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Sample records for ptbi model increased

  1. Early and sustained increase in the expression of hippocampal IGF-1, but not EPO, in a developmental rodent model of traumatic brain injury.

    Science.gov (United States)

    Schober, Michelle E; Block, Benjamin; Beachy, Joanna C; Statler, Kimberly D; Giza, Christopher C; Lane, Robert H

    2010-11-01

    Pediatric traumatic brain injury (pTBI) is the leading cause of traumatic death and disability in children in the United States. Impaired learning and memory in these young survivors imposes a heavy toll on society. In adult TBI (aTBI) models, cognitive outcome improved after administration of erythropoietin (EPO) or insulin-like growth factor-1 (IGF-1). Little is known about the production of these agents in the hippocampus, a brain region critical for learning and memory, after pTBI. Our objective was to describe hippocampal expression of EPO and IGF-1, together with their receptors (EPOR and IGF-1R, respectively), over time after pTBI in 17-day-old rats. We used the controlled cortical impact (CCI) model and measured hippocampal mRNA levels of EPO, IGF-1, EPOR, IGF-1R, and markers of caspase-dependent apoptosis (bcl2, bax, and p53) at post-injury days (PID) 1, 2, 3, 7, and 14. CCI rats performed poorly on Morris water maze testing of spatial working memory, a hippocampally-based cognitive function. Apoptotic markers were present early and persisted for the duration of the study. EPO in our pTBI model increased much later (PID7) than in aTBI models (12 h), while EPOR and IGF-1 increased at PID1 and PID2, respectively, similar to data from aTBI models. Our data indicate that EPO expression showed a delayed upregulation post-pTBI, while EPOR increased early. We speculate that administration of EPO in the first 1-2 days after pTBI would increase hippocampal neuronal survival and function.

  2. Electrocatalytic properties of Pt-Bi electrodes towards the electrooxidation of formic acid

    Directory of Open Access Journals (Sweden)

    Lović Jelena D.

    2013-01-01

    Full Text Available Formic acid oxidation was studied on two Pt-Bi catalysts, Pt2Bi and polycrystalline Pt modified by irreversible adsorbed Bi (Pt/Biirr in order to establish the difference between the effects of Biirr and Bi in alloyed state. The results were compared to pure Pt. It was found that both bimetallic catalysts were more active than Pt with the onset potentials shifted to more negative values and the currents at 0.0 V vs. SCE (under steady state conditions improved up to two order of magnitude. The origin of Pt2Bi high activity and stability is increased selectivity toward formic acid dehydrogenation caused by the ensemble and electronic effect and suppression of Bi leaching from the surface during formic acid oxidation. However, although Pt/Biirr also shows remarkable initial activity compared to pure Pt, dissolution of Bi is not suppressed and the poisoning of the electrode surface induced by dehydration path is observed. Comparison of the initial quasi-steady state and potentiodynamic results obtained for these two Pt-Bi catalysts revealed that the electronic effect, existing only in the alloy, contributes earlier start of the reaction, while the maximum current density is determined by the ensemble effect. [Projekat Ministarstva nauke Republike Srbije, br. H-172060

  3. Synthesis, physical properties, and band structure of the layered bismuthide PtBi2

    Science.gov (United States)

    Xu, C. Q.; Xing, X. Z.; Xu, Xiaofeng; Li, Bin; Chen, B.; Che, L. Q.; Lu, Xin; Dai, Jianhui; Shi, Z. X.

    2016-10-01

    We report details of single-crystal growth of stoichiometric bismuthide PtBi2 whose structure consists of alternate stacking of a Pt layer and Bi bilayer along the c axis. The compound crystallizes in space group P 3 with a hexagonal unit cell of a =b =6.553 Å,c =6.165 Å . Its T -dependent resistivity is typical of a metal whereas a large anisotropy was observed for the in-plane and interplane electrical transport. The magnetization data show opposite sign for fields parallel and perpendicular to the Pt layers, respectively. The magnetic field response of this material shows clearly two types of charge carriers, consistent with the multiple Fermi surfaces revealed in our band structure calculations. The hydrostatic pressure is shown to suppress the resistivity at high T systematically but has little bearing on its low-T transport. Through calorimetric measurements, the density of states at the Fermi level and the Debye temperature are determined to be 0.94 eV-1 per molecule and 145 K, respectively. In addition, the electronic structures and parity analyses are also presented. We find a minimum value of 0.05 eV gap opening at around 2 eV under the Fermi level by invoking spin-orbit interaction. A slab calculation further indicates a surface Dirac cone appearing in the gap of bulk states. We discuss the possibility of PtBi 2 being a candidate for a bulk topological metal, in analogy to the recently proposed topological superconductor β -PdBi2 .

  4. Pt-Bi decorated nanoporous gold for high performance direct glucose fuel cell.

    Science.gov (United States)

    Guo, Hong; Yin, Huiming; Yan, Xiuling; Shi, Shuai; Yu, Qingyang; Cao, Zhen; Li, Jian

    2016-12-14

    Binary PtBi decorated nanoporous gold (NPG-PtBi) electrocatalyst is specially designed and prepared for the anode in direct glucose fuel cells (DGFCs). By using electroless and electrochemical plating methods, a dense Pt layer and scattered Bi particles are sequentially coated on NPG. A simple DGFC with NPG-PtBi as anode and commercial Pt/C as cathode is constructed and operated to study the effect of operating temperatures and concentrations of glucose and NaOH. With an anode noble metal loading of only 0.45 mg cm(-2) (Au 0.3 mg and Pt 0.15 mg), an open circuit voltage (OCV) of 0.9 V is obtained with a maximum power density of 8 mW cm(-2). Furthermore, the maximum gravimetric power density of NPG-PtBi is 18 mW mg(-1), about 4.5 times higher than that of commercial Pt/C.

  5. Pt-Bi decorated nanoporous gold for high performance direct glucose fuel cell

    Science.gov (United States)

    Guo, Hong; Yin, Huiming; Yan, Xiuling; Shi, Shuai; Yu, Qingyang; Cao, Zhen; Li, Jian

    2016-12-01

    Binary PtBi decorated nanoporous gold (NPG-PtBi) electrocatalyst is specially designed and prepared for the anode in direct glucose fuel cells (DGFCs). By using electroless and electrochemical plating methods, a dense Pt layer and scattered Bi particles are sequentially coated on NPG. A simple DGFC with NPG-PtBi as anode and commercial Pt/C as cathode is constructed and operated to study the effect of operating temperatures and concentrations of glucose and NaOH. With an anode noble metal loading of only 0.45 mg cm-2 (Au 0.3 mg and Pt 0.15 mg), an open circuit voltage (OCV) of 0.9 V is obtained with a maximum power density of 8 mW cm-2. Furthermore, the maximum gravimetric power density of NPG-PtBi is 18 mW mg-1, about 4.5 times higher than that of commercial Pt/C.

  6. 电沉积铂铋纳米颗粒在甲酸电化学氧化中的催化性能%Electrodeposited PtBi Nanoparticles for Electrocatalytic Oxidation of Formic Acid

    Institute of Scientific and Technical Information of China (English)

    李甜; 杨民力

    2012-01-01

    In the studies of direct formic acid fuel cells, the choice, preparation and performance of catalysts are still at the central position. PtBi alloy was used as the catalyst for formic acid electrooxidation and showed good performance. However, neither physical melting nor chemical reduction was convenient to fabrication and electrochemical characterization because of their fussy and time-consuming operations. It was necessary to explore new and simple preparation methods. In the present work, well-distributed spherical PtBi nanoparticles were deposited on glassy carbon surface by a potentiostatic technique. The average size of PtBi nanoparticles was (63 ± 20 ) nm in diameter. The atomic ratio of Pt to Bi (1.18) was close to the molar ratio of [ PtCl6]2- to Bi3+ ions in electrolyte (1.11). These results proved that potentiostatic electrodeposition could act as a simple and effective method to produce spherical PtBi nanoparticles with uniform size and preset chemical composition. Their catalytic performances toward formic acid electrooxidation were studied with cyclic voltammetry and chronoamperometry. The experimental results showed that, in 0.5 mol·L-1 H2SO4 solution, the onset potential for formic acid electrooxidation at PtBi nanoparticles was more negative than that at PtRu nanoparticles by at least 200 mV. In 1. 0 mol·L-1 NaOH solution, the difference between the onset potentials for formic acid electrooxidation at PtBi nanoparticles and at PtRu nanoparticles was about 400 mV. Besides, either in acid media or in alkaline media, the formic acid electrooxidation had higher current on PtBi nanoparticles than on PtRu nanoparticles. All these results displayed that PtBi nanoparticles had better catalytic activities toward formic acid electrooxidation than PtRu nanoparticles.%在直接甲酸燃料电池的研究中,催化剂的选择、制备和性能研究依然是探索的重点.虽然PtBi合金已被报道用于甲酸的电化学催化氧化且具有良好的

  7. DUAL RANDOM MODEL OF INCREASING ANNUITY

    Institute of Scientific and Technical Information of China (English)

    HeWenjiong; ZhangYi

    2001-01-01

    The dual random models about the life insurance and social pension insurance have received considerable attention in the recent articles on actuarial theory and applications. This paper discusses a general kind of increasing annuity based on its force of interest accumulationfunction as a general random process. The dual random model of the present value of the benefits of the increasing annuity has been set, and their moments have been calculated under certainconditions.

  8. Increasing the discrimination of SAR recognition models

    Science.gov (United States)

    Bhanu, Bir; Jones, Grinnell, III

    2001-08-01

    The focus of this paper is optimizing recognition models for Synthetic Aperture Radar signatures of vehicles to improve the performance of a recognition algorithm under the extended operating conditions of target articulation, occlusion and configuration variants. The recognition models are based on quasi-invariant local features, scattering center locations and magnitudes. The approach determines the similarities and differences among the various vehicle models. Methods to penalize similar features or reward dissimilar features are used to increase the distinguishability of the recognition model instances. Extensive experimental recognition results are presented in terms of confusion matrices and receiver operating characteristic curves to show the improvements in recognition performance for MSTAR vehicle targets with articulation, configuration variants and occlusion.

  9. 常压下Pt-Bi双金属催化剂上甘油选择性氧化%Glycerol Oxidation with Oxygen over Bimetallic Pt-Bi Catalysts under Atmospheric Pressure

    Institute of Scientific and Technical Information of China (English)

    梁丹; 崔世玉; 高静; 王军华; 陈平; 侯昭胤

    2011-01-01

    制备了一系列活性碳(AC)负载的Pt-Bi双金属催化剂,考察了催化剂中Bi含量对其催化甘油选择性氧化反应性能的影响.结果表明,适量Bi的添加可以改善催化剂中Pt的氧化还原性能,从而有利于催化剂活性的提高和二羟基丙酮(DIHA)产物的生成.当Bi的含量为5%时,该催化剂的活性最高,甘油转化率和DIHA选择性分别达到91.5%和49.0%.表征结果显示,Pt-Bi颗粒的平均粒径为3.8 nm,且高度分散在催化剂表面,这是该催化剂具有较高活性的主要原因.%A series of bimetallic Pt-Bi catalysts with a constant platinum content of 5.0 wt% and a varied bismuth content (3.0-7.0 wt%)supported on active carbon were prepared and used for glycerol oxidation with oxygen under atmospheric pressure.The bimetallic Pt-Bi/C was efficient for the selective oxidation of glycerol to dihydroxyacetone (DIHA) and the selectivity for DIHA reached 49.0% at a 91.5%conversion of glycerol over the 5%Pt-5%Bi/C catalyst.X-ray diffraction and transmission electron microscopy analysis revealed that the specially configured Pt-Bi nanoparticles in 5%Pt-5%Bi/C were highly dispersed (3.8 nm) over the active carbon support,which is proposed to contribute to the improved performance.

  10. Systemic change increases model projection uncertainty

    Science.gov (United States)

    Verstegen, Judith; Karssenberg, Derek; van der Hilst, Floor; Faaij, André

    2014-05-01

    the neighbourhood doubled, while the influence of slope and potential yield decreased by 75% and 25% respectively. Allowing these systemic changes to occur in our CA in the future (up to 2022) resulted in an increase in model projection uncertainty by a factor two compared to the assumption of a stationary system. This means that the assumption of a constant model structure is not adequate and largely underestimates uncertainty in the projection. References Verstegen, J.A., Karssenberg, D., van der Hilst, F., Faaij, A.P.C., 2014. Identifying a land use change cellular automaton by Bayesian data assimilation. Environmental Modelling & Software 53, 121-136. Verstegen, J.A., Karssenberg, D., van der Hilst, F., Faaij, A.P.C., 2012. Spatio-Temporal Uncertainty in Spatial Decision Support Systems: a Case Study of Changing Land Availability for Bioenergy Crops in Mozambique. Computers , Environment and Urban Systems 36, 30-42. Wald, A., Wolfowitz, J., 1940. On a test whether two samples are from the same population. The Annals of Mathematical Statistics 11, 147-162.

  11. 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

  12. Systemic change increases model projection uncertainty

    NARCIS (Netherlands)

    Verstegen, Judith; Karssenberg, Derek; van der Hilst, Floortje; Faaij, André

    2014-01-01

    Most spatio-temporal models are based on the assumption that the relationship between system state change and its explanatory processes is stationary. This means that model structure and parameterization are usually kept constant over time, ignoring potential systemic changes in this relationship re

  13. Numerical Modeling of Rotary Kiln Productivity Increase

    OpenAIRE

    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 further modeling work to improve the understanding of the processes taking place within the kiln. The kiln being studied in this work produces calcium aluminate cements (CAC). In a first stage of the pro...

  14. 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 furthe

  15. Increasing pulse wave velocity in a realistic cardiovascular model does not increase pulse pressure with age

    Science.gov (United States)

    Mohiuddin, Mohammad W.; Rihani, Ryan J.; Laine, Glen A.

    2012-01-01

    The mechanism of the well-documented increase in aortic pulse pressure (PP) with age is disputed. Investigators assuming a classical windkessel model believe that increases in PP arise from decreases in total arterial compliance (Ctot) and increases in total peripheral resistance (Rtot) with age. Investigators assuming a more sophisticated pulse transmission model believe PP rises because increases in pulse wave velocity (cph) make the reflected pressure wave arrive earlier, augmenting systolic pressure. It has recently been shown, however, that increases in cph do not have a commensurate effect on the timing of the reflected wave. We therefore used a validated, large-scale, human arterial system model that includes realistic pulse wave transmission to determine whether increases in cph cause increased PP with age. First, we made the realistic arterial system model age dependent by altering cardiac output (CO), Rtot, Ctot, and cph to mimic the reported changes in these parameters from age 30 to 70. Then, cph was theoretically maintained constant, while Ctot, Rtot, and CO were altered. The predicted increase in PP with age was similar to the observed increase in PP. In a complementary approach, Ctot, Rtot, and CO were theoretically maintained constant, and cph was increased. The predicted increase in PP was negligible. We found that increases in cph have a limited effect on the timing of the reflected wave but cause the system to degenerate into a windkessel. Changes in PP can therefore be attributed to a decrease in Ctot. PMID:22561301

  16. The Gradual Increase of Responsibility Model: Coaching for Teacher Change

    Science.gov (United States)

    Collet, Vicki S.

    2012-01-01

    This study examines the gradual increase of responsibility (GIR) model for teacher coaching (Collet, 2008), an adaptation of Pearson and Gallagher's (1983) Gradual Release of Responsibility model. In GIR, instructional coaches model, make recommendations, ask probing questions, affirm teachers' appropriate decisions, and praise in order to provide…

  17. An e-Procurement Model for Logistic Performance Increase

    NARCIS (Netherlands)

    Toma, Cristina; Vasilescu, Bogdan; Popescu, Catalin; Soliman, KS

    2009-01-01

    This paper discusses the suitability of an e-procurement system in increasing logistic performance, given the growth in fast Internet availability,. In consequence, a model is derived and submitted for analysis. The scope of the research is limited at the intermediary goods importing sector for a be

  18. A model of regional economic development with increasing returns

    Institute of Scientific and Technical Information of China (English)

    QIAN Edward Y.; YAO Yao-jun; CHEN Gary

    2007-01-01

    This paper develops mathematically and empirically tractable regional and interregional model of economic development with increasing returns to scale (IRS) under the neoclassical assumptions. A one-sector, two-region model in which one region exhibits IRS is presented and the whole nation presents constant returns to scale. The development of the local IRS economy is shown to be constrained to a "moving equilibrium" path. The preliminary empirical results are sufficiently supportive of the argument to encourage further research along the lines of the model. In particular, the neoclassical model does not predict negative coefficients on the real rental value of capital in regressions explaining population or employment relative to that in the nation.

  19. Modelling the brightness increase signature due to asteroid collisions

    CERN Document Server

    McLoughlin, Ev; McLoughlin, Alan

    2015-01-01

    We have developed a model to predict the post-collision brightness increase of sub-catastrophic collisions between asteroids and to evaluate the likelihood of a survey detecting these events. It is based on the cratering scaling laws of Holsapple and Housen (2007) and models the ejecta expansion following an impact as occurring in discrete shells each with their own velocity. We estimate the magnitude change between a series of target/impactor pairs, assuming it is given by the increase in reflecting surface area within a photometric aperture due to the resulting ejecta. As expected the photometric signal increases with impactor size, but we find also that the photometric signature decreases rapidly as the target asteroid diameter increases, due to gravitational fallback. We have used the model results to make an estimate of the impactor diameter for the (596) Scheila collision of D=49-65m depending on the impactor taxonomy, which is broadly consistent with previous estimates. We varied both the strength regi...

  20. 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.

  1. Increasing Computational Efficiency of Cochlear Models Using Boundary Layers

    Science.gov (United States)

    Alkhairy, Samiya A.; Shera, Christopher A.

    2016-01-01

    Our goal is to develop methods to improve the efficiency of computational models of the cochlea for applications that require the solution accurately only within a basal region of interest, specifically by decreasing the number of spatial sections needed for simulation of the problem with good accuracy. We design algebraic spatial and parametric transformations to computational models of the cochlea. These transformations are applied after the basal region of interest and allow for spatial preservation, driven by the natural characteristics of approximate spatial causality of cochlear models. The project is of foundational nature and hence the goal is to design, characterize and develop an understanding and framework rather than optimization and globalization. Our scope is as follows: designing the transformations; understanding the mechanisms by which computational load is decreased for each transformation; development of performance criteria; characterization of the results of applying each transformation to a specific physical model and discretization and solution schemes. In this manuscript, we introduce one of the proposed methods (complex spatial transformation) for a case study physical model that is a linear, passive, transmission line model in which the various abstraction layers (electric parameters, filter parameters, wave parameters) are clearer than other models. This is conducted in the frequency domain for multiple frequencies using a second order finite difference scheme for discretization and direct elimination for solving the discrete system of equations. The performance is evaluated using two developed simulative criteria for each of the transformations. In conclusion, the developed methods serve to increase efficiency of a computational traveling wave cochlear model when spatial preservation can hold, while maintaining good correspondence with the solution of interest and good accuracy, for applications in which the interest is in the solution

  2. Increasing computational efficiency of cochlear models using boundary layers

    Science.gov (United States)

    Alkhairy, Samiya A.; Shera, Christopher A.

    2015-12-01

    Our goal is to develop methods to improve the efficiency of computational models of the cochlea for applications that require the solution accurately only within a basal region of interest, specifically by decreasing the number of spatial sections needed for simulation of the problem with good accuracy. We design algebraic spatial and parametric transformations to computational models of the cochlea. These transformations are applied after the basal region of interest and allow for spatial preservation, driven by the natural characteristics of approximate spatial causality of cochlear models. The project is of foundational nature and hence the goal is to design, characterize and develop an understanding and framework rather than optimization and globalization. Our scope is as follows: designing the transformations; understanding the mechanisms by which computational load is decreased for each transformation; development of performance criteria; characterization of the results of applying each transformation to a specific physical model and discretization and solution schemes. In this manuscript, we introduce one of the proposed methods (complex spatial transformation) for a case study physical model that is a linear, passive, transmission line model in which the various abstraction layers (electric parameters, filter parameters, wave parameters) are clearer than other models. This is conducted in the frequency domain for multiple frequencies using a second order finite difference scheme for discretization and direct elimination for solving the discrete system of equations. The performance is evaluated using two developed simulative criteria for each of the transformations. In conclusion, the developed methods serve to increase efficiency of a computational traveling wave cochlear model when spatial preservation can hold, while maintaining good correspondence with the solution of interest and good accuracy, for applications in which the interest is in the solution

  3. Physics Of Eclipsing Binaries. II. The Increased Model Precision

    CERN Document Server

    Prsa, Andrej; Horvat, Martin; Pablo, Herbert; Kochoska, Angela; Bloemen, Steven; Nemravova, Jana; 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 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. ...

  4. Physics Of Eclipsing Binaries. II. Toward the Increased Model Fidelity

    Science.gov (United States)

    Prša, A.; Conroy, K. E.; Horvat, M.; Pablo, H.; Kochoska, A.; Bloemen, S.; Giammarco, J.; Hambleton, K. M.; Degroote, P.

    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.

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

    Science.gov (United States)

    Selten, Martijn M; Meyer, Francisca; Ba, Wei; Vallès, Astrid; Maas, Dorien A; Negwer, Moritz; Eijsink, Vivian D; van Vugt, Ruben W M; van Hulten, Josephus A; van Bakel, Nick H M; Roosen, Joey; van der Linden, Robert J; Schubert, Dirk; Verheij, Michel M M; Kasri, Nael Nadif; Martens, Gerard J M

    2016-09-30

    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 animal model displaying schizophrenia-relevant features, the apomorphine-susceptible (APO-SUS) rat and its phenotypic counterpart, the apomorphine-unsusceptible (APO-UNSUS) rat at postnatal day 20-22. We found changes in the expression of the GABA-synthesizing enzyme GAD67 specifically in the prelimbic- but not the infralimbic region of the medial prefrontal cortex (mPFC), indicative of reduced inhibitory function in this region in APO-SUS rats. While we did not observe changes in basal synaptic transmission onto LII/III pyramidal cells in the mPFC of APO-SUS compared to APO-UNSUS rats, we report reduced paired-pulse ratios at longer inter-stimulus intervals. The GABAB receptor antagonist CGP 55845 abolished this reduction, indicating that the decreased paired-pulse ratio was caused by increased GABAB signaling. Consistently, we find an increased expression of the GABAB1 receptor subunit in APO-SUS rats. Our data provide physiological evidence for increased presynaptic GABAB signaling in the mPFC of APO-SUS rats, further supporting an important role for the GABAergic system in the pathophysiology of schizophrenia.

  6. 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

  7. 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.

  8. Complementary Gompertz survival models: decreasing alive versus increasing dead.

    Science.gov (United States)

    Easton, Dexter M

    2009-05-01

    The survival patterns of many animals can be classified into one of two asymmetric sigmoid forms: One group can be predicted from the standard, classical Gompertz assumption that, with age, the number of individuals alive in the population decreases exponentially at an exponentially increasing rate. The other can be predicted from the alternative Gompertz assumption that, with age, the number of individuals that have died increases exponentially at an exponentially decreasing rate. The two models have similar mathematical forms, but the curves are not the same. In contrast to the standard, the alternative form has an early rapid fall and terminates in a gradual decay of the number of live individuals. It fits "non-Gompertzian" survival plots that are not predicted by the number-alive assumption. Analyses of published data show one or the other survival mode in various animal populations, depending on sex, genetic strain, nutrition, or activity.

  9. 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.

  10. Increased levels of inosine in a mouse model of inflammation

    Science.gov (United States)

    Prestwich, Erin G; Mangerich, Aswin; Pang, Bo; McFaline, Jose L; Lonkar, Pallavi; Sullivan, Matthew R; Trudel, Laura J; Taghizedeh, Koli; Dedon, Peter C

    2013-01-01

    One possible mechanism linking inflammation with cancer involves the generation of reactive oxygen, nitrogen and halogen species by activated macrophages and neutrophils infiltrating sites of infection or tissue damage, with these chemical mediators causing damage that ultimately leads to cell death and mutation. To determine the most biologically deleterious chemistries of inflammation, we previously assessed products across the spectrum of DNA damage arising in inflamed tissues in the SJL mouse model nitric oxide over-production (Pang et al., Carcinogenesis 28: 1807–1813, 2007). Among the anticipated DNA damage chemistries, we observed significant changes only in lipid peroxidation-derived etheno adducts. We have now developed an isotope-dilution, liquid chromatography-coupled, tandem quadrupole mass spectrometric method to quantify representative species across the spectrum of RNA damage products predicted to arise at sites of inflammation, including nucleobase deamination (xanthosine, inosine), oxidation (8-oxoguanosine), and alkylation (1,N6-etheno-adenosine). Application of the method to liver, spleen, and kidney from the SJL mouse model revealed generally higher levels of oxidative background RNA damage than was observed in DNA in control mice. However, compared to control mice, RcsX treatment to induce nitric oxide overproduction resulted in significant increases only in inosine and only in the spleen. Further, the nitric oxide synthase inhibitor, N-methylarginine, did not significantly affect the levels of inosine in control and RcsX-treated mice. The differences between DNA and RNA damage in the same animal model of inflammation point to possible influences from DNA repair, RcsX-induced alterations in adenosine deaminase activity, and differential accessibility of DNA and RNA to reactive oxygen and nitrogen species as determinants of nucleic acid damage during inflammation. PMID:23506120

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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 ra...

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

    NARCIS (Netherlands)

    Selten, M.M.; Ba, W.; Valles, A.; Maas, D.A.; Negwer, M.; Eijsink, V.D.; Vugt, R.W. van; Hulten, J.A; Bakel, N.H. 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

  18. Increasing security through public health: a practical model.

    Science.gov (United States)

    Parker, R David

    2011-01-01

    As political and social changes sweep the globe, there are opportunities to increase national security through innovative approaches. While traditional security methods such as defense forces and homeland security provide both pre-emptive and defensive protection, new methods could meet emerging challenges by responding to the political, financial, and social trends. One method is the integration of defense, medicine and public health. By assisting a nation by providing basic services, such as healthcare, collaborative efforts can increase stabilization in areas of unrest. Improved health outcomes leads to increased domestic security, which can create a ripple effect across a region. Assessment, uptake and sustainability by the host nation are critical for program success. The proposed methodology focuses on the use of primarily extant resources, such as programs used by Special Operations Forces and other health and defense programs. Additional components include evaluation, set objectives and mission collaborations. As the nexus between foreign affairs, security, and public health is increasingly validated through research and practice, standardized interventions should be developed to minimize overlapping expenditures, promote security and strengthen international relations.

  19. 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…

  20. Building a Business Model to Increase Funding for Karlskrona Makerspace

    OpenAIRE

    2016-01-01

    The past decade spotlighted a trend, which is that of individual users taking the role of innovators and physically creating their own products by explooting model additive manufacturing techniques. This trend emphasized the need for facilities able to serve as a platform for passionate makers to share knowledge, meet others and provides opportunities to realize their ideas. One of these platforms is Karlskrona Makerspace (KMS). KMS is located at Blekinge Institute of Technology (BTH) and pro...

  1. Using Target Network Modelling to Increase Battlespace Agility

    Science.gov (United States)

    2013-06-01

    network model breakdown of specific elements of the Master TNM. For example if there are two insurgent clans visualised on a master TNM, two...secondary TNMs representing the two clans, could be visualised , produced, and populated. Helmand Case Study The following TNM approach was applied...02-01, “Predictive Battlespace Understandingto Improve Military Effectiveness, Air Force Scientific Advisory Board, August, 2002. Royal Danish

  2. Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores.

    Science.gov (United States)

    Vilhjálmsson, Bjarni J; Yang, Jian; Finucane, Hilary K; Gusev, Alexander; Lindström, Sara; Ripke, Stephan; Genovese, Giulio; Loh, Po-Ru; Bhatia, Gaurav; Do, Ron; Hayeck, Tristan; Won, Hong-Hee; Kathiresan, Sekar; Pato, Michele; Pato, Carlos; Tamimi, Rulla; Stahl, Eli; Zaitlen, Noah; Pasaniuc, Bogdan; Belbin, Gillian; Kenny, Eimear E; Schierup, Mikkel H; De Jager, Philip; Patsopoulos, Nikolaos A; McCarroll, Steve; Daly, Mark; Purcell, Shaun; Chasman, Daniel; Neale, Benjamin; Goddard, Michael; Visscher, Peter M; Kraft, Peter; Patterson, Nick; Price, Alkes L

    2015-10-01

    Polygenic risk scores have shown great promise in predicting complex disease risk and will become more accurate as training sample sizes increase. The standard approach for calculating risk scores involves linkage disequilibrium (LD)-based marker pruning and applying a p value threshold to association statistics, but this discards information and can reduce predictive accuracy. We introduce LDpred, a method that infers the posterior mean effect size of each marker by using a prior on effect sizes and LD information from an external reference panel. Theory and simulations show that LDpred outperforms the approach of pruning followed by thresholding, particularly at large sample sizes. Accordingly, predicted R(2) increased from 20.1% to 25.3% in a large schizophrenia dataset and from 9.8% to 12.0% in a large multiple sclerosis dataset. A similar relative improvement in accuracy was observed for three additional large disease datasets and for non-European schizophrenia samples. The advantage of LDpred over existing methods will grow as sample sizes increase. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  3. Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores

    Science.gov (United States)

    Vilhjálmsson, Bjarni J.; Yang, Jian; Finucane, Hilary K.; Gusev, Alexander; Lindström, Sara; Ripke, Stephan; Genovese, Giulio; Loh, Po-Ru; Bhatia, Gaurav; Do, Ron; Hayeck, Tristan; Won, Hong-Hee; Ripke, Stephan; Neale, Benjamin M.; Corvin, Aiden; Walters, James T.R.; Farh, Kai-How; Holmans, Peter A.; Lee, Phil; Bulik-Sullivan, Brendan; Collier, David A.; Huang, Hailiang; Pers, Tune H.; Agartz, Ingrid; Agerbo, Esben; Albus, Margot; Alexander, Madeline; Amin, Farooq; Bacanu, Silviu A.; Begemann, Martin; Belliveau, Richard A.; Bene, Judit; Bergen, Sarah E.; Bevilacqua, Elizabeth; Bigdeli, Tim B.; Black, Donald W.; Bruggeman, Richard; Buccola, Nancy G.; Buckner, Randy L.; Byerley, William; Cahn, Wiepke; Cai, Guiqing; Campion, Dominique; Cantor, Rita M.; Carr, Vaughan J.; Carrera, Noa; Catts, Stanley V.; Chambert, Kimberly D.; Chan, Raymond C.K.; Chen, Ronald Y.L.; Chen, Eric Y.H.; Cheng, Wei; Cheung, Eric F.C.; Chong, Siow Ann; Cloninger, C. Robert; Cohen, David; Cohen, Nadine; Cormican, Paul; Craddock, Nick; Crowley, James J.; Curtis, David; Davidson, Michael; Davis, Kenneth L.; Degenhardt, Franziska; Del Favero, Jurgen; DeLisi, Lynn E.; Demontis, Ditte; Dikeos, Dimitris; Dinan, Timothy; Djurovic, Srdjan; Donohoe, Gary; Drapeau, Elodie; Duan, Jubao; Dudbridge, Frank; Durmishi, Naser; Eichhammer, Peter; Eriksson, Johan; Escott-Price, Valentina; Essioux, Laurent; Fanous, Ayman H.; Farrell, Martilias S.; Frank, Josef; Franke, Lude; Freedman, Robert; Freimer, Nelson B.; Friedl, Marion; Friedman, Joseph I.; Fromer, Menachem; Genovese, Giulio; Georgieva, Lyudmila; Gershon, Elliot S.; Giegling, Ina; Giusti-Rodrguez, Paola; Godard, Stephanie; Goldstein, Jacqueline I.; Golimbet, Vera; Gopal, Srihari; Gratten, Jacob; Grove, Jakob; de Haan, Lieuwe; Hammer, Christian; Hamshere, Marian L.; Hansen, Mark; Hansen, Thomas; Haroutunian, Vahram; Hartmann, Annette M.; Henskens, Frans A.; Herms, Stefan; Hirschhorn, Joel N.; Hoffmann, Per; Hofman, Andrea; Hollegaard, Mads V.; Hougaard, David M.; Ikeda, Masashi; Joa, Inge; Julia, Antonio; Kahn, Rene S.; Kalaydjieva, Luba; Karachanak-Yankova, Sena; Karjalainen, Juha; Kavanagh, David; Keller, Matthew C.; Kelly, Brian J.; Kennedy, James L.; Khrunin, Andrey; Kim, Yunjung; Klovins, Janis; Knowles, James A.; Konte, Bettina; Kucinskas, Vaidutis; Kucinskiene, Zita Ausrele; Kuzelova-Ptackova, Hana; Kahler, Anna K.; Laurent, Claudine; Keong, Jimmy Lee Chee; Lee, S. Hong; Legge, Sophie E.; Lerer, Bernard; Li, Miaoxin; Li, Tao; Liang, Kung-Yee; Lieberman, Jeffrey; Limborska, Svetlana; Loughland, Carmel M.; Lubinski, Jan; Lnnqvist, Jouko; Macek, Milan; Magnusson, Patrik K.E.; Maher, Brion S.; Maier, Wolfgang; Mallet, Jacques; Marsal, Sara; Mattheisen, Manuel; Mattingsdal, Morten; McCarley, Robert W.; McDonald, Colm; McIntosh, Andrew M.; Meier, Sandra; Meijer, Carin J.; Melegh, Bela; Melle, Ingrid; Mesholam-Gately, Raquelle I.; Metspalu, Andres; Michie, Patricia T.; Milani, Lili; Milanova, Vihra; Mokrab, Younes; Morris, Derek W.; Mors, Ole; Mortensen, Preben B.; Murphy, Kieran C.; Murray, Robin M.; Myin-Germeys, Inez; Mller-Myhsok, Bertram; Nelis, Mari; Nenadic, Igor; Nertney, Deborah A.; Nestadt, Gerald; Nicodemus, Kristin K.; Nikitina-Zake, Liene; Nisenbaum, Laura; Nordin, Annelie; O’Callaghan, Eadbhard; O’Dushlaine, Colm; O’Neill, F. Anthony; Oh, Sang-Yun; Olincy, Ann; Olsen, Line; Van Os, Jim; Pantelis, Christos; Papadimitriou, George N.; Papiol, Sergi; Parkhomenko, Elena; Pato, Michele T.; Paunio, Tiina; Pejovic-Milovancevic, Milica; Perkins, Diana O.; Pietilinen, Olli; Pimm, Jonathan; Pocklington, Andrew J.; Powell, John; Price, Alkes; Pulver, Ann E.; Purcell, Shaun M.; Quested, Digby; Rasmussen, Henrik B.; Reichenberg, Abraham; Reimers, Mark A.; Richards, Alexander L.; Roffman, Joshua L.; Roussos, Panos; Ruderfer, Douglas M.; Salomaa, Veikko; Sanders, Alan R.; Schall, Ulrich; Schubert, Christian R.; Schulze, Thomas G.; Schwab, Sibylle G.; Scolnick, Edward M.; Scott, Rodney J.; Seidman, Larry J.; Shi, Jianxin; Sigurdsson, Engilbert; Silagadze, Teimuraz; Silverman, Jeremy M.; Sim, Kang; Slominsky, Petr; Smoller, Jordan W.; So, Hon-Cheong; Spencer, Chris C.A.; Stahl, Eli A.; Stefansson, Hreinn; Steinberg, Stacy; Stogmann, Elisabeth; Straub, Richard E.; Strengman, Eric; Strohmaier, Jana; Stroup, T. Scott; Subramaniam, Mythily; Suvisaari, Jaana; Svrakic, Dragan M.; Szatkiewicz, Jin P.; Sderman, Erik; Thirumalai, Srinivas; Toncheva, Draga; Tooney, Paul A.; Tosato, Sarah; Veijola, Juha; Waddington, John; Walsh, Dermot; Wang, Dai; Wang, Qiang; Webb, Bradley T.; Weiser, Mark; Wildenauer, Dieter B.; Williams, Nigel M.; Williams, Stephanie; Witt, Stephanie H.; Wolen, Aaron R.; Wong, Emily H.M.; Wormley, Brandon K.; Wu, Jing Qin; Xi, Hualin Simon; Zai, Clement C.; Zheng, Xuebin; Zimprich, Fritz; Wray, Naomi R.; Stefansson, Kari; Visscher, Peter M.; Adolfsson, Rolf; Andreassen, Ole A.; Blackwood, Douglas H.R.; Bramon, Elvira; Buxbaum, Joseph D.; Børglum, Anders D.; Cichon, Sven; Darvasi, Ariel; Domenici, Enrico; Ehrenreich, Hannelore; Esko, Tonu; Gejman, Pablo V.; Gill, Michael; Gurling, Hugh; Hultman, Christina M.; Iwata, Nakao; Jablensky, Assen V.; Jonsson, Erik G.; Kendler, Kenneth S.; Kirov, George; Knight, Jo; Lencz, Todd; Levinson, Douglas F.; Li, Qingqin S.; Liu, Jianjun; Malhotra, Anil K.; McCarroll, Steven A.; McQuillin, Andrew; Moran, Jennifer L.; Mortensen, Preben B.; Mowry, Bryan J.; Nthen, Markus M.; Ophoff, Roel A.; Owen, Michael J.; Palotie, Aarno; Pato, Carlos N.; Petryshen, Tracey L.; Posthuma, Danielle; Rietschel, Marcella; Riley, Brien P.; Rujescu, Dan; Sham, Pak C.; Sklar, Pamela; St. Clair, David; Weinberger, Daniel R.; Wendland, Jens R.; Werge, Thomas; Daly, Mark J.; Sullivan, Patrick F.; O’Donovan, Michael C.; Kraft, Peter; Hunter, David J.; Adank, Muriel; Ahsan, Habibul; Aittomäki, Kristiina; Baglietto, Laura; Berndt, Sonja; Blomquist, Carl; Canzian, Federico; Chang-Claude, Jenny; Chanock, Stephen J.; Crisponi, Laura; Czene, Kamila; Dahmen, Norbert; Silva, Isabel dos Santos; Easton, Douglas; Eliassen, A. Heather; Figueroa, Jonine; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M.; Gibson, Lorna; Haiman, Christopher A.; Hall, Per; Hazra, Aditi; Hein, Rebecca; Henderson, Brian E.; Hofman, Albert; Hopper, John L.; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G.; Lichtner, Peter; Lindström, Sara; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Meijers-Heijboer, Hanne; Müller-Myhsok, Bertram; Muranen, Taru A.; Nevanlinna, Heli; Peeters, Petra H.; Peto, Julian; Prentice, Ross L.; Rahman, Nazneen; Sánchez, María José; Schmidt, Daniel F.; Schmutzler, Rita K.; Southey, Melissa C.; Tamimi, Rulla; Travis, Ruth; Turnbull, Clare; Uitterlinden, Andre G.; van der Luijt, Rob B.; Waisfisz, Quinten; Wang, Zhaoming; Whittemore, Alice S.; Yang, Rose; Zheng, Wei; Kathiresan, Sekar; Pato, Michele; Pato, Carlos; Tamimi, Rulla; Stahl, Eli; Zaitlen, Noah; Pasaniuc, Bogdan; Belbin, Gillian; Kenny, Eimear E.; Schierup, Mikkel H.; De Jager, Philip; Patsopoulos, Nikolaos A.; McCarroll, Steve; Daly, Mark; Purcell, Shaun; Chasman, Daniel; Neale, Benjamin; Goddard, Michael; Visscher, Peter M.; Kraft, Peter; Patterson, Nick; Price, Alkes L.

