curves obtained with a real contact network and a homogeneous mixing approach in a population of the same size. The use of such recalibrated homogeneous mixing approximations would enhance the accuracy and realism of agent-based simulations and limit the intrinsic biases of

  6. A hybrid model of QFD, SERVQUAL and KANO to increase bank's capabilities

    Directory of Open Access Journals (Sweden)

    Hasan Rajabi

    2012-10-01

    Full Text Available In global market, factors such as precedence of competitors extending shave on market, promoting quality of services and identifying customers' needs are important. This paper attempts to identify strategic services in one of the biggest governmental banks in Iran called Melli bank for getting competition merit using Kano and SERVQUAL compound models and to extend operation quality and to provide suitable strategies. The primary question of this paper is on how to introduce high quality services in this bank. The proposed model of this paper uses a hybrid of three quality-based methods including SERVQUAL, QFD and Kano models. Statistical society in this article is all clients and customers of Melli bank who use this banks' services and based on random sampling method, 170 customers were selected. The study was held in one of provinces located in west part of Iran called Semnan. Research findings show that Melli banks' customers are dissatisfied from the quality of services and to solve this problem the bank should do some restructuring to place some special characteristics to reach better operation at the heed of its affairs. The characteristics include, in terms of their priorities, possibility of transferring money by sale terminal, possibility of creating wireless pos, accelerating in doing bank works, getting special merits to customers who use electronic services, eliminating such bank commission, solving problems in least time as disconnecting system, possibility of receiving foreign exchange by ATM and suitable parking in city.

  7. Accuracy increase of the coordinate measurement based on the model production of geometrical parts specifications

    Science.gov (United States)

    Zlatkina, O. Yu

    2018-04-01

    There is a relationship between the service properties of component parts and their geometry; therefore, to predict and control the operational characteristics of parts and machines, it is necessary to measure their geometrical specifications. In modern production, a coordinate measuring machine is the advanced measuring instrument of the products geometrical specifications. The analysis of publications has shown that during the coordinate measurements the problems of choosing locating chart of parts and coordination have not been sufficiently studied. A special role in the coordination of the part is played by the coordinate axes informational content. Informational content is the sum of the degrees of freedom limited by the elementary item of a part. The coordinate planes of a rectangular coordinate system have different informational content (three, two, and one). The coordinate axes have informational content of four, two and zero. The higher the informational content of the coordinate plane or axis, the higher its priority for reading angular and linear coordinates is. The geometrical model production of the coordinate measurements object taking into account the information content of coordinate planes and coordinate axes allows us to clearly reveal the interrelationship of the coordinates of the deviations in location, sizes and deviations of their surfaces shape. The geometrical model helps to select the optimal locating chart of parts for bringing the machine coordinate system to the part coordinate system. The article presents an algorithm the model production of geometrical specifications using the example of the piston rod of a compressor.

  8. Increasing dimension of structures by 4D printing shape memory polymers via fused deposition modeling

    Science.gov (United States)

    Hu, G. F.; Damanpack, A. R.; Bodaghi, M.; Liao, W. H.

    2017-12-01

    The main objective of this paper is to introduce a 4D printing method to program shape memory polymers (SMPs) during fabrication process. Fused deposition modeling (FDM) as a filament-based printing method is employed to program SMPs during depositing the material. This method is implemented to fabricate complicated polymeric structures by self-bending features without need of any post-programming. Experiments are conducted to demonstrate feasibility of one-dimensional (1D)-to 2D and 2D-to-3D self-bending. It is shown that 3D printed plate structures can transform into masonry-inspired 3D curved shell structures by simply heating. Good reliability of SMP programming during printing process is also demonstrated. A 3D macroscopic constitutive model is established to simulate thermo-mechanical features of the printed SMPs. Governing equations are also derived to simulate programming mechanism during printing process and shape change of self-bending structures. In this respect, a finite element formulation is developed considering von-Kármán geometric nonlinearity and solved by implementing iterative Newton-Raphson scheme. The accuracy of the computational approach is checked with experimental results. It is demonstrated that the theoretical model is able to replicate the main characteristics observed in the experiments. This research is likely to advance the state of the art FDM 4D printing, and provide pertinent results and computational tool that are instrumental in design of smart materials and structures with self-bending features.

  9. Model-Based Nutrient Feeding Strategies for the Increased Production of Polyhydroxybutyrate (PHB) by Alcaligenes latus.

    Science.gov (United States)

    Gahlawat, Geeta; Srivastava, Ashok K

    2017-10-01

    Polyhydroxyalkanoates (PHAs) are biodegradable polymers which are considered as an effective alternative for conventional plastics due to their mechanical properties similar to the latter. However, the widespread use of these polymers is still hampered due to their higher cost of production as compared to plastics. The production cost could be overcome by obtaining high yields and productivity. The goal of the present research was to enhance the yield of polyhydroxybutyrate (PHB) with the help of two simple fed-batch cultivation strategies. In the present study, average batch kinetic and substrate limitation/inhibition study data of Alcaligenes latus was used for the development of PHB model which was then adopted for designing various off-line nutrient feeding strategies to enhance PHB accumulation. The predictive ability of the model was validated by experimental implementation of two fed-batch strategies. One such dynamic strategy of fed-batch cultivation under pseudo-steady state with respect to nitrogen and simultaneous carbon feeding strategy resulted in significantly high biomass and PHB concentration of 39.17 g/L and 29.64 g/L, respectively. This feeding strategy demonstrated a high PHB productivity and PHB content of 0.6 g/L h and 75%, respectively, which were remarkably high in comparison to batch cultivation. The mathematical model can also be employed for designing various other nutrient feeding strategies.

  10. Increasing black, asian and minority ethnic (bame) patient & community awareness--using the peer educator model.

    Science.gov (United States)

    Jain, Neerja

    2014-09-01

    Kidney Research UK, have been working since 2001 to raise health awareness, fund and oversee research into kidney related issues disproportionately affecting the BAME communities in the UK. Almost 10 years ago, the charity initiated its Peer Educator model which uses the natural skills of lay people and patients to raise awareness in these communities. This article will describe the work of the Charity in relation to patient and public engagement, describing the Peer Educator model and providing examples of how it has been used. It will then focus on the deployment and impact of Peer Educators in an end of life project that the charity was involved in. Peer Educators (PEs) are ordinary people from the targeted community. In the case of our health improvement work, this has largely been the BAME communities. These people do not need any prior knowledge, training or experience in the subject matter. However, they do need to have a desire to give something back to their community in terms of health messages and also be passionate about the subject matter. They tend to have a natural empathy with the target groups in terms of culture, religion and language. The Peer Educator model, is it has been found, to be a flexible and highly adaptable approach to addressing health issues in the BAME communities. It has been utilised by the charity to address everything from early disease detection, prevention, management, organ donation awareness, right through to end of life issues. The model has been well evaluated in the area of organ donation whereby its effectiveness has been proven. Moreover, there have been several notable outcomes from the end of life work including training and deployment of 10 Peer Educators who reached over 2,700 people from diverse South Asian communities, providing important information on who does what, when, and how to access it--in a culturally competent manner. Kidney Research UK's Peer Educator initiative has been well established as an

  11. Increasing competitiveness of service companies: developing conceptual models for implementing Lean Management in service companies

    OpenAIRE

    Damrath, Felix

    2012-01-01

    Lean management is a philosophy focused on identifying and eliminating waste throughout a product’s entire value stream. It originates from the manufacturing system of Japanese automotive manufacturer Toyota and attracted due to its tremendous success widespread attention worldwide. Lean promises significant benefits in terms of waste reduction, and increased organizational and supply chain communication and integration.Generally, in terms of operations and improvements service companies are ...

  12. Phosphodiesterase type 5 inhibitors increase Herceptin transport and treatment efficacy in mouse metastatic brain tumor models.

    Directory of Open Access Journals (Sweden)

    Jinwei Hu

    2010-04-01

    Full Text Available Chemotherapeutic drugs and newly developed therapeutic monoclonal antibodies are adequately delivered to most solid and systemic tumors. However, drug delivery into primary brain tumors and metastases is impeded by the blood-brain tumor barrier (BTB, significantly limiting drug use in brain cancer treatment.We examined the effect of phosphodiesterase 5 (PDE5 inhibitors in nude mice on drug delivery to intracranially implanted human lung and breast tumors as the most common primary tumors forming brain metastases, and studied underlying mechanisms of drug transport. In vitro assays demonstrated that PDE5 inhibitors enhanced the uptake of [(14C]dextran and trastuzumab (Herceptin, a humanized monoclonal antibody against HER2/neu by cultured mouse brain endothelial cells (MBEC. The mechanism of drug delivery was examined using inhibitors for caveolae-mediated endocytosis, macropinocytosis and coated pit/clathrin endocytosis. Inhibitor analysis strongly implicated caveolae and macropinocytosis endocytic pathways involvement in the PDE5 inhibitor-enhanced Herceptin uptake by MBEC. Oral administration of PDE5 inhibitor, vardenafil, to mice with HER2-positive intracranial lung tumors led to an increased tumor permeability to high molecular weight [(14C]dextran (2.6-fold increase and to Herceptin (2-fold increase. Survival time of intracranial lung cancer-bearing mice treated with Herceptin in combination with vardenafil was significantly increased as compared to the untreated, vardenafil- or Herceptin-treated mice (p0.05.These findings suggest that PDE5 inhibitors may effectively modulate BTB permeability, and enhance delivery and therapeutic efficacy of monoclonal antibodies in hard-to-treat brain metastases from different primary tumors that had metastasized to the brain.

  13. Pedicle distraction increases intervertebral and spinal canal area in a cadaver and bone model

    OpenAIRE

    Hughes Matthew; Papadakos Nikolaos; Bishop Tim; Bernard Jason

    2018-01-01

    Introduction: Lumbar spinal stenosis is degenerative narrowing of the spinal canal and/or intervertebral foramen causing compression of the spinal cord and nerve roots. Traditional decompression techniques can often cause significant trauma and vertebral instability. This paper evaluates a method of increasing pedicle length to decompress the spinal and intervertebral foramen, which could be done minimally invasive. Methods: Three Sawbone (Sawbones Europe, Sweden) and 1 cadaveric lumbar sp...

  14. Climate implications of increased wood use in the construction sector - towards an integrated modeling framework

    OpenAIRE

    Eriksson, Ljusk Ola; Gustavsson, Leif; Hänninen, Riitta; Kallio, Maarit; Lyhykäinen, Henna; Pingoud, Kim; Pohjola, Johanna; Sathre, Roger; Solberg, Birger; Svanaes, Jarle; Valsta, Lauri

    2009-01-01

    There is a growing interest in efficient ways to use biomass for the substitution of fossil fuels and non-biomass materials. Wood-based building material can affect the energy and carbon balances through at least four mechanisms: the relatively low fossil energy needed to manufacture wood products compared with alternative materials; the avoidance of industrial process carbon emissions; the increased availability of biofuels from biomass byproducts that can be used to replace fossil fuels; an...

  15. Increased blood-brain transfer in a rabbit model of acute liver failure

    International Nuclear Information System (INIS)

    Horowitz, M.E.; Schafer, D.F.; Molnar, P.; Jones, E.A.; Blasberg, R.G.; Patlak, C.S.; Waggoner, J.; Fenstermacher, J.D.

    1983-01-01

    The blood-to-brain transfer of [ 14 C]alpha-aminoisobutyric acid was investigated by quantitative autoradiography in normal rabbits and rabbits with acute liver failure induced by the selective hepatotoxin galactosamine. The blood-to-brain transfer of alpha-aminoisobutyric acid was similar in control animals and animals 2 and 7 h after galactosamine injections, but was increased five- to tenfold in certain gray-matter areas of the brain in animals 11 and 18 h after galactosamine treatment. No detectable differences in white-matter uptake of [ 14 C]alpha-aminoisobutyric acid were found between the control and treated groups. The increase in alpha-aminoisobutyric acid transfer within the gray-matter areas suggested that a general or nonspecific increase in brain capillary permeability occurred in these areas. No clinical signs of early hepatic encephalopathy were observed in the treated rabbits, except for 1 animal from the 18-h postgalactosamine group. Thus, enhanced blood-brain transfer of alpha-aminoisobutyric acid preceded the development of overt hepatic encephalopathy. The distribution of radioactivity after the intravenous administration of [ 14 C]galactosamine showed that virtually none of the hepatotoxin localized in the brain, suggesting that the drug itself does not have a direct effect upon the blood-brain barrier or the brain. The increased uptake of alpha-aminoisobutyric acid at 11 and 18 h implies that the transfer of other solutes would also be enhanced, that central nervous system homeostasis would be compromised, and that the resulting changes in brain fluid composition could contribute to or cause hepatic encephalopathy

  16. Temperature and Snowfall in Western Queen Maud Land Increasing Faster Than Climate Model Projections

    Science.gov (United States)

    Medley, B.; McConnell, J. R.; Neumann, T. A.; Reijmer, C. H.; Chellman, N.; Sigl, M.; Kipfstuhl, S.

    2018-02-01

    East Antarctic Ice Sheet (EAIS) mass balance is largely driven by snowfall. Recently, increased snowfall in Queen Maud Land led to years of EAIS mass gain. It is difficult to determine whether these years of enhanced snowfall are anomalous or part of a longer-term trend, reducing our ability to assess the mitigating impact of snowfall on sea level rise. We determine that the recent snowfall increases in western Queen Maud Land (QML) are part of a long-term trend (+5.2 ± 3.7% decade-1) and are unprecedented over the past two millennia. Warming between 1998 and 2016 is significant and rapid (+1.1 ± 0.7°C decade-1). Using these observations, we determine that the current accumulation and temperature increases in QML from an ensemble of global climate simulations are too low, which suggests that projections of the QML contribution to sea level rise are potentially overestimated with a reduced mitigating impact of enhanced snowfall in a warming world.

  17. Increased consumer density reduces the strength of neighborhood effects in a model system.

    Science.gov (United States)

    Merwin, Andrew C; Underwood, Nora; Inouye, Brian D

    2017-11-01

    An individual's susceptibility to attack can be influenced by conspecific and heterospecifics neighbors. Predicting how these neighborhood effects contribute to population-level processes such as competition and evolution requires an understanding of how the strength of neighborhood effects is modified by changes in the abundances of both consumers and neighboring resource species. We show for the first time that consumer density can interact with the density and frequency of neighboring organisms to determine the magnitude of neighborhood effects. We used the bean beetle, Callosobruchus maculatus, and two of its host beans, Vigna unguiculata and V. radiata, to perform a response-surface experiment with a range of resource densities and three consumer densities. At low beetle density, damage to beans was reduced with increasing conspecific density (i.e., resource dilution) and damage to the less preferred host, V. unguiculata, was reduced with increasing V. radiata frequency (i.e., frequency-dependent associational resistance). As beetle density increased, however, neighborhood effects were reduced; at the highest beetle densities neither focal nor neighboring resource density nor frequency influenced damage. These findings illustrate the importance of consumer density in mediating indirect effects among resources, and suggest that accounting for consumer density may improve our ability to predict population-level outcomes of neighborhood effects and our use of them in applications such as mixed-crop pest management. © 2017 by the Ecological Society of America.

  18. Increased Cerebral Tff1 Expression in Two Murine Models of Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Eva B Znalesniak

    2016-11-01

    Full Text Available Background/Aims: The trefoil factor family (TFF peptide TFF1 is a typical secretory product of the gastric mucosa and a very low level of expression occurs in nearly all regions of the murine brain. TFF1 possesses a lectin activity and binding to a plethora of transmembrane glycoproteins could explain the diverse biological effects of TFF1 (e.g., anti-apoptotic effect. It was the aim to test whether TFF expression is changed during neuroinflammation. Methods: Expression profiling was performed using semi-quantitative RT-PCR analyses in two murine models of neuroinflammation, i.e. Toxoplasma gondii-induced encephalitis and experimental autoimmune encephalomyelitis (EAE, the latter being the most common animal model of multiple sclerosis. Tff1 expression was also localized using RNA in situ hybridization histochemistry. Results: We report for the first time on a significant transcriptional induction in cerebral Tff1 expression in both T. gondii-induced encephalitis and EAE. In contrast, Tff2 and Tff3 expression were not altered. Tff1 transcripts were predominantly localized in the internal granular layer of the cerebellum indicating neuronal expression. Furthermore, also glial cells are expected to express Tff1. Characterization of both experimental models by expression profiling (e.g., inflammasome sensors, inflammatory cytokines, microglial marker Iba1, ependymin related protein 1 revealed differences concerning the expression of the inflammasome sensor Nlrp1 and interleukin 17a. Conclusion: The up-regulated expression of Tff1 is probably the result of a complex inflammatory process as its expression is induced by tumor necrosis factor α as well as interleukins 1β and 17. However on the transcript level, Tff1KO mice did not show any significant signs of an altered immune response after infection with T. gondii in comparison with the wild type animals.

  19. Increasing Predictive Ability by Modeling Interactions between Environments, Genotype and Canopy Coverage Image Data for Soybeans

    Directory of Open Access Journals (Sweden)

    Diego Jarquin

    2018-04-01

    Full Text Available Phenomics is a new area that offers numerous opportunities for its applicability in plant breeding. One possibility is to exploit this type of information obtained from early stages of the growing season by combining it with genomic data. This opens an avenue that can be capitalized by improving the predictive ability of the common prediction models used for genomic prediction. Imagery (canopy coverage data recorded between days 14–71 using two collection methods (ground information in 2013 and 2014; aerial information in 2014 and 2015 on a soybean nested association mapping population (SoyNAM was used to calibrate the prediction models together with the inclusion of several types of interactions between canopy coverage data, environments, and genomic data. Three different scenarios were considered that breeders might face testing lines in fields: (i incomplete field trials (CV2; (ii newly developed lines (CV1; and (iii predicting lines in unobserved environments (CV0. Two different traits were evaluated in this study: yield and days to maturity (DTM. Results showed improvements in the predictive ability for yield with respect to those models that solely included genomic data. These relative improvements ranged 27–123%, 27–148%, and 65–165% for CV2, CV1, and CV0, respectively. No major changes were observed for DTM. Similar improvements were observed for both traits when the reduced canopy information for days 14–33 was used to build the training-testing relationships, showing a clear advantage of using phenomics in very early stages of the growing season.

  20. NEW SOLUTION AND ITS IMPACT ON INCREASING, DECREASING AND BATHTUB SHAPED FAILURE RATE MODEL

    Directory of Open Access Journals (Sweden)

    Mahmudul Alam

    2009-01-01

    Full Text Available The maximum likelihood equations of IDB distribution can’t be solved analytically. Solutions of the MLE equations can be obtained numerically. But the problem is to detect the initial value of the parameters to solve the nonlinear MLE equations. A technique is developed for formulating the initial value of the parameter to solve the MLE equations of IDB distribution. Considering all the facts, though IDB distribution is not suitable for graduating mortality data but the model can graduate mortality data of Bangladesh in the age range of 0-8 very well.

  1. Participatory System Dynamics Modeling: Increasing Stakeholder Engagement and Precision to Improve Implementation Planning in Systems.

    Science.gov (United States)

    Zimmerman, Lindsey; Lounsbury, David W; Rosen, Craig S; Kimerling, Rachel; Trafton, Jodie A; Lindley, Steven E

    2016-11-01

    Implementation planning typically incorporates stakeholder input. Quality improvement efforts provide data-based feedback regarding progress. Participatory system dynamics modeling (PSD) triangulates stakeholder expertise, data and simulation of implementation plans prior to attempting change. Frontline staff in one VA outpatient mental health system used PSD to examine policy and procedural "mechanisms" they believe underlie local capacity to implement evidence-based psychotherapies (EBPs) for PTSD and depression. We piloted the PSD process, simulating implementation plans to improve EBP reach. Findings indicate PSD is a feasible, useful strategy for building stakeholder consensus, and may save time and effort as compared to trial-and-error EBP implementation planning.

  2. A model to obtain an optimum erbium desity for gain increasing in EDFA

    OpenAIRE

    E. Arzi; A. Hassani; F. E. Seraji

    2003-01-01

      In this paper, we suggest a novel model, based on input pump power and wave guidestructure, to calculate the Er-density profile in Erbium doped fiber amplifiers. This optimization is carried out for both SMF and DSF fibers. These optimized profiles have a Gaussian-like shape. Using the SMF optimized Er-density profile, high gain enhancement is obtained in a relatively short length of fibers. On the other hand, the DSF optimized profile shows small changes in the gain, which agrees with the ...

  3. Increased airway reactivity in a neonatal mouse model of Continuous Positive Airway Pressure (CPAP)

    OpenAIRE

    Mayer, Catherine A.; Martin, Richard J.; MacFarlane, Peter M.

    2015-01-01

    Background Continuous positive airway pressure (CPAP) is a primary form of respiratory support used in the intensive care of preterm infants, but its long-term effects on airway (AW) function are unknown. Methods We developed a neonatal mouse model of CPAP treatment to determine whether it modifies later AW reactivity. Un-anesthetized spontaneously breathing mice were fitted with a mask to deliver CPAP (6cmH2O, 3hrs/day) for 7 consecutive days starting at postnatal day 1. Airway reactivity to...

  4. SOLUTION OF THE PROBLEM OF INCREASING THE CAPACITY OF POWER SYSTEM BY USING THE MATLAB MODELING

    International Nuclear Information System (INIS)

    Mshvidobadze, T.

    2008-01-01

    A mathematical model of power system was constructed. It included eight types of electric power plants essential for covering a deficit and bringing the generating capacities of the power system to the level which would provide its normal operation. The restrictions were stated in terms of inequalities, the efficiency function was chosen and the corresponding problem was solved by using the Matlab system. The obtained values of variables represented the values of generated capacities of appropriate power plants providing the minimum value of the efficiency function. (author)

  5. Does plasticity in plant physiological traits explain the rapid increase in water use efficiency? An ecohydrological modeling approach

    Science.gov (United States)

    Mastrotheodoros, Theodoros; Fatichi, Simone; Pappas, Christoforos; Molnar, Peter; Burlando, Paolo

    2016-04-01

    The rise of atmospheric CO2 concentration is expected to stimulate plant productivity by enhancing photosynthesis and reducing stomatal conductance and thus increasing plant water use efficiency (WUE) worldwide. An analysis of eddy covariance flux tower data from 21 forested ecosystems across the north hemisphere detected an unexpectedly large increase in WUE (Keenan et al, 2013), which was six times larger than the increase found by most previous studies based on controlled experiments (e.g., FACE), leaf-scale analyses, and numerical modelling. This increase could be solely attributed to the increase in atmospheric CO2 since other confounding factors were ruled out. Here, we investigate the potential contribution of plant plasticity, reflected in the temporal adjustment of major plant physiological traits, on changes in WUE using the ecohydrological model Tethys and Chloris (T&C). We hypothesize that the increase in WUE can be attributed to small variations in plant physiological traits, undetectable through observations, eventually triggered by the atmospheric CO2 increase. Data from the 21 sites in the above mentioned study are used to force the model. Simulation results with and without plasticity in the physiological traits (i.e., model parameters in our numerical experiments) are compared with the observed trends in WUE. We test several plant adaptation strategies in being effective in explaining the observed increase in WUE using a multifactorial numerical experiment in which we perturb in a systematic way selected plant parameters. Keenan, T. F., Hollinger, D. Y., Bohrer, G., Dragoni, D., Munger, J. W., Schmid, H. P., and Richardson, A. D. (2013). Increase in forest water-use efficiency as atmospheric carbon dioxide concentrations rise. Nature, 499(7458), 324-7.

  6. A method for increase abrasive wear resistance parts by obtaining on methods casting on gasifying models

    Science.gov (United States)

    Sedukhin, V. V.; Anikeev, A. N.; Chumanov, I. V.

    2017-11-01

    Method optimizes hardening working layer parts’, working in high-abrasive conditions looks in this work: bland refractory particles WC and TiC in respect of 70/30 wt. % prepared by beforehand is applied on polystyrene model in casting’ mould. After metal poured in mould, withstand for crystallization, and then a study is carried out. Study macro- and microstructure received samples allows to say that thickness and structure received hardened layer depends on duration interactions blend harder carbides and liquid metal. Different character interactions various dispersed particles and matrix metal observed under the same conditions. Tests abrasive wear resistance received materials of method calculating residual masses was conducted in laboratory’ conditions. Results research wear resistance showed about that method obtaining harder coating of blend carbide tungsten and carbide titanium by means of drawing on surface foam polystyrene model before moulding, allows receive details with surface has wear resistance in 2.5 times higher, than details of analogy steel uncoated. Wherein energy costs necessary for transformation units mass’ substances in powder at obtained harder layer in 2.06 times higher, than materials uncoated.

  7. Seasonally timed treatment programs for Ascaris lumbricoides to increase impact-An investigation using mathematical models.

    Directory of Open Access Journals (Sweden)

    Emma L Davis

    2018-01-01

    Full Text Available There is clear empirical evidence that environmental conditions can influence Ascaris spp. free-living stage development and host reinfection, but the impact of these differences on human infections, and interventions to control them, is variable. A new model framework reflecting four key stages of the A. lumbricoides life cycle, incorporating the effects of rainfall and temperature, is used to describe the level of infection in the human population alongside the environmental egg dynamics. Using data from South Korea and Nigeria, we conclude that settings with extreme fluctuations in rainfall or temperature could exhibit strong seasonal transmission patterns that may be partially masked by the longevity of A. lumbricoides infections in hosts; we go on to demonstrate how seasonally timed mass drug administration (MDA could impact the outcomes of control strategies. For the South Korean setting the results predict a comparative decrease of 74.5% in mean worm days (the number of days the average individual spend infected with worms across a 12 month period between the best and worst MDA timings after four years of annual treatment. The model found no significant seasonal effect on MDA in the Nigerian setting due to a narrower annual temperature range and no rainfall dependence. Our results suggest that seasonal variation in egg survival and maturation could be exploited to maximise the impact of MDA in certain settings.

  8. Increased brain uptake of gamma-aminobutyric acid in a rabbit model of hepatic encephalopathy

    International Nuclear Information System (INIS)

    Bassett, M.L.; Mullen, K.D.; Scholz, B.; Fenstermacher, J.D.; Jones, E.A.

    1990-01-01

    Transfer of the inhibitory neurotransmitter gamma-aminobutyric acid across the normal blood-brain barrier is minimal. One prerequisite for gamma-aminobutyric acid in plasma contributing to the neural inhibition of hepatic encephalopathy would be that increased transfer of gamma-aminobutyric acid across the blood-brain barrier occurs in liver failure. The aim of the present study was to determine if brain gamma-aminobutyric acid uptake is increased in rabbits with stage II-III (precoma) hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure. A modification of the Oldendorf intracarotid artery-injection technique was applied. [3H] gamma-aminobutyric acid, [14C] butanol, and 113mIn-labeled serum protein (transferrin) were injected simultaneously 4 s before decapitation. The ipsilateral brain uptake index of gamma-aminobutyric acid was determined from measurements of the 3 isotopes in 5 brain regions. Uncorrected or simple brain uptake indices of [3H] gamma-aminobutyric acid and [113mIn] transferrin were calculated using [14C] butanol as the highly extracted reference compound. The [113mIn] transferrin data were also used to correct the brain uptake index of [3H] gamma-aminobutyric acid for intravascular retention of [3H] gamma-aminobutyric acid. The methodology adopted minimized problems attributable to rapid [3H] gamma-aminobutyric acid metabolism, and slow brain washout and recirculation of the radiolabeled tracers. Both the uncorrected and corrected brain uptake indices of gamma-aminobutyric acid as well as the simple brain uptake index of transferrin were significantly increased in both stage II and III hepatic encephalopathy in all brain regions studied. Moreover, these brain uptake indices were significantly greater in stage III hepatic encephalopathy than in stage II hepatic encephalopathy

  9. Clean Technology Application : Kupola Model Burner for Increasing the Performance of Spent Accu Recycle

    International Nuclear Information System (INIS)

    Titiresmi

    2000-01-01

    Recycling of used battery for recovering lead done by either small household/small scale industries has been identified as a source of air pollution, especially by heavy metal (Pb). This condition give an adverse impact toward workers and societies. Technological aspect is one of the causal. The process apply an open system. Therefore, a lot of energy, as well as dust wasted to the air without prior treatment. For overcoming this condition, closed system by utilizing Cupola furnace will be offered as one of the alternatives clean technology application and to increase the recovering performance in order to set an effective and efficient result. (author)

  10. Chronic alcohol ingestion increases mortality and organ injury in a murine model of septic peritonitis.

    Science.gov (United States)

    Yoseph, Benyam P; Breed, Elise; Overgaard, Christian E; Ward, Christina J; Liang, Zhe; Wagener, Maylene E; Lexcen, Daniel R; Lusczek, Elizabeth R; Beilman, Greg J; Burd, Eileen M; Farris, Alton B; Guidot, David M; Koval, Michael; Ford, Mandy L; Coopersmith, Craig M

    2013-01-01

    Patients admitted to the intensive care unit with alcohol use disorders have increased morbidity and mortality. The purpose of this study was to determine how chronic alcohol ingestion alters the host response to sepsis in mice. Mice were randomized to receive either alcohol or water for 12 weeks and then subjected to cecal ligation and puncture. Mice were sacrificed 24 hours post-operatively or followed seven days for survival. Septic alcohol-fed mice had a significantly higher mortality than septic water-fed mice (74% vs. 41%, p = 0.01). This was associated with worsened gut integrity in alcohol-fed mice with elevated intestinal epithelial apoptosis, decreased crypt proliferation and shortened villus length. Further, alcohol-fed mice had higher intestinal permeability with decreased ZO-1 and occludin protein expression in the intestinal tight junction. The frequency of splenic and bone marrow CD4+ T cells was similar between groups; however, splenic CD4+ T cells in septic alcohol-fed mice had a marked increase in both TNF and IFN-γ production following ex vivo stimulation. Neither the frequency nor function of CD8+ T cells differed between alcohol-fed and water-fed septic mice. NK cells were decreased in both the spleen and bone marrow of alcohol-fed septic mice. Pulmonary myeloperoxidase levels and BAL levels of G-CSF and TFG-β were higher in alcohol-fed mice. Pancreatic metabolomics demonstrated increased acetate, adenosine, xanthine, acetoacetate, 3-hydroxybutyrate and betaine in alcohol-fed mice and decreased cytidine, uracil, fumarate, creatine phosphate, creatine, and choline. Serum and peritoneal cytokines were generally similar between alcohol-fed and water-fed mice, and there were no differences in bacteremia, lung wet to dry weight, or pulmonary, liver or splenic histology. When subjected to the same septic insult, mice with chronic alcohol ingestion have increased mortality. Alterations in intestinal integrity, the host immune response, and

  11. Chronic alcohol ingestion increases mortality and organ injury in a murine model of septic peritonitis.

    Directory of Open Access Journals (Sweden)

    Benyam P Yoseph

    Full Text Available Patients admitted to the intensive care unit with alcohol use disorders have increased morbidity and mortality. The purpose of this study was to determine how chronic alcohol ingestion alters the host response to sepsis in mice.Mice were randomized to receive either alcohol or water for 12 weeks and then subjected to cecal ligation and puncture. Mice were sacrificed 24 hours post-operatively or followed seven days for survival.Septic alcohol-fed mice had a significantly higher mortality than septic water-fed mice (74% vs. 41%, p = 0.01. This was associated with worsened gut integrity in alcohol-fed mice with elevated intestinal epithelial apoptosis, decreased crypt proliferation and shortened villus length. Further, alcohol-fed mice had higher intestinal permeability with decreased ZO-1 and occludin protein expression in the intestinal tight junction. The frequency of splenic and bone marrow CD4+ T cells was similar between groups; however, splenic CD4+ T cells in septic alcohol-fed mice had a marked increase in both TNF and IFN-γ production following ex vivo stimulation. Neither the frequency nor function of CD8+ T cells differed between alcohol-fed and water-fed septic mice. NK cells were decreased in both the spleen and bone marrow of alcohol-fed septic mice. Pulmonary myeloperoxidase levels and BAL levels of G-CSF and TFG-β were higher in alcohol-fed mice. Pancreatic metabolomics demonstrated increased acetate, adenosine, xanthine, acetoacetate, 3-hydroxybutyrate and betaine in alcohol-fed mice and decreased cytidine, uracil, fumarate, creatine phosphate, creatine, and choline. Serum and peritoneal cytokines were generally similar between alcohol-fed and water-fed mice, and there were no differences in bacteremia, lung wet to dry weight, or pulmonary, liver or splenic histology.When subjected to the same septic insult, mice with chronic alcohol ingestion have increased mortality. Alterations in intestinal integrity, the host immune

  12. Modelling the correlations of e-waste quantity with economic increase.

    Science.gov (United States)

    Awasthi, Abhishek Kumar; Cucchiella, Federica; D'Adamo, Idiano; Li, Jinhui; Rosa, Paolo; Terzi, Sergio; Wei, Guoyin; Zeng, Xianlai

    2018-02-01

    Waste from Electrical and Electronic Equipment (WEEE or e-waste) is regarded as one of the fastest growing waste streams in the world and is becoming an emerging issue owing to adverse consequences on the natural environment and the human health. This research article reveals the presence of a strong linear correlation among global e-waste generation and Gross Domestic Product. The obtained results indicate that the best fit for data can be reached by comparing e-waste collected volumes and GDP PPS. More in detail, an increase of 1000 GDP PPS means an additional 0.27kg of e-waste collected and 0.22kg of e-waste reused/recycled. Furthermore, for each additional citizen, there will be an increase of 7.7kg of e-waste collected and 6.2kg of e-waste reused/recycled. The better collection of e-waste acts an important role concerning the circular economy, and it can be an advantageous approach. Therefore, e-waste could be considered as an opportunity for recycling or recovery of valuable metals (e.g., copper, gold, silver, and palladium), given their significant content in precious metals than in mineral ores. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Bevacizumab exacerbates sinusoidal obstruction syndrome (SOS) in the animal model and increases MMP 9 production.

    Science.gov (United States)

    Jafari, Azin; Matthaei, Hanno; Wehner, Sven; Tonguc, Tolga; Kalff, Jörg C; Manekeller, Steffen

    2018-04-24

    Thanks to modern multimodal treatment the ouctome of patients with colorectal cancer has experienced significant improvements. As a downside, agent specific side effects have been observed such as sinusoidal obstruction syndrome (SOS) after oxaliplatin chemotherapy (OX). Bevazicumab targeting VEGF is nowadays comprehensively used in combination protocols with OX but its impact on hepatotoxicity is thus far elusive and focus of the present study. After MCT administration 67% of animals developed SOS. GOT serum concentration significantly increased in animals developing SOS ( p SOS. In contrast, animals receiving VEGF developed SOS merely in 40% while increasing the VEGF dose led to a further decrease in SOS development to 25%. MMP 9 concentration in animals developing SOS was significantly higher compared to controls ( p SOS paralleled by MMP 9 production. Therefore, OX-Bevacizumab combination therapies should be administered with caution, especially if liver parenchyma damage is apparent. Male Sprague-Dawley rats were gavaged Monocrotaline (MCT) to induce SOS. Recombinant VEGF or an Anti-VEGF antibody was administered to MCT-treated rats and the hepatotoxic effect monitored in defined time intervals. MMP 9 expression in the liver was measured by ELISA.

  14. Modeling Leptospirosis in Trinidad, West Indies: A Waterborne Zoonosis of Increasing Public Health Importance

    Science.gov (United States)

    Vega, M. C.; Opadeyi, J.

    2012-12-01

    Leptospirosis is a waterborne disease which is considered one of the most common and widely spread bacterial zoonosis and a growing global public health problem. Transmission in humans is caused by direct or indirect contact with contaminated water, soil or infected urine, blood or tissue of carrier animals. Because of the similarity with influenza, dengue and viral hepatitis symptoms it is often misdiagnosed with these diseases, but as the leptospirosis progresses, internal organs can be compromised, causing severe syndromes (e.g. Weil's disease), and potentially can cause death. In less developed countries, leptospirosis is often poorly recognized. In humid tropics and subtropics, where this disease has a high impact, climatic and environmental factors, such as rainfall, floods, land cover and their modifications have been frequently related to the occurrence of leptospirosis. In these regions one of the main problems for the study of the role of environmental factors on disease dynamics is the lack of accurate data since, in many cases, data are either unavailable or do not exist at all. Between 1980 and 2005 a total of 12,475 cases of leptospirosis were reported from all Caribbean countries, with 2,370 (19%) of these corresponding to Trinidad and Tobago, where the current average annual incidence rate is 1.84 per 100,000 population based on confirmed cases. In order to explore the underlying spatial variability of leptospirosis occurrence as related to environmental and socio-economic factors, a series of Geographically Weighted Regression (GWR) models were developed. GWR was used to examine the determinants of leptospirosis in the communities of Trinidad using a total of 1,549 reported cases and 250 confirmed cases from 1998 to 2008. MODIS satellite imagery and GIS analysis were used to develop a series of covariables for each community including land cover, vegetation indices, wetness index (ln (α/tanβ)), river length per Ha, topography, percentage of free

  15. Increased Arginine and Ornithine Flux in Islets of Langerhans Cultured in a Microgravity Model System

    Science.gov (United States)

    Tobin, B. W.; Sams, C. F.; Smith, S. M.

    2000-01-01

    Microgravity is associated with alterations in protein metabolism of both muscle and bone. That pancreas-derived insulin is essential to the normal maintenance of body protein balance is well known. The importance of altered endocrine pancreas function in microgravity is not yet established. We proposed to examine the influence of a microgravity model system, the High Aspect Ratio Vessel (HARV) upon islets of Langerhans from Wistar Furth rats. Islets were cultured in the HARV for 48 hr in Medium-199 and contrasted to static control islets (PLATE). Nitrogenous compounds elaborated into the media (micromoles/ml) were analyzed at 0 and 48 hr of culture and compared to PLATE with a 2-way ANOVA (HARV vs Hour).

  16. The pulmonary vasculature in a neonatal porcine model with increased pulmonary blood flow and pressure

    DEFF Research Database (Denmark)

    Stenbøg, Elisabeth Vidstid; Steinbruchel, Daniel Andreas; Thomsen, Anne Bloch

    2001-01-01

    Introduction: Hypertension and hyperperfusion of the pulmonary vascular bed in the setting of congenital cardiac malformations may lead to progressive pulmonary vascular disease. To improve the understanding of the basic mechanisms of this disease, there is a need for clinically relevant animal....... By three months of age, nearly all shunts had closed spontaneously, and haemodynamics were normal. Ligation of the left pulmonary artery resulted in a normal total pulmonary blood flow, despite only the right lung being perfused, and a 33% increase in systolic pulmonary arterial pressure...... in humans. Elevated circulating levels of endothelin were associated with abnormal haemodynamics rather than abnormal pathology. These findings could be valuable for future studies on the pathogenesis of hypertensive pulmonary vascular disease associated with congenital cardiac malformations....

  17. Myriocin significantly increases the mortality of a non-mammalian model host during Candida pathogenesis.

    Directory of Open Access Journals (Sweden)

    Nadja Rodrigues de Melo

    Full Text Available Candida albicans is a major human pathogen whose treatment is challenging due to antifungal drug toxicity, drug resistance and paucity of antifungal agents available. Myrocin (MYR inhibits sphingosine synthesis, a precursor of sphingolipids, an important cell membrane and signaling molecule component. MYR also has dual immune suppressive and antifungal properties, potentially modulating mammalian immunity and simultaneously reducing fungal infection risk. Wax moth (Galleria mellonella larvae, alternatives to mice, were used to establish if MYR suppressed insect immunity and increased survival of C. albicans-infected insects. MYR effects were studied in vivo and in vitro, and compared alone and combined with those of approved antifungal drugs, fluconazole (FLC and amphotericin B (AMPH. Insect immune defenses failed to inhibit C. albicans with high mortalities. In insects pretreated with the drug followed by C. albicans inoculation, MYR+C. albicans significantly increased mortality to 93% from 67% with C. albicans alone 48 h post-infection whilst AMPH+C. albicans and FLC+C. albicans only showed 26% and 0% mortalities, respectively. MYR combinations with other antifungal drugs in vivo also enhanced larval mortalities, contrasting the synergistic antifungal effect of the MYR+AMPH combination in vitro. MYR treatment influenced immunity and stress management gene expression during C. albicans pathogenesis, modulating transcripts putatively associated with signal transduction/regulation of cytokines, I-kappaB kinase/NF-kappaB cascade, G-protein coupled receptor and inflammation. In contrast, all stress management gene expression was down-regulated in FLC and AMPH pretreated C. albicans-infected insects. Results are discussed with their implications for clinical use of MYR to treat sphingolipid-associated disorders.

  18. Increased collagen maturity with sildenafil citrate: experimental high risk colonic anastomosis model.

    Science.gov (United States)

    Cakir, Tebessum; Ozer, Ilter; Bostanci, Erdal Birol; Keklik, Tulay Timucin; Ercin, Ugur; Bilgihan, Ayse; Akoglu, Musa

    2015-01-01

    Inadequate healing and high anastomosis leak rates at rectal anastomosis may be due to lack of supportive serosal layer and technical difficulty of low anterior resections. Positive effects of sildenafil on wound healing were observed. The aim of this study was to simulate rectal anastomosis as a technical insufficient anastomosis and investigate the effects of sildenafil on anastomosis healing. Colonic anastomoses were carried out in 64 rats and randomized into four groups, CA-S, complete anastomoses without sildenafil (10 mg/kg for 5 days); CA+S, complete anastomoses with sildenafil; IA-S, incomplete anastomoses without sildenafil; IA+S, incomplete anastomoses with sildenafil. Half of the rats in every group were sacrificed on post-operative day (POD) 3, half of them sacrificed on POD 7. Tissues from the anastomoses were used for functional, histochemical, biochemical investigations. Sildenafil treatment resulted in increased bursting pressures in IA+S on POD 7 (p=0.010). Collagen maturity was higher in IA+S on POD 3 and POD 7, CA+S on POD 7 (p=0.010; p=0.010; p<0.007). Collagen content was higher in IA+S on POD 7 (p<0.001). Glutathione, hydroxyproline levels were similar. Malondialdehyde levels were lower in IA+S on POD 3 (p<0.001). Epithelization score was higher in IA+S on POD 7 (p=0.007). Inflammation score was higher in CA-S group on POD 3 and POD 7 (p<0.001; p<0.001). Neutrophil score was lower in CA+S on POD 3 (p=0.005). An increase in collagen content, maturity, and epithelization, a decrease in neutrophil infiltration, oxidative stress and better mechanical strength were observed with the administration of sildenafil. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  19. Melatonin attenuates prenatal dexamethasone-induced blood pressure increase in a rat model.