    2015-01-01

    Polygenic risk scores have shown great promise in predicting complex disease risk and will become more accurate as training sample sizes increase. The standard approach for calculating risk scores involves linkage disequilibrium (LD)-based marker pruning and applying a p value threshold to association statistics, but this discards information and can reduce predictive accuracy. We introduce LDpred, a method that infers the posterior mean effect size of each marker by using a prior on effect sizes and LD information from an external reference panel. Theory and simulations show that LDpred outperforms the approach of pruning followed by thresholding, particularly at large sample sizes. Accordingly, predicted R2 increased from 20.1% to 25.3% in a large schizophrenia dataset and from 9.8% to 12.0% in a large multiple sclerosis dataset. A similar relative improvement in accuracy was observed for three additional large disease datasets and for non-European schizophrenia samples. The advantage of LDpred over existing methods will grow as sample sizes increase. PMID:26430803

  4. 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.

  5. Effectiveness of the famer-to-farmer extension model in increasing ...

    African Journals Online (AJOL)

    Journal Home > Vol 39, No 2 (2011) > ... However, the success of the new model has not been tested or established. ... iii) increased food availability; iv) the multiplier effect in information-sharing; and v) increased sales of commodities.

  6. Plant Growth Modelling and Applications: The Increasing Importance of Plant Architecture in Growth Models

    Science.gov (United States)

    Fourcaud, Thierry; Zhang, Xiaopeng; Stokes, Alexia; Lambers, Hans; Körner, Christian

    2008-01-01

    Background Modelling plant growth allows us to test hypotheses and carry out virtual experiments concerning plant growth processes that could otherwise take years in field conditions. The visualization of growth simulations allows us to see directly and vividly the outcome of a given model and provides us with an instructive tool useful for agronomists and foresters, as well as for teaching. Functional–structural (FS) plant growth models are nowadays particularly important for integrating biological processes with environmental conditions in 3-D virtual plants, and provide the basis for more advanced research in plant sciences. Scope In this viewpoint paper, we ask the following questions. Are we modelling the correct processes that drive plant growth, and is growth driven mostly by sink or source activity? In current models, is the importance of soil resources (nutrients, water, temperature and their interaction with meristematic activity) considered adequately? Do classic models account for architectural adjustment as well as integrating the fundamental principles of development? Whilst answering these questions with the available data in the literature, we put forward the opinion that plant architecture and sink activity must be pushed to the centre of plant growth models. In natural conditions, sinks will more often drive growth than source activity, because sink activity is often controlled by finite soil resources or developmental constraints. PMA06 This viewpoint paper also serves as an introduction to this Special Issue devoted to plant growth modelling, which includes new research covering areas stretching from cell growth to biomechanics. All papers were presented at the Second International Symposium on Plant Growth Modeling, Simulation, Visualization and Applications (PMA06), held in Beijing, China, from 13–17 November, 2006. Although a large number of papers are devoted to FS models of agricultural and forest crop species, physiological and genetic

  7. Increasing secondary and renewable material use: a chance constrained modeling approach to manage feedstock quality variation.

    Science.gov (United States)

    Olivetti, Elsa A; Gaustad, Gabrielle G; Field, Frank R; Kirchain, Randolph E

    2011-05-01

    The increased use of secondary (i.e., recycled) and renewable resources will likely be key toward achieving sustainable materials use. Unfortunately, these strategies share a common barrier to economical implementation - increased quality variation compared to their primary and synthetic counterparts. Current deterministic process-planning models overestimate the economic impact of this increased variation. This paper shows that for a range of industries from biomaterials to inorganics, managing variation through a chance-constrained (CC) model enables increased use of such variable raw materials, or heterogeneous feedstocks (hF), over conventional, deterministic models. An abstract, analytical model and a quantitative model applied to an industrial case of aluminum recycling were used to explore the limits and benefits of the CC formulation. The results indicate that the CC solution can reduce cost and increase potential hF use across a broad range of production conditions through raw materials diversification. These benefits increase where the hFs exhibit mean quality performance close to that of the more homogeneous feedstocks (often the primary and synthetic materials) or have large quality variability. In terms of operational context, the relative performance grows as intolerance for batch error increases and as the opportunity to diversify the raw material portfolio increases.

  8. 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...

  9. Pronounced increase in breathing rate in the "hair dryer model" of experimental febrile seizures.

    Science.gov (United States)

    Schuchmann, Sebastian; Tolner, Else A; Marshall, Pepin; Vanhatalo, Sampsa; Kaila, Kai

    2008-05-01

    In a study using a heated chamber for induction of experimental febrile seizures (eFS) in rat pups, ictal activity was shown to be precipitated by a respiratory alkalosis (Schuchmann et al., 2006). In sharp contrast to this, in a recent review Dubé et al., (2007) suggest that the respiratory alkalosis is model specific, and that no increase in respiratory rate is observed in the widely used "hair dryer model" of eFS. The data in the present work, based on well-established techniques for measuring respiratory rates in rat pups, show a pronounced increase in the "hair dryer model" with values that are slightly higher than those recorded in the heated chamber model. Hence, a temperature-evoked increase in respiration is a common feature of these two models of eFS.

  10. Use of video modeling to increase generalization of social play by children with autism

    OpenAIRE

    Nikopoulos, C K

    2007-01-01

    The use of video modeling to increase generalization of social play skills in children with autism is discussed. The possible reasons that have made this procedure so favorable among researchers and practitioners are explored. Two studies are described in which video modeling increased the generalization of social play in 6 children, and critical features of procedure are emphasized. Suggestions regarding the potential mechanisms responsible for the effectiveness of this procedure are discuss...

  11. 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...

  12. A Model for Planning Career Continuation and Change through Increased Awareness, Knowledge, and Skill.

    Science.gov (United States)

    Pedersen, Paul; And Others

    1991-01-01

    Presents three-stage sequence based on increased awareness of assumptions, knowledge of relevant information, and skill in taking appropriate action as model for outplacement counseling. Rationale, structure, assumptions, principles, and evaluation of outplacement counseling program using this model are discussed. (Author)

  13. A Model for Planning Career Continuation and Change through Increased Awareness, Knowledge, and Skill.

    Science.gov (United States)

    Pedersen, Paul; And Others

    1991-01-01

    Presents three-stage sequence based on increased awareness of assumptions, knowledge of relevant information, and skill in taking appropriate action as model for outplacement counseling. Rationale, structure, assumptions, principles, and evaluation of outplacement counseling program using this model are discussed. (Author)

  14. Characterization of Pt/Bi3.15Nd0.85Ti3O12/HfO2/Si structure using a hafnium oxide as buffer layer for ferroelectric-gate field effect transistors

    Science.gov (United States)

    Xie, Dan; Luo, Yafeng; Han, Xueguang; Ren, Tianling; Liu, Litian

    2009-12-01

    We have investigated the structural and electrical properties of metal-ferroelectric-insulator-semiconductor (MFIS) capacitors with Bi3.15Nd0.85Ti3O12 (BNdT) thin film deposited on Si and hafnium oxide (HfO2)/Si substrates. Microstructural analysis reveals the formation of well-crystallized BNdT perovskite film and good interface between BNdT film and HfO2 buffer layer. Pt/BNdT/HfO2/Si structure exhibits a memory window of 1.12 V at an operation voltage of 3.5 V. The width of memory window for the MFIS structure varies with increasing thickness of HfO2 layer, and 4-nm-thickness is optimum. The results from the fatigue test indicate a slight degradation of the memory window after 1010 switching cycles. These properties are encouraging for the development of ferroelectric memory transistors.

  15. Subcutaneous preconditioning increases invasion and metastatic dissemination in mouse colorectal cancer models

    Directory of Open Access Journals (Sweden)

    Patricia Alamo

    2014-03-01

    Full Text Available Mouse colorectal cancer (CRC models generated by orthotopic microinjection of human CRC cell lines reproduce the pattern of lymphatic, haematological and transcoelomic spread but generate low metastatic efficiency. Our aim was to develop a new strategy that could increase the metastatic efficiency of these models. We used subcutaneous implantation of the human CRC cell lines HCT116 or SW48 prior to their orthotopic microinjection in the cecum of nude mice (SC+ORT. This subcutaneous preconditioning significantly enhanced metastatic dissemination. In the HCT116 model it increased the number and size of metastatic foci in lymph nodes, lung, liver and peritoneum, whereas, in the SW48 model, it induced a shift from non-metastatic to metastatic. In both models the number of apoptotic bodies in the primary tumour in the SC+ORT group was significantly reduced compared with that in the direct orthotopic injection (ORT group. Moreover, in HCT116 tumours the number of keratin-positive tumour buddings and single epithelial cells increased at the invasion front in SC+ORT mice. In the SW48 tumour model, we observed a trend towards a higher number of tumour buds and single cells in the SC+ORT group but this did not reach statistical significance. At a molecular level, the enhanced metastatic efficiency observed in the HCT116 SC+ORT model was associated with an increase in AKT activation, VEGF-A overexpression and downregulation of β1 integrin in primary tumour tissue, whereas, in SW48 SC+ORT mice, the level of expression of these proteins remained unchanged. In summary, subcutaneous preconditioning increased the metastatic dissemination of both orthotopic CRC models by increasing tumour cell survival and invasion at the tumour invasion front. This approach could be useful to simultaneously study the mechanisms of metastases and to evaluate anti-metastatic drugs against CRC.

  16. Subcutaneous preconditioning increases invasion and metastatic dissemination in mouse colorectal cancer models

    Science.gov (United States)

    Alamo, Patricia; Gallardo, Alberto; Pavón, Miguel A.; Casanova, Isolda; Trias, Manuel; Mangues, Maria A.; Vázquez, Esther; Villaverde, Antonio; Mangues, Ramon; Céspedes, Maria V.

    2014-01-01

    Mouse colorectal cancer (CRC) models generated by orthotopic microinjection of human CRC cell lines reproduce the pattern of lymphatic, haematological and transcoelomic spread but generate low metastatic efficiency. Our aim was to develop a new strategy that could increase the metastatic efficiency of these models. We used subcutaneous implantation of the human CRC cell lines HCT116 or SW48 prior to their orthotopic microinjection in the cecum of nude mice (SC+ORT). This subcutaneous preconditioning significantly enhanced metastatic dissemination. In the HCT116 model it increased the number and size of metastatic foci in lymph nodes, lung, liver and peritoneum, whereas, in the SW48 model, it induced a shift from non-metastatic to metastatic. In both models the number of apoptotic bodies in the primary tumour in the SC+ORT group was significantly reduced compared with that in the direct orthotopic injection (ORT) group. Moreover, in HCT116 tumours the number of keratin-positive tumour buddings and single epithelial cells increased at the invasion front in SC+ORT mice. In the SW48 tumour model, we observed a trend towards a higher number of tumour buds and single cells in the SC+ORT group but this did not reach statistical significance. At a molecular level, the enhanced metastatic efficiency observed in the HCT116 SC+ORT model was associated with an increase in AKT activation, VEGF-A overexpression and downregulation of β1 integrin in primary tumour tissue, whereas, in SW48 SC+ORT mice, the level of expression of these proteins remained unchanged. In summary, subcutaneous preconditioning increased the metastatic dissemination of both orthotopic CRC models by increasing tumour cell survival and invasion at the tumour invasion front. This approach could be useful to simultaneously study the mechanisms of metastases and to evaluate anti-metastatic drugs against CRC. PMID:24487410

  17. Methods to Increase the Robustness of Finite-Volume Flow Models in Thermodynamic Systems

    Directory of Open Access Journals (Sweden)

    Sylvain Quoilin

    2014-03-01

    Full Text Available This paper addresses the issues linked to simulation failures during integration in finite-volume flow models, especially those involving a two-phase state. This kind of model is particularly useful when modeling 1D heat exchangers or piping, e.g., in thermodynamic cycles involving a phase change. Issues, such as chattering or stiff systems, can lead to low simulation speed, instabilities and simulation failures. In the particular case of two-phase flow models, they are usually linked to a discontinuity in the density derivative between the liquid and two-phase zones. In this work, several methods to tackle numerical problems are developed, described, implemented and compared. In addition, methods available in the literature are also implemented and compared to the proposed approaches. Results suggest that the robustness of the models can be significantly increased with these different methods, at the price of a small increase of the error in the mass and energy balances.

  18. Precipitation extreme changes exceeding moisture content increases in MIROC and IPCC climate models.

    Science.gov (United States)

    Sugiyama, Masahiro; Shiogama, Hideo; Emori, Seita

    2010-01-12

    Precipitation extreme changes are often assumed to scale with, or are constrained by, the change in atmospheric moisture content. Studies have generally confirmed the scaling based on moisture content for the midlatitudes but identified deviations for the tropics. In fact half of the twelve selected Intergovernmental Panel on Climate Change (IPCC) models exhibit increases faster than the climatological-mean precipitable water change for high percentiles of tropical daily precipitation, albeit with significant intermodel scatter. Decomposition of the precipitation extreme changes reveals that the variations among models can be attributed primarily to the differences in the upward velocity. Both the amplitude and vertical profile of vertical motion are found to affect precipitation extremes. A recently proposed scaling that incorporates these dynamical effects can capture the basic features of precipitation changes in both the tropics and midlatitudes. In particular, the increases in tropical precipitation extremes significantly exceed the precipitable water change in Model for Interdisciplinary Research on Climate (MIROC), a coupled general circulation model with the highest resolution among IPCC climate models whose precipitation characteristics have been shown to reasonably match those of observations. The expected intensification of tropical disturbances points to the possibility of precipitation extreme increases beyond the moisture content increase as is found in MIROC and some of IPCC models.

  19. Consistent increase in Indian monsoon rainfall and its variability across CMIP-5 models

    Directory of Open Access Journals (Sweden)

    A. Menon

    2013-01-01

    Full Text Available The possibility of an impact of global warming on the Indian monsoon is of critical importance for the large population of this region. Future projections within the Coupled Model Intercomparison Project Phase 3 (CMIP-3 showed a wide range of trends with varying magnitude and sign across models. Here the Indian summer monsoon rainfall is evaluated in 20 CMIP-5 models for the period 1850 to 2100. In the new generation of climate models a consistent increase in seasonal mean rainfall during the summer monsoon periods arises. All models simulate stronger seasonal mean rainfall in the future compared to the historic period under the strongest warming scenario RCP-8.5. Increase in seasonal mean rainfall is the largest for the RCP-8.5 scenario compared to other RCPs. The interannual variability of the Indian monsoon rainfall also shows a consistent positive trend under unabated global warming. Since both the long-term increase in monsoon rainfall as well as the increase in interannual variability in the future is robust across a wide range of models, some confidence can be attributed to these projected trends.

  20. Increased congruence does not necessarily indicate increased phylogenetic accuracy--the behavior of the incongruence length difference test in mixed-model analyses.

    Science.gov (United States)

    Dowton, Mark; Austin, Andrew D

    2002-02-01

    Comprehensive phylogenetic analyses utilize data from distinct sources, including nuclear, mitochondrial, and plastid molecular sequences and morphology. Such heterogeneous datasets are likely to require distinct models of analysis, given the different histories of mutational biases operating on these characters. The incongruence length difference (ILD) test is increasingly being used to arbitrate between competing models of phylogenetic analysis in cases where multiple data partitions have been collected. Our work suggests that the ILD test is unlikely to be an effective measure of congruence when two datasets differ markedly in size. We show that models that increase the contribution of one data partition over another are likely to increase congruence, as measured by this test. More alarmingly, for many bipartition comparisons, character congruence increases bimodally - either increasing or decreasing the contribution of one data partition will increase congruence - making it impossible to arrive at a single optimally congruent model of analysis.

  1. Projected increase in total knee arthroplasty in the United States - an alternative projection model.

    Science.gov (United States)

    Inacio, M C S; Paxton, E W; Graves, S E; Namba, R S; Nemes, S

    2017-08-08

    The purpose of our study was to estimate the future incidence rate (IR) and volume of primary total knee arthroplasty (TKA) in the United States from 2015 to 2050 using a conservative projection model that assumes a maximum IR of procedures. Furthermore, our study compared these projections to a model assuming exponential growth, as done in previous studies, for illustrative purposes. A population based epidemiological study was conducted using data from US National Inpatient Sample (NIS) and Census Bureau. Primary TKA procedures performed between 1993 and 2012 were identified. The IR, 95% confidence intervals (CI), or prediction intervals (PI) of TKA per 100,000 US citizens over the age of 40 years were calculated. The estimated IR was used as the outcome of a regression modelling with a logistic regression (i.e., conservative model) and Poisson regression equation (i.e., exponential growth model). Logistic regression modelling suggests the IR of TKA is expected to increase 69% by 2050 compared to 2012, from 429 (95%CI 374-453) procedures/100,000 in 2012 to 725 (95%PI 121-1041) in 2050. This translates into a 143% projected increase in TKA volume. Using the Poisson model, the IR in 2050 was projected to increase 565%, to 2854 (95%CI 2278-4004) procedures/100,000 IR, which is an 855% projected increase in volume compared to 2012. Even after using a conservative projection approach, the number of TKAs in the US, which already has the highest IR of knee arthroplasty in the world, is expected to increase 143% by 2050. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  2. The models of optimization for increasing of copper and gold recoveries in Bucim Mine

    OpenAIRE

    Gocev, Zivko; Krstev, Aleksandar; Krstev, Boris; Golomeova, Mirjana; Zendelska, Afrodita

    2015-01-01

    The increasing in the chalcopyrite copper Bucim mine are gone forward to renewed reagent regime, including and involving new reagents for increased recovery of copper and gold. The optimization and mathematical linear are good example for improvement of industrial recoveries in flotation circuit. Nevertheless, the choice between flotation and new leaching or bioleaching method are challenge for future. The optimization techniques, for matting the mathematical model and adequate...

  3. DUAL RANDOM MODEL OF INCREASING LIFE INSURANCE FOR MULTIPLE-LIFE STATUS

    Institute of Scientific and Technical Information of China (English)

    ZhangYi; HeWenjiong

    2002-01-01

    In this paper the dual random model of increasing life insurance for multiple-life status is discussed. The rnth moment of the present value of benefits are calculated and the respective expressions of the moments under joint life status or last- survivor status are presented.Fur-thermore,the limiting distribution of average cost of a portfolio of increasing life insurance for multiple-life status is studied.

  4. Sensitivity of the recent increase in Antarctic sea ice in ocean models

    Science.gov (United States)

    Kjellsson, Joakim; Holland, Paul; Marshall, Gareth; Coward, Andrew; Aksenov, Yevgeny; Bacon, Sheldon; Megann, Alexis; Ridley, Jeff

    2015-04-01

    We study the recent increase in Antarctic sea ice using a coupled ocean--sea ice model forced by atmospheric reanalysis. We investigate the impact on sea ice from both model parameters (e.g. vertical mixing and eddy parameterisation) as well as external forcing (e.g. precipitation and melt water from the Antarctic continent). We use the NEMO ocean model coupled to the CICE sea-ice model at 1 degree horizontal resolution forced with ERA-Interim reanalysis. The results will have impacts for our understanding of the Southern Ocean, its sea ice and their representation in future coupled climate-model studies, e.g. CMIP6. Since the dawn of the satellite era there has been a slow increase in Antarctic sea ice with pronounced spatial structure. The reason for this increase is not yet fully understood and very few climate-model simulations reproduce the observed mean state and/or increase. By varying model parameters and external forcing, we determine that obtaining a realistic sea ice cover requires a complex balance of horizontal and vertical mixing as well as fresh water input. The surface fresh water balance impacts the vertical salinity gradient and thus vertical fluxes of heat and salt. Underestimation of precipitation or melt water results in deep convection in the open ocean and the opening of large polynyas in the Weddell and Ross sea. The presence of polynyas reduces the sea ice extent. The depth of the mixed layer has a large impact on the sea ice seasonal cycle. The summer mixed layer must be sufficiently deep to prevent SST from becoming too high but not so deep as to mix up heat and salt from below. In winter, a deep mixed layer lets brine rejected from sea ice mix down to depths below that of the summer mixed layer thus maintaining a necessary stratification.

  5. 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

  6. What Works Clearinghouse Quick Review: "A Model for Success: CART's Linked Learning Program Increases College Enrollment"

    Science.gov (United States)

    What Works Clearinghouse, 2012

    2012-01-01

    The study, "A Model for Success: CART's Linked Learning Program Increases College Enrollment" examined whether students who enrolled in courses at a high school that combined academics and technical education had higher college enrollment rates than students who did not. The research described in this report does not meet What Works…

  7. Increasing Women's Aspirations and Achievement in Science: The Effect of Role Models on Implicit Cognitions

    Science.gov (United States)

    Phelan, Julie E.

    2010-01-01

    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…

  8. Increasing Women's Aspirations and Achievement in Science: The Effect of Role Models on Implicit Cognitions

    Science.gov (United States)

    Phelan, Julie E.

    2010-01-01

    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…

  9. 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

  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 scal

  12. Brief but chronic increase in allopregnanolone cause accelerated AD pathology differently in two mouse models.

    Science.gov (United States)

    Bengtsson, Sara K; Johansson, Maja; Backstrom, Torbjorn; Nitsch, Roger M; Wang, Mingde

    2013-01-01

    Previously, we have shown that chronic treatment with allopregnanolone (ALLO) for three months impaired learning function in the Swe/PS1 mouse model. ALLO is a neurosteroid, produced in the CNS and a GABAA receptor agonist. ALLO modulates the general inhibitory system in the CNS by enhancing the effect of GABA. Chronic treatment with other GABAA receptor active compounds, such as benzodiazepines, ethanol and medroxy-progesterone acetate has been associated to cognitive decline and/or increased risk for dementia. In this study, we sufficed with a treatment period of one month for the Swe/PS1 mouse, and included another Alzheimer's disease mouse model; the Swe/Arc model. We found that one month of chronic treatment with elevated ALLO levels within physiological range impaired learning and memory function in the Swe/Arc female and male mice. Male Swe/PS1 mice also showed marginally impaired function, while the female mice did not. Furthermore, the chronic ALLO treatment caused increased levels of soluble Aβ in the Swe/PS1 mouse model while the levels were unchanged in the Swe/Arc model. Therefore, both Swe/Arc and Swe/PS1 mice showed signs of accelerated disease progression. Still, further studies are required to determine the mechanisms behind the cognitive impairment and the increased Aβ-levels caused by mildly elevated ALLO-levels.

  13. Cholesterol Synthesis Increased in the MMI-Induced Subclinical Hypothyroidism Mice Model

    Science.gov (United States)

    Zhang, Xiujuan; Chen, Wenbin

    2017-01-01

    Subclinical hypothyroidism (SCH) is defined as increased serum thyroid-stimulating hormone (TSH) concentrations and normal serum thyroid hormone (TH) levels as well as an increased serum cholesterol level, which is an important cause of secondary hypercholesterolemia and cardiovascular diseases. Some studies have demonstrated a direct effect of TSH on cholesterol metabolism via in vivo and in vitro experiments. However, because no suitable SCH model has been established until now, the changes in cholesterol synthesis that occur in SCH patients remain unknown. Here, we establish an SCH mouse model by using long-term low-dose MMI administered in drinking water. Compared with the control group, the MMI-treated mice had elevated circulating TSH levels, but the serum FT3 levels in these mice did not change. Additionally, the TC levels increased in both the serum and liver of the experimental mice. Both the protein expression and activity of hepatic HMGCR, the rate-limiting enzyme for cholesterol synthesis in the liver, increased in these mice. We also found that the SCH mice had decreased phospho-HMGCR and phospho-AMPK expression, while the expression of AMPK showed no change. In conclusion, we established a suitable SCH model in which cholesterol synthesis is increased. PMID:28386276

  14. Animal models of sugar and fat bingeing: relationship to food addiction and increased body weight.

    Science.gov (United States)

    Avena, Nicole M; Bocarsly, Miriam E; Hoebel, Bartley G

    2012-01-01

    Binge eating is a behavior that occurs in some eating disorders, as well as in obesity and in nonclinical populations. Both sugars and fats are readily consumed by human beings and are common components of binges. This chapter describes animal models of sugar and fat bingeing, which allow for a detailed analysis of these behaviors and their concomitant physiological effects. The model of sugar bingeing has been used successfully to elicit behavioral and neurochemical signs of dependence in rats; e.g., indices of opiate-like withdrawal, increased intake after abstinence, cross-sensitization with drugs of abuse, and the repeated release of dopamine in the nucleus accumbens following repeated bingeing. Studies using the model of fat bingeing suggest that it can produce some, but not all, of the signs of dependence that are seen with sugar binge eating, as well as increase body weight, potentially leading to obesity.

  15. Altered lymphatics in an ovine model of congenital heart disease with increased pulmonary blood flow.

    Science.gov (United States)

    Datar, Sanjeev A; Johnson, Eric G; Oishi, Peter E; Johengen, Michael; Tang, Eric; Aramburo, Angela; Barton, Jubilee; Kuo, Hsuan-Chang; Bennett, Stephen; Xoinis, Konstantine; Reel, Bhupinder; Kalkan, Gokhan; Sajti, Eniko; Osorio, Oscar; Raff, Gary W; Matthay, Michael A; Fineman, Jeffrey R

    2012-03-15

    Abnormalities of the lymphatic circulation are well recognized in patients with congenital heart defects. However, it is not known how the associated abnormal blood flow patterns, such as increased pulmonary blood flow (PBF), might affect pulmonary lymphatic function and structure. Using well-established ovine models of acute and chronic increases in PBF, we cannulated the efferent lymphatic duct of the caudal mediastinal node and collected and analyzed lymph effluent from the lungs of lambs with acutely increased PBF (n = 6), chronically increased PBF (n = 6), and age-matched normal lambs (n = 8). When normalized to PBF, we found that lymph flow was unchanged following acute increases in PBF but decreased following chronic increases in PBF. The lymph:plasma protein ratio decreased with both acute and chronic increases in PBF. Lymph bioavailable nitric oxide increased following acute increases in PBF but decreased following chronic increases in PBF. In addition, we found perturbations in the transit kinetics of contrast material through the pleural lymphatics of lambs with chronic increases in PBF. Finally, there were structural changes in the pulmonary lymphatic system in lambs with chronic increases in PBF: lymphatics from these lambs were larger and more dilated, and there were alterations in the expression of vascular endothelial growth factor-C, lymphatic vessel endothelial hyaluronan receptor-1, and Angiopoietin-2, proteins known to be important for lymphatic growth, development, and remodeling. Taken together these data suggest that chronic increases in PBF lead to both functional and structural aberrations of lung lymphatics. These findings have important therapeutic implications that warrant further study.

  16. 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.

  17. From 'solution shop' model to 'focused factory' in hospital surgery: increasing care value and predictability.

    Science.gov (United States)

    Cook, David; Thompson, Jeffrey E; Habermann, Elizabeth B; Visscher, Sue L; Dearani, Joseph A; Roger, Veronique L; Borah, Bijan J

    2014-05-01

    The full-service US hospital has been described organizationally as a "solution shop," in which medical problems are assumed to be unstructured and to require expert physicians to determine each course of care. If universally applied, this model contributes to unwarranted variation in care, which leads to lower quality and higher costs. We purposely disrupted the adult cardiac surgical practice that we led at Mayo Clinic, in Rochester, Minnesota, by creating a "focused factory" model (characterized by a uniform approach to delivering a limited set of high-quality products) within the practice's solution shop. Key elements of implementing the new model were mapping the care process, segmenting the patient population, using information technology to communicate clearly defined expectations, and empowering nonphysician providers at the bedside. Using a set of criteria, we determined that the focused-factory model was appropriate for 67 percent of cardiac surgical patients. We found that implementation of the model reduced resource use, length-of-stay, and cost. Variation was markedly reduced, and outcomes were improved. Assigning patients to different care models increases care value and the predictability of care process, outcomes, and costs while preserving (in a lesser clinical footprint) the strengths of the solution shop. We conclude that creating a focused-factory model within a solution shop, by applying industrial engineering principles and health information technology tools and changing the model of work, is very effective in both improving quality and reducing costs.

  18. 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.

  19. 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.

  20. Translational PK/PD modeling to increase probability of success in drug discovery and early development.

    Science.gov (United States)

    Lavé, Thierry; Caruso, Antonello; Parrott, Neil; Walz, Antje

    In this review we present ways in which translational PK/PD modeling can address opportunities to enhance probability of success in drug discovery and early development. This is achieved by impacting efficacy and safety-driven attrition rates, through increased focus on the quantitative understanding and modeling of translational PK/PD. Application of the proposed principles early in the discovery and development phases is anticipated to bolster confidence of successfully evaluating proof of mechanism in humans and ultimately improve Phase II success. The present review is centered on the application of predictive modeling and simulation approaches during drug discovery and early development, and more specifically of mechanism-based PK/PD modeling. Case studies are presented, focused on the relevance of M&S contributions to real-world questions and the impact on decision making.

  1. Localization in band random matrix models with and without increasing diagonal elements.

    Science.gov (United States)

    Wang, Wen-ge

    2002-06-01

    It is shown that localization of eigenfunctions in the Wigner band random matrix model with increasing diagonal elements can be related to localization in a band random matrix model with random diagonal elements. The relation is obtained by making use of a result of a generalization of Brillouin-Wigner perturbation theory, which shows that reduced Hamiltonian matrices with relatively small dimensions can be introduced for nonperturbative parts of eigenfunctions, and by employing intermediate basis states, which can improve the method of the reduced Hamiltonian matrix. The latter model deviates from the standard band random matrix model mainly in two aspects: (i) the root mean square of diagonal elements is larger than that of off-diagonal elements within the band, and (ii) statistical distributions of the matrix elements are close to the Lévy distribution in their central parts, except in the high top regions.

  2. Municipal household solid waste fee based on an increasing block pricing model in Beijing, China.

    Science.gov (United States)

    Chu, Zhujie; Wu, Yunga; Zhuang, Jun

    2017-03-01

    This article aims to design an increasing block pricing model to estimate the waste fee with the consideration of the goals and principles of municipal household solid waste pricing. The increasing block pricing model is based on the main consideration of the per capita disposable income of urban residents, household consumption expenditure, production rate of waste disposal industry, and inflation rate. The empirical analysis is based on survey data of 5000 households in Beijing, China. The results indicate that the current uniform price of waste disposal is set too high for low-income people, and waste fees to the household disposable income or total household spending ratio are too low for the medium- and high-income families. An increasing block pricing model can prevent this kind of situation, and not only solve the problem of lack of funds, but also enhance the residents' awareness of environmental protection. A comparative study based on the grey system model is made by having a preliminary forecast for the waste emissions reduction effect of the pay-as-you-throw programme in the next 5 years of Beijing, China. The results show that the effect of the pay-as-you-throw programme is not only to promote the energy conservation and emissions reduction, but also giving a further improvement of the environmental quality.

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

    Science.gov (United States)

    McCloskey, Douglas; Young, Jamey D; Xu, Sibei; Palsson, Bernhard O; Feist, Adam M

    2016-04-05

    Metabolic flux analysis (MFA) is considered to be the gold standard for determining the intracellular flux distribution of biological systems. The majority of work using MFA has been limited to core models of metabolism due to challenges in implementing genome-scale MFA and the undesirable trade-off between increased scope and decreased precision in flux estimations. This work presents a tunable workflow for expanding the scope of MFA to the genome-scale without trade-offs in flux precision. The genome-scale MFA model presented here, iDM2014, accounts for 537 net reactions, which includes the core 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 distributions (MIDs),1 it was found that a total of 232 net fluxes of central and peripheral metabolism could be resolved in the E. coli network. The increase in scope was shown to cover the full biosynthetic route to an expanded set of bioproduction pathways, which should facilitate applications such as the design of more complex bioprocessing strains and aid in identifying new antimicrobials. Importantly, it was found that there was no loss in precision of core fluxes when compared to a traditional core model, and additionally there was an overall increase in precision when considering all observable reactions.

  4. Beneficial effects of increased lysozyme levels in Alzheimer's disease modelled in Drosophila melanogaster.

    Science.gov (United States)

    Sandin, Linnea; Bergkvist, Liza; Nath, Sangeeta; Kielkopf, Claudia; Janefjord, Camilla; Helmfors, Linda; Zetterberg, Henrik; Blennow, Kaj; Li, Hongyun; Nilsberth, Camilla; Garner, Brett; Brorsson, Ann-Christin; Kågedal, Katarina

    2016-10-01

    Genetic polymorphisms of immune genes that associate with higher risk to develop Alzheimer's disease (AD) have led to an increased research interest on the involvement of the immune system in AD pathogenesis. A link between amyloid pathology and immune gene expression was suggested in a genome-wide gene expression study of transgenic amyloid mouse models. In this study, the gene expression of lysozyme, a major player in the innate immune system, was found to be increased in a comparable pattern as the amyloid pathology developed in transgenic mouse models of AD. A similar pattern was seen at protein levels of lysozyme in human AD brain and CSF, but this lysozyme pattern was not seen in a tau transgenic mouse model. Lysozyme was demonstrated to be beneficial for different Drosophila melanogaster models of AD. In flies that expressed Aβ1-42 or AβPP together with BACE1 in the eyes, the rough eye phenotype indicative of toxicity was completely rescued by coexpression of lysozyme. In Drosophila flies bearing the Aβ1-42 variant with the Arctic gene mutation, lysozyme increased the fly survival and decreased locomotor dysfunction dose dependently. An interaction between lysozyme and Aβ1-42 in the Drosophila eye was discovered. We propose that the increased levels of lysozyme, seen in mouse models of AD and in human AD cases, were triggered by Aβ1-42 and caused a beneficial effect by binding of lysozyme to toxic species of Aβ1-42 , which prevented these from exerting their toxic effects. These results emphasize the possibility of lysozyme as biomarker and therapeutic target for AD. © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  5. 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.

  6. 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.

  7. 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

    Metabolic flux analysis (MFA) is considered to be the gold standard for determining the intracellular flux distribution of biological systems. The majority of work using MFA has been limited to core models of metabolism due to challenges in implementing genome-scale MFA and the undesirable trade...... distributions (MIDs),(1) it was found that a total of 232 net fluxes of central and peripheral metabolism could be resolved in the E. coli network. The increase in scope was shown to cover the full biosynthetic route to an expanded set of bioproduction pathways, which should facilitate applications......-off between increased scope and decreased precision in flux estimations. This work presents a tunable workflow for expanding the scope of MFA to the genome-scale without trade-offs in flux precision. The genome-scale MFA model presented here, iDM2014, accounts for 537 net reactions, which includes the core...

  8. 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...

  9. 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.

  10. Synthetic feedback loop model for increasing microbial biofuel production using a biosensor

    Directory of Open Access Journals (Sweden)

    Mary eHarrison

    2012-10-01

    Full Text Available Current biofuel production methods use engineered bacteria to break down cellulose and convert it to biofuel. A major challenge in microbial fuel production is that increasing biofuel yields can be limited by the toxicity of the biofuel to the organism that is producing it. Previous research has demonstrated that efflux pumps are effective at increasing tolerance to various biofuels. However, when overexpressed, efflux pumps burden cells, which hinders growth and slows biofuel production. Therefore, the toxicity of the biofuel must be balanced with the toxicity of pump overexpression. We have developed a mathematical model for cell growth and biofuel production that implements a synthetic feedback loop using a biosensor to control efflux pump expression. In this way, the production rate will be maximal when the concentration of biofuel is low because the cell does not expend energy expressing efflux pumps when they are not needed. Additionally, the microbe is able to adapt to toxic conditions by triggering the expression of efflux pumps, which allow it to continue biofuel production. Sensitivity analysis indicates that the feedback sensor model is insensitive to most system parameters, but a few key parameters can influence growth and production. In comparison to systems that express efflux pumps at a constant level, the feedback sensor increases overall biofuel production by delaying pump expression until it is needed. This result is more pronounced when model parameters are variable because the system can use feedback to adjust to the actual rate of biofuel production.

  11. Modeling the effects of aerosols to increase rainfall in regions with shortage

    Science.gov (United States)

    Shukla, J. B.; Sundar, Shyam; Misra, A. K.; Naresh, Ram

    2013-05-01

    It is well known that the emissions of hot gases from various power stations and other industrial sources in the regional atmosphere cause decrease in rainfall around these complexes. To overcome this shortage, one method is to introduce artificially conducive aerosol particles in the atmosphere using aeroplane to increase rainfall. To prove the feasibility of this idea, in this paper, a nonlinear mathematical model is proposed involving five dependent variables, namely, the volume density of water vapour, number densities of cloud droplets and raindrops, and the concentrations of small and large size conducive aerosol particles. It is assumed that two types of aerosol particles are introduced in the regional atmosphere, one of them is of small size CCN type which is conducive to increase cloud droplets from vapour phase, while the other is of large size and is conducive to transform the cloud droplets to raindrops. The model is analyzed using stability theory of differential equations and computer simulation. The model analysis shows that due to the introduction of conducive aerosol particles in the regional atmosphere, the rainfall increases as compared to the case when no aerosols are introduced in the atmosphere of the region under consideration. The computer simulation confirms the analytical results.

  12. Analysis of Seismicity Risk Increase Triggered by Longtan Reservoir, China, Using a Fully Coupled Poroelastic Model

    Science.gov (United States)

    Deng, K.; Zhang, S.; Guo, Y.; Zhou, S.; Liu, Y.

    2015-12-01

    Impoundment of reservoirs can lead to increase in crustal pore pressure and Coulomb stress, and promotes nearby faults to fail. Abnormal seismicity increase around reservoir is often thought to be triggered by the water impounded behind the dam. In this study, we analyze the impact of Longtan reservoir in Guangxi province, southwest China, on local seismicity, which has increased significantly since the initial impoundment in October, 2006. Most of the earthquakes cluster around the reservoir according to local seismic network and CEA reports, and the greatest earthquake is of magnitude 4.2. We introduce an improved Bayesian method to show that the temporal variation of b-value is inversely correlated with the seasonal fluctuation of reservoir water level. Upon extracting background seismicity using the Epidemic Type Aftershock Sequence (ETAS) model, we show that background seismicity variation is highly related to the filling rate and volume We further investigate the mechanism of seismicity increase and reservoir impoundment by performing a fully coupled 3-D poroelastic model with the reservoir loading history as a dynamic boundary condition. An optimally oriented fault plane is chosen according to the regional stress field and GPS deformation data when calculating the induced Coulomb stress. Our results demonstrate that most earthquakes occurred within positive Coulomb stress regime, and the seismicity rate is highly related to the rate of pore pressure increase. In the next step we plan to apply the coupled poroelastic model to understand hydraulic fracturing induced earthquakes in shale gas exploration, such as the recent Fox Creek event cluster, in the western Canada sedimentary basin.

  13. Childhood onset generalised dystonia can be modelled by increased gain in the indirect basal ganglia pathway.

    Science.gov (United States)

    Sanger, T D

    2003-11-01

    Clinical experience suggests an important role of the indirect basal ganglia pathway in the genesis of childhood onset generalised dystonia, but it has been difficult to reconcile the increased muscle activity in dystonia with the current model of basal ganglia function in which the indirect pathway is considered primarily inhibitory. The aim of this study was to present a modification of the direct-indirect pathway model, in which the indirect pathway is inverting rather than purely inhibitory, so that while high signals are inhibited, low signals are amplified. As the basal ganglia may be a feedback loop that modifies cortical activity, instability from excessive gain in this feedback loop could explain features of dystonia. A detailed mathematical model is provided, together with simulations of cortical cell population spiking behaviour when connected through a basal ganglia loop. The simulations show that increased gain in the indirect pathway relative to the direct pathway can lead to unstable uncontrolled synchronous oscillations in cortex and basal ganglia. This behaviour could result in dystonia. The model provides a consistent explanation for the association of dystonia with parkinsonism and disorders characterised by dopamine depletion, the ability to treat some dystonias with dopamine, the ability of neuroleptic drug treatment to cause an acute dystonic reaction treatable with anticholinergic drugs, and the ability of pallidotomy or deep brain stimulation of the internal pallidum to alleviate symptoms of generalised dystonia.

  14. 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.

  15. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease.

    Science.gov (United States)

    Estes, Chris; Razavi, Homie; Loomba, Rohit; Younossi, Zobair; Sanyal, Arun J

    2017-08-12

    Nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) are highly prevalent in the US, where they are a growing cause of cirrhosis and hepatocellular carcinoma (HCC), and increasingly, an indicator for liver transplantation. A Markov model was used to forecast NAFLD disease progression. Incidence of NAFLD was based on historical and projected changes in adult prevalence of obesity and type 2 diabetes mellitus (DM). Assumptions were derived from published literature where available, and validated using national surveillance data for incidence of NAFLD-related HCC. Projected changes in NAFLD-related cirrhosis, advanced liver disease, and liver-related mortality were quantified through 2030. Prevalent NAFLD cases are forecasted to increase 21%, from 83.1 (2015) to 100.9 million (2030), while prevalent NASH cases will increase 63% from 16.52 to 27.00 million cases. Overall NAFLD prevalence among the adult population (aged ≥15 years) is projected at 33.5% in 2030, and the median age of the NAFLD population will increase from 50 to 55 years during 2015-2030. In 2015, approximately 20% of NAFLD cases were classified as NASH, increasing to 27% by 2030, a reflection of both disease progression and an aging population. Incidence of decompensated cirrhosis will increase 168% to 105,430 cases by 2030, while incidence of HCC will increase by 137% to 12,240 cases. Liver deaths will increase 178% to an estimated 78,300 deaths in 2030. During 2015-2030, there are nearly 800,000 excess liver deaths. With continued high rates of adult obesity and DM, and an aging population, NAFLD-related liver disease and mortality will increase in the US. Strategies to slow the growth of NAFLD cases and therapeutic options are necessary to mitigate disease burden. This article is protected by copyright. All rights reserved. © 2017 by the American Association for the Study of Liver Diseases.

  16. A theoretical model of virtual water trade under increasing water scarcity conditions

    Science.gov (United States)

    de Vos, Lotte; Pande, Saket

    2016-04-01

    This paper proposes a virtual water trade model to obtain a better understanding of how hydro-climatic change affects societies through changes in virtual water trade. In previous studies it has been shown that global trade patterns can be influenced by water scarcity and vice-versa. The extent to which this relationship holds is still a topic under discussion. With the model introduced in this paper, the dynamics behind these trade patterns are further explored. First, a model is constructed of a society suffering from an increase in water scarcity. This model is shown to be capable of replicating patterns of technological, population, production and consumption per capita changes. In order to incorporate the effects of globalization and trade, the model has been extended to a toy model of virtual water trade between two societies. The two societies are represented by overlapping generations models. The individuals of each generation provide the labour needed for the production of the composite goods. In addition to this labour, water and technology are also incorporated as factors of production. There are two goods being produced; one is labour intensive and the other water intensive. Trade emerges from the principle of comparative advantage, with differences in labour-abundance and water resources availability between the two societies. Using this model of two societies interconnected by trade, it is examined how trade of water-intensive commodities alters under changing scarcity conditions. In particular we explore the conditions under which trade emerges, and to what extent. Furthermore, we present the conditions for the sustainable development within these two societies.

  17. 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.

  18. Response of the Atlantic Thermohaline Circulation to Increased Atmospheric CO2 in a Coupled Model.

    Science.gov (United States)

    Hu, Aixue; Meehl, Gerald A.; Washington, Warren M.; Dai, Aiguo

    2004-11-01

    Changes in the thermohaline circulation (THC) due to increased CO2 are important in future climate regimes. Using a coupled climate model, the Parallel Climate Model (PCM), regional responses of the THC in the North Atlantic to increased CO2 and the underlying physical processes are studied here. The Atlantic THC shows a 20-yr cycle in the control run, qualitatively agreeing with other modeling results. Compared with the control run, the simulated maximum of the Atlantic THC weakens by about 5 Sv (1 Sv 106 m3 s-1) or 14% in an ensemble of transient experiments with a 1% CO2 increase per year at the time of CO2 doubling. The weakening of the THC is accompanied by reduced poleward heat transport in the midlatitude North Atlantic. Analyses show that oceanic deep convective activity strengthens significantly in the Greenland Iceland Norway (GIN) Seas owing to a saltier (denser) upper ocean, but weakens in the Labrador Sea due to a fresher (lighter) upper ocean and in the south of the Denmark Strait region (SDSR) because of surface warming. The saltiness of the GIN Seas are mainly caused by an increased salty North Atlantic inflow, and reduced sea ice volume fluxes from the Arctic into this region. The warmer SDSR is induced by a reduced heat loss to the atmosphere, and a reduced sea ice flux into this region, resulting in less heat being used to melt ice. Thus, sea ice related salinity effects appear to be more important in the GIN Seas, but sea ice melt-related thermal effects seem to be more important in the SDSR region. On the other hand, the fresher Labrador Sea is mainly attributed to increased precipitation. These regional changes produce the overall weakening of the THC in the Labrador Sea and SDSR, and more vigorous ocean overturning in the GIN Seas. The northward heat transport south of 60°N is reduced with increased CO2, but increased north of 60°N due to the increased flow of North Atlantic water across this latitude.

  19. 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

    models which reflect the disease process. Material and Results: We randomly allocated 45 newborn pigs, at the age of 48 hrs, to groups in which there was either construction of a 3 mm central aorto-pulmonary shunt, undertaken in 9, or ligation of the left pulmonary artery, achieved in 13. Controls...... included sham operations in 13, or no operations in 10 pigs. Follow-up was continued for three months. The interventions were compatible with survival in most pigs. The shunts resulted in an acute 85% increase in systolic pulmonary arterial pressure, and a more than twofold increase in pulmonary blood flow....... 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...

  20. Unraveling protein folding mechanism by analyzing the hierarchy of models with increasing level of detail

    Science.gov (United States)

    Hayashi, Tomohiko; Yasuda, Satoshi; Škrbić, Tatjana; Giacometti, Achille; Kinoshita, Masahiro

    2017-09-01

    Taking protein G with 56 residues for a case study, we investigate the mechanism of protein folding. In addition to its native structure possessing α-helix and β-sheet contents of 27% and 39%, respectively, we construct a number of misfolded decoys with a wide variety of α-helix and β-sheet contents. We then consider a hierarchy of 8 different models with increasing level of detail in terms of the number of entropic and energetic physical factors incorporated. The polyatomic structure is always taken into account, but the side chains are removed in half of the models. The solvent is formed by either neutral hard spheres or water molecules. Protein intramolecular hydrogen bonds (H-bonds) and protein-solvent H-bonds (the latter is present only in water) are accounted for or not, depending on the model considered. We then apply a physics-based free-energy function (FEF) corresponding to each model and investigate which structures are most stabilized. This special approach taken on a step-by-step basis enables us to clarify the role of each physical factor in contributing to the structural stability and separately elucidate its effect. Depending on the model employed, significantly different structures such as very compact configurations with no secondary structures and configurations of associated α-helices are optimally stabilized. The native structure can be identified as that with lowest FEF only when the most detailed model is employed. This result is significant for at least the two reasons: The most detailed model considered here is able to capture the fundamental aspects of protein folding notwithstanding its simplicity; and it is shown that the native structure is stabilized by a complex interplay of minimal multiple factors that must be all included in the description. In the absence of even a single of these factors, the protein is likely to be driven towards a different, more stable state.

  1. The cost-effectiveness of increasing alcohol taxes: a modelling study

    Directory of Open Access Journals (Sweden)

    de Wit G

    2008-11-01

    Full Text Available Abstract Background Excessive alcohol use increases risks of chronic diseases such as coronary heart disease and several types of cancer, with associated losses of quality of life and life-years. Alcohol taxes can be considered as a public health instrument as they are known to be able to decrease alcohol consumption. In this paper, we estimate the cost-effectiveness of an alcohol tax increase for the entire Dutch population from a health-care perspective focusing on health benefits and health-care costs in alcohol users. Methods The chronic disease model of the National Institute for Public Health and the Environment was used to extrapolate from decreased alcohol consumption due to tax increases to effects on health-care costs, life-years gained and quality-adjusted life-years gained, A Dutch scenario in which tax increases for beer are planned, and a Swedish scenario representing one of the highest alcohol taxes in Europe, were compared with current practice in the Netherlands. To estimate cost-effectiveness ratios, yearly differences in model outcomes between intervention and current practice scenarios were discounted and added over the time horizon of 100 years to find net present values for incremental life-years gained, quality-adjusted life-years gained, and health-care costs. Results In the Swedish scenario, many more quality-adjusted life-years were gained than in the Dutch scenario, but both scenarios had almost equal incremental cost-effectiveness ratios: €5100 per quality-adjusted life-year and €5300 per quality-adjusted life-year, respectively. Conclusion Focusing on health-care costs and health consequences for drinkers, an alcohol tax increase is a cost-effective policy instrument.

  2. 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

  3. 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.

  4. 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.

  5. Modeling Amazon forest vegetation dynamics and community response to increased wind disturbance

    Science.gov (United States)

    Holm, J. A.; Negron Juarez, R. I.; Chambers, J. Q.; Marra, D.; Rifai, S. W.; Knox, R. G.; Riley, W. J.; Koven, C. D.; McGroddy, M. E.; Urquiza-Muñoz, J. D.; Tello-Espinoza, R.; Ribeiro, G. H. P. M.; Higuchi, N.

    2015-12-01

    Determining the drivers of tree mortality in Amazonia is a complex task, yet essential to reliable prediction of carbon storage in a warmer climate. Past studies have shown an east-west gradient of forest disturbance and rainfall amount across Amazonia. This study uses remote sensing and dynamic vegetation modeling to take a deeper look at drivers of tree mortality and community composition shifts associated with varying mortality rates. Our analysis, using 20 years of Landsat 5 images, showed that ever-wet Amazonia (located in north-west Amazonia, i.e. NWA) was more susceptible to windthrows than the Central Amazon (i.e. CA), which has a a well-defined dry season. The higher frequency of windthrows in NWA forest correlates with higher frequency and intensity of deep convection events in this region, observed using Tropical Rainfall Measuring Mission (TRMM) data. While a combination of factors including: soil characteristics (and by proxy rooting depth) and community composition exacerbate the regional gradient of disturbance, wind was the mechanistic agent of disturbance. Using an individual-based gap model for tropical forests populated with the most representative NWA tree species and increased mortality rates, we found a decrease of biomass in this region and a slight increase in NPP compared to a control simulation, a pattern that is similar to observations. The model predicted which species had the largest response in basal area change due to elevated disturbance, but there was a non-significant shift in community composition in the NWA forests. However, analysis found strong differences in community composition between the modeled NWA and CA regions, consistent with observed results. When CA forests were subject to higher mortality rate similar to the current NWA region, dissimilarity in community composition continued to persist. In addition the model identified species-specific maximum tree height and maximum diameter as the most influential predictors of

  6. Impacts of increasing the aerosol complexity in the Met Office global NWP model

    Science.gov (United States)

    Mulcahy, Jane; Walters, David; Bellouin, Nicolas; Milton, Sean

    2014-05-01

    Inclusion of the direct and indirect radiative effects of aerosols in high resolution global numerical weather prediction (NWP) models is being increasingly recognised as important for the improved accuracy of short-range weather forecasts. In this study the impacts of increasing the aerosol complexity in the global NWP configuration of the Met Office Unified Model (MetUM) are investigated. A hierarchy of aerosol representations are evaluated including three dimensional monthly mean speciated aerosol climatologies, fully prognostic aerosols modelled using the CLASSIC aerosol scheme and finally, initialised aerosols using assimilated aerosol fields from the GEMS project. The prognostic aerosol schemes are better able to predict the temporal and spatial variation of atmospheric aerosol optical depth, which is particularly important in cases of large sporadic aerosol events such as large dust storms or forest fires. Including the direct effect of aerosols improves model biases in outgoing longwave radiation over West Africa due to a better representation of dust. Inclusion of the indirect aerosol effects has significant impacts on the SW radiation particularly at high latitudes due to lower cloud amounts in high latitude clean air regions. This leads to improved surface radiation biases at the North Slope of Alaska ARM site. Verification of temperature and height forecasts is also improved in this region. Impacts on the global mean model precipitation and large-scale circulation fields were found to be generally small in the short range forecasts. However, the indirect aerosol effect leads to a strengthening of the low level monsoon flow over the Arabian Sea and Bay of Bengal and an increase in precipitation over Southeast Asia. This study highlights the importance of including a more realistic treatment of aerosol-cloud interactions in global NWP models and the potential for improved global environmental prediction systems through the incorporation of more complex

  7. Implementation of a combined algorithm designed to increase the reliability of information systems: simulation modeling

    Science.gov (United States)

    Popov, A.; Zolotarev, V.; Bychkov, S.

    2016-11-01

    This paper examines the results of experimental studies of a previously submitted combined algorithm designed to increase the reliability of information systems. The data that illustrates the organization and conduct of the studies is provided. Within the framework of a comparison of As a part of the study conducted, the comparison of the experimental data of simulation modeling and the data of the functioning of the real information system was made. The hypothesis of the homogeneity of the logical structure of the information systems was formulated, thus enabling to reconfigure the algorithm presented, - more specifically, to transform it into the model for the analysis and prediction of arbitrary information systems. The results presented can be used for further research in this direction. The data of the opportunity to predict the functioning of the information systems can be used for strategic and economic planning. The algorithm can be used as a means for providing information security.

  8. 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

  9. Increasing access to specialty surgical care: application of a new resource allocation model to bariatric surgery.

    Science.gov (United States)

    Leroux, Eric J; Morton, John M; Rivas, Homero

    2014-08-01

    To calculate the public health impact and economic benefit of using ancillary health care professionals for routine postoperative care. The need for specialty surgical care far exceeds its supply, particularly in weight loss surgery. Bariatric surgery is cost-effective and the only effective long-term weight loss strategy for morbidly obese patients. Without clinically appropriate task shifting, surgeons, hospitals, and untreated patients incur a high opportunity cost. Visit schedules, time per visit, and revenues were obtained from bariatric centers of excellence. Case-specific surgeon fees were derived from published Current Procedural Terminology data. The novel Microsoft Excel model was allowed to run until a steady state was evident (status quo). This model was compared with one in which the surgeon participates in follow-up visits beyond 3 months only if there is a complication (task shifting). Changes in operative capacity and national quality-adjusted life years (QALYs) were calculated. In the status quo model, per capita surgical volume capacity equilibrates at 7 surgical procedures per week, with 27% of the surgeon's time dedicated to routine long-term follow-up visits. Task shifting increases operative capacity by 38%, resulting in 143,000 to 882,000 QALYs gained annually. Per surgeon, task shifting achieves an annual increase of 95 to 588 QALYs, $5 million in facility revenue, 48 cases of cure of obstructive sleep apnea, 44 cases of remission of type 2 diabetes mellitus, and 35 cases of cure of hypertension. Optimal resource allocation through task shifting is economically appealing and can achieve dramatic public health benefit by increasing access to specialty surgery.

  10. Plant functional diversity increases grassland productivity-related water vapor fluxes: an Ecotron and modeling approach.

    Science.gov (United States)

    Milcu, Alexandru; Eugster, Werner; Bachmann, Dörte; Guderle, Marcus; Roscher, Christiane; Gockele, Annette; Landais, Damien; Ravel, Olivier; Gessler, Arthur; Lange, Markus; Ebeling, Anne; Weisser, Wolfgang W; Roy, Jacques; Hildebrandt, Anke; Buchmann, Nina

    2016-08-01

    The impact of species richness and functional diversity of plants on ecosystem water vapor fluxes has been little investigated. To address this knowledge gap, we combined a lysimeter setup in a controlled environment facility (Ecotron) with large ecosystem samples/monoliths originating from a long-term biodiversity experiment (The Jena Experiment) and a modeling approach. Our goals were (1) quantifying the impact of plant species richness (four vs. 16 species) on day- and nighttime ecosystem water vapor fluxes; (2) partitioning ecosystem evapotranspiration into evaporation and plant transpiration using the Shuttleworth and Wallace (SW) energy partitioning model; and (3) identifying the most parsimonious predictors of water vapor fluxes using plant functional-trait-based metrics such as functional diversity and community weighted means. Daytime measured and modeled evapotranspiration were significantly higher in the higher plant diversity treatment, suggesting increased water acquisition. The SW model suggests that, at low plant species richness, a higher proportion of the available energy was diverted to evaporation (a non-productive flux), while, at higher species richness, the proportion of ecosystem transpiration (a productivity-related water flux) increased. While it is well established that LAI controls ecosystem transpiration, here we also identified that the diversity of leaf nitrogen concentration among species in a community is a consistent predictor of ecosystem water vapor fluxes during daytime. The results provide evidence that, at the peak of the growing season, higher leaf area index (LAI) and lower percentage of bare ground at high plant diversity diverts more of the available water to transpiration, a flux closely coupled with photosynthesis and productivity. Higher rates of transpiration presumably contribute to the positive effect of diversity on productivity.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  12. MEDIA AND INCREASING PUBLIC TRUST IN MODERN IRAN: A CONCEPTUAL MODEL

    Directory of Open Access Journals (Sweden)

    Habib Ebrahimpour

    2012-06-01

    Full Text Available Public trust is one of the social capitals that can lead to integration in social systems. Trust links the citizens to organizations and institutions which represent them and in this way it increases the government’s legitimacy and effectiveness. In industrial communications nothing is more important than establishing public trust in media. Therefore, building trust and reflecting the facts on social, political, and economical issues are the essentials of media work. Hence, this study set out to investigate the effective factors which contribute to increasing public trust toward media and giving a conceptual model for them in Iran. Based on the five effective factors of public trust in media, some suggestions are finally given which can be manipulated in order to enhance media trust in modern Iran.

  13. Shuganjieyu capsule increases neurotrophic factor expression in a rat model of depression

    Institute of Scientific and Technical Information of China (English)

    Jinhua Fu; Yingjin Zhang; Renrong Wu; Yingjun Zheng; Xianghui Zhang; Mei Yang; Jingping Zhao; Yong Liu

    2014-01-01

    Shuganjieyu capsule has been approved for clinical treatment by the State Food and Drug Ad-ministration of China since 2008. In the clinic, Shuganjieyu capsule is often used to treat mild to moderate depression. In the rat model of depression established in this study, Shuganjieyu capsule was administered intragastrically daily before stress. Behavioral results conifrmed that depressive symptoms lessened after treatment with high-dose (150 mg/kg) Shuganjieyu capsule. Immunohistochemistry results showed that high-dose Shuganjieyu capsule signiifcantly increased phosphorylation levels of phosphorylation cyclic adenosine monophosphate response element binding protein and brain-derived neurotrophic factor expression in the medial prefrontal cortex and hippocampal CA3 area. Overall, our results suggest that in rats, Shuganjieyu capsule effec-tively reverses depressive-like behaviors by increasing expression levels of neurotrophic factors in the brain.

  14. IL-10 supplementation increases Tregs and decreases hypertension in the RUPP rat model of preeclampsia.

    Science.gov (United States)

    Harmon, Ashlyn; Cornelius, Denise; Amaral, Lorena; Paige, Adrienne; Herse, Florian; Ibrahim, Tarek; Wallukat, Gerd; Faulkner, Jessica; Moseley, Janae; Dechend, Ralf; LaMarca, Babbette

    2015-01-01

    The reduced uterine perfusion pressure (RUPP) rat model of preeclampsia was used to determine the effects of added interleukin-10 (IL-10) on Tregs and hypertension in response to placental ischemia and how the decrease in these anti-inflammatory factors mediates the pathophysiology of preeclampsia. IL-10 (2.5 ng/kg/d) was infused via osmotic mini-pump implanted intraperitoneally on day 14 of gestation and, at the same time, the RUPP procedure was performed. IL-10 reduced mean arterial pressure (p increasing Tregs (p = 0.043) which led to lower IL-6 and TNF-α (p = 0.008 and p = 0.003), reduced AT1-AA production (p increases Tregs and helps to balance the altered immune system seen during preeclampsia.

  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 acid responsiveness in vagal sensory neurons in a guinea pig model of eosinophilic esophagitis.

    Science.gov (United States)

    Hu, Youtian; Liu, Zhenyu; Yu, Xiaoyun; Pasricha, Pankaj J; Undem, Bradley J; Yu, Shaoyong

    2014-07-15

    Eosinophilic esophagitis (EoE) is characterized with eosinophils and mast cells predominated allergic inflammation in the esophagus and present with esophageal dysfunctions such as dysphagia, food impaction, and heartburn. However, the underlying mechanism of esophageal dysfunctions is unclear. This study aims to determine whether neurons in the vagal sensory ganglia are modulated in a guinea pig model of EoE. Animals were actively sensitized by ovalbumin (OVA) and then challenged with aerosol OVA inhalation for 2 wk. This results in a mild esophagitis with increases in mast cells and eosinophils in the esophageal wall. Vagal nodose and jugular neurons were disassociated, and their responses to acid, capsaicin, and transient receptor potential vanilloid type 1 (TRPV1) antagonist AMG-9810 were studied by calcium imaging and whole cell patch-clamp recording. Compared with naïve animals, antigen challenge significantly increased acid responsiveness in both nodose and jugular neurons. Their responses to capsaicin were also increased after antigen challenge. AMG-9810, at a concentration that blocked capsaicin-evoked calcium influx, abolished the increase in acid-induced activation in both nodose and jugular neurons. Vagotomy strongly attenuated those increased responses of nodose and jugular neurons to both acid and capsaicin induced by antigen challenge. These data for the first time demonstrated that prolonged antigen challenge significantly increases acid responsiveness in vagal nodose and jugular ganglia neurons. This sensitization effect is mediated largely through TRPV1 and initiated at sensory nerve endings in the peripheral tissues. Allergen-induced enhancement of responsiveness to noxious stimulation by acid in sensory nerve may contribute to the development of esophageal dysfunctions such as heartburn in EoE.

  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. Cannabidiol increases survival and promotes rescue of cognitive function in a murine model of cerebral malaria.

    Science.gov (United States)

    Campos, A C; Brant, F; Miranda, A S; Machado, F S; Teixeira, A L

    2015-03-19

    Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection that might cause permanent neurological deficits. Cannabidiol (CBD) is a nonpsychotomimetic compound of Cannabis sativa with neuroprotective properties. In the present work, we evaluated the effects of CBD in a murine model of CM. Female mice were infected with Plasmodium berghei ANKA (PbA) and treated with CBD (30mg/kg/day - 3 or 7days i.p.) or vehicle. On 5th day-post-infection (dpi), at the peak of the disease), animals were treated with single or repeated doses of Artesunate, an antimalarial drug. All groups were tested for memory impairment (Novel Object Recognition or Morris Water Maze) and anxiety-like behaviors (Open field or elevated plus maze test) in different stages of the disease (at the peak or after the complete clearance of the disease). Th1/Th2 cytokines and neurotrophins (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) were measured in the prefrontal cortex and hippocampus of experimental groups. PbA-infected mice displayed memory deficits and exhibited increase in anxiety-like behaviors on the 5dpi or after the clearance of the parasitemia, effects prevented by CBD treatment. On 5dpi, TNF-α and IL-6 increased in the hippocampus, while only IL-6 increased in the prefrontal cortex. CBD treatment resulted in an increase in BDNF expression in the hippocampus and decreased levels of proinflammatory cytokines in the hippocampus (TNF-α) and prefrontal cortex (IL-6). Our results indicate that CBD exhibits neuroprotective effects in CM model and might be useful as an adjunctive therapy to prevent neurological symptoms following this disease.

  19. Anticholinergics boost the pathological process of neurodegeneration with increased inflammation in a tauopathy mouse model.

    Science.gov (United States)

    Yoshiyama, Yasumasa; Kojima, Ayako; Itoh, Kimiko; Uchiyama, Tomoyuki; Arai, Kimihito

    2012-01-01

    Anticholinergics, and drugs with anticholinergic properties, are widely and frequently prescribed, especially to the elderly. It is well known that these drugs decrease cognitive function and increase the risk of dementia. Although the mechanism of anticholinergic drug-induced cognitive impairment has been assumed to be functionally reduced acetylcholine (ACh) neurotransmission, some data have indicated that anticholinergics might enhance the pathology of Alzheimer's disease. In this study, we investigated the pathological effects of anticholinergics on neurodegeneration. We chronically administered two anticholinergics, trihexyphenidyl (TP) and propiverine (PP) (the latter with less central anticholinergic action), to neurodegenerative tauopathy model mice 2 to 10 months old. Furthermore, because the ACh nervous system regulates both central and peripheral inflammation, we administered TP or PP to PS19 mice in which we had artificially induced inflammation by lipopolysaccharide injection. Tau pathology, synaptic loss, and neurodegeneration in the hippocampal region, as well as tau insolubility and phosphorylation, were markedly increased in TP-treated mice and mildly increased in PP-treated mice. Furthermore, immunohistochemical analysis revealed microglial proliferation and activation. Moreover, anticholinergics increased interleukin-1β expression in both the spleen and brain of the tauopathy model mice intraperitoneally injected with lipopolysaccharide to induce systemic inflammation. Interestingly, these alterations were more strongly observed in TP-treated mice than in PP-treated mice, consistent with the level of central anticholinergic action. Anticholinergic drugs not only impair cognitive function by decreased ACh neurotransmission, but also accelerate neurodegeneration by suppressing an ACh-dependent anti-inflammatory system. Anticholinergics should be less readily prescribed to reduce the risk of dementia.

  20. Depletion of natural killer cells increases mice susceptibility in a Pseudomonas aeruginosa pneumonia model.

    Science.gov (United States)

    Broquet, Alexis; Roquilly, Antoine; Jacqueline, Cédric; Potel, Gilles; Caillon, Jocelyne; Asehnoune, Karim

    2014-06-01

    Pseudomonas aeruginosa infection is a clinically relevant infection involved in pneumonia in ICUs. Understanding the type of immune response initiated by the host during pneumonia would help defining new strategies to interfere with the bacteria pathogenicity. In this setting, the role of natural killer cells remains controversial. We assessed the role of systemic natural killer cells in a Pseudomonas aeruginosa mouse pneumonia model. Experimental study. Research laboratory from a university hospital. RjOrl:SWISS and BALB/cJ mice (weight, 20-24 g). Lung injuries were assessed by bacterial load, myeloperoxidase activity, endothelial permeability (pulmonary edema), immune cell infiltrate (histological analysis), proinflammatory cytokine release, and Ly6-G immunohistochemistry. Bacterial loads were assessed in the lungs and spleen. Natural killer cell number and status were assessed in spleen (flow cytometry and quantitative polymerase chain reaction). Depletion of natural killer cells was achieved through an IV anti-asialo-GM1 antibody injection. Pseudomonas aeruginosa tracheal instillation led to an acute pneumonia with a rapid decrease of bacterial load in lungs and with an increase of endothelial permeability, proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β), and myeloperoxidase activity followed by Ly6-G positive cell infiltrate in lungs. Pseudomonas aeruginosa was detected in the spleen. Membrane markers of activation and maturation (CD69 and KLRG1 molecules) were increased in splenic natural killer cells during Pseudomonas aeruginosa infection. Splenic natural killer cells activated upon Pseudomonas aeruginosa infection produced interferon-γ but not interleukin-10. Ultimately, mice depleted of natural killer cells displayed an increased neutrophil numbers in the lungs and an increased mortality rate without bacterial load modifications in the lungs, indicating that mice depleted of natural killer cells were much more susceptible to

  1. Ts65Dn, a mouse model of Down syndrome, exhibits increased GABAB-induced potassium current.

    Science.gov (United States)

    Best, Tyler K; Siarey, Richard J; Galdzicki, Zygmunt

    2007-01-01

    Down syndrome (DS) is the most common nonheritable cause of mental retardation. DS is the result of the presence of an extra chromosome 21 and its phenotype may be a consequence of overexpressed genes from that chromosome. One such gene is Kcnj6/Girk2, which encodes the G-protein-coupled inward rectifying potassium channel subunit 2 (GIRK2). We have recently shown that the DS mouse model, Ts65Dn, overexpresses GIRK2 throughout the brain and in particular the hippocampus. Here we report that this overexpression leads to a significant increase ( approximately 2-fold) in GABA(B)-mediated GIRK current in primary cultured hippocampal neurons. The dose response curves for peak and steady-state GIRK current density is significantly shifted left toward lower concentrations of baclofen in Ts65Dn neurons compared with diploid controls, consistent with increased functional expression of GIRK channels. Stationary fluctuation analysis of baclofen-induced GIRK current from Ts65Dn neurons indicated no significant change in single-channel conductance compared with diploid. However, significant increases in GIRK channel density was found in Ts65Dn neurons. In normalized baclofen-induced GIRK current and GIRK current kinetics no difference was found between diploid and Ts65Dn neurons, which suggests unimpaired mechanisms of interaction between GIRK channel and GABA(B) receptor. These results indicate that increased expression of GIRK2 containing channels have functional consequences that likely affect the balance between excitatory and inhibitory neuronal transmission.