    Science.gov (United States)

    Tain, You-Lin; Chen, Chih-Cheng; Sheen, Jiunn-Ming; Yu, Hong-Ren; Tiao, Mao-Meng; Kuo, Ho-Chang; Huang, Li-Tung

    2014-04-01

    Although antenatal corticosteroid is recommended to accelerate fetal lung maturation, prenatal dexamethasone exposure results in hypertension in the adult offspring. Since melatonin is a potent antioxidant and has been known to regulate blood pressure, we examined the beneficial effects of melatonin therapy in preventing prenatal dexamethasone-induced programmed hypertension. Male offspring of Sprague-Dawley rats were assigned to four groups (n = 12/group): control, dexamethasone (DEX), control + melatonin, and DEX + melatonin. Pregnant rats received intraperitoneal dexamethasone (0.1 mg/kg) from gestational day 16 to 22. In the melatonin-treatment groups, rats received 0.01% melatonin in drinking water during their entire pregnancy and lactation. Blood pressure was measured by an indirect tail-cuff method. Gene expression and protein levels were analyzed by real-time quantitative polymerase chain reaction and Western blotting, respectively. At 16 weeks of age, the DEX group developed hypertension, which was partly reversed by maternal melatonin therapy. Reduced nephron numbers due to prenatal dexamethasone exposure were prevented by melatonin therapy. Renal superoxide and NO levels were similar in all groups. Prenatal dexamethasone exposure led to increased mRNA expression of renin and prorenin receptor and up-regulated histone deacetylase (HDAC)-1 expression in the kidneys of 4-month-old offspring. Maternal melatonin therapy augmented renal Mas protein levels in DEX + melatonin group, and increased renal mRNA expression of HDAC-1, HDAC-2, and HDAC-8 in control and DEX offspring. Melatonin attenuated prenatal DEX-induced hypertension by restoring nephron numbers, altering RAS components, and modulating HDACs. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  20. Increased survival rate by local release of diclofenac in a murine model of recurrent oral carcinoma

    Directory of Open Access Journals (Sweden)

    Will OM

    2016-10-01

    Full Text Available Olga Maria Will,1,* Nicolai Purcz,2,* Athena Chalaris,3 Carola Heneweer,4,5 Susann Boretius,1 Larissa Purcz,2 Lila Nikkola,6 Nureddin Ashammakhi,6 Holger Kalthoff,7 Claus-Christian Glüer,1 Jörg Wiltfang,2 Yahya Açil,2 Sanjay Tiwari1 1Section Biomedical Imaging, Clinic for Radiology and Neuroradiology, MOIN CC, 2Department of Oral and Maxillofacial Surgery, University Hospital Schleswig-Holstein, 3Institute of Biochemistry, Christian-Albrechts-Universität zu Kiel, 4Clinic for Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Kiel, 5Institute for Diagnostic and Interventional Radiology, University Hospital Cologne, Cologne, Germany; 6Department of Biomedical Engineering, Tampere University of Technology, Tampere, Finland; 7Institute for Experimental Cancer Research, University Hospital Schleswig-Holstein, Kiel, Germany *These authors contributed equally to this work Abstract: Despite aggressive treatment with radiation and combination chemotherapy following tumor resection, the 5-year survival rate for patients with head and neck cancer is at best only 50%. In this study, we examined the therapeutic potential of localized release of diclofenac from electrospun nanofibers generated from poly(d,l-lactide-co-glycolide polymer. Diclofenac was chosen since anti-inflammatory agents that inhibit cyclooxygenase have shown great potential in their ability to directly inhibit tumor growth as well as suppress inflammation-mediated tumor growth. A mouse resection model of oral carcinoma was developed by establishing tumor growth in the oral cavity by ultrasound-guided injection of 1 million SCC-9 cells in the floor of the mouth. Following resection, mice were allocated into four groups with the following treatment: 1 no treatment, 2 implanted scaffolds without diclofenac, 3 implanted scaffolds loaded with diclofenac, and 4 diclofenac given orally. Small animal ultrasound and magnetic resonance imaging were utilized for longitudinal

  1. Fast Cloud Adjustment to Increasing CO2 in a Superparameterized Climate Model

    Directory of Open Access Journals (Sweden)

    Marat Khairoutdinov

    2012-05-01

    Full Text Available Two-year simulation experiments with a superparameterized climate model, SP-CAM, are performed to understand the fast tropical (30S-30N cloud response to an instantaneous quadrupling of CO2 concentration with SST held fixed at present-day values.The greenhouse effect of the CO2 perturbation quickly warms the tropical land surfaces by an average of 0.5 K. This shifts rising motion, surface precipitation, and cloud cover at all levels from the ocean to the land, with only small net tropical-mean cloud changes. There is a widespread average reduction of about 80 m in the depth of the trade inversion capping the marine boundary layer (MBL over the cooler subtropical oceans.One apparent contributing factor is CO2-enhanced downwelling longwave radiation, which reduces boundary-layer radiative cooling, a primary driver of turbulent entrainment through the trade inversion. A second contributor is a slight CO2-induced heating of the free troposphere above the MBL, which strengthens the trade inversion and also inhibits entrainment. There is a corresponding downward displacement of MBL clouds with a very slight decrease in mean cloud cover and albedo.Two-dimensional cloud-resolving model (CRM simulations of this MBL response are run to steady state using composite SP-CAM simulated thermodynamic and wind profiles from a representative cool subtropical ocean regime, for the control and 4xCO2 cases. Simulations with a CRM grid resolution equal to that of SP-CAM are compared with much finer resolution simulations. The coarse-resolution simulations maintain a cloud fraction and albedo comparable to SP-CAM, but the fine-resolution simulations have a much smaller cloud fraction. Nevertheless, both CRM configurations simulate a reduction in inversion height comparable to SP-CAM. The changes in low cloud cover and albedo in the CRM simulations are small, but both simulations predict a slight reduction in low cloud albedo as in SP-CAM.

  2. Second-Hand Smoke Increases Bronchial Hyperreactivity and Eosinophilia in a Murine Model of Allergic Aspergillosis

    Directory of Open Access Journals (Sweden)

    Brian W. P. Seymour

    2003-01-01

    Full Text Available Involuntary inhalation of tobacco smoke has been shown to aggravate the allergic response. Antibodies to fungal antigens such as Aspergillus fumigatus (Af cause an allergic lung disease in humans. This study was carried out to determine the effect of environmental tobacco smoke (ETS on a murine model of allergic bronchopulmonary aspergillosis (ABPA. BALB/c mice were exposed to aged and diluted sidestream cigarette smoke to simulate 'second-hand smoke'. The concentration was consistent with that achieved in enclosed public areas or households where multiple people smoke. During exposure, mice were sensitized to Af antigen intranasally. Mice that were sensitized to Af antigen and exposed to ETS developed significantly greater airway hyperreactivity than did mice similarly sensitized to Af but housed in ambient air. The effective concentration of aerosolized acetylcholine needed to double pulmonary flow resistance was significantly lower in Af + ETS mice compared to the Af + AIR mice. Immunological data that supports this exacerbation of airway hyperresponsiveness being mediated by an enhanced type 1 hypersensitivity response include: eosinophilia in peripheral blood and lung sections. All Af sensitized mice produced elevated levels of IL4, IL5 and IL10 but no IFN-γ indicating a polarized Th2 response. Thus, ETS can cause exacerbation of asthma in ABPA as demonstrated by functional airway hyperresponsiveness and elevated levels of blood eosinophilia.

  3. Serotonin depletion increases seizure susceptibility and worsens neuropathological outcomes in kainate model of epilepsy.

    Science.gov (United States)

    Maia, Gisela H; Brazete, Cátia S; Soares, Joana I; Luz, Liliana L; Lukoyanov, Nikolai V

    2017-09-01

    Serotonin is implicated in the regulation of seizures, but whether or not it can potentiate the effects of epileptogenic factors is not fully established. Using the kainic acid model of epilepsy in rats, we tested the effects of serotonin depletion on (1) susceptibility to acute seizures, (2) development of spontaneous recurrent seizures and (3) behavioral and neuroanatomical sequelae of kainic acid treatment. Serotonin was depleted by pretreating rats with p-chlorophenylalanine. In different groups, kainic acid was injected at 3 different doses: 6.5mg/kg, 9.0mg/kg or 12.5mg/kg. A single dose of 6.5mg/kg of kainic acid reliably induced status epilepticus in p-chlorophenylalanine-pretreated rats, but not in saline-pretreated rats. The neuroexcitatory effects of kainic acid in the p-chlorophenylalanine-pretreated rats, but not in saline-pretreated rats, were associated with the presence of tonic-clonic convulsions and high lethality. Compared to controls, a greater portion of serotonin-depleted rats showed spontaneous recurrent seizures after kainic acid injections. Loss of hippocampal neurons and spatial memory deficits associated with kainic acid treatment were exacerbated by prior depletion of serotonin. The present findings are of particular importance because they suggest that low serotonin activity may represent one of the major risk factors for epilepsy and, thus, offer potentially relevant targets for prevention of epileptogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Increased precipitation of spasms in an animal model of infantile spasms by prenatal stress exposure.

    Science.gov (United States)

    Shi, Xiu-Yu; Ju, Jun; Zou, Li-Ping; Wang, Juan; Shang, Ning-Xiu; Zhao, Jian-Bo; Wang, Jing; Zhang, Jun-Yan

    2016-05-01

    Infantile spasms (IS) represent a serious epileptic syndrome, called West syndrome (WS) that occurs in the early infantile age. Although several hypotheses and animal models have been proposed to explain the pathogenesis of IS, the pathophysiology of IS has not been elucidated. Recently, we proposed a hypothesis for IS under prenatal stress exposure (also called Zou's hypothesis) by correlating diverse etiologies and prenatal stresses with IS development. This research aims to determine the mechanism through which prenatal stress affects the offspring and establish the potential underlying mechanisms. Pregnant rats were subjected to forced swimming in cold water. Rat pups exposed to prenatal stress were administered with N-methyl-D-aspartate (NMDA). Exposure to prenatal stress sensitized the rats against development of NMDA-induced spasms. However, this phenomenon was altered by administering adrenocorticotropin. Prenatal stress exposure also altered the hormonal levels and neurotransmitter receptor expression of the developing rats as well as influenced the tissue structure of the brain. These findings suggest that maternal stress could alter the level of endogenous glucocorticoid, which is the basis of IS, and cerebral dysplasia, hypoxic-ischemic encephalopathy (HIE), inherited metabolic diseases, and other factors activated this disease in developmental brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. What can business model innovation bring to transport service operations in a context of increasing liberalization

    Energy Technology Data Exchange (ETDEWEB)

    Perez Casan, J.A.

    2016-07-01

    Transport services continue to be liberalized across the entire European Union, although at differing speeds in each Member State. This momentum is expected to continue in the coming years. Against this background, attention to new dimensions of transport services becomes imperative. The focus, which has so far centred on managing infrastructure, must now shift to lesser explored areas, like product innovation and customer relationship management. The efficiency and competitiveness of new private operators will depend to a large extent on achieving a balanced development of the three aforementioned areas, as well as paying particular attention to their inherent logic, in order to build a strong value proposition. Business model innovation emerged in the field of strategic management yet goes beyond the traditional framework of competition 'for the market' and 'in the market', opening a wider and more promising space, i.e. the market creation framework. The goal is no longer to discover and exploit opportunities, but to create new opportunities and generate new market spaces. (Author)

  6. Mapping brucellosis increases relative to elk density using hierarchical Bayesian models

    Science.gov (United States)

    Cross, Paul C.; Heisey, Dennis M.; Scurlock, Brandon M.; Edwards, William H.; Brennan, Angela; Ebinger, Michael R.

    2010-01-01

    The relationship between host density and parasite transmission is central to the effectiveness of many disease management strategies. Few studies, however, have empirically estimated this relationship particularly in large mammals. We applied hierarchical Bayesian methods to a 19-year dataset of over 6400 brucellosis tests of adult female elk (Cervus elaphus) in northwestern Wyoming. Management captures that occurred from January to March were over two times more likely to be seropositive than hunted elk that were killed in September to December, while accounting for site and year effects. Areas with supplemental feeding grounds for elk had higher seroprevalence in 1991 than other regions, but by 2009 many areas distant from the feeding grounds were of comparable seroprevalence. The increases in brucellosis seroprevalence were correlated with elk densities at the elk management unit, or hunt area, scale (mean 2070 km2; range = [95–10237]). The data, however, could not differentiate among linear and non-linear effects of host density. Therefore, control efforts that focus on reducing elk densities at a broad spatial scale were only weakly supported. Additional research on how a few, large groups within a region may be driving disease dynamics is needed for more targeted and effective management interventions. Brucellosis appears to be expanding its range into new regions and elk populations, which is likely to further complicate the United States brucellosis eradication program. This study is an example of how the dynamics of host populations can affect their ability to serve as disease reservoirs.

  7. Mapping brucellosis increases relative to elk density using hierarchical Bayesian models.

    Directory of Open Access Journals (Sweden)

    Paul C Cross

    Full Text Available The relationship between host density and parasite transmission is central to the effectiveness of many disease management strategies. Few studies, however, have empirically estimated this relationship particularly in large mammals. We applied hierarchical Bayesian methods to a 19-year dataset of over 6400 brucellosis tests of adult female elk (Cervus elaphus in northwestern Wyoming. Management captures that occurred from January to March were over two times more likely to be seropositive than hunted elk that were killed in September to December, while accounting for site and year effects. Areas with supplemental feeding grounds for elk had higher seroprevalence in 1991 than other regions, but by 2009 many areas distant from the feeding grounds were of comparable seroprevalence. The increases in brucellosis seroprevalence were correlated with elk densities at the elk management unit, or hunt area, scale (mean 2070 km(2; range = [95-10237]. The data, however, could not differentiate among linear and non-linear effects of host density. Therefore, control efforts that focus on reducing elk densities at a broad spatial scale were only weakly supported. Additional research on how a few, large groups within a region may be driving disease dynamics is needed for more targeted and effective management interventions. Brucellosis appears to be expanding its range into new regions and elk populations, which is likely to further complicate the United States brucellosis eradication program. This study is an example of how the dynamics of host populations can affect their ability to serve as disease reservoirs.

  8. Using dynamic walking models to identify factors that contribute to increased risk of falling in older adults.

    Science.gov (United States)

    Roos, Paulien E; Dingwell, Jonathan B

    2013-10-01

    Falls are common in older adults. The most common cause of falls is tripping while walking. Simulation studies demonstrated that older adults may be restricted by lower limb strength and movement speed to regain balance after a trip. This review examines how modeling approaches can be used to determine how different measures predict actual fall risk and what some of the causal mechanisms of fall risk are. Although increased gait variability predicts increased fall risk experimentally, it is not clear which variability measures could best be used, or what magnitude of change corresponded with increased fall risk. With a simulation study we showed that the increase in fall risk with a certain increase in gait variability was greatly influenced by the initial level of variability. Gait variability can therefore not easily be used to predict fall risk. We therefore explored other measures that may be related to fall risk and investigated the relationship between stability measures such as Floquet multipliers and local divergence exponents and actual fall risk in a dynamic walking model. We demonstrated that short-term local divergence exponents were a good early predictor for fall risk. Neuronal noise increases with age. It has however not been fully understood if increased neuronal noise would cause an increased fall risk. With our dynamic walking model we showed that increased neuronal noise caused increased fall risk. Although people who are at increased risk of falling reduce their walking speed it had been questioned whether this slower speed would actually cause a reduced fall risk. With our model we demonstrated that a reduced walking speed caused a reduction in fall risk. This may be due to the decreased kinematic variability as a result of the reduced signal-dependent noise of the smaller muscle forces that are required for slower. These insights may be used in the development of fall prevention programs in order to better identify those at increased risk of

  9. Using Dynamic Walking Models to Identify Factors that Contribute to Increased Risk of Falling in Older Adults

    Science.gov (United States)

    Roos, Paulien E.; Dingwell, Jonathan B.

    2013-01-01

    Falls are common in older adults. The most common cause of falls is tripping while walking. Simulation studies demonstrated that older adults may be restricted by lower limb strength and movement speed to regain balance after a trip. This review examines how modeling approaches can be used to determine how different measures predict actual fall risk and what some of the causal mechanisms of fall risk are. Although increased gait variability predicts increased fall risk experimentally, it is not clear which variability measures could best be used, or what magnitude of change corresponded with increased fall risk. With a simulation study we showed that the increase in fall risk with a certain increase in gait variability was greatly influenced by the initial level of variability. Gait variability can therefore not easily be used to predict fall risk. We therefore explored other measures that may be related to fall risk and investigated the relationship between stability measures such as Floquet multipliers and local divergence exponents and actual fall risk in a dynamic walking model. We demonstrated that short-term local divergence exponents were a good early predictor for fall risk. Neuronal noise increases with age. It has however not been fully understood if increased neuronal noise would cause an increased fall risk. With our dynamic walking model we showed that increased neuronal noise caused increased fall risk. Although people who are at increased risk of falling reduce their walking speed it had been questioned whether this slower speed would actually cause a reduced fall risk. With our model we demonstrated that a reduced walking speed caused a reduction in fall risk. This may be due to the decreased kinematic variability as a result of the reduced signal-dependent noise of the smaller muscle forces that are required for slower. These insights may be used in the development of fall prevention programs in order to better identify those at increased risk of

  10. Increasing persistence in undergraduate science majors: a model for institutional support of underrepresented students.

    Science.gov (United States)

    Toven-Lindsey, Brit; Levis-Fitzgerald, Marc; Barber, Paul H; Hasson, Tama

    2015-01-01

    The 6-yr degree-completion rate of undergraduate science, technology, engineering, and mathematics (STEM) majors at U.S. colleges and universities is less than 40%. Persistence among women and underrepresented minorities (URMs), including African-American, Latino/a, Native American, and Pacific Islander students, is even more troubling, as these students leave STEM majors at significantly higher rates than their non-URM peers. This study utilizes a matched comparison group design to examine the academic achievement and persistence of students enrolled in the Program for Excellence in Education and Research in the Sciences (PEERS), an academic support program at the University of California, Los Angeles, for first- and second-year science majors from underrepresented backgrounds. Results indicate that PEERS students, on average, earned higher grades in most "gatekeeper" chemistry and math courses, had a higher cumulative grade point average, completed more science courses, and persisted in a science major at significantly higher rates than the comparison group. With its holistic approach focused on academics, counseling, creating a supportive community, and exposure to research, the PEERS program serves as an excellent model for universities interested in and committed to improving persistence of underrepresented science majors and closing the achievement gap. © 2015 B. Toven-Lindsey et al. CBE—Life Sciences Education © 2015 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  11. Nutritional intra-amniotic therapy increases survival in a rabbit model of fetal growth restriction

    Science.gov (United States)

    Illa, Miriam; Pla, Laura; Zamora, Monica; Crispi, Fatima; Gratacos, Eduard

    2018-01-01

    Objective To evaluate the perinatal effects of a prenatal therapy based on intra-amniotic nutritional supplementation in a rabbit model of intrauterine growth restriction (IUGR). Methods IUGR was surgically induced in pregnant rabbits at gestational day 25 by ligating 40–50% of uteroplacental vessels of each gestational sac. At the same time, modified-parenteral nutrition solution (containing glucose, amino acids and electrolytes) was injected into the amniotic sac of nearly half of the IUGR fetuses (IUGR-T group n = 106), whereas sham injections were performed in the rest of fetuses (IUGR group n = 118). A control group without IUGR induction but sham injection was also included (n = 115). Five days after the ligation procedure, a cesarean section was performed to evaluate fetal cardiac function, survival and birth weight. Results Survival was significantly improved in the IUGR fetuses that were treated with intra-amniotic nutritional supplementation as compared to non-treated IUGR animals (survival rate: controls 71% vs. IUGR 44% p = 0.003 and IUGR-T 63% vs. IUGR 44% p = 0.02), whereas, birth weight (controls mean 43g ± SD 9 vs. IUGR 36g ± SD 9 vs. IUGR-T 35g ± SD 8, p = 0.001) and fetal cardiac function were similar among the IUGR groups. Conclusion Intra-amniotic injection of a modified-parenteral nutrient solution appears to be a promising therapy for reducing mortality among IUGR. These results provide an opportunity to develop new intra-amniotic nutritional strategies to reach the fetus by bypassing the placental insufficiency. PMID:29466434

  12. Video Modeling of SBIRT for Alcohol Use Disorders Increases Student Empathy in Standardized Patient Encounters.

    Science.gov (United States)

    Crisafio, Anthony; Anderson, Victoria; Frank, Julia

    2018-04-01

    The purpose of this study was to assess the usefulness of adding video models of brief alcohol assessment and counseling to a standardized patient (SP) curriculum that covers and tests acquisition of this skill. The authors conducted a single-center, retrospective cohort study of third- and fourth-year medical students between 2013 and 2015. All students completed a standardized patient (SP) encounter illustrating the diagnosis of alcohol use disorder, followed by an SP exam on the same topic. Beginning in August 2014, the authors supplemented the existing formative SP exercise on problem drinking with one of two 5-min videos demonstrating screening, brief intervention, and referral for treatment (SBIRT). P values and Z tests were performed to evaluate differences between students who did and did not see the video in knowledge and skills related to alcohol use disorders. One hundred ninety-four students were included in this analysis. Compared to controls, subjects did not differ in their ability to uncover and accurately characterize an alcohol problem during a standardized encounter (mean exam score 41.29 vs 40.93, subject vs control, p = 0.539). However, the SPs' rating of students' expressions of empathy were significantly higher for the group who saw the video (81.63 vs 69.79%, p videos would improve students' recognition and knowledge of alcohol-related conditions. However, feedback from the SPs produced the serendipitous finding that the communication skills demonstrated in the videos had a sustained effect in enhancing students' professional behavior.

  13. Process-based modeling of silicate mineral weathering responses to increasing atmospheric CO2 and climate change

    Science.gov (United States)

    Banwart, Steven A.; Berg, Astrid; Beerling, David J.

    2009-12-01

    A mathematical model describes silicate mineral weathering processes in modern soils located in the boreal coniferous region of northern Europe. The process model results demonstrate a stabilizing biological feedback mechanism between atmospheric CO2 levels and silicate weathering rates as is generally postulated for atmospheric evolution. The process model feedback response agrees within a factor of 2 of that calculated by a weathering feedback function of the type generally employed in global geochemical carbon cycle models of the Earth's Phanerozoic CO2 history. Sensitivity analysis of parameter values in the process model provides insight into the key mechanisms that influence the strength of the biological feedback to weathering. First, the process model accounts for the alkalinity released by weathering, whereby its acceleration stabilizes pH at values that are higher than expected. Although the process model yields faster weathering with increasing temperature, because of activation energy effects on mineral dissolution kinetics at warmer temperature, the mineral dissolution rate laws utilized in the process model also result in lower dissolution rates at higher pH values. Hence, as dissolution rates increase under warmer conditions, more alkalinity is released by the weathering reaction, helping maintain higher pH values thus stabilizing the weathering rate. Second, the process model yields a relatively low sensitivity of soil pH to increasing plant productivity. This is due to more rapid decomposition of dissolved organic carbon (DOC) under warmer conditions. Because DOC fluxes strongly influence the soil water proton balance and pH, this increased decomposition rate dampens the feedback between productivity and weathering. The process model is most sensitive to parameters reflecting soil structure; depth, porosity, and water content. This suggests that the role of biota to influence these characteristics of the weathering profile is as important, if not

  14. Agricultural Capacity to Increase the Production of Select Fruits and Vegetables in the US: A Geospatial Modeling Analysis.

    Science.gov (United States)

    Conrad, Zach; Peters, Christian J; Chui, Kenneth; Jahns, Lisa; Griffin, Timothy S

    2017-09-23

    The capacity of US agriculture to increase the output of specific foods to accommodate increased demand is not well documented. This research uses geospatial modeling to examine the capacity of the US agricultural landbase to increase the per capita availability of an example set of nutrient-dense fruits and vegetables. These fruits and vegetables were selected based on nutrient content and an increasing trend of domestic production and consumption. Geographic information system models were parameterized to identify agricultural land areas meeting crop-specific growing requirements for monthly precipitation and temperature; soil depth and type; cropland availability; and proximity to existing production centers. The results of these analyses demonstrate that crop production can be expanded by nearly 144,000 ha within existing national production centers, generating an additional 0.05 cup-equivalents of fruits and vegetables per capita per day, representing a 1.7% increase above current total F&V availability. Expanding the size of national crop production centers can further increase the availability of all F&V by 2.5%-5.4%, which is still less than the recommended amount. Challenges to increasing F&V production in the US include lack of labor availability, barriers to adoption among producers, and threats to crop yields from environmental concerns.

  15. An Instructional Design Model for Developing a Computer Curriculum To Increase Employee Productivity in a Pharmaceutical Company.

    Science.gov (United States)

    Stumpf, Mark R.

    This report presents an instructional design model that was developed for use by the End-Users Computing department of a large pharmaceutical company in developing effective--but not lengthy--microcomputer training seminars to train office workers and executives in the proper use of computers and thus increase their productivity. The 14 steps of…

  16. Translocation of differently sized and charged polystyrene nanoparticles in in vitro intestinal cell models of increasing complexity

    NARCIS (Netherlands)

    Walczak, A.P.; Kramer, E.; Hendriksen, P.J.M.; Tromp, P.; Helsper, J.P.F.G.; Zande, M. van der; Rietjens, I.M.C.M.; Bouwmeester, H.

    2015-01-01

    Intestinal translocation is a key factor for determining bioavailability of nanoparticles (NPs) after oral uptake. Therefore, we evaluated three in vitro intestinal cell models of increasing complexity which might affect the translocation of NPs: a mono-culture (Caco-2 cells), a co-culture with

  17. The Influence of Herbivory on the net rate of Increase of Gypsy Moth Abundance: A Modeling Analysis

    Science.gov (United States)

     Harry T.  Valentine

    1983-01-01

    A differential equation model of gypsy moth abundance, average larval dry weight, and food abundance was used to analyze the effects of changes in foliar chemistry on the net per capita rate of increase in a gypsy moth population. If relative consumption rate per larva is unaffected by herbivory, a reduction in the nutritional value of foliage reduces the net rate of...

  18. Increasing Employability by Implementing a Work-Integrated Learning Partnership Model in South Africa--A Student Perspective

    Science.gov (United States)

    Taylor, Susanne; Govender, Cookie M.

    2017-01-01

    In South Africa, 70 per cent of the population is under 35 years old. South Africa has a vision to increase youth employment by focusing on education, training and skills development that will promote employment opportunities. A work-integrated learning (WIL) partnership model was developed to provide students with work experience and to increase…

  19. Creative Accounting Model for Increasing Banking Industries’ Competitive Advantage in Indonesia

    Directory of Open Access Journals (Sweden)

    Supriyati

    2015-12-01

    Full Text Available Bank Indonesia demands that the national banks should improve their transparency of financial condition and performance for public in line with the development of their products and activities. Furthermore, the banks’ financial statements of Bank Indonesia have become the basis for determining the status of their soundness. In fact, they tend to practice earnings management in order that they can meet the crite-ria required by Bank Indonesia. For internal purposes, the initiative of earning management has a positive impact on the performance of management. However, for the users of financial statements, it may dif-fer, for example for the value of company, length of time the financial audit, and other aspects of tax evasion by the banks. This study tries to find out 1 the effect of GCG on Earnings Management, 2 the effect of earning management on Company value, theAudit Report Lag, and Taxation, and 3 the effect of Audit Report Lag on Corporate Value and Taxation. This is a quantitative research with the data collected from the bank financial statements, GCG implementation report, and the banks’ annual reports of 2003-2013. There were 41 banks taken using purposive sampling, as listed on the Indonesia Stock Exchange. The results showed that the implementation of GCG affects the occurrence of earning management. Accounting policy flexibility through earning management is expected to affect the length of the audit process and the accuracy of the financial statements presentation on public side. This research is expected to provide managerial implications in order to consider the possibility of earnings management practices in the banking industry. In the long term, earning management is expected to improve the banks’ competitiveness through an increase in the value of the company. Explicitly, earning management also affects the tax avoidance; therefore, the banks intend to pay lower taxes without breaking the existing legislation Taxation

  20. Creative Accounting Model for Increasing Banking Industries’ Competitive Advantage in Indonesia (P.197-207

    Directory of Open Access Journals (Sweden)

    Supriyati Supriyati

    2017-01-01

    Full Text Available Bank Indonesia demands that the national banks should improve their transparency of financial condition and performance for public in line with the development of their products and activities. Furthermore, the banks’ financial statements of Bank Indonesia have become the basis for determining the status of their soundness. In fact, they tend to practice earnings management in order that they can meet the criteria required by Bank Indonesia. For internal purposes, the initiative of earning management has a positive impact on the performance of management. However, for the users of financial statements, it may differ, for example for the value of company, length of time the financial audit, and other aspects of tax evasion by the banks. This study tries to find out 1 the effect of GCG on Earnings Management, 2 the effect of earning management on Company value, the Audit Report Lag, and Taxation, and 3 the effect of Audit Report Lag on Corporate Value and Taxation. This is a quantitative research with the data collected from the bank financial statements, GCG implementation report, and the banks’ annual reports of 2003-2013. There were 41 banks taken using purposive sampling, as listed on the Indonesia Stock Exchange. The results showed that the implementation of GCG affects the occurrence of earning management. Accounting policy flexibility through earning management is expected to affect the length of the audit process and the accuracy of the financial statements presentation on public side. This research is expected to provide managerial implications in order to consider the possibility of earnings management practices in the banking industry. In the long term, earning management is expected to improve the banks’ competitiveness through an increase in the value of the company. Explicitly, earning management also affects the tax avoidance; therefore, the banks intend to pay lower taxes without breaking the existing legislation Taxation

  1. Increased chemokine signaling in a model of HIV1-associated peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Buchanan David J

    2009-08-01

    Full Text Available Abstract Painful distal sensory polyneuropathy (DSP is the most common neurological complication of HIV1 infection. Although infection with the virus itself is associated with an incidence of DSP, patients are more likely to become symptomatic following initiation of nucleoside reverse transcriptase inhibitor (NRTI treatment. The chemokines monocyte chemoattractant protein-1 (MCP1/CCL2 and stromal derived factor-1 (SDF1/CXCL12 and their respective receptors, CCR2 and CXCR4, have been implicated in HIV1 related neuropathic pain mechanisms including NRTI treatment in rodents. Utilizing a rodent model that incorporates the viral coat protein, gp120, and the NRTI, 2'3'-dideoxycytidine (ddC, we examined the degree to which chemokine receptor signaling via CCR2 and CXCR4 potentially influences the resultant chronic hypernociceptive behavior. We observed that following unilateral gp120 sciatic nerve administration, rats developed profound tactile hypernociception in the hindpaw ipsilateral to gp120 treatment. Behavioral changes were also present in the hindpaw contralateral to the injury, albeit delayed and less robust. Using immunohistochemical studies, we demonstrated that MCP1 and CCR2 were upregulated by primary sensory neurons in lumbar ganglia by post-operative day (POD 14. The functional nature of these observations was confirmed using calcium imaging in acutely dissociated lumbar dorsal root ganglion (DRG derived from gp120 injured rats at POD 14. Tactile hypernociception in gp120 treated animals was reversed following treatment with a CCR2 receptor antagonist at POD 14. Some groups of animals were subjected to gp120 sciatic nerve injury in combination with an injection of ddC at POD 14. This injury paradigm produced pronounced bilateral tactile hypernociception from POD 14–48. More importantly, functional MCP1/CCR2 and SDF1/CXCR4 signaling was present in sensory neurons. In contrast to gp120 treatment alone, the hypernociceptive behavior

  2. Using 3D Printers to Model Earth Surface Topography for Increased Student Understanding and Retention

    Science.gov (United States)

    Thesenga, David; Town, James

    2014-05-01

    visualization and exporting as a .stl file for 3D printing. A proposal for improving the method and making it more accessible to middle school aged students is provided. Using the SRTM data to print a hand-held visual representation of a portion of the Earth's surface would utilize existing technology in the school and alter how topography can be taught in the classroom. Combining methods of 2D paper representations, on-screen 3D visualizations, and 3D hand-held models, give students the opportunity to truly grasp and retain the information being provided.

  3. Early coordinated rehabilitation in acute phase after hip fracture - a model for increased patient participation.

    Science.gov (United States)

    Asplin, Gillian; Carlsson, Gunnel; Zidén, Lena; Kjellby-Wendt, Gunilla

    2017-10-17

    Studies have shown that patients with hip fracture treated in a Comprehensive Geriatric Care (CGC) unit report better results in comparison to orthopaedic care. Furthermore, involving patients in their healthcare by encouraging patient participation can result in better quality of care and improved outcomes. To our knowledge no study has been performed comparing rehabilitation programmes within a CGC unit during the acute phase after hip fracture with focus on improving patients' perceived participation and subsequent effect on patients' function. A prospective, controlled, intervention performed in a CGC unit and compared with standard care. A total of 126 patients with hip fracture were recruited who were prior to fracture; community dwelling, mobile indoors and independent in personal care. Intervention Group (IG): 63 patients, mean age 82.0 years and Control Group (CG): 63 patients mean age 80.5 years. coordinated rehabilitation programme with early onset of patient participation and intensified occupational therapy and physiotherapy after hip fracture surgery. The primary outcome measure was self-reported patient participation at discharge. Secondary outcome measures were: TLS-BasicADL; Bergs Balance Scale (BBS); Falls Efficacy Scale FES(S); Short Physical Performance Battery (SPPB) and Timed Up and Go (TUG) at discharge and 1 month and ADL staircase for instrumental ADL at 1 month. At discharge a statistically significant greater number of patients in the IG reported higher levels of participation (p < 0.05) and independence in lower body hygiene (p < 0.05) and dressing (p < 0.001). There were however no statistically significant differences at discharge and 1 month between groups in functional balance and confidence, performance measures or risk for falls. This model of OT and PT coordinated inpatient rehabilitation had a positive effect on patients' perceived participation in their rehabilitation and ADL at discharge but did not appear to

  4. Understanding why the volume of suboxic waters does not increase over centuries of global warming in an Earth System Model

    Directory of Open Access Journals (Sweden)

    A. Gnanadesikan

    2012-03-01

    Full Text Available Global warming is expected to reduce oxygen solubility and vertical exchange in the ocean, changes which would be expected to result in an increase in the volume of hypoxic waters. A simulation made with a full Earth System model with dynamical atmosphere, ocean, sea ice and biogeochemical cycling (the Geophysical Fluid Dynamics Laboratory's Earth System Model 2.1 shows that this holds true if the condition for hypoxia is set relatively high. However, the volume of the most hypoxic (i.e., suboxic waters does not increase under global warming, as these waters actually become more oxygenated. We show that the rise in dissolved oxygen in the tropical Pacific is associated with a drop in ventilation time. A term-by-term analysis within the least oxygenated waters shows an increased supply of dissolved oxygen due to lateral diffusion compensating an increase in remineralization within these highly hypoxic waters. This lateral diffusive flux is the result of an increase of ventilation along the Chilean coast, as a drying of the region under global warming opens up a region of wintertime convection in our model. The results highlight the potential sensitivity of suboxic waters to changes in subtropical ventilation as well as the importance of constraining lateral eddy transport of dissolved oxygen in such waters.

  5. Understanding why the volume of suboxic waters does not increase over centuries of global warming in an Earth System Model

    Science.gov (United States)

    Gnanadesikan, A.; Dunne, J. P.; John, J.

    2012-03-01

    Global warming is expected to reduce oxygen solubility and vertical exchange in the ocean, changes which would be expected to result in an increase in the volume of hypoxic waters. A simulation made with a full Earth System model with dynamical atmosphere, ocean, sea ice and biogeochemical cycling (the Geophysical Fluid Dynamics Laboratory's Earth System Model 2.1) shows that this holds true if the condition for hypoxia is set relatively high. However, the volume of the most hypoxic (i.e., suboxic) waters does not increase under global warming, as these waters actually become more oxygenated. We show that the rise in dissolved oxygen in the tropical Pacific is associated with a drop in ventilation time. A term-by-term analysis within the least oxygenated waters shows an increased supply of dissolved oxygen due to lateral diffusion compensating an increase in remineralization within these highly hypoxic waters. This lateral diffusive flux is the result of an increase of ventilation along the Chilean coast, as a drying of the region under global warming opens up a region of wintertime convection in our model. The results highlight the potential sensitivity of suboxic waters to changes in subtropical ventilation as well as the importance of constraining lateral eddy transport of dissolved oxygen in such waters.

  6. Application of experiential learning model using simple physical kit to increase attitude toward physics student senior high school in fluid

    Science.gov (United States)

    Johari, A. H.; Muslim

    2018-05-01

    Experiential learning model using simple physics kit has been implemented to get a picture of improving attitude toward physics senior high school students on Fluid. This study aims to obtain a description of the increase attitudes toward physics senior high school students. The research method used was quasi experiment with non-equivalent pretest -posttest control group design. Two class of tenth grade were involved in this research 28, 26 students respectively experiment class and control class. Increased Attitude toward physics of senior high school students is calculated using an attitude scale consisting of 18 questions. Based on the experimental class test average of 86.5% with the criteria of almost all students there is an increase and in the control class of 53.75% with the criteria of half students. This result shows that the influence of experiential learning model using simple physics kit can improve attitude toward physics compared to experiential learning without using simple physics kit.

  7. Intraperitoneal administration of docosahexaenoic acid for 14days increases serum unesterified DHA and seizure latency in the maximal pentylenetetrazol model.

    Science.gov (United States)

    Trépanier, Marc-Olivier; Lim, Joonbum; Lai, Terence K Y; Cho, Hye Jin; Domenichiello, Anthony F; Chen, Chuck T; Taha, Ameer Y; Bazinet, Richard P; Burnham, W M

    2014-04-01

    Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) which has been shown to raise seizure thresholds following acute administration in rats. The aims of the present experiment were the following: 1) to test whether subchronic DHA administration raises seizure threshold in the maximal pentylenetetrazol (PTZ) model 24h following the last injection and 2) to determine whether the increase in seizure threshold is correlated with an increase in serum and/or brain DHA. Animals received daily intraperitoneal (i.p.) injections of 50mg/kg of DHA, DHA ethyl ester (DHA EE), or volume-matched vehicle (albumin/saline) for 14days. On day 15, one subset of animals was seizure tested in the maximal PTZ model (Experiment 1). In a separate (non-seizure tested) subset of animals, blood was collected, and brains were excised following high-energy, head-focused microwave fixation. Lipid analysis was performed on serum and brain (Experiment 2). For data analysis, the DHA and DHA EE groups were combined since they did not differ significantly from each other. In the maximal PTZ model, DHA significantly increased seizure latency by approximately 3-fold as compared to vehicle-injected animals. This increase in seizure latency was associated with an increase in serum unesterified DHA. Total brain DHA and brain unesterified DHA concentrations, however, did not differ significantly in the treatment and control groups. An increase in serum unesterified DHA concentration reflecting increased flux of DHA to the brain appears to explain changes in seizure threshold, independent of changes in brain DHA concentrations. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. An herbal medicine, Go-sha-jinki-gan (GJG, increases muscle weight in severe muscle dystrophy model mice

    Directory of Open Access Journals (Sweden)

    Yusei Takemoto

    2017-12-01

    Full Text Available Go-sha-jinki-gan (GJG, a traditional Japanese herbal medicine has a clinical implication to alleviate age-related symptoms, especially in some motor disorders. However, the scientific evidence is limited, and there is a possibility to expand the medical application range of GJG. Using senescence-accelerated mice, our group showed that GJG exerted an effect to prevent sarcopenia, the aged-related loss of skeletal muscle. Because muscular dystrophy is characterized by a progressive loss of skeletal muscle, we examined the effects of GJG on a mouse model of muscular dystrophy. Using a newly established mouse model for Duchenne muscular dystrophy (DMD, DBA/2-mdx, we showed that GJG significantly increased the body and skeletal muscle weights in comparison to the control DBA/2-mdx mice, regardless of gender. The increased skeletal muscle mass resulted from an increment in the myofiber size, but not from the myofiber number. Both the skeletal muscle regenerative ability and the accumulation of fibrosis (the dystrophic pathology in GJG-fed DBA/2-mdx mice were comparable to those in control DBA/2-mdx mice, suggesting that the cellular target of GJG is myofibers, with no contribution from the muscle satellite cells neither in an direct nor in an indirect manner. Taken together, GJG increased the skeletal muscle mass in a mouse model of muscular dystrophy, in addition to our previously tested sarcopenia mouse model.

  9. Increased trabecular bone and improved biomechanics in an osteocalcin-null rat model created by CRISPR/Cas9 technology

    Directory of Open Access Journals (Sweden)

    Laura J. Lambert

    2016-10-01

    Full Text Available Osteocalcin, also known as bone γ-carboxyglutamate protein (Bglap, is expressed by osteoblasts and is commonly used as a clinical marker of bone turnover. A mouse model of osteocalcin deficiency has implicated osteocalcin as a mediator of changes to the skeleton, endocrine system, reproductive organs and central nervous system. However, differences between mouse and human osteocalcin at both the genome and protein levels have challenged the validity of extrapolating findings from the osteocalcin-deficient mouse model to human disease. The rat osteocalcin (Bglap gene locus shares greater synteny with that of humans. To further examine the role of osteocalcin in disease, we created a rat model with complete loss of osteocalcin using the CRISPR/Cas9 system. Rat osteocalcin was modified by injection of CRISPR/Cas9 mRNA into the pronuclei of fertilized single cell Sprague-Dawley embryos, and animals were bred to homozygosity and compound heterozygosity for the mutant alleles. Dual-energy X-ray absorptiometry (DXA, glucose tolerance testing (GTT, insulin tolerance testing (ITT, microcomputed tomography (µCT, and a three-point break biomechanical assay were performed on the excised femurs at 5 months of age. Complete loss of osteocalcin resulted in bones with significantly increased trabecular thickness, density and volume. Cortical bone volume and density were not increased in null animals. The bones had improved functional quality as evidenced by an increase in failure load during the biomechanical stress assay. Differences in glucose homeostasis were observed between groups, but there were no differences in body weight or composition. This rat model of complete loss of osteocalcin provides a platform for further understanding the role of osteocalcin in disease, and it is a novel model of increased bone formation with potential utility in osteoporosis and osteoarthritis research.

  10. Modeling caspian sea water level oscilLations Under Diffrent Scenarioes of Increasing Atmospheric Carbon Dioxide Concentrations

    Directory of Open Access Journals (Sweden)

    GholamReza Roshan

    2012-12-01

    Full Text Available The rapid rise of Caspian Sea water level (about 2.25 meters since 1978 has caused much concern to all five surrounding countries, primarily because flooding has destroyed or damaged buildings and other engineering structures, roads, beaches and farm lands in thecoastal zone. Given that climate, and more specifically climate change, is a primary factor influencing oscillations in Caspian Sea water levels, the effect of different climate change scenarios on future Caspian Sea levels was stimulated. Variations in environmentalparameters such as temperature, precipitation, evaporation, tmospheric carbon dioxide and water level oscillations of the Caspian sea and surrounding regions, are considered for bothpast (1951-2006 and future (2025-2100 time frames. The output of the UKHADGEM general circulation model and five alternative scenarios including A1CAI, BIASF, BIMES WRE450 and WRE750 were extracted using the MAGICC SCENGEN Model software(version 5.3. The results suggest that the mean temperature of the Caspian Sea region (Bandar-E-Anzali monitoring site has increased by ca. 0.17ºC per decade under the impacts of atmospheric carbon dioxide changes (r=0.21. The Caspian Sea water level has increasedby ca. +36 mm per decade (r=0.82 between the years 1951-2006. Mean results from all modeled scenarios indicate that the temperature will increase by ca. 3.64ºC and precipitation will decrease by ca. 10% (182 mm over the Caspian Sea, whilst in the Volga river basin,temperatures are projected to increase by ca. 4.78ºC and precipitation increase by ca. 12% (58 mm by the year 2100. Finally, statistical modeling of the Caspian Sea water levels projectfuture water level increases of between 86 cm and 163 cm by the years 2075 and 2100, respectively.

  11. Increased drought impacts on temperate rainforests from southern South America: results of a process-based, dynamic forest model.