  2. Elimination of African onchocerciasis: modeling the impact of increasing the frequency of ivermectin mass treatment.

    Directory of Open Access Journals (Sweden)

    Luc E Coffeng

    Full Text Available The African Programme for Onchocerciasis Control (APOC is currently shifting its focus from morbidity control to elimination of infection. To enhance the likelihood of elimination and speed up its achievement, programs may consider to increase the frequency of ivermectin mass treatment from annual to 6-monthly or even higher. In a computer simulation study, we examined the potential impact of increasing the mass treatment frequency for different settings. With the ONCHOSIM model, we simulated 92,610 scenarios pertaining to different assumptions about transmission conditions, history of mass treatment, the future mass treatment strategy, and ivermectin efficacy. Simulation results were used to determine the minimum remaining program duration and number of treatment rounds required to achieve 99% probability of elimination. Doubling the frequency of treatment from yearly to 6-monthly or 3-monthly was predicted to reduce remaining program duration by about 40% or 60%, respectively. These reductions come at a cost of additional treatment rounds, especially in case of 3-monthly mass treatment. Also, aforementioned reductions are highly dependent on maintained coverage, and could be completely nullified if coverage of mass treatment were to fall in the future. In low coverage settings, increasing treatment coverage is almost just as effective as increasing treatment frequency. We conclude that 6-monthly mass treatment may only be worth the effort in situations where annual treatment is expected to take a long time to achieve elimination in spite of good treatment coverage, e.g. because of unfavorable transmission conditions or because mass treatment started recently.

  3. Structural Changes in Ceramide Bilayers Rationalize Increased Permeation through Stratum Corneum Models with Shorter Acyl Tails.

    Science.gov (United States)

    Paloncýová, Markéta; Vávrová, Kateřina; Sovová, Žofie; DeVane, Russell; Otyepka, Michal; Berka, Karel

    2015-07-30

    Ceramides are indispensable constituents of the stratum corneum (SC), the uppermost impermeable layer of human skin. Ceramides with shorter (four- to eight-carbon acyl chains) fatty acid chains increase skin and model membrane permeability, while further shortening of the chain leads to increased resistance to penetration almost as good as that of ceramides from healthy skin (24 carbons long on average). Here we address the extent to which the atomistic CHARMM36 and coarse-grain MARTINI molecular dynamics (MD) simulations reflect the skin permeability data. As a result, we observed the same bell-shaped permeability trend for water that was observed in the skin and multilayer membrane experiments for model compounds. We showed that the enhanced permeability of the short ceramides is mainly caused by the disturbance of their headgroup conformation because of their inability to accommodate the shorter lipid acyl chain into a typical hairpin conformation, which further led to their destabilization and phase separation. As MD simulations described well delicate structural features of SC membranes, they seem to be suitable for further studies of the SC superstructure, including the development of skin penetration enhancers for transdermal drug delivery and skin toxicity risk assessment studies.

  4. 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.

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

    Science.gov (United States)

    Bargiela, Ariadna; Cerro-Herreros, Estefanía; Fernandez-Costa, Juan M; Vilchez, Juan J; Llamusi, Beatriz; Artero, Ruben

    2015-07-01

    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.

  6. A pig model of acute right ventricular afterload increase by hypoxic pulmonary vasoconstriction.

    Science.gov (United States)

    Knai, Kathrine; Skjaervold, Nils Kristian

    2017-01-03

    The aim of this study was to construct a non-invasive model for acute right ventricular afterload increase by hypoxic pulmonary vasoconstriction. Intact animal models are vital to improving our understanding of the pathophysiology of acute right ventricular failure. Acute right ventricular failure is caused by increased afterload of the right ventricle by chronic or acute pulmonary hypertension combined with regionally or globally reduced right ventricular contractile capacity. Previous models are hampered by their invasiveness; this is unfortunate as the pulmonary circulation is a low-pressure system that needs to be studied in closed chest animals. Hypoxic pulmonary vasoconstriction is a mechanism that causes vasoconstriction in alveolar vessels in response to alveolar hypoxia. In this study we explored the use of hypoxic pulmonary vasoconstriction as a means to increase the pressure load on the right ventricle. Pulmonary hypertension was induced by lowering the FiO2 to levels below the physiological range in eight anesthetized and mechanically ventilated pigs. The pigs were monitored with blood pressure measurements and blood gases. The mean pulmonary artery pressures (mPAP) of the animals increased from 18.3 (4.2) to 28.4 (4.6) mmHg and the pulmonary vascular resistance (PVR) from 254 (76) dyns/cm(5) to 504 (191) dyns/cm(5), with a lowering of FiO2 from 0.30 to 0.15 (0.024). The animals' individual baseline mPAPs varied substantially as did their response to hypoxia. The reduced FiO2 level yielded an overall lowering in oxygen offer, but the global oxygen consumption was unaltered. We showed in this study that the mPAP and the PVR could be raised by approximately 100% in the study animals by lowering the FiO2 from 0.30 to 0.15 (0.024). We therefore present a novel method for minimally invasive (closed chest) right ventricular afterload manipulations intended for future studies of acute right ventricular failure. The method should in theory be reversible

  7. 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.

  8. A mouse model of Alzheimer's disease displays increased susceptibility to kindling and seizure-associated death.

    Science.gov (United States)

    Chan, Jianxiong; Jones, Nigel C; Bush, Ashley I; O'Brien, Terence J; Kwan, Patrick

    2015-06-01

    People with Alzheimer's disease (AD) are up to 10 times more likely to develop epilepsy than the age-matched general population. However, given that only a proportion of patients with AD develop epilepsy, it is likely that additional factors may be required for the epilepsy to emerge. This study aimed to better understand the relationship between AD pathology and seizure susceptibility. It also aimed to investigate a "two-hit" hypothesis for seizure susceptibility through amygdala kindling of rodent AD models. Aged AD mice (Tg2576 model) and wild-type (WT) mice underwent electrical amygdala kindling. Compared with WT mice, Tg2576 mice had significantly lower afterdischarge threshold. Significantly fewer stimulations were required for the Tg2576 mice to reach the first class V seizure. Higher death rate was observed with Tg2576 mice in the kindling group. Both sham and kindled Tg2576 animals had increased levels of sprouting in the supragranular layer of the dentate gyrus compared with the WT counterparts. These findings support the "two-hit" hypothesis and represent a potentially novel research model to help better understand the relationship between AD pathology and epilepsy.

  9. 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.

  10. Modeling effectiveness of gradual increases in source level to mitigate effects of sonar on marine mammals.

    Science.gov (United States)

    Von Benda-Beckmann, Alexander M; Wensveen, Paul J; Kvadsheim, Petter H; Lam, Frans-Peter A; Miller, Patrick J O; Tyack, Peter L; Ainslie, Michael A

    2014-02-01

    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 effectiveness of ramp-up procedures in reducing the area within which changes in hearing thresholds can occur. We modeled the level of sound killer whales (Orcinus orca) were exposed to from a generic sonar operation preceded by different ramp-up schemes. In our model, ramp-up procedures reduced the risk of killer whales receiving sounds of sufficient intensity to affect their hearing. The effectiveness of the ramp-up procedure depended strongly on the assumed response threshold and differed with ramp-up duration, although extending the duration of the ramp up beyond 5 min did not add much to its predicted mitigating effect. The main factors that limited effectiveness of ramp up in a typical antisubmarine warfare scenario were high source level, rapid moving sonar source, and long silences between consecutive sonar transmissions. Our exposure modeling approach can be used to evaluate and optimize mitigation procedures. © 2013 Society for Conservation Biology.

  11. Increasing thickness and fibrosis of the cartilage in acetabular dysplasia: a rabbit model research

    Institute of Scientific and Technical Information of China (English)

    LI Tian-you; MA Rui-xue

    2010-01-01

    Background The order and mechanism of pathological changes in acetabular dysplasia are still unclear. This study investigated cartilage changes in rabbit acetabular dysplasia models at different ages.Methods Twenty-seven 1-month-old New Zealand rabbits underwent cast immobilization of the left hind limb in knee extension. Serial acetabular dysplasia models were established by assessment of the acetabular index and Sharp's angle on radiographs. The thickness of the acetabular cartilage was measured under a microscope, and fibrosis was observed. Ultrastructural changes were investigated with scanning electron microscopy and transmission electron microscopy. The messenger RNA expression of collagen Ⅰ and Ⅱ, β1 integrin, and caspase-9 were measured by real-time fluorescence quantitative polymerase chain reaction.Results In an immature group of rabbits, the acetabular index of the treated hip increased with animal growth. The cartilage on the brim of the left acetabulum was significantly thicker than that on the right side. The collagen fibrils on the surface of the cartilage became gross, and the chondrocytes in the enlargement layer underwent necrosis. In a mature group of rabbits, the left Sharp's angle increased in the rabbits with 6-week casting. The cartilage on the brim of the left acetabulum underwent fibrosis. The chondrocytes were weakly stained, and the number of lysosomes was much larger than normal. The messenger RNA expression of collagen Ⅰ and Ⅱ, β1 integrin, and caspase-9 in the cartilage differed significantly at different ages.Conclusions Increasing thickness followed by fibrosis may be the order of pathological cartilage changes in acetabular dysplasia, with changes in ultrastructure and collagen expression contributing to the process.

  12. Increased white matter neuron density in a rat model of maternal immune activation - Implications for schizophrenia.

    Science.gov (United States)

    Duchatel, Ryan J; Jobling, Phillip; Graham, Brett A; Harms, Lauren R; Michie, Patricia T; Hodgson, Deborah M; Tooney, Paul A

    2016-02-01

    Interstitial neurons are located among white matter tracts of the human and rodent brain. Post-mortem studies have identified increased interstitial white matter neuron (IWMN) density in the fibre tracts below the cortex in people with schizophrenia. The current study assesses IWMN pathology in a model of maternal immune activation (MIA); a risk factor for schizophrenia. Experimental MIA was produced by an injection of polyinosinic:polycytidylic acid (PolyI:C) into pregnant rats on gestational day (GD) 10 or GD19. A separate control group received saline injections. The density of neuronal nuclear antigen (NeuN(+)) and somatostatin (SST(+)) IWMNs was determined in the white matter of the corpus callosum in two rostrocaudally adjacent areas in the 12week old offspring of GD10 (n=10) or GD19 polyI:C dams (n=18) compared to controls (n=20). NeuN(+) IWMN density trended to be higher in offspring from dams exposed to polyI:C at GD19, but not GD10. A subpopulation of these NeuN(+) IWMNs was shown to express SST. PolyI:C treatment of dams induced a significant increase in the density of SST(+) IWMNs in the offspring when delivered at both gestational stages with more regionally widespread effects observed at GD19. A positive correlation was observed between NeuN(+) and SST(+) IWMN density in animals exposed to polyI:C at GD19, but not controls. This is the first study to show that MIA increases IWMN density in adult offspring in a similar manner to that seen in the brain in schizophrenia. This suggests the MIA model will be useful in future studies aimed at probing the relationship between IWMNs and schizophrenia.

  13. Prophylactic Chronic Zinc Administration Increases Neuroinflammation in a Hypoxia-Ischemia Model

    Science.gov (United States)

    Tomas-Sanchez, Constantino; Blanco-Alvarez, Victor Manuel; Gonzalez-Barrios, Juan Antonio; Martinez-Fong, Daniel; Garcia-Robles, Guadalupe; Soto-Rodriguez, Guadalupe; Torres-Soto, Maricela; Gonzalez-Vazquez, Alejandro; Aguilar-Peralta, Ana Karina; Garate-Morales, José-Luis; Aguilar-Carrasco, Luis-Angel; Limón, Daniel I.; Cebada, Jorge

    2016-01-01

    Acute and subacute administration of zinc exert neuroprotective effects in hypoxia-ischemia animal models; yet the effect of chronic administration of zinc still remains unknown. We addressed this issue by injecting zinc at a tolerable dose (0.5 mg/kg weight, i.p.) for 14 days before common carotid artery occlusion (CCAO) in a rat. After CCAO, the level of zinc was measured by atomic absorption spectrophotometry, nitrites were determined by Griess method, lipoperoxidation was measured by Gerard-Monnier assay, and mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors was measured by qRT-PCR, whereas nitrotyrosine, chemokines, and their receptors were assessed by ELISA and histopathological changes in the temporoparietal cortex-hippocampus at different time points. Long-term memory was evaluated using Morris water maze. Following CCAO, a significant increase in nitrosative stress, inflammatory chemokines/receptors, and cell death was observed after 8 h, and a 2.5-fold increase in zinc levels was detected after 7 days. Although CXCL12 and FGF2 protein levels were significantly increased, the long-term memory was impaired 12 days after reperfusion in the Zn+CCAO group. Our data suggest that the chronic administration of zinc at tolerable doses causes nitrosative stress, toxic zinc accumulation, and neuroinflammation, which might account for the neuronal death and cerebral dysfunction after CCAO. PMID:27635404

  14. 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.

  15. Reduced thermal sensitivity and increased opioidergic tone in the TASTPM mouse model of Alzheimer's disease.

    Science.gov (United States)

    Aman, Yahyah; Pitcher, Thomas; Simeoli, Raffaele; Ballard, Clive; Malcangio, Marzia

    2016-10-01

    Individuals with Alzheimer's disease (AD) are in susceptible patient groups in which pain is an important clinical issue that is often underdiagnosed. However, it is unclear whether decreased pain complaints in patients with AD result from elevated pain tolerance or an impaired ability to communicate sensations. Here, we explored if AD-related pathology is present in key regions of the pain pathway and assessed whether nociceptive thresholds to acute noxious stimulation are altered in the double-mutant APPswe × PS1.M146V (TASTPM) transgenic mouse model of AD. TASTPM mice exhibited an age-dependant cognitive deficit at the age of 6 months, but not at 4 months, a deficit that was accompanied by amyloid plaques in the cortex, hippocampus, and thalamus. In the spinal cord, β-amyloid (APP/Aβ) immunoreactivity was observed in dorsal and ventral horn neurons, and the expression of vesicular glutamate transporter 2 (VGLUT2) was significantly reduced, while the expression of the inhibitory peptides enkephalins was increased in TASTPM dorsal horn, consistent with an increased inhibitory tone. TASTPM mice displayed reduced sensitivity to acute noxious heat, which was reversed by naloxone, an opioid antagonist. This study suggests that increased inhibition and decreased excitation in the spinal cord may be responsible for the reduced thermal sensitivity associated with AD-related pathology.

  16. Increased upper airway collapsibility in a mouse model of Marfan syndrome.

    Science.gov (United States)

    da Palma, Renata Kelly; Farré, Ramon; Montserrat, Josep Maria; Gorbenko Del Blanco, Darya; Egea, Gustavo; de Oliveira, Luís Vicente Franco; Navajas, Daniel; Almendros, Isaac

    2015-02-01

    Marfan syndrome (MFS) is a genetic disorder caused by mutations in the FBN1 gene that codifies for fibrilin-1. MFS affects elastic fiber formation and the resulting connective tissue shows abnormal tissue laxity and organization. Although an increased prevalence of obstructive sleep apnea among patients with MFS has been described, the potential effects of this genetic disease on the collapsible properties of the upper airway are unknown. The aim of this study was to assess the collapsible properties of the upper airway in a mouse model of MFS Fbn1((C1039G/+)) that is representative of most of the clinical manifestations observed in human patients. The upper airway in wild-type and Marfan mice was cannulated and its critical pressure (Pcrit) was measured in vivo by increasing the negative pressure through a controlled pressure source. Pcrit values from MFS mice were higher (less negative) compared to wild-type mice (-3.1±0.9cmH2O vs. -7.8±2.0cm H2O) suggesting that MFS increases the upper airway collapsibility, which could in turn explain the higher prevalence of OSA in MFS patients.

  17. 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 B1(+) 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.

  18. 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.

  19. Prophylactic Chronic Zinc Administration Increases Neuroinflammation in a Hypoxia-Ischemia Model

    Directory of Open Access Journals (Sweden)

    Constantino Tomas-Sanchez

    2016-01-01

    Full Text Available Acute and subacute administration of zinc exert neuroprotective effects in hypoxia-ischemia animal models; yet the effect of chronic administration of zinc still remains unknown. We addressed this issue by injecting zinc at a tolerable dose (0.5 mg/kg weight, i.p. for 14 days before common carotid artery occlusion (CCAO in a rat. After CCAO, the level of zinc was measured by atomic absorption spectrophotometry, nitrites were determined by Griess method, lipoperoxidation was measured by Gerard-Monnier assay, and mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors was measured by qRT-PCR, whereas nitrotyrosine, chemokines, and their receptors were assessed by ELISA and histopathological changes in the temporoparietal cortex-hippocampus at different time points. Long-term memory was evaluated using Morris water maze. Following CCAO, a significant increase in nitrosative stress, inflammatory chemokines/receptors, and cell death was observed after 8 h, and a 2.5-fold increase in zinc levels was detected after 7 days. Although CXCL12 and FGF2 protein levels were significantly increased, the long-term memory was impaired 12 days after reperfusion in the Zn+CCAO group. Our data suggest that the chronic administration of zinc at tolerable doses causes nitrosative stress, toxic zinc accumulation, and neuroinflammation, which might account for the neuronal death and cerebral dysfunction after CCAO.

  20. Power-Law Dynamics of Membrane Conductances Increase Spiking Diversity in a Hodgkin-Huxley Model.

    Science.gov (United States)

    Teka, Wondimu; Stockton, David; Santamaria, Fidel

    2016-03-01

    We studied the effects of non-Markovian power-law voltage dependent conductances on the generation of action potentials and spiking patterns in a Hodgkin-Huxley model. To implement slow-adapting power-law dynamics of the gating variables of the potassium, n, and sodium, m and h, conductances we used fractional derivatives of order η≤1. The fractional derivatives were used to solve the kinetic equations of each gate. We systematically classified the properties of each gate as a function of η. We then tested if the full model could generate action potentials with the different power-law behaving gates. Finally, we studied the patterns of action potential that emerged in each case. Our results show the model produces a wide range of action potential shapes and spiking patterns in response to constant current stimulation as a function of η. In comparison with the classical model, the action potential shapes for power-law behaving potassium conductance (n gate) showed a longer peak and shallow hyperpolarization; for power-law activation of the sodium conductance (m gate), the action potentials had a sharp rise time; and for power-law inactivation of the sodium conductance (h gate) the spikes had wider peak that for low values of η replicated pituitary- and cardiac-type action potentials. With all physiological parameters fixed a wide range of spiking patterns emerged as a function of the value of the constant input current and η, such as square wave bursting, mixed mode oscillations, and pseudo-plateau potentials. Our analyses show that the intrinsic memory trace of the fractional derivative provides a negative feedback mechanism between the voltage trace and the activity of the power-law behaving gate variable. As a consequence, power-law behaving conductances result in an increase in the number of spiking patterns a neuron can generate and, we propose, expand the computational capacity of the neuron.

  1. Power-Law Dynamics of Membrane Conductances Increase Spiking Diversity in a Hodgkin-Huxley Model.

    Directory of Open Access Journals (Sweden)

    Wondimu Teka

    2016-03-01

    Full Text Available We studied the effects of non-Markovian power-law voltage dependent conductances on the generation of action potentials and spiking patterns in a Hodgkin-Huxley model. To implement slow-adapting power-law dynamics of the gating variables of the potassium, n, and sodium, m and h, conductances we used fractional derivatives of order η≤1. The fractional derivatives were used to solve the kinetic equations of each gate. We systematically classified the properties of each gate as a function of η. We then tested if the full model could generate action potentials with the different power-law behaving gates. Finally, we studied the patterns of action potential that emerged in each case. Our results show the model produces a wide range of action potential shapes and spiking patterns in response to constant current stimulation as a function of η. In comparison with the classical model, the action potential shapes for power-law behaving potassium conductance (n gate showed a longer peak and shallow hyperpolarization; for power-law activation of the sodium conductance (m gate, the action potentials had a sharp rise time; and for power-law inactivation of the sodium conductance (h gate the spikes had wider peak that for low values of η replicated pituitary- and cardiac-type action potentials. With all physiological parameters fixed a wide range of spiking patterns emerged as a function of the value of the constant input current and η, such as square wave bursting, mixed mode oscillations, and pseudo-plateau potentials. Our analyses show that the intrinsic memory trace of the fractional derivative provides a negative feedback mechanism between the voltage trace and the activity of the power-law behaving gate variable. As a consequence, power-law behaving conductances result in an increase in the number of spiking patterns a neuron can generate and, we propose, expand the computational capacity of the neuron.

  2. 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

  3. 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

  4. 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

  5. Increase in osteoclastogenesis in an obese Otsuka Long-Evans Tokushima fatty rat model.

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    Ootsuka, Tomoyo; Nakanishi, Atsuko; Tsukamoto, Ikuyo

    2015-09-01

    In the present study, the effects of obesity on bone metabolism were investigated using a hyperphagic and obese rat model, the Otsuka Long‑Evans Tokushima fatty (OLETF) rat, which exhibits normal glycemic control at 8 weeks of age. Body weight, food intake, fat mass, markers of bone resorption, the activities of tartrate‑resistant acid phosphatase (TRAP) and cathepsin K, the number of osteoclasts in the proximal tibia, and the serum C‑terminal crosslinking telopeptide level were higher in OLETF rats than those in control rats (Long‑Evans Tokushima Otsuka; LETO). However, no differences in markers of bone formation, alkaline phosphatase activity, the number of osteoblasts in the proximal tibia or the serum osteocalcin level were observed. mRNA and protein levels of c‑fms, receptor for activation of nuclear factor‑κB (RANK), RANK ligand (RANKL), TRAP and cathepsin K were significantly increased in OLETF rats, although those levels of macrophage colony‑stimulating factor (M‑CSF) and osteoprotegerin (OPG) were similar to those in LETO rats. The level of serum tumor necrosis factor α (TNFα), and that of TNFα mRNA in bone, increased in association with the activation of NFκB. Furthermore, a frequency analysis and a colony formation assay respectively showed that the number of osteoclast precursors and the number of colony‑forming cells induced by M‑CSF each increased in OLETF rats compared with the control group. These results suggested that hyperphagia‑induced obesity with normal glycemic control induces the upregulation of osteoclastogenesis that is associated with an increase in the expression of c‑fms, RANK and RANKL, which is induced by TNFα, via the activation of NFκB.

  6. Modifications of the fiber in adenovirus vectors increase tropism for malignant glioma models.

    Science.gov (United States)

    Staba, M J; Wickham, T J; Kovesdi, I; Hallahan, D E

    2000-01-01

    Recombinant adenovirus (Ad) vectors provide a means of local, therapeutic gene delivery to a wide range of neoplasms. Ad-mediated gene therapy trials in malignant glioma models have been limited by the need for high viral titers and multiple dosages. In an attempt to improve Ad vector gene transfer, we studied human (U87, D54) and rodent (GL261, C6) malignant glioma cell lines transfected with various doses of unmodified Ad vectors (AdZ), Ad vectors that contain an alteration of the fiber-coat protein and that direct virus binding to heparan sulfate receptors (AdZ.F(pK7)), and Ad vectors with modifications of the fiber-coat protein that direct virus binding to alpha1, integrin cellular receptors (AdZ.F(RGD)). AdZ.F(pK7) increased the frequency of cells expressing the reporter gene, beta-galactosidase, and improved transduction by 2- to 20-fold compared with AdZ in U87, D54, and GL261 cells. In U87, D54, GL261, and C6 tumors, AdZ.F(pK7) increased gene transfer by 10- to 100-fold compared with AdZ. AdZ.F(RGD) increased gene expression in C6 xenografts compared with AdZ, but had reduced transduction compared with the C6 xenografts of AdZ in all other glioma tumors. These findings suggest that the increased tropisms resulting from alterations of the Ad vector fiber-coat protein as in AdZ.F(pK7) and AdZ.F(RGD) offer a feasible approach to improving in vitro and in vivo transduction efficiencies in certain malignant glioma cell lines.

  7. Modelling increased landslide susceptibility near highways in the Andes of southern Ecuador

    Science.gov (United States)

    Brenning, Alexander; Muenchow, Jannes

    2016-04-01

    Modelling increased landslide susceptibility near highways in the Andes of southern Ecuador A. Brenning (1), J. Muenchow (1) (1) Department of Geography, Friedrich Schiller University Jena, Loebdergraben 32, 07743 Jena, Germany Mountain roads are affected by and also affect themselves landslide suceptibility. Especially in developing countries, inadequate drainage systems and mechanical destabilization of hillslopes by undercutting and overloading are known processes through which road construction and maintenance can enhance landslide activity within the immediate surroundings of road infrastructure. In the Andes of southern Ecuador, strong precipitation gradients as well as lithological differences provide an excellent study site in which the relationship between highways and landslide susceptibility and its regional differentiation can be studied. This study uses Generalized Additive Models (GAM) to investigate patterns of landslide susceptibility along two paved interurban highways in the tropical Andes of southern Ecuador. The relationship of landslides to distance from road is modeled while accounting for topographic, climatic and lithological predictors as possible confounders and modifiers, focusing on the odds ratio of landslide occurrence at 25 m versus 200 m distance from the highway. Spatial attention is given to uncertainties in estimated odds ratios of landslide occurrence using spatial block bootstrap techniques. The GAM is able to represent nonlinear additive terms as well as bivariate smooth interaction terms, providing a good tradeoff between model complexity and interpretability. The estimated odds of landslide occurrence were 18-21 times higher near the highway than at 200 m distance, based on different analyses, with lower 95% confidence limits always >13. (Semi-) parametric estimates confirmed this general range of values but suggests slightly higher odds ratios (95% confidence interval: 15.5-25.3). Highway-related effects were observed to

  8. Impaired satiation and increased feeding behaviour in the triple-transgenic Alzheimer's disease mouse model.

    Directory of Open Access Journals (Sweden)

    Adedolapo Adebakin

    Full Text Available Alzheimer's disease (AD is associated with non-cognitive symptoms such as changes in feeding behaviour that are often characterised by an increase in appetite. Increased food intake is observed in several mouse models of AD including the triple transgenic (3×TgAD mouse, but the mechanisms underlying this hyperphagia are unknown. We therefore examined feeding behaviour in 3×TgAD mice and tested their sensitivity to exogenous and endogenous satiety factors by assessing food intake and activation of key brain regions. In the behavioural satiety sequence (BSS, 3×TgAD mice consumed more food after a fast compared to Non-Tg controls. Feeding and drinking behaviours were increased and rest decreased in 3×TgAD mice, but the overall sequence of behaviours in the BSS was maintained. Exogenous administration of the satiety factor cholecystokinin (CCK; 8-30 µg/kg, i.p. dose-dependently reduced food intake in Non-Tg controls and increased inactive behaviour, but had no effect on food intake or behaviour in 3×TgAD mice. CCK (15 µg/kg, i.p. increased c-Fos protein expression in the supraoptic nucleus of the hypothalamus, and the nucleus tractus solitarius (NTS and area postrema of the brainstem to the same extent in Non-Tg and 3×TgAD mice, but less c-Fos positive cells were detected in the paraventricular hypothalamic nucleus of CCK-treated 3×TgAD compared to Non-Tg mice. In response to a fast or a period of re-feeding, there was no difference in the number of c-Fos-positive cells detected in the arcuate nucleus of the hypothalamus, NTS and area postrema of 3×TgAD compared to Non-Tg mice. The degree of c-Fos expression in the NTS was positively correlated to food intake in Non-Tg mice, however, this relationship was absent in 3×TgAD mice. These data demonstrate that 3×TgAD mice show increased feeding behaviour and insensitivity to satiation, which is possibly due to defective gut-brain signalling in response to endogenous satiety factors released

  9. Increased wall thickness using ultrasonography is associated with inflammation in an animal model of experimental colitis

    Directory of Open Access Journals (Sweden)

    Lied GA

    2012-10-01

    Full Text Available Gülen Arslan Lied,1 Anne Marita Milde,2 Kim Nylund,1,3 Maja Mujic,1 Tore Grimstad,1,4 Trygve Hausken,1,3 Odd Helge Gilja1,31Institute of Medicine, University of Bergen, Norway; 2Department of Biological and Medical Psychology, University of Bergen, Norway; 3National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway; 4Division of Gastroenterology, Stavanger University Hospital, Stavanger, NorwayAbstract: Experimentally induced colitis is used in animals to investigate pathophysiological mechanisms in inflammatory bowel disease. When following disease course and treatment effects, it should be possible to perform repeated measurements without harming the animals. This pilot study was performed to investigate whether transabdominal ultrasound using a clinical scanner could be used on rats to demonstrate bowel inflammation in an experimental colitis model. Colitis was induced by either 5% dextran sodium sulfate (DSS in drinking water for 7 days or a single dose of intracolonic trinitrobenzene sulfonic acid (TNBS. Using ultrasonography, wall thickness of distal colon, cecum, and small bowel was recorded prior to and after DSS, and prior to, 2, and 7 days after TNBS. Blood (tumor necrosis factor [TNF]-alpha and fecal samples (HemoFEC occult blood were taken from each group on the same days as sonography. Thereafter, rats were killed and specimens for histology were taken. Wall thickness of distal colon, not of cecum or small bowel, increased significantly after 7 days of DSS, and wall thickness of both distal colon and small bowel increased on day 2 and 7 after TNBS. TNF-alpha increased after 7 days in the latter group only. There was a significant correlation between ultrasonographic measurements and combined histology score of distal colon in the DSS group. HemoFEC was also positive in accordance with sonographic and histological features. Increased intestinal wall thickness in response to both DSS- and TNBS

  10. The increase in the number of astrocytes in the total cerebral ischemia model in rats

    Science.gov (United States)

    Kudabayeva, M.; Kisel, A.; Chernysheva, G.; Smol'yakova, V.; Plotnikov, M.; Khodanovich, M.

    2017-08-01

    Astrocytes are the most abundant cell class in the CNS. Astrocytic therapies have a huge potential for neuronal repair after stroke. The majority of brain stroke studies address the damage to neurons. Modern studies turn to the usage of morphological and functional changes in astroglial cells after stroke in regenerative medicine. Our study is focused on the changes in the number of astrocytes in the hippocampus (where new glia cells divide) after brain ischemia. Ischemia was modeled by occlusion of tr. brachiocephalicus, a. subclavia sin., a. carotis communis sin. Astrocytes were determined using immunohistochemical labeling with anti GFAP antibody. We found out that the number of astrocytes increased on the 10th and 30th days after stroke in the CA1, CA2 fields, the granular layer of dentate gyrus (GrDG) and hilus. The morphology of astrocytes became reactive in these regions. Therefore, our results revealed long-term reactive astrogliosis in the hippocampus region after total ischemia in rats.

  11. Loss of dystrophin is associated with increased myocardial stiffness in a model of left ventricular hypertrophy.

    Science.gov (United States)

    Donato, Martín; Buchholz, Bruno; Morales, Celina; Valdez, Laura; Zaobornyj, Tamara; Baratta, Sergio; Paez, Diamela T; Matoso, Mirian; Vaccarino, Guillermo; Chejtman, Demian; Agüero, Oscar; Telayna, Juan; Navia, José; Hita, Alejandro; Boveris, Alberto; Gelpi, Ricardo J

    2017-08-01

    Transition from compensated to decompensated left ventricular hypertrophy (LVH) is accompanied by functional and structural changes. Here, the aim was to evaluate dystrophin expression in murine models and human subjects with LVH by transverse aortic constriction (TAC) and aortic stenosis (AS), respectively. We determined whether doxycycline (Doxy) prevented dystrophin expression and myocardial stiffness in mice. Additionally, ventricular function recovery was evaluated in patients 1 year after surgery. Mice were subjected to TAC and monitored for 3 weeks. A second group received Doxy treatment after TAC. Patients with AS were stratified by normal left ventricular end-diastolic wall stress (LVEDWS) and high LVEDWS, and groups were compared. In mice, LVH decreased inotropism and increased myocardial stiffness associated with a dystrophin breakdown and a decreased mitochondrial O2 uptake (MitoMVO2). These alterations were attenuated by Doxy. Patients with high LVEDWS showed similar results to those observed in mice. A correlation between dystrophin and myocardial stiffness was observed in both mice and humans. Systolic function at 1 year post-surgery was only recovered in the normal-LVEDWS group. In summary, mice and humans present diastolic dysfunction associated with dystrophin degradation. The recovery of ventricular function was observed only in patients with normal LVEDWS and without dystrophin degradation. In mice, Doxy improved MitoMVO2. Based on our results it is concluded that the LVH with high LVEDWS is associated to a degradation of dystrophin and increase of myocardial stiffness. At least in a murine model these alterations were attenuated after the administration of a matrix metalloprotease inhibitor.

  12. 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.

  13. Increased Skin Tumor Incidence and Keratinocyte Hyper-Proliferation in a Mouse Model of Down Syndrome.

    Science.gov (United States)

    Yang, Annan; Currier, Duane; Poitras, Jennifer L; Reeves, Roger H

    2016-01-01

    Down syndrome (DS) is a genetic disorder caused by the presence of an extra copy of human chromosome 21 (Hsa21). People with DS display multiple clinical traits as a result of the dosage imbalance of several hundred genes. While many outcomes of trisomy are deleterious, epidemiological studies have shown a significant risk reduction for most solid tumors in DS. Reduced tumor incidence has also been demonstrated in functional studies using trisomic DS mouse models. Therefore, it was interesting to find that Ts1Rhr trisomic mice developed more papillomas than did their euploid littermates in a DMBA-TPA chemical carcinogenesis paradigm. Papillomas in Ts1Rhr mice also proliferated faster. The increased proliferation was likely caused by a stronger response of trisomy to TPA induction. Treatment with TPA caused hyperkeratosis to a greater degree in Ts1Rhr mice than in euploid, reminiscent of hyperkeratosis seen in people with DS. Cultured trisomic keratinocytes also showed increased TPA-induced proliferation compared to euploid controls. These outcomes suggest that altered gene expression in trisomy could elevate a proliferation signalling pathway. Gene expression analysis of cultured keratinocytes revealed upregulation of several trisomic and disomic genes may contribute to this hyperproliferation. The contributions of these genes to hyper-proliferation were further validated in a siRNA knockdown experiment. The unexpected findings reported here add a new aspect to our understanding of tumorigenesis with clinical implications for DS and demonstrates the complexity of the tumor repression phenotype in this frequent condition.

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

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    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.

  15. 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.