    Directory of Open Access Journals (Sweden)

    Alvaro G Gutiérrez

    Full Text Available Increased droughts due to regional shifts in temperature and rainfall regimes are likely to affect forests in temperate regions in the coming decades. To assess their consequences for forest dynamics, we need predictive tools that couple hydrologic processes, soil moisture dynamics and plant productivity. Here, we developed and tested a dynamic forest model that predicts the hydrologic balance of North Patagonian rainforests on Chiloé Island, in temperate South America (42°S. The model incorporates the dynamic linkages between changing rainfall regimes, soil moisture and individual tree growth. Declining rainfall, as predicted for the study area, should mean up to 50% less summer rain by year 2100. We analysed forest responses to increased drought using the model proposed focusing on changes in evapotranspiration, soil moisture and forest structure (above-ground biomass and basal area. We compared the responses of a young stand (YS, ca. 60 years-old and an old-growth forest (OG, >500 years-old in the same area. Based on detailed field measurements of water fluxes, the model provides a reliable account of the hydrologic balance of these evergreen, broad-leaved rainforests. We found higher evapotranspiration in OG than YS under current climate. Increasing drought predicted for this century can reduce evapotranspiration by 15% in the OG compared to current values. Drier climate will alter forest structure, leading to decreases in above ground biomass by 27% of the current value in OG. The model presented here can be used to assess the potential impacts of climate change on forest hydrology and other threats of global change on future forests such as fragmentation, introduction of exotic tree species, and changes in fire regimes. Our study expands the applicability of forest dynamics models in remote and hitherto overlooked regions of the world, such as southern temperate rainforests.

  12. Increased drought impacts on temperate rainforests from southern South America: results of a process-based, dynamic forest model.

    Science.gov (United States)

    Gutiérrez, Alvaro G; Armesto, Juan J; Díaz, M Francisca; Huth, Andreas

    2014-01-01

    Increased droughts due to regional shifts in temperature and rainfall regimes are likely to affect forests in temperate regions in the coming decades. To assess their consequences for forest dynamics, we need predictive tools that couple hydrologic processes, soil moisture dynamics and plant productivity. Here, we developed and tested a dynamic forest model that predicts the hydrologic balance of North Patagonian rainforests on Chiloé Island, in temperate South America (42°S). The model incorporates the dynamic linkages between changing rainfall regimes, soil moisture and individual tree growth. Declining rainfall, as predicted for the study area, should mean up to 50% less summer rain by year 2100. We analysed forest responses to increased drought using the model proposed focusing on changes in evapotranspiration, soil moisture and forest structure (above-ground biomass and basal area). We compared the responses of a young stand (YS, ca. 60 years-old) and an old-growth forest (OG, >500 years-old) in the same area. Based on detailed field measurements of water fluxes, the model provides a reliable account of the hydrologic balance of these evergreen, broad-leaved rainforests. We found higher evapotranspiration in OG than YS under current climate. Increasing drought predicted for this century can reduce evapotranspiration by 15% in the OG compared to current values. Drier climate will alter forest structure, leading to decreases in above ground biomass by 27% of the current value in OG. The model presented here can be used to assess the potential impacts of climate change on forest hydrology and other threats of global change on future forests such as fragmentation, introduction of exotic tree species, and changes in fire regimes. Our study expands the applicability of forest dynamics models in remote and hitherto overlooked regions of the world, such as southern temperate rainforests.

  13. Will building new reservoirs always help increase the water supply reliability? - insight from a modeling-based global study

    Science.gov (United States)

    Zhuang, Y.; Tian, F.; Yigzaw, W.; Hejazi, M. I.; Li, H. Y.; Turner, S. W. D.; Vernon, C. R.

    2017-12-01

    More and more reservoirs are being build or planned in order to help meet the increasing water demand all over the world. However, is building new reservoirs always helpful to water supply? To address this question, the river routing module of Global Change Assessment Model (GCAM) has been extended with a simple yet physical-based reservoir scheme accounting for irrigation, flood control and hydropower operations at each individual reservoir. The new GCAM river routing model has been applied over the global domain with the runoff inputs from the Variable Infiltration Capacity Model. The simulated streamflow is validated at 150 global river basins where the observed streamflow data are available. The model performance has been significantly improved at 77 basins and worsened at 35 basins. To facilitate the analysis of additional reservoir storage impacts at the basin level, a lumped version of GCAM reservoir model has been developed, representing a single lumped reservoir at each river basin which has the regulation capacity of all reservoir combined. A Sequent Peak Analysis is used to estimate how much additional reservoir storage is required to satisfy the current water demand. For basins with water deficit, the water supply reliability can be improved with additional storage. However, there is a threshold storage value at each basin beyond which the reliability stops increasing, suggesting that building new reservoirs will not help better relieve the water stress. Findings in the research can be helpful to the future planning and management of new reservoirs.

  14. Understanding why the volume of suboxic waters does not increase over centuries of global warming in an Earth System Model

    OpenAIRE

    A. Gnanadesikan; J. P. Dunne; J. John

    2012-01-01

    Global warming is expected to reduce oxygen solubility and vertical exchange in the ocean, changes which would be expected to result in an increase in the volume of hypoxic waters. A simulation made with a full Earth System model with dynamical atmosphere, ocean, sea ice and biogeochemical cycling (the Geophysical Fluid Dynamics Laboratory's Earth System Model 2.1) shows that this holds true if the condition for hypoxia is set relatively high. However, the volume of the most hypoxic (i.e., su...

  15. Modeling the response of forest isoprene emissions to future increases in atmospheric CO2 concentration and changes in climate (Invited)

    Science.gov (United States)

    Monson, R. K.; Heald, C. L.; Guenther, A. B.; Wilkinson, M.

    2009-12-01

    Isoprene emissions from plants to the atmosphere are sensitive to changes in temperature, light and atmospheric CO2 concentration in both the short- (seconds-to-minutes) and long-term (hours-to-months). We now understand that the different time constants for these responses are due to controls by different sets of biochemical and physiological processes n leaves. Progress has been made in the past few years toward converting this process-level understanding into quantitative models. In this talk, we consider this progress with special emphasis on the short- and long-term responses to atmospheric CO2 concentration and temperature. A new biochemically-based model is presented for describing the CO2 responses, and the model is deployed in a global context to predict interactions between the influences of temperature and CO2 on the global isoprene emission rate. The model is based on the theory of enzyme-substrate kinetics, particularly with regard to those reactions that produce puruvate or glyceraldehyde 3-phosphate, the two chloroplastic substrates for isoprene biosynthesis. In the global model, when we accounted for CO2 inhibition of isoprene emission in the long-term response, we observed little impact on present-day global isoprene emission (increase from 508 to 523 Tg C yr-1). However, the large increases in future isoprene emissions predicted from past models which are due to a projected warmer climate, were entirely offset by including the CO2 effects. The isoprene emission response to CO2 was dominated by the long-term growth environment effect, with modulations of 10% or less from the short-term effect. We use this analysis as a framework for grounding future global models of isoprene emission in biochemical and physiological observations.

  16. Increasing taurine intake and taurine synthesis improves skeletal muscle function in the mdx mouse model for Duchenne muscular dystrophy.

    Science.gov (United States)

    Terrill, Jessica R; Pinniger, Gavin J; Graves, Jamie A; Grounds, Miranda D; Arthur, Peter G

    2016-06-01

    Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease associated with increased inflammation, oxidative stress and myofibre necrosis. Cysteine precursor antioxidants such as N-acetyl cysteine (NAC) and l-2-oxothiazolidine-4-carboxylate (OTC) reduce dystropathology in the mdx mouse model for DMD, and we propose this is via increased synthesis of the amino acid taurine. We compared the capacity of OTC and taurine treatment to increase taurine content of mdx muscle, as well as effects on in vivo and ex vivo muscle function, inflammation and oxidative stress. Both treatments increased taurine in muscles, and improved many aspects of muscle function and reduced inflammation. Taurine treatment also reduced protein thiol oxidation and was overall more effective, as OTC treatment reduced body and muscle weight, suggesting some adverse effects of this drug. These data suggest that increasing dietary taurine is a better candidate for a therapeutic intervention for DMD. Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease for which there is no widely available cure. Whilst the mechanism of loss of muscle function in DMD and the mdx mouse model are not fully understood, disruptions in intracellular calcium homeostasis, inflammation and oxidative stress are implicated. We have shown that protein thiol oxidation is increased in mdx muscle, and that the indirect thiol antioxidant l-2-oxothiazolidine-4-carboxylate (OTC), which increases cysteine availability, decreases pathology and increases in vivo strength. We propose that the protective effects of OTC are a consequence of conversion of cysteine to taurine, which has itself been shown to be beneficial to mdx pathology. This study compares the efficacy of taurine with OTC in decreasing dystropathology in mdx mice by measuring in vivo and ex vivo contractile function and measurements of inflammation and protein thiol oxidation. Increasing the taurine content of mdx muscle improved both in vivo and ex

  17. Can broader diffusion of value-based insurance design increase benefits from US health care without increasing costs? Evidence from a computer simulation model.

    Science.gov (United States)

    Braithwaite, R Scott; Omokaro, Cynthia; Justice, Amy C; Nucifora, Kimberly; Roberts, Mark S

    2010-02-16

    Evidence suggests that cost sharing (i.e.,copayments and deductibles) decreases health expenditures but also reduces essential care. Value-based insurance design (VBID) has been proposed to encourage essential care while controlling health expenditures. Our objective was to estimate the impact of broader diffusion of VBID on US health care benefits and costs. We used a published computer simulation of costs and life expectancy gains from US health care to estimate the impact of broader diffusion of VBID. Two scenarios were analyzed: (1) applying VBID solely to pharmacy benefits and (2) applying VBID to both pharmacy benefits and other health care services (e.g., devices). We assumed that cost sharing would be eliminated for high-value services (value services ($100,000-$300,000 per life-year or unknown), and would be increased for low-value services (>$300,000 per life-year). All costs are provided in 2003 US dollars. Our simulation estimated that approximately 60% of health expenditures in the US are spent on low-value services, 20% are spent on intermediate-value services, and 20% are spent on high-value services. Correspondingly, the vast majority (80%) of health expenditures would have cost sharing that is impacted by VBID. With prevailing patterns of cost sharing, health care conferred 4.70 life-years at a per-capita annual expenditure of US$5,688. Broader diffusion of VBID to pharmaceuticals increased the benefit conferred by health care by 0.03 to 0.05 additional life-years, without increasing costs and without increasing out-of-pocket payments. Broader diffusion of VBID to other health care services could increase the benefit conferred by health care by 0.24 to 0.44 additional life-years, also without increasing costs and without increasing overall out-of-pocket payments. Among those without health insurance, using cost saving from VBID to subsidize insurance coverage would increase the benefit conferred by health care by 1.21 life-years, a 31% increase

  18. Demographic population model for American shad: will access to additional habitat upstream of dams increase population sizes?

    Science.gov (United States)

    Harris, Julianne E.; Hightower, Joseph E.

    2012-01-01

    American shad Alosa sapidissima are in decline in their native range, and modeling possible management scenarios could help guide their restoration. We developed a density-dependent, deterministic, stage-based matrix model to predict the population-level results of transporting American shad to suitable spawning habitat upstream of dams on the Roanoke River, North Carolina and Virginia. We used data on sonic-tagged adult American shad and oxytetracycline-marked American shad fry both above and below dams on the Roanoke River with information from other systems to estimate a starting population size and vital rates. We modeled the adult female population over 30 years under plausible scenarios of adult transport, effective fecundity (egg production), and survival of adults (i.e., to return to spawn the next year) and juveniles (from spawned egg to age 1). We also evaluated the potential effects of increased survival for adults and juveniles. The adult female population size in the Roanoke River was estimated to be 5,224. With no transport, the model predicted a slow population increase over the next 30 years. Predicted population increases were highest when survival was improved during the first year of life. Transport was predicted to benefit the population only if high rates of effective fecundity and juvenile survival could be achieved. Currently, transported adults and young are less likely to successfully out-migrate than individuals below the dams, and the estimated adult population size is much smaller than either of two assumed values of carrying capacity for the lower river; therefore, transport is not predicted to help restore the stock under present conditions. Research on survival rates, density-dependent processes, and the impacts of structures to increase out-migration success would improve evaluation of the potential benefits of access to additional spawning habitat for American shad.

  19. STRUCTURAL AND METHODICAL MODEL OF INCREASING THE LEVEL OF THEORETICAL TRAINING OF CADETS USING INFORMATION AND COMMUNICATION TECHNOLOGIES

    Directory of Open Access Journals (Sweden)

    Vladislav V. Bulgakov

    2018-03-01

    Full Text Available Features of training in higher educational institutions of system of EMERCOM of Russia demand introduction of the new educational techniques and the technical means directed on intensification of educational process, providing an opportunity of preparation of cadets at any time in the independent mode and improving quality of their theoretical knowledge. The authors have developed a structural and methodological model of increasing the level of theoretical training of cadets using information and communication technologies. The proposed structural and methodological model that includes elements to stimulate and enhance cognitive activity, allows you to generate the trajectory of theoretical training of cadets for the entire period of study at the University, to organize a systematic independent work, objective, current and final control of theoretical knowledge. The structural and methodological model for improving the level of theoretical training consists of three main elements: the base of theoretical questions, functional modules "teacher" and "cadet". The basis of the structural and methodological model of increasing the level of theoretical training of cadets is the base of theoretical issues, developed in all disciplines specialty 20.05.01 – fire safety. The functional module "teacher" allows you to create theoretical questions of various kinds, edit questions and delete them from the database if necessary, as well as create tests and monitor their implementation. The functional module "cadet" provides ample opportunities for theoretical training through independent work, testing for current and final control, the implementation of the game form of training in the form of a duel, as well as for the formation of the results of the cadets in the form of statistics and rankings. Structural and methodical model of increasing the level of theoretical training of cadets is implemented in practice in the form of a multi-level automated system

  20. Using agent based modeling to assess the effect of increased Bus Rapid Transit system infrastructure on walking for transportation.

    Science.gov (United States)

    Lemoine, Pablo D; Cordovez, Juan Manuel; Zambrano, Juan Manuel; Sarmiento, Olga L; Meisel, Jose D; Valdivia, Juan Alejandro; Zarama, Roberto

    2016-07-01

    The effect of transport infrastructure on walking is of interest to researchers because it provides an opportunity, from the public policy point of view, to increase physical activity (PA). We use an agent based model (ABM) to examine the effect of transport infrastructure on walking. Particular relevance is given to assess the effect of the growth of the Bus Rapid Transit (BRT) system in Bogotá on walking. In the ABM agents are assigned a home, work location, and socioeconomic status (SES) based on which they are assigned income for transportation. Individuals must decide between the available modes of transport (i.e., car, taxi, bus, BRT, and walking) as the means of reaching their destination, based on resources and needed travel time. We calibrated the model based on Bogota's 2011 mobility survey. The ABM results are consistent with previous empirical findings, increasing BRT access does indeed increase the number of minutes that individuals walk for transportation, although this effect also depends on the availability of other transport modes. The model indicates a saturation process: as more BRT lanes are added, the increment in minutes walking becomes smaller, and eventually the walking time decreases. Our findings on the potential contribution of the expansion of the BRT system to walking for transportation suggest that ABMs may prove helpful in designing policies to continue promoting walking. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Can broader diffusion of value-based insurance design increase benefits from US health care without increasing costs? Evidence from a computer simulation model.

    Directory of Open Access Journals (Sweden)

    R Scott Braithwaite

    2010-02-01

    Full Text Available BACKGROUND: Evidence suggests that cost sharing (i.e.,copayments and deductibles decreases health expenditures but also reduces essential care. Value-based insurance design (VBID has been proposed to encourage essential care while controlling health expenditures. Our objective was to estimate the impact of broader diffusion of VBID on US health care benefits and costs. METHODS AND FINDINGS: We used a published computer simulation of costs and life expectancy gains from US health care to estimate the impact of broader diffusion of VBID. Two scenarios were analyzed: (1 applying VBID solely to pharmacy benefits and (2 applying VBID to both pharmacy benefits and other health care services (e.g., devices. We assumed that cost sharing would be eliminated for high-value services ($300,000 per life-year. All costs are provided in 2003 US dollars. Our simulation estimated that approximately 60% of health expenditures in the US are spent on low-value services, 20% are spent on intermediate-value services, and 20% are spent on high-value services. Correspondingly, the vast majority (80% of health expenditures would have cost sharing that is impacted by VBID. With prevailing patterns of cost sharing, health care conferred 4.70 life-years at a per-capita annual expenditure of US$5,688. Broader diffusion of VBID to pharmaceuticals increased the benefit conferred by health care by 0.03 to 0.05 additional life-years, without increasing costs and without increasing out-of-pocket payments. Broader diffusion of VBID to other health care services could increase the benefit conferred by health care by 0.24 to 0.44 additional life-years, also without increasing costs and without increasing overall out-of-pocket payments. Among those without health insurance, using cost saving from VBID to subsidize insurance coverage would increase the benefit conferred by health care by 1.21 life-years, a 31% increase. CONCLUSION: Broader diffusion of VBID may amplify benefits from

  2. Novel distribution of calreticulin to cardiomyocyte mitochondria and its increase in a rat model of dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ming [Department of Cardiology, Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi (China); Department of Respiratory Medicine, Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi (China); Wei, Jin, E-mail: weijindr@163.com [Department of Cardiology, Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi (China); Li, Yali [Department of Respiratory Medicine, Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi (China); Shan, Hu; Yan, Rui; Lin, Lin [Department of Cardiology, Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi (China); Zhang, Qiuhong [Department of Respiratory Medicine, Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi (China); Xue, Jiahong [Department of Cardiology, Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi (China)

    2014-06-20

    Highlights: • Calreticulin can also be found in cardiomyocyte mitochondria. • The mitochondrial content of calreticulin is increased in DCM hearts. • Increased expression of mitochondrial CRT may induce mitochondrial damage. • Mitochondrial CRT may inhibit the phosphorylation of mitochondrial STAT3. - Abstract: Background: Calreticulin (CRT), a Ca{sup 2+}-binding chaperone of the endoplasmic reticulum, can also be found in several other locations including the cytosol, nucleus, secretory granules, the outer side of the plasma membrane, and the extracellular matrix. Whether CRT is localized at mitochondria of cardiomyocytes and whether such localization is affected under DCM are still unclear. Methods and results: The DCM model was generated in rats by the daily oral administration of furazolidone for thirty weeks. Echocardiographic and hemodynamic studies demonstrated enlarged left ventricular dimensions and reduced systolic and diastolic function in DCM rats. Immuno-electron microscopy and Western blot showed that CRT was present in cardiomyocyte mitochondria and the mitochondrial content of CRT was increased in DCM hearts (P < 0.05). Morphometric analysis showed notable myocardial apoptosis and mitochondrial swelling with fractured or dissolved cristae in the DCM hearts. Compared with the control group, the mitochondrial membrane potential level of the freshly isolated cardiac mitochondria and the enzyme activities of cytochrome c oxidase and succinate dehydrogenase in the model group were significantly decreased (P < 0.05), and the myocardial apoptosis index and the caspase activities of caspase-9 and caspase-3 were significantly increased (P < 0.05). Pearson linear correlation analysis showed that the mitochondrial content of CRT had negative correlations with the mitochondrial function, and a positive correlation with myocardial apoptosis index (P < 0.001). The protein expression level of cytochrome c and the phosphorylation activity of STAT3 in the

  3. Characterization of increasing stages of invasiveness identifies stromal/cancer cell crosstalk in rat models of mesothelioma.

    Science.gov (United States)

    Nader, Joëlle S; Abadie, Jérôme; Deshayes, Sophie; Boissard, Alice; Blandin, Stéphanie; Blanquart, Christophe; Boisgerault, Nicolas; Coqueret, Olivier; Guette, Catherine; Grégoire, Marc; Pouliquen, Daniel L

    2018-03-27

    Sarcomatoid mesothelioma (SM) is a devastating cancer associated with one of the poorest outcome. Therefore, representative preclinical models reproducing different tumor microenvironments (TME) observed in patients would open up new prospects for the identification of markers and evaluation of innovative therapies. Histological analyses of four original models of rat SM revealed their increasing infiltrative and metastatic potential were associated with differences in Ki67 index, blood-vessel density, and T-lymphocyte and macrophage infiltration. In comparison with the noninvasive tumor M5-T2, proteomic analysis demonstrated the three invasive tumors F4-T2, F5-T1 and M5-T1 shared in common a very significant increase in the abundance of the multifunctional proteins galectin-3, prohibitin and annexin A5, and a decrease in proteins involved in cell adhesion, tumor suppression, or epithelial differentiation. The increased metastatic potential of the F5-T1 tumor, relative to F4-T2, was associated with an increased macrophage vs T-cell infiltrate, changes in the levels of expression of a panel of cytokine genes, an increased content of proteins involved in chromatin organization, ribosome structure, splicing, or presenting anti-adhesive properties, and a decreased content of proteins involved in protection against oxidative stress, normoxia and intracellular trafficking. The most invasive tumor, M5-T1, was characterized by a pattern of specific phenotypic and molecular features affecting the presentation of MHC class I-mediated antigens and immune cell infiltration, or involved in the reorganization of the cytoskeleton and composition of the extracellular matrix. These four preclinical models and data represent a new resource available to the cancer research community to catalyze further investigations on invasiveness.

  4. Application of solution focused brief counseling model to increase of counselee resilience as a part of multicultural society

    Directory of Open Access Journals (Sweden)

    Dita Kurnia Sari

    2016-12-01

    Full Text Available Modern multicultural society and is a dynamic life marked by interaction between the components of a diverse society based on the rule of science and technology. A society that is increasingly complex due to the rapid changes in various aspects of life often creates problems for the individual's life. For example, inner tension, internal and external conflicts, and emotional disturbance. Facing these challenges, the individual is expected to have resilience was good. The role of the counselor is to help the counselee improve resilience with counseling approach effectively. Counseling models that meet the criteria of an effective and efficient is the Solution Focused Brief Counseling. Counseling model emphasizes the collaborative process between counselor and counselee to find solutions to achieve the expected goals. In the process of this counseling model uses questioning techniques to uncover the story, advantages, strengths and exceptions problems experienced by counselee in a short time.

  5. Peripheral Inflammation Increases the Damage in Animal Models of Nigrostriatal Dopaminergic Neurodegeneration: Possible Implication in Parkinson's Disease Incidence

    Directory of Open Access Journals (Sweden)

    A. Machado

    2011-01-01

    Full Text Available Inflammatory processes described in Parkinson’s disease (PD and its animal models appear to be important in the progression of the pathogenesis, or even a triggering factor. Here we review that peripheral inflammation enhances the degeneration of the nigrostriatal dopaminergic system induced by different insults; different peripheral inflammations have been used, such as IL-1β and the ulcerative colitis model, as well as insults to the dopaminergic system such as 6-hydroxydopamine or lipopolysaccharide. In all cases, an increased loss of dopaminergic neurons was described; inflammation in the substantia nigra increased, displaying a great activation of microglia along with an increase in the production of cytokines such as IL-1β and TNF-α. Increased permeability or disruption of the BBB, with overexpression of the ICAM-1 adhesion molecule and infiltration of circulating monocytes into the substantia nigra, is also involved, since the depletion of circulating monocytes prevents the effects of peripheral inflammation. Data are reviewed in relation to epidemiological studies of PD.

  6. A modeling analysis of the interaction between forest age and forest responsiveness to increasing CO2 concentration

    International Nuclear Information System (INIS)

    Kirschbaum, M.U.F.

    2005-01-01

    In this study, both young forest plants and established forest stands were examined to gain insight into likely plant responses to increases in carbon dioxide (CO 2 ), temperature and altered rainfall patterns. Forests have rotations of about 10 to 200 years, during which time anthropogenic increases in atmospheric CO 2 concentrations and the associated changes in climate change can be substantial. The changes are most likely to influence the growth of established forest stands. The CenW forest growth model was used to examine the mechanisms that are responsible for the slowing of forest growth with age, including the response to increasing carbon dioxide. It was shown that inclusion of allocation shifts with tree height, individual tree mortality, changing respiration load and nutrient changes has only a small effect on the response to increasing carbon dioxide. When photosynthesis of mature trees decreases, growth response to increasing CO 2 is reduced. Since the number of interacting processes is so large, no simple and broad interaction between increased carbon dioxide and forest age were identified. It was concluded that it is not yet possible to predict the change in carbon dioxide response by forest age. 54 refs., 1 tab., 7 figs

  7. Increase in Total Joint Arthroplasty Projected from 2014 to 2046 in Australia: A Conservative Local Model With International Implications.

    Science.gov (United States)

    Inacio, Maria C S; Graves, Stephen E; Pratt, Nicole L; Roughead, Elizabeth E; Nemes, Szilard

    2017-08-01

    The incidence of joint arthroplasty is increasing worldwide. International estimates of future demand for joint arthroplasty have used models that propose either an exponential future increase, despite obvious system constraints, or static increases, which do not account for past trends. Country-specific projection estimates that address limitations of past projections are necessary. In Australia, a high-income country with the 7th highest incidence of TKA and 15th highest incidence of THA of the Organization for Economic Cooperation and Development (OECD) countries, the volume of TKAs and THAs increased 198% between 1994 and 2014. To determine the projected incidence and volume of primary TKAs and THAs from 2014 to 2046 in the Australian population older than 40 years. Australian State and Territory Health Department data were used to identify TKAs and THAs performed between 1994 and 1995 and 2013 and 2014. The Australian Bureau of Statistics was the source of the population estimates for the same periods and population-projected estimates until 2046. The incidence rate (IR), 95% CI, and prediction interval (PI) of TKAs and THAs per 100,000 Australian citizens older than 40 years were calculated. Future IRs were estimated using a logistic model, and volume was calculated from projected IR and population. The logistic growth model assumes the existence of an upper limit of the TKA and THA incidences and a growth rate directly related to this incidence. At the beginning, when the observed incidence is much lower than the asymptote, the increase is exponential, but it decreases as it approaches the upper limit. A 66% increase in the IR of primary THAs between 2013 and 2046 is projected for Australia (2013: IR = 307 per 100,000, [95% CI, 262-329 per 100,000] compared with 2046: IR= 510 per 100,000, [95% PI, 98-567 per 100,000]), which translates to a 219% increase in the volume during this period. For TKAs the IR is expected to increase by 26% by 2046 (IR = 575 per

  8. Robust Hadley Circulation Changes and Increasing Global Dryness Due to CO2 Warming from CMIP-5 Model Projections

    Science.gov (United States)

    Lau, William K. M.; Kim, K. M.

    2015-01-01

    In this paper, we investigate changes in the Hadley Circulation (HC) and their connections to increased global dryness under CO2 warming from CMIP-5 model projections. We find a strengthening of the ascending branch of the HC manifested in a deep-tropics squeeze (DTS), i.e., a deepening and narrowing of the convective zone, increased high clouds, and a rise of the level of maximum meridional mass outflow in the upper troposphere (200-100 hectopascals) of the deep tropics. The DTS induces atmospheric moisture divergence, reduces tropospheric relative humidity in the tropics and subtropics, in conjunction with a widening of the subsiding branches of the HC, resulting in increased frequency of dry events in preferred geographic locations worldwide. Among water cycle parameters examined, global dryness has the highest signal-to-noise ratio. Our results provide scientific bases for inferring that the observed tend of prolonged droughts in recent decades is likely attributable to greenhouse warming.

  9. Increased intake of energy-dense diet and negative energy balance in a mouse model of chronic psychosocial defeat.

    Science.gov (United States)

    Coccurello, Roberto; Romano, Adele; Giacovazzo, Giacomo; Tempesta, Bianca; Fiore, Marco; Giudetti, Anna Maria; Marrocco, Ilaria; Altieri, Fabio; Moles, Anna; Gaetani, Silvana

    2018-06-01

    Chronic exposure to stress may represent a risk factor for developing metabolic and eating disorders, mostly driven by the overconsumption of easily accessible energy-dense palatable food, although the mechanisms involved remain still unclear. In this study, we used an ethologically oriented murine model of chronic stress caused by chronic psychosocial defeat (CPD) to investigate the effects of unrestricted access to a palatable high fat diet (HFD) on food intake, body weight, energy homeostasis, and expression of different brain neuropeptides. Our aim was to shed light on the mechanisms responsible for body weight and body composition changes due to chronic social stress. In our model of subordinate (defeated), mice (CPD) cohabitated in constant sensory contact with dominants, being forced to interact on daily basis, and were offered ad libitum access either to an HFD or to a control diet (CD). Control mice (of the same strain as CPD mice) were housed in pairs and left unstressed in their home cage (UN). In all these mice, we evaluated body weight, different adipose depots, energy metabolism, caloric intake, and neuropeptide expression. CPD mice increased the intake of HFD and reduced body weight in the presence of enhanced lipid oxidation. Resting energy expenditure and interscapular brown adipose tissue (iBAT) were increased in CPD mice, whereas epididymal adipose tissue increased only in HFD-fed unstressed mice. Propiomelanocortin mRNA levels in hypothalamic arcuate nucleus increased only in HFD-fed unstressed mice. Oxytocin mRNA levels in the paraventricular nucleus and neuropeptide Y mRNA levels within the arcuate were increased only in CD-fed CPD mice. In the arcuate, CART was increased in HFD-fed UN mice and in CD-fed CPD mice, while HFD intake suppressed CART increase in defeated animals. In the basolateral amygdala, CART expression was increased only in CPD animals on HFD. CPD appears to uncouple the intake of HFD from energy homeostasis causing higher

  10. Increasing organic C and N fluxes from a northern Boreal river basin - monitoring and modelling suggest climate related controls

    Science.gov (United States)

    Lepistö, A.; Futter, M.; Kortelainen, P.

    2012-04-01

    Increasing trends in total organic carbon (TOC) concentrations in lakes and streams across northern Europe and North America have been reported. Various hypotheses including enhanced decomposition of organic soils, changes in hydrology and flow paths, decreased acid deposition and land use changes have been put forward to explain the widespread occurrence of this phenomenon. Both observational and modelling studies are needed to identify the most important drivers and relevant processes controlling observed trends in TOC concentrations. Typically, TOC concentrations in Finnish rivers and lakes are high. The Simojoki river basin (3160 km2) is located in the northern Boreal zone of Finland and experiences low, declining sulphate deposition and limited other human impacts. Forest harvest, land drainage and ditch maintenance are the main land management activities in the catchment. Long-term changes (30-40 years) and seasonal trends of total organic nitrogen (TON) and carbon (TOC) concentrations and fluxes in the Simojoki river system were studied. Concentrations of TOC and TON increased particularly during high flows. TOC concentrations are slowly but continuously increasing, fluctuating between droughts and wet periods. The highest concentrations were detected in 1998-2000 during a period of very high flows, after the drought period 1994-1997. Trends in concentrations of TOC and TON in Simojoki were not linked to declines in sulphate deposition but were more related to trends in climate and hydrology. The autumn season is particularly sensitive to climate change impacts. The INCA-C model was applied to simulate TOC dynamics in the catchment. Model results showed that climate change driven patterns in runoff and soil moisture and soil temperature were more important than temporal patterns of sulphate deposition and land management in controlling surface water TOC concentrations. The possible factors behind changes of TOC and TON concentrations and increasing fluxes to

  11. Higher Mortality in registrants with sudden model for end-stage liver disease increase: Disadvantaged by the current allocation policy.

    Science.gov (United States)

    Massie, Allan B; Luo, Xun; Alejo, Jennifer L; Poon, Anna K; Cameron, Andrew M; Segev, Dorry L

    2015-05-01

    Liver allocation is based on current Model for End-Stage Liver Disease (MELD) scores, with priority in the case of a tie being given to those waiting the longest with a given MELD score. We hypothesized that this priority might not reflect risk: registrants whose MELD score has recently increased receive lower priority but might have higher wait-list mortality. We studied wait-list and posttransplant mortality in 69,643 adult registrants from 2002 to 2013. By likelihood maximization, we empirically defined a MELD spike as a MELD increase ≥ 30% over the previous 7 days. At any given time, only 0.6% of wait-list patients experienced a spike; however, these patients accounted for 25% of all wait-list deaths. Registrants who reached a given MELD score after a spike had higher wait-list mortality in the ensuing 7 days than those with the same resulting MELD score who did not spike, but they had no difference in posttransplant mortality. The spike-associated wait-list mortality increase was highest for registrants with medium MELD scores: specifically, 2.3-fold higher (spike versus no spike) for a MELD score of 10, 4.0-fold higher for a MELD score of 20, and 2.5-fold higher for a MELD score of 30. A model incorporating the MELD score and spikes predicted wait-list mortality risk much better than a model incorporating only the MELD score. Registrants with a sudden MELD increase have a higher risk of short-term wait-list mortality than is indicated by their current MELD score but have no increased risk of posttransplant mortality; allocation policy should be adjusted accordingly. © 2015 American Association for the Study of Liver Diseases.

  12. Self-Tuning Method for Increased Obstacle Detection Reliability Based on Internet of Things LiDAR Sensor Models.

    Science.gov (United States)

    Castaño, Fernando; Beruvides, Gerardo; Villalonga, Alberto; Haber, Rodolfo E

    2018-05-10

    On-chip LiDAR sensors for vehicle collision avoidance are a rapidly expanding area of research and development. The assessment of reliable obstacle detection using data collected by LiDAR sensors has become a key issue that the scientific community is actively exploring. The design of a self-tuning methodology and its implementation are presented in this paper, to maximize the reliability of LiDAR sensors network for obstacle detection in the 'Internet of Things' (IoT) mobility scenarios. The Webots Automobile 3D simulation tool for emulating sensor interaction in complex driving environments is selected in order to achieve that objective. Furthermore, a model-based framework is defined that employs a point-cloud clustering technique, and an error-based prediction model library that is composed of a multilayer perceptron neural network, and k-nearest neighbors and linear regression models. Finally, a reinforcement learning technique, specifically a Q-learning method, is implemented to determine the number of LiDAR sensors that are required to increase sensor reliability for obstacle localization tasks. In addition, a IoT driving assistance user scenario, connecting a five LiDAR sensor network is designed and implemented to validate the accuracy of the computational intelligence-based framework. The results demonstrated that the self-tuning method is an appropriate strategy to increase the reliability of the sensor network while minimizing detection thresholds.

  13. The effects of honey (Apis dorsata) supplements on increased bone strength in ovariectomized rat as animal model of osteoporosis

    Science.gov (United States)

    Yudaniayanti, Ira Sari; Primarizky, Hardany; Nangoi, Lianny

    2018-04-01

    Osteoporosis is a chronic skeletal disease characterized by low bone mass and microarchitectural deterioration with a consequent increase in bone fragility and fracture risk. The aim of the study was to evaluate the effects of honey (Apis dorsata) supplements on increased bone strength in ovariectomized rat as animal models of osteoporosis. Twenty female rats at 3 months of age, weighing 150-200 g were used in the study. The rats were divided into five groups (n=4) : Sham operation group (SH); ovariectomy group no treatment(OVX); ovariectomy with treatment Apis dorsata 1g/Kg BW (AD-1); ovariectomy with treatment Apis dorsata 2g/Kg BW (AD-2); ovariectomy with treatment Apis dorsata 4g/Kg BW (AD-3). The treatment started to be given the next day after ovariectomy operation for 12 weeks. The Rats were sacrified within 12 weeks, and then the right femur were taken bone strength test. Based on the statistical analysis of the bone strength test, the greatest score belongs to the Sham operation group (SH) that have significant difference (p0,05). In conclusion, honey (Apis dorsata) supplements has the effect of increasing bone strength in ovariectomized rat as animal models of osteoporosis, so that honey (Apis dorsata) supplements has the potential to be used as an alternative treatment for osteoporosis.

  14. Health, Health Inequality, and Cost Impacts of Annual Increases in Tobacco Tax: Multistate Life Table Modeling in New Zealand.

    Directory of Open Access Journals (Sweden)

    Tony Blakely

    2015-07-01

    Full Text Available Countries are increasingly considering how to reduce or even end tobacco consumption, and raising tobacco taxes is a potential strategy to achieve these goals. We estimated the impacts on health, health inequalities, and health system costs of ongoing tobacco tax increases (10% annually from 2011 to 2031, compared to no tax increases from 2011 ["business as usual," BAU], in a country (New Zealand with large ethnic inequalities in smoking-related and noncommunicable disease (NCD burden.We modeled 16 tobacco-related diseases in parallel, using rich national data by sex, age, and ethnicity, to estimate undiscounted quality-adjusted life-years (QALYs gained and net health system costs over the remaining life of the 2011 population (n = 4.4 million. A total of 260,000 (95% uncertainty interval [UI]: 155,000-419,000 QALYs were gained among the 2011 cohort exposed to annual tobacco tax increases, compared to BAU, and cost savings were US$2,550 million (95% UI: US$1,480 to US$4,000. QALY gains and cost savings took 50 y to peak, owing to such factors as the price sensitivity of youth and young adult smokers. The QALY gains per capita were 3.7 times greater for Māori (indigenous population compared to non-Māori because of higher background smoking prevalence and price sensitivity in Māori. Health inequalities measured by differences in 45+ y-old standardized mortality rates between Māori and non-Māori were projected to be 2.31% (95% UI: 1.49% to 3.41% less in 2041 with ongoing tax rises, compared to BAU. Percentage reductions in inequalities in 2041 were maximal for 45-64-y-old women (3.01%. As with all such modeling, there were limitations pertaining to the model structure and input parameters.Ongoing tobacco tax increases deliver sizeable health gains and health sector cost savings and are likely to reduce health inequalities. However, if policy makers are to achieve more rapid reductions in the NCD burden and health inequalities, they will also

  15. Health, Health Inequality, and Cost Impacts of Annual Increases in Tobacco Tax: Multistate Life Table Modeling in New Zealand

    Science.gov (United States)

    Blakely, Tony; Cobiac, Linda J.; Cleghorn, Christine L.; Pearson, Amber L.; van der Deen, Frederieke S.; Kvizhinadze, Giorgi; Nghiem, Nhung; McLeod, Melissa; Wilson, Nick

    2015-01-01

    Background Countries are increasingly considering how to reduce or even end tobacco consumption, and raising tobacco taxes is a potential strategy to achieve these goals. We estimated the impacts on health, health inequalities, and health system costs of ongoing tobacco tax increases (10% annually from 2011 to 2031, compared to no tax increases from 2011 [“business as usual,” BAU]), in a country (New Zealand) with large ethnic inequalities in smoking-related and noncommunicable disease (NCD) burden. Methods and Findings We modeled 16 tobacco-related diseases in parallel, using rich national data by sex, age, and ethnicity, to estimate undiscounted quality-adjusted life-years (QALYs) gained and net health system costs over the remaining life of the 2011 population (n = 4.4 million). A total of 260,000 (95% uncertainty interval [UI]: 155,000–419,000) QALYs were gained among the 2011 cohort exposed to annual tobacco tax increases, compared to BAU, and cost savings were US$2,550 million (95% UI: US$1,480 to US$4,000). QALY gains and cost savings took 50 y to peak, owing to such factors as the price sensitivity of youth and young adult smokers. The QALY gains per capita were 3.7 times greater for Māori (indigenous population) compared to non-Māori because of higher background smoking prevalence and price sensitivity in Māori. Health inequalities measured by differences in 45+ y-old standardized mortality rates between Māori and non-Māori were projected to be 2.31% (95% UI: 1.49% to 3.41%) less in 2041 with ongoing tax rises, compared to BAU. Percentage reductions in inequalities in 2041 were maximal for 45–64-y-old women (3.01%). As with all such modeling, there were limitations pertaining to the model structure and input parameters. Conclusions Ongoing tobacco tax increases deliver sizeable health gains and health sector cost savings and are likely to reduce health inequalities. However, if policy makers are to achieve more rapid reductions in the NCD

  16. Can Broader Diffusion of Value-Based Insurance Design Increase Benefits from US Health Care without Increasing Costs? Evidence from a Computer Simulation Model

    OpenAIRE

    Scott Braithwaite, R.; Omokaro, Cynthia; Justice, Amy C.; Nucifora, Kimberly; Roberts, Mark S.

    2010-01-01

    Editors' Summary Background More money is spent per person on health care in the US than in any other country. US health care expenditure accounts for 16.2% of the gross domestic product and this figure is rising. Indeed, the increase in health care costs is outstripping the economy's growth rate. Consequently, US policy makers and providers of health insurance?health care in the US is largely provided by the private sector and is paid for through private health insurance or through governmen...

  17. TLR4 mutation reduces microglial activation, increases Aβ deposits and exacerbates cognitive deficits in a mouse model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Song Min

    2011-08-01

    Full Text Available Abstract Background Amyloid plaques, a pathological hallmark of Alzheimer's disease (AD, are accompanied by activated microglia. The role of activated microglia in the pathogenesis of AD remains controversial: either clearing Aβ deposits by phagocytosis or releasing proinflammatory cytokines and cytotoxic substances. Microglia can be activated via toll-like receptors (TLRs, a class of pattern-recognition receptors in the innate immune system. We previously demonstrated that an AD mouse model homozygous for a loss-of-function mutation of TLR4 had increases in Aβ deposits and buffer-soluble Aβ in the brain as compared with a TLR4 wild-type AD mouse model at 14-16 months of age. However, it is unknown if TLR4 signaling is involved in initiation of Aβ deposition as well as activation and recruitment of microglia at the early stage of AD. Here, we investigated the role of TLR4 signaling and microglial activation in early stages using 5-month-old AD mouse models when Aβ deposits start. Methods Microglial activation and amyloid deposition in the brain were determined by immunohistochemistry in the AD models. Levels of cerebral soluble Aβ were determined by ELISA. mRNA levels of cytokines and chemokines in the brain and Aβ-stimulated monocytes were quantified by real-time PCR. Cognitive functions were assessed by the Morris water maze. Results While no difference was found in cerebral Aβ load between AD mouse models at 5 months with and without TLR4 mutation, microglial activation in a TLR4 mutant AD model (TLR4M Tg was less than that in a TLR4 wild-type AD model (TLR4W Tg. At 9 months, TLR4M Tg mice had increased Aβ deposition and soluble Aβ42 in the brain, which were associated with decrements in cognitive functions and expression levels of IL-1β, CCL3, and CCL4 in the hippocampus compared to TLR4W Tg mice. TLR4 mutation diminished Aβ-induced IL-1β, CCL3, and CCL4 expression in monocytes. Conclusion This is the first demonstration of TLR4

  18. A Teacher Competency Enhancement Model based on the Coaching Processes to Increase Mathematical Reasoning Abilities of Lower-Secondary Students

    Directory of Open Access Journals (Sweden)

    Uaychai Sukanalam

    2017-09-01

    Full Text Available This research study aimed to: 1 investigate problems and needs for the learning management that helps increase capacities of mathematics teachers at the lower-secondary level, 2 develop a teacher competency enhancement model based on the coaching processes to enhance mathematical reasoning abilities of lower-secondary students, 3 find out the educational supervisors’ opinions on the model designed. The samples of the study comprised 212 mathematics teachers at the lower-secondary level from 60 schools under jurisdiction of the Office of Secondary Educational Service Area 27, who were selected through the simple random sampling technique ; and 201 educational supervisors in charge of the mathematics learning strand from 42 educational service areas, who were selected through the purposive sampling technique. This study was conducted in the academic year 2015. The research instruments included: 1 a teacher competency enhancement manual that illustrated the steps and procedures for increasing the teacher’s capacities based on the coaching processes in order to enhance mathematical reasoning abilities of lower-secondary students, 2 a survey on problems and needs for the learning management to enhance capacities of mathematics teachers at the lower-secondary level, 3 A questionnaire concerning the educational supervisor’s opinion on the model designed. The statistics used included percentage, mean, and standard deviation. The study results showed that: 1. According to the study and analysis of basic data, problems and needs, it was found that the needs for increasing capacities of mathematics teachers at the lower-secondary level was overall at the high level. In terms of identifying behaviors as “mathematical competencies”, there were some problems associated with thinking and reasoning abilities of the teachers, and their needs in developing the learning management were at the highest level. To solve such problems, it is suggested that

  19. A Chronic Autoimmune Dry Eye Rat Model with Increase in Effector Memory T Cells in Eyeball Tissue.

    Science.gov (United States)

    Hou, Aihua; Bose, Tanima; Chandy, K George; Tong, Louis

    2017-06-07

    Dry eye disease is a very common condition that causes morbidity and healthcare burden and decreases the quality of life. There is a need for a suitable dry eye animal model to test novel therapeutics to treat autoimmune dry eye conditions. This protocol describes a chronic autoimmune dry eye rat model. Lewis rats were immunized with an emulsion containing lacrimal gland extract, ovalbumin, and complete Freund's adjuvant. A second immunization with the same antigens in incomplete Freund's adjuvant was administered two weeks later. These immunizations were administered subcutaneously at the base of the tail. To boost the immune response at the ocular surface and lacrimal glands, lacrimal gland extract and ovalbumin were injected into the forniceal subconjunctiva and lacrimal glands 6 weeks after the first immunization. The rats developed dry eye features, including reduced tear production, decreased tear stability, and increased corneal damage. Immune profiling by flow cytometry showed a preponderance of CD3 + effector memory T cells in the eyeball.

  20. Using Portable Video Modeling Technology to Increase the Compliment Behaviors of Children with Autism During Athletic Group Play.

    Science.gov (United States)

    Macpherson, Kevin; Charlop, Marjorie H; Miltenberger, Catherine A

    2015-12-01

    A multiple baseline design across participants was used to examine the effects of a portable video modeling intervention delivered in the natural environment on the verbal compliments and compliment gestures demonstrated by five children with autism. Participants were observed playing kickball with peers and adults. In baseline, participants demonstrated few compliment behaviors. During intervention, an iPad(®) was used to implement the video modeling treatment during the course of the athletic game. Viewing the video rapidly increased the verbal compliments participants gave to peers. Participants also demonstrated more response variation after watching the videos. Some generalization to an untrained activity occurred and compliment gestures also occurred. Results are discussed in terms of contributions to the literature.

  1. Increasing the Accuracy of Mapping Urban Forest Carbon Density by Combining Spatial Modeling and Spectral Unmixing Analysis

    Directory of Open Access Journals (Sweden)

    Hua Sun

    2015-11-01

    Full Text Available Accurately mapping urban vegetation carbon density is challenging because of complex landscapes and mixed pixels. In this study, a novel methodology was proposed that combines a linear spectral unmixing analysis (LSUA with a linear stepwise regression (LSR, a logistic model-based stepwise regression (LMSR and k-Nearest Neighbors (kNN, to map the forest carbon density of Shenzhen City of China, using Landsat 8 imagery and sample plot data collected in 2014. The independent variables that contributed to statistically significantly improving the fit of a model to data and reducing the sum of squared errors were first selected from a total of 284 spectral variables derived from the image bands. The vegetation fraction from LSUA was then added as an independent variable. The results obtained using cross-validation showed that: (1 Compared to the methods without the vegetation information, adding the vegetation fraction increased the accuracy of mapping carbon density by 1%–9.3%; (2 As the observed values increased, the LSR and kNN residuals showed overestimates and underestimates for the smaller and larger observations, respectively, while LMSR improved the systematical over and underestimations; (3 LSR resulted in illogically negative and unreasonably large estimates, while KNN produced the greatest values of root mean square error (RMSE. The results indicate that combining the spatial modeling method LMSR and the spectral unmixing analysis LUSA, coupled with Landsat imagery, is most promising for increasing the accuracy of urban forest carbon density maps. In addition, this method has considerable potential for accurate, rapid and nondestructive prediction of urban and peri-urban forest carbon stocks with an acceptable level of error and low cost.

  2. Testes mass, but not sperm length, increases with higher levels of polyandry in an ancient sex model.

    Directory of Open Access Journals (Sweden)

    David E Vrech

    Full Text Available There is strong evidence that polyandrous taxa have evolved relatively larger testes than monogamous relatives. Sperm size may either increase or decrease across species with the risk or intensity of sperm competition. Scorpions represent an ancient direct mode with spermatophore-mediated sperm transfer and are particularly well suited for studies in sperm competition. This work aims to analyze for the first time the variables affecting testes mass, ejaculate volume and sperm length, according with their levels of polyandry, in species belonging to the Neotropical family Bothriuridae. Variables influencing testes mass and sperm length were obtained by model selection analysis using corrected Akaike Information Criterion. Testes mass varied greatly among the seven species analyzed, ranging from 1.6 ± 1.1 mg in Timogenes dorbignyi to 16.3 ± 4.5 mg in Brachistosternus pentheri with an average of 8.4 ± 5.0 mg in all the species. The relationship between testes mass and body mass was not significant. Body allocation in testes mass, taken as Gonadosomatic Index, was high in Bothriurus cordubensis and Brachistosternus ferrugineus and low in Timogenes species. The best-fitting model for testes mass considered only polyandry as predictor with a positive influence. Model selection showed that body mass influenced sperm length negatively but after correcting for body mass, none of the variables analyzed explained sperm length. Both body mass and testes mass influenced spermatophore volume positively. There was a strong phylogenetic effect on the model containing testes mass. As predicted by the sperm competition theory and according to what happens in other arthropods, testes mass increased in species with higher levels of sperm competition, and influenced positively spermatophore volume, but data was not conclusive for sperm length.

  3. INCREASE OF READABILITY AND ACCURACY OF 3D MODELS USING FUSION OF CLOSE RANGE PHOTOGRAMMETRY AND LASER SCANNING

    Directory of Open Access Journals (Sweden)

    M. Gašparović

    2012-07-01

    Full Text Available The development of laser scanning technology has opened a new page in geodesy and enabled an entirely new way of presenting data. Products obtained by the method of laser scanning are used in many sciences, as well as in archaeology. It should be noted that 3D models of archaeological artefacts obtained by laser scanning are fully measurable, written in 1:1 scale and have high accuracy. On the other hand, texture and RGB values of the surface of the object obtained by a laser scanner have lower resolution and poorer radiometric characteristics in relation to the textures captured with a digital camera. Scientific research and the goal of this paper are to increase the accuracy and readability of the 3D model with textures obtained with a digital camera. Laser scanning was performed with triangulation scanner of high accuracy, Vivid 9i (Konica Minolta, while for photogrammetric recording digital camera Nikon D90 with a lens of fixed focal length 20 mm, was used. It is important to stress that a posteriori accuracy score of the global registration of point clouds in the form of the standard deviation was ± 0.136 mm while the average distance was only ± 0.080 mm. Also research has proven that the quality projection texture model increases readability. Recording of archaeological artefacts and making their photorealistic 3D model greatly contributes to archaeology as a science, accelerates processing and reconstruction of the findings. It also allows the presentation of findings to the general public, not just to the experts.

  4. Increased oxidative stress and apoptosis in the hypothalamus of diabetic male mice in the insulin receptor substrate-2 knockout model

    Science.gov (United States)

    Canelles, Sandra; Argente, Jesús; Barrios, Vicente

    2016-01-01

    ABSTRACT Insulin receptor substrate-2-deficient (IRS2−/−) mice are considered a good model to study the development of diabetes because IRS proteins mediate the pleiotropic effects of insulin-like growth factor-I (IGF-I) and insulin on metabolism, mitogenesis and cell survival. The hypothalamus might play a key role in the early onset of diabetes, owing to its involvement in the control of glucose homeostasis and energy balance. Because some inflammatory markers are elevated in the hypothalamus of diabetic IRS2−/− mice, our aim was to analyze whether the diabetes associated with the absence of IRS2 results in hypothalamic injury and to analyze the intracellular mechanisms involved. Only diabetic IRS2−/− mice showed increased cell death and activation of caspase-8 and -3 in the hypothalamus. Regulators of apoptosis such as FADD, Bcl-2, Bcl-xL and p53 were also increased, whereas p-IκB and c-FLIPL were decreased. This was accompanied by increased levels of Nox-4 and catalase, enzymes involved in oxidative stress. In summary, the hypothalamus of diabetic IRS2−/− mice showed an increase in oxidative stress and inflammatory markers that finally resulted in cell death via substantial activation of the extrinsic apoptotic pathway. Conversely, non-diabetic IRS2−/− mice did not show cell death in the hypothalamus, possibly owing to an increase in the levels of circulating IGF-I and in the enhanced hypothalamic IGF-IR phosphorylation that would lead to the stimulation of survival pathways. In conclusion, diabetes in IRS2-deficient male mice is associated with increased oxidative stress and apoptosis in the hypothalamus. PMID:27013528

  5. A new method to model electroconvulsive therapy in rats with increased construct validity and enhanced translational value.

    Science.gov (United States)

    Theilmann, Wiebke; Löscher, Wolfgang; Socala, Katarzyna; Frieling, Helge; Bleich, Stefan; Brandt, Claudia

    2014-06-01

    Electroconvulsive therapy is the most effective therapy for major depressive disorder (MDD). The remission rate is above 50% in previously pharmacoresistant patients but the mechanisms of action are not fully understood. Electroconvulsive stimulation (ECS) in rodents mimics antidepressant electroconvulsive therapy (ECT) in humans and is widely used to investigate the underlying mechanisms of ECT. For the translational value of findings in animal models it is essential to establish models with the highest construct, face and predictive validity possible. The commonly used model for ECT in rodents does not meet the demand for high construct validity. For ECT, cortical surface electrodes are used to induce therapeutic seizures whereas ECS in rodents is exclusively performed by auricular or corneal electrodes. However, the stimulation site has a major impact on the type and spread of the induced seizure activity and its antidepressant effect. We propose a method in which ECS is performed by screw electrodes placed above the motor cortex of rats to closely simulate the clinical situation and thereby increase the construct validity of the model. Cortical ECS in rats induced reliably seizures comparable to human ECT. Cortical ECS was more effective than auricular ECS to reduce immobility in the forced swim test. Importantly, auricular stimulation had a negative influence on the general health condition of the rats with signs of fear during the stimulation sessions. These results suggest that auricular ECS in rats is not a suitable ECT model. Cortical ECS in rats promises to be a valid method to mimic ECT. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Effects of increased small-scale biomass combustion on local air quality - A theoretical dispersion modelling study

    International Nuclear Information System (INIS)

    Boman, C.

    1997-01-01

    The decided phasing out of nuclear power and the goal of reducing CO 2 emissions from fossil fuels causes a substantial estimated increase in the use of biomass fuels for energy production. Thus, a significant shift from small scale heating generated by electricity or fuel oil to biomass fuels is desirable. If a drastic deterioration of the local air quality is to be avoided, a reduction of today's emission limits is necessary. The objective of this report was therefore to describe the use of biomass fuels and small scale pellet fuel combustion, to make a theoretical study of the effects of increased pellets heating on the air quality in a residential area, and to discuss necessary emission limits for small biomass fuel plants. The general description is based on literature studies. In the theoretical study, several different dispersion model calculations were performed using the computer program Dispersion 1.1.0. The contents of tar and total hydrocarbons (THC) in the air were calculated for different scenarios with conversion from electricity to pellets and with different pellet plant performance. A sensitivity analysis was performed with additional variables and dispersion calculations according to an underlying statistical experimental design. The modeling and design computer program MODDE was used to facilitate design, evaluation and illustration of the calculated results. The results show that a substantial increase in the use of small scale pellets heating with worst calculated plant performance, will lead to a drastic increase of the content of hydrocarbons in the air. Thus, with best available performance, the content only increases marginally. Conversion from electricity to pellets, plant performance and time of year were the most influential variables. Also conversion from wood to pellets showed a significant effect, despite the small number of wood heated houses within the studied area. If a significant deterioration of the air quality is to be avoided

  7. Loss of laforin or malin results in increased Drp1 level and concomitant mitochondrial fragmentation in Lafora disease mouse models.

    Science.gov (United States)

    Upadhyay, Mamta; Agarwal, Saloni; Bhadauriya, Pratibha; Ganesh, Subramaniam

    2017-04-01

    Lafora disease (LD) is an autosomal recessive form of a fatal disorder characterized by the myoclonus epilepsy, ataxia, psychosis, dementia, and dysarthria. A hallmark of LD is the presence of abnormal glycogen inclusions called Lafora bodies in the affected tissues including the neurons. LD can be caused by defects either in the laforin phosphatase coded by the EPM2A gene or in the malin E3 ubiquitin ligase coded by the NHLRC1 gene. The mouse models of LD, created by the targeted disruption of the LD genes, display several neurodegenerative changes. Prominent among them are the autophagic defects, abnormally large lysosomes, neurofibrillary tangles, amyloid beta deposits, and abnormal mitochondria. However, whether or not such neurodegenerative changes are a direct effect of the loss of laforin/malin was not unequivocally established. Here, we show that laforin- or malin-deficient neurons and fibroblasts display a significantly higher number of fragmented mitochondria. Loss of laforin or malin resulted in increased levels of the mitochondrial fission GTPase Drp1, its enhanced mitochondrial targeting, and increased intracellular calcium levels. Intriguingly, laforin and malin display opposite effects on the cellular level of parkin, an ubiquitin ligase of Drp1; loss of laforin led to reduced levels of parkin while the loss of malin resulted in increased parkin levels. Laforin and malin, however, interact with and positively regulate the activity of parkin, thus explaining the molecular basis of increased Drp1 levels in LD tissues. Our results suggest that laforin and malin are novel regulators of mitochondrial quality control pathway and that the mitochondrial dysfunction resulting from the increased Drp1 levels could underlie neuropathology in LD. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Sildenafil Citrate Increases Fetal Weight in a Mouse Model of Fetal Growth Restriction with a Normal Vascular Phenotype

    Science.gov (United States)

    Dilworth, Mark Robert; Andersson, Irene; Renshall, Lewis James; Cowley, Elizabeth; Baker, Philip; Greenwood, Susan; Sibley, Colin Peter; Wareing, Mark

    2013-01-01

    Fetal growth restriction (FGR) is defined as the inability of a fetus to achieve its genetic growth potential and is associated with a significantly increased risk of morbidity and mortality. Clinically, FGR is diagnosed as a fetus falling below the 5th centile of customised growth charts. Sildenafil citrate (SC, Viagra™), a potent and selective phosphodiesterase-5 inhibitor, corrects ex vivo placental vascular dysfunction in FGR, demonstrating potential as a therapy for this condition. However, many FGR cases present without an abnormal vascular phenotype, as assessed by Doppler measures of uterine/umbilical artery blood flow velocity. Thus, we hypothesized that SC would not increase fetal growth in a mouse model of FGR, the placental-specific Igf2 knockout mouse, which has altered placental exchange capacity but normal placental blood flow. Fetal weights were increased (by 8%) in P0 mice following maternal SC treatment (0.4 mg/ml) via drinking water. There was also a trend towards increased placental weight in treated P0 mice (P = 0.056). Additionally, 75% of the P0 fetal weights were below the 5th centile, the criterion used to define human FGR, of the non-treated WT fetal weights; this was reduced to 51% when dams were treated with SC. Umbilical artery and vein blood flow velocity measures confirmed the lack of an abnormal vascular phenotype in the P0 mouse; and were unaffected by SC treatment. 14C-methylaminoisobutyric acid transfer (measured to assess effects on placental nutrient transporter activity) per g placenta was unaffected by SC, versus untreated, though total transfer was increased, commensurate with the trend towards larger placentas in this group. These data suggest that SC may improve fetal growth even in the absence of an abnormal placental blood flow, potentially affording use in multiple sub-populations of individuals presenting with FGR. PMID:24204949

  9. Sildenafil citrate increases fetal weight in a mouse model of fetal growth restriction with a normal vascular phenotype.

    Directory of Open Access Journals (Sweden)

    Mark Robert Dilworth

    Full Text Available Fetal growth restriction (FGR is defined as the inability of a fetus to achieve its genetic growth potential and is associated with a significantly increased risk of morbidity and mortality. Clinically, FGR is diagnosed as a fetus falling below the 5(th centile of customised growth charts. Sildenafil citrate (SC, Viagra™, a potent and selective phosphodiesterase-5 inhibitor, corrects ex vivo placental vascular dysfunction in FGR, demonstrating potential as a therapy for this condition. However, many FGR cases present without an abnormal vascular phenotype, as assessed by Doppler measures of uterine/umbilical artery blood flow velocity. Thus, we hypothesized that SC would not increase fetal growth in a mouse model of FGR, the placental-specific Igf2 knockout mouse, which has altered placental exchange capacity but normal placental blood flow. Fetal weights were increased (by 8% in P0 mice following maternal SC treatment (0.4 mg/ml via drinking water. There was also a trend towards increased placental weight in treated P0 mice (P = 0.056. Additionally, 75% of the P0 fetal weights were below the 5(th centile, the criterion used to define human FGR, of the non-treated WT fetal weights; this was reduced to 51% when dams were treated with SC. Umbilical artery and vein blood flow velocity measures confirmed the lack of an abnormal vascular phenotype in the P0 mouse; and were unaffected by SC treatment. (14C-methylaminoisobutyric acid transfer (measured to assess effects on placental nutrient transporter activity per g placenta was unaffected by SC, versus untreated, though total transfer was increased, commensurate with the trend towards larger placentas in this group. These data suggest that SC may improve fetal growth even in the absence of an abnormal placental blood flow, potentially affording use in multiple sub-populations of individuals presenting with FGR.

  10. The Impact of Albedo Increase to Mitigate the Urban Heat Island in Terni (Italy Using the WRF Model

    Directory of Open Access Journals (Sweden)

    Elena Morini

    2016-10-01

    Full Text Available The impacts of the urban heat island (UHI phenomenon on energy consumption, air quality, and human health have been widely studied and described. Mitigation strategies have been developed to fight the UHI and its detrimental consequences. A potential countermeasure is the increase of urban albedo by using cool materials. Cool materials are highly reflective materials that can maintain lower surface temperatures and thus can present an effective solution to mitigate the UHI. Terni’s proven record of high temperatures along with related environmental and comfort issues in its urban areas have reflected the local consequences of global warming. On the other hand, it promoted integrated actions by the government and research institutes to investigate solutions to mitigate the UHI effects. In this study, the main goal is to investigate the effectiveness of albedo increase as a strategy to tackle the UHI, by using the Weather Research and Forecasting (WRF mesoscale model to simulate the urban climate of Terni (Italy. Three different scenarios through a summer heat wave in the summer of 2015 are analyzed. The Base Scenario, which simulates the actual conditions of the urban area, is the control case. In the Albedo Scenario (ALB Scenario, the albedo of the roof, walls and road of the whole urban area is increased. In the Albedo-Industrial Scenario (ALB-IND Scenario, the albedo of the roof, walls and road of the area occupied by the main industrial site of Terni, located in close proximity to the city center, is increased. The simulation results show that the UHI is decreased up to 2 °C both at daytime and at nighttime in the ALB and in ALB-IND Scenarios. Peak temperatures in the urban area can be decreased by 1 °C at daytime, and by about 2 °C at nighttime. Albedo increase in the area of interest might thus represent an opportunity to decrease the UHI effect and its consequences.

  11. Fluorescence-guided surgery of human colon cancer increases complete resection resulting in cures in an orthotopic nude mouse model.

    Science.gov (United States)

    Metildi, Cristina A; Kaushal, Sharmeela; Snyder, Cynthia S; Hoffman, Robert M; Bouvet, Michael

    2013-01-01

    We inquired if fluorescence-guided surgery (FGS) could improve surgical outcomes in fluorescent orthotopic nude mouse models of human colon cancer. We established fluorescent orthotopic mouse models of human colon cancer expressing a fluorescent protein. Tumors were resected under bright light surgery (BLS) or FGS. Pre- and post-operative images with the OV-100 Small Animal Imaging System (Olympus Corp, Tokyo Japan) were obtained to assess the extent of surgical resection. All mice with primary tumor that had undergone FGS had complete resection compared with 58% of mice in the BLS group (P = 0.001). FGS resulted in decreased recurrence compared with BLS (33% versus 62%, P = 0.049) and lengthened disease-free median survival from 9 to >36 wk. The median overall survival increased from 16 wk in the BLS group to 31 weeks in the FGS group. FGS resulted in a cure in 67% of mice (alive without evidence of tumor at >6 mo after surgery) compared with only 37% of mice that underwent BLS (P = 0.049). Surgical outcomes in orthotopic nude mouse models of human colon cancer were significantly improved with FGS. The present study can be translated to the clinic by various effective methods of fluorescently labeling tumors. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Adult Brtl/+ mouse model of osteogenesis imperfecta demonstrates anabolic response to sclerostin antibody treatment with increased bone mass and strength.

    Science.gov (United States)

    Sinder, B P; White, L E; Salemi, J D; Ominsky, M S; Caird, M S; Marini, J C; Kozloff, K M

    2014-08-01

    Treatments to reduce fracture rates in adults with osteogenesis imperfecta are limited. Sclerostin antibody, developed for treating osteoporosis, has not been explored in adults with OI. This study demonstrates that treatment of adult OI mice respond favorably to sclerostin antibody therapy despite retention of the OI-causing defect. Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk. Although OI fracture risk is greatest before puberty, adults with OI remain at risk of fracture. Antiresorptive bisphosphonates are commonly used to treat adult OI, but have shown mixed efficacy. New treatments which consistently improve bone mass throughout the skeleton may improve patient outcomes. Neutralizing antibodies to sclerostin (Scl-Ab) are a novel anabolic therapy that have shown efficacy in preclinical studies by stimulating bone formation via the canonical wnt signaling pathway. The purpose of this study was to evaluate Scl-Ab in an adult 6 month old Brtl/+ model of OI that harbors a typical heterozygous OI-causing Gly > Cys substitution on Col1a1. Six-month-old WT and Brtl/+ mice were treated with Scl-Ab (25 mg/kg, 2×/week) or Veh for 5 weeks. OCN and TRACP5b serum assays, dynamic histomorphometry, microCT and mechanical testing were performed. Adult Brtl/+ mice demonstrated a strong anabolic response to Scl-Ab with increased serum osteocalcin and bone formation rate. This anabolic response led to improved trabecular and cortical bone mass in the femur. Mechanical testing revealed Scl-Ab increased Brtl/+ femoral stiffness and strength. Scl-Ab was successfully anabolic in an adult Brtl/+ model of OI.

  13. AMPK activation through mitochondrial regulation results in increased substrate oxidation and improved metabolic parameters in models of diabetes.

    Directory of Open Access Journals (Sweden)

    Yonchu Jenkins

    Full Text Available Modulation of mitochondrial function through inhibiting respiratory complex I activates a key sensor of cellular energy status, the 5'-AMP-activated protein kinase (AMPK. Activation of AMPK results in the mobilization of nutrient uptake and catabolism for mitochondrial ATP generation to restore energy homeostasis. How these nutrient pathways are affected in the presence of a potent modulator of mitochondrial function and the role of AMPK activation in these effects remain unclear. We have identified a molecule, named R419, that activates AMPK in vitro via complex I inhibition at much lower concentrations than metformin (IC50 100 nM vs 27 mM, respectively. R419 potently increased myocyte glucose uptake that was dependent on AMPK activation, while its ability to suppress hepatic glucose production in vitro was not. In addition, R419 treatment of mouse primary hepatocytes increased fatty acid oxidation and inhibited lipogenesis in an AMPK-dependent fashion. We have performed an extensive metabolic characterization of its effects in the db/db mouse diabetes model. In vivo metabolite profiling of R419-treated db/db mice showed a clear upregulation of fatty acid oxidation and catabolism of branched chain amino acids. Additionally, analyses performed using both (13C-palmitate and (13C-glucose tracers revealed that R419 induces complete oxidation of both glucose and palmitate to CO2 in skeletal muscle, liver, and adipose tissue, confirming that the compound increases mitochondrial function in vivo. Taken together, our results show that R419 is a potent inhibitor of complex I and modulates mitochondrial function in vitro and in diabetic animals in vivo. R419 may serve as a valuable molecular tool for investigating the impact of modulating mitochondrial function on nutrient metabolism in multiple tissues and on glucose and lipid homeostasis in diabetic animal models.

  14. Ghrelin treatment causes increased food intake and retention of lean body mass in a rat model of cancer cachexia.

    Science.gov (United States)

    DeBoer, Mark D; Zhu, Xin Xia; Levasseur, Peter; Meguid, Michael M; Suzuki, Susumu; Inui, Akio; Taylor, John E; Halem, Heather A; Dong, Jesse Z; Datta, Rakesh; Culler, Michael D; Marks, Daniel L

    2007-06-01

    Cancer cachexia is a debilitating syndrome of anorexia and loss of lean body mass that accompanies many malignancies. Ghrelin is an orexigenic hormone with a short half-life that has been shown to improve food intake and weight gain in human and animal subjects with cancer cachexia. We used a rat model of cancer cachexia and administered human ghrelin and a synthetic ghrelin analog BIM-28131 via continuous infusion using sc osmotic minipumps. Tumor-implanted rats receiving human ghrelin or BIM-28131 exhibited a significant increase in food consumption and weight gain vs. saline-treated animals. We used dual-energy x-ray absorptiometry scans to show that the increased weight was due to maintenance of lean mass vs. a loss of lean mass in saline-treated animals. Also, BIM-28131 significantly limited the loss of fat mass normally observed in tumor-implanted rats. We further performed real-time PCR analysis of the hypothalami and brainstems and found that ghrelin-treated animals exhibited a significant increase in expression of orexigenic peptides agouti-related peptide and neuropeptide Y in the hypothalamus and a significant decrease in the expression of IL-1 receptor-I transcript in the hypothalamus and brainstem. We conclude that ghrelin and a synthetic ghrelin receptor agonist improve weight gain and lean body mass retention via effects involving orexigenic neuropeptides and antiinflammatory changes.

  15. Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down syndrome

    International Nuclear Information System (INIS)

    Epstein, C.J.; Avraham, K.B.; Lovett, M.; Smith, S.; Elroy-Stein, O.; Rotman, G.; Bry, C.; Groner, Y.

    1987-01-01

    Down syndrome, the phenotypic expression of human trisomy 21, is presumed to result from a 1.5-fold increase in the expression of the genes on human chromosome 21. As an approach to the development of an animal model for Down syndrome, several strains of transgenic mice that carry the human Cu/Zn-superoxide dismutase gene have been prepared. The animals express the transgene in a manner similar to that of humans, with 0.9- and 0.7-kilobase transcripts in a 1:4 ratio, and synthesize the human enzyme in an active form capable of forming human-mouse enzyme heterodimers. Cu/Zn-superoxide dismutase activity is increased from 1.6- to 6.0-fold in the brains of four transgenic strains and to an equal or lesser extent in several other tissues. These animals provide a unique system for studying the consequences of increased dosage of the Cu/Zn-superoxide dismutase gene in Down syndrome and the role of this enzyme in a variety of other pathological processes

  16. Electromechanical modeling of a honeycomb core integrated vibration energy converter with increased specific power for energy harvesting applications

    Science.gov (United States)

    Chandrasekharan, Nataraj

    especially if the application imposes a space/size constraint. Moreover, the bimorph with increased thickness will now require a larger mechanical force to deform the structure which can fall outside the input ambient excitation amplitude range. In contrast, the honeycomb core bimorph offers an advantage in terms of preserving the global geometric dimensions. The natural frequency of the honeycomb core bimorph can be altered by manipulating honeycomb cell design parameters, such as cell angle, cell wall thickness, vertical cell height and inclined cell length. This results in a change in the mass and stiffness properties of the substrate and hence the bimorph, thereby altering the natural frequency of the harvester. Design flexibility of honeycomb core bimorphs is demonstrated by varying honeycomb cell parameters to alter mass and stiffness properties for power harvesting. The influence of honeycomb cell parameters on power generation is examined to evaluate optimum design to attain highest specific power. In addition, the more compliant nature of a honeycomb core bimorph decreases susceptibility towards fatigue and can increase the operating lifetime of the harvester. The second component of this dissertation analyses an uncoupled equivalent circuit model for piezoelectric energy harvesting. Open circuit voltage developed on the piezoelectric materials can be easily computed either through analytical or finite element models. The efficacy of a method to determine power developed across a resistive load, by representing the coupled piezoelectric electromechanical problem with an external load as an open circuit voltage driven equivalent circuit, is evaluated. The lack of backward feedback at finite resistive loads resulting from such an equivalent representation is examined by comparing the equivalent circuit model to the governing equations of a fully coupled circuit model for the electromechanical problem. It is found that the backward feedback is insignificant for weakly

  17. Increases in guanylin and uroguanylin in a mouse model of osmotic diarrhea are guanylate cyclase C-independent.

    Science.gov (United States)

    Steinbrecher, K A; Mann, E A; Giannella, R A; Cohen, M B

    2001-11-01

    Guanylin and uroguanylin are peptide hormones that are homologous to the diarrhea-causing Escherichia coli enterotoxins. These secretagogues are released from the intestinal epithelia into the intestinal lumen and systemic circulation and bind to the receptor guanylate cyclase C (GC-C). We hypothesized that a hypertonic diet would result in osmotic diarrhea and cause a compensatory down-regulation of guanylin/uroguanylin. Gut-to-carcass weights were used to measure fluid accumulation in the intestine. Northern and/or Western analysis was used to determine the levels of guanylin, uroguanylin, and GC-C in mice with osmotic diarrhea. Wild-type mice fed a polyethylene glycol or lactose-based diet developed weight loss, diarrhea, and an increased gut-to-carcass ratio. Unexpectedly, 2 days on either diet resulted in increased guanylin/uroguanylin RNA and prohormone throughout the intestine, elevated uroguanylin RNA, and prohormone levels in the kidney and increased levels of circulating prouroguanylin. GC-C-deficient mice given the lactose diet reacted with higher gut-to-carcass ratios. Although they did not develop diarrhea, GC-C-sufficient and -deficient mice on the lactose diet responded with elevated levels of guanylin and uroguanylin RNA and protein. A polyethylene glycol drinking water solution resulted in diarrhea, higher gut-to-carcass ratios, and induction of guanylin and uroguanylin in both GC-C heterozygous and null animals. We conclude that this model of osmotic diarrhea results in a GC-C-independent increase in intestinal fluid accumulation, in levels of these peptide ligands in the epithelia of the intestine, and in prouroguanylin in the kidney and blood.

  18. Brain urea increase is an early Huntington's disease pathogenic event observed in a prodromal transgenic sheep model and HD cases.

    Science.gov (United States)

    Handley, Renee R; Reid, Suzanne J; Brauning, Rudiger; Maclean, Paul; Mears, Emily R; Fourie, Imche; Patassini, Stefano; Cooper, Garth J S; Rudiger, Skye R; McLaughlan, Clive J; Verma, Paul J; Gusella, James F; MacDonald, Marcy E; Waldvogel, Henry J; Bawden, C Simon; Faull, Richard L M; Snell, Russell G

    2017-12-26

    The neurodegenerative disorder Huntington's disease (HD) is typically characterized by extensive loss of striatal neurons and the midlife onset of debilitating and progressive chorea, dementia, and psychological disturbance. HD is caused by a CAG repeat expansion in the Huntingtin ( HTT ) gene, translating to an elongated glutamine tract in the huntingtin protein. The pathogenic mechanism resulting in cell dysfunction and death beyond the causative mutation is not well defined. To further delineate the early molecular events in HD, we performed RNA-sequencing (RNA-seq) on striatal tissue from a cohort of 5-y-old OVT73 -line sheep expressing a human CAG-expansion HTT cDNA transgene. Our HD OVT73 sheep are a prodromal model and exhibit minimal pathology and no detectable neuronal loss. We identified significantly increased levels of the urea transporter SLC14A1 in the OVT73 striatum, along with other important osmotic regulators. Further investigation revealed elevated levels of the metabolite urea in the OVT73 striatum and cerebellum, consistent with our recently published observation of increased urea in postmortem human brain from HD cases. Extending that finding, we demonstrate that postmortem human brain urea levels are elevated in a larger cohort of HD cases, including those with low-level neuropathology (Vonsattel grade 0/1). This elevation indicates increased protein catabolism, possibly as an alternate energy source given the generalized metabolic defect in HD. Increased urea and ammonia levels due to dysregulation of the urea cycle are known to cause neurologic impairment. Taken together, our findings indicate that aberrant urea metabolism could be the primary biochemical disruption initiating neuropathogenesis in HD.

  19. The effect of nano-silver packaging in increasing the shelf life of nuts: An in vitro model.

    Science.gov (United States)

    Tavakoli, Hamidreza; Rastegar, Hossein; Taherian, Mahdi; Samadi, Mohammad; Rostami, Hossein

    2017-10-20

    Nano packaging is currently one of the most important topics in food packaging technologies. The aim of the application of this technology in food packaging is increasing shelf life of foods by preventing internal and external corruption and microbial contaminations. Use of silver nanoparticles in food packaging has recently attracted much attention. The aim of this study was to investigate the effect of nano-silver packaging in increasing the shelf life packages of nuts in an In vitro model. In this experimental study, the effects of different nano-silver concentrations (0, 1, 2 and 3 percent) on biological and chemical properties of 432 samples of nuts including walnuts, hazelnuts, almonds and pistachios were evaluated during 0, 3, 6, 9, 12, 15, 18, 21 and 24 months. In most samples, different concentrations of nano-silver (1, 2 and 3 %) significantly reduced total microbial count, mold and coliform counts compared to control group and the 3% nano-silver concentration was more effective than other concentrations (Pnano-silver concentrations were used. Nano-silver also prevented growth of mold and so prevented aflatoxin production in all treatment groups. Results of chemical and biological tests showed that the silver nanoparticles had a significant effect on increasing the shelf life of nuts. The highest shelf life belonged to pistachios, almonds, hazelnuts and walnuts with 20, 19, 18 and 18 months, respectively. The shelf life was associated with amount of silver nanoparticles. The highest antimicrobial activity was observed when 3% nano-silver concentration was used in pistachios. The shelf life of control groups in similar storage conditions were calculated for an average of 13 months. In conclusion, the results of this study demonstrate the efficacy of nano-silver packing in increasing shelf life of nuts. Hence, use of nano-silver packaging in food industry, especially in food packaging is recommended.

  20. A modified Wright-Fisher model that incorporates Ne: A variant of the standard model with increased biological realism and reduced computational complexity.

    Science.gov (United States)

    Zhao, Lei; Gossmann, Toni I; Waxman, David

    2016-03-21

    The Wright-Fisher model is an important model in evolutionary biology and population genetics. It has been applied in numerous analyses of finite populations with discrete generations. It is recognised that real populations can behave, in some key aspects, as though their size that is not the census size, N, but rather a smaller size, namely the effective population size, Ne. However, in the Wright-Fisher model, there is no distinction between the effective and census population sizes. Equivalently, we can say that in this model, Ne coincides with N. The Wright-Fisher model therefore lacks an important aspect of biological realism. Here, we present a method that allows Ne to be directly incorporated into the Wright-Fisher model. The modified model involves matrices whose size is determined by Ne. Thus apart from increased biological realism, the modified model also has reduced computational complexity, particularly so when Ne⪡N. For complex problems, it may be hard or impossible to numerically analyse the most commonly-used approximation of the Wright-Fisher model that incorporates Ne, namely the diffusion approximation. An alternative approach is simulation. However, the simulations need to be sufficiently detailed that they yield an effective size that is different to the census size. Simulations may also be time consuming and have attendant statistical errors. The method presented in this work may then be the only alternative to simulations, when Ne differs from N. We illustrate the straightforward application of the method to some problems involving allele fixation and the determination of the equilibrium site frequency spectrum. We then apply the method to the problem of fixation when three alleles are segregating in a population. This latter problem is significantly more complex than a two allele problem and since the diffusion equation cannot be numerically solved, the only other way Ne can be incorporated into the analysis is by simulation. We have

  1. Joint bleeds increase the inhibitor response to human factor VIII in a rat model of severe haemophilia A

    DEFF Research Database (Denmark)

    Löfgren, Karin Maria; Søndergaard, H.; Skov, Søren

    2016-01-01

    Introduction The most serious complication in haemophilia A (HA) replacement therapy with coagulation factor VIII (FVIII) is neutralizing antibodies, i.e. inhibitors. It has been hypothesized that danger signals generated during a bleed might have an adjuvant effect on the immune response to FVIII...... in on-demand treatment, increasing the inhibitor risk. Aim To compare the antibody response to treatment with recombinant human FVIII (rhFVIII) in relation to induced knee joint bleeds and treatment without concurrent bleeds in a HA rat model. Method HA rats were divided into two groups: one group (n...... = 10) receiving three needle induced knee joint bleeds 14 days apart and a control group (n = 9) receiving three sham procedures. Three hours after each injury/sham 50 IU kg−1 rhFVIII was administrated intravenously. Subsequently, both groups continued rhFVIII treatment for another 9 weeks. Binding...

  2. Microbial Adhesion and Biofilm Formation on Microfiltration Membranes: A Detailed Characterization Using Model Organisms with Increasing Complexity

    Directory of Open Access Journals (Sweden)

    L. Vanysacker

    2013-01-01

    Full Text Available Since many years, membrane biofouling has been described as the Achilles heel of membrane fouling. In the present study, an ecological assay was performed using model systems with increasing complexity: a monospecies assay using Pseudomonas aeruginosa or Escherichia coli separately, a duospecies assay using both microorganisms, and a multispecies assay using activated sludge with or without spiked P. aeruginosa. The microbial adhesion and biofilm formation were evaluated in terms of bacterial cell densities, species richness, and bacterial community composition on polyvinyldifluoride, polyethylene, and polysulfone membranes. The data show that biofouling formation was strongly influenced by the kind of microorganism, the interactions between the organisms, and the changes in environmental conditions whereas the membrane effect was less important. The findings obtained in this study suggest that more knowledge in species composition and microbial interactions is needed in order to understand the complex biofouling process. This is the first report describing the microbial interactions with a membrane during the biofouling development.

  3. Microbial Adhesion and Biofilm Formation on Microfiltration Membranes: A Detailed Characterization Using Model Organisms with Increasing Complexity

    Science.gov (United States)

    Vanysacker, L.; Denis, C.; Declerck, P.; Piasecka, A.; Vankelecom, I. F. J.

    2013-01-01

    Since many years, membrane biofouling has been described as the Achilles heel of membrane fouling. In the present study, an ecological assay was performed using model systems with increasing complexity: a monospecies assay using Pseudomonas aeruginosa or Escherichia coli separately, a duospecies assay using both microorganisms, and a multispecies assay using activated sludge with or without spiked P. aeruginosa. The microbial adhesion and biofilm formation were evaluated in terms of bacterial cell densities, species richness, and bacterial community composition on polyvinyldifluoride, polyethylene, and polysulfone membranes. The data show that biofouling formation was strongly influenced by the kind of microorganism, the interactions between the organisms, and the changes in environmental conditions whereas the membrane effect was less important. The findings obtained in this study suggest that more knowledge in species composition and microbial interactions is needed in order to understand the complex biofouling process. This is the first report describing the microbial interactions with a membrane during the biofouling development. PMID:23986906

  4. MicroCT and microMRI imaging of a prenatal mouse model of increased brain size

    Science.gov (United States)

    López, Elisabeth K. N.; Stock, Stuart R.; Taketo, Makoto M.; Chenn, Anjen; Ravosa, Matthew J.

    2008-08-01

    There are surprisingly few experimental models of neural growth and cranial integration. This and the dearth of information regarding fetal brain development detract from a mechanistic understanding of cranial integration and its relevance to the patterning of skull form, specifically the role of encephalization on basicranial flexion. To address this shortcoming, our research uses transgenic mice expressing a stabilized form of β-catenin to isolate the effects of relative brain size on craniofacial development. These mice develop highly enlarged brains due to an increase in neural precursors, and differences between transgenic and wild-type mice are predicted to result solely from variation in brain size. Comparisons of wild-type and transgenic mice at several prenatal ages were performed using microCT (Scanco Medical MicroCT 40) and microMRI (Avance 600 WB MR spectrometer). Statistical analyses show that the larger brain of the transgenic mice is associated with a larger neurocranium and an altered basicranial morphology. However, body size and postcranial ossification do not seem to be affected by the transgene. Comparisons of the rate of postcranial and cranial ossification using microCT also point to an unexpected effect of neural growth on skull development: increased fetal encephalization may result in a compensatory decrease in the level of cranial ossification. Therefore, if other life history factors are held constant, the ontogeny of a metabolically costly structure such as a brain may occur at the expense of other cranial structures. These analyses indicate the benefits of a multifactorial approach to cranial integration using a mouse model.

  5. Irrigated Agriculture in Morocco: An Agent-Based Model of Adaptation and Decision Making Amid Increasingly Frequent Drought Events

    Science.gov (United States)

    Norton, M.

    2015-12-01

    In the past 100 years, Morocco has undertaken a heavy investment in developing water infrastructure that has led to a dramatic expansion of irrigated agriculture. Irrigated agriculture is the primary user of water in many arid countries, often accounting for 80-90% of total water usage. Irrigation is adopted by farmers not only because it leads to increased production, but also because it improves resilience to an uncertain climate. However, the Mediterranean region as a whole has also seen an increase in the frequency and severity of drought events. These droughts have had a dramatic impact on farmer livelihoods and have led to a number of coping strategies, including the adoption or disadoption of irrigation. In this study, we use a record of the annual extent of irrigated agriculture in Morocco to model the effect of drought on the extent of irrigated agriculture. Using an agent-based socioeconomic model, we seek to answer the following questions: 1) Do farmers expand irrigated agriculture in response to droughts? 2) Do drought events entail the removal of perennial crops like orchards? 3) Can we detect the retreat of irrigated agriculture in the more fragile watersheds of Morocco? Understanding the determinants of irrigated crop expansion and contractions will help us understand how agro-ecological systems transition from 20th century paradigms of expansion of water supply to a 21st century paradigm of water use efficiency. The answers will become important as countries learn how to manage water in new climate regimes characterized by less reliable and available precipitation.

  6. SU-F-T-119: Development of Heart Prediction Model to Increase Accuracy of Dose Reconstruction for Radiotherapy Patients

    Energy Technology Data Exchange (ETDEWEB)

    Mosher, E; Choi, M; Lee, C [Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (United States); Jones, E [Radiology and Imaging Sciences Clinical Center, National Institutes of Health, Bethesda, MD (United States)

    2016-06-15

    Purpose: To assess individual variation in heart volume and location in order to develop a prediction model of the heart. This heart prediction model will be used to calculate individualized heart doses for radiotherapy patients in epidemiological studies. Methods: Chest CT images for 30 adult male and 30 adult female patients were obtained from NIH Clinical Center. Image-analysis computer programs were used to segment the whole heart and 8 sub-regions and to measure the volume of each sub- region and the dimension of the whole heart. An analytical dosimetry method was used for the 30 adult female patients to estimate mean heart dose during conventional left breast radiotherapy. Results: The average volumes of the whole heart were 803.37 cm{sup 3} (COV 18.8%) and 570.19 cm{sup 3} (COV 18.8%) for adult male and female patients, respectively, which are comparable with the international reference volumes of 807.69 cm{sup 3} for males and 596.15 cm{sup 3} for females. Some patient characteristics were strongly correlated (R{sup 2}>0.5) with heart volume and heart dimensions (e.g., Body Mass Index vs. heart depth in males: R{sup 2}=0.54; weight vs. heart width in the adult females: R{sup 2}=0.63). We found that the mean heart dose 3.805 Gy (assuming prescribed dose of 50 Gy) in the breast radiotherapy simulations of the 30 adult females could be an underestimate (up to 1.6-fold) or overestimate (up to 1.8-fold) of the patient-specific heart dose. Conclusion: The study showed the significant variation in patient heart volumes and dimensions, resulting in substantial dose errors when a single average heart model is used for retrospective dose reconstruction. We are completing a multivariate analysis to develop a prediction model of the heart. This model will increase accuracy in dose reconstruction for radiotherapy patients and allow us to individualize heart dose calculations for patients whose CT images are not available.