  16. 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

  17. Increased intestinal protein permeability in a model of lung injury induced by phorbol myristate acetate.

    Science.gov (United States)

    St John, R C; Mizer, L A; Weisbrode, S E; Dorinsky, P M

    1991-11-01

    Multiple nonpulmonary organ failure is a frequent complication of the adult respiratory distress syndrome (ARDS), and contributes significantly to the high mortality rate associated with this disorder. Although previous studies suggest that systemic organ injury may be an integral component of ARDS, little is known about the specific functional alterations that occur in these target organs. The present study was designed, therefore, to test the hypothesis that endothelial damage, as assessed by microvascular permeability changes, develops in systemic organs in a model of acute lung injury. To test this postulate, the microvascular permeability for total protein was estimated using the steady-state relationship between the lymph (CL) to plasma (Cp) protein concentration ratio (i.e., CL/Cp) and lymph flow in autoperfused cat ileum preparations. Specifically, CL/Cp was measured in five cats, 2 h after acute lung injury was induced by intravenously administered phorbol myristate acetate (PMA), 15 micrograms/kg, and the results were compared with those of seven time-matched control animals. Prior to PMA infusion, the PaO2/FIO2 ratio was 451 +/- 28 in both groups and remained unchanged (486 +/- 26) in the control group. By contrast, the PaO2/FIO2 ratio fell to 275 +/- 95 after PMA infusion (p less than 0.05). In addition, whereas CL/Cp was 0.099 +/- 0.008 in the control animals, it increased to 0.36 +/- 0.06 in the PMA-injured animals (p less than 0.01). In summary, this study demonstrated that in this model of acute lung injury produced by PMA-induced activation of circulating inflammatory cells, both acute lung injury and systemic organ injury (i.e., morphologic and permeability alterations) occurred.

  18. Hyperactivity, perseveration and increased responding during attentional rule acquisition in the Fragile X mouse model.

    Science.gov (United States)

    Kramvis, Ioannis; Mansvelder, Huibert D; Loos, Maarten; Meredith, Rhiannon

    2013-01-01

    Attentional deficits and executive function impairments are common to many neurodevelopmental disorders of intellectual disability and autism, including Fragile X syndrome (FXS). In the knockout mouse model for FXS, significant changes in synaptic plasticity and connectivity are found in the prefrontal cortex (PFC)-a prominent region for attentional processing and executive control. Given these alterations in PFC synaptic function, we tested whether adult Fragile X knockout mice exhibited corresponding impairments in inhibitory control, perseveration, and sustained attention. Furthermore, we investigated individual performance during attentional rule acquisition. Using the 5-choice serial reaction time task, our results show no impairments in inhibitory control and sustained attention. Fragile X knockout mice exhibited enhanced levels of correct and incorrect responding, as well as perseveration of responding during initial phases of rule acquisition, that normalized with training. For both knockout and wild type mice, pharmacological attenuation of metabotropic glutamate receptor 5 signaling did not affect response accuracy but reduced impulsive responses and increased omission errors. Upon rule reversal, Fragile X knockout mice made more correct and incorrect responses, similar to the initial phases of rule acquisition. Analogous to heightened activity upon novel rule acquisition, Fragile X knockout mice were transiently hyperactive in both a novel open field (OF) arena and novel home cage. Hyperactivity ceased with familiarization to the environment. Our findings demonstrate normal inhibitory control and sustained attention but heightened perseveration, responding, and hyperactivity during novel rule acquisition and during exposure to novel environments in Fragile X knockout mice. We therefore provide evidence for subtle but significant differences in the processing of novel stimuli in the mouse model for the FXS.

  19. Increased forest carbon storage with increased atmospheric CO2 despite nitrogen limitation: a game-theoretic allocation model for trees in competition for nitrogen and light.

    Science.gov (United States)

    Dybzinski, Ray; Farrior, Caroline E; Pacala, Stephen W

    2015-03-01

    Changes in resource availability often cause competitively driven changes in tree allocation to foliage, wood, and fine roots, either via plastic changes within individuals or through turnover of individuals with differing strategies. Here, we investigate how optimally competitive tree allocation should change in response to elevated atmospheric CO2 along a gradient of nitrogen and light availability, together with how those changes should affect carbon storage in living biomass. We present a physiologically-based forest model that includes the primary functions of wood and nitrogen. From a tree's perspective, wood is an offensive and defensive weapon used against neighbors in competition for light. From a biogeochemical perspective, wood is the primary living reservoir of stored carbon. Nitrogen constitutes a tree's photosynthetic machinery and the support systems for that machinery, and its limited availability thus reduces a tree's ability to fix carbon. This model has been previously successful in predicting allocation to foliage, wood, and fine roots along natural productivity gradients. Using game theory, we solve the model for competitively optimal foliage, wood, and fine root allocation strategies for trees in competition for nitrogen and light as a function of CO2 and nitrogen mineralization rate. Instead of down-regulating under nitrogen limitation, carbon storage under elevated CO2 relative to carbon storage at ambient CO2 is approximately independent of the nitrogen mineralization rate. This surprising prediction is a consequence of both increased competition for nitrogen driving increased fine root biomass and increased competition for light driving increased allocation to wood under elevated CO2 .

  20. Increased Foraging in Outdoor Organic Pig Production-Modeling Environmental Consequences.

    Science.gov (United States)

    Jakobsen, Malene; Preda, Teodora; Kongsted, Anne Grete; Hermansen, John Erik

    2015-11-02

    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.

  1. Capsular switching as a strategy to increase pneumococcal virulence in experimental otitis media model.

    Science.gov (United States)

    Sabharwal, Vishakha; Stevenson, Abbie; Figueira, Marisol; Orthopoulos, George; Trzciński, Krzysztof; Pelton, Stephen I

    2014-04-01

    We hypothesized that capsular switch event, in which pneumococcus acquires a new capsule operon by horizontal gene transfer, may result in emergence of strains with increased virulence in acute otitis media. Using serotype 6A strain from a patient with invasive pneumococcal disease and clonally distant serotype 6C strain isolated from asymptomatic carrier we created 6A:6C (6A background with 6C capsule) capsular transformants and applied whole genome macro-restriction analysis to assess conservation of the 6A chassis. Next, we assessed complement (C3) and antibodies deposition on surface of pneumococcal cells and tested capsule recipient, capsule donor and two 6A:6C transformants for virulence in chinchilla experimental otitis media model. Both 6A:6C(1 or 2) transformants bound less C3 compared to 6C capsule-donor strain but more compared to serotype 6A capsule-recipient strain. Pneumococci were present in significantly higher proportion of ears among animals challenged with either of two 6A:6C(1 or 2) transformants compared to chinchillas infected with 6C capsule-donor strain [p < 0.001] whereas a significantly decreased proportion of ears were infected with 6A:6C(1 or 2) transformants as compared to 6A capsule-recipient strain. Our observations though limited to two serotypes demonstrate that capsular switch events can result in Streptococcus pneumoniae strains of enhanced virulence for respiratory tract infection.

  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. Agricultural capacity to increase the production of select fruits and vegetables in the US: A geospatial modeling analysis

    Science.gov (United States)

    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 land base to increase the per capita availability of an example set of nutrient-dense ...

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

    Directory of Open Access Journals (Sweden)

    Hartono -

    2013-06-01

    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

  5. Chronic nerve growth factor exposure increases apoptosis in a model of in vitro induced conjunctival myofibroblasts.

    Directory of Open Access Journals (Sweden)

    Alessandra Micera

    Full Text Available In the conjunctiva, repeated or prolonged exposure to injury leads to tissue remodeling and fibrosis associated with dryness, lost of corneal transparency and defect of ocular function. At the site of injury, fibroblasts (FB migrate and differentiate into myofibroblasts (myoFB, contributing to the healing process together with other cell types, cytokines and growth factors. While the physiological deletion of MyoFB is necessary to successfully end the healing process, myoFB prolonged survival characterizes the pathological process of fibrosis. The reason for myoFB persistence is poorly understood. Nerve Growth Factor (NGF, often increased in inflamed stromal conjunctiva, may represent an important molecule both in many inflammatory processes characterized by tissue remodeling and in promoting wound-healing and well-balanced repair in humans. NGF effects are mediated by the specific expression of the NGF neurotrophic tyrosine kinase receptor type 1 (trkA(NGFR and/or the pan-neurotrophin glycoprotein receptor (p75(NTR. Therefore, a conjunctival myoFB model (TGFβ1-induced myoFB was developed and characterized for cell viability/proliferation as well as αSMA, p75(NTR and trkA(NGFR expression. MyoFB were exposed to acute and chronic NGF treatment and examined for their p75(NTR/trkA(NGFR, αSMA/TGFβ1 expression, and apoptosis. Both NGF treatments significantly increased the expression of p75(NTR, associated with a deregulation of both αSMA/TGFβ1 genes. Acute and chronic NGF exposures induced apoptosis in p75(NTR expressing myoFB, an effect counteracted by the specific trkA(NGFR and/or p75(NTR inhibitors. Focused single p75(NTR and double trkA(NGFR/p75(NTR knocking-down experiments highlighted the role of p75(NTR in NGF-induced apoptosis. Our current data indicate that NGF is able to trigger in vitro myoFB apoptosis, mainly via p75(NTR. The trkA(NGFR/p75(NTR ratio in favor of p75(NTR characterizes this process. Due to the lack of effective

  6. A model intercomparison of changes in the Atlantic thermohaline circulation in response to increasing atmospheric CO2 concentration

    OpenAIRE

    Gregory, J; Dixon, K; Stouffer, R.; Weaver, A.; E. Driesschaert; Eby, M.; Fichefet, T.; Hasumi, H.; Hu, A.; J. Jungclaus; Kamenkovich, I.; A. Levermann; Montoya, M.; Murakami, S.; Nawrath , S.

    2005-01-01

    As part of the Coupled Model Intercomparison Project, integrations with a common design have been undertaken with eleven different climate models to compare the response of the Atlantic thermohaline circulation ( THC) to time-dependent climate change caused by increasing atmospheric CO2 concentration. Over 140 years, during which the CO2 concentration quadruples, the circulation strength declines gradually in all models, by between 10 and 50%. No model shows a rapid or complete collapse, desp...

  7. Climate warming due to increasing atmospheric CO2 - Simulations with a multilayer coupled atmosphere-ocean seasonal energy balance model

    Science.gov (United States)

    Li, Peng; Chou, Ming-Dah; Arking, Albert

    1987-01-01

    The transient response of the climate to increasing CO2 is studied using a modified version of the multilayer energy balance model of Peng et al. (1982). The main characteristics of the model are described. Latitudinal and seasonal distributions of planetary albedo, latitude-time distributions of zonal mean temperatures, and latitudinal distributions of evaporation, water vapor transport, and snow cover generated from the model and derived from actual observations are analyzed and compared. It is observed that in response to an atmospheric doubling of CO2, the model reaches within 1/e of the equilibrium response of global mean surface temperature in 9-35 years for the probable range of vertical heat diffusivity in the ocean. For CO2 increases projected by the National Research Council (1983), the model's transient response in annually and globally averaged surface temperatures is 60-75 percent of the corresponding equilibrium response, and the disequilibrium increases with increasing heat diffusivity of the ocean.

  8. 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 frequency

  9. Increased persistent sodium current determines cortical hyperexcitability in a genetic model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Pieri, Massimo; Carunchio, Irene; Curcio, Livia; Mercuri, Nicola Biagio; Zona, Cristina

    2009-02-01

    Cortical hyperexcitability has been observed in Amyotrophic Lateral Sclerosis (ALS) patients. Familial ALS accounts for 10% of all cases and mutations of the Cu,Zn superoxide dismutase (SOD1) gene have been identified in about 20% of the familial cases. The aim of this study was to investigate whether in a mouse model of ALS the cortical neurons developed hyperexcitability due to intrinsic properties of the single cell. We first examined the passive membrane properties and the pattern of repetitive firing in cultured cortical neurons from Control mice and transgenic mice expressing high levels of the human mutated protein (Gly(93)-->Ala, G93A). The former did not display significantly differing values between Control and G93A cortical neurons. However, the threshold potential and time of the first action potential decreased significantly and the firing frequency increased significantly in the G93A compared to Control neurons. The analysis of the voltage-dependent sodium currents revealed that the fast transient sodium current was unaffected by the SOD1 mutation whereas the persistent sodium current was significantly higher in the mutated neurons. Finally, Riluzole, a selective blocker of the persistent sodium current at low concentrations, decreased the firing frequency in G93A neurons, strongly indicating an involvement of this current in the observed hyperexcitability. These are the first data that demonstrate an intrinsic hyperexcitability in the G93A cortical neurons due to a higher current density of the persistent sodium current in the mutated neurons and open up new prospects of understanding ALS disease etiopathology.

  10. Dystropathology increases energy expenditure and protein turnover in the mdx mouse model of duchenne muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Hannah G Radley-Crabb

    Full Text Available 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.

  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.

  12. Influence of an increased intracranial pressure on cerebral and systemic haemodynamics during endoscopic neurosurgery : an animal model

    NARCIS (Netherlands)

    Kalmar, A. F.; De Ley, G.; Van Den Broecke, C.; Van Aken, J.; Struys, M. M. R. F.; Praet, M. M.; Mortier, E. P.

    2009-01-01

    During endoscopic neurosurgery, direct mechanical stimulation of the brain by the endoscope and increased intracranial pressure (ICP) caused by the continuous rinsing can induce potentially lethal haemodynamic reflexes, brain ischaemia, and excessive fluid resorption. In a newly presented rat model

  13. Influence of an increased intracranial pressure on cerebral and systemic haemodynamics during endoscopic neurosurgery : an animal model

    NARCIS (Netherlands)

    Kalmar, A. F.; De Ley, G.; Van Den Broecke, C.; Van Aken, J.; Struys, M. M. R. F.; Praet, M. M.; Mortier, E. P.

    2009-01-01

    During endoscopic neurosurgery, direct mechanical stimulation of the brain by the endoscope and increased intracranial pressure (ICP) caused by the continuous rinsing can induce potentially lethal haemodynamic reflexes, brain ischaemia, and excessive fluid resorption. In a newly presented rat model

  14. Positive Outcomes Increase over Time with the Implementation of a Semiflipped Teaching Model

    Science.gov (United States)

    Gorres-Martens, Brittany K.; Segovia, Angela R.; Pfefer, Mark T.

    2016-01-01

    The flipped teaching model can engage students in the learning process and improve learning outcomes. The purpose of the present study was to assess the outcomes of a semiflipped teaching model over time. Neurophysiology students spent the majority of class time listening to traditional didactic lectures, but they also listened to 5 online…

  15. Increasing Parental Involvement in the Primary Grades: The Magowan School Model.

    Science.gov (United States)

    Galen, Harlene

    Each school's version of a partnership with parents is unique, and no generic model exists. Designated in 1988 as one of 14 model schools in the New Jersey State Department of Education "Parents as Partners in Learning" project, the Mildred Magowan school in Edgewater Park has followed a systematic approach that has consistently led to…

  16. Direct Instruction Model to Increase Physical Science Competence of Students as One Form of Classroom Assesment

    Science.gov (United States)

    Wenno, Hendrik

    2014-01-01

    In designing the lesson teachers have to adapt the method or learning model with the material to be taught. In the teaching of measuring concept, students frequently faced with measuring instruments, micrometer, screw, scale, and so on. Direct Instruction Model would be suitable for teaching the measurement concepts specifically the skill of using…

  17. 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.…

  18. Increasing Engineering Students' Awareness to Environment through Innovative Teaching of Mathematical Modelling

    Science.gov (United States)

    Klymchuk, Sergiy; Zverkova, Tatyana; Gruenwald, Norbert; Sauerbier, Gabriele

    2008-01-01

    This article presents the results of two studies on using an innovative pedagogical strategy in teaching mathematical modelling and applications to engineering students. Both studies are dealing with introducing non-traditional contexts for engineering students in teaching/learning of mathematical modelling and applications: environment and…

  19. Using Video Modeling to Increase Variation in the Conversation of Children with Autism

    Science.gov (United States)

    Charlop, Marjorie H.; Gilmore, Laura; Chang, Gina T.

    2009-01-01

    The present study assessed the effects of video modeling on acquisition and generalization of variation in the conversational speech of two boys with autism. A video was made showing several versions of several topics of conversation, thus providing multiple exemplars of each conversation. Video modeling consisted of showing each child a video…

  20. 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.…

  1. 递增年金的双随机模型%DUAL RANDOM MODEL OF INCREASING ANNUITY

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The dual random models about the life insurance and social pension insurance have received considerable attention in the recent articles on actuarial theory and applications. This paper discusses a general kind of increasing annuity based on its force of interest accumulation function as a general random process. The dual random model of the present value of the benefits of the increasing annuity has been set, and their moments have been calculated under certain conditions.

  2. Oxidative stress is increased in C. elegans models of Huntington's disease but does not contribute to polyglutamine toxicity phenotypes.

    Science.gov (United States)

    Machiela, Emily; Dues, Dylan J; Senchuk, Megan M; Van Raamsdonk, Jeremy M

    2016-12-01

    Huntington's disease (HD) is an adult onset neurodegenerative disorder for which there is currently no cure. While HD patients and animal models of the disease exhibit increased oxidative damage, it is currently uncertain to what extent oxidative stress contributes to disease pathogenesis. In this work, we use a genetic approach to define the role of oxidative stress in HD. We find that a C. elegans model of HD expressing a disease-length polyglutamine tract in the body wall muscle is hypersensitive to oxidative stress and shows an upregulation of antioxidant defense genes, indicating that the HD worm model has increased levels of oxidative stress. To determine whether this increase in oxidative stress contributes to the development of polyglutamine-toxicity phenotypes in this HD model, we examined the effect of deleting individual superoxide dismutase (sod) genes in the HD worm model. As predicted, we found that deletion of sod genes in the HD worm model resulted in a clear increase in sensitivity to oxidative stress. However, we found that increasing oxidative stress in the HD worm model did not exacerbate deficits caused by polyglutamine toxicity. We confirmed these observations in two worm models expressing disease-length polyglutamine tracts in neurons. Furthermore, we found that treatment with antioxidants failed to rescue movement deficits or decrease aggregation in HD worm models. Combined, this suggests that the increase in oxidative stress in worm models of HD does not contribute to the phenotypic deficits observed in these worms, and provides a possible explanation for the failure of antioxidants in HD clinical trials.

  3. Loss of adiabaticity with increasing tunneling gap in nonintegrable multistate Landau-Zener models

    Science.gov (United States)

    Malla, Rajesh K.; Raikh, M. E.

    2017-09-01

    We consider the simplest nonintegrable model of the multistate Landau-Zener transition. In this model, two pairs of levels in two tunnel-coupled quantum dots are swept past each other by the gate voltage. Although this 2 ×2 model is nonintegrable, it can be solved analytically in the limit when the interlevel energy distance is much smaller than their tunnel splitting. The result is contrasted to the similar 2 ×1 model, in which one of the dots contains only one level. The latter model does not allow interference of the virtual transition amplitudes, and it is exactly solvable. In the 2 ×1 model, the probability for a particle, residing at time t →-∞ in one dot, to remain in the same dot at t →∞ , falls off exponentially with tunnel coupling. By contrast, in the 2 ×2 model, this probability grows rapidly with tunnel coupling. The physical origin of this growth is the formation of the tunneling-induced collective states in the system of two dots. This can be viewed as a manifestation of the Dicke effect.

  4. A Pedagogical Model for Increasing Race-Related Multicultural Counseling Competency

    Science.gov (United States)

    Buckley, Tamara R.; Foldy, Erica Gabrielle

    2010-01-01

    With the increasing need for multicultural competence, questions have emerged about the appropriate classroom strategies to cultivate growth in this area. These questions have been further complicated by a growing focus on self-awareness, which has increased the affective demands of and student resistance to the material. This article proposes a…

  5. Increased Circulatory Asymmetric Dimethylarginine and Multiple Organ Failure: Bile Duct Ligation in Rat as a Model

    Directory of Open Access Journals (Sweden)

    Jiunn-Ming Sheen

    2014-03-01

    Full Text Available Bile duct ligation (BDL-treated rats exhibit cholestasis, increased systemic oxidative stress, and liver fibrosis, which ultimately lead to liver cirrhosis. Asymmetric dimethylarginine (ADMA is a competitive inhibitor of nitric oxide synthase that can decrease the synthesis of nitric oxide. BDL rats have higher plasma and hepatic ADMA levels, which may be due to increased hepatic protein arginine methyltransferase-1 and decreased dimethylarginine dimethylaminohydrolase expression. BDL rats also exhibit renal and brain damage characterized by increased tissue ADMA concentrations. The increased plasma ADMA levels and multiple organ damages seen here are also observed following multiple organ failures associated with critical illness. This review discusses the dysregulation of ADMA in major organs in BDL rats and the role of increased ADMA in multiple organ damages.

  6. The Effects of the Behavior Analysis Model of Follow Through to Increase Native American Involvement in the Classroom Educational Process.

    Science.gov (United States)

    McLaughlin, T. F.; And Others

    1980-01-01

    The effects of the Behavior Analysis Model of Follow Through as to the percent of Native Americans in instructional roles were examined. Large percentage increases were found in the use of Native Americans in the classroom as a function of the adoption of the Behavior Analysis Model of Follow Through. (Author)

  7. 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.

  8. Pramipexole-induced increased probabilistic discounting: comparison between a rodent model of Parkinson's disease and controls

    National Research Council Canada - National Science Library

    Rokosik, Sandra L; Napier, T Celeste

    2012-01-01

    .... We included assessments of a rodent model of PD, wherein 6-OHDA was injected into the dorsolateral striatum of both hemispheres, which produced persistent PD-like deficits in posture adjustment...

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

    NARCIS (Netherlands)

    Engqvist, Leif

    2012-01-01

    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 suppo

  10. Modelling changes in nitrogen cycling to sustain increases in forest productivity under elevated atmospheric CO2 and contrasting site conditions

    Directory of Open Access Journals (Sweden)

    R. F. Grant

    2013-04-01

    Full Text Available If increases in net primary productivity (NPP caused by rising concentrations of atmospheric CO2 (Ca are to be sustained, key N processes such as soil mineralization, biological fixation, root uptake and plant translocation must be hastened. Simulating the response of these processes to elevated Ca is therefore vital for models used to project the effects of rising Ca on NPP. In this modelling study, hypotheses are proposed for changes in soil mineralization, biological fixation, root uptake and plant translocation with changes in Ca. Algorithms developed from these hypotheses were tested in the ecosystem model ecosys against changes in N and C cycling measured over several years under ambient vs. elevatedCa in Free Air CO2 Enrichment (FACE experiments at the Duke Forest in North Carolina, the Oak Ridge National Laboratory forest in Tennessee, and the USDA research forest in Wisconsin, USA. Simulating more rapid soil N mineralization was found to be vital for modelling sustained increases in NPP measured under elevated vs. ambient Ca at all three FACE sites. This simulation was accomplished by priming decomposition of N-rich humus from increases in microbial biomass generated by increased litterfall modelled under elevated Ca. Simulating more rapid nonsymbiotic N2 fixation, root N uptake and plant N translocation under elevated Ca was found to make much smaller contributions to modelled increases in NPP, although such contributions might be greater over longer periods and under more N-limited conditions than those simulated here. Greater increases in NPP with Ca were also modelled with increased temperature and water stress, and with coniferous vs. deciduous plant functional types. These increases were also associated with changes in N cycling.

  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. 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

  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. Modelling changes in nitrogen cycling to sustain increases in forest productivity under elevated atmospheric CO2 and contrasting site conditions

    Science.gov (United States)

    Grant, R. F.

    2013-11-01

    If increases in net primary productivity (NPP) caused by rising concentrations of atmospheric CO2 (Ca) are to be sustained, key N processes such as soil mineralization, biological fixation, root uptake and nutrient conservation must also be increased. Simulating the response of these processes to elevated Ca is therefore vital for models used to project the effects of rising Ca on NPP. In this modelling study, hypotheses are proposed for changes in soil mineralization, biological fixation, root nutrient uptake and plant nutrient conservation with changes in Ca. Algorithms developed from these hypotheses were tested in the ecosystem model ecosys against changes in N and C cycling measured over several years under ambient vs. elevated Ca in Free Air CO2 Enrichment (FACE) experiments in the USA at the Duke Forest in North Carolina, the Oak Ridge National Laboratory forest in Tennessee, and the USDA research forest in Wisconsin. More rapid soil N mineralization was found to be vital for simulating sustained increases in NPP measured under elevated vs. ambient Ca at all three FACE sites. This simulation was accomplished by priming decomposition of N-rich humus from increases in microbial biomass generated by increased litterfall modelled under elevated Ca. Greater nonsymbiotic N2 fixation from increased litterfall, root N uptake from increased root growth, and plant N conservation from increased translocation under elevated Ca were found to make smaller contributions to simulated increases in NPP. However greater nutrient conservation enabled larger increases in NPP with Ca to be modelled with coniferous vs. deciduous plant functional types. The effects of these processes on productivity now need to be examined over longer periods under transient rises in Ca and a greater range of site conditions.

  15. Impacts of increased bioenergy demand on global food markets: an AgMIP economic model intercomparison

    Energy Technology Data Exchange (ETDEWEB)

    Lotze-Campen, Hermann; von Lampe, Martin; Kyle, G. Page; Fujimori, Shinichiro; Havlik, Petr; van Meijl, Hans; Hasegawa, Tomoko; Popp, Alexander; Schmitz, Christoph; Tabeau, Andrzej; Valin, Hugo; Willenbockel, Dirk; Wise, Marshall A.

    2014-01-01

    Integrated Assessment studies have shown that meeting ambitious greenhouse gas mitigation targets will require substantial amounts of bioenergy as part of the future energy mix. In the course of the Agricultural Model Comparison and Improvement Project (AgMIP), five global agro-economic models were used to analyze a future scenario with global demand for ligno-cellulosic bioenergy rising to about 100 ExaJoule in 2050. From this exercise a tentative conclusion can be drawn that ambitious climate change mitigation need not drive up global food prices much, if the extra land required for bioenergy production is accessible or if the feedstock, e.g. from forests, does not directly compete for agricultural land. Agricultural price effects across models by the year 2050 from high bioenergy demand in an RCP2.6-type scenario appear to be much smaller (+5% average across models) than from direct climate impacts on crop yields in an RCP8.5-type scenario (+25% average across models). However, potential future scarcities of water and nutrients, policy-induced restrictions on agricultural land expansion, as well as potential welfare losses have not been specifically looked at in this exercise.

  16. Models to increase enrollment of minority females in science-based careers.

    Science.gov (United States)

    Taylor, V. S.; Erwin, K. W.; Ghose, M.; Perry-Thornton, E.

    2001-01-01

    Enrollment of African-American females in academic pathways that lead to science based-careers may be limited by gender discrepancies in standardized test scores, academic preparation, selecting "college-prep" course work in the high school curriculum, and lack of mentors or role models. Barriers related to teacher characteristics are: (a) lack of self-confidence, (b) learning environment, (c) teacher behavior, (d) lack of female role models, and (e) failure to see the relevance between the classes and a female's expected role in life. Other limiting factors include differences in access to educational resources, differences in economic status, differences in interest or choice, cultural barriers, and lack of encouragement. Confidence building models that improve enrollment of minority females in science-based careers include equitable teaching instruction, inquiry-based pedagogy, and cooperative learning. Practices that correlate with achievement and success include challenging curricula, a nurturing learning environment, high expectations, community service, research experiences, and mentoring relationships. PMID:12653386

  17. 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.

  18. Various emetogens increase the secretion of salivary amylase in rats: a potential model in emesis research.

    Science.gov (United States)

    Fukui, Hideo; Miwa, Eri; Iwachido, Takako; Kitaura, Harumi; Furukawa, Hatsue

    2010-01-01

    We investigated the effects of various emetic agents: cisplatin, apomorphine, lithium chloride (LiCl), rolipram, sibutramine, and the beta(3)-adrenoceptor (AR) agonist CL316243 on salivary amylase secretion in rats. We also determined the inhibitory effect of granisetron, a 5-HT(3)-receptor antagonist, on cisplatin-induced increased salivary amylase activity and the inhibitory effect of bilateral abdominal vagotomy on increases in salivary amylase activity induced by cisplatin and LiCl. Granisetron was administered 15 min before and 1 h after cisplatin administration. Cisplatin (10 - 15 mg/kg, i.v.) increased salivary amylase activity dose-dependently and induced an acute increase from 1.5 h post-treatment with 15 mg/kg. Apomorphine (1 - 3 mg/kg, s.c.), LiCl (120 mg/kg, i.p.), rolipram (3 - 10 mg/kg, p.o.), and sibutramine (10 mg/kg, p.o.) induced significant increases in salivary amylase secretion. On the other hand, CL316243 did not stimulate salivary amylase secretion. The increased amylase activity induced by cisplatin (15 mg/kg, i.v.) was inhibited significantly by granisetron (1 or 3 mg/kg x 2, i.v.) or tended to be inhibited by bilateral abdominal vagotomy, whereas an increase in amylase activity produced by LiCl was not inhibited by abdominal visceral nerve section. These results suggest that salivary amylase activity is useful as a marker for emesis in rats, a species that does not exhibit vomiting.

  19. Several statins increase body and liver fat accumulation in a model of metabolic syndrome.

    Science.gov (United States)

    Aguirre, L; Hijona, E; Macarulla, M T; Gracia, A; Larrechi, I; Bujanda, L; Hijona, L; Portillo, M P

    2013-06-01

    Statins are a family of drugs used in hypercholesterolemia. The aim of this study was to analyze the effect of statins on body and liver fat accumulation in obese Zucker rats. Seventy Zucker (fa/fa) rats were divided into seven groups. Rats from six statin groups were treated with pravastatin, simvastatin, atorvastatin, rosuvastatin, fluvastatin and lovastatin respectively, at a dose of 0.6 mg/kg body weight/day. After 6 weeks, liver and white adipose tissue from intra-abdominal and subcutaneous locations were dissected and weighed. Subcutaneous adipose tissue from rosuvastatin, atorvastatin, fluvastatin and lovastatin treated rats was significantly increased. Fatty acid synthase (FAS) activity was increased by the administration of fluvastatin and lovastatin, as was glucose-6-P dehydrogenase (G6PDH) by the administration of atorvastatin and lovastatin. No changes were observed in malic enzyme (ME) activity. Furthermore, heparin-releasable lipoprotein lipase (HR-LPL) was increased in all groups where the subcutaneous depot was increased, and total LPL increased only in rosuvastatin and fluvastatin-treated groups. With regard to liver, there were no changes in weight but the amount of triacylglycerols was increased in rosuvastatin group, as well as its liver damage was higher. In this group FAS and G6PDH activities were increased and no changes were observed in ME, acyl CoA oxidase (ACO) and carnitine palmitoyltransferase-1a (CPT-1a) activities. All statins, with the exception of simvastatin, worsen insulin resistance. These results show that statins have different effects on body fat accumulation. Moreover, rosuvastatin also shows a prosteatotic effect. These results should be taken into account for statin choice in prescription.

  20. 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-concentra......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...

  1. 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 .

  2. Corn stover harvest increases herbicide movement to subsurface drains – Root Zone Water Quality Model simulations

    Science.gov (United States)

    BACKGROUND: Removal of crop residues for bioenergy production can alter soil hydrologic properties, but there is little information on its impact on transport of herbicides and their degradation products to subsurface drains. The Root Zone Water Quality Model, previously calibrated using measured fl...

  3. Knockdown of Filaggrin Impairs Diffusion Barrier Function and Increases UV Sensitivity in a Human Skin Model

    NARCIS (Netherlands)

    M. Mildner; J. Jin; L. Eckhart; S. Kezic; F. Gruber; C. Barresi; C. Stremnitzer; M. Buchberger; V. Mlitz; C. Ballaun; B. Sterniczky; D. Födinger; E. Tschachler

    2010-01-01

    Loss-of-function mutations in the filaggrin gene are associated with ichthyosis vulgaris and atopic dermatitis. To investigate the impact of filaggrin deficiency on the skin barrier, filaggrin expression was knocked down by small interfering RNA (siRNA) technology in an organotypic skin model in vit

  4. The Operations Intent and Effects Model: A Command and Control Methodology for Increased Automation

    Science.gov (United States)

    2013-06-01

    graphics overlays, in matrices, or described textually . An End-State can either be direct (e.g. destroying a bridge, when the bridge is destroyed the end...amongst C2 information elements along with C2 processes in a cohesive way and provides: 1) a model of Intent for C2; and, 2) a foundation for developing

  5. Topic Teamwork: A Collaborative Integrative Model for Increasing Student-Centered Learning in Grades K-12.

    Science.gov (United States)

    Christie, Brett

    2000-01-01

    Describes the benefits of "topic teamwork," an interdisciplinary model designed to make integrative teaching a well-structured, cooperative effort involving all teachers and students. The article presents examples of and strategies for integrating physical education with other subject areas and for assessing topic teamwork, concluding that topic…

  6. In the Opponent's Shoes: Increasing the Behavioral Validity of Attackers' Judgments in Counterterrorism Models.

    Science.gov (United States)

    Sri Bhashyam, Sumitra; Montibeller, Gilberto

    2016-04-01

    A key objective for policymakers and analysts dealing with terrorist threats is trying to predict the actions that malicious agents may take. A recent trend in counterterrorism risk analysis is to model the terrorists' judgments, as these will guide their choices of such actions. The standard assumptions in most of these models are that terrorists are fully rational, following all the normative desiderata required for rational choices, such as having a set of constant and ordered preferences, being able to perform a cost-benefit analysis of their alternatives, among many others. However, are such assumptions reasonable from a behavioral perspective? In this article, we analyze the types of assumptions made across various counterterrorism analytical models that represent malicious agents' judgments and discuss their suitability from a descriptive point of view. We then suggest how some of these assumptions could be modified to describe terrorists' preferences more accurately, by drawing knowledge from the fields of behavioral decision research, politics, philosophy of choice, public choice, and conflict management in terrorism. Such insight, we hope, might help make the assumptions of these models more behaviorally valid for counterterrorism risk analysis.

  7. Identifying Admired Models to Increase Emulation: Development of a Multidimensional Admiration Scale

    Science.gov (United States)

    Sarapin, Susan H.; Christy, Katheryn; Lareau, Louise; Krakow, Melinda; Jensen, Jakob D.

    2015-01-01

    According to social cognitive theory, people are most likely to emulate the behaviors of admired models. Though potentially valuable to researchers and practitioners, this postulate remains untested, as there is no validated measure of admiration. To facilitate research on admiration, a 14-item measure was constructed and the resulting scores were…

  8. 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...