  7. SU-F-T-119: Development of Heart Prediction Model to Increase Accuracy of Dose Reconstruction for Radiotherapy Patients

    International Nuclear Information System (INIS)

    Mosher, E; Choi, M; Lee, C; Jones, E

    2016-01-01

    Purpose: To assess individual variation in heart volume and location in order to develop a prediction model of the heart. This heart prediction model will be used to calculate individualized heart doses for radiotherapy patients in epidemiological studies. Methods: Chest CT images for 30 adult male and 30 adult female patients were obtained from NIH Clinical Center. Image-analysis computer programs were used to segment the whole heart and 8 sub-regions and to measure the volume of each sub- region and the dimension of the whole heart. An analytical dosimetry method was used for the 30 adult female patients to estimate mean heart dose during conventional left breast radiotherapy. Results: The average volumes of the whole heart were 803.37 cm"3 (COV 18.8%) and 570.19 cm"3 (COV 18.8%) for adult male and female patients, respectively, which are comparable with the international reference volumes of 807.69 cm"3 for males and 596.15 cm"3 for females. Some patient characteristics were strongly correlated (R"2>0.5) with heart volume and heart dimensions (e.g., Body Mass Index vs. heart depth in males: R"2=0.54; weight vs. heart width in the adult females: R"2=0.63). We found that the mean heart dose 3.805 Gy (assuming prescribed dose of 50 Gy) in the breast radiotherapy simulations of the 30 adult females could be an underestimate (up to 1.6-fold) or overestimate (up to 1.8-fold) of the patient-specific heart dose. Conclusion: The study showed the significant variation in patient heart volumes and dimensions, resulting in substantial dose errors when a single average heart model is used for retrospective dose reconstruction. We are completing a multivariate analysis to develop a prediction model of the heart. This model will increase accuracy in dose reconstruction for radiotherapy patients and allow us to individualize heart dose calculations for patients whose CT images are not available.

  8. Increased diacylglycerols characterize hepatic lipid changes in progression of human nonalcoholic fatty liver disease; comparison to a murine model.

    Science.gov (United States)

    Gorden, D Lee; Ivanova, Pavlina T; Myers, David S; McIntyre, J Oliver; VanSaun, Michael N; Wright, J Kelly; Matrisian, Lynn M; Brown, H Alex

    2011-01-01

    The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and progression to cirrhosis. While differences in liver lipids between disease states have been reported, precise composition of phospholipids and diacylglycerols (DAG) at a lipid species level has not been previously described. The goal of this study was to characterize changes in lipid species through progression of human NAFLD using advanced lipidomic technology and compare this with a murine model of early and advanced NAFLD. Utilizing mass spectrometry lipidomics, over 250 phospholipid and diacylglycerol species (DAGs) were identified in normal and diseased human and murine liver extracts. Significant differences between phospholipid composition of normal and diseased livers were demonstrated, notably among DAG species, consistent with previous reports that DAG transferases are involved in the progression of NAFLD and liver fibrosis. In addition, a novel phospholipid species (ether linked phosphatidylinositol) was identified in human cirrhotic liver extracts. Using parallel lipidomics analysis of murine and human liver tissues it was determined that mice maintained on a high-fat diet provide a reproducible model of NAFLD in regards to specificity of lipid species in the liver. These studies demonstrated that novel lipid species may serve as markers of advanced liver disease and importantly, marked increases in DAG species are a hallmark of NAFLD. Elevated DAGs may contribute to altered triglyceride, phosphatidylcholine (PC), and phosphatidylethanolamine (PE) levels characteristic of the disease and specific DAG species might be important lipid signaling molecules in the progression of NAFLD.

  9. Bee Venom Acupuncture Reduces Interleukin-6, Increases Interleukin-10, and Induces Locomotor Recovery in a Model of Spinal Cord Compression.

    Science.gov (United States)

    Nascimento de Souza, Raquel; Silva, Fernanda Kohn; Alves de Medeiros, Magda

    2017-06-01

    Spinal cord injuries (SCIs) initiate a series of molecular and cellular events in which inflammatory responses can lead to major neurological dysfunctions. The present study aims to investigate whether bee venom (BV) acupuncture applied at acupoints ST36 (Zusanli) and GV3 (Yaoyangquan) could minimize locomotor deficits and the magnitude of neural tissue losses, and change the balance between pro- and anti-inflammatory cytokines after an SCI by compression. Wistar rats were subjected to an SCI model by compression in which a 2-French Fogarty embolectomy catheter was inflated in the extradural space. The effects of BV acupuncture, in which 20 μL of BV diluted in saline (0.08 mg/kg) was injected at acupoints GV3 and ST36 [BV(ST36+GV3)-SCI] was compared with BV injected at nonacupoints [BV(NP)-SCI] and with no treatment [group subjected only to SCI (CTL-SCI)]. The BV(ST36+GV3)-SCI group showed a significant improvement in the locomotor performance and a decrease of lesion size compared with the controls. BV acupuncture at the ST36 + GV3 increased the expression of interleukin-10 (anti-inflammatory) at 6 hours and reduced the expression of interleukin-6 (proinflammatory) at 24 hours after SCI compared with the controls. Our results suggest that BV acupuncture can reduce neuroinflammation and induce recovery in the SCI compression model. Copyright © 2017. Published by Elsevier B.V.

  10. Modeling of steroid estrogen contamination in UK and South Australian rivers predicts modest increases in concentrations in the future.

    Science.gov (United States)

    Green, Christopher; Williams, Richard; Kanda, Rakesh; Churchley, John; He, Ying; Thomas, Shaun; Goonan, Peter; Kumar, Anu; Jobling, Susan

    2013-07-02

    The prediction of risks posed by pharmaceuticals and personal care products in the aquatic environment now and in the future is one of the top 20 research questions regarding these contaminants following growing concern for their biological effects on fish and other animals. To this end it is important that areas experiencing the greatest risk are identified, particularly in countries experiencing water stress, where dilution of pollutants entering river networks is more limited. This study is the first to use hydrological models to estimate concentrations of pharmaceutical and natural steroid estrogens in a water stressed catchment in South Australia alongside a UK catchment and to forecast their concentrations in 2050 based on demographic and climate change predictions. The results show that despite their differing climates and demographics, modeled concentrations of steroid estrogens in effluents from Australian sewage treatment works and a receiving river were predicted (simulated) to be similar to those observed in the UK and Europe, exceeding the combined estradiol equivalent's predicted no effect concentration for feminization in wild fish. Furthermore, by 2050 a moderate increase in estrogenic contamination and the potential risk to wildlife was predicted with up to a 2-fold rise in concentrations.

  11. Factors affecting increased risk for substance use disorders following traumatic brain injury: What we can learn from animal models.

    Science.gov (United States)

    Merkel, Steven F; Cannella, Lee Anne; Razmpour, Roshanak; Lutton, Evan; Raghupathi, Ramesh; Rawls, Scott M; Ramirez, Servio H

    2017-06-01

    Recent studies have helped identify multiple factors affecting increased risk for substance use disorders (SUDs) following traumatic brain injury (TBI). These factors include age at the time of injury, repetitive injury and TBI severity, neurocircuits, neurotransmitter systems, neuroinflammation, and sex differences. This review will address each of these factors by discussing 1) the clinical and preclinical data identifying patient populations at greatest risk for SUDs post-TBI, 2) TBI-related neuropathology in discrete brain regions heavily implicated in SUDs, and 3) the effects of TBI on molecular mechanisms that may drive substance abuse behavior, like dopaminergic and glutamatergic transmission or neuroimmune signaling in mesolimbic regions of the brain. Although these studies have laid the groundwork for identifying factors that affect risk of SUDs post-TBI, additional studies are required. Notably, preclinical models have been shown to recapitulate many of the behavioral, cellular, and neurochemical features of SUDs and TBI. Therefore, these models are well suited for answering important questions that remain in future investigations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Model based hydropower gate operation for mitigation of CSO impacts by means of river base flow increase.

    Science.gov (United States)

    Achleitner, S; De Toffol, S; Engelhard, C; Rauch, W

    2005-01-01

    In river stretches being subjected to flow regulation, usually for the purpose of energy production (e.g. Hydropower) or flood protection (river barrage), a special measure can be taken against the effect of combined sewer overflows (CSOs). The basic idea is the temporal increase of the river base flow (during storm weather) as an in-stream measure for mitigation of CSO spilling. The focus is the mitigation of the negative effect of acute pollution of substances. The measure developed can be seen as an application of the classic real time control (RTC) concept onto the river system. Upstream gate operation is to be based on real time monitoring and forecasting of precipitation. The main objective is the development of a model based predictive control system for the gate operation, by modelling of the overall wastewater system (incl. the receiving water). The main emphasis is put on the operational strategy and the appropriate short-term forecast of spilling events. The potential of the measure is tested for the application of the operational strategy and its ecological and economic feasibility. The implementation of such an in-stream measure into the hydropower's operational scheme is unique. Advantages are (a) the additional in-stream dilution of acute pollutants entering the receiving water and (b) the resulting minimization of the required CSO storage volume.

  13. Increasing parameter certainty and data utility through multi-objective calibration of a spatially distributed temperature and solute model

    Directory of Open Access Journals (Sweden)

    C. Bandaragoda

    2011-05-01

    Full Text Available To support the goal of distributed hydrologic and instream model predictions based on physical processes, we explore multi-dimensional parameterization determined by a broad set of observations. We present a systematic approach to using various data types at spatially distributed locations to decrease parameter bounds sampled within calibration algorithms that ultimately provide information regarding the extent of individual processes represented within the model structure. Through the use of a simulation matrix, parameter sets are first locally optimized by fitting the respective data at one or two locations and then the best results are selected to resolve which parameter sets perform best at all locations, or globally. This approach is illustrated using the Two-Zone Temperature and Solute (TZTS model for a case study in the Virgin River, Utah, USA, where temperature and solute tracer data were collected at multiple locations and zones within the river that represent the fate and transport of both heat and solute through the study reach. The result was a narrowed parameter space and increased parameter certainty which, based on our results, would not have been as successful if only single objective algorithms were used. We also found that the global optimum is best defined by multiple spatially distributed local optima, which supports the hypothesis that there is a discrete and narrowly bounded parameter range that represents the processes controlling the dominant hydrologic responses. Further, we illustrate that the optimization process itself can be used to determine which observed responses and locations are most useful for estimating the parameters that result in a global fit to guide future data collection efforts.

  14. Amphiphilic HPMA-LMA copolymers increase the transport of Rhodamine 123 across a BBB model without harming its barrier integrity.

    Science.gov (United States)

    Hemmelmann, Mirjam; Metz, Verena V; Koynov, Kaloian; Blank, Kerstin; Postina, Rolf; Zentel, Rudolf

    2012-10-28

    The successful non-invasive treatment of diseases associated with the central nervous system (CNS) is generally limited by poor brain permeability of various developed drugs. The blood-brain barrier (BBB) prevents the passage of therapeutics to their site of action. Polymeric drug delivery systems are promising solutions to effectively transport drugs into the brain. We recently showed that amphiphilic random copolymers based on the hydrophilic p(N-(2-hydroxypropyl)-methacrylamide), pHPMA, possessing randomly distributed hydrophobic p(laurylmethacrylate), pLMA, are able to mediate delivery of domperidone into the brain of mice in vivo. To gain further insight into structure-property relations, a library of carefully designed polymers based on p(HPMA) and p(LMA) was synthesized and tested applying an in vitro BBB model which consisted of human brain microvascular endothelial cells (HBMEC). Our model drug Rhodamine 123 (Rh123) exhibits, like domperidone, a low brain permeability since both substances are recognized by efflux transporters at the BBB. Transport studies investigating the impact of the polymer architecture in relation to the content of hydrophobic LMA revealed that random p(HPMA)-co-p(LMA) having 10mol% LMA is the most auspicious system. The copolymer significantly increased the permeability of Rh123 across the HBMEC monolayer whereas transcytosis of the polymer was very low. Further investigations on the mechanism of transport showed that integrity and barrier function of the BBB model were not harmed by the polymer. According to our results, p(HPMA)-co-p(LMA) copolymers are a promising delivery system for neurological therapeutics and their application might open alternative treatment strategies. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Higher molecular weight polyethylene glycol increases cell proliferation while improving barrier function in an in vitro colon cancer model.

    Science.gov (United States)

    Bharadwaj, Shruthi; Vishnubhotla, Ramana; Shan, Sun; Chauhan, Chinmay; Cho, Michael; Glover, Sarah C

    2011-01-01

    Polyethylene glycol (PEG) has been previously shown to protect against enteric pathogens and prevent colon cancer invasion. To determine if PEG could indeed protect against previously observed pro-invasive effects of commensal E. coli and EPEC, Caco-2 cells grown in an in vitro model of colon cancer were infected with strains of human commensal E. coli or EPEC and treated with 10% PEG 3350, PEG 8000, and PEG 20,000, respectively. At 24 hours after infection, MMP-1 and MMP-13 activities, cell cluster thickness, depth of invasion, and proliferation were determined using standard molecular biology techniques and advanced imaging. We found that higher molecular weight PEG, especially PEG 8000 and 20,000, regardless of bacterial infection, increased proliferation and depth of invasion although a decrease in cellular density and MMP-1 activity was also noted. Maximum proliferation and depth of invasion of Caco-2 cells was observed in scaffolds treated with a combination of commensal E. coli strain, HS4 and PEG 8000. In conclusion, we found that PEG 8000 increased cell proliferation and led to the preservation of cell density in cells treated with commensal bacteria. This is important, because the preservation of a proliferative response in colon cancer results in a more chemo-responsive tumor.

  16. Transcriptome and DNA Methylome Analysis in a Mouse Model of Diet-Induced Obesity Predicts Increased Risk of Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Ruifang Li

    2018-01-01

    Full Text Available Colorectal cancer (CRC tends to occur at older age; however, CRC incidence rates have been rising sharply among young age groups. The increasing prevalence of obesity is recognized as a major risk, yet the mechanistic underpinnings remain poorly understood. Using a diet-induced obesity mouse model, we identified obesity-associated molecular changes in the colonic epithelium of young and aged mice, and we further investigated whether the changes were reversed after weight loss. Transcriptome analysis indicated that obesity-related colonic cellular metabolic switch favoring long-chain fatty acid oxidation happened in young mice, while obesity-associated downregulation of negative feedback regulators of pro-proliferative signaling pathways occurred in older mice. Strikingly, colonic DNA methylome was pre-programmed by obesity at young age, priming for a tumor-prone gene signature after aging. Furthermore, obesity-related changes were substantially preserved after short-term weight loss, but they were largely reversed after long-term weight loss. We provided mechanistic insights into increased CRC risk in obesity.

  17. Higher Molecular Weight Polyethylene Glycol Increases Cell Proliferation While Improving Barrier Function in an In Vitro Colon Cancer Model

    Directory of Open Access Journals (Sweden)

    Shruthi Bharadwaj

    2011-01-01

    Full Text Available Polyethylene glycol (PEG has been previously shown to protect against enteric pathogens and prevent colon cancer invasion. To determine if PEG could indeed protect against previously observed pro-invasive effects of commensal E. coli and EPEC, Caco-2 cells grown in an in vitro model of colon cancer were infected with strains of human commensal E. coli or EPEC and treated with 10% PEG 3350, PEG 8000, and PEG 20,000, respectively. At 24 hours after infection, MMP-1 and MMP-13 activities, cell cluster thickness, depth of invasion, and proliferation were determined using standard molecular biology techniques and advanced imaging. We found that higher molecular weight PEG, especially PEG 8000 and 20,000, regardless of bacterial infection, increased proliferation and depth of invasion although a decrease in cellular density and MMP-1 activity was also noted. Maximum proliferation and depth of invasion of Caco-2 cells was observed in scaffolds treated with a combination of commensal E. coli strain, HS4 and PEG 8000. In conclusion, we found that PEG 8000 increased cell proliferation and led to the preservation of cell density in cells treated with commensal bacteria. This is important, because the preservation of a proliferative response in colon cancer results in a more chemo-responsive tumor.

  18. Growth Modeling of the Maternal Cytokine Milieu throughout Normal Pregnancy: Macrophage-Derived Chemokine Decreases as Inflammation/Counterregulation Increases

    Directory of Open Access Journals (Sweden)

    Shernan G. Holtan

    2015-01-01

    Full Text Available Several recent studies have shown differences in the maternal immune milieu at different phases of pregnancy, but most studies have been cross-sectional or of relatively few time points. Levels of 42 cytokines were determined using a multiplex bead-based assay on archived serum from a cohort of pregnant women N=16 at median of 18 time points tested, from the first trimester through to parturition, per woman. Unconditional growth modeling was then used to determine time-dependent changes in levels of these cytokines. Macrophage-derived chemokine (MDC, aka CCL22 decreases as pregnancy progresses. IL-1β, IL-6, IL-8, IL-12p70, IL-13, IL-15, IP-10, and FLT3-ligand increase as a function of gestational weeks, and IFNα2, IL-1ra, IL-3, IL-9, IL-12p40, and soluble CD40 ligand increase as a function of trimester. As pregnancy normally progresses, a maternal shift away from a type 2-biased immune response and toward an inflammatory/counterregulatory response is observed.

  19. UCAO (UNILATERAL CEREBRAL ARTERY OCCLUSSION METHOD INCREASES THE LEVEL OF MMP- 9 BRAIN TISSUE IN RATS MODEL OF ISCHEMIC STROKE

    Directory of Open Access Journals (Sweden)

    M. Rasjad Indra

    2016-07-01

    Full Text Available Background. For the last 5 years, 15.4% of total population died because of stroke, which 42.9% of those are caused by ischemic stroke. UCAO (Unilateral Cerebral Artery Occlusion is a stroke induction method by ligating mice’s carotid artery for 45 minutes. Thus, giving a hypoxic condition similar to stroke attack in human. This method is less complicated and far more efficient. MMP-9 is a stroke marker which is assayed by ELISA from the blood of test animal. Objective. This research was conducted to prove UCAO (Unilateral Cerebral Artery Occlusion method is capable to raise MMP-9 concentration in mice’s blood. Methods. This research was an experimental laboratory research with post-test only controlled group design. 8 male rats (8-10 weeks were divided into 2 groups, control and treatment which would be inducted into stroke by UCAO method. A day after the treatment group had been induced to stroke, both group were tested to measure the MMP-9 blood concentration through ELISA. Results. In this research, UCAO method had increased MMP-9 blood concentration in treatment group, compared to the control group. It is proved by the statistic tests, Mann-Whitney and Kruskal-Wallis, which showed a significant increase in treatment group (p < 0.05. Conclusion. Based on this result, it can be concluded that UCAO method is accepted as a method to create an ischemic stroke mice model.

  20. Evaluation results of the GlobalWatershed GK-12 Fellowship Program - a model for increased science literacy and partnership

    Science.gov (United States)

    Mayer, A. S.; Vye, E.

    2016-12-01

    The Michigan Tech GlobalWatershed GK-12 Fellowship program bridges the gap between K-12 learning institutions and the scientific community with a focus on watershed research. Michigan Tech graduate students (fellows) work in tandem with teachers on the development of relevant hands-on, inquiry based lesson plans and activities based on their doctoral research projects in watershed science. By connecting students and teachers to state of the art academic research in watershed science, teachers are afforded a meaningful way in which to embed scientific research as a component of K-12 curricula, while mentoring fellows on the most pertinent and essential topics for lesson plan development. Fellows fulfill their vital responsibility of communicating their academic research to a broader public while fostering improved teaching and communication skills. A goal of the project is to increase science literacy among students so they may understand, communicate and participate in decisions made at local, regional, and global levels. The project largely works with schools located in Michigan's western Upper Peninsula but also partners with K-12 systems in Sonora, Mexico. While focusing on local and regional issues, the international element of the project helps expand student, teacher, and fellow worldviews and global awareness of watershed issues and creates meaningful partnerships. Lesson plans are available online and teacher workshops are held regularly to disseminate the wealth of information and resources available to the broader public. Evaluation results indicate that fellows' skill and confidence in their ability to communicate science increased as a results of their participation of the program, as well as their desire to communicate science in their future careers. Teachers' confidence in their capacity to present watershed science to their students increased, along with their understanding of how scientific research contributes to understanding of water

  1. TMG-123, a novel glucokinase activator, exerts durable effects on hyperglycemia without increasing triglyceride in diabetic animal models.

    Science.gov (United States)

    Tsumura, Yoshinori; Tsushima, Yu; Tamura, Azusa; Hasebe, Makiko; Kanou, Masanobu; Kato, Hirotsugu; Kobayashi, Tsunefumi

    2017-01-01

    Glucokinase (GK) plays a critical role for maintaining glucose homeostasis with regulating glucose uptake in liver and insulin secretion in pancreas. GK activators have been reported to decrease blood glucose levels in patients with type 2 diabetes mellitus. However, clinical development of GK activators has failed due to the loss of glucose-lowering effects and increased plasma triglyceride levels after chronic treatment. Here, we generated a novel GK activator, TMG-123, examined its in vitro and in vivo pharmacological characteristics, and evaluated its risks of aforementioned clinical issues. TMG-123 selectively activated GK enzyme activity without increasing Vmax. TMG-123 improved glucose tolerance without increasing plasma insulin levels in both insulin-deficient (Goto-Kakizaki rats) and insulin-resistant (db/db mice) models. The beneficial effect on glucose tolerance was greater than results observed with clinically available antidiabetic drugs such as metformin and glibenclamide in Zucker Diabetic Fatty rats. TMG-123 also improved glucose tolerance in combination with metformin. After 4 weeks of administration, TMG-123 reduced the Hemoglobin A1c levels without affecting liver and plasma triglyceride levels in Goto-Kakizaki rats and Diet-Induced Obesity mice. Moreover, TMG-123 sustained its effect on Hemoglobin A1c levels even after 24 weeks of administration without affecting triglycerides. Taken together, these data indicate that TMG-123 exerts glucose-lowering effects in both insulin-deficient and -resistant diabetes, and sustains reduced Hemoglobin A1c levels without affecting hepatic and plasma triglycerides even after chronic treatment. Therefore, TMG-123 is expected to be an antidiabetic drug that overcomes the concerns previously reported with other GK activators.

  2. Accelerated Growth Rate and Increased Drought Stress Resilience of the Model Grass Brachypodium distachyon Colonized by Bacillus subtilis B26.

    Directory of Open Access Journals (Sweden)

    François Gagné-Bourque

    Full Text Available Plant growth-promoting bacteria (PGB induce positive effects in plants, for instance, increased growth and reduced abiotic stresses susceptibility. The mechanisms by which these bacteria impact the host plant are numerous, diverse and often specific. Here, we studied the agronomical, molecular and biochemical effects of the endophytic PGB Bacillus subtilis B26 on the full life cycle of Brachypodium distachyon Bd21, an established model species for functional genomics in cereal crops and temperate grasses. Inoculation of Brachypodium with B. subtilis strain B26 increased root and shoot weights, accelerated growth rate and seed yield as compared to control plants. B. subtilis strain B26 efficiently colonized the plant and was recovered from roots, stems and blades as well as seeds of Brachypodium, indicating that the bacterium is able to migrate, spread systemically inside the plant, establish itself in the aerial plant tissues and organs, and is vertically transmitted to seeds. The presence of B. subtilis strain B26 in the seed led to systemic colonization of the next generation of Brachypodium plants. Inoculated Brachypodium seedlings and mature plants exposed to acute and chronic drought stress minimized the phenotypic effect of drought compared to plants not harbouring the bacterium. Protection from the inhibitory effects of drought by the bacterium was linked to upregulation of the drought-response genes, DREB2B-like, DHN3-like and LEA-14-A-like and modulation of the DNA methylation genes, MET1B-like, CMT3-like and DRM2-like, that regulate the process. Additionally, total soluble sugars and starch contents increased in stressed inoculated plants, a biochemical indication of drought tolerance. In conclusion, we show a single inoculation of Brachypodium with a PGB affected the whole growth cycle of the plant, accelerating its growth rates, shortening its vegetative period, and alleviating drought stress effects. These effects are relevant to

  3. Cost-effectiveness of investing in sidewalks as a means of increasing physical activity: a RESIDE modelling study.

    Science.gov (United States)

    Veerman, J Lennert; Zapata-Diomedi, Belen; Gunn, Lucy; McCormack, Gavin R; Cobiac, Linda J; Mantilla Herrera, Ana Maria; Giles-Corti, Billie; Shiell, Alan

    2016-09-20

    Studies consistently find that supportive neighbourhood built environments increase physical activity by encouraging walking and cycling. However, evidence on the cost-effectiveness of investing in built environment interventions as a means of promoting physical activity is lacking. In this study, we assess the cost-effectiveness of increasing sidewalk availability as one means of encouraging walking. Using data from the RESIDE study in Perth, Australia, we modelled the cost impact and change in health-adjusted life years (HALYs) of installing additional sidewalks in established neighbourhoods. Estimates of the relationship between sidewalk availability and walking were taken from a previous study. Multistate life table models were used to estimate HALYs associated with changes in walking frequency and duration. Sensitivity analyses were used to explore the impact of variations in population density, discount rates, sidewalk costs and the inclusion of unrelated healthcare costs in added life years. Installing and maintaining an additional 10 km of sidewalk in an average neighbourhood with 19 000 adult residents was estimated to cost A$4.2 million over 30 years and gain 24 HALYs over the lifetime of an average neighbourhood adult resident population. The incremental cost-effectiveness ratio was A$176 000/HALY. However, sensitivity results indicated that increasing population densities improves cost-effectiveness. In low-density cities such as in Australia, installing sidewalks in established neighbourhoods as a single intervention is unlikely to cost-effectively improve health. Sidewalks must be considered alongside other complementary elements of walkability, such as density, land use mix and street connectivity. Population density is particularly important because at higher densities, more residents are exposed and this improves the cost-effectiveness. Health gain is one of many benefits of enhancing neighbourhood walkability and future studies might

  4. Testosterone depletion increases the susceptibility of brain tissue to oxidative damage in a restraint stress mouse model.

    Science.gov (United States)

    Son, Seung-Wan; Lee, Jin-Seok; Kim, Hyeong-Geug; Kim, Dong-Woon; Ahn, Yo-Chan; Son, Chang-Gue

    2016-01-01

    Among sex hormones, estrogen is particularly well known to act as neuroprotective agent. Unlike estrogen, testosterone has not been well investigated in regard to its effects on the brain, especially under psychological stress. To investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. BALB/c mice were subjected to either an orchiectomy or sham operation. After allowing 15 days for recovery, mice were re-divided into four groups according to exposure of restraint stress: sham, sham plus stress, orchiectomy, and orchiectomy plus stress. Serum testosterone was undetectable in orchiectomized groups and restraint-induced stress significantly reduced testosterone levels in sham plus stress group. The serum levels of corticosterone and adrenaline were notably elevated by restraint stress, and these elevated hormones were markedly augmented by orchiectomy. Two oxidative stressors and biomarkers for lipid and protein peroxidation were significantly increased in the cerebral cortex and hippocampus by restraint stress, while the reverse pattern was observed in antioxidant enzymes. These results were supported by histopathological findings, with 4-hydroxynonenal staining for oxidative injury and Fluoro-Jade B staining showing the degenerating neurons. The aforementioned patterns of oxidative injury were accelerated by orchiectomy. These findings strongly suggest the conclusion that testosterone exerts a protective effect against oxidative brain damage, especially under stressed conditions. Unlike estrogen, the effects of testosterone on the brain have not been thoroughly investigated. In order to investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. Orchiectomy markedly augmented the restraint stress-induced elevation of serum corticosterone and adrenaline levels as well as oxidative alterations

  5. 3D modeling of effects of increased oxygenation and activity concentration in tumors treated with radionuclides and antiangiogenic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Lagerloef, Jakob H.; Kindblom, Jon; Bernhardt, Peter [Department of Radiation Physics, Goeteborg University, Goeteborg 41345 (Sweden); Department of Oncology, Sahlgrenska University Hospital, Goeteborg 41345 (Sweden); Department of Radiation Physics, Goeteborg University, Goeteborg, Sweden and Department of Nuclear Medicine, Sahlgrenska University Hospital, Goeteborg 41345 (Sweden)

    2011-08-15

    Purpose: Formation of new blood vessels (angiogenesis) in response to hypoxia is a fundamental event in the process of tumor growth and metastatic dissemination. However, abnormalities in tumor neovasculature often induce increased interstitial pressure (IP) and further reduce oxygenation (pO{sub 2}) of tumor cells. In radiotherapy, well-oxygenated tumors favor treatment. Antiangiogenic drugs may lower IP in the tumor, improving perfusion, pO{sub 2} and drug uptake, by reducing the number of malfunctioning vessels in the tissue. This study aims to create a model for quantifying the effects of altered pO{sub 2}-distribution due to antiangiogenic treatment in combination with radionuclide therapy. Methods: Based on experimental data, describing the effects of antiangiogenic agents on oxygenation of GlioblastomaMultiforme (GBM), a single cell based 3D model, including 10{sup 10} tumor cells, was developed, showing how radionuclide therapy response improves as tumor oxygenation approaches normal tissue levels. The nuclides studied were {sup 90}Y, {sup 131}I, {sup 177}Lu, and {sup 211}At. The absorbed dose levels required for a tumor control probability (TCP) of 0.990 are compared for three different log-normal pO{sub 2}-distributions: {mu}{sub 1} = 2.483, {sigma}{sub 1} = 0.711; {mu}{sub 2} = 2.946, {sigma}{sub 2} = 0.689; {mu}{sub 3} = 3.689, and {sigma}{sub 3} = 0.330. The normal tissue absorbed doses will, in turn, depend on this. These distributions were chosen to represent the expected oxygen levels in an untreated hypoxic tumor, a hypoxic tumor treated with an anti-VEGF agent, and in normal, fully-oxygenated tissue, respectively. The former two are fitted to experimental data. The geometric oxygen distributions are simulated using two different patterns: one Monte Carlo based and one radially increasing, while keeping the log-normal volumetric distributions intact. Oxygen and activity are distributed, according to the same pattern. Results: As tumor pO{sub 2

  6. Increased protein kinase C gamma activity induces Purkinje cell pathology in a mouse model of spinocerebellar ataxia 14.

    Science.gov (United States)

    Ji, Jingmin; Hassler, Melanie L; Shimobayashi, Etsuko; Paka, Nagendher; Streit, Raphael; Kapfhammer, Josef P

    2014-10-01

    Spinocerebellar ataxias (SCAs) are hereditary diseases leading to Purkinje cell degeneration and cerebellar dysfunction. Most forms of SCA are caused by expansion of CAG repeats similar to other polyglutamine disorders such as Huntington's disease. In contrast, in the autosomal dominant SCA-14 the disease is caused by mutations in the protein kinase C gamma (PKCγ) gene which is a well characterized signaling molecule in cerebellar Purkinje cells. The study of SCA-14, therefore, offers the unique opportunity to reveal the molecular and pathological mechanism eventually leading to Purkinje cell dysfunction and degeneration. We have created a mouse model of SCA-14 in which PKCγ protein with a mutation found in SCA-14 is specifically expressed in cerebellar Purkinje cells. We find that in mice expressing the mutated PKCγ protein the morphology of Purkinje cells in cerebellar slice cultures is drastically altered and mimics closely the morphology seen after pharmacological PKC activation. Similar morphological abnormalities were seen in localized areas of the cerebellum of juvenile transgenic mice in vivo. In adult transgenic mice there is evidence for some localized loss of Purkinje cells but there is no overall cerebellar atrophy. Transgenic mice show a mild cerebellar ataxia revealed by testing on the rotarod and on the walking beam. Our findings provide evidence for both an increased PKCγ activity in Purkinje cells in vivo and for pathological changes typical for cerebellar disease thus linking the increased and dysregulated activity of PKCγ tightly to the development of cerebellar disease in SCA-14 and possibly also in other forms of SCA. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. In vitro gastrointestinal digestion increases the translocation of polystyrene nanoparticles in an in vitro intestinal co-culture model.

    Science.gov (United States)

    Walczak, Agata P; Kramer, Evelien; Hendriksen, Peter J M; Helsdingen, Richard; van der Zande, Meike; Rietjens, Ivonne M C M; Bouwmeester, Hans

    2015-01-01

    The conditions of the gastrointestinal tract may change the physicochemical properties of nanoparticles (NPs) and therewith the bioavailability of orally taken NPs. Therefore, we assessed the impact of in vitro gastrointestinal digestion on the protein corona of polystyrene NPs (PS-NPs) and their subsequent translocation across an in vitro intestinal barrier. A co-culture of intestinal Caco-2 and HT29-MTX cells was exposed to 50 nm PS-NPs of different charges (positive and negative) in two forms: pristine and digested in an in vitro gastrointestinal digestion model. In vitro digestion significantly increased the translocation of all, except the "neutral", PS-NPs. Upon in vitro digestion, translocation was 4-fold higher for positively charged NPs and 80- and 1.7-fold higher for two types of negatively charged NPs. Digestion significantly reduced the amount of protein in the corona of three out of four types of NPs. This reduction of proteins was 4.8-fold for "neutral", 3.5-fold for positively charged and 1.8-fold for one type of negatively charged PS-NPs. In vitro digestion also affected the composition of the protein corona of PS-NPs by decreasing the presence of higher molecular weight proteins and shifting the protein content of the corona to low molecular weight proteins. These findings are the first to report that in vitro gastrointestinal digestion significantly affects the protein corona and significantly increases the in vitro translocation of differently charged PS-NPs. These findings stress the importance of including the in vitro digestion in future in vitro intestinal translocation screening studies for risk assessment of orally taken NPs.

  8. Increasing the Usage of Personal Protective Equipments in Constructing Subway Stations: An Application of Social Marketing Model

    Directory of Open Access Journals (Sweden)

    M Shams

    2013-10-01

    Full Text Available Abstract Background & aim: Although the relationship between the use of personal protective equipment and the reduction of workplace injuries is well-known the use of these devices during operation by the staff is not so desirable. This study was based on a model of social marketing interventions to increase the use of safety devices and personal protection on the subway-station staff. Methods: The present quasi-experimental study was based on the results of a formative research consisted of a qualitative (exploring employees’ views through focus group discussions and a quantitative study (measuring attitudes and behaviors by questionnaire and checklist. Based on the formative research findings, a free package includes a helmet with a label containing the message, an anti-cut safety gloves, a dust mask, and an educational pamphlet were delivered to intervention group. After four weeks, the check list of observational behaviors in two constructing stations was completed and the results were compared with before intervention. The data were analyzed by paired t-test, t-test and logistic regression. Results: Three common behaviors were observed among staff not using caps, masks and gloves. The odds ratio for helmet and mask usage in the intervention group was more than other groups. After the intervention, the use of safety helmets and masks significantly increased (p < 0.05. The odds ratio for the use of helmets and masks after intervention in the intervention group was significantly higher than other groups (p < 0.05. Conclusion: The experimental basis of the safety devices and personal protection needs and demands of the audience, material and immaterial costs of the equipment, supplies, and promoting their use in the right place, can encourage the staff to continuously use the safety devices at workplace. Key Words: Workplace, Injuries, Personal Protective Equipment, Social Marketing

  9. THE EFFECTS OF DIFFERENT MODELS OF SWIMMING TRAINING (DEFINED IN RELATION TO ANAEROBIC THRESHOLD ON THE INCREASE OF SWIM SPEED

    Directory of Open Access Journals (Sweden)

    Dragan Krivokapić

    2007-05-01

    Full Text Available On the sample of 32 fourth grade students of some Belgrade highs schools, who had the physical education classes carried out at the city’s swimming pools, an attempt was made to evaluate the effects of the two different programmes of swimming training in different intensity zones, defi ned relative to the anaerobic threshold. The examinees were divided into two groups out of 15 i.e. 17 participants who were not (according to statistics signifi cantly different in terms of average time and heart frequency during the 400 m swimming test and heart frequency and time measured after 50 m in the moment of reaching the anaerobic threshold. The fi rst training model consisted of swimming at the intensity level within the zone below anaerobic threshold, while the second model involved occasional swimming at a higher intensity sometimes surpassing the anaerobic threshold. The experimentalprogramme with both sub-groups lasted 8 weeks with 3 training sessions per week, 2 ‘of which we’re identical for both experimental groups, with the third one differing regarding the swimming intensity, this in the fi rst group being still in the zone below, and in the second group occasionally in the zone above the anaerobic threshold. The amount of training and the duration were the same in both programmes. The aim of the research , was to evaluate and to compare the effects of the two training models, using as the basic criteria possible changes of average time and heart frequency during the 400 m swimming test and heart frequency and time measured after 50 m in the moment of reaching the anaerobic thereshold. On the basis of the statistical analysis of the obtained data, it is possible to conclude that in both experimental groups there were statistically signifi cant changes of average values concerning all the physiological variables. Although the difference in effi ciency of applied experimental programmes is not defi ned, we can claim that both of experimental

  10. Effect of increasing taurine and methionine supplementation on urinary taurine excretion in a model insectivore, the giant anteater (Myrmecophaga tridactyla).

    Science.gov (United States)

    Nofs, S A; Dierenfeld, E S; Backus, R C

    2018-02-01

    The giant anteater (Mymercophaga tridactyla) is a highly specialized insectivore for which nutrient requirements are not clearly established, making diet formulation challenging for this species. Multiple clinical reports suggest anteaters have an obligate dietary taurine (TAU) requirement. Sulphur amino acid (SAA) metabolism in adult anteaters was evaluated using noninvasive methods to measure TAU synthesis potential from dietary methionine (MET) and a basal diet containing on a dry matter (DM) basis 1.7 mg TAU/kg DM and 6.9 g MET/kg DM. Urinary equilibrium times for TAU excretion were determined by feeding the basal diet with or without 1.5 g/kg DM supplemental TAU (crossover design; n = 4). Effects of supplemental dietary TAU (1.7, 2.0, 2.4, 2.7, 3.0, 3.3 g/kg DM) or MET (6.9, 9.0, 11.2 g/kg DM) on urinary TAU were evaluated (randomized block trials; n = 5 or 4 respectively). All urinary values (TAU, MET, unbound inorganic sulphate) were normalized to creatinine (CRT). Results indicate urinary TAU equilibrium in anteaters requires at least 2 weeks of feeding. Urinary ratio of TAU to CRT (TAU:CRT) increased as dietary TAU content increased from 1.7 to 3.0 g/kg DM, consistent with renal homoeostatic modulation of TAU excretion. Our data indicate that TAU needs were met by TAU in the basal diet or by de novo synthesis. Supplemental MET resulted in ~five- to eightfold increases in urinary TAU:CRT excretion, further supporting existence of mechanisms for TAU synthesis from dietary SAA in anteaters. Adult anteaters appear able to synthesize TAU when diets contain adequate SAA, but dietary TAU may be critical if protein intakes are low or of poor quality. This study may provide guidance on choice of domestic canids vs. felids as suitable physiologic models for improved nutrition in giant anteaters, and also outlines a noninvasive method for assessing TAU status/metabolism that may be useful across species. © 2017 Blackwell Verlag GmbH.

  11. Administration of soluble activin receptor 2B increases bone and muscle mass in a mouse model of osteogenesis imperfecta

    Science.gov (United States)

    DiGirolamo, Douglas J.; Singhal, Vandana; Chang, Xiaoli; Lee, Se-Jin; Germain-Lee, Emily L.

    2015-01-01

    Osteogenesis imperfecta (OI) comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI, many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B (ACVR2B) in a mouse model of type III OI (oim). Treatment of 12-week-old oim mice with ACVR2B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy, wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system. PMID:26161291

  12. Increase in peripheral oxidative stress during hypercholesterolemia is not reflected in the central nervous system: evidence from two mouse models.

    Science.gov (United States)

    Ding, Tao; Yao, Yeumang; Praticò, Domenico

    2005-05-01

    In recent years oxidative stress has been widely implicated as a pathogenetic mechanism of several diseases, and a variety of indices and assays have been developed to assess this phenomenon in complex biological systems. Most of these biomarkers can be measured virtually in every biological fluid and tissue, providing us with the opportunity to assess their formation at local site of oxidative injury. However, despite their widespread use, it is still not completely clear how their peripheral formation correlates with the levels measured in the central nervous system. For this reason, we utilized two well-characterized animal models of chronic peripheral oxidative stress, low-density lipoprotein receptor (LDLR)-deficient and C57BL/6 mice on a high fat diet. After 8 weeks on the diet, we assessed isoprostane, marker of lipid peroxidation, and carbonyls, marker of protein oxidation, in several organs of these animals. Compared with animals on chow, mice on the high fat diet showed a significant increase in both biomarkers in plasma, heart, aorta and liver but not in brain tissues. This observation was confirmed by the selective accumulation of radioactivity in the peripheral organs but not in the brains of mice injected with tritiated isoprostane. Our findings indicate that in hypercholesterolemia the peripheral formation of oxidative products does not contribute to their levels found in the central nervous system.

  13. A Markov chain approach to modelling charge exchange processes of an ion beam in monotonically increasing or decreasing potentials

    International Nuclear Information System (INIS)

    Shrier, O; Khachan, J; Bosi, S

    2006-01-01

    A Markov chain method is presented as an alternative approach to Monte Carlo simulations of charge exchange collisions by an energetic hydrogen ion beam with a cold background hydrogen gas. This method was used to determine the average energy of the resulting energetic neutrals along the path of the beam. A comparison with Monte Carlo modelling showed a good agreement but with the advantage that it required much less computing time and produced no numerical noise. In particular, the Markov chain method works well for monotonically increasing or decreasing electrostatic potentials. Finally, a good agreement is obtained with experimental results from Doppler shift spectroscopy on energetic beams from a hollow cathode discharge. In particular, the average energy of ions that undergo charge exchange reaches a plateau that can be well below the full energy that might be expected from the applied voltage bias, depending on the background gas pressure. For example, pressures of ∼20 mTorr limit the ion energy to ∼20% of the applied voltage

  14. Increased Asics Expression via the Camkii-CREB Pathway in a Novel Mouse Model of Trigeminal Pain

    Directory of Open Access Journals (Sweden)

    Yan Wang

    2018-03-01

    Full Text Available Background/Aims: Migraine is a disabling condition that severely impacts socioeconomic function and quality of life. The focus of this study was to develop a mouse model of trigeminal pain that mimics migraine. Methods: After undergoing dural cannulation surgery, mice were treated with repeated dural doses of an acidic solution to induce trigeminal pain. Results: The method elicited intermittent, head-directed wiping and scratching as well as the expression of both the c-FOS gene in the spinal trigeminal nucleus caudalis and calcitonin gene related peptide (CGRP in the periaqueductal grey matter. Interestingly, the acid-induced trigeminal pain behaviour was inhibited by amiloride, an antagonist of acid-sensing ion channels (ASICs, but not by AMG-9810, an inhibitor of transient receptor potential cation channel V1(TRPV1. In addition, the relative mRNA and protein expression levels of ASIC1a and ASIC3 were increased in the acid-induced trigeminal nociceptive pathways. Furthermore, blocking CaMKII with KN-93 significantly reduced the acid-induced trigeminal pain behaviour and c-FOS gene expression. Conclusion: The data suggested that chronic intermittent administration of an acidic solution to mice resulted in trigeminal hypersensitivity and that dural acid-induced trigeminal pain behaviour in mice may mechanistically mimic migraine. The observations here identify an entirely novel treatment strategy for migraine.

  15. Estrogen therapy may counterbalance eutrophic remodeling of coronary arteries and increase bradykinin relaxation in a rat model of menopausal hypertension.

    Science.gov (United States)

    Matrai, Mate; Hetthéssy, Judit R; Nadasy, Gyorgy L; Szekacs, Bela; Mericli, Metin; Acs, Nandor; Monos, Emil; Arbib, Nissim; Varbiro, Szabolcs

    2016-07-01

    Hypertension causes adverse remodeling and vasomotor alterations in coronaries. Hormones such as estrogen may help counterbalance some of these effects. The aim of this study was to analyze the effects of ovariectomy and estrogen therapy in a rat model of menopausal hypertension induced by angiotensin II (AII). We investigated diameter, tone, and mechanics of intramural coronaries taken from ovariectomized female rats (n = 11) that received chronic AII treatment to induce hypertension, and compared the results with those found in female rats that were also given estrogen therapy (n = 11). The "hypertensive control" group (n = 11) underwent an abdominal sham operation, and received AII. After 4 weeks of AII treatment, side branches of left anterior descendent coronary (approximately 200 μm in diameter) were isolated, cannulated with plastic microcannulas at both ends, and studied in vitro in a vessel chamber. The inner and outer diameter of the arteries were measured by microangiometry, and spontenuous tone, wall thickness, wall cross-sectional area, tangential stress, incremental distensibility, circumferential incremental elastic modulus, thromboxane agonist-induced tone, and bradykinin-induced dilation were calculated. In hypertension, intramural small coronaries show inward eutrophic remodeling after ovariectomy comparing with hypertensive controls. Estrogen therapy had an opposite effect on vessel diameter. Hormone therapy led to an increase in spontaneous tone, allowing for greater dilatative capacity. Estrogen may therefore be considered to counterbalance some of the adverse changes seen in the wall of intramural coronaries in the early stages of chronic hypertension.

  16. Mask leak increases and minute ventilation decreases when chest compressions are added to bag ventilation in a neonatal manikin model.

    Science.gov (United States)

    Tracy, Mark B; Shah, Dharmesh; Hinder, Murray; Klimek, Jan; Marceau, James; Wright, Audrey

    2014-05-01

    To determine changes in respiratory mechanics when chest compressions are added to mask ventilation, as recommended by the International Liaison Committee on Resuscitation (ILCOR) guidelines for newborn infants. Using a Laerdal Advanced Life Support leak-free baby manikin and a 240-mL self-inflating bag, 58 neonatal staff members were randomly paired to provide mask ventilation, followed by mask ventilation with chest compressions with a 1:3 ratio, for two minutes each. A Florian respiratory function monitor was used to measure respiratory mechanics, including mask leak. The addition of chest compressions to mask ventilation led to a significant reduction in inflation rate, from 63.9 to 32.9 breaths per minute (p mask leak of 6.8% (p mask ventilation, in accordance with the ILCOR guidelines, in a manikin model is associated with a significant reduction in delivered ventilation and increase in mask leak. If similar findings occur in human infants needing an escalation in resuscitation, there is a potential risk of either delay in recovery or inadequate response to resuscitation. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  17. Maillard reaction products from highly heated food prevent mast cell number increase and inflammation in a mouse model of colitis.

    Science.gov (United States)

    Al Amir, Issam; Dubayle, David; Héron, Anne; Delayre-Orthez, Carine; Anton, Pauline M

    2017-12-01

    Links between food and inflammatory bowel diseases (IBDs) are often suggested, but the role of food processing has not been extensively studied. Heat treatment is known to cause the loss of nutrients and the appearance of neoformed compounds such as Maillard reaction products. Their involvement in gut inflammation is equivocal, as some may have proinflammatory effects, whereas other seem to be protective. As IBDs are associated with the recruitment of immune cells, including mast cells, we raised the hypothesis that dietary Maillard reaction products generated through heat treatment of food may limit the colitic response and its associated recruitment of mast cells. An experimental model of colitis was used in mice submitted to mildly and highly heated rodent food. Adult male mice were divided in 3 groups and received nonheated, mildly heated, or highly heated chow during 21 days. In the last week of the study, each group was split into 2 subgroups, submitted or not (controls) to dextran sulfate sodium (DSS) colitis. Weight variations, macroscopic lesions, colonic myeloperoxidase activity, and mucosal mast cell number were evaluated at the end of the experiment. Only highly heated chow significantly prevented DSS-induced weight loss, myeloperoxidase activity, and mast cell number increase in the colonic mucosa of DSS-colitic mice. We suggest that Maillard reaction products from highly heated food may limit the occurrence of inflammatory phases in IBD patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Intermittent hypoxia causes histological kidney damage and increases growth factor expression in a mouse model of obstructive sleep apnea.

    Directory of Open Access Journals (Sweden)

    Bisher Abuyassin

    Full Text Available Epidemiological studies demonstrate an association between obstructive sleep apnea (OSA and accelerated loss of kidney function. It is unclear whether the decline in function is due to OSA per se or to other confounding factors such as obesity. In addition, the structural kidney abnormalities associated with OSA are unclear. The objective of this study was to determine whether intermittent hypoxia (IH, a key pathological feature of OSA, induces renal histopathological damage using a mouse model. Ten 8-week old wild-type male CB57BL/6 mice were randomly assigned to receive either IH or intermittent air (IA for 60 days. After euthanasia, one kidney per animal was paraformaldehyde-fixed and then sectioned for histopathological and immunohistochemical analysis. Measurements of glomerular hypertrophy and mesangial matrix expansion were made in periodic acid-Schiff stained kidney sections, while glomerular transforming growth factor-β1 (TGF-β1, connective tissue growth factor (CTGF and vascular endothelial growth factor-A (VEGF-A proteins were semi-quantified by immunohistochemistry. The antigen-antibody reaction was detected by 3,3'-diaminobenzidine chromogen where the color intensity semi-quantified glomerular protein expression. To enhance the accuracy of protein semi-quantification, the percentage of only highly-positive staining was used for analysis. Levels of TGF-β, CTGF and VEGF-A proteins in the kidney cortex were further quantified by western blotting. Cellular apoptosis was also investigated by measuring cortical antiapoptotic B-cell lymphoma 2 (Bcl-2 and apoptotic Bcl-2-associated X (Bax proteins by western blotting. Further investigation of cellular apoptosis was carried out by fluorometric terminal deoxynucleotidyl transferase (TdT dUTP Nick-End Labeling (TUNEL staining. Finally, the levels of serum creatinine and 24-hour urinary albumin were measured as a general index of renal function. Our results indicate that mice exposed to IH

  19. Intermittent hypoxia causes histological kidney damage and increases growth factor expression in a mouse model of obstructive sleep apnea.

    Science.gov (United States)

    Abuyassin, Bisher; Badran, Mohammad; Ayas, Najib T; Laher, Ismail

    2018-01-01

    Epidemiological studies demonstrate an association between obstructive sleep apnea (OSA) and accelerated loss of kidney function. It is unclear whether the decline in function is due to OSA per se or to other confounding factors such as obesity. In addition, the structural kidney abnormalities associated with OSA are unclear. The objective of this study was to determine whether intermittent hypoxia (IH), a key pathological feature of OSA, induces renal histopathological damage using a mouse model. Ten 8-week old wild-type male CB57BL/6 mice were randomly assigned to receive either IH or intermittent air (IA) for 60 days. After euthanasia, one kidney per animal was paraformaldehyde-fixed and then sectioned for histopathological and immunohistochemical analysis. Measurements of glomerular hypertrophy and mesangial matrix expansion were made in periodic acid-Schiff stained kidney sections, while glomerular transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) and vascular endothelial growth factor-A (VEGF-A) proteins were semi-quantified by immunohistochemistry. The antigen-antibody reaction was detected by 3,3'-diaminobenzidine chromogen where the color intensity semi-quantified glomerular protein expression. To enhance the accuracy of protein semi-quantification, the percentage of only highly-positive staining was used for analysis. Levels of TGF-β, CTGF and VEGF-A proteins in the kidney cortex were further quantified by western blotting. Cellular apoptosis was also investigated by measuring cortical antiapoptotic B-cell lymphoma 2 (Bcl-2) and apoptotic Bcl-2-associated X (Bax) proteins by western blotting. Further investigation of cellular apoptosis was carried out by fluorometric terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining. Finally, the levels of serum creatinine and 24-hour urinary albumin were measured as a general index of renal function. Our results indicate that mice exposed to IH have an

  20. Increased hippocampal excitability in the 3xTgAD mouse model for Alzheimer's disease in vivo.

    Directory of Open Access Journals (Sweden)

    Katherine E Davis

    Full Text Available Mouse Alzheimer's disease (AD models develop age- and region-specific pathology throughout the hippocampal formation. One recently established pathological correlate is an increase in hippocampal excitability in vivo. Hippocampal pathology also produces episodic memory decline in human AD and we have shown a similar episodic deficit in 3xTg AD model mice aged 3-6 months. Here, we tested whether hippocampal synaptic dysfunction accompanies this cognitive deficit by probing dorsal CA1 and DG synaptic responses in anaesthetized, 4-6 month-old 3xTgAD mice. As our previous reports highlighted a decline in episodic performance in aged control mice, we included aged cohorts for comparison. CA1 and DG responses to low-frequency perforant path stimulation were comparable between 3xTgAD and controls at both age ranges. As expected, DG recordings in controls showed paired-pulse depression; however, paired-pulse facilitation was observed in DG and CA1 of young and old 3xTgAD mice. During stimulus trains both short-latency (presumably monosynaptic: 'direct' and long-latency (presumably polysynaptic: 're-entrant' responses were observed. Facilitation of direct responses was modest in 3xTgAD animals. However, re-entrant responses in DG and CA1 of young 3xTgAD mice developed earlier in the stimulus train and with larger amplitude when compared to controls. Old mice showed less DG paired-pulse depression and no evidence for re-entrance. In summary, DG and CA1 responses to low-frequency stimulation in all groups were comparable, suggesting no loss of synaptic connectivity in 3xTgAD mice. However, higher-frequency activation revealed complex change in synaptic excitability in DG and CA1 of 3xTgAD mice. In particular, short-term plasticity in DG and CA1 was facilitated in 3xTgAD mice, most evidently in younger animals. In addition, re-entrance was facilitated in young 3xTgAD mice. Overall, these data suggest that the episodic-like memory deficit in 3xTgAD mice

  1. Coadministration of doxorubicin and etoposide loaded in camel milk phospholipids liposomes showed increased antitumor activity in a murine model

    Directory of Open Access Journals (Sweden)

    Maswadeh HM

    2015-04-01

    Full Text Available Hamzah M Maswadeh,1 Ahmed N Aljarbou,1 Mohammed S Alorainy,2 Arshad H Rahmani,3 Masood A Khan3 1Department of Pharmaceutics, College of Pharmacy, 2Department of Pharmacology and Therapeutics, College of Medicine, 3College of Applied Medical Sciences, Qassim University, Buraydah, Kingdom of Saudi Arabia Abstract: Small unilamellar vesicles from camel milk phospholipids (CML mixture or from 1,2 dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC were prepared, and anticancer drugs doxorubicin (Dox or etoposide (ETP were loaded. Liposomal formulations were used against fibrosarcoma in a murine model. Results showed a very high percentage of Dox encapsulation (~98% in liposomes (Lip prepared from CML-Lip or DPPC-Lip, whereas the percentage of encapsulations of ETP was on the lower side, 22% of CML-Lip and 18% for DPPC-Lip. Differential scanning calorimetry curves show that Dox enhances the lamellar formation in CML-Lip, whereas ETP enhances the nonlamellar formation. Differential scanning calorimetry curves also showed that the presence of Dox and ETP together into DPPC-Lip produced the interdigitation effect. The in vivo anticancer activity of liposomal formulations of Dox or ETP or a combination of both was assessed against benzopyrene (BAP-induced fibrosarcoma in a murine model. Tumor-bearing mice treated with a combination of Dox and ETP loaded into CML-Lip showed increased survival and reduced tumor growth compared to other groups, including the combination of Dox and ETP in DPPC-Lip. Fibrosarcoma-bearing mice treated with a combination of free (Dox + ETP showed much higher tumor growth compared to those groups treated with CML-Lip-(Dox + ETP or DPPC-Lip-(Dox + ETP. Immunohistochemical study was also performed to show the expression of tumor-suppressor PTEN, and it was found that the tumor tissues from the group of mice treated with a combination of free (Dox + ETP showed greater loss of cytoplasmic PTEN than tumor tissues obtained from the

  2. Increased accuracy in mineral and hydrogeophysical modelling of HTEM data via detailed description of system transfer function and constrained inversion

    DEFF Research Database (Denmark)

    Viezzoli, Andrea; Christiansen, Anders Vest; Auken, Esben

    This paper aims at providing more insight into the parameters that need to be modelled during inversion of Helicopter TEM data for accurate modelling, both for hydrogeophysical and exploration applications. We use synthetic data to show in details the effect, both in data and in model space...

  3. Toward the identification of communities with increased tobacco-associated cancer burden: Application of spatial modeling techniques

    Directory of Open Access Journals (Sweden)

    Noella A Dietz

    2011-01-01

    Full Text Available Introduction: Smoking-attributable risks for lung, esophageal, and head and neck (H/N cancers range from 54% to 90%. Identifying areas with higher than average cancer risk and smoking rates, then targeting those areas for intervention, is one approach to more rapidly lower the overall tobacco disease burden in a given state. Our research team used spatial modeling techniques to identify areas in Florida with higher than expected tobacco-associated cancer incidence clusters. Materials and Methods: Geocoded tobacco-associated incident cancer data from 1998 to 2002 from the Florida Cancer Data System were used. Tobacco-associated cancers included lung, esophageal, and H/N cancers. SaTScan was used to identify geographic areas that had statistically significant (P<0.10 excess age-adjusted rates of tobacco-associated cancers. The Poisson-based spatial scan statistic was used. Phi correlation coefficients were computed to examine associations among block groups with/without overlapping cancer clusters. The logistic regression was used to assess associations between county-level smoking prevalence rates and being diagnosed within versus outside a cancer cluster. Community-level smoking rates were obtained from the 2002 Florida Behavioral Risk Factor Surveillance System (BRFSS. Analyses were repeated using 2007 BRFSS to examine the consistency of associations. Results: Lung cancer clusters were geographically larger for both squamous cell and adenocarcinoma cases in Florida from 1998 to 2002, than esophageal or H/N clusters. There were very few squamous cell and adenocarcinoma esophageal cancer clusters. H/N cancer mapping showed some squamous cell and a very small amount of adenocarcinoma cancer clusters. Phi correlations were generally weak to moderate in strength. The odds of having an invasive lung cancer cluster increased by 12% per increase in the county-level smoking rate. Results were inconsistent for esophageal and H/N cancers, with some

  4. Novel rat Alzheimer's disease models based on AAV-mediated gene transfer to selectively increase hippocampal Aβ levels

    Directory of Open Access Journals (Sweden)

    Dicker Bridget L

    2007-06-01

    Full Text Available Abstract Background Alzheimer's disease (AD is characterized by a decline in cognitive function and accumulation of amyloid-β peptide (Aβ in extracellular plaques. Mutations in amyloid precursor protein (APP and presenilins alter APP metabolism resulting in accumulation of Aβ42, a peptide essential for the formation of amyloid deposits and proposed to initiate the cascade leading to AD. However, the role of Aβ40, the more prevalent Aβ peptide secreted by cells and a major component of cerebral Aβ deposits, is less clear. In this study, virally-mediated gene transfer was used to selectively increase hippocampal levels of human Aβ42 and Aβ40 in adult Wistar rats, allowing examination of the contribution of each to the cognitive deficits and pathology seen in AD. Results Adeno-associated viral (AAV vectors encoding BRI-Aβ cDNAs were generated resulting in high-level hippocampal expression and secretion of the specific encoded Aβ peptide. As a comparison the effect of AAV-mediated overexpression of APPsw was also examined. Animals were tested for development of learning and memory deficits (open field, Morris water maze, passive avoidance, novel object recognition three months after infusion of AAV. A range of impairments was found, with the most pronounced deficits observed in animals co-injected with both AAV-BRI-Aβ40 and AAV-BRI-Aβ42. Brain tissue was analyzed by ELISA and immunohistochemistry to quantify levels of detergent soluble and insoluble Aβ peptides. BRI-Aβ42 and the combination of BRI-Aβ40+42 overexpression resulted in elevated levels of detergent-insoluble Aβ. No significant increase in detergent-insoluble Aβ was seen in the rats expressing APPsw or BRI-Aβ40. No pathological features were noted in any rats, except the AAV-BRI-Aβ42 rats which showed focal, amorphous, Thioflavin-negative Aβ42 deposits. Conclusion The results show that AAV-mediated gene transfer is a valuable tool to model aspects of AD pathology in

  5. Summary of innovation models on a company level – creating a framework for an innovation model that will increase a company’s innovation activity

    OpenAIRE

    Stefanovska Ceravolo, Ljubica; Polenakovik, Radmil; Dzidrov, Misko

    2016-01-01

    There are six known and generally accepted generations of innovation models. Innovation models transform from simple, linear models, to integrated and networking models that are dynamic and interactive. Each generation of innovation models is presented in this paper with their characteristics as well as drawbacks. The main goal of this paper is to show the transformation path of innovation models and create a framework for a new innovation model on a company level, that could be used by compa...

  6. Increasing Trustworthiness of Face Authentication in Mobile Devices by Modeling Gesture Behavior and Location Using Neural Networks

    Directory of Open Access Journals (Sweden)

    Blerim Rexha

    2018-02-01

    Full Text Available Personal mobile devices currently have access to a significant portion of their user’s private sensitive data and are increasingly used for processing mobile payments. Consequently, securing access to these mobile devices is a requirement for securing access to the sensitive data and potentially costly services. Face authentication is one of the promising biometrics-based user authentication mechanisms that has been widely available in this era of mobile computing. With a built-in camera capability on smartphones, tablets, and laptops, face authentication provides an attractive alternative of legacy passwords for its memory-less authentication process, which is so sophisticated that it can unlock the device faster than a fingerprint. Nevertheless, face authentication in the context of smartphones has proven to be vulnerable to attacks. In most current implementations, a sufficiently high-resolution face image displayed on another mobile device will be enough to circumvent security measures and bypass the authentication process. In order to prevent such bypass attacks, gesture recognition together with location is proposed to be additionally modeled. Gestures provide a faster and more convenient method of authentication compared to a complex password. The focus of this paper is to build a secure authentication system with face, location and gesture recognition as components. User gestures and location data are a sequence of time series; therefore, in this paper we propose to use unsupervised learning in the long short-term memory recurrent neural network to actively learn to recognize, group and discriminate user gestures and location. Moreover, a clustering-based technique is also implemented for recognizing gestures and location.

  7. BDNF levels are increased by aminoindan and rasagiline in a double lesion model of Parkinson׳s disease.

    Science.gov (United States)

    Ledreux, Aurélie; Boger, Heather A; Hinson, Vanessa K; Cantwell, Kelsey; Granholm, Ann-Charlotte

    2016-01-15

    The anti-Parkinsonian drug rasagiline is a selective, irreversible inhibitor of monoamine oxidase and is used in the treatment of Parkinson׳s disease (PD). Its postulated neuroprotective effects may be attributed to MAO inhibition, or to its propargylamine moiety. The major metabolite of rasagiline, aminoindan, has shown promising neuroprotective properties in vitro but there is a paucity of studies investigating in vivo effects of this compound. Therefore, we examined neuroprotective effects of rasagiline and its metabolite aminoindan in a double lesion model of PD. Male Fisher 344 rats received i.p. injections of the noradrenergic neurotoxin DSP-4 and intra-striatal stereotaxic microinjections of the dopamine neurotoxin 6-OHDA. Saline, rasagiline or aminoindan (3mg/kg/day s.c.) were delivered via Alzet minipumps for 4 weeks. Rats were then tested for spontaneous locomotion and a novel object recognition task. Following behavioral testing, brain tissue was processed for ELISA measurements of growth factors and immunohistochemistry. Double-lesioned rats treated with rasagiline or aminoindan had reduced behavioral deficits, both in motor and cognitive tasks compared to saline-treated double-lesioned rats. BDNF levels were significantly increased in the hippocampus and striatum of the rasagiline- and aminoindan-lesioned groups compared to the saline-treated lesioned group. Double-lesioned rats treated with rasagiline or aminoindan exhibited a sparing in the mitochondrial marker Hsp60, suggesting mitochondrial involvement in neuroprotection. Tyrosine hydroxylase (TH) immunohistochemistry revealed a sparing of TH-immunoreactive terminals in double-lesioned rats treated with rasagiline or aminoindan in the striatum, hippocampus, and substantia nigra. These data provide evidence of neuroprotection by aminoindan and rasagiline via their ability to enhance BDNF levels. Published by Elsevier B.V.

  8. Cigarette smoke inhalation increases the alveolar bone loss caused by primary occlusal trauma in a rat model.

    Science.gov (United States)

    Campos, M L G; Corrêa, M G; Júnior, F H N; Casati, M Z; Sallum, E A; Sallum, A W

    2014-04-01

    Occlusal trauma (OT) and smoking are both factors that alter alveolar bone metabolism and therefore could synergistically act on alveolar bone loss. The aim of this experimental study was to evaluate the influence of short-term cigarette smoke inhalation (CSI) on inter-radicular alveolar bone loss promoted by primary OT in a rat model. Forty-eight animals were randomly assigned to one of three groups based on treatment type: OT + CSI (n = 16), animals were exposed to CSI three times per day, for 8 min per exposure, and they concomitantly received unilateral vertical augmentation creating an occlusal interference inducing experimental OT; OT (n = 16), animals received only unilateral vertical augmentation; negative control (NC; n = 16), animals maintained for equal periods to achieve periodontal baseline values of periodontal ligament dimension. Each group was divided into two subgroups (n = 8) based on treatment length: 7 or 14 d. After 7 d, the OT + CSI group exhibited significantly higher bone loss compared to the NC group (p = 0.0022). After 14 d, the OT (p < 0.0001) and OT + CSI (p < 0.0001) groups presented significantly higher bone loss compared to the NC group, and OT + CSI resulted in significantly higher bone loss than OT alone (p = 0.0241). The number of tartrate-resistant acid phosphatase-positive cells on the linear surface of the bone crest after 7 d was significantly higher in the OT + CSI group as compared to the NC and OT groups (p < 0.0001 and p = 0.0045, respectively) and remained significantly higher in the OT + CSI group after 14 d, compared to the OT group (p < 0.0001). Short-term CSI increases early bone loss in association with OT after 7 d, and this worsens in severity after 14 d of exposure. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Using a Participatory Culture-Specific Model to Increase the Effectiveness of Social Justice Courses in School Psychology

    Science.gov (United States)

    Graybill, Emily C.; Varjas, Kris; Meyers, Joel; Greenberg, Daphne; Roach, Andrew T.

    2013-01-01

    The Participatory Culture-Specific Model of Course Development (PCSMCD), adapted from the Participatory Culture-Specific Intervention Model, is a proposed framework to address challenges to social justice education by addressing the following four course variables: instructor characteristics, instructor experiences, student characteristics, and…

  10. Increasing security of supply: The search for stable models of financing for new nuclear build in the European Union

    International Nuclear Information System (INIS)

    Heffron, Raphael James

    2009-01-01

    Full text: This research assesses models for financing of new nuclear build in European Union (EU) member states to find the most stable form. The countries examined in this study are France, the United Kingdom, Finland and Romania. The results attest that due to various historical, political, competition, and electricity market structural conditions Romania has emerged with the most secure and stable model for financing of new nuclear projects. This paper begins with an assessment of the effects on the nuclear sector from energy, environment and competition legislation in the EU. Then the political and economic climate of the afore mentioned EU member states is completed. Following this an overview of the market structure of the electricity sector in those respective countries is conducted. Then the key research on the models of financing of new nuclear build is explored, contrasted and analysed. The research concludes that there are four main models for financing new nuclear projects in Europe. Each model has transcended from different political and economic forces, and consequently each model has met with varied levels of success. Electricity market structures while operating to the same legal requirements, have been dissimilar in their evolution. The combination of the above factors has led to different models for financing new nuclear build. Upon further analysis it is concluded and demonstrated that the Romanian financing model is the most suitable and provides an example for any new nuclear build aspiring nations in the EU and beyond. (author)

  11. Can the confidence in long range atmospheric transport models be increased? The Pan-European experience of ENSEMBLE

    DEFF Research Database (Denmark)

    Galmarini, S.; Bianconi, R.; Klug, W.

    2004-01-01

    Is atmospheric dispersion forecasting an important asset of the early-phase nuclear emergency response management? Is there a 'perfect atmospheric dispersion model'? Is there a way to make the results of dispersion models more reliable and trustworthy? While seeking to answer these questions the ...

  12. Role Models of Australian Female Adolescents: A Longitudinal Study to Inform Programmes Designed to Increase Physical Activity and Sport Participation

    Science.gov (United States)

    Young, Janet A.; Symons, Caroline M.; Pain, Michelle D.; Harvey, Jack T.; Eime, Rochelle M.; Craike, Melinda J.; Payne, Warren R.

    2015-01-01

    In light of the importance attributed to the presence of positive role models in promoting physical activity during adolescence, this study examined role models of adolescent girls and their influence on physical activity. Seven hundred and thirty two girls in Years 7 and 11 from metropolitan and non-metropolitan regions of Victoria, Australia,…

  13. A nested modeling study of elevation-dependent climate change signals in California induced by increased atmospheric CO2

    International Nuclear Information System (INIS)

    Kim, Jinwon

    2001-01-01

    Dynamically downscaled climate change signals due to increased atmospheric CO2 are investigated for three California basins. The downscaled signals show strong elevation dependence, mainly due to elevated freezing levels in the increased CO2 climate. Below 2.5 km, rainfall increases by over 150% while snowfall decreases by 20-40% in the winter. Above 2.5 km, rainfall and snowfall both increase in the winter, as the freezing levels appear mostly below this level. Winter snowmelt increases in all elevations due to warmer temperatures in the increased CO2 climate. Reduced snowfall and enhanced snowmelt during the winter decreases snowmelt-driven spring runoff below the 2.5 km level, where the peak snowmelt occurs one month earlier in the increased CO2 climate. Above 2.5km, increased winter snowfall maintains snowmelt-driven runoff through most of the warm season. The altered hydrologic characteristics in the increased CO2 climate affect the diurnal temperature variation mainly via snow-albedo-soil moisture feedback

  14. Differential Reinforcement of Alternative Behavior Increases Resistance to Extinction: Clinical Demonstration, Animal Modeling, and Clinical Test of One Solution

    Science.gov (United States)

    Mace, F. Charles; McComas, Jennifer J.; Mauro, Benjamin C.; Progar, Patrick R.; Taylor, Bridget; Ervin, Ruth; Zangrillo, Amanda N.

    2010-01-01

    Basic research with pigeons on behavioral momentum suggests that differential reinforcement of alternative behavior (DRA) can increase the resistance of target behavior to change. This finding suggests that clinical applications of DRA may inadvertently increase the persistence of target behavior even as it decreases its frequency. We conducted…

  15. Enhanced hepatocarcinogenesis in mouse models and human hepatocellular carcinoma by coordinate KLF6 depletion and increased messenger RNA splicing

    NARCIS (Netherlands)

    Vetter, Diana; Cohen-Naftaly, Michal; Villanueva, Augusto; Lee, Youngmin A.; Kocabayoglu, Peri; Hannivoort, Rebekka; Narla, Goutham; M. Llovet, Josep; Thung, Swan N.; Friedman, Scott L.

    2012-01-01

    KLF6-SV1 (SV1), the major splice variant of KLF6, antagonizes the KLF6 tumor suppressor by an unknown mechanism. Decreased KLF6 expression in human hepatocellular carcinoma (HCC) correlates with increased mortality, but the contribution of increased SV1 is unknown. We sought to define the impact of

  16. Induced hypothermia is protective in a rat model of pneumococcal pneumonia associated with increased adenosine triphosphate availability and turnover

    NARCIS (Netherlands)

    Beurskens, Charlotte J. P.; Aslami, Hamid; Kuipers, Maria T.; Horn, Janneke; Vroom, Margreeth B.; van Kuilenburg, André B. P.; Roelofs, Joris J. T. H.; Schultz, Marcus J.; Juffermans, Nicole P.

    2012-01-01

    Objective: To determine the effect of induced hypothermia on bacterial growth, lung injury, and mitochondrial function in a rat model of pneumococcal pneumosepsis. Design: Animal study. Setting: University research laboratory. Subjects: Male Sprague-Dawley rats. Interventions: Subjects were

  17. Dynamic Properties of the Solow Model with Increasing or Decreasing Population and Time-to-Build Technology

    Directory of Open Access Journals (Sweden)

    Luca Guerrini

    2013-01-01

    Full Text Available We introduce a time-to-build technology in a Solow model with nonconstant population. Our analysis shows that the population dynamics may be a source of stability switches and Hopf bifurcations. The analytical results are obtained using the recent technique introduced by Beretta and Kuang (2002 in the studying of delayed differential equations with delay-dependent coefficients in characteristic equation. Numerical simulations are performed in order to illustrate the main dynamic features of the model.

  18. INCREASED PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM -INDUCED ALLERGIC ASTHMA MODEL IN MICE

    Science.gov (United States)

    Increased levels of neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and/or NT-4) have been associated with asthmatics and in animal models of allergic asthma. In our mouse model for fungal allergic asthma, repeated pulmona...

  19. DOSE-DEPENDENT INCREASE IN THE PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM-INDUCED ALLERGIC ASTHMA MODEL

    Science.gov (United States)

    Increased levels of neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and/or NT-4) have been associated with asthma as well as in animal models of allergic asthma. In our mouse model for fungal allergic asthma, repeated ...

  20. Development Of Entrepreneur Learning Model Based On Problem Based Learning To Increase Competency Independence And Creativity Students Of Industrial Engineering

    Directory of Open Access Journals (Sweden)

    Leola Dewiyani

    2017-10-01

    Full Text Available Currently it is undeniable that the competition to get a job is very tight and of course universities have an important role in printing human resources that can compete globally not least with the Department of Industrial Engineering Faculty of Engineering Muhammadiyah University of Jakarta FT UMJ. Problems that occur is based on the analysis obtained from the track record of graduates researchers found that 60 percent of students of Industrial Engineering FT UMJ work not in accordance with the level of education owned so financially their income is still below the standard. This study aims to improve the competence of students of Industrial Engineering Department FT UMJ in entrepreneurship courses especially through the development of Problem Based Learning based learning model. Specific targets of this research were conducted with the aim to identify and analyze the need to implement learning model based on Problem Based Learning Entrepreneurship and to design and develop the model of entrepreneurship based on Problem Based Learning to improve the competence independence and creativity of Industrial Engineering students of FT UMJ in Entrepreneurship course. To achieve the above objectives this research uses research and development R amp D method. The product produced in this research is the detail of learning model of entrepreneurial model based on Problem Based Learning entrepreneurship model based on Problem Based Learning and international journals

  1. Can the confidence in long range atmospheric transport models be increased? The pan European experience of ensemble

    International Nuclear Information System (INIS)

    Galmarini, S.; Bianconi, R.; Mikkelsen, T.

    2003-01-01

    Full text: In the unfortunate event of an accidental release of radioactive material to the environment, the first concern for early-phase emergency response is atmospheric dispersion. For this purpose, several countries worldwide use operational Long Range Atmospheric Transport (LRAT) models to produce predictions of the event evolution over the continental scale to determine whether, when and how the radioactive cloud is going to hit their country. While presenting the multi-model ensemble dispersion forecast system (ENSEMBLE), the paper seeks to answer the following questions: is atmospheric dispersion forecasting an important asset of the early-phase emergency response management?; Is there a 'Perfect Atmospheric Dispersion Model'?; Is there a way to make the results of dispersion models more reliable and trustworthy? Several activities conducted during the 1990's, sought to estimate quantitatively the capability of LRAT models to forecast the atmospheric dispersion of radionuclides in the atmosphere. The results obtained clearly demonstrated that: the predictions of the various operational LRAT models used worldwide do not systematically agree (mainly due to conceptual differences in model structure and differences in the meteorological forecasts used to simulate the dispersion); none of the models used in the various countries is better than others under all circumstances and therefore there is no objective indication that shows one or few models to be the 'perfect model/s'. Given the realistic scenario that an accident can take place any time, any national authority is however faced with the practical need of managing the emergency and therefore with the dilemma: 'shall one rely an a LRAT model or only an the now cast provided by a monitoring network?' and 'to what extent are a model predictions going to be deceptive in the decision making process?' Since it goes without saying that even a vague idea an the future evolution of a dispersion process is better

  2. ADAPTIF CONSERVATION (ACM MODEL IN INCREASING FAMILY SUPPORT AND COMPLIANCE TREATMENT IN PATIENT WITH PULONARY TUBERCULOSIS IN SURABAYA CITY REGION

    Directory of Open Access Journals (Sweden)

    Siti Nur Kholifah

    2017-04-01

    Full Text Available Introduction: Tuberculosis (TB in Indonesia is still health problem and the prevalence rate is high. Discontinuing medication and lack of family support are the causalities. Numbers of strategies to overcome are seemingly not succeeded. Roles and responsibilities of family nursing are crucial to improve participation, motivation of individual, family and community in prevention, including pulmonary tuberculosis. Unfortunately, models of pulmonary tuberculosis currently unavailable. The combination of adaptation and conservation in complementarily improving family support and compliance in medication is introduced in this study. Method: This research intended to analyze Adaptive Conservation Model (ACM in extending family support and treatment compliance. Modeling steps including model analysis, expert validation, field trial, implementation and recommending the output model. Research subject involves 15 families who implement family Assistance and supervision in Medication (ASM and other 15 families with ACM. Result: The study revealed ACM is better than ASM on the case of family support and medication compliances. It supports the role of environment as influential factor on individual health belief, values and decision making. Therefore, it is advised to apply ACM in enhancing family support and compliance of pulmonary TB patients. Discussion: Social and family supports to ACM group obtained by developing interaction through communication. Family interaction necessary to improve family support to pulmonary tuberculosis patients. And social support plays as motivator to maintain compliance on medication

  3. Quality assurance of sterilized products: verification of a model relating frequency of contaminated items and increasing radiation dose

    International Nuclear Information System (INIS)

    Khan, A.A.; Tallentire, A.; Dwyer, J.

    1977-01-01

    Values of the γ-radiation resistance parameters (k and n of the 'multi-hit' expression) for Bacillus pumilus E601 spores and Serratia marcescens cells have been determined and the constancy of values for a given test condition demonstrated. These organisms, differing by a factor of about 50 in k value, have been included in a laboratory test system for use in verification of a model describing the dependence of the proportion of contaminated items in a population of items on radiation dose. The proportions of contaminated units of the test system at various γ-radiation doses have been measured for different initial numbers and types of organisms present in units either singly or together. Using the model, the probabilities of contaminated units for corresponding sets of conditions have been evaluated together with associated variances. Measured proportions and predicted probabilities agree well, showing that the model holds in a laboratory contrived situation. (author)

  4. Surface energy balances of three general circulation models: Current climate and response to increasing atmospheric CO2

    International Nuclear Information System (INIS)

    Gutowski, W.J.; Gutzler, D.S.; Portman, D.; Wang, W.C.

    1988-04-01

    The surface energy balance simulated by state-of-the-art general circulation models at GFDL, GISS and NCAR for climates with current levels of atmospheric CO 2 concentration (control climate) and with twice the current levels. The work is part of an effort sponsored by the US Department of Energy to assess climate simulations produced by these models. The surface energy balance enables us to diagnose differences between models in surface temperature climatology and sensitivity to doubling CO 2 in terms of the processes that control surface temperature. Our analysis compares the simulated balances by averaging the fields of interest over a hierarchy of spatial domains ranging from the entire globe down to regions a few hundred kilometers across

  5. Omeprazole increases the efficacy of a soluble epoxide hydrolase inhibitor in a PGE2 induced pain model

    International Nuclear Information System (INIS)

    Goswami, Sumanta Kumar; Inceoglu, Bora; Yang, Jun; Wan, Debin; Kodani, Sean D.; Trindade da Silva, Carlos Antonio; Morisseau, Christophe; Hammock, Bruce D.

    2015-01-01

    Epoxyeicosatrienoic acids (EETs) are potent endogenous analgesic metabolites produced from arachidonic acid by cytochrome P450s (P450s). Metabolism of EETs by soluble epoxide hydrolase (sEH) reduces their activity, while their stabilization by sEH inhibition decreases both inflammatory and neuropathic pain. Here, we tested the complementary hypothesis that increasing the level of EETs through induction of P450s by omeprazole (OME), can influence pain related signaling by itself, and potentiate the anti-hyperalgesic effect of sEH inhibitor. Rats were treated with OME (100 mg/kg/day, p.o., 7 days), sEH inhibitor TPPU (3 mg/kg/day, p.o.) and OME (100 mg/kg/day, p.o., 7 days) + TPPU (3 mg/kg/day, p.o., last 3 days of OME dose) dissolved in vehicle PEG400, and their effect on hyperalgesia (increased sensitivity to pain) induced by PGE 2 was monitored. While OME treatment by itself exhibited variable effects on PGE 2 induced hyperalgesia, it strongly potentiated the effect of TPPU in the same assay. The significant decrease in pain with OME + TPPU treatment correlated with the increased levels of EETs in plasma and increased activities of P450 1A1 and P450 1A2 in liver microsomes. The results show that reducing catabolism of EETs with a sEH inhibitor yielded a stronger analgesic effect than increasing generation of EETs by OME, and combination of both yielded the strongest pain reducing effect under the condition of this study. - Highlights: • The soluble epoxide hydrolase (sEH) inhibitor TPPU is anti-hyperalgesic. • Omeprazole potentiates the anti-hyperalgesic actions of TPPU. • This potentiation is associated with increased P450 activity. • The potentiation is associated with an increase in fatty acid epoxide/diol ratio. • Joint use of sEH inhibitors and P450 inducers could result in drug–drug interactions.

  6. Prolonged seizure activity leads to increased Protein Kinase A activation in the rat pilocarpine model of status epilepticus.

    Science.gov (United States)

    Bracey, James M; Kurz, Jonathan E; Low, Brian; Churn, Severn B

    2009-08-04

    Status epilepticus is a life-threatening form of seizure activity that represents a major medical emergency associated with significant morbidity and mortality. Protein Kinase A is an important regulator of synaptic strength that may play an important role in the development of status epilepticus-induced neuronal pathology. This study demonstrated an increase in PKA activity against exogenous and endogenous substrates during later stages of SE. As SE progressed, a significant increase in PKA-mediated phosphorylation of an exogenous peptide substrate was demonstrated in cortical structures. The increased activity was not due to altered expression of either regulatory or catalytic subunits of the enzyme. Through the use of phospho-specific antibodies, this study also investigated the effects of SE on the phosphorylation of the GluR1 subunit of the AMPA subtype of glutamate receptor. After the onset of continuous seizure activity, an increase in phosphorylation of the PKA site on the GluR1 subunit of the AMPA receptor was observed. These data suggest a potential mechanism by which SE may increase neuronal excitability in the cortex, potentially leading to maintenance of seizure activity or long-term neuronal pathology.

  7. Uranium(VI) sorption onto magnetite. Increasing confidence in surface complexation models using chemically evident surface chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Bok, Frank [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Surface Processes

    2017-06-01

    Surface complexation models have made great efforts in describing the sorption of various radionuclides on naturally occurring mineral phases. Unfortunately, many of the published sorption parameter sets are built upon unrealistic or even wrong surface chemistry. This work describes the benefit of combining spectroscopic and batch sorption experimental data to create a reliable and consistent surface complexation parameter set.

  8. Increasing the Reliability of Circulation Model Validation: Quantifying Drifter Slip to See how Currents are Actually Moving

    Science.gov (United States)

    Anderson, T.

    2016-02-01

    Ocean circulation forecasts can help answer questions regarding larval dispersal, passive movement of injured sea animals, oil spill mitigation, and search and rescue efforts. Circulation forecasts are often validated with GPS-tracked drifter paths, but how accurately do these drifters actually move with ocean currents? Drifters are not only moved by water, but are also forced by wind and waves acting on the exposed buoy and transmitter; this imperfect movement is referred to as drifter slip. The quantification and further understanding of drifter slip will allow scientists to differentiate between drifter imperfections and actual computer model error when comparing trajectory forecasts with actual drifter tracks. This will avoid falsely accrediting all discrepancies between a trajectory forecast and an actual drifter track to computer model error. During multiple deployments of drifters in Nantucket Sound and using observed wind and wave data, we attempt to quantify the slip of drifters developed by the Northeast Fisheries Science Center's (NEFSC) Student Drifters Program. While similar studies have been conducted previously, very few have directly attached current meters to drifters to quantify drifter slip. Furthermore, none have quantified slip of NEFSC drifters relative to the oceanographic-standard "CODE" drifter. The NEFSC drifter archive has over 1000 drifter tracks primarily off the New England coast. With a better understanding of NEFSC drifter slip, modelers can reliably use these tracks for model validation.

  9. Increasing Student Communication and Spontaneous Language Use in the L2 Classroom: A Careful Consideration of the Flipped Classroom Model

    Science.gov (United States)

    Bachelor, Jeremy W.

    2017-01-01

    There is an ongoing debate among L2 educators regarding the best way for students to achieve effective communication and language spontaneity. The flipped classroom refers to an educational model where the traditional practice of dedicating class time to direct instruction is flipped so that students receive initial instruction at home and then…

  10. Using Portable Video Modeling Technology to Increase the Compliment Behaviors of Children with Autism during Athletic Group Play

    Science.gov (United States)

    Macpherson, Kevin; Charlop, Marjorie H.; Miltenberger, Catherine A.

    2015-01-01

    A multiple baseline design across participants was used to examine the effects of a portable video modeling intervention delivered in the natural environment on the verbal compliments and compliment gestures demonstrated by five children with autism. Participants were observed playing kickball with peers and adults. In baseline, participants…

  11. Gear fatigue damage for a 500 kW wind turbine exposed to increasing turbulence using a flexible multibody model

    Directory of Open Access Journals (Sweden)

    Martin Felix Jørgensen

    2014-04-01

    Full Text Available This paper investigates gear tooth fatigue damage in a 500 kW wind turbine using FLEX5 and own multibody code. FLEX5 provides the physical wind field, rotor and generator torque and the multibody code is used for obtaining gear tooth reaction forces in the planetary gearbox. Different turbulence levels are considered and the accumulated fatigue damage levels are compared. An example where the turbulence/fatigue sensitivity could be important, is in the middle of a big wind farm. Interior wind turbines in large wind farms will always operate in the wake of other wind turbines, causing increased turbulence and therefore increased fatigue damage levels. This article contributes to a better understanding of gear fatigue damage when turbulence is increased (e.g. in the center of large wind farms or at places where turbulence is pronounced.

  12. Overexpression of let-7a increases neurotoxicity in a PC12 cell model of Alzheimer's disease via regulating autophagy.

    Science.gov (United States)

    Gu, Huizi; Li, Lan; Cui, Chen; Zhao, Zihui; Song, Guijun

    2017-10-01

    Increased deposition of β-amyloid (Aβ) protein is one of the typical characteristics of Alzheimer's disease (AD). Recent evidence has demonstrated that the microRNA let-7 family, which is highly expressed in the central nervous system, participates in the regulation of pathologic processes of AD. In the present study, the effect of let-7a overexpression on Aβ1-40-induced neurotoxicity was evaluated in PC12 and SK-N-SH cells. The results indicated that overexpression of let-7a enhanced the neurotoxicity induced by Aβ1-40 in PC12 and SK-N-SH cells. In addition, the apoptosis induced by Aβ1-40 in PC12 and SK-N-SH cells was increased by let-7a overexpression. Furthermore, Aβ1-40 treatment increased the protein levels of microtubule-associated protein 1A/1B-light chain 3 (LC3) and beclin-1 and increased the LC3 II/I ratio. The mRNA expression levels of beclin-1, autophagy protein 5 (Atg-5) and Atg-7 were also increased by Aβ1-40 treatment in PC12 cells. Let-7a overexpression further upregulated the above autophagy-related markers. Furthermore, the protein level of p62 was increased by Aβ1-40 treatment, and this was further enhanced by let-7a overexpression. Finally, the present results demonstrated that the phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway was involved in the autophagy regulation by let-7a. In conclusion, the present study demonstrates that the neurotoxicity induced by Aβ1-40 is augmented by let-7a overexpression via regulation of autophagy, and the PI3K/Akt/mTOR signaling pathway also serves a function in this process.