  9. Supervision of Group Work: A Model to Increase Supervisee Cognitive Complexity

    Science.gov (United States)

    Granello, Darcy Haag; Underfer-Babalis, Jean

    2004-01-01

    This article describes a model for supervisors of group counselors to use to promote cognitive complexity in their supervisees. Counselor cognitive complexity has been linked to many positive counseling skills, including greater flexibility, empathy, confidence, and client conceptualization. Bloom's Taxonomy of Educational Objectives provides a…

  10. Core Needle Biopsy of Breast Cancer Tumors Increases Distant Metastases in a Mouse Model12

    Science.gov (United States)

    Mathenge, Edward Gitau; Dean, Cheryl Ann; Clements, Derek; Vaghar-Kashani, Ahmad; Photopoulos, Steffany; Coyle, Krysta Mila; Giacomantonio, Michael; Malueth, Benjamin; Nunokawa, Anna; Jordan, Julie; Lewis, John D.; Gujar, Shashi Ashok; Marcato, Paola; Lee, Patrick W.K.; Giacomantonio, Carman Anthony

    2014-01-01

    INTRODUCTION: Incisional biopsies, including the diagnostic core needle biopsy (CNB), routinely performed before surgical excision of breast cancer tumors are hypothesized to increase the risk of metastatic disease. In this study, we experimentally determined whether CNB of breast cancer tumors results in increased distant metastases and examine important resultant changes in the primary tumor and tumor microenvironment associated with this outcome. METHOD: To evaluate the effect of CNB on metastasis development, we implanted murine mammary 4T1 tumor cells in BALB/c mice and performed CNB on palpable tumors in half the mice. Subsequently, emulating the human scenario, all mice underwent complete tumor excision and were allowed to recover, with attendant metastasis development. Tumor growth, lung metastasis, circulating tumor cell (CTC) levels, variation in gene expression, composition of the tumor microenvironment, and changes in immunologic markers were compared in biopsied and non-biopsied mice. RESULTS: Mice with biopsied tumors developed significantly more lung metastases compared to non-biopsied mice. Tumors from biopsied mice contained a higher frequency of myeloid-derived suppressor cells (MDSCs) accompanied by reduced CD4 + T cells, CD8 + T cells, and macrophages, suggesting biopsy-mediated development of an increasingly immunosuppressive tumor microenvironment. We also observed a CNB-dependent up-regulation in the expression of SOX4, Ezh2, and other key epithelial-mesenchymal transition (EMT) genes, as well as increased CTC levels among the biopsy group. CONCLUSION: CNB creates an immunosuppressive tumor microenvironment, increases EMT, and facilitates release of CTCs, all of which likely contribute to the observed increase in development of distant metastases. PMID:25425969

  11. Increased virulence of Mycobacterium tuberculosis H37Rv overexpressing LipY in a murine model.

    Science.gov (United States)

    Singh, Vipul K; Srivastava, Mrigank; Dasgupta, Arunava; Singh, Mohan P; Srivastava, Ranjana; Srivastava, Brahm S

    2014-05-01

    We have investigated the role of Rv3097c-encoded lipase (LipY) on the virulence of Mycobacterium tuberculosis. It has been shown that the overexpression of LipY in strain H37Rv induced increase in virulence of recombinant H37Rv::LipY strain. Compared to H37Rv, infection with H37Rv::LipY caused enhanced mortality, weight loss, bacterial load in lungs, splenomegaly, worsening lung morphology and pathology. Mice immunized with recombinant LipY antigen were protected against challenge with H37Rv::LipY, which correlated with enhanced survival of challenged mice and striking decrease in pathological features observed in unimmunized mice. To probe the cause of increase in virulence of H37Rv::LipY, the immune status of the host infected with H37Rv and H37Rv::LipY was compared. It was found that overexpression of LipY compromised immune responses resulting in attenuation of Th1 and Th17 responses, significant increase in IL-10, decrease in number of macrophages and T cells, and increase in numbers of Treg, and DCs in the lungs whereas in mice immunized with LipY an increased pool of T cells and DCs was observed. This led us to conclude that the increase in the virulence of H37Rv::LipY was due to downregulation of the host's protective immunity and the Rv3097c encoded LipY lipase is a virulence factor of M. tuberculosis.

  12. Increasing Self-Efficacy Expectations and Outcome Expectations: A Model to Facilitate Transfer of Training.

    Science.gov (United States)

    Bryan, Jean M.; And Others

    1993-01-01

    Without organizationwide commitment to training programs, educators may be able to increase learners' self-efficacy to acquire desired skills or behavior. But behavior and skills will not be transferred to the job if learners have low expectations about their use or if positive reinforcement is lacking. (SK)

  13. Testing models of the attentional blink : Does masking increase processing duration in RSVP?

    NARCIS (Netherlands)

    Wyble, Brad; Sense, Florian; Nieuwenstein, Mark

    2012-01-01

    Theories of the attentional blink (AB) – an impairment in perceiving the second of two targets shown within less than 500 ms of each other – generally assume that this effect reflects the time required to consolidate the first target in memory. In this view, the fact that the AB is strongly increase

  14. Time Delay Embedding Increases Estimation Precision of Models of Intraindividual Variability

    Science.gov (United States)

    von Oertzen, Timo; Boker, Steven M.

    2010-01-01

    This paper investigates the precision of parameters estimated from local samples of time dependent functions. We find that "time delay embedding," i.e., structuring data prior to analysis by constructing a data matrix of overlapping samples, increases the precision of parameter estimates and in turn statistical power compared to standard…

  15. Adaptive models for operational use in dairy farming : increasing economic results utilising individual variation in response

    NARCIS (Netherlands)

    Andre, G.

    2011-01-01

    During the last century in the Netherlands milk production per cow has almost tripled. Accordingly, the amount of concentrates yearly fed per cow strongly increased. Furthermore, automation and robotisation has changed dairy management, especially by the introduction of automatic concentrate feeders

  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. 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…

  18. Increasing Student Evaluation Capacity through a Collaborative Community-Based Program Evaluation Teaching Model

    Science.gov (United States)

    Carlisle, Shauna K.; Kruzich, Jean M.

    2013-01-01

    The evaluation literature reflects a long-standing interest in ways to provide practical hands-on training experience in evaluation courses. Concomitantly, some funders have shown rising expectations for increased accountability on the part of Community-Based organizations (CBOs), even though agencies often lack the associated funding and…

  19. Polyploidization increases meiotic recombination frequency in Arabidopsis: a close look at statistical modeling and data analysis.

    Science.gov (United States)

    Wang, Lin; Luo, Zewei

    2012-04-18

    This paper is a response to Pecinka A, Fang W, Rehmsmeier M, Levy AA, Mittelsten Scheid, O: Polyploidization increases meiotic recombination frequency in Arabidopsis. BMC Biology 2011, 9:24.See research article at http://www.biomedcentral.com/1741-7007/9/24.

  20. Polyploidization increases meiotic recombination frequency in Arabidopsis: a close look at statistical modeling and data analysis

    Directory of Open Access Journals (Sweden)

    Wang Lin

    2012-04-01

    Full Text Available Abstract This paper is a response to Pecinka A, Fang W, Rehmsmeier M, Levy AA, Mittelsten Scheid, O: Polyploidization increases meiotic recombination frequency in Arabidopsis. BMC Biology 2011, 9:24. See research article at http://www.biomedcentral.com/1741-7007/9/24

  1. 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

  2. Prediction of the dynamic oscillation threshold in a clarinet model with a linearly increasing blowing pressure

    CERN Document Server

    Bergeot, Baptiste; Vergez, Christophe; Gazengel, Bruno

    2012-01-01

    Reed instruments are modeled as self-sustained oscillators driven by the pressure inside the mouth of the musician. A set of nonlinear equations connects the control parameters (mouth pressure, lip force) to the system output, hereby considered as the mouthpiece pressure. Clarinets can then be studied as dynamical systems, their steady behavior being dictated uniquely by the values of the control parameters. Considering the resonator as a lossless straight cylinder is a dramatic yet common simplification that allows for simulations using nonlinear iterative maps. In this paper, we investigate analytically the effect of a time-varying blowing pressure on the behavior of this simplified clarinet model. When the control parameter varies, results from the so-called dynamic bifurcation theory are required to properly analyze the system. This study highlights the phenomenon of bifurcation delay and defines a new quantity, the dynamic oscillation threshold. A theoretical estimation of the dynamic oscillation thresho...

  3. Increased Eicosanoid Levels in the Sugen/Chronic Hypoxia Model of Severe Pulmonary Hypertension

    OpenAIRE

    Aysar Al-Husseini; Wijesinghe, Dayanjan S.; Laszlo Farkas; Donatas Kraskauskas; Drake, Jennifer I.; Ben Van Tassel; Antonio Abbate; Chalfant, Charles E.; Norbert F Voelkel

    2015-01-01

    Inflammation and altered immunity are recognized components of severe pulmonary arterial hypertension in human patients and in animal models of PAH. While eicosanoid metabolites of cyclooxygenase and lipoxygenase pathways have been identified in the lungs from pulmonary hypertensive animals their role in the pathogenesis of severe angioobliterative PAH has not been examined. Here we investigated whether a cyclooxygenase-2 (COX-2) inhibitor or diethylcarbamazine (DEC), that is known for its 5-...

  4. The oceanic response to Greenland melting: the effect of increasing model resolution

    OpenAIRE

    Behrens, Erik

    2013-01-01

    This study investigates the oceanic response to an enhanced melting of the Greenland Ice Sheet. A series of forced ocean simulations with different horizontal resolutions from 0.5° to 0.05° is used. The main focus is to investigate the oceanic behaviour to a freshwater input within models of different horizontal resolutions and differing in the representation of mesoscale processes. In particular, the role of the mesoscale eddies on the spreading of freshwater in the subpolar North Atlantic i...

  5. 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.

  6. Models for nutrition education to increase consumption of calcium and dairy products among African Americans.

    Science.gov (United States)

    Bronner, Yvonne L; Hawkins, Anita S; Holt, Mckessa L; Hossain, Mian B; Rowel, Randolph H; Sydnor, Kim L; Divers, Shaquana P

    2006-04-01

    Calcium and dairy consumption are documented to be low among African Americans and have demonstrated benefits to bone growth, overall nutritional status, and health throughout the life cycle. There is also an emerging relationship to the prevention of obesity. This low consumption has been attributed to both cultural and community/environmental barriers. Using a life course construct and an ecological model of health behavior, this paper will illustrate why nutrition education and food consumption behavior at one stage of the life cycle may influence health status at that stage as well as influence health and consumption of calcium and dairy products at subsequent stages. The life course construct recognizes that both past and present behavior and experiences (in this case food and nutrient intake) are shaped by the wider social, economic, and cultural context and therefore may provide clues to current patterns of health and disease. The ecological model, concerned with constructs of environmental change, behavior, and policies that may help people make choices in their daily life, complements the life course approach when examining the potential influence of nutrition education provided by federally funded food and nutrition programs on calcium and dairy consumption behavior across the life cycle. The "critical period model" within the life course construct is operative for calcium, a nutrient for which adequate intake is critically important during adolescence when peak bone density development, necessary for later protection against osteoporosis, is important.

  7. Reference interaction site model and optimized perturbation theories of colloidal dumbbells with increasing anisotropy

    Energy Technology Data Exchange (ETDEWEB)

    Munaò, Gianmarco, E-mail: gmunao@unime.it; Costa, Dino; Caccamo, Carlo [Dipartimento di Fisica e di Scienze della Terra, Università degli Studi di Messina, Viale F. Stagno d’Alcontres 31, 98166 Messina (Italy); Gámez, Francisco [C/Clavel 101, Mairena del Aljarafe, 41927 Seville (Spain); Sciortino, Francesco [Dipartimento di Fisica and CNR-ISC, Università di Roma “Sapienza,” Piazzale Aldo Moro 2, 00185 Roma (Italy); Giacometti, Achille [Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca’ Foscari Venezia, Calle Larga S.Marta DD2137, Venezia I-30123 (Italy)

    2015-06-14

    We investigate thermodynamic properties of anisotropic colloidal dumbbells in the frameworks provided by the Reference Interaction Site Model (RISM) theory and an Optimized Perturbation Theory (OPT), this latter based on a fourth-order high-temperature perturbative expansion of the free energy, recently generalized to molecular fluids. Our model is constituted by two identical tangent hard spheres surrounded by square-well attractions with same widths and progressively different depths. Gas-liquid coexistence curves are obtained by predicting pressures, free energies, and chemical potentials. In comparison with previous simulation results, RISM and OPT agree in reproducing the progressive reduction of the gas-liquid phase separation as the anisotropy of the interaction potential becomes more pronounced; in particular, the RISM theory provides reasonable predictions for all coexistence curves, bar the strong anisotropy regime, whereas OPT performs generally less well. Both theories predict a linear dependence of the critical temperature on the interaction strength, reproducing in this way the mean-field behavior observed in simulations; the critical density—that drastically drops as the anisotropy increases—turns to be less accurate. Our results appear as a robust benchmark for further theoretical studies, in support to the simulation approach, of self-assembly in model colloidal systems.

  8. Immunoreactive atrial natriuretic factor is increased in ovine model of endotoxemia

    Energy Technology Data Exchange (ETDEWEB)

    Lubbesmeyer, H.J.; Woodson, L.; Traber, L.D.; Flynn, J.T.; Herndon, D.N.; Traber, D.L. (Univ. of Texas Medical Branch, Galveston (USA) Thomas Jefferson Medical College, Philadelphia, PA (USA) Westfaelian Wilhelms Univ., Muenster (West Germany))

    1988-04-01

    A bolus of Escherichia coli endotoxin (1.5 {mu}g/kg) was administered to chronically instrumented sheep. Immunoreactive atrial natriuretic factor (IR-ANF) was measured in extracted plasma by radioimmunoassay. There was a thirteenfold increase in IR-ANF 2 h after endotoxin administration, and IR-ANF levels remained significantly elevated during the first 6 h. A marked diuresis and natriuresis occurred between 4 and 6 h. ANF not only affects renal function but is also associated with decreased cardiac output, increased peripheral resistance (in sheep), and decreased capillary absorption (in rats). These renal and hemodynamic changes are also characteristic of the early (first 6 h) response to endotoxin. Therefore ANF should be considered as a potential mediator of renal and hemodynamic changes induced by sepsis. It is difficult to determine if ANF elevation is an epiphenomenon or a causative factor, because no antagonist of ANF is currently available.

  9. Increased efficacy of early spinal cord stimulation in an animal model of neuropathic pain.

    Science.gov (United States)

    Truin, Michiel; van Kleef, Maarten; Linderoth, Bengt; Smits, Helwin; Janssen, Sofie P M; Joosten, Elbert A J

    2011-02-01

    Although spinal cord stimulation (SCS) is an established treatment for chronic neuropathic pain, pain relief is still not successful in a large group of patients. We suggest that the success of SCS may be related to the timing of SCS during the development of chronic neuropathic pain. We therefore compared the effect of SCS applied after 24h of neuropathic pain (early SCS) and after 16days of neuropathic pain (late SCS). For early SCS, male Sprague-Dawley rats (n=13) were implanted with an SCS device, followed by a partial ligation of the sciatic nerve. Using von Frey monofilaments, tactile allodynia was assessed 24h after ligation. Animals with tactile allodynia received 30min of SCS. Withdrawal thresholds were assessed just before SCS, during SCS and until the return to pre-stimulation withdrawal threshold. Results were compared with the data from late SCS (n=29). Out of the 13 allodynic animals that received early SCS, 10 (77%) responded to SCS with significantly increased withdrawal thresholds, compared to 38% in the late SCS group. The increase of the withdrawal threshold in the early SCS group could still be noticed 90min after termination of SCS. In more than half of these animals, pre-stimulation withdrawal thresholds were reached only the next day. Early SCS resulted in an increased number of responders to SCS and furthermore an increased duration of the effect of SCS as compared to late SCS. Early SCS treatment of neuropathic rats is more effective as compared to the late SCS treatment. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

  10. Bending the cost curve and increasing revenue: a family medicine model that works!

    Science.gov (United States)

    Katz, Bernard J; Needham, Mark R

    2012-12-01

    This article attempts to illustrate ways in which family physician practices are able to demonstrate high value, enhanced quality, and streamlined costs, essential components of practice sustainability. Specific examples are provided to assist practices to consider questions and information that allow for skillful engagement during contract negotiations, consider increasing practice revenues by adopting practice enhancements that make sense for the location of the practice and community needs, develop workflow analyses, and review opportunities for expense reduction.

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

    Directory of Open Access Journals (Sweden)

    Jinwei Hu

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

  12. Support Framework for First Responder Family Members: A Proposed Model for Increasing Responder Effectiveness

    Science.gov (United States)

    2009-12-01

    http://www.npr.org/templates/story/story.php?storyid=1093 Stover, C.W. & Coffman, J. L. (1993). Historic earthquakes, Santa Cruz ( Loma Prieta ...INCREASING RESPONDER EFFECTIVENESS by Brian E. Sturdivant December 2009 Thesis Advisor: Nola Joyce Second Reader: Nadav Morag Approved...Responder Effectiveness 6. AUTHOR(S) Brian E. Sturdivant 5. FUNDING NUMBERS 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Naval Postgraduate School

  13. A Metadata Model Based on Coupling Testing Information to Increase Testability of Component

    Institute of Scientific and Technical Information of China (English)

    MA Liang-li; GUO Fu-liang; WU Zhao-hui

    2008-01-01

    A software component must be tested every time it is reused in order to assure quality of component itself and system in which it is to be integrated. So how to increase testability of component has become a key technology in the software engineering community. Here a method is introduced to increase component testability. And meanings of component testability and relative effective ways to increase testability are summarized. Then definitions of component coupling testing criterion, DU-I (Definition-Use Information) and OP-Vs (Observation-Point Values) are given. Base on these, a definition-use table is introduced, which includes DU-A and OP-Vs item, to help component testers to understand and observe interior details about component under test better. Then a framework of testable component based on above DU-table is given. These facilities provide ways to detect errors, observe state variables by observation-points based monitor mechanism. Moreover, above methods are applied to our application developed by ourselves before, and some test cases are generated. Then our method is compared with Orso method and Kan method using the same example, presenting the comparison results. The results illustrate the validity of our method, effectively generating test cases and killing more mutants.

  14. Increase in vastus lateralis aponeurosis width induced by resistance training: implications for a hypertrophic model of pennate muscle.

    Science.gov (United States)

    Wakahara, Taku; Ema, Ryoichi; Miyamoto, Naokazu; Kawakami, Yasuo

    2015-02-01

    This study aimed to ascertain whether training-induced muscle hypertrophy is accompanied by an increase in the aponeurosis width, and to infer its impact on the training-induced increase in the pennation angle. Eleven young men completed a resistance training program of unilateral knee extensions for 12 weeks. Before and after training, anatomical cross-sectional area (ACSA) of the vastus lateralis and its distal aponeurosis width in the transverse plane were measured with magnetic resonance imaging. The pennation angle and fascicle length were also determined with ultrasonography at the midbelly of the muscle. The effect of change in aponeurosis width on the magnitude of training-induced increase in pennation angle was estimated by using a parallelepipedon model. After the training, there were significant increases in ACSA (10.7 ± 7.6 %), pennation angle (10.8 ± 7.3 %) and aponeurosis width (1.9 ± 3.1 %), whereas no significant change was found in the fascicle length. The model simulation shows that the increase in aponeurosis width by 1.9 % reduces the magnitude of increase in pennation angle by only 0.4°. These results indicate that (1) the aponeurosis width of the vastus lateralis increases after 12 weeks of resistance training and (2) the increase in the aponeurosis width accompanying muscle hypertrophy by the amount of ~10 % does not substantially affect the increase in pennation angle.

  15. 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.

  16. 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.

  17. Evaluating the road safety effects of a fuel cost increase measure by means of zonal crash prediction modeling.

    Science.gov (United States)

    Pirdavani, Ali; Brijs, Tom; Bellemans, Tom; Kochan, Bruno; Wets, Geert

    2013-01-01

    Travel demand management (TDM) consists of a variety of policy measures that affect the transportation system's effectiveness by changing travel behavior. The primary objective to implement such TDM strategies is not to improve traffic safety, although their impact on traffic safety should not be neglected. The main purpose of this study is to evaluate the traffic safety impact of conducting a fuel-cost increase scenario (i.e. increasing the fuel price by 20%) in Flanders, Belgium. Since TDM strategies are usually conducted at an aggregate level, crash prediction models (CPMs) should also be developed at a geographically aggregated level. Therefore zonal crash prediction models (ZCPMs) are considered to present the association between observed crashes in each zone and a set of predictor variables. To this end, an activity-based transportation model framework is applied to produce exposure metrics which will be used in prediction models. This allows us to conduct a more detailed and reliable assessment while TDM strategies are inherently modeled in the activity-based models unlike traditional models in which the impact of TDM strategies are assumed. The crash data used in this study consist of fatal and injury crashes observed between 2004 and 2007. The network and socio-demographic variables are also collected from other sources. In this study, different ZCPMs are developed to predict the number of injury crashes (NOCs) (disaggregated by different severity levels and crash types) for both the null and the fuel-cost increase scenario. The results show a considerable traffic safety benefit of conducting the fuel-cost increase scenario apart from its impact on the reduction of the total vehicle kilometers traveled (VKT). A 20% increase in fuel price is predicted to reduce the annual VKT by 5.02 billion (11.57% of the total annual VKT in Flanders), which causes the total NOCs to decline by 2.83%.

  18. Busulfan administration flexibility increases the applicability of scid repopulating cell assay in NSG mouse model.

    Directory of Open Access Journals (Sweden)

    Jean Chevaleyre

    Full Text Available BACKGROUND: Xenotransplantation models allowing the identification and quantification of human Hematopoietic stem cells (HSC in immunodeficient mice remain the only way to appropriately address human HSC function despite the recent progress in phenotypic characterization. However, these in vivo experiments are technically demanding, time consuming and expensive. Indeed, HSCs engraftment in mouse requires pre-conditioning of animals either by irradiation or cytotoxic drugs to allow homing of injected cells in specific stem cell niches and their subsequent expansion and differentiation in bone marrow. Recently, the development of busulfan pre-conditioning of animals improved the flexibility of experimentation in comparison with irradiation. DESIGN AND METHODS: In order to further facilitate the organization of these complex experiments we investigated the effect of extending the period between mice pre-conditioning and cell injection on the engraftment efficiency. In the meantime, we also explored the role of busulfan doses, mouse gender and intravenous injection route (caudal or retro orbital on engraftment efficiency. RESULTS AND CONCLUSION: We showed that a period of up to 7 days did not modify engraftment efficiency of human HSCs in NSG model. Moreover, retro orbital cell injection to female mice pre-conditioned with 2x25 mg/kg of busulfan seems to be the best adapted schema to detect the human HSC in xenotransplantation experiments.

  19. Increased eicosanoid levels in the Sugen/chronic hypoxia model of severe pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Aysar Al-Husseini

    Full Text Available Inflammation and altered immunity are recognized components of severe pulmonary arterial hypertension in human patients and in animal models of PAH. While eicosanoid metabolites of cyclooxygenase and lipoxygenase pathways have been identified in the lungs from pulmonary hypertensive animals their role in the pathogenesis of severe angioobliterative PAH has not been examined. Here we investigated whether a cyclooxygenase-2 (COX-2 inhibitor or diethylcarbamazine (DEC, that is known for its 5-lipoxygenase inhibiting and antioxidant actions, modify the development of PAH in the Sugen 5416/hypoxia (SuHx rat model. The COX-2 inhibitor SC-58125 had little effect on the right ventricular pressure and did not prevent the development of pulmonary angioobliteration. In contrast, DEC blunted the muscularization of pulmonary arterioles and reduced the number of fully obliterated lung vessels. DEC treatment of SuHx rats, after the lung vascular disease had been established, reduced the degree of PAH, the number of obliterated arterioles and the degree of perivascular inflammation. We conclude that the non-specific anti-inflammatory drug DEC affects developing PAH and is partially effective once angioobliterative PAH has been established.

  20. Increased eicosanoid levels in the Sugen/chronic hypoxia model of severe pulmonary hypertension.

    Science.gov (United States)

    Al-Husseini, Aysar; Wijesinghe, Dayanjan S; Farkas, Laszlo; Kraskauskas, Donatas; Drake, Jennifer I; Van Tassel, Ben; Abbate, Antonio; Chalfant, Charles E; Voelkel, Norbert F

    2015-01-01

    Inflammation and altered immunity are recognized components of severe pulmonary arterial hypertension in human patients and in animal models of PAH. While eicosanoid metabolites of cyclooxygenase and lipoxygenase pathways have been identified in the lungs from pulmonary hypertensive animals their role in the pathogenesis of severe angioobliterative PAH has not been examined. Here we investigated whether a cyclooxygenase-2 (COX-2) inhibitor or diethylcarbamazine (DEC), that is known for its 5-lipoxygenase inhibiting and antioxidant actions, modify the development of PAH in the Sugen 5416/hypoxia (SuHx) rat model. The COX-2 inhibitor SC-58125 had little effect on the right ventricular pressure and did not prevent the development of pulmonary angioobliteration. In contrast, DEC blunted the muscularization of pulmonary arterioles and reduced the number of fully obliterated lung vessels. DEC treatment of SuHx rats, after the lung vascular disease had been established, reduced the degree of PAH, the number of obliterated arterioles and the degree of perivascular inflammation. We conclude that the non-specific anti-inflammatory drug DEC affects developing PAH and is partially effective once angioobliterative PAH has been established.

  1. 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

    2017-09-04

    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 to use them in applications such as mixed-crop pest management. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. 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

    2017-01-01

    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...... in teleost fish using the concentrations and vehicles tested here. We emphasize the importance of validation studies across all new species/taxa when possible and suggest that more investigation is required with regard toNAC manipulation in fish if this approach is to be used...

  3. 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 BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: When subjected to the same septic insult, mice with chronic alcohol ingestion have increased mortality

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

    DEFF Research Database (Denmark)

    Wiese, Lothar; Hempel, Casper; Penkowa, Milena;

    2008-01-01

    with recombinant human Epo (rhEpo; 50-5000 U/kg/OD, i.p.) at different time points. The effect on survival was measured. Brain pathology was investigated by TUNEL (Terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labelling), as a marker of apoptosis. Gene...... expression in brain tissue was measured by real time PCR. RESULTS: Treatment with rhEpo increased survival in mice with CM in a dose- and time-dependent manner and reduced apoptotic cell death of neurons as well as the expression of pro-inflammatory cytokines in the brain. This neuroprotective effect...

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

    Directory of Open Access Journals (Sweden)

    Hempel Casper

    2008-01-01

    Full Text Available Abstract Background Cerebral malaria (CM is an acute encephalopathy with increased pro-inflammatory cytokines, sequestration of parasitized erythrocytes and localized ischaemia. In children CM induces cognitive impairment in about 10% of the survivors. Erythropoietin (Epo has – besides of its well known haematopoietic properties – significant anti-inflammatory, antioxidant and anti-apoptotic effects in various brain disorders. The neurobiological responses to exogenously injected Epo during murine CM were examined. Methods Female C57BL/6j mice (4–6 weeks, infected with Plasmodium berghei ANKA, were treated with recombinant human Epo (rhEpo; 50–5000 U/kg/OD, i.p. at different time points. The effect on survival was measured. Brain pathology was investigated by TUNEL (Terminal deoxynucleotidyl transferase (TdT-mediated deoxyuridine triphosphate (dUTP-digoxigenin nick end labelling, as a marker of apoptosis. Gene expression in brain tissue was measured by real time PCR. Results Treatment with rhEpo increased survival in mice with CM in a dose- and time-dependent manner and reduced apoptotic cell death of neurons as well as the expression of pro-inflammatory cytokines in the brain. This neuroprotective effect appeared to be independent of the haematopoietic effect. Conclusion These results and its excellent safety profile in humans makes rhEpo a potential candidate for adjunct treatment of CM.

  6. Formation of Tumorspheres with Increased Stemness without External Mitogens in a Lung Cancer Model

    Directory of Open Access Journals (Sweden)

    Juan Sebastian Yakisich

    2016-01-01

    Full Text Available Like with most solid tumors, the presence of a subpopulation of cancer stem cells (CSCs or cancer stem-like cells (CS-LCs has been associated with chemoresistance and tumor relapse in lung cancer cells. In the absence of serum, CSCs/CS-LCs have the ability to grow as lung tumorspheres (LTSs, and this system is routinely used for isolation and characterization of putative CSCs/CS-LCs. Methods to isolate LTSs are usually performed in serum-free media supplemented with specific additives such as epidermal growth factor and basic fibroblast growth factor. In this study, we report the generation of LTSs without the addition of any external mitogenic stimulation. LTSs generated in this manner demonstrated several traits usually associated with increased stemness such as elevated expression of the stemness-associated marker Sox2 and increased chemoresistance to conventional anticancer drugs. In addition, we report that the FDA-approved drug Digitoxin, at concentration close to its therapeutic level, decreased the viability of LTSs and downregulated Sox2 independent of the PI3K/AKT pathway. The potential use of LTSs generated without the addition of any external mitogenic stimulation to study the role of specific factor(s associated with stemness properties is also discussed.

  7. Increased Expression of p-Akt correlates with Chronic Allograft Nephropathy in a Rat Kidney Model.

    Science.gov (United States)

    Zhou, Li-Na; Wang, Ning; Dong, Yang; Zhang, Yiqin; Zou, Hequn; Li, Qingqin; Shi, Yangling; Chen, Ling; Zhou, Wenying; Han, Conghui; Wang, Yuxin

    2015-04-01

    Chronic allograft nephropathy (CAN) is the most common cause of chronic graft dysfunction leading to graft failure, our study investigates the expression and significance of p-Akt in the pathogenesis of CAN in rats. Kidneys of Fisher (F344) rats were orthotopically transplanted into Lewis (LEW) rats. The animals were evaluated at 4, 8, 12, 16, and 24 weeks post-transplantation for renal function and histopathology. Phosphorate Akt (p-Akt) protein expression was determined by Western blot and immunohistological assays. Our data show that 24-h urinary protein excretion in CAN rats increased significantly at week 16 as compared with F344/LEW controls. Allografts got severe interstitial infiltration of mononuclear cells at week 4 and week 8, but it was degraded as the time went on after week 16. Allografts markedly presented with severe interstitial fibrosis (IF) and tubular atrophy at 16 and 24 weeks. p-Akt expression was upregulated in rat kidneys with CAN, and the increase became more significant over time after transplantation. p-Akt expression correlated significantly with 24-h urinary protein excretion, serum creatinine levels, tubulointerstitial mononuclear cells infiltration, smooth muscle cells (SMCs) migration in vascular wall, and IF. It was concluded that p-Akt overexpression might be the key event that involved mononuclear cells infiltration and vascular SMCs migration at early stage, and IF and allograft nephroangiosclerosis at the late stage of CAN pathogenesis in rats.

  8. 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).

  9. Increasing 13C CP-MAS NMR resolution using single crystals: application to model octaethyl porphyrins.

    Science.gov (United States)

    Dugar, Sneha; Fu, Riqiang; Dalal, Naresh S

    2012-08-02

    Octaethyl porphyrin (OEP) and its Ni and Zn derivatives are considered as model compounds in biochemical, photophysical, and fossil fuel chemistry. They have thus been investigated by high-resolution solid-state (13)C NMR using powders, but peak assignment has been difficult because of large line widths. Arguing that a significant cause of broadening might be the anisotropic bulk magnetic susceptibility, we utilized single crystals in our (13)C cross-polarization magic angle spinning (CP-MAS) measurements and observed a nearly 2-fold line narrowing. This enhanced resolution enabled us to assign chemical shifts to each carbon for all the three compounds. The new assignments are now in agreement with X-ray structural data and allowed us to probe the motional dynamics of the methyl and methylene carbons of the OEP side chains. It is apparent that the use of single crystals in (13)C CP-MAS measurements has a significantly wider impact than previously thought.

  10. Hydroxysafflor yellow A increases BDNF and NMDARs in the hippocampus in a vascular dementia rat model.

    Science.gov (United States)

    Xing, Mengya; Sun, Qingna; Wang, Yiyi; Cheng, Yan; Zhang, Nan

    2016-07-01

    Hydroxysafflor yellow A (HSYA) is a drug that exerts angiogenesis regulatory and neuroprotective effects and has become an effective therapy for brain and heart ischemic disorders. There is no definite evidence supporting a therapeutic effect of HSYA in vascular dementia (VaD). We used HSYA in a rat model of chronic cerebral ischemia to determine its potential therapeutic effects in VaD. The Morris water maze (MWM) was used to evaluate spatial cognitive function, and long-term potentiation (LTP) was tested as a marker of synaptic plasticity. The expression levels of brain-derived neurotrophic factor (BDNF) and two subunits of N-methyl-d-aspartate receptor (NMDAR; GluN2A and GluN2B) in the hippocampus were measured via western blotting. The MWM results showed that the experimental VaD group had longer escape latencies than the sham group, whereas the HSYA group had a decreased escape latency compared with the VaD group (PCA3-CA1 synapses in the hippocampus was also enhanced in the HSYA compared with the VaD group (P<0.05). The western blotting results revealed lower hippocampal BDNF and GluN2B expression in the VaD group compared with the sham group and significantly higher hippocampal expression in the HSYA group compared with the VaD group. No significant change in GluN2A expression was detected. The results indicate that HSYA may enhance the endogenous expression of BDNF and GluN2B, which are associated with the synaptic plasticity of the hippocampus, and may improve spatial learning and memory abilities in a rat model of VaD.

  11. Fast cloud adjustment to increasing CO2 in a superparameterized climate model

    Science.gov (United States)

    Wyant, Matthew C.; Bretherton, Christopher S.; Blossey, Peter N.; Khairoutdinov, Marat

    2012-05-01

    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.

  12. Magnetic nanoparticles from Magnetospirillum gryphiswaldense increase the efficacy of thermotherapy in a model of colon carcinoma.

    Directory of Open Access Journals (Sweden)

    Silvia Mannucci

    Full Text Available Magnetic nanoparticles (MNPs are capable of generate heating power under the influence of alternating magnetic fields (AMF; this behaviour recently opened new scenarios for advanced biomedical applications, mainly as new promising tumor therapies. In this paper we have tested magnetic nanoparticles called magnetosomes (MNs: a class of MNPs naturally produced by magnetotactic bacteria. We extracted MNs from Magnetospirillum gryphiswaldense strain MSR-1 and tested the interaction with cellular elements and anti-neoplastic activity both in vitro and in vivo, with the aim of developing new therapeutic approaches for neoplastic diseases. In vitro experiments performed on Human Colon Carcinoma HT-29 cell cultures demonstrated a strong uptake of MNs with no evident signs of cytotoxicity and revealed three phases in the interaction: adherence, transport and accumulation in Golgi vesicles. In vivo studies were performed on subcutaneous tumors in mice; in this model MNs are administered by direct injection in the tumor volume, then a protocol consisting of three exposures to an AMF rated at 187 kHz and 23kA/m is carried out on alternate days, over a week. Tumors were monitored by Magnetic Resonance Imaging (MRI to obtain information about MNs distribution and possible tissue modifications induced by hyperthermia. Histological analysis showed fibrous and necrotic areas close to MNs injection sites in mice subjected to a complete thermotherapy protocol. These results, although concerning a specific tumor model, could be useful to further investigate the feasibility and efficacy of protocols based on MFH. Magnetic nanoparticles naturally produced and extracted from bacteria seem to be promising candidates for theranostic applications in cancer therapy.

  13. Increasing transcultural awareness: the McMaster-Aga Khan-CIDA Project workshop model.

    Science.gov (United States)

    Smith, S E

    1997-01-01

    McMaster-Aga Khan-CIDA Project personnel at McMaster University School of Nursing over a period of four years designed and conducted eight one-day introductory workshops for nurses, faculty, staff, host families, and others involved with Pakistani nurses and Lady Health Visitors studying in Canada. The workshops (entitled Increasing Intercultural Awareness) assisted the Canadian and international participants to improve their awareness and knowledge of transcultural communication in preparation for working and socializing together. Using a participatory and active-learning approach, the workshop method introduced participants to transcultural communication; emphasized appreciation of cultural values, similarities and differences; and provided country-specific information on Pakistan. This article outlines the workshop design and rationale and describes specific examples of the transcultural nursing principles, practices, and teaching activities included in the one-day event.

  14. 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.