  13. The Iowa new practice model: Advancing technician roles to increase pharmacists' time to provide patient care services.

    Science.gov (United States)

    Andreski, Michael; Myers, Megan; Gainer, Kate; Pudlo, Anthony

    Determine the effects of an 18-month pilot project using tech-check-tech in 7 community pharmacies on 1) rate of dispensing errors not identified during refill prescription final product verification; 2) pharmacist workday task composition; and 3) amount of patient care services provided and the reimbursement status of those services. Pretest-posttest quasi-experimental study where baseline and study periods were compared. Pharmacists and pharmacy technicians in 7 community pharmacies in Iowa. The outcome measures were 1) percentage of technician verified refill prescriptions where dispensing errors were not identified on final product verification; 2) percentage of time spent by pharmacists in dispensing, management, patient care, practice development, and other activities; 3) the number of pharmacist patient care services provided per pharmacist hours worked; and 4) percentage of time that technician product verification was used. There was no significant difference in overall errors (0.2729% vs. 0.5124%, P = 0.513), patient safety errors (0.0525% vs. 0.0651%, P = 0.837), or administrative errors (0.2204% vs. 0.4784%, P = 0.411). Pharmacist's time in dispensing significantly decreased (67.3% vs. 49.06%, P = 0.005), and time in direct patient care (19.96% vs. 34.72%, P = 0.003), increased significantly. Time in other activities did not significantly change. Reimbursable services per pharmacist hour (0.11 vs. 0.30, P = 0.129), did not significantly change. Non-reimbursable services increased significantly (2.77 vs. 4.80, P = 0.042). Total services significantly increased (2.88 vs. 5.16, P = 0.044). Pharmacy technician product verification of refill prescriptions preserved dispensing safety while significantly increasing the time spent in delivery of pharmacist provided patient care services. The total number of pharmacist services provided per hour also increased significantly, driven primarily by a significant increase in the number of non

  14. Gear fatigue damage for a 500 kW wind turbine exposed to increasing turbulence using a flexible multibody model

    DEFF Research Database (Denmark)

    Jørgensen, Martin Felix; Pedersen, Niels Leergaard; Sørensen, Jens Nørkær

    2014-01-01

    This paper investigates gear tooth fatigue damage in a 500 kW wind turbine using FLEX5 and own multibody code. FLEX5 provides the physical wind eld, rotor and generator torque and the multibody code is used for obtaining gear tooth reaction forces in the planetary gearbox. Dierent turbulence levels...... and therefore increased fatigue damage levels. This article contributes to a better understanding of gear fatigue damage when turbulence is increased (e.g. in the center of large wind farms or at places where turbulence is pronounced)....

  15. Sacral nerve stimulation increases activation of the primary somatosensory cortex by anal canal stimulation in an experimental model.

    LENUS (Irish Health Repository)

    Griffin, K M

    2011-08-01

    Sacral and posterior tibial nerve stimulation may be used to treat faecal incontinence; however, the mechanism of action is unknown. The aim of this study was to establish whether sensory activation of the cerebral cortex by anal canal stimulation was increased by peripheral neuromodulation.

  16. A model for removing the increased recall of recent events from the temporal distribution of autobiographical memory

    NARCIS (Netherlands)

    Janssen, S.M.J.; Gralak, A.; Murre, J.M.J.

    2011-01-01

    The reminiscence bump is the tendency to recall relatively many personal events from the period in which the individual was between 10 and 30 years old. This effect has only been found in autobiographical memory studies that used participants who were older than 40 years of age. The increased recall

  17. Quantifying and reducing uncertainty in land use change model projections : Case studies on the implications of increasing bioenergy demands

    NARCIS (Netherlands)

    Verstegen, J.A.

    2016-01-01

    Land use change is a central issue in the sustainability debate, because of its impacts on e.g. climate change, water availability and quality, soil quality and erosion, and biodiversity. Continuing population growth, shifting diets towards higher meat consumption and increasing bioenergy demands

  18. Cost-effectiveness of counseling and pedometer use to increase physical activity in the Netherlands: a modeling study

    NARCIS (Netherlands)

    E.A.B. Over (Eelco); G.C.W. Wendel-Vos (Wanda); M. van den Berg (Matthijs); H.H.H. Reenen (Heleen ); L. Tariq (Luqman); R.T. Hoogenveen (Rudolf); P.H.M. Van Baal (Pieter)

    2012-01-01

    textabstractBackground: Counseling in combination with pedometer use has proven to be effective in increasing physical activity and improving health outcomes. We investigated the cost-effectiveness of this intervention targeted at one million insufficiently active adults who visit their general

  19. Omeprazole increases the efficacy of a soluble epoxide hydrolase inhibitor in a PGE{sub 2} induced pain model

    Energy Technology Data Exchange (ETDEWEB)

    Goswami, Sumanta Kumar; Inceoglu, Bora; Yang, Jun; Wan, Debin; Kodani, Sean D. [Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California, Davis, CA (United States); Trindade da Silva, Carlos Antonio [Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California, Davis, CA (United States); Department of Genetics and Biochemistry, Federal University of Uberlandia, MG (Brazil); Morisseau, Christophe [Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California, Davis, CA (United States); Hammock, Bruce D., E-mail: bdhammock@ucdavis.edu [Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California, Davis, CA (United States)

    2015-12-15

    Epoxyeicosatrienoic acids (EETs) are potent endogenous analgesic metabolites produced from arachidonic acid by cytochrome P450s (P450s). Metabolism of EETs by soluble epoxide hydrolase (sEH) reduces their activity, while their stabilization by sEH inhibition decreases both inflammatory and neuropathic pain. Here, we tested the complementary hypothesis that increasing the level of EETs through induction of P450s by omeprazole (OME), can influence pain related signaling by itself, and potentiate the anti-hyperalgesic effect of sEH inhibitor. Rats were treated with OME (100 mg/kg/day, p.o., 7 days), sEH inhibitor TPPU (3 mg/kg/day, p.o.) and OME (100 mg/kg/day, p.o., 7 days) + TPPU (3 mg/kg/day, p.o., last 3 days of OME dose) dissolved in vehicle PEG400, and their effect on hyperalgesia (increased sensitivity to pain) induced by PGE{sub 2} was monitored. While OME treatment by itself exhibited variable effects on PGE{sub 2} induced hyperalgesia, it strongly potentiated the effect of TPPU in the same assay. The significant decrease in pain with OME + TPPU treatment correlated with the increased levels of EETs in plasma and increased activities of P450 1A1 and P450 1A2 in liver microsomes. The results show that reducing catabolism of EETs with a sEH inhibitor yielded a stronger analgesic effect than increasing generation of EETs by OME, and combination of both yielded the strongest pain reducing effect under the condition of this study. - Highlights: • The soluble epoxide hydrolase (sEH) inhibitor TPPU is anti-hyperalgesic. • Omeprazole potentiates the anti-hyperalgesic actions of TPPU. • This potentiation is associated with increased P450 activity. • The potentiation is associated with an increase in fatty acid epoxide/diol ratio. • Joint use of sEH inhibitors and P450 inducers could result in drug–drug interactions.

  20. Forced treadmill exercise can induce stress and increase neuronal damage in a mouse model of global cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Martina Svensson

    2016-12-01

    Full Text Available Physical exercise is known to be a beneficial factor by increasing the cellular stress tolerance. In ischemic stroke, physical exercise is suggested to both limit the brain injury and facilitate behavioral recovery. In this study we investigated the effect of physical exercise on brain damage following global cerebral ischemia in mice. We aimed to study the effects of 4.5 weeks of forced treadmill running prior to ischemia on neuronal damage, neuroinflammation and its effect on general stress by measuring corticosterone in feces. We subjected C57bl/6 mice (n = 63 to either treadmill running or a sedentary program prior to induction of global ischemia. Anxious, depressive, and cognitive behaviors were analyzed. Stress levels were analyzed using a corticosterone ELISA. Inflammatory and neurological outcomes were analyzed using immunohistochemistry, multiplex electrochemoluminescence ELISA and Western blot. To our surprise, we found that forced treadmill running induced a stress response, with increased anxiety in the Open Field test and increased levels of corticosterone. In accordance, mice subjected to forced exercise prior to ischemia developed larger neuronal damage in the hippocampus and showed higher cytokine levels in the brain and blood compared to non-exercised mice. The extent of neuronal damage correlated with increased corticosterone levels. To compare forced treadmill with voluntary wheel running, we used a different set of mice that exercised freely on running wheels. These mice did not show any anxiety or increased corticosterone levels. Altogether, our results indicate that exercise pre-conditioning may not be beneficial if the animals are forced to run as it can induce a detrimental stress response.

  1. Malnutrition induces gut atrophy and increases hepatic fat infiltration: studies in a pig model of childhood malnutrition.

    Science.gov (United States)

    Lykke, Mikkel; Hother, Anne-Louise; Hansen, Christian F; Friis, Henrik; Mølgaard, Christian; Michaelsen, Kim F; Briend, André; Larsen, Torben; Sangild, Per T; Thymann, Thomas

    2013-01-01

    Childhood malnutrition is a problem in developing countries, and pathological changes in digestive organs such as the intestine and liver are poorly understood. An animal model to study the progression of severe acute malnutrition could elucidate pathological changes in the intestine and liver. We sought to characterize growth and clinical changes during malnutrition related to structural and functional indices in the intestine and liver. Newly weaned piglets were given ad libitum access to a maize flour diet (MAIZE, n=9) or a nutritionally optimized reference diet (REFERENCE, n=12) for 7 weeks. Growth, hematology and clinical biochemistry where recorded weekly. After 7 weeks, the MAIZE pigs had lower body weights than the REF pigs (8.3 kg vs. 32.4 kg, P malnutrition and are associated with temporal changes in growth and hematological and biochemical endpoints. The pig model is relevant for malnourished infants and can act as a valuable tool for understanding the pathophysiology of malnutrition.

  2. Climate Modelling Shows Increased Risk to Eucalyptus sideroxylon on the Eastern Coast of Australia Compared to Eucalyptus albens

    Directory of Open Access Journals (Sweden)

    Farzin Shabani

    2017-11-01

    Full Text Available Aim: To identify the extent and direction of range shift of Eucalyptus sideroxylon and E. albens in Australia by 2050 through an ensemble forecast of four species distribution models (SDMs. Each was generated using four global climate models (GCMs, under two representative concentration pathways (RCPs. Location: Australia. Methods: We used four SDMs of (i generalized linear model, (ii MaxEnt, (iii random forest, and (iv boosted regression tree to construct SDMs for species E. sideroxylon and E. albens under four GCMs including (a MRI-CGCM3, (b MIROC5, (c HadGEM2-AO and (d CCSM4, under two RCPs of 4.5 and 6.0. Here, the true skill statistic (TSS index was used to assess the accuracy of each SDM. Results: Results showed that E. albens and E. sideroxylon will lose large areas of their current suitable range by 2050 and E. sideroxylon is projected to gain in eastern and southeastern Australia. Some areas were also projected to remain suitable for each species between now and 2050. Our modelling showed that E. sideroxylon will lose suitable habitat on the western side and will not gain any on the eastern side because this region is one the most heavily populated areas in the country, and the populated areas are moving westward. The predicted decrease in E. sideroxylon’s distribution suggests that land managers should monitor its population closely, and evaluate whether it meets criteria for a protected legal status. Main conclusions: Both Eucalyptus sideroxylon and E. albens will be negatively affected by climate change and it is projected that E. sideroxylon will be at greater risk of losing habitat than E. albens.

  3. Optical modeling of a corneal inlay in real eyes to increase depth of focus: optimum centration and residual defocus.

    Science.gov (United States)

    Tabernero, Juan; Artal, Pablo

    2012-02-01

    To determine the optimum position to center a small-aperture corneal inlay and the effect of residual defocus in the surgical eye to maximize depth of focus. Laboratorio de Óptica, Universidad de Murcia, Murcia, Spain. Cohort study. Personalized eye models were built using actual data (corneal topography, eye length, ocular aberrations, and eye alignment). A small aperture 1.6 mm in diameter was placed at the corneal plane in each model. The monochromatic and polychromatic Strehl ratios were calculated as a function of the pinhole position. Different residual defocus values were also incorporated into the models, and the through-focus Strehl ratios were calculated. Sixteen eye models were built. For most subjects, the optimum location of the aperture for distance vision was close to the corneal reflex position. For a given optimized centration of the aperture, the best compromise of depth of focus was obtained when the eyes had some residual myopic defocus (range -0.75 to -1.00 diopter [D]). Strehl ratio values were over 0.1 for far distance, which led to visual acuities better than 20/20. The depth of focus was 2.50 D with a mean near visual acuity of Jaeger 1 or better. In eyes with little astigmatism and aberrations, the optimum centration of the small aperture was near the corneal reflex position. To improve optical outcomes with the inlay, some small residual myopia and correction of corneal astigmatism might be required. Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  4. Ube3a loss increases excitability and blunts orientation tuning in the visual cortex of Angelman syndrome model mice.

    Science.gov (United States)

    Wallace, Michael L; van Woerden, Geeske M; Elgersma, Ype; Smith, Spencer L; Philpot, Benjamin D

    2017-07-01

    Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of the maternally inherited allele of UBE3A Ube3a STOP/p+ mice recapitulate major features of AS in humans and allow conditional reinstatement of maternal Ube3a with the expression of Cre recombinase. We have recently shown that AS model mice exhibit reduced inhibitory drive onto layer (L)2/3 pyramidal neurons of visual cortex, which contributes to a synaptic excitatory/inhibitory imbalance. However, it remains unclear how this loss of inhibitory drive affects neural circuits in vivo. Here we examined visual cortical response properties in individual neurons to explore the consequences of Ube3a loss on intact cortical circuits and processing. Using in vivo patch-clamp electrophysiology, we measured the visually evoked responses to square-wave drifting gratings in L2/3 regular-spiking (RS) neurons in control mice, Ube3a -deficient mice, and mice in which Ube3a was conditionally reinstated in GABAergic neurons. We found that Ube3a -deficient mice exhibited enhanced pyramidal neuron excitability in vivo as well as weaker orientation tuning. These observations are the first to show alterations in cortical computation in an AS model, and they suggest a basis for cortical dysfunction in AS. NEW & NOTEWORTHY Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of the gene UBE3A Using electrophysiological recording in vivo, we describe visual cortical dysfunctions in a mouse model of AS. Aberrant cellular properties in AS model mice could be improved by reinstating Ube3a in inhibitory neurons. These findings suggest that inhibitory neurons play a substantial role in the pathogenesis of AS. Copyright © 2017 the American Physiological Society.

  5. Dynamics of resistance development to imatinib under increasing selection pressure: a combination of mathematical models and in vitro data.

    Directory of Open Access Journals (Sweden)

    Benjamin Werner

    Full Text Available In the last decade, cancer research has been a highly active and rapidly evolving scientific area. The ultimate goal of all efforts is a better understanding of the mechanisms that discriminate malignant from normal cell biology in order to allow the design of molecular targeted treatment strategies. In individual cases of malignant model diseases addicted to a specific, ideally single oncogene, e.g. Chronic myeloid leukemia (CML, specific tyrosine kinase inhibitors (TKI have indeed been able to convert the disease from a ultimately life-threatening into a chronic disease with individual patients staying in remission even without treatment suggestive of operational cure. These developments have been raising hopes to transfer this concept to other cancer types. Unfortunately, cancer cells tend to develop both primary and secondary resistance to targeted drugs in a substantially higher frequency often leading to a failure of treatment clinically. Therefore, a detailed understanding of how cells can bypass targeted inhibition of signaling cascades crucial for malignant growths is necessary. Here, we have performed an in vitro experiment that investigates kinetics and mechanisms underlying resistance development in former drug sensitive cancer cells over time in vitro. We show that the dynamics observed in these experiments can be described by a simple mathematical model. By comparing these experimental data with the mathematical model, important parameters such as mutation rates, cellular fitness and the impact of individual drugs on these processes can be assessed. Excitingly, the experiment and the model suggest two fundamentally different ways of resistance evolution, i.e. acquisition of mutations and phenotype switching, each subject to different parameters. Most importantly, this complementary approach allows to assess the risk of resistance development in the different phases of treatment and thus helps to identify the critical periods where

  6. E2F transcription factor-1 deficiency reduces pathophysiology in the mouse model of Duchenne muscular dystrophy through increased muscle oxidative metabolism.

    Science.gov (United States)

    Blanchet, Emilie; Annicotte, Jean-Sébastien; Pradelli, Ludivine A; Hugon, Gérald; Matecki, Stéfan; Mornet, Dominique; Rivier, François; Fajas, Lluis

    2012-09-01

    E2F1 deletion leads to increased mitochondrial number and function, increased body temperature in response to cold and increased resistance to fatigue with exercise. Since E2f1-/- mice show increased muscle performance, we examined the effect of E2f1 genetic inactivation in the mdx background, a mouse model of Duchenne muscular dystrophy (DMD). E2f1-/-;mdx mice demonstrated a strong reduction of physiopathological signs of DMD, including preservation of muscle structure, decreased inflammatory profile, increased utrophin expression, resulting in better endurance and muscle contractile parameters, comparable to normal mdx mice. E2f1 deficiency in the mdx genetic background increased the oxidative metabolic gene program, mitochondrial activity and improved muscle functions. Interestingly, we observed increased E2F1 protein levels in DMD patients, suggesting that E2F1 might represent a promising target for the treatment of DMD.

  7. Modeling of rotary movement of the articulating crane with increased gaps in the hinge joints of the links

    Directory of Open Access Journals (Sweden)

    Lagerev I.A.

    2016-06-01

    Full Text Available The article made computer simulation of dynamics of hydraulic articulating cranes with fully rotary motion for the case when the cylindrical hinges have an increased gap. Considered the use of special damping devices to reduce shock loads due to the presence of increased gaps. In previously developed software package KBCrane performed a series of calcu-lations made it possible to establish the relationship between the stiffness and damping devices the effectiveness of their use in varying the magnitude of the gap. In the case of the rotary movement of the articulating crane, a comparative analysis of work of joints of the connection node of the boom and lifting device with no gap and with high gaps. The features of the damping devices work joints and cushioning. Conclusions on positive and negative sides of the use of elastic damping devices.

  8. Reactive or proactive approach towards sustainability? A conceptual framework based on sustainable business models to increase stakeholders' sustainable value capture

    DEFF Research Database (Denmark)

    Rosati, Francesco; Morioka, Sandra; Monteiro de Carvalho, Marly

    2016-01-01

    and challenging companies to seek for business opportunities with an entrepreneurial attitude to help solving sustainable development challenges. By combining both approaches, organizations have the opportunity to increase sustainable value capture by its stakeholders, acting on their institutional responsibility...... as instrument to help companies describe, analyze, manage and communicate their sustainable value proposition, creation, delivery and capture mechanism. In particular, this research focuses on value capture dynamics, aiming to explore how companies can increase their contribution to sustainable development...... sustainability. In this sense, a proactive approach to foster sustainable value capture can complement the reactive approach by delivering value beyond stakeholders' expectations. In this case, companies use their capabilities to identify opportunities to create and deliver sustainable value that stakeholders...

  9. β-cell dysfunction due to increased ER stress in a stem cell model of Wolfram syndrome.

    Science.gov (United States)

    Shang, Linshan; Hua, Haiqing; Foo, Kylie; Martinez, Hector; Watanabe, Kazuhisa; Zimmer, Matthew; Kahler, David J; Freeby, Matthew; Chung, Wendy; LeDuc, Charles; Goland, Robin; Leibel, Rudolph L; Egli, Dieter

    2014-03-01

    Wolfram syndrome is an autosomal recessive disorder caused by mutations in WFS1 and is characterized by insulin-dependent diabetes mellitus, optic atrophy, and deafness. To investigate the cause of β-cell failure, we used induced pluripotent stem cells to create insulin-producing cells from individuals with Wolfram syndrome. WFS1-deficient β-cells showed increased levels of endoplasmic reticulum (ER) stress molecules and decreased insulin content. Upon exposure to experimental ER stress, Wolfram β-cells showed impaired insulin processing and failed to increase insulin secretion in response to glucose and other secretagogues. Importantly, 4-phenyl butyric acid, a chemical protein folding and trafficking chaperone, restored normal insulin synthesis and the ability to upregulate insulin secretion. These studies show that ER stress plays a central role in β-cell failure in Wolfram syndrome and indicate that chemical chaperones might have therapeutic relevance under conditions of ER stress in Wolfram syndrome and other forms of diabetes.

  10. Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer's disease.

    Science.gov (United States)

    Warner, Timothy A; Kang, Jing-Qiong; Kennard, John A; Harrison, Fiona E

    2015-02-01

    Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Zonulin transgenic mice show altered gut permeability and increased morbidity/mortality in the DSS colitis model.

    Science.gov (United States)

    Sturgeon, Craig; Lan, Jinggang; Fasano, Alessio

    2017-06-01

    Increased small intestinal permeability (IP) has been proposed to be an integral element, along with genetic makeup and environmental triggers, in the pathogenies of chronic inflammatory diseases (CIDs). We identified zonulin as a master regular of intercellular tight junctions linked to the development of several CIDs. We aim to study the role of zonulin-mediated IP in the pathogenesis of CIDs. Zonulin transgenic Hp2 mice (Ztm) were subjected to dextran sodium sulfate (DSS) treatment for 7 days, followed by 4-7 days' recovery and compared to C57Bl/6 (wild-type (WT)) mice. IP was measured in vivo and ex vivo, and weight, histology, and survival were monitored. To mechanistically link zonulin-dependent impairment of small intestinal barrier function with clinical outcome, Ztm were treated with the zonulin inhibitor AT1001 added to drinking water in addition to DSS. We observed increased morbidity (more pronounced weight loss and colitis) and mortality (40-70% compared with 0% in WT) at 11 days post-DSS treatment in Ztm compared with WT mice. Both in vivo and ex vivo measurements showed an increased IP at baseline in Ztm compared to WT mice, which was exacerbated by DSS treatment and was associated with upregulation of zonulin gene expression (fourfold in the duodenum, sixfold in the jejunum). Treatment with AT1001 prevented the DSS-induced increased IP both in vivo and ex vivo without changing zonulin gene expression and completely reverted morbidity and mortality in Ztm. Our data show that zonulin-dependent small intestinal barrier impairment is an early step leading to the break of tolerance with subsequent development of CIDs. © 2017 New York Academy of Sciences.

  12. Increased Autoreactivity of the Complement-Activating Molecule Mannan-Binding Lectin in a Type 1 Diabetes Model

    Directory of Open Access Journals (Sweden)

    Jakob Appel Østergaard

    2016-01-01

    Full Text Available Background. Diabetic kidney disease is the leading cause of end-stage renal failure despite intensive treatment of modifiable risk factors. Identification of new drug targets is therefore of paramount importance. The complement system is emerging as a potential new target. The lectin pathway of the complement system, initiated by the carbohydrate-recognition molecule mannan-binding lectin (MBL, is linked to poor kidney prognosis in diabetes. We hypothesized that MBL activates complement upon binding within the diabetic glomerulus. Methods. We investigated this by comparing complement deposition and activation in kidneys from streptozotocin-induced diabetic mice and healthy control mice. Results. After 20 weeks of diabetes, glomerular deposition of MBL was significantly increased. Diabetic animals had 2.0-fold higher (95% CI 1.6–2.5 immunofluorescence intensity from anti-MBL antibodies compared with controls (P<0.001. Diabetes and control groups did not differ in glomerular immunofluorescence intensity obtained by antibodies against complement factors C4, C3, and C9. However, the circulating complement activation product C3a was increased in diabetes as compared to control mice (P=0.04. Conclusion. 20 weeks of diabetes increased MBL autoreactivity in the kidney and circulating C3a concentration. Together with previous findings, these results indicate direct effects of MBL within the kidney in diabetes.

  13. Structural models of increasing complexity for icosahedral boron carbide with compositions throughout the single-phase region from first principles

    Science.gov (United States)

    Ektarawong, A.; Simak, S. I.; Alling, B.

    2018-05-01

    We perform first-principles calculations to investigate the phase stability of boron carbide, concentrating on the recently proposed alternative structural models composed not only of the regularly studied B11Cp (CBC) and B12(CBC), but also of B12(CBCB) and B12( B4 ). We find that a combination of the four structural motifs can result in low-energy electron precise configurations of boron carbide. Among several considered configurations within the composition range of B10.5C and B4C , we identify in addition to the regularly studied B11Cp (CBC) at the composition of B4C two low-energy configurations, resulting in a new view of the B-C convex hull. Those are [B12 (CBC)]0.67[B12(B4)] 0.33 and [B12 (CBC)]0.67[ B12 (CBCB)]0.33, corresponding to compositions of B10.5C and B6.67C , respectively. As a consequence, B12(CBC) at the composition of B6.5C , previously suggested in the literature as a stable configuration of boron carbide, is no longer part of the B -C convex hull. By inspecting the electronic density of states as well as the elastic moduli, we find that the alternative models of boron carbide can provide a reasonably good description for electronic and elastic properties of the material in comparison with the experiments, highlighting the importance of considering B12(CBCB) and B12( B4 ), together with the previously proposed B11Cp (CBC) and B12(CBC), as the crucial ingredients for modeling boron carbide with compositions throughout the single-phase region.

  14. ANALYTICAL MODELING OF ELECTRON BACK-BOMBARDMENT INDUCED CURRENT INCREASE IN UN-GATED THERMIONIC CATHODE RF GUNS

    Energy Technology Data Exchange (ETDEWEB)

    Edelen, J. P. [Fermilab; Sun, Y. [Argonne; Harris, J. R. [AFRL, NM; Lewellen, J. W. [Los Alamos Natl. Lab.

    2016-09-28

    In this paper we derive analytical expressions for the output current of an un-gated thermionic cathode RF gun in the presence of back-bombardment heating. We provide a brief overview of back-bombardment theory and discuss comparisons between the analytical back-bombardment predictions and simulation models. We then derive an expression for the output current as a function of the RF repetition rate and discuss relationships between back-bombardment, fieldenhancement, and output current. We discuss in detail the relevant approximations and then provide predictions about how the output current should vary as a function of repetition rate for some given system configurations.

  15. Intracerebroventricular delivery of glucocerebrosidase reduces substrates and increases lifespan in a mouse model of neuronopathic Gaucher disease.

    Science.gov (United States)

    Cabrera-Salazar, M A; Bercury, S D; Ziegler, R J; Marshall, J; Hodges, B L; Chuang, W-L; Pacheco, J; Li, L; Cheng, S H; Scheule, R K

    2010-10-01

    Gaucher disease is caused by a deficit in the enzyme glucocerebrosidase. As a consequence, degradation of the glycolipids glucosylceramide (GluCer) and glucosylsphingosine (GluSph) is impaired, and their subsequent buildup can lead to significant pathology and early death. Type 1 Gaucher patients can be treated successfully with intravenous replacement enzyme, but this enzyme does not reach the CNS and thus does not ameliorate the neurological involvement in types 2 and 3 Gaucher disease. As one potential approach to treating these latter patients, we have evaluated intracerebroventricular (ICV) administration of recombinant human glucocerebrosidase (rhGC) in a mouse model of neuronopathic Gaucher disease. ICV administration resulted in enzyme distribution throughout the brain and alleviated neuropathology in multiple brain regions of this mouse model. Treatment also resulted in dose-dependent decreases in GluCer and GluSph and significantly extended survival. To evaluate the potential of continuous enzyme delivery, a group of animals was treated ICV with an adeno-associated viral vector encoding hGC and resulted in a further extension of survival. These data suggest that ICV administration of rhGC may represent a potential therapeutic approach for type 2/3 Gaucher patients. Preclinical evaluation in larger animals will be needed to ascertain the translatability of this approach to the clinic. Copyright © 2010 Elsevier Inc. All rights reserved.

  16. Phencyclidine increased while isolation rearing did not affect progressive ratio responding in rats: Investigating potential models of amotivation in schizophrenia.

    Science.gov (United States)

    Amitai, Nurith; Powell, Susan B; Young, Jared W

    2017-11-22

    Schizophrenia is a debilitating neurodevelopmental disorder affecting 1% of the global population with heterogeneous symptoms including positive, negative, and cognitive. While treatment for positive symptoms exists, none have been developed to treat negative symptoms. Animal models of schizophrenia are required to test targeted treatments and since patients exhibit reduced effort (breakpoints) for reward in a progressive ratio (PR) task, we examined the PR breakpoints of rats treated with the NMDA receptor antagonist phencyclidine or those reared in isolation - two common manipulations used to induce schizophrenia-relevant behaviors in rodents. In two cohorts, the PR breakpoint for a palatable food reward was examined in Long Evans rats after: 1) a repeated phencyclidine regimen; 2) A subchronic phencyclidine regimen followed by drug washout; and 3) post-weaning social isolation. Rats treated with repeated phencyclidine and those following washout from phencyclidine exhibited higher PR breakpoints than vehicle-treated rats. The breakpoint of isolation reared rats did not differ from those socially reared, despite abnormalities of these rats in other schizophrenia-relevant behaviors. Despite their common use for modeling other schizophrenia-relevant behaviors neither phencyclidine treatment nor isolation rearing recreated the motivational deficits observed in patients with schizophrenia, as measured by PR breakpoint. Other manipulations, and negative symptom-relevant behaviors, require investigation prior to testing putative therapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Galvanic microparticles increase migration of human dermal fibroblasts in a wound-healing model via reactive oxygen species pathway.

    Science.gov (United States)

    Tandon, Nina; Cimetta, Elisa; Villasante, Aranzazu; Kupferstein, Nicolette; Southall, Michael D; Fassih, Ali; Xie, Junxia; Sun, Ying; Vunjak-Novakovic, Gordana

    2014-01-01

    Electrical signals have been implied in many biological mechanisms, including wound healing, which has been associated with transient electrical currents not present in intact skin. One method to generate electrical signals similar to those naturally occurring in wounds is by supplementation of galvanic particles dispersed in a cream or gel. We constructed a three-layered model of skin consisting of human dermal fibroblasts in hydrogel (mimic of dermis), a hydrogel barrier layer (mimic of epidermis) and galvanic microparticles in hydrogel (mimic of a cream containing galvanic particles applied to skin). Using this model, we investigated the effects of the properties and amounts of Cu/Zn galvanic particles on adult human dermal fibroblasts in terms of the speed of wound closing and gene expression. The collected data suggest that the effects on wound closing are due to the ROS-mediated enhancement of fibroblast migration, which is in turn mediated by the BMP/SMAD signaling pathway. These results imply that topical low-grade electric currents via microparticles could enhance wound healing. © 2013 Elsevier Inc. All rights reserved.

  18. Utilizing a Pediatric Disaster Coalition Model to Increase Pediatric Critical Care Surge Capacity in New York City.

    Science.gov (United States)

    Frogel, Michael; Flamm, Avram; Sagy, Mayer; Uraneck, Katharine; Conway, Edward; Ushay, Michael; Greenwald, Bruce M; Pierre, Louisdon; Shah, Vikas; Gaffoor, Mohamed; Cooper, Arthur; Foltin, George

    2017-08-01

    A mass casualty event can result in an overwhelming number of critically injured pediatric victims that exceeds the available capacity of pediatric critical care (PCC) units, both locally and regionally. To address these gaps, the New York City (NYC) Pediatric Disaster Coalition (PDC) was established. The PDC includes experts in emergency preparedness, critical care, surgery, and emergency medicine from 18 of 25 major NYC PCC-capable hospitals. A PCC surge committee created recommendations for making additional PCC beds available with an emphasis on space, staff, stuff (equipment), and systems. The PDC assisted 15 hospitals in creating PCC surge plans by utilizing template plans and site visits. These plans created an additional 153 potential PCC surge beds. Seven hospitals tested their plans through drills. The purpose of this article was to demonstrate the need for planning for disasters involving children and to provide a stepwise, replicable model for establishing a PDC, with one of its primary goals focused on facilitating PCC surge planning. The process we describe for developing a PDC can be replicated to communities of any size, setting, or location. We offer our model as an example for other cities. (Disaster Med Public Health Preparedness. 2017;11:473-478).

  19. Regular nicotine intake increased tooth movement velocity, osteoclastogenesis and orthodontically induced dental root resorptions in a rat model

    Science.gov (United States)

    Kirschneck, Christian; Maurer, Michael; Wolf, Michael; Reicheneder, Claudia; Proff, Peter

    2017-01-01

    Orthodontic forces have been reported to significantly increase nicotine-induced periodontal bone loss. At present, however, it is unknown, which further (side) effects can be expected during orthodontic treatment at a nicotine exposure corresponding to that of an average European smoker. 63 male Fischer344 rats were randomized in three consecutive experiments of 21 animals each (A/B/C) to 3 experimental groups (7 rats, 1/2/3): (A) cone-beam-computed tomography (CBCT); (B) histology/serology; (C) reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR)/cotinine serology—(1) control; (2) orthodontic tooth movement (OTM) of the first and second upper left molar (NiTi closed coil spring, 0.25 N); (3) OTM with 1.89 mg·kg−1 per day s.c. of L(−)-nicotine. After 14 days of OTM, serum cotinine and IL-6 concentration as well as orthodontically induced inflammatory root resorption (OIIRR), osteoclast activity (histology), orthodontic tooth movement velocity (CBCT, within 14 and 28 days of OTM) and relative gene expression of known inflammatory and osteoclast markers were quantified in the dental-periodontal tissue (RT–qPCR). Animals exposed to nicotine showed significantly heightened serum cotinine and IL-6 levels corresponding to those of regular European smokers. Both the extent of root resorption, osteoclast activity, orthodontic tooth movement and gene expression of inflammatory and osteoclast markers were significantly increased compared to controls with and without OTM under the influence of nicotine. We conclude that apart from increased periodontal bone loss, a progression of dental root resorption and accelerated orthodontic tooth movement are to be anticipated during orthodontic therapy, if nicotine consumption is present. Thus patients should be informed about these risks and the necessity of nicotine abstinence during treatment. PMID:28960194

  20. The common inhaled anesthetic isoflurane increases aggregation of huntingtin and alters calcium homeostasis in a cell model of Huntington's disease

    International Nuclear Information System (INIS)

    Wang Qiujun; Liang Ge; Yang Hui; Wang Shouping; Eckenhoff, Maryellen F.; Wei Huafeng

    2011-01-01

    Isoflurane is known to increase β-amyloid aggregation and neuronal damage. We hypothesized that isoflurane will have similar effects on the polyglutamine huntingtin protein and will cause alterations in intracellular calcium homeostasis. We tested this hypothesis in striatal cells from the expanded glutamine huntingtin knock-in mouse (STHdh Q111/Q111 ) and wild type (STHdh Q7/Q7 ) striatal neurons. The primary cultured neurons were exposed for 24 h to equipotent concentrations of isoflurane, sevoflurane, and desflurane in the presence or absence of extracellular calcium and with or without xestospongin C, a potent endoplasmic reticulum inositol 1,4,5-trisphosphate (InsP 3 ) receptor antagonist. Aggregation of huntingtin protein, cell viability, and calcium concentrations were measured. Isoflurane, sevoflurane, and desflurane all increased the aggregation of huntingtin in STHdh Q111/Q111 cells, with isoflurane having the largest effect. Isoflurane induced greater calcium release from the ER and relatively more cell damage in the STHdh Q111/Q111 huntingtin cells than in the wild type STHdh Q7/Q7 striatal cells. However, sevoflurane and desflurane caused less calcium release from the ER and less cell damage. Xestospongin C inhibited the isoflurane-induced calcium release from the ER, aggregation of huntingtin, and cell damage in the STHdh Q111/Q111 cells. In summary, the Q111 form of huntingtin increases the vulnerability of striatal neurons to isoflurane neurotoxicity through combined actions on the ER IP 3 receptors. Calcium release from the ER contributes to the anesthetic induced huntingtin aggregation in STHdh Q111/Q111 striatal cells.

  1. A Preclinical Model of Chronic Alcohol Consumption Reveals Increased Metastatic Seeding of Colon Cancer Cells in the Liver.

    Science.gov (United States)

    Im, Hwi-Jin; Kim, Hyeong-Geug; Lee, Jin-Seok; Kim, Hyo-Seon; Cho, Jung-Hyo; Jo, Il-Joo; Park, Sung-Joo; Son, Chang-Gue

    2016-04-01

    Liver metastasis is the main cause of death from colorectal cancer. Alcohol consumption impacts liver function and is suggested to be an independent risk factor for liver metastasis of colorectal cancer, but no experimental evidence supporting this hypothesis has been demonstrated to date. In this study, we investigated the effect of alcohol intake on liver metastasis. We examined colon cancer cell spread from the spleen in mice provided with water (control group), alcohol for 4 weeks before tumor injection (prealcohol), alcohol for 3 weeks after tumor injection (postalcohol), or alcohol throughout the 7-week study (alcohol). Alcohol intake significantly increased hepatic metastatic burden in the prealcohol (2.4-fold, P < 0.001), postalcohol (2.0-fold, P < 0.01), and alcohol groups (2.2-fold, P < 0.001). A fluorescence-based metastasis tracking assay also confirmed an alcohol-induced increase in the abundance of tumor cells in the liver (2.5-fold, P < 0.001). Investigation of the host microenvironment revealed an alcohol-induced inflammatory response marked by elevated TNFα, IL1β, IL6, and IFNγ protein levels, as well as increased expression of intercellular molecule-1 (ICAM1) in hepatic tissues after 4 weeks of alcohol consumption. Moreover, the peripheral blood of mice provided with alcohol for 4 weeks exhibited reduced natural killer and CD8(+) T-cell counts. Collectively, our findings suggest that chronic alcohol consumption accelerates liver metastasis of colorectal cancer cells through alterations to the liver microenvironment and inactivation of immune surveillance. Cancer Res; 76(7); 1698-704. ©2016 AACR. ©2016 American Association for Cancer Research.

  2. Increased ghrelin but low ghrelin-reactive immunoglobulins in a rat model of methotrexate chemotherapy-induced anorexia

    Directory of Open Access Journals (Sweden)

    Marie François

    2016-07-01

    Full Text Available Background and aims: Cancer chemotherapy is commonly accompanied by mucositis, anorexia, weight loss and anxiety independently from cancer-induced anorexia-cachexia, further aggravating clinical outcome. Ghrelin is a peptide hormone produced in gastric mucosa that reaches the brain to stimulate appetite. In plasma, ghrelin is protected from degradation by ghrelin-reactive immunoglobulins (Ig. To analyze possible involvement of ghrelin in the chemotherapy-induced anorexia and anxiety, gastric ghrelin expression, plasma levels of ghrelin and ghrelin-reactive IgG were studied in rats treated with methotrexate (MTX.Methods: Rats received MTX (2.5 mg/kg, S.C. for three consecutive days and were killed 3 days later, at the peak of anorexia and weight loss. Control rats received phosphate-buffered saline. Preproghrelin mRNA expression in the stomach was analyzed by in situ hybridization. Plasma levels of ghrelin and ghrelin-reactive IgG were measured by immunoenzymatic assays and IgG affinity kinetics by surface plasmon resonance. Anxiety- and depression-like behaviors in MTX-treated anorectic and in control rats were evaluated in the elevated plus-maze and the forced-swim test, respectively.Results: In MTX-treated anorectic rats the number of preproghrelin mRNA-producing cells was found increased (by 51.3%, p<0.001 as well were plasma concentrations of both ghrelin and des-acyl-ghrelin (by 70.4%, p<0.05 and 98.3%, p<0.01, respectively. In contrast, plasma levels of total IgG reactive with ghrelin and des-acyl-ghrelin were drastically decreased (by 87.2% and 88.4%, respectively, both p<0.001, and affinity kinetics of these IgG were characterized by increased small and big Kd, respectively. MTX-treated rats displayed increased anxiety- but not depression-like behavior.Conclusion: MTX-induced anorexia, weight loss and anxiety are accompanied by increased ghrelin production and by a decrease of ghrelin-reactive IgG levels and affinity binding properties

  3. Antibody directed against human YKL-40 increases tumor volume in a human melanoma xenograft model in scid mice

    DEFF Research Database (Denmark)

    Salamon, Johannes; Hoffmann, Tatjana; Elies, Eva

    2014-01-01

    were treated with intraperitoneal injections of anti-YKL-40, isoptype control or PBS. Non-YKL-40 expressing human pancreatic carcinoma cell line PaCa 5061 served as additional control. MR imaging was used for evaluation of tumor growth. Two days after the first injections of anti-YKL-40, tumor volume...... had increased significantly compared with controls, whereas no effects were observed for control tumors from PaCa 5061 cells lacking YKL-40 expression. After 18 days, mean tumor size of the mice receiving repeated anti-YKL-40 injections was 1.82 g, >4 times higher than mean tumor size of the controls...

  4. Notch1 and 4 Signaling Responds to an Increasing Vascular Wall Shear Stress in a Rat Model of Arteriovenous Malformations

    Directory of Open Access Journals (Sweden)

    Jian Tu

    2014-01-01

    Full Text Available Notch signaling is suggested to promote the development and maintenance of cerebral arteriovenous malformations (AVMs, and an increasing wall shear stress (WSS contributes to AVM rupture. Little is known about whether WSS impacts Notch signaling, which is important for understanding the angiogenesis of AVMs. WSS was measured in arteriovenous fistulas (AVF surgically created in 96 rats at different time points over a period of 84 days. The expression of Notch receptors 1 and 4 and their ligands, Delta1 and 4, Jagged1, and Notch downstream gene target Hes1 was quantified in “nidus” vessels. The interaction events between Notch receptors and their ligands were quantified using proximity ligation assay. There was a positive correlation between WSS and time (r=0.97; P<0.001. The expression of Notch receptors and their ligands was upregulated following AVF formation. There was a positive correlation between time and the number of interactions between Notch receptors and their ligands aftre AVF formation (r=0.62, P<0.05 and a positive correlation between WSS and the number of interactions between Notch receptors and their ligands (r=0.87, P<0.005. In conclusion, an increasing WSS may contribute to the angiogenesis of AVMs by activation of Notch signaling.

  5. Consequences of increasing bioenergy demand on wood and forests: An application of the Global Forest Products Model

    Science.gov (United States)

    Buongiorno, J.; Raunikar, R.; Zhu, S.

    2011-01-01

    The Global Forest Products Model (GFPM) was applied to project the consequences for the global forest sector of doubling the rate of growth of bioenergy demand relative to a base scenario, other drivers being maintained constant. The results showed that this would lead to the convergence of the price of fuelwood and industrial roundwood, raising the price of industrial roundwood by nearly 30% in 2030. The price of sawnwood and panels would be 15% higher. The price of paper would be 3% higher. Concurrently, the demand for all manufactured wood products would be lower in all countries, but the production would rise in countries with competitive advantage. The global value added in wood processing industries would be 1% lower in 2030. The forest stock would be 2% lower for the world and 4% lower for Asia. These effects varied substantially by country. ?? 2011 Department of Forest Economics, SLU Ume??, Sweden.