  15. Serelaxin increases the antifibrotic action of rosiglitazone in a model of hepatic fibrosis.

    Science.gov (United States)

    Bennett, Robert G; Simpson, Ronda L; Hamel, Frederick G

    2017-06-14

    To determine the effect of combined serelaxin and rosiglitazone treatment on established hepatic fibrosis. Hepatic fibrosis was induced in mice by carbon tetrachloride administration for 6 wk, or vehicle alone (nonfibrotic mice). For the final 2 wk, mice were treated with rosiglitazone, serelaxin, or both rosiglitazone and serelaxin. Serum liver enzymes and relaxin levels were determined by standard methods. The degree of liver collagen content was determined by histology and immunohistochemistry. Expression of type I collagen was determined by quantitative PCR. Activation of hepatic stellate cells was assessed by alpha-smooth muscle actin (SMA) levels. Liver peroxisome proliferator activated receptor-gamma coactivator 1 alpha (PGC1α) was determined by Western blotting. Treatment of mice with CCl4 resulted in hepatic fibrosis as evidenced by increased liver enzyme levels (ALT and AST), and increased liver collagen and SMA. Monotherapy with either serelaxin or rosiglitazone for 2 wk was generally without effect. In contrast, the combination of serelaxin and rosiglitazone resulted in significantly improved ALT levels (P < 0.05). Total liver collagen content as determined by Sirius red staining revealed that only combination treatment was effective in reducing total liver collagen (P < 0.05). These results were supported by immunohistochemistry for type I collagen, in which only combination treatment reduced fibrillar collagen levels (P < 0.05). The level of hepatic stellate cell activation was modestly, but significantly, reduced by serelaxin treatment alone, but combination treatment resulted in significantly lower SMA levels. Finally, while hepatic fibrosis reduced liver PGC1α levels, the combination of serelaxin and rosiglitazone resulted in restoration of PGC1α protein levels. The combination of serelaxin and rosiglitazone treatment for 2 wk was effective in significantly reducing established hepatic fibrosis, providing a potential new treatment strategy.

  16. Simulation Modeling of Lakes in Undergraduate and Graduate Classrooms Increases Comprehension of Climate Change Concepts and Experience with Computational Tools

    Science.gov (United States)

    Carey, Cayelan C.; Gougis, Rebekka Darner

    2017-02-01

    Ecosystem modeling is a critically important tool for environmental scientists, yet is rarely taught in undergraduate and graduate classrooms. To address this gap, we developed a teaching module that exposes students to a suite of modeling skills and tools (including computer programming, numerical simulation modeling, and distributed computing) that students apply to study how lakes around the globe are experiencing the effects of climate change. In the module, students develop hypotheses about the effects of different climate scenarios on lakes and then test their hypotheses using hundreds of model simulations. We taught the module in a 4-hour workshop and found that participation in the module significantly increased both undergraduate and graduate students' understanding about climate change effects on lakes. Moreover, participation in the module also significantly increased students' perceived experience level in using different software, technologies, and modeling tools. By embedding modeling in an environmental science context, non-computer science students were able to successfully use and master technologies that they had previously never been exposed to. Overall, our findings suggest that modeling is a powerful tool for catalyzing student learning on the effects of climate change.

  17. Simulation Modeling of Lakes in Undergraduate and Graduate Classrooms Increases Comprehension of Climate Change Concepts and Experience with Computational Tools

    Science.gov (United States)

    Carey, Cayelan C.; Gougis, Rebekka Darner

    2016-08-01

    Ecosystem modeling is a critically important tool for environmental scientists, yet is rarely taught in undergraduate and graduate classrooms. To address this gap, we developed a teaching module that exposes students to a suite of modeling skills and tools (including computer programming, numerical simulation modeling, and distributed computing) that students apply to study how lakes around the globe are experiencing the effects of climate change. In the module, students develop hypotheses about the effects of different climate scenarios on lakes and then test their hypotheses using hundreds of model simulations. We taught the module in a 4-hour workshop and found that participation in the module significantly increased both undergraduate and graduate students' understanding about climate change effects on lakes. Moreover, participation in the module also significantly increased students' perceived experience level in using different software, technologies, and modeling tools. By embedding modeling in an environmental science context, non-computer science students were able to successfully use and master technologies that they had previously never been exposed to. Overall, our findings suggest that modeling is a powerful tool for catalyzing student learning on the effects of climate change.

  18. Atorvastatin increases dynamin 1 expression in hippocampal CA1 region in a rat model of vascular dementia

    Institute of Scientific and Technical Information of China (English)

    Qinghua Li; Wensheng Zhou

    2011-01-01

    The current study examined a rat model of vascular dementia. The model rats exhibited obvious morphological and ultrastructural changes in neurons in the brain, and significantly reduced dynamin 1 expression in hippocampal CA1 region along with decreased learning and memory performance. Following atorvastatin treatment, the morphology and ultrastructure of cells in the model rat brain were significantly improved, dynamin 1 expression in hippocampal CA1 region was significantly enhanced, and learning and memory ability was significantly improved. The results demonstrated that impaired learning and memory abilities in vascular dementia model rats were closely correlated with decreased dynamin 1 expression. These findings indicate that atorvastatin can protect model rats against cognitive impairment by increasing dynamin 1 expression.

  19. 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

  20. 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

  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. Graphical modeling of gene expression in monocytes suggests molecular mechanisms explaining increased atherosclerosis in smokers.

    Directory of Open Access Journals (Sweden)

    Ricardo A Verdugo

    Full Text Available Smoking is a risk factor for atherosclerosis with reported widespread effects on gene expression in circulating blood cells. We hypothesized that a molecular signature mediating the relation between smoking and atherosclerosis may be found in the transcriptome of circulating monocytes. Genome-wide expression profiles and counts of atherosclerotic plaques in carotid arteries were collected in 248 smokers and 688 non-smokers from the general population. Patterns of co-expressed genes were identified by Independent Component Analysis (ICA and network structure of the pattern-specific gene modules was inferred by the PC-algorithm. A likelihood-based causality test was implemented to select patterns that fit models containing a path "smoking→gene expression→plaques". Robustness of the causal inference was assessed by bootstrapping. At a FDR ≤0.10, 3,368 genes were associated to smoking or plaques, of which 93% were associated to smoking only. SASH1 showed the strongest association to smoking and PPARG the strongest association to plaques. Twenty-nine gene patterns were identified by ICA. Modules containing SASH1 and PPARG did not show evidence for the "smoking→gene expression→plaques" causality model. Conversely, three modules had good support for causal effects and exhibited a network topology consistent with gene expression mediating the relation between smoking and plaques. The network with the strongest support for causal effects was connected to plaques through SLC39A8, a gene with known association to HDL-cholesterol and cellular uptake of cadmium from tobacco, while smoking was directly connected to GAS6, a gene reported to have anti-inflammatory effects in atherosclerosis and to be up-regulated in the placenta of women smoking during pregnancy. Our analysis of the transcriptome of monocytes recovered genes relevant for association to smoking and atherosclerosis, and connected genes that before, were only studied in separate contexts

  3. Increasing the Depth of Current Understanding: Sensitivity Testing of Deep-Sea Larval Dispersal Models for Ecologists.

    Science.gov (United States)

    Ross, Rebecca E; Nimmo-Smith, W Alex M; Howell, Kerry L

    2016-01-01

    Larval dispersal is an important ecological process of great interest to conservation and the establishment of marine protected areas. Increasing numbers of studies are turning to biophysical models to simulate dispersal patterns, including in the deep-sea, but for many ecologists unassisted by a physical oceanographer, a model can present as a black box. Sensitivity testing offers a means to test the models' abilities and limitations and is a starting point for all modelling efforts. The aim of this study is to illustrate a sensitivity testing process for the unassisted ecologist, through a deep-sea case study example, and demonstrate how sensitivity testing can be used to determine optimal model settings, assess model adequacy, and inform ecological interpretation of model outputs. Five input parameters are tested (timestep of particle simulator (TS), horizontal (HS) and vertical separation (VS) of release points, release frequency (RF), and temporal range (TR) of simulations) using a commonly employed pairing of models. The procedures used are relevant to all marine larval dispersal models. It is shown how the results of these tests can inform the future set up and interpretation of ecological studies in this area. For example, an optimal arrangement of release locations spanning a release area could be deduced; the increased depth range spanned in deep-sea studies may necessitate the stratification of dispersal simulations with different numbers of release locations at different depths; no fewer than 52 releases per year should be used unless biologically informed; three years of simulations chosen based on climatic extremes may provide results with 90% similarity to five years of simulation; and this model setup is not appropriate for simulating rare dispersal events. A step-by-step process, summarising advice on the sensitivity testing procedure, is provided to inform all future unassisted ecologists looking to run a larval dispersal simulation.

  4. Modeling a Dynamic Data Replication Strategy to Increase System Availability in Cloud Computing Environments

    Institute of Scientific and Technical Information of China (English)

    Da-Wei Sun; Gui-Ran Chang; Shang Gao; Li-Zhong Jin; Xing-Wei Wang

    2012-01-01

    Failures are normal rather than exceptional in the cloud computing environmcnts.To improve system availability,replicating the popular data to multiple suitable locations is an advisable choice,as users can access the data from a nearby site.This is,however,not the case for replicas which must have a fixed number of copies on several locations.How to decide a reasonable number and right locations for replicas has become a challenge in the cloud computing.In this paper,a dynamic data replication strategy is put forward with a brief survey of replication strategy suitable for distributed computing environments.It includes:1) analyzing and modeling the relationship between system availability and the number of replicas; 2) evaluating and identifying the popular data and triggering a replication operation when the popularity data passes a dynamic threshold; 3) calculating a suitable number of copies to meet a reasonable system byte effective rate requirement and placing replicas among data nodes in a balanced way; 4) designing the dynamic data replication algorithm in a cloud.Experimental results demonstrate the efficiency and effectiveness of the improved system brought by the proposed strategy in a cloud.

  5. Salvianolate increases heat shock protein expression in a cerebral ischemia-reperfusion injury model

    Institute of Scientific and Technical Information of China (English)

    Jinnan Zhang; Wei Lu; Qiang Lei; Xi Tao; Hong You; Pinghui Xie

    2013-01-01

    Stroke remains a worldwide health problem. Salvianolate exerts a protective effect in various mi-crocirculatory disturbance-related diseases, but studies of the mechanisms underlying its protective action have mainly focused on the myocardium, whereas little research has been carried out in brain tissue fol owing ischemia-reperfusion. We assessed the neuroprotective effects of salvianolate in a rat model of cerebral ischemia-reperfusion injury induced using the suture method. At onset and 24 and 48 hours after reperfusion, rats were intraperitoneal y injected with salvianolate (18 mg/kg) or saline. Neurological deficit scores at 72 hours showed that the neurological functions of rats that had received salvianolate were significantly better than those of the rats that had received saline. 2,3,5-Triphenyltetrazolium chloride was used to stain cerebral tissue to determine the extent of the infarct area. A significantly smal er infarct area and a significantly lower number of apoptotic cel s were observed after treatment with salvianolate compared with the saline treatment. Expression of heat shock protein 22 and phosphorylated protein kinase B in ischemic brain tissue was significantly greater in rats treated with salvianolate compared with rats treated with saline. Our findings suggest that salvianolate provides neuroprotective effects against cerebral ischemia-reperfusion injury by upregulating heat shock protein 22 and phosphorylated protein kinase B expression.

  6. A fitness screening model for increasing fitness assessment and research experiences in undergraduate exercise science students.

    Science.gov (United States)

    Brown, Gregory A; Lynott, Frank; Heelan, Kate A

    2008-09-01

    When students analyze and present original data they have collected, and hence have a cultivated sense of curiosity about the data, student learning is enhanced. It is often difficult to provide students an opportunity to practice their skills, use their knowledge, and gain research experiences during a typical course laboratory. This article describes a model of an out-of-classroom experience during which undergraduate exercise science students provide a free health and fitness screening to the campus community. Although some evidence of the effectiveness of this experience is presented, this is not a detailed evaluation of either the service or learning benefits of the fitness screening. Working in small learning groups in the classroom, students develop hypotheses about the health and fitness of the population to be screened. Then, as part of the health and fitness screening, participants are evaluated for muscular strength, aerobic fitness, body composition, blood pressure, physical activity, and blood cholesterol levels. Students then analyze the data collected during the screening, accept or reject their hypotheses based on statistical analyses of the data, and make in-class presentations of their findings. This learning experience has been used successfully to illustrate the levels of obesity, hypercholesterolemia, and lack of physical fitness in the campus community as well as provide an opportunity for students to use statistical procedures to analyze data. It has also provided students with an opportunity to practice fitness assessment and interpersonal skills that will enhance their future careers.

  7. Increased brain iron coincides with early plaque formation in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Leskovjan, Andreana C; Kretlow, Ariane; Lanzirotti, Antonio; Barrea, Raul; Vogt, Stefan; Miller, Lisa M

    2011-03-01

    Elevated brain iron content, which has been observed in late-stage human Alzheimer's disease, is a potential target for early diagnosis. However, the time course for iron accumulation is currently unclear. Using the PSAPP mouse model of amyloid plaque formation, we conducted a time course study of metal ion content and distribution [iron (Fe), copper (Cu), and zinc (Zn)] in the cortex and hippocampus using X-ray fluorescence microscopy (XFM). We found that iron in the cortex was 34% higher than age-matched controls at an early stage, corresponding to the commencement of plaque formation. The elevated iron was not associated with the amyloid plaques. Interestingly, none of the metal ions were elevated in the amyloid plaques until the latest time point (56 weeks), where only the Zn content was significantly elevated by 38%. Since neuropathological changes in human Alzheimer's disease are presumed to occur years before the first cognitive symptoms appear, quantification of brain iron content could be a powerful marker for early diagnosis of Alzheimer's disease.

  8. Type 1 copper site synthetic model complexes with increased redox potentials.

    Science.gov (United States)

    Yang, Lei; Tolman, William B

    2012-02-01

    Reactions of NaSCPh(3) with (R(3)tacn)Cu(OTf)(2) (R is Me, iPr; tacn is 1,4,7-triazacyclononane; OTf is CF(3)SO(3)(-)) yield blue complexes identified as ((R(3)tacn)CuSCPh(3))(OTf) on the basis of UV-vis, resonance Raman, and electron paramagnetic resonance (EPR) spectroscopy and electrospray ionization mass spectrometry. These complexes exhibit spectroscopic properties typical of type 1 copper sites in proteins, including diagnostic Sπ → Cu(d(x(2)-y(2))) ligand-to-metal charge transfer transitions at approximately 610-630 nm and small A(||) values in EPR spectra of less than 100 × 10(-4) cm(-1). Cyclic voltammetry experiments revealed redox potentials for the complexes similar to those of several low-potential type 1 copper proteins (e.g., azurin, stellacyanin) and approximately 0.5 V higher than those of previously reported model compounds. Thus, the new complexes mimic key aspects of both the structure and the function of type 1 copper sites.

  9. 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.

  10. 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

  11. Genistein Attenuates Nonalcoholic Steatohepatitis and Increases Hepatic PPARγ in a Rat Model

    Directory of Open Access Journals (Sweden)

    Warinda Susutlertpanya

    2015-01-01

    Full Text Available Nonalcoholic steatohepatitis (NASH has become a global chronic liver disease, but no effective medicine has been proven to cure it. This study investigated the protective effects of genistein, a phytoestrogen, on NASH and examined whether it has any effect on hepatic PPARγ. Male Sprague-Dawley rats were divided into four groups: control group fed ad libitum with standard rat diet, NASH group fed ad libitum with high-fat diet to induce NASH and NASH + Gen8 group and NASH + Gen16 group fed with high-fat diet plus intragastric administration of 8 or 16 mg/kg genistein once daily. After 6 weeks, liver samples were collected to determine MDA, TNF-α, PPARγ, and histopathology. The findings were that levels of hepatic MDA and TNF-α increased in NASH group, but 16 mg/kg genistein reduced these levels significantly. Downregulation of hepatic PPARγ was observed in NASH group, but genistein significantly upregulated the expression of PPARγ in both NASH + Gen groups. The histological appearance of liver in NASH group presented pathological features of steatohepatitis which were diminished in both NASH + Gen groups. The results suggest that genistein attenuates the liver histopathology of NASH with upregulation of hepatic PPARγ, reduction of oxidative stress, and inhibition of inflammatory cytokine.

  12. 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.

  13. 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.

  14. The Use of Video Self-Modeling to Increase On-Task Behavior in Children with High-Functioning Autism

    Science.gov (United States)

    Schatz, Rochelle B.; Peterson, Rachel K.; Bellini, Scott

    2016-01-01

    In the present study, the researchers implemented a video self-modeling intervention for increasing on-task classroom behavior for three elementary school students diagnosed with an autism spectrum disorder. The researchers observed the students' on-task engagement three times a week during their respective math classes. A multiple baseline design…

  15. Use of video modeling to increase positive peer interactions of four preschool children with social skills difficulties

    NARCIS (Netherlands)

    Green, V.A.; Drysdale, H.; Boelema, T.; Smart, E.; Meer, L. van der; Achmadi, D.; Prior, T.; O'Reilly, M.F.; Didden, H.C.M.; Lancioni, G.E.

    2013-01-01

    Difficulties initiating and maintaining positive social interactions with peers represents a significant problem for many preschool children. The present study sought to evaluate the use of a video modeling intervention for increasing positive peer interactions among four preschool boys who were ass

  16. Activation of Retinoid X Receptor increases dopamine cell survival in models for Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Bergsland Maria

    2009-12-01

    Full Text Available Abstract Background Parkinson's disease (PD is caused by degeneration of dopamine (DA neurons in the ventral midbrain (vMB and results in severely disturbed regulation of movement. The disease inflicts considerable suffering for the affected and their families. Today, the opportunities for pharmacological treatment are meager and new technologies are needed. Previous studies have indicated that activation of the nuclear receptor Retinoid X Receptor (RXR provides trophic support for DA neurons. Detailed investigations of these neurotrophic effects have been hampered by the lack of readily available DA neurons in vitro. The aim of this study was to further describe the potential neurotrophic actions of RXR ligands and, for this and future purposes, develop a suitable in vitro-platform using mouse embryonic stem cells (mESCs. Results We studied the potential neurotrophic effects of the RXR ligand LG100268 (LG268 and the RXR-Nurr1 ligand XCT0139508 (XCT in neuronal cultures derived from rat primary vMB and mESCs. RXR ligands protect DA neurons from stress, such as that induced by the PD-modeling toxin 6-hydroxy dopamine (6-OHDA and hypoxia, but not from stress induced by oxidative hydrogen peroxide (H2O2 or the excitotoxic agent kainic acid (KA. The neurotrophic effect is selective for DA neurons. DA neurons from rat primary vMB and mESCs behaved similarly, but the mESC-derived cultures contained a much higher fraction of DA cells and thus provided more accessible experimental conditions. Conclusions RXR ligands rescue DA neurons from degeneration caused by the PD simulating 6-OHDA as well as hypoxia. Thus, RXR is a novel promising target for PD research. mESC-derived DA cells provide a valid and accessible in vitro-platform for studying PD inducing toxins and potential trophic agents.

  17. Carcinogenically relevant split dose repair increased with age in rat skin model.

    Science.gov (United States)

    Burns, Fredric; Tang, Moon-Shong Eric; Wu, Feng; Uddin, Ahmed

    2012-07-01

    These experiments utilize cancer induction to evaluate cancer-relevant repair during the interval between dose fractions. Low LET electron radiation(LET ~ 0.34 keV/u) were utilized in experiments that involved exposing rat dorsal skin to 2 equal 8 Gy dose fractions separated at various intervals from 0.25 h to 24 h. Cancer onset was established for 80 weeks after the exposures and only histologically verified cancers were included in the analysis. This experiment involved a total of 540 rats and 880 induced cancers. In the youngest rats (irradiated at 28 days of age) the cancer yield declined with a halftime of approximately 3.5 hrs. In 113 day old rats the cancer yield halftime was shortened to 1.3 hrs. In the oldest rats (182 days of age), the halftime could not be established quantitatively, because it was less than the shortest interval (15 min) utilized in the protocol (best estimate ~5 min). In the oldest rats the cancer yields for all fractionated exposures dropped essentially to the expected level of 2 single fractions, below which theoretically no further reduction is possible. The follow-up times for obtaining cancer yields were the same for all exposure groups in spite of the differing ages at exposure. These results indicate that repair of carcinogenically-relevant damage accelerates with age of the rat. No information is available on the possible mechanistic basis for this finding, although the model might be useful for delineating which of the many postulated split dose repair pathways is the correct one. The finding indicates that older rats should be less susceptible to the carcinogenic action of single doses of low LET radiation in comparison to younger rats, which has been verified in separate studies.

  18. A dynamic warm-up model increases quadriceps strength and hamstring flexibility.

    Science.gov (United States)

    Aguilar, Alain J; DiStefano, Lindsay J; Brown, Cathleen N; Herman, Daniel C; Guskiewicz, Kevin M; Padua, Darin A

    2012-04-01

    Research suggests that static stretching can negatively influence muscle strength and power and may result in decreased functional performance. The dynamic warm-up (DWU) is a common alternative to static stretching before physical activity, but there is limited research investigating the effects of a DWU. The purpose of this study was to compare the acute effects of a DWU and static stretching warm-up (SWU) on muscle flexibility, strength, and vertical jump using a randomized controlled trial design. Forty-five volunteers were randomly assigned into a control (CON), SWU, or DWU group. All participants rode a stationary bicycle for 5 minutes and completed a 10-minute warm-up protocol. During this protocol, the DWU group performed dynamic stretching and running, the SWU group performed static stretching, and the CON group rested. Dependent variables were measured immediately before and after the warm-up protocol. A digital inclinometer measured flexibility (degrees) for the hamstrings, quadriceps, and hip flexor muscles. An isokinetic dynamometer measured concentric and eccentric peak torque (N·m/kg) for the hamstrings and quadriceps. A force plate was used to measure vertical jump height (meters) and power (watts). In the DWU group, there was a significant increase in hamstring flexibility (pretest: 26.4 ± 13.5°, posttest: 16.9 ± 9.4°; p 0.05). The DWU significantly improved eccentric quadriceps strength and hamstrings flexibility, whereas the SWU did not facilitate any positive or negative changes in muscle flexibility, strength, power, or vertical jump. Therefore, the DWU may be a better preactivity warm-up choice than an SWU.

  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. Nonlinear modeling and dynamic analysis of a hydro-turbine governing system in the process of sudden load increase transient

    Science.gov (United States)

    Li, Huanhuan; Chen, Diyi; Zhang, Hao; Wang, Feifei; Ba, Duoduo

    2016-12-01

    In order to study the nonlinear dynamic behaviors of a hydro-turbine governing system in the process of sudden load increase transient, we establish a novel nonlinear dynamic model of the hydro-turbine governing system which considers the elastic water-hammer model of the penstock and the second-order model of the generator. The six nonlinear dynamic transfer coefficients of the hydro-turbine are innovatively proposed by utilizing internal characteristics and analyzing the change laws of the characteristic parameters of the hydro-turbine governing system. Moreover, from the point of view of engineering, the nonlinear dynamic behaviors of the above system are exhaustively investigated based on bifurcation diagrams and time waveforms. More importantly, all of the above analyses supply theoretical basis for allowing a hydropower station to maintain a stable operation in the process of sudden load increase transient.

  2. Remarkable increase in 14C-acetate uptake in an epilepsy model rat brain induced by lithium-pilocarpine.

    Science.gov (United States)

    Hosoi, Rie; Kitano, Daisuke; Momosaki, Sotaro; Kuse, Kenji; Gee, Antony; Inoue, Osamu

    2010-01-22

    The present study demonstrates changes in rat brain glial metabolism during the acute phase of epilepsy. Status epilepticus (SE) was induced using the lithium-pilocarpine model. Glial metabolism was measured with (14)C-acetate. Local cerebral blood flow and glucose metabolism were also measured using (14)C-N-isopropyl-p-iodoamphetamine (IMP) and (14)C-2-deoxyglucose (2DG), respectively. At the initiation of the seizure, (14)C-acetate uptake did not change significantly. However, a marked increase was observed 2 h after the pilocarpine injection in all brain regions studied. The increase of brain uptake was transient, and the maximum enhancement was seen at 2 h after the pilocarpine injection. The increase of (14)C-acetate uptake was almost to the same degree in all regions, whereas (14)C-IMP and (14)C-2DG uptakes showed a heterogeneous increase. In the case of (14)C-IMP, the highest increase was observed in the thalamus (280%), and a moderate increase (120 to 150%) was seen in the orbital cortex, cingulate cortex and pyriform cortex. (14)C-2DG uptake increased by 130 to 240% in most regions of the brain, however, an increase of only 40 and 20% was observed in the cerebellum and pons-medulla, respectively. These results demonstrated that glial energy metabolism was markedly enhanced during a prolonged seizure. To our knowledge, this study is the first observation showing large and widespread glial metabolic increases in the rat brain during status epilepticus.

  3. 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.

  4. 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

  5. Increasing the Depth of Current Understanding: Sensitivity Testing of Deep-Sea Larval Dispersal Models for Ecologists

    Science.gov (United States)

    Nimmo-Smith, W. Alex M.; Howell, Kerry L.

    2016-01-01

    Larval dispersal is an important ecological process of great interest to conservation and the establishment of marine protected areas. Increasing numbers of studies are turning to biophysical models to simulate dispersal patterns, including in the deep-sea, but for many ecologists unassisted by a physical oceanographer, a model can present as a black box. Sensitivity testing offers a means to test the models’ abilities and limitations and is a starting point for all modelling efforts. The aim of this study is to illustrate a sensitivity testing process for the unassisted ecologist, through a deep-sea case study example, and demonstrate how sensitivity testing can be used to determine optimal model settings, assess model adequacy, and inform ecological interpretation of model outputs. Five input parameters are tested (timestep of particle simulator (TS), horizontal (HS) and vertical separation (VS) of release points, release frequency (RF), and temporal range (TR) of simulations) using a commonly employed pairing of models. The procedures used are relevant to all marine larval dispersal models. It is shown how the results of these tests can inform the future set up and interpretation of ecological studies in this area. For example, an optimal arrangement of release locations spanning a release area could be deduced; the increased depth range spanned in deep-sea studies may necessitate the stratification of dispersal simulations with different numbers of release locations at different depths; no fewer than 52 releases per year should be used unless biologically informed; three years of simulations chosen based on climatic extremes may provide results with 90% similarity to five years of simulation; and this model setup is not appropriate for simulating rare dispersal events. A step-by-step process, summarising advice on the sensitivity testing procedure, is provided to inform all future unassisted ecologists looking to run a larval dispersal simulation. PMID

  6. Modeling clustered activity increase in amyloid-beta positron emission tomographic images with statistical descriptors

    Directory of Open Access Journals (Sweden)

    Shokouhi S

    2015-04-01

    correlated with the increase in mean SUVR but showed lower variance. The whole brain results showed a higher inverse correlation between the cerebrospinal Aβ and wS2 than between the cerebrospinal Aβ and SUVR mean/median. We did not observe any confounding of wS2 by region size or injected dose.Conclusion: The wS2 detects subtle changes and provides additional information about the binding characteristics of radiotracers and Aβ accumulation that are difficult to verify with mean SUVR alone.Keywords: amyloid-beta plaques, positron emission tomography, 11C-Pittsburgh compound B, statistical descriptors, two-point correlation function

  7. Increased sensitivity to light-induced damage in a mouse model of autosomal dominant retinal disease.

    Science.gov (United States)

    White, D Alan; Fritz, Jason J; Hauswirth, William W; Kaushal, Shalesh; Lewin, Alfred S

    2007-05-01

    rhodopsin transgene. The results suggest that elimination of the glycosylation site at N15 is associated with increased sensitivity to light-induced damage.

  8. Climate sensitivity due to increased CO2: experiments with a coupled atmosphere and ocean general circulation model

    Science.gov (United States)

    Washington, Warren M.; Meehl, Gerald A.

    1989-06-01

    A version of the National Center for Atmospheric Research community climate model — a global, spectral (R15) general circulation model — is coupled to a coarse-grid (5° latitude-] longitude, four-layer) ocean general circulation model to study the response of the climate system to increases of atmospheric carbon dioxide (CO2). Three simulations are run: one with an instantaneous doubling of atmospheric CO2 (from 330 to 660 ppm), another with the CO2 concentration starting at 330 ppm and increasing linearly at a rate of 1% per year, and a third with CO2 held constant at 330 pm. Results at the end of 30 years of simulation indicate a globally averaged surface air temperature increase of 1.6° C for the instantaneous doubling case and 0.7°C for the transient forcing case. Inherent characteristics of the coarse-grid ocean model flow sea-surface temperatures (SSTs) in the tropics and higher-than-observed SSTs and reduced sea-ice extent at higher latitudes] produce lower sensitivity in this model after 30 years than in earlier simulations with the same atmosphere coupled to a 50-m, slab-ocean mixed layer. Within the limitations of the simulated meridional overturning, the thermohaline circulation weakens in the coupled model with doubled CO2 as the high-latitude ocean-surface layer warms and freshens and westerly wind stress is decreased. In the transient forcing case with slowly increasing CO2 (30% increase after 30 years), the zonal mean warming of the ocean is most evident in the surface layer near 30° 50° S. Geographical plots of surface air temperature change in the transient case show patterns of regional climate anomalies that differ from those in the instantaneous CO2 doubling case, particularly in the North Atlantic and northern European regions. This suggests that differences in CO2 forcing in the climate system are important in CO2 response in regard to time-dependent climate anomaly regimes. This confirms earlier studies with simple climate models

  9. Modeling the Roles of Precipitation Increasing in Glacier Systems Responding to Climate Warming - Taking Xinjiang Glaciated Region as Example

    Institute of Scientific and Technical Information of China (English)

    WANG Xin; XIE Zichu; LIU Shiyin; TAO Jianjun; HAN Yongshun; YANG Yuelong

    2005-01-01

    The studies on prediction of climate in Xinjiang almost show that the precipitation would increase in the coming 50 years, although there were surely some uncertainties in precipitation predictions.On the basis of the structure of glacier system and nature of equilibrium line altitude at steady state (ELAo), a functional model of the glacier system responding to climate changes was established, and it simultaneously involved the rising of summer mean temperature and increasing of mean precipitation.The results from the functional model under the climatic scenarios with temperature increasing rates of 0.01, 0.03 and 0.05 K/year indicated that the precipitation increasing would play an evident role in glacier system responding to climate change: if temperature become 1℃ higher, the precipitation would be increased by 10%, which can slow down the glaciers retreating rate in the area by 4%, accelerate runoff increasing rate by 8% and depress the ELAo rising gradient by 24 m in northern Xinjiang glacier system where semi-continental glaciers dominate,while it has corresponding values of only 1%, 5 % and 18m respectively in southern Xinjiang glacier system,where extremely continental glaciers dominate.

  10. Reaching Nutritional Adequacy Does Not Necessarily Increase Exposure to Food Contaminants: Evidence from a Whole-Diet Modeling Approach.

    Science.gov (United States)

    Barré, Tangui; Vieux, Florent; Perignon, Marlène; Cravedi, Jean-Pierre; Amiot, Marie-Josèphe; Micard, Valérie; Darmon, Nicole

    2016-10-01

    Dietary guidelines are designed to help meet nutritional requirements, but they do not explicitly or quantitatively account for food contaminant exposures. In this study, we aimed to test whether dietary changes needed to achieve nutritional adequacy were compatible with acceptable exposure to food contaminants. Data from the French national dietary survey were linked with food contaminant data from the French Total Diet Study to estimate the mean intake of 204 representative food items and mean exposure to 27 contaminants, including pesticides, heavy metals, mycotoxins, nondioxin-like polychlorinated biphenyls (NDL-PCBs) and dioxin-like compounds. For each sex, 2 modeled diets that departed the least from the observed diet were designed: 1) a diet respecting only nutritional recommendations (NUT model), and 2) a diet that met nutritional recommendations without exceeding Toxicological Reference Values (TRVs) and observed contaminant exposures (NUTOX model). Food, nutrient, and contaminant contents in observed diets and NUT and NUTOX diets were compared with the use of paired t tests. Mean observed diets did not meet all nutritional recommendations, but no contaminant was over 48% of its TRV. Achieving all the nutrient recommendations through the NUT model mainly required increases in fruit, vegetable, and fish intake and decreases in meat, cheese, and animal fat intake. These changes were associated with significantly increased dietary exposure to some contaminants, but without exceeding 57% of TRVs. The highest increases were found for NDL-PCBs (from 26% to 57% of TRV for women). Reaching nutritional adequacy without exceeding observed contaminant exposure (NUTOX model) was possible but required further departure from observed food quantities. Based on a broad range of nutrients and contaminants, this first assessment of compatibility between nutritional adequacy and toxicological exposure showed that reaching nutritional adequacy might increase exposure to food

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

    Science.gov (United States)

    Lambert, Laura J.; Challa, Anil K.; Niu, Aidi; Zhou, Lihua; Tucholski, Janusz; Johnson, Maria S.; Nagy, Tim R.; Eberhardt, Alan W.; Estep, Patrick N.; Kesterson, Robert A.

    2016-01-01

    ABSTRACT 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. PMID:27483347

  12. 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.

  13. Using modelling to predict impacts of sea level rise and increased turbidity on seagrass distributions in estuarine embayments

    Science.gov (United States)

    Davis, Tom R.; Harasti, David; Smith, Stephen D. A.; Kelaher, Brendan P.

    2016-11-01

    Climate change induced sea level rise will affect shallow estuarine habitats, which are already under threat from multiple anthropogenic stressors. Here, we present the results of modelling to predict potential impacts of climate change associated processes on seagrass distributions. We use a novel application of relative environmental suitability (RES) modelling to examine relationships between variables of physiological importance to seagrasses (light availability, wave exposure, and current flow) and seagrass distributions within 5 estuarine embayments. Models were constructed separately for Posidonia australis and Zostera muelleri subsp. capricorni using seagrass data from Port Stephens estuary, New South Wales, Australia. Subsequent testing of models used independent datasets from four other estuarine embayments (Wallis Lake, Lake Illawarra, Merimbula Lake, and Pambula Lake) distributed along 570 km of the east Australian coast. Relative environmental suitability models provided adequate predictions for seagrass distributions within Port Stephens and the other estuarine embayments, indicating that they may have broad regional application. Under the predictions of RES models, both sea level rise and increased turbidity are predicted to cause substantial seagrass losses in deeper estuarine areas, resulting in a net shoreward movement of seagrass beds. Seagrass species distribution models developed in this study provide a valuable tool to predict future shifts in estuarine seagrass distributions, allowing identification of areas for protection, monitoring and rehabilitation.

  14. Driving forces behind the increasing cardiovascular treatment intensity.A dynamic epidemiologic model of trends in Danish cardiovascular drug utilization.

    DEFF Research Database (Denmark)

    Kildemoes, Helle Wallach; Andersen, Morten

    followed with respect to out-of-hospital redemptions of cardiovascular prescription drugs in the period 1996-2005. The impact of population ageing on cardiovascular treatment intensity was investigated by comparing crude and age/gender standardised intensities. Epidemiologic model: We developed a three...... prevalence. Conclusions: Increasing cardiovascular treatment intensity was driven by increases in age/gender specific drug use - rather than by population ageing. Although the increased prevalence of use in all age groups reflects an increasing incidence, recruitment of long-term users is expected to add......Background: In many Western countries cardiovascular treatment intensity (DDD/1000 inhabitants/day, DDD/TID) has grown substantially during the last decades. Changed drug utilization pattern - rather than population ageing - was hypothesized to be the main driving force behind the growth...

  15. Driving forces behind the increasing cardiovascular treatment intensity.A dynamic epidemiologic model of trends in Danish cardiovascular drug utilization.

    DEFF Research Database (Denmark)

    Kildemoes, Helle Wallach; Andersen, Morten

    to 619 DDD/TID from 1996 to 2005 (117%). Population ageing accounted for 22 percentage points. Treatment intensity with statins increased from 5 to 121 DDD/TID. Population ageing accounted for one eighth of this increase. Increasing incidence rates was the main driving force behind the growing statin......Background: In many Western countries cardiovascular treatment intensity (DDD/1000 inhabitants/day, DDD/TID) has grown substantially during the last decades. Changed drug utilization pattern - rather than population ageing - was hypothesized to be the main driving force behind the growth....... Objectives: To investigate the driving forces behind the increasing treatment prevalence of cardiovascular drugs, in particular statins, by means of a dynamic epidemiologic drug utilization model. Methods: Material: All Danish residents older than 20 years by January 1, 1996 (4.0 million inhabitants), were...