  6. Does Leisure Time as a Stress Coping Resource Increase Affective Complexity? Applying the Dynamic Model of Affect (DMA)

    Science.gov (United States)

    Qian, Xinyi (Lisa); Yarnal, Careen M.; Almeida, David M.

    2013-01-01

    Affective complexity, a manifestation of psychological well-being, refers to the relative independence between positive and negative affect (PA, NA). According to the Dynamic Model of Affect (DMA), stressful situations lead to highly inverse PA-NA relationship, reducing affective complexity. Meanwhile, positive events can sustain affective complexity by restoring PA-NA independence. Leisure, a type of positive events, has been identified as a coping resource. This study used the DMA to assess whether leisure time helps restore affective complexity on stressful days. We found that on days with more leisure time than usual, an individual experienced less negative PA-NA relationship after daily stressful events. The finding demonstrates the value of leisure time as a coping resource and the DMA’s contribution to coping research. PMID:24659826

  7. Characteristics of Women Who Have Had Cosmetic Breast Implants That Could Be Associated with Increased Suicide Risk: A Systematic Review, Proposing a Suicide Prevention Model

    Directory of Open Access Journals (Sweden)

    Nikolaos Manoloudakis

    2015-03-01

    Full Text Available Literature indicates an increased risk of suicide among women who have had cosmetic breast implants. An explanatory model for this association has not been established. Some studies conclude that women with cosmetic breast implants demonstrate some characteristics that are associated with increased suicide risk while others support that the breast augmentation protects from suicide. A systematic review including data collection from January 1961 up to February 2014 was conducted. The results were incorporated to pre-existing suicide risk models of the general population. A modified suicide risk model was created for the female cosmetic augmentation mammaplasty candidate. A 2-3 times increased suicide risk among women that undergo cosmetic breast augmentation has been identified. Breast augmentation patients show some characteristics that are associated with increased suicide risk. The majority of women reported high postoperative satisfaction. Recent research indicates that the Autoimmune syndrome induced by adjuvants and fibromyalgia syndrome are associated with silicone implantation. A thorough surgical, medical and psycho-social (psychiatric, family, reproductive, and occupational history should be included in the preoperative assessment of women seeking to undergo cosmetic breast augmentation. Breast augmentation surgery can stimulate a systematic stress response and increase the risk of suicide. Each risk factor of suicide has poor predictive value when considered independently and can result in prediction errors. A clinical management model has been proposed considering the overlapping risk factors of women that undergo cosmetic breast augmentation with suicide.

  8. A wireless partially glaciated watershed in a virtual globe: Integrating data, models, and visualization to increase climate change understanding

    Science.gov (United States)

    Jones, J.; Hood, E.; Fatland, D. R.; Berner, L.; Heavner, M.; Connor, C.; O'Brien, W.

    2008-12-01

    SEAMONSTER, a NASA funded sensor web project, is the SouthEast Alaska MOnitoring Network for Science, Telecommunications, Education and Research. SEAMONSTER is operating in the partially glaciated Mendenhall and Lemon Creek Watersheds, in the Juneau area, on the margins of the Juneau Icefield. These watersheds are studied for both 1. long term monitoring of changes, and 2. detection and analysis of transient events (such as glacier lake outburst floods). The diverse sensors (meteorological, dual frequency GPS, water quality, lake level, etc), power and bandwidth constraints, and competing time scales of interest require autonomous reactivity of the sensor web. The sensors are deployed throughout two partially glaciated watersheds and facilitated data acquisition in temperate rain forest, alpine, lacustrine, and glacial environments. Understanding these environments is important for public understanding of climate change. These environments are geographically isolated, limiting public access to, and understanding of, such locales. In an effort to inform the general public and primary educators about the basic processes occurring in these unique natural systems, we have developed an interactive website. This web portal supplements and enhances environmental science primary education by providing educators and students with interactive access to basic information from the glaciological, hydrological, and meteorological systems we are studying. In addition, we have developed an interactive virtual tour of the Lemon Glacier and its watershed. The focus of this presentation is using the data gathered by the SEAMONSTER sensor web, coupled with a temperature-indexed glacial melt model, to educate students and the public on topics ranging from modeling responses due to environmental changes to glacial hydrology. The interactive SEAMONSTER web site is the primary source for visualizing the data, while Google Earth can be used to visualize the isolated Lemon Creek watershed

  9. Preparation of pre-confluent retinal cells increases graft viability in vitro and in vivo: a mouse model.

    Directory of Open Access Journals (Sweden)

    Kevin P Kennelly

    Full Text Available PURPOSE: Graft failure remains an obstacle to experimental subretinal cell transplantation. A key step is preparing a viable graft, as high levels of necrosis and apoptosis increase the risk of graft failure. Retinal grafts are commonly harvested from cell cultures. We termed the graft preparation procedure "transplant conditions" (TC. We hypothesized that culture conditions influenced graft viability, and investigated whether viability decreased following TC using a mouse retinal pigment epithelial (RPE cell line, DH01. METHODS: Cell viability was assessed by trypan blue exclusion. Levels of apoptosis and necrosis in vitro were determined by flow cytometry for annexin V and propidium iodide and Western blot analysis for the pro- and cleaved forms of caspases 3 and 7. Graft viability in vivo was established by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL and cleaved caspase 3 immunolabeling of subretinal allografts. RESULTS: Pre-confluent cultures had significantly less nonviable cells than post-confluent cultures (6.6%±0.8% vs. 13.1%±0.9%, p<0.01. Cell viability in either group was not altered significantly following TC. Caspases 3 and 7 were not altered by levels of confluence or following TC. Pre-confluent cultures had low levels of apoptosis/necrosis (5.6%±1.1% that did not increase following TC (4.8%±0.5%. However, culturing beyond confluence led to progressively increasing levels of apoptosis and necrosis (up to 16.5%±0.9%. Allografts prepared from post-confluent cultures had significantly more TUNEL-positive cells 3 hours post-operatively than grafts of pre-confluent cells (12.7%±3.1% vs. 4.5%±1.4%, p<0.001. Subretinal grafts of post-confluent cells also had significantly higher rates of cleaved caspase 3 than pre-confluent grafts (20.2%±4.3% vs. 7.8%±1.8%, p<0.001. CONCLUSION: Pre-confluent cells should be used to maximize graft cell viability.

  10. Collagen induced arthritis increases secondary metastasis in MMTV-PyV MT mouse model of mammary cancer

    Directory of Open Access Journals (Sweden)

    Gruber Helen E

    2011-08-01

    Full Text Available Abstract Background Several studies have demonstrated that sites of chronic inflammation are often associated with the establishment and growth of various malignancies. A common inflammatory condition in humans is autoimmune arthritis (AA. Although AA and cancer are different diseases, many of the underlying processes that contribute to the disorders of the joints and connective tissue that characterize AA also affect cancer progression and metastasis. Systemically, AA can lead to cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge being available, there has been minimal research linking breast cancer, arthritis, and metastasis associated with breast cancer. Notably both diseases are extremely prevalent in older post-menopausal women. Methods To establish the novel link between arthritis induced inflammation and secondary metastasis associated with breast cancer, PyV MT mice that spontaneously develop mammary gland carcinoma were injected with Type II collagen (CII to induce arthritis at 9 and 18 weeks of age for pre-metastatic and metastatic condition. The sites of secondary metastasis and the associated inflammatory microenvironment were evaluated. Results A significant increase in breast cancer-associated secondary metastasis to the lungs and bones was observed in the arthritic versus the non-arthritic PyV MT mice along with an increase in primary tumor burden. We report significant increases in the levels of interstitial cellular infiltrates and pro-inflammatory cytokines such as interleukin-17 (IL-17, interleukin-6 (IL-6, Pro- Matrix metallopeptidase 9 (Pro-MMP9, insulin like growth factor-II (GF-II and macrophage colony stimulating factor (M-CSF in the arthritic lung and bone milieu as well as in the circulation. These pro-inflammatory cytokines along with the inflammatory microenvironment may be the underlying factors

  11. Collagen induced arthritis increases secondary metastasis in MMTV-PyV MT mouse model of mammary cancer

    International Nuclear Information System (INIS)

    Roy, Lopamudra Das; Ghosh, Sriparna; Pathangey, Latha B; Tinder, Teresa L; Gruber, Helen E; Mukherjee, Pinku

    2011-01-01

    Several studies have demonstrated that sites of chronic inflammation are often associated with the establishment and growth of various malignancies. A common inflammatory condition in humans is autoimmune arthritis (AA). Although AA and cancer are different diseases, many of the underlying processes that contribute to the disorders of the joints and connective tissue that characterize AA also affect cancer progression and metastasis. Systemically, AA can lead to cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge being available, there has been minimal research linking breast cancer, arthritis, and metastasis associated with breast cancer. Notably both diseases are extremely prevalent in older post-menopausal women. To establish the novel link between arthritis induced inflammation and secondary metastasis associated with breast cancer, PyV MT mice that spontaneously develop mammary gland carcinoma were injected with Type II collagen (CII) to induce arthritis at 9 and 18 weeks of age for pre-metastatic and metastatic condition. The sites of secondary metastasis and the associated inflammatory microenvironment were evaluated. A significant increase in breast cancer-associated secondary metastasis to the lungs and bones was observed in the arthritic versus the non-arthritic PyV MT mice along with an increase in primary tumor burden. We report significant increases in the levels of interstitial cellular infiltrates and pro-inflammatory cytokines such as interleukin-17 (IL-17), interleukin-6 (IL-6), Pro- Matrix metallopeptidase 9 (Pro-MMP9), insulin like growth factor-II (GF-II) and macrophage colony stimulating factor (M-CSF) in the arthritic lung and bone milieu as well as in the circulation. These pro-inflammatory cytokines along with the inflammatory microenvironment may be the underlying factors facilitating tumor progression and metastasis in

  12. Collagen induced arthritis increases secondary metastasis in MMTV-PyV MT mouse model of mammary cancer.

    Science.gov (United States)

    Roy, Lopamudra Das; Ghosh, Sriparna; Pathangey, Latha B; Tinder, Teresa L; Gruber, Helen E; Mukherjee, Pinku

    2011-08-22

    Several studies have demonstrated that sites of chronic inflammation are often associated with the establishment and growth of various malignancies. A common inflammatory condition in humans is autoimmune arthritis (AA). Although AA and cancer are different diseases, many of the underlying processes that contribute to the disorders of the joints and connective tissue that characterize AA also affect cancer progression and metastasis. Systemically, AA can lead to cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge being available, there has been minimal research linking breast cancer, arthritis, and metastasis associated with breast cancer. Notably both diseases are extremely prevalent in older post-menopausal women. To establish the novel link between arthritis induced inflammation and secondary metastasis associated with breast cancer, PyV MT mice that spontaneously develop mammary gland carcinoma were injected with Type II collagen (CII) to induce arthritis at 9 and 18 weeks of age for pre-metastatic and metastatic condition. The sites of secondary metastasis and the associated inflammatory microenvironment were evaluated. A significant increase in breast cancer-associated secondary metastasis to the lungs and bones was observed in the arthritic versus the non-arthritic PyV MT mice along with an increase in primary tumor burden. We report significant increases in the levels of interstitial cellular infiltrates and pro-inflammatory cytokines such as interleukin-17 (IL-17), interleukin-6 (IL-6), Pro- Matrix metallopeptidase 9 (Pro-MMP9), insulin like growth factor-II (GF-II) and macrophage colony stimulating factor (M-CSF) in the arthritic lung and bone milieu as well as in the circulation. These pro-inflammatory cytokines along with the inflammatory microenvironment may be the underlying factors facilitating tumor progression and metastasis in

  13. Prostaglandin-E2 Mediated Increase in Calcium and Phosphate Excretion in a Mouse Model of Distal Nephron Salt Wasting.

    Directory of Open Access Journals (Sweden)

    Manoocher Soleimani

    Full Text Available Contribution of salt wasting and volume depletion to the pathogenesis of hypercalciuria and hyperphosphaturia is poorly understood. Pendrin/NCC double KO (pendrin/NCC-dKO mice display severe salt wasting under basal conditions and develop profound volume depletion, prerenal renal failure, and metabolic alkalosis and are growth retarded. Microscopic examination of the kidneys of pendrin/NCC-dKO mice revealed the presence of calcium phosphate deposits in the medullary collecting ducts, along with increased urinary calcium and phosphate excretion. Confirmatory studies revealed decreases in the expression levels of sodium phosphate transporter-2 isoforms a and c, increases in the expression of cytochrome p450 family 4a isotypes 12 a and b, as well as prostaglandin E synthase 1, and cyclooxygenases 1 and 2. Pendrin/NCC-dKO animals also had a significant increase in urinary prostaglandin E2 (PGE-2 and renal content of 20-hydroxyeicosatetraenoic acid (20-HETE levels. Pendrin/NCC-dKO animals exhibit reduced expression levels of the sodium/potassium/2chloride co-transporter 2 (NKCC2 in their medullary thick ascending limb. Further assessment of the renal expression of NKCC2 isoforms by quantitative real time PCR (qRT-PCR reveled that compared to WT mice, the expression of NKCC2 isotype F was significantly reduced in pendrin/NCC-dKO mice. Provision of a high salt diet to rectify volume depletion or inhibition of PGE-2 synthesis by indomethacin, but not inhibition of 20-HETE generation by HET0016, significantly improved hypercalciuria and salt wasting in pendrin/NCC dKO mice. Both high salt diet and indomethacin treatment also corrected the alterations in NKCC2 isotype expression in pendrin/NCC-dKO mice. We propose that severe salt wasting and volume depletion, irrespective of the primary originating nephron segment, can secondarily impair the reabsorption of salt and calcium in the thick ascending limb of Henle and/or proximal tubule, and reabsorption of

  14. An experimental study of the job demand-control model with measures of heart rate variability and salivary alpha-amylase: Evidence of increased stress responses to increased break autonomy.

    Science.gov (United States)

    O'Donnell, Emma; Landolt, Kathleen; Hazi, Agnes; Dragano, Nico; Wright, Bradley J

    2015-01-01

    We assessed in an experimental design whether the stress response towards a work task was moderated by the autonomy to choose a break during the assigned time to complete the task. This setting is defined in accordance with the theoretical framework of the job-demand-control (JDC) model of work related stress. The findings from naturalistic investigations of a stress-buffering effect of autonomy (or 'buffer hypothesis') are equivocal and the experimental evidence is limited, especially with relation to physiological indices of stress. Our objective was to investigate if increased autonomy in a particular domain (break time control) was related with adaptive physiology using objective physiological markers of stress; heart rate variability (HRV) and salivary alpha amylase (sAA). We used a within-subject design and the 60 female participants were randomly assigned to an autonomy (free timing of break) and standard conditions (fixed timing of break) of a word processing task in a simulated office environment in a random order. Participants reported increased perceptions of autonomy, no difference in demand and performed worse in the task in the break-time autonomy versus the standard condition. The results revealed support for the manipulation of increased autonomy, but in the opposing direction. Increased autonomy was related with dysregulated physiological reactivity, synonymous with typical increased stress responses. Potentially, our findings may indicate that autonomy is not necessary a resource but could become an additional stressor when it adds additional complexity while the amount of work (demands) remains unchanged. Further, our findings underscore the need to collect objective physiological evidence of stress to supplement self-reported information. Self-report biases may partially explain the inconsistent findings with the buffer hypothesis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Inadvertent Splenectomy During Resection for Colorectal Cancer Does Not Increase Long-term Mortality in a Propensity Score Model

    DEFF Research Database (Denmark)

    Lolle, Ida; Pommergaard, Hans-Christian; Schefte, David F

    2016-01-01

    BACKGROUND: Previous studies suggest that long-term mortality is increased in patients who undergo splenectomy during surgery for colorectal cancer. The reason for this association remains unclear. OBJECTIVE: The purpose of this study was to investigate the association between inadvertent...... splenectomy attributed to iatrogenic lesion to the spleen during colorectal cancer resections and long-term mortality in a national cohort of unselected patients. DESIGN: This was a retrospective, nationwide cohort study. SETTINGS: Data were collected from the database of the Danish Colorectal Cancer Group...... for patients surviving 30 days after surgery. Secondary outcomes were 30-day mortality and risk factors for inadvertent splenectomy. Multivariable and propensity-score matched Cox regression analyses were used to adjust for potential confounding. RESULTS: In total, 23,727 patients were included, of which 277...

  16. Exercise training prevents increased intraocular pressure and sympathetic vascular modulation in an experimental model of metabolic syndrome

    International Nuclear Information System (INIS)

    Castro, E.F.S.; Mostarda, C.T.; Rodrigues, B.; Moraes-Silva, I.C.; Feriani, D.J.; De Angelis, K.; Irigoyen, M.C.

    2015-01-01

    The present study aimed to study the effects of exercise training (ET) performed by rats on a 10-week high-fructose diet on metabolic, hemodynamic, and autonomic changes, as well as intraocular pressure (IOP). Male Wistar rats receiving fructose overload in drinking water (100 g/L) were concomitantly trained on a treadmill for 10 weeks (FT group) or kept sedentary (F group), and a control group (C) was kept in normal laboratory conditions. The metabolic evaluation comprised the Lee index, glycemia, and insulin tolerance test (KITT). Arterial pressure (AP) was measured directly, and systolic AP variability was performed to determine peripheral autonomic modulation. ET attenuated impaired metabolic parameters, AP, IOP, and ocular perfusion pressure (OPP) induced by fructose overload (FT vs F). The increase in peripheral sympathetic modulation in F rats, demonstrated by systolic AP variance and low frequency (LF) band (F: 37±2, 6.6±0.3 vs C: 26±3, 3.6±0.5 mmHg 2 ), was prevented by ET (FT: 29±3, 3.4±0.7 mmHg 2 ). Positive correlations were found between the LF band and right IOP (r=0.57, P=0.01) and left IOP (r=0.64, P=0.003). Negative correlations were noted between KITT values and right IOP (r=-0.55, P=0.01) and left IOP (r=-0.62, P=0.005). ET in rats effectively prevented metabolic abnormalities and AP and IOP increases promoted by a high-fructose diet. In addition, ocular benefits triggered by exercise training were associated with peripheral autonomic improvement

  17. Exercise training prevents increased intraocular pressure and sympathetic vascular modulation in an experimental model of metabolic syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Castro, E.F.S. [Unidade de Hipertensão, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Mostarda, C.T. [Universidade Federal do Maranhão, São Luís, MA (Brazil); Rodrigues, B. [Laboratório do Movimento Humano, Universidade São Judas Tadeu, São Paulo, SP (Brazil); Moraes-Silva, I.C. [Unidade de Hipertensão, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Feriani, D.J. [Laboratório do Movimento Humano, Universidade São Judas Tadeu, São Paulo, SP (Brazil); De Angelis, K. [Laboratório de Fisiologia Translacional, Universidade Nove de Julho, São Paulo, SP (Brazil); Irigoyen, M.C. [Unidade de Hipertensão, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2015-02-13

    The present study aimed to study the effects of exercise training (ET) performed by rats on a 10-week high-fructose diet on metabolic, hemodynamic, and autonomic changes, as well as intraocular pressure (IOP). Male Wistar rats receiving fructose overload in drinking water (100 g/L) were concomitantly trained on a treadmill for 10 weeks (FT group) or kept sedentary (F group), and a control group (C) was kept in normal laboratory conditions. The metabolic evaluation comprised the Lee index, glycemia, and insulin tolerance test (KITT). Arterial pressure (AP) was measured directly, and systolic AP variability was performed to determine peripheral autonomic modulation. ET attenuated impaired metabolic parameters, AP, IOP, and ocular perfusion pressure (OPP) induced by fructose overload (FT vs F). The increase in peripheral sympathetic modulation in F rats, demonstrated by systolic AP variance and low frequency (LF) band (F: 37±2, 6.6±0.3 vs C: 26±3, 3.6±0.5 mmHg{sup 2}), was prevented by ET (FT: 29±3, 3.4±0.7 mmHg{sup 2}). Positive correlations were found between the LF band and right IOP (r=0.57, P=0.01) and left IOP (r=0.64, P=0.003). Negative correlations were noted between KITT values and right IOP (r=-0.55, P=0.01) and left IOP (r=-0.62, P=0.005). ET in rats effectively prevented metabolic abnormalities and AP and IOP increases promoted by a high-fructose diet. In addition, ocular benefits triggered by exercise training were associated with peripheral autonomic improvement.

  18. 17-AAG improves cognitive process and increases heat shock protein response in a model lesion with Aβ25-35.

    Science.gov (United States)

    Ortega, Laura; Calvillo, Minerva; Luna, Félix; Pérez-Severiano, Francisca; Rubio-Osornio, Moisés; Guevara, Jorge; Limón, Ilhuicamina Daniel

    2014-08-01

    Molecular chaperones, or heat shock proteins (HSP), have been implicated in numerous neurodegenerative disorders characterized by the accumulation of protein aggregates, such as Alzheimer disease. The agglomeration of insoluble structures of Aβ is thought to be responsible for neuronal death, which in turn leads to the loss of cognitive functions. Recent findings have shown that the induction of HSP decreases the level of abnormal protein aggregates, as well as demonstrating that 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), an analogue of geldanamycin (GA), increases Aβ clearance through the induction of molecular chaperones in cell culture. In light of this discovery that HSP overexpression can be neuroprotective, the search for a way to pharmacologically induce the overexpression of HSP and other associated chaperones may lead to a promising approach for the treatment of neurodegenerative diseases. The aim of our study was to evaluate both the effect of 17-AAG on the cognitive process and the HSP response in rats injected with Aβ25-35 into the CA1 of the hippocampus. The results show that the injection of Aβ caused a significant increase in the expression of the HSP involved in the regulation of cellular proteostasis. While the HSP did not reverse excitotoxic damage, given that experimental subjects showed learning and memory deficits, the administration of 17-AAG prior to the injection of Aβ25-35 did show an improvement in the behavioral assessment that correlated with the upregulation of HSP70 in subjects injured with Aβ. Overall, our data shows that the pharmacological induction of HSP using 17-AAG may be an alternative treatment of neurodegenerative diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Androgen receptor agonists increase lean mass, improve cardiopulmonary functions and extend survival in preclinical models of Duchenne muscular dystrophy.

    Science.gov (United States)

    Ponnusamy, Suriyan; Sullivan, Ryan D; You, Dahui; Zafar, Nadeem; He Yang, Chuan; Thiyagarajan, Thirumagal; Johnson, Daniel L; Barrett, Maron L; Koehler, Nikki J; Star, Mayra; Stephenson, Erin J; Bridges, Dave; Cormier, Stephania A; Pfeffer, Lawrence M; Narayanan, Ramesh

    2017-07-01

    Duchenne muscular dystrophy (DMD) is a neuromuscular disease that predominantly affects boys as a result of mutation(s) in the dystrophin gene. DMD is characterized by musculoskeletal and cardiopulmonary complications, resulting in shorter life-span. Boys afflicted by DMD typically exhibit symptoms within 3-5 years of age and declining physical functions before attaining puberty. We hypothesized that rapidly deteriorating health of pre-pubertal boys with DMD could be due to diminished anabolic actions of androgens in muscle, and that intervention with an androgen receptor (AR) agonist will reverse musculoskeletal complications and extend survival. While castration of dystrophin and utrophin double mutant (mdx-dm) mice to mimic pre-pubertal nadir androgen condition resulted in premature death, maintenance of androgen levels extended the survival. Non-steroidal selective-AR modulator, GTx-026, which selectively builds muscle and bone was tested in X-linked muscular dystrophy mice (mdx). GTx-026 significantly increased body weight, lean mass and grip strength by 60-80% over vehicle-treated mdx mice. While vehicle-treated castrated mdx mice exhibited cardiopulmonary impairment and fibrosis of heart and lungs, GTx-026 returned cardiopulmonary function and intensity of fibrosis to healthy control levels. GTx-026 elicits its musculoskeletal effects through pathways that are distinct from dystrophin-regulated pathways, making AR agonists ideal candidates for combination approaches. While castration of mdx-dm mice resulted in weaker muscle and shorter survival, GTx-026 treatment increased the muscle mass, function and survival, indicating that androgens are important for extended survival. These preclinical results support the importance of androgens and the need for intervention with AR agonists to treat DMD-affected boys. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Platelet-Rich Plasma Increases the Levels of Catabolic Molecules and Cellular Dedifferentiation in the Meniscus of a Rabbit Model

    Directory of Open Access Journals (Sweden)

    Hye-Rim Lee

    2016-01-01

    Full Text Available Despite the susceptibility to frequent intrinsic and extrinsic injuries, especially in the inner zone, the meniscus does not heal spontaneously owing to its poor vascularity. In this study, the effect of platelet-rich plasma (PRP, containing various growth factors, on meniscal mechanisms was examined under normal and post-traumatic inflammatory conditions. Isolated primary meniscal cells of New Zealand white (NZW rabbits were incubated for 3, 10, 14 and 21 days with PRP(−, 10% PRP (PRP(+, IL(+ or IL(+PRP(+. The meniscal cells were collected and examined using reverse-transcription polymerase chain reaction (RT-PCR. Culture media were examined by immunoblot analyses for matrix metalloproteinases (MMP catabolic molecules. PRP containing growth factors improved the cellular viability of meniscal cells in a concentration-dependent manner at Days 1, 4 and 7. However, based on RT-PCR, meniscal cells demonstrated dedifferentiation, along with an increase in type I collagen in the PRP(+ and in IL(+PRP(+. In PRP(+, the aggrecan expression levels were lower than in the PRP(− until Day 21. The protein levels of MMP-1 and MMP-3 were higher in each PRP group, i.e., PRP(+ and IL(+PRP(+, at each culture time. A reproducible 2-mm circular defect on the meniscus of NZW rabbit was used to implant fibrin glue (control or PRP in vivo. After eight weeks, the lesions in the control and PRP groups were occupied with fibrous tissue, but not with meniscal cells. This study shows that PRP treatment of the meniscus results in an increase of catabolic molecules, especially those related to IL-1α-induced inflammation, and that PRP treatment for an in vivo meniscus injury accelerates fibrosis, instead of meniscal cartilage.

  1. Levels of α7 integrin and laminin-α2 are increased following prednisone treatment in the mdx mouse and GRMD dog models of Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Ryan D. Wuebbles

    2013-09-01

    Duchenne muscular dystrophy (DMD is a fatal neuromuscular disease for which there is no cure and limited treatment options. Prednisone is currently the first line treatment option for DMD and studies have demonstrated that it improves muscle strength. Although prednisone has been used for the treatment of DMD for decades, the mechanism of action of this drug remains unclear. Recent studies have shown that the α7β1 integrin is a major modifier of disease progression in mouse models of DMD and is therefore a target for drug-based therapies. In this study we examined whether prednisone increased α7β1 integrin levels in mdx mouse and GRMD dog models and myogenic cells from humans with DMD. Our results show that prednisone promotes an increase in α7 integrin protein in cultured myogenic cells and in the muscle of mdx and GRMD animal models of DMD. The prednisone-mediated increase in α7 integrin was associated with increased laminin-α2 in prednisone-treated dystrophin-deficient muscle. Together, our results suggest that prednisone acts in part through increased merosin in the muscle basal lamina and through sarcolemmal stabilization of α7β1 integrin in dystrophin-deficient muscle. These results indicate that therapies that target an increase in muscle α7β1 integrin, its signaling pathways and/or laminin could be therapeutic in DMD.

  2. Sparing Healthy Tissue and Increasing Tumor Dose Using Bayesian Modeling of Geometric Uncertainties for Planning Target Volume Personalization

    International Nuclear Information System (INIS)

    Herschtal, Alan; Te Marvelde, Luc; Mengersen, Kerrie; Foroudi, Farshad; Eade, Thomas; Pham, Daniel; Caine, Hannah; Kron, Tomas

    2015-01-01

    Objective: To develop a mathematical tool that can update a patient's planning target volume (PTV) partway through a course of radiation therapy to more precisely target the tumor for the remainder of treatment and reduce dose to surrounding healthy tissue. Methods and Materials: Daily on-board imaging was used to collect large datasets of displacements for patients undergoing external beam radiation therapy for solid tumors. Bayesian statistical modeling of these geometric uncertainties was used to optimally trade off between displacement data collected from previously treated patients and the progressively accumulating data from a patient currently partway through treatment, to optimally predict future displacements for that patient. These predictions were used to update the PTV position and margin width for the remainder of treatment, such that the clinical target volume (CTV) was more precisely targeted. Results: Software simulation of dose to CTV and normal tissue for 2 real prostate displacement datasets consisting of 146 and 290 patients treated with a minimum of 30 fractions each showed that re-evaluating the PTV position and margin width after 8 treatment fractions reduced healthy tissue dose by 19% and 17%, respectively, while maintaining CTV dose. Conclusion: Incorporating patient-specific displacement patterns from early in a course of treatment allows PTV adaptation for the remainder of treatment. This substantially reduces the dose to healthy tissues and thus can reduce radiation therapy–induced toxicities, improving patient outcomes

  3. Sparing Healthy Tissue and Increasing Tumor Dose Using Bayesian Modeling of Geometric Uncertainties for Planning Target Volume Personalization

    Energy Technology Data Exchange (ETDEWEB)

    Herschtal, Alan, E-mail: Alan.Herschtal@petermac.org [Department of Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne (Australia); Faculty of Health, Arts and Design, Swinburne University of Technology, Melbourne (Australia); Te Marvelde, Luc [Department of Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne (Australia); Mengersen, Kerrie [School of Mathematical Sciences, Science and Engineering Faculty, Queensland University of Technology, Brisbane (Australia); Foroudi, Farshad [Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne (Australia); The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne (Australia); Eade, Thomas [Northern Sydney Cancer Centre, Radiation Oncology Department, Royal North Shore Hospital, St. Leonards, Sydney (Australia); Northern Clinical School, University of Sydney (Australia); Pham, Daniel [Department of Radiation Therapy, Peter MacCallum Cancer Centre, Melbourne (Australia); Caine, Hannah [Northern Sydney Cancer Centre, Radiation Oncology Department, Royal North Shore Hospital, St. Leonards, Sydney (Australia); Kron, Tomas [The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne (Australia); Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne (Australia)

    2015-06-01

    Objective: To develop a mathematical tool that can update a patient's planning target volume (PTV) partway through a course of radiation therapy to more precisely target the tumor for the remainder of treatment and reduce dose to surrounding healthy tissue. Methods and Materials: Daily on-board imaging was used to collect large datasets of displacements for patients undergoing external beam radiation therapy for solid tumors. Bayesian statistical modeling of these geometric uncertainties was used to optimally trade off between displacement data collected from previously treated patients and the progressively accumulating data from a patient currently partway through treatment, to optimally predict future displacements for that patient. These predictions were used to update the PTV position and margin width for the remainder of treatment, such that the clinical target volume (CTV) was more precisely targeted. Results: Software simulation of dose to CTV and normal tissue for 2 real prostate displacement datasets consisting of 146 and 290 patients treated with a minimum of 30 fractions each showed that re-evaluating the PTV position and margin width after 8 treatment fractions reduced healthy tissue dose by 19% and 17%, respectively, while maintaining CTV dose. Conclusion: Incorporating patient-specific displacement patterns from early in a course of treatment allows PTV adaptation for the remainder of treatment. This substantially reduces the dose to healthy tissues and thus can reduce radiation therapy–induced toxicities, improving patient outcomes.

  4. Increasing safety of a robotic system for inner ear surgery using probabilistic error modeling near vital anatomy

    Science.gov (United States)

    Dillon, Neal P.; Siebold, Michael A.; Mitchell, Jason E.; Blachon, Gregoire S.; Balachandran, Ramya; Fitzpatrick, J. Michael; Webster, Robert J.

    2016-03-01

    Safe and effective planning for robotic surgery that involves cutting or ablation of tissue must consider all potential sources of error when determining how close the tool may come to vital anatomy. A pre-operative plan that does not adequately consider potential deviations from ideal system behavior may lead to patient injury. Conversely, a plan that is overly conservative may result in ineffective or incomplete performance of the task. Thus, enforcing simple, uniform-thickness safety margins around vital anatomy is insufficient in the presence of spatially varying, anisotropic error. Prior work has used registration error to determine a variable-thickness safety margin around vital structures that must be approached during mastoidectomy but ultimately preserved. In this paper, these methods are extended to incorporate image distortion and physical robot errors, including kinematic errors and deflections of the robot. These additional sources of error are discussed and stochastic models for a bone-attached robot for otologic surgery are developed. An algorithm for generating appropriate safety margins based on a desired probability of preserving the underlying anatomical structure is presented. Simulations are performed on a CT scan of a cadaver head and safety margins are calculated around several critical structures for planning of a robotic mastoidectomy.

  5. Effects of a peer modelling and rewards-based intervention to increase fruit and vegetable consumption in children.

    Science.gov (United States)

    Lowe, C F; Horne, P J; Tapper, K; Bowdery, M; Egerton, C

    2004-03-01

    To measure children's consumption of, and liking for, fruit and vegetables and how these are altered by a peer modelling and rewards-based intervention. In this initial evaluation of the programme, children's consumption of fruit and vegetables were compared within and across baseline and intervention phases. Three primary schools in England and Wales. In total, 402 children, aged from 4 to 11 y. Over 16 days, children watched six video adventures featuring heroic peers (the Food Dudes) who enjoy eating fruit and vegetables, and received small rewards for eating these foods themselves. Fruit and vegetable consumption was measured (i) in school at lunchtime and snacktime using a five-point observation scale, with inter-rated reliability and weighed validation tests; and (ii) at home using parental recall. A questionnaire measured children's liking for fruit and vegetables before and after the intervention. Consumption during the intervention was significantly higher than during baseline at lunchtime and at snacktime (PASDA, Co-operative Group, Safeway, Sainsbury, Somerfield, Tesco and Birds Eye Wall's.

  6. In vitro comparison in a manikin model: increasing apical enlargement with K3 and K3XF rotary instruments.

    Science.gov (United States)

    Olivieri, Juan Gonzalo; Stöber, Eva; García Font, Marc; González, Jose Antonio; Bragado, Pablo; Roig, Miguel; Duran-Sindreu, Fernando

    2014-09-01

    The aim of the study was to compare the K3 and K3XF systems (SybronEndo, Glendora, CA) after 1 and 2 uses by evaluating apical transportation, working length loss, and working time in a manikin model. Mesial canals of 40 extracted first mandibular molars were instrumented. Radiographs taken after instrumentation with #25, #30, #35, and #40 files were superimposed on the preoperative image in both mesiodistal and buccolingual angulations. AutoCAD (Autodesk Inc, San Rafael, CA) was used to measure working length loss and apical transportation at 0, 0.5, and 1 mm from the working length (WL). The working time was measured. Group comparison was analyzed using post hoc Tukey honestly significant difference tests (P < .05). No significant differences were found in apical transportation, working length loss between K3 and K3XF systems, or between the number of uses. Significant differences were found when canal enlargement was performed to a #35-40 (P < .05). K3 instrumentation performed significantly faster (29.6 ± 15.4) than with the K3XF system (40.2 ± 17.7) (P < .05). No differences were observed in working time when comparing the number of uses. K3 and R-phase K3XF rotary systems shaped curved root canals safely with minimal apical transportation, even up to a 40/04 file. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  7. A mouse anti-myostatin antibody increases muscle mass and improves muscle strength and contractility in the mdx mouse model of Duchenne muscular dystrophy and its humanized equivalent, domagrozumab (PF-06252616), increases muscle volume in cynomolgus monkeys.

    Science.gov (United States)

    St Andre, Michael; Johnson, Mark; Bansal, Prashant N; Wellen, Jeremy; Robertson, Andrew; Opsahl, Alan; Burch, Peter M; Bialek, Peter; Morris, Carl; Owens, Jane

    2017-11-09

    The treatments currently approved for Duchenne muscular dystrophy (DMD), a progressive skeletal muscle wasting disease, address the needs of only a small proportion of patients resulting in an urgent need for therapies that benefit all patients regardless of the underlying mutation. Myostatin is a member of the transforming growth factor-β (TGF-β) family of ligands and is a negative regulator of skeletal muscle mass. Loss of myostatin has been shown to increase muscle mass and improve muscle function in both normal and dystrophic mice. Therefore, myostatin blockade via a specific antibody could ameliorate the muscle weakness in DMD patients by increasing skeletal muscle mass and function, thereby reducing patients' functional decline. A murine anti-myostatin antibody, mRK35, and its humanized analog, domagrozumab, were developed and their ability to inhibit several TGB-β ligands was measured using a cell-based Smad-activity reporter system. Normal and mdx mice were treated with mRK35 to examine the antibody's effect on body weight, lean mass, muscle weights, grip strength, ex vivo force production, and fiber size. The humanized analog (domagrozumab) was tested in non-human primates (NHPs) for changes in skeletal muscle mass and volume as well as target engagement via modulation of circulating myostatin. Both the murine and human antibodies are specific and potent inhibitors of myostatin and GDF11. mRK35 is able to increase body weight, lean mass, and muscle weights in normal mice. In mdx mice, mRK35 significantly increased body weight, muscle weights, grip strength, and ex vivo force production in the extensor digitorum longus (EDL) muscle. Further, tibialis anterior (TA) fiber size was significantly increased. NHPs treated with domagrozumab demonstrated a dose-dependent increase in lean mass and muscle volume and exhibited increased circulating levels of myostatin demonstrating target engagement. We demonstrated that the potent anti-myostatin antibody mRK35 and

  8. INFLAMMATION IS INCREASED WITH ANXIETY- AND DEPRESSION-LIKE SIGNS IN A RAT MODEL OF SPINAL CORD INJURY

    Science.gov (United States)

    Maldonado-Bouchard, Sioui; Peters, Kelsey; Woller, Sarah A.; Madahian, Behrouz; Faghihi, Usef; Patel, Shivani; Bake, Shameena; Hook, Michelle A

    2015-01-01

    Spinal cord injury (SCI) leads to increased anxiety and depression in as many as 60% of patients. Yet, despite extensive clinical research focused on understanding the variables influencing psychological well-being following SCI, risk factors that decrease it remain unclear. We hypothesized that excitation of the immune system, inherent to SCI, may contribute to the decrease in psychological well-being. To test this hypothesis, we used a battery of established behavioral tests to assess depression and anxiety in spinally contused rats. The behavioral tests, and subsequent statistical analyses, revealed three cohorts of subjects that displayed behavioral characteristics of 1) depression, 2) depression and anxiety, or 3) no signs of decreased psychological well-being. Subsequent molecular analyses demonstrated that the psychological cohorts differed not only in behavioral symptoms, but also in peripheral (serum) and central (hippocampi and spinal cord) levels of pro-inflammatory cytokines. Subjects exhibiting a purely depression-like profile showed higher levels of pro-inflammatory cytokines peripherally, whereas subjects exhibiting a depression- and anxiety-like profile showed higher levels of pro-inflammatory cytokines centrally (hippocampi and spinal cord). These changes in inflammation were not associated with injury severity; suggesting that the association between inflammation and the expression of behaviors characteristic of decreased psychological well-being was not confounded by differential impairments in motor ability. These data support the hypothesis that inflammatory changes are associated with decreased psychological well-being following SCI. PMID:26296565

  9. Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

    Science.gov (United States)

    Argibay, Bárbara; Trekker, Jesse; Himmelreich, Uwe; Beiras, Andrés; Topete, Antonio; Taboada, Pablo; Pérez-Mato, María; Vieites-Prado, Alba; Iglesias-Rey, Ramón; Rivas, José; Planas, Anna M.; Sobrino, Tomás; Castillo, José; Campos, Francisco

    2017-01-01

    Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.

  10. Ventricular, but not atrial, M2-muscarinic receptors increase in the canine pacing-overdrive model of heart failure.

    Science.gov (United States)

    Wilkinson, M; Giles, A; Armour, J A; Cardinal, R

    1996-01-01

    To investigate the effects of heart failure induced by chronic rapid ventricular pacing (six weeks) on canine atrial and ventricular muscarinic receptors. Dogs (n = 4) were fitted with a bipolar pacing electrode connected to a Medtronic pacemaker set at 240 stimuli/min. Pacing was maintained for six weeks. Tissue samples obtained from the left atrium and ventral wall of the left ventricle were frozen at -70 degrees C. Control tissue was obtained from normal dogs (n = 6) following anesthesia and thoracotomy. M2-muscarinic receptors were characterized and quantified in tissue micropunches using the hydrophilic ligand [3H] N-methyl-scopolamine (NMS). Cardiac tissue bound [3H] NMS with the specificity of an M2 subtype. Tachycardia-induced heart failure did not affect atrial muscarinic receptors but signify left ventricular myocytes (control 160.0 +/- 10.0 fmol/mg protein versus heart failure 245.0 +/- 25.0 fmol/mg protein; P failure was accompanied by an increase (+ 53%) in ventricular, but not atrial, M2 receptors compared with normal dogs.

  11. A Model For Teaching Advanced Neuroscience Methods: A Student-Run Seminar to Increase Practical Understanding and Confidence.

    Science.gov (United States)

    Harrison, Theresa M; Ching, Christopher R K; Andrews, Anne M

    2016-01-01

    Neuroscience doctoral students must master specific laboratory techniques and approaches to complete their thesis work (hands-on learning). Due to the highly interdisciplinary nature of the field, learning about a diverse range of methodologies through literature surveys and coursework is also necessary for student success (hands-off learning). Traditional neuroscience coursework stresses what is known about the nervous system with relatively little emphasis on the details of the methods used to obtain this knowledge. Furthermore, hands-off learning is made difficult by a lack of detail in methods sections of primary articles, subfield-specific jargon and vague experimental rationales. We designed a student-taught course to enable first-year neuroscience doctoral students to overcome difficulties in hands-off learning by introducing a new approach to reading and presenting primary research articles that focuses on methodology. In our literature-based course students were encouraged to present a method with which they had no previous experience. To facilitate weekly discussions, "experts" were invited to class sessions. Experts were advanced graduate students who had hands-on experience with the method being covered and served as discussion co-leaders. Self-evaluation worksheets were administered on the first and last days of the 10-week course and used to assess students' confidence in discussing research and methods outside of their primary research expertise. These evaluations revealed that the course significantly increased the students' confidence in reading, presenting and discussing a wide range of advanced neuroscience methods.

  12. Mild hypothermia increases pulmonary anti-inflammatory response during protective mechanical ventilation in a piglet model of acute lung injury.

    Science.gov (United States)

    Cruces, Pablo; Erranz, Benjamín; Donoso, Alejandro; Carvajal, Cristóbal; Salomón, Tatiana; Torres, María Fernanda; Díaz, Franco

    2013-11-01

    The effects of mild hypothermia (HT) on acute lung injury (ALI) are unknown in species with metabolic rate similar to that of humans, receiving protective mechanical ventilation (MV). We hypothesized that mild hypothermia would attenuate pulmonary and systemic inflammatory responses in piglets with ALI managed with a protective MV. Acute lung injury (ALI) was induced with surfactant deactivation in 38 piglets. The animals were then ventilated with low tidal volume, moderate positive end-expiratory pressure (PEEP), and permissive hypercapnia throughout the experiment. Subjects were randomized to HT (33.5°C) or normothermia (37°C) groups over 4 h. Plasma and tissue cytokines, tissue apoptosis, lung mechanics, pulmonary vascular permeability, hemodynamic, and coagulation were evaluated. Lung interleukin-10 concentrations were higher in subjects that underwent HT after ALI induction than in those that maintained normothermia. No difference was found in other systemic and tissue cytokines. HT did not induce lung or kidney tissue apoptosis or influence lung mechanics or markers of pulmonary vascular permeability. Heart rate, cardiac output, oxygen uptake, and delivery were significantly lower in subjects that underwent HT, but no difference in arterial lactat