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. Levodopa methyl ester increases nerve growth factor expression in visual cortex area 17 in a feline model of strabismic amblyopia

    Institute of Scientific and Technical Information of China (English)

    Yongwen Li; Xing Lin; Shijun Zhang; Rong Li; Weizhe Jiang; Renbin Huang

    2011-01-01

    In the present study, a feline model of strabismic amblyopia was established during a sensitive developmental period, and the influence of levodopa methyl ester and levodopa on nerve growth factor expression in the visual cortex (area 17) was compared. Pattern visual-evoked potential and immunohistochemistry results showed that levodopa methyl ester and levodopa treatment shortened P100 wave latency, increased P100 amplitude, and increased the number of endogenous nerve growth factor-positive cells in visual cortex levels. In particular, the effects of levodopa methyl ester were superior to levodopa treatment.

  1. Climate Justice: High-Status Ingroup Social Models Increase Pro-Environmental Action Through Making Actions Seem More Moral.

    Science.gov (United States)

    Sweetman, Joseph; Whitmarsh, Lorraine E

    2016-01-01

    Recent work has suggested that our cognitive biases and moral psychology may pose significant barriers to tackling climate change. Here, we report evidence that through status and group-based social influence processes, and our moral sense of justice, it may be possible to employ such characteristics of the human mind in efforts to engender pro-environmental action. We draw on applied work demonstrating the efficacy of social modeling techniques in order to examine the indirect effects of social model status and group membership (through perceptions of efficacy, pro-environmental social identity and moral judgments of how fair it is for individuals to perform particular pro-environmental actions) on pro-environmental action tendencies. We find evidence that high- (vs. low-) status models increase pro-environmental action, in part, through making such actions seem morally fairer to undertake. This effect of high-status models only occurs when they share a meaningful ingroup membership with the target of influence. Further, we find evidence that this conditional effect of high-status models may also have a direct impact on action tendencies. While the exact behaviors that are influenced may vary across student and non-student samples, we argue that a focus on the "justice pathway" to action and the social-cognitive features of models may offer a good opportunity for cognitive and behavioral scientists to integrate insights from basic research with those stemming from more applied research efforts.

  2. 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.

  3. Combining Bevacizumab with Temozolomide Increases the Antitumor Efficacy of Temozolomide in a Human Glioblastoma Orthotopic Xenograft Model

    OpenAIRE

    Véronique Mathieu; Nancy De Nève; Marie Le Mercier; Janique Dewelle; Jean-François Gaussin; Mischael Dehoux; Robert Kiss; Florence Lefranc

    2008-01-01

    Purpose: The aims of the present work were to investigate the in vitro and in vivo antiangiogenic effects of chronic temozolomide treatment on various glioma models and to demonstrate whether bevacizumab (Avastin) increased the therapeutic benefits contributed by temozolomide in glioma. Experimental Design: The expression levels of various antiangiogenic factors in four glioma cell lines were evaluated after chronic in vitro treatment with temozolomide by Western blot. Proliferation and migra...

  4. 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

  5. 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.

  6. 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

  7. Prediction of the dynamic oscillation threshold in a clarinet model with a linearly increasing blowing pressure : Influence of noise

    CERN Document Server

    Bergeot, Baptiste; Vergez, Christophe; Gazengel, Bruno

    2013-01-01

    This paper presents an analysis of the effects of noise and precision on a simplified model of the clarinet driven by a variable control parameter. In a previous work [5], the dynamic oscillation threshold of a simplified model of a clarinet is obtained analytically. In the present article, the sensitivity of the dynamic threshold on precision is analyzed as a stochastic variable introduced in the model. A new theoretical expression is given for the dynamic thresholds in presence of the stochastic variable, providing a fair prediction of the thresholds found in finite-precision simulations. The dynamic thresholds are found to depend on increase rate and are independent on the initial value of the parameter, both in simulations and in theory.

  8. Modeling and Management of Increased Urban Stormwater Runoff Using InfoSWMM Sustain in the Berkeley Neighborhood of Denver, Colorado

    Science.gov (United States)

    Panos, C.; Hogue, T. S.; McCray, J. E.

    2016-12-01

    Few urban studies have evaluated the hydrologic impacts of redevelopment - for example, a rapid conversion from single to multi-family homes - known as infill, or re-urbanization. Redevelopment provides unique stormwater challenges as private property owners in many cities are not mandated to undertake stormwater retrofits leading to an overall increase in stormwater quantity and decrease in quality. This research utilizes a version of the EPA's Storm Water Management Model (SWMM), InfoSWMM Sustain, to model and analyze the impacts of impervious cover change due to redevelopment on stormwater quantity and quality in Denver, Colorado, with a focus on the Berkeley Neighborhood, where the percent imperviousness is expected to increase significantly from a current value of 53% by 2025. We utilize flow data from multiple pressure transducers installed directly within the storm sewer network as well as water quality data from storm and low flow sampling to initially calibrate InfoSWMM Sustain using September 2015 through September 2016 storm data. Model scenarios include current land cover conditions as well as future imperviousness predictions from redevelopment. The Urban Drainage and Flood Control District's Colorado Urban Hydrograph Procedure (CUHP) model is also implemented and used for calibration and comparison to the InfoSWMM stormwater model. Model simulations predicting an average annual stormwater runoff for the basin will be used to inform stormwater capture for the Berkeley Neighborhood on the downstream Willis Case Golf Course, where treatment trains are being designed to provide irrigation water (a 250 ac-ft per year demand) and improved water quality for discharge to the nearby receiving waters of Clear Creek. Ultimately, study results will better inform regional stormwater capture requirements when transitioning from single to multi-family units by providing a quantitative basis for treatment and regulation priorities.

  9. Increased Calcium-Sensing Receptor Immunoreactivity in the Hippocampus of a Triple Transgenic Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Gardenal, Emanuela; Chiarini, Anna; Armato, Ubaldo; Dal Prà, Ilaria; Verkhratsky, Alexei; Rodríguez, José J

    2017-01-01

    The Calcium-Sensing Receptor (CaSR) is a G-protein coupled, 7-transmembrane domain receptor ubiquitously expressed throughout the body, brain including. The role of CaSR in the CNS is not well understood; its expression is increasing during development, which has been implicated in memory formation and consolidation, and CaSR localization in nerve terminals has been related to synaptic plasticity and neurotransmission. There is an emerging evidence of CaSR involvement in neurodegenerative disorders and Alzheimer's disease (AD) in particular, where the over-production of β-amyloid peptides was reported to activate CaSR. In the present study, we performed CaSR immunohistochemical and densitometry analysis in the triple transgenic mouse model of AD (3xTg-AD). We found an increase in the expression of CaSR in hippocampal CA1 area and in dentate gyrus in the 3xTg-AD mice when compared to non-transgenic control animals. This increase was significant at 9 months of age and further increased at 12 and 18 months of age. This increase paralleled the accumulation of β-amyloid plaques with age. Increased expression of CaSR favors β-amyloidogenic pathway following direct interactions between β-amyloid and CaSR and hence may contribute to the pathological evolution of the AD. In the framework of this paradigm CaSR may represent a novel therapeutic target.

  10. Increased Calcium-Sensing Receptor Immunoreactivity in the Hippocampus of a Triple Transgenic Mouse Model of Alzheimer's Disease

    Science.gov (United States)

    Gardenal, Emanuela; Chiarini, Anna; Armato, Ubaldo; Dal Prà, Ilaria; Verkhratsky, Alexei; Rodríguez, José J.

    2017-01-01

    The Calcium-Sensing Receptor (CaSR) is a G-protein coupled, 7-transmembrane domain receptor ubiquitously expressed throughout the body, brain including. The role of CaSR in the CNS is not well understood; its expression is increasing during development, which has been implicated in memory formation and consolidation, and CaSR localization in nerve terminals has been related to synaptic plasticity and neurotransmission. There is an emerging evidence of CaSR involvement in neurodegenerative disorders and Alzheimer's disease (AD) in particular, where the over-production of β-amyloid peptides was reported to activate CaSR. In the present study, we performed CaSR immunohistochemical and densitometry analysis in the triple transgenic mouse model of AD (3xTg-AD). We found an increase in the expression of CaSR in hippocampal CA1 area and in dentate gyrus in the 3xTg-AD mice when compared to non-transgenic control animals. This increase was significant at 9 months of age and further increased at 12 and 18 months of age. This increase paralleled the accumulation of β-amyloid plaques with age. Increased expression of CaSR favors β-amyloidogenic pathway following direct interactions between β-amyloid and CaSR and hence may contribute to the pathological evolution of the AD. In the framework of this paradigm CaSR may represent a novel therapeutic target.

  11. 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.

  12. Testing and optical modeling of novel concentrating solar receiver geometries to increase light trapping and effective solar absorptance

    Science.gov (United States)

    Yellowhair, Julius; Ho, Clifford K.; Ortega, Jesus D.; Christian, Joshua M.; Andraka, Charles E.

    2015-09-01

    Concentrating solar power receivers are comprised of panels of tubes arranged in a cylindrical or cubical shape on top of a tower. The tubes contain heat-transfer fluid that absorbs energy from the concentrated sunlight incident on the tubes. To increase the solar absorptance, black paint or a solar selective coating is applied to the surface of the tubes. However, these coatings degrade over time and must be reapplied, which reduces the system performance and increases costs. This paper presents an evaluation of novel receiver shapes and geometries that create a light-trapping effect, thereby increasing the effective solar absorptance and efficiency of the solar receiver. Several prototype shapes were fabricated from Inconel 718 and tested in Sandia's solar furnace at an irradiance of ~30 W/cm2. Photographic methods were used to capture the irradiance distribution on the receiver surfaces. The irradiance profiles were compared to results from raytracing models. The effective solar absorptance was also evaluated using the ray-tracing models. Results showed that relative to a flat plate, the new geometries could increase the effective solar absorptance from 86% to 92% for an intrinsic material absorptance of 86%, and from 60% to 73% for an intrinsic material absorptance of 60%.

  13. Cost savings of reduced constipation rates attributed to increased dietary fiber intakes: a decision-analytic model.

    Science.gov (United States)

    Schmier, Jordana K; Miller, Paige E; Levine, Jessica A; Perez, Vanessa; Maki, Kevin C; Rains, Tia M; Devareddy, Latha; Sanders, Lisa M; Alexander, Dominik D

    2014-04-17

    Nearly five percent of Americans suffer from functional constipation, many of whom may benefit from increasing dietary fiber consumption. The annual constipation-related healthcare cost savings associated with increasing intakes may be considerable but have not been examined previously. The objective of the present study was to estimate the economic impact of increased dietary fiber consumption on direct medical costs associated with constipation. Literature searches were conducted to identify nationally representative input parameters for the U.S. population, which included prevalence of functional constipation; current dietary fiber intakes; proportion of the population meeting recommended intakes; and the percentage that would be expected to respond, in terms of alleviation of constipation, to a change in dietary fiber consumption. A dose-response analysis of published data was conducted to estimate the percent reduction in constipation prevalence per 1 g/day increase in dietary fiber intake. Annual direct medical costs for constipation were derived from the literature and updated to U.S. $ 2012. Sensitivity analyses explored the impact on adult vs. pediatric populations and the robustness of the model to each input parameter. The base case direct medical cost-savings was $12.7 billion annually among adults. The base case assumed that 3% of men and 6% of women currently met recommended dietary fiber intakes; each 1 g/day increase in dietary fiber intake would lead to a reduction of 1.9% in constipation prevalence; and all adults would increase their dietary fiber intake to recommended levels (mean increase of 9 g/day). Sensitivity analyses, which explored numerous alternatives, found that even if only 50% of the adult population increased dietary fiber intake by 3 g/day, annual medical costs savings exceeded $2 billion. All plausible scenarios resulted in cost savings of at least $1 billion. Increasing dietary fiber consumption is associated with

  14. Reduced erythrocyte susceptibility and increased host clearance of young parasites slows Plasmodium growth in a murine model of severe malaria

    Science.gov (United States)

    Khoury, David S.; Cromer, Deborah; Best, Shannon E.; James, Kylie R.; Sebina, Ismail; Haque, Ashraful; Davenport, Miles P.

    2015-05-01

    The best correlate of malaria severity in human Plasmodium falciparum (Pf) infection is the total parasite load. Pf-infected humans could control parasite loads by two mechanisms, either decreasing parasite multiplication, or increasing parasite clearance. However, few studies have directly measured these two mechanisms in vivo. Here, we have directly quantified host clearance of parasites during Plasmodium infection in mice. We transferred labelled red blood cells (RBCs) from Plasmodium infected donors into uninfected and infected recipients, and tracked the fate of donor parasites by frequent blood sampling. We then applied age-based mathematical models to characterise parasite clearance in the recipient mice. Our analyses revealed an increased clearance of parasites in infected animals, particularly parasites of a younger developmental stage. However, the major decrease in parasite multiplication in infected mice was not mediated by increased clearance alone, but was accompanied by a significant reduction in the susceptibility of RBCs to parasitisation.

  15. 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

  16. The role of aerosols to increase rainfall in the regions with less intensity rain: A modeling study

    Directory of Open Access Journals (Sweden)

    Shyam Sundar

    2013-03-01

    Full Text Available In this paper, we established an ecological type three-dimensional nonlinear mathematical model to study the effect of aerosol particles in increasing rainfall in the regions of less intensity rain. The phenomenon of nonlinearity is based on the concepts of ecology related to growth rate, death rate and interaction process (Smith, 1974. It is assumed that clouds are formed in the atmosphere but are not able to develop uninterrupted rainfall. The rainfall can be enhanced by introducing aerosol particles conducive to raindrops formation from cloud droplets. It is shown that the intensity of rainfall increases as the concentration of externally introduced aerosols and the density of cloud droplets increases. The numerical simulation has also been performed tosupport analytical results.

  17. Model and Effectiveness of Endurance Exercise to Increase Physical Fitness in Intellectual Disability Subjects with Obesity: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Tirza Z Tamin

    2015-04-01

    Full Text Available Aim: to design a model and assess the effectiveness of endurance exercise to increase physical fitness in intelectual disability (ID patients with obesity. Methods: a randomized-controlled clinical trial was performed in ID patients with obesity aged 10-30 years old from all Special School in DKI Jakarta, which were randomly allocated into 3 groups and then given 3 different type of exercises: lower extremity muscles endurance exercise for 20 RM followed by cardiorespiratory endurance exercise for 24-25 minutes (type I, lower extremity muscles endurance exercises for 10 RM followed by cardiorespiratory endurance exercises for 26-27 minutes (type II, and threw a tennis ball with 10 m distance for 10 minutes as control (type III. These program was performed 3 times a week for 4 months. Assesment of the exercise effectiveness was done by measuring maximum load that can be lifted and six-minutes walking test on rectangular track which was converted with the VO2 max prediction formula. Analysis was perfomed with Kruskal Wallis test. Results: two hundred and twelve (212 subjects were included in the study, randomly allocated into three types (I, II, and III of exercises groups. The type II of endurance exercise model was proved to be more effective in increasing lower extremity muscles endurance level compared to type I and III for ID patients with obesity (p<0.05. Meanwhile, type I of endurance exercise model was proved to be more effective in increasing cardiorespiratory endurance level compared to type II and III for ID patients with obesity (p<0.05. Conclusion: lower extremity muscles endurance exercise followed by a cardiorespiratory endurance exercise can be used to increase physical fitness in ID patients with obesity. Key words: intelectual disability patient, obesity, lower extremity muscles and cardiorespiratory endurance exercise, lower extremity muscles endurance level, cardiorespiratory endurance level.

  18. High-fat Western diet-induced obesity contributes to increased tumor growth in mouse models of human colon cancer.

    Science.gov (United States)

    O'Neill, Ann Marie; Burrington, Christine M; Gillaspie, Erin A; Lynch, Darin T; Horsman, Melissa J; Greene, Michael W

    2016-12-01

    Strong epidemiologic evidence links colon cancer to obesity. The increasing worldwide incidence of colon cancer has been linked to the spread of the Western lifestyle, and in particular consumption of a high-fat Western diet. In this study, our objectives were to establish mouse models to examine the effects of high-fat Western diet-induced obesity on the growth of human colon cancer tumor xenografts, and to examine potential mechanisms driving obesity-linked human colon cancer tumor growth. We hypothesize that mice rendered insulin resistant due to consumption of a high-fat Western diet will show increased and accelerated tumor growth. Homozygous Rag1(tm1Mom) mice were fed either a low-fat Western diet or a high-fat Western diet (HFWD), then human colon cancer xenografts were implanted subcutaneously or orthotopically. Tumors were analyzed to detect changes in receptor tyrosine kinase-mediated signaling and expression of inflammatory-associated genes in epididymal white adipose tissue. In both models, mice fed an HFWD weighed more and had increased intra-abdominal fat, and tumor weight was greater compared with in the low-fat Western diet-fed mice. They also displayed significantly higher levels of leptin; however, there was a negative correlation between leptin levels and tumor size. In the orthotopic model, tumors and adipose tissue from the HFWD group displayed significant increases in both c-Jun N-terminal kinase activation and monocyte chemoattractant protein 1 expression, respectively. In conclusion, this study suggests that human colon cancer growth is accelerated in animals that are obese and insulin resistant due to the consumption of an HFWD. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Model to explain the effects of halide ions on the increase in surface enhanced Raman spectral intensity over time

    Science.gov (United States)

    Cole, Michael A.

    Understanding the mechanisms responsible for the large increase in spectral intensity when molecules are adsorbed to nanoparticle surfaces such as occurs during surface enhanced Raman (SER) spectroscopy will allow scientists to probe ever smaller scales, even allowing single molecule detection. One particular scenario that increased the SER scattering efficiency was the addition of halide ions to Rhodamine 6G (R6G)-ethanol solution. This thesis presents a theoretical model explaining the effects of halide ions on the SER spectral intensity of the Rhodamine 6G (R6G) molecule when co-adsorbed to a silver nanoparticle surface. Glaspell et al. 2005, found a linear correlation between the increase in spectral intensities of selected vibrational normal modes of R6G over time and the polarizabilities of co-adsorbed halide ions. When the R6G molecule co-adsorbs to the silver nanoparticle surface with the halide ions, the molecule is exposed to three external electric fields that add vectorially, creating a total external electric field. Modelling the fields from the halide ions and the silver nanoparticles as electric dipole fields introduces the polarizability of the halide ion linearly into the Raman spectral intensity equation. This model also shows that there is a necessary interaction between the halide ions and the silver nanoparticle surface in order to see the effects as described by Glaspell et al. Furthermore, we will present experimental results that show that there is a necessary interaction between the halide ions and the nanoparticle surface. Without this interaction there was no increase in the SER spectral intensity of R6G or pyridine molecules in solution with the halide ions but without the silver nanoparticles.

  20. Mesenchymal Stem Cells Increase Hippocampal Neurogenesis and Neuronal Differentiation by Enhancing the Wnt Signaling Pathway in an Alzheimer's Disease Model.

    Science.gov (United States)

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

    2015-01-01

    Neurogenesis in the subgranular zone of the hippocampal dentate gyrus may act as an endogenous repair mechanism in Alzheimer's disease (AD), and the Wnt signaling pathway has been suggested to closely modulate neurogenesis in amyloid-β (Aβ)-related AD models. The present study investigated whether mesenchymal stem cells (MSCs) would modulate hippocampal neurogenesis via modulation of the Wnt signaling pathway in a model of AD. In Aβ-treated neuronal progenitor cells (NPCs), the coculture with MSCs increased significantly the expression of Ki-67, GFAP, SOX2, nestin, and HuD compared to Aβ treatment alone. In addition, MSC treatment in Aβ-treated NPCs enhanced the expression of β-catenin and Ngn1 compared to Aβ treatment alone. MSC treatment in Aβ-treated animals significantly increased the number of BrdU-ir cells in the hippocampus at 2 and 4 weeks compared to Aβ treatment alone. In addition, quantitative analysis showed that the number of BrdU and HuD double-positive cells in the dentate gyrus was significantly higher in the MSC-treated group than in controls or after Aβ treatment alone. These results demonstrate that MSC administration significantly augments hippocampal neurogenesis and enhances the differentiation of NPCs into mature neurons in AD models by augmenting the Wnt signaling pathway. The use of MSCs to modulate endogenous adult neurogenesis may have a significant impact on future strategies for AD treatment.

  1. Determination of local optical response functions of nanostructures with increasing complexity by using single and coupled Lorentzian oscillator models

    Science.gov (United States)

    Aeschlimann, Martin; Brixner, Tobias; Fischer, Alexander; Hensen, Matthias; Huber, Bernhard; Kilbane, Deirdre; Kramer, Christian; Pfeiffer, Walter; Piecuch, Martin; Thielen, Philip

    2016-07-01

    We reconstruct the optical response of nanostructures of increasing complexity by fitting interferometric time-resolved photoemission electron microscopy (PEEM) data from an ultrashort (21 fs) laser excitation source with different harmonic oscillator-based models. Due to its high spatial resolution of ~40 nm, PEEM is a true near-field imaging system and enables in normal incidence mode a mapping of plasmon polaritons and an intuitive interpretation of the plasmonic behaviour. Using an actively stabilized Mach-Zehnder interferometer, we record two-pulse correlation signals with 50 as time resolution that contain information about the temporal plasmon polariton evolution. Spectral amplitude and phase of excited plasmon polaritons are extracted from the recorded phase-resolved interferometric two-pulse correlation traces. We show that the optical response of a plasmon polariton generated at a gold nanoparticle can be reconstructed from the interferometric two-pulse correlation signal using a single harmonic oscillator model. In contrast, for a corrugated silver surface, a system with increased plasmonic complexity, in general an unambiguous reconstruction of the local optical response based on coupled and uncoupled harmonic oscillators, fails. Whereas for certain local responses different models can be discriminated, this is impossible for other positions. Multidimensional spectroscopy offers a possibility to overcome this limitation.

  2. 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

  3. How does increasing horizontal resolution in a global climate model improve the simulation of aerosol-cloud interactions?

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Po -Lun [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Rasch, Philip J. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Wang, Minghuai [Nanjing Univ., Nanjing (China); Jiangsu Collaborative Innovation Center Climate Change, Nanjing (China); Wang, Hailong [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Ghan, Steven J. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Easter, Richard C. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Gustafson, Jr., William I. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Liu, Xiaohong [Univ. of Wyo; Zhang, Yuying [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Ma, Hsi -Yen [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-06-28

    The Community Atmosphere Model Version 5 is run at horizontal grid spacing of 2, 1, 0.5, and 0.25 degrees, with the meteorology nudged towards the Year Of Tropical Convection analysis, and cloud simulators and the collocated A-Train satellite observations are used to explore the resolution dependence of aerosol-cloud interactions. The higher-resolution model produces results that agree better with observations, showing an increase of susceptibility of cloud droplet size, indicating a stronger first aerosol indirect forcing (AIF), and a decrease of susceptibility of precipitation probability, suggesting a weaker second AIF. The resolution sensitivities of AIF are attributed to those of droplet nucleation and precipitation parameterizations. The annual average AIF in the northern hemisphere mid-latitudes (where most anthropogenic emissions occur) in the 0.25° model is reduced by about 1 W m⁻² (-30%) compared to the 2° model, leading to a 0.26 W m⁻² reduction (-15%) in the global annual average AIF.

  4. Minocycline rescues decrease in neurogenesis, increase in microglia cytokines and deficits in sensorimotor gating in an animal model of schizophrenia.

    Science.gov (United States)

    Mattei, Daniele; Djodari-Irani, Anaïs; Hadar, Ravit; Pelz, Andreas; de Cossío, Lourdes Fernandez; Goetz, Thomas; Matyash, Marina; Kettenmann, Helmut; Winter, Christine; Wolf, Susanne A

    2014-05-01

    Adult neurogenesis in the hippocampus is impaired in schizophrenic patients and in an animal model of schizophrenia. Amongst a plethora of regulators, the immune system has been shown repeatedly to strongly modulate neurogenesis under physiological and pathological conditions. It is well accepted, that schizophrenic patients have an aberrant peripheral immune status, which is also reflected in the animal model. The microglia as the intrinsic immune competent cells of the brain have recently come into focus as possible therapeutic targets in schizophrenia. We here used a maternal immune stimulation rodent model of schizophrenia in which polyinosinic-polycytidilic acid (Poly I:C) was injected into pregnant rats to mimic an anti-viral immune response. We identified microglia IL-1β and TNF-α increase constituting the factors correlating best with decreases in net-neurogenesis and impairment in pre-pulse inhibition of a startle response in the Poly I:C model. Treatment with the antibiotic minocycline (3mg/kg/day) normalized microglial cytokine production in the hippocampus and rescued neurogenesis and behavior. We could also show that enhanced microglial TNF-α and IL-1β production in the hippocampus was accompanied by a decrease in the pro-proliferative TNFR2 receptor expression on neuronal progenitor cells, which could be attenuated by minocycline. These findings strongly support the idea to use anti-inflammatory drugs to target microglia activation as an adjunctive therapy in schizophrenic patients.

  5. Regional Agricultural Input-Output Model and Countermeasure for Production and Income Increase of Farmers in Southern Xinjiang,China

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Agricultural input and output status in southern Xinjiang,China is introduced,such as lack of agricultural input,low level of agricultural modernization,excessive fertilizer use,serious damage of environment,shortage of water resources,tremendous pressure on ecological balance,insignificant economic and social benefits of agricultural production in southern Xinjiang,agriculture remaining a weak industry,agricultural economy as the economic subject of southern Xinjiang,and backward economic development of southern Xinjiang.Taking the Aksu area as an example,according to the input and output data in the years 2002-2007,input-output model about regional agriculture of the southern Xinjiang is established by principal component analysis.DPS software is used in the process of solving the model.Then,Eviews software is adopted to revise and test the model in order to analyze and evaluate the economic significance of the results obtained,and to make additional explanations of the relevant model.Since the agricultural economic output is seriously restricted in southern Xinjiang at present,the following countermeasures are put forward,such as adjusting the structure of agricultural land,improving the utilization ratio of land,increasing agricultural input,realizing agricultural modernization,rationally utilizing water resources,maintaining eco-environmental balance,enhancing the awareness of agricultural insurance,minimizing the risk and loss,taking the road of industrialization of characteristic agricultural products,and realizing the transfer of surplus labor force.

  6. 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;

    for the various actors in society. This is also valid for organizations, which are expected to assume a more proactive and entrepreneurial posture towards tackling sustainable development challenges. In this sense, sustainable business model approach can support organizations to be more sustainable, serving...... were not expecting or demanding, but that are positive in terms of sustainability. The proactive approach on managing stakeholders finds its justification on questioning companies about their institutional role in society, demanding sustainability innovation in companies' business models...... 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...

  7. 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.

  8. Combining Bevacizumab with Temozolomide Increases the Antitumor Efficacy of Temozolomide in a Human Glioblastoma Orthotopic Xenograft Model

    Directory of Open Access Journals (Sweden)

    Véronique Mathieu

    2008-12-01

    Full Text Available Purpose: The aims of the present work were to investigate the in vitro and in vivo antiangiogenic effects of chronic temozolomide treatment on various glioma models and to demonstrate whether bevacizumab (Avastin increased the therapeutic benefits contributed by temozolomide in glioma. Experimental Design: The expression levels of various antiangiogenic factors in four glioma cell lines were evaluated after chronic in vitro treatment with temozolomide by Western blot. Proliferation and migration assays were performed on human endothelial cells incubated with supernatants of glioma cells treated with and without temozolomide. Orthotopic glioma models were used to evaluate the antiangiogenic effects of temozolomide in vivo and the therapeutic benefits of different temozolomide treatment schedules used alone or in combination with bevacizumab. Results: Temozolomide, a proautophagic and proapoptotic drug, decreased the expression levels of HIF-1α, ID-1, ID-2, and cMyc in the glioma models investigated, all of which playing major roles in angiogenesis and the switch to hypoxic metabolism. These changes could be, at least partly, responsible for the impairment of angiogenesis observed in vitro and in vivo. Moreover, combining bevacizumab with temozolomide increased the survival of glioma-bearing mice in comparison to each compound administered alone. Conclusions: In addition to the numerous mechanisms of action already identified for temozolomide, we report here that it also exerts antitumor effects by impairing angiogenic processes. We further emphasize that bevacizumab, which is an antiangiogenic drug with a different mechanism of action, could be useful in combination with temozolomide to increase the latter's therapeutic benefit in glioma patients.

  9. 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.

  10. Multi-Model CIMP5 projected impacts of increased greenhouse gases on the Niger basin and implications for hydropower production

    Science.gov (United States)

    Oyerinde, Ganiyu; Wisser, Dominik

    2014-05-01

    Climate change could potentially have large impacts on water availability in West Africa and the predictions are accrued with high uncertainties in this region. Countries in the Niger River basin (West Africa) plan the investment of 200 million in the installation of an additional 400MW of hydropower in the nearest future, adding to the existing 685MW. With the impacts of climate change in the basin already occurring, there is a need for comprehending the influence of future hydro-climatic changes on water resources and hydro-power generation in the basin. This study uses a hydrological model to simulate river flow under present and future conditions and evaluates the impacts of potential changes on electricity production of the largest hydroelectric dam (Kainji) in the Niger Basin. The Kainji reservoir produces 25 per cent of the current energy needs of Nigeria and was subject to large fluctuations in energy production as a result of variable inflow and operational reasons. Inflow into the reservoir was simulated using hydroclimatic data from a set of 7 regional climate models (RCM) with two emission scenarios from the CORDEX-Africa regional downscaling experiment, driven with CMIP5 data. Based on observations of inflow, water level in the reservoir, and energy production we developed a simple hydroelectricity production model to simulate future energy production for the reservoir. Results suggest increases in river flow for the majority of RCM data as a result of increases in precipitation in the headwaters of the basin around 2050 and slightly decreasing trends for low emission scenarios by the end of the century. Despite this consistent increase, shifts in timing of river flow can challenge the reliable production of energy. This analysis could help assess the planning of hydropower schemes in the basin for a sustainable production of hydroelectricity in the future.

  11. 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.

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

    Science.gov (United States)

    Vrech, David E; Olivero, Paola A; Mattoni, Camilo I; Peretti, Alfredo V

    2014-01-01

    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.

  13. The Classroom Check-up: A Classwide Teacher Consultation Model for Increasing Praise and Decreasing Disruptive Behavior.

    Science.gov (United States)

    Reinke, Wendy M; Lewis-Palmer, Teri; Merrell, Kenneth

    2008-01-01

    School-based consultation typically focuses on individual student problems and on a small number of students rather than on changing the classroom system. The Classroom Check-up (CCU) was developed as a classwide consultation model to address the need for classroom level support while minimizing treatment integrity problems common to school-based consultation. The purpose of the study was to evaluate the effects of the CCU and Visual Performance Feedback on teacher and student behavior. Results indicated that implementation of the CCU plus Visual Performance Feedback increased teacher implementation of classroom management strategies, including increased use of praise, use of behavior specific praise, and decreased use of reprimands. Further, these changes in teacher behavior contributed to decreases in classroom disruptive behavior. The results are encouraging because they suggest that consultation at the classroom level can create meaningful teacher and student behavior change.

  14. Morphine increases hippocampal viral load and suppresses frontal lobe CCL5 expression in the LP-BM5 AIDS model.

    Science.gov (United States)

    McLane, Virginia D; Cao, Ling; Willis, Colin L

    2014-04-15

    Chronic opiate abuse accelerates the development of cognitive deficits in human immunodeficiency virus (HIV)-1 patients. To investigate morphine's effects on viral infection of the central nervous system, we applied chronic morphine treatment to the LP-BM5 murine acquired immunodeficiency syndrome (MAIDS) model. LP-BM5 infection induces proinflammatory cytokine/chemokine production, correlating to increased blood-brain barrier permeability. Morphine treatment significantly increased LP-BM5 viral load in the hippocampus, but not in the frontal lobe. Morphine reduced the chemokine CCL5 to non-infected levels in the frontal lobe, but not in the hippocampus. These data indicate a region-specific mechanism for morphine's effects on virally-induced neurocognitive deficits.

  15. The Kidney Disease Screening and Awareness Program (KDSAP): a novel translatable model for increasing interest in nephrology careers.

    Science.gov (United States)

    Hsiao, Li-Li; Wu, Jingshing; Yeh, Albert C; Shieh, Eric C; Cui, Cheryl; Li, Ang; Polding, Laura C; Ahmed, Rayhnuma; Lim, Kenneth; Lu, Tzong-Shi; Rhee, Connie M; Bonventre, Joseph V

    2014-09-01

    Despite the increasing prevalence of CKD in the United States, there is a declining interest among United States medical graduates in nephrology as a career choice. Effective programs are needed to generate interest at early educational stages when career choices can be influenced. The Kidney Disease Screening and Awareness Program (KDSAP) is a novel program initiated at Harvard College that increases student knowledge of and interest in kidney health and disease, interest in nephrology career paths, and participation in kidney disease research. This model, built on physician mentoring, kidney screening of underserved populations, direct interactions with kidney patients, and opportunities to participate in kidney research, can be reproduced and translated to other workforce-challenged subspecialties.

  16. The protective effect of modified intravenous immunoglobulin in LPS sepsis model is associated with an increased IRA B cells response.

    Science.gov (United States)

    Djoumerska-Alexieva, Iglika; Pashova, Shina; Vassilev, Tchavdar; Pashov, Anastas

    2013-04-01

    Intravenous immunoglobulin preparations (IVIg) that have undergone a mild oxidizing treatment with ferrous ions have an increased polyspecificity, which is not associated with a higher propensity to form aggregates. Among other biological properties of the modified IVIg, a protective effect in LPS sepsis model stands out as the native preparation is totally devoid of it or even exacerbates sepsis. A recent finding identified an LPS induced subset of B1 lymphocytes that migrate from the peritoneal cavity to the spleen acquiring the expression of CD93, GM-CSF as well as the capacity to control sepsis. This report demonstrates that modified IVIg, but not the native preparation, causes a further increase in this population during LPS sepsis. Partial targeted suppression of the peritoneal B cell proliferation by an intracellular dye abrogates this effect and the clinical benefit of modified IVIg.

  17. 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

  18. Cannabinoids increase type 1 cannabinoid receptor expression in a cell culture model of striatal neurons: implications for Huntington's disease.

    Science.gov (United States)

    Laprairie, Robert B; Kelly, Melanie E M; Denovan-Wright, Eileen M

    2013-09-01

    The type 1 cannabinoid receptor (CB1) is a G protein-coupled receptor that is expressed at high levels in the striatum. Activation of CB1 increases expression of neuronal trophic factors and inhibits neurotransmitter release from GABA-ergic striatal neurons. CB1 mRNA levels can be elevated by treatment with cannabinoids in non-neuronal cells. We wanted to determine whether cannabinoid treatment could induce CB1 expression in a cell culture model of striatal neurons and, if possible, determine the molecular mechanism by which this occurred. We found that treatment of STHdh(7/7) cells with the cannabinoids ACEA, mAEA, and AEA produced a CB1receptor-dependent increase in CB1 promoter activity, mRNA, and protein expression. This response was Akt- and NF-κB-dependent. Because decreased CB1 expression is thought to contribute to the pathogenesis of Huntington's disease (HD), we wanted to determine whether cannabinoids could increase CB1 expression in STHdh(7/111) and (111/111) cells expressing the mutant huntingtin protein. We observed that cannabinoid treatment increased CB1 mRNA levels approximately 10-fold in STHdh(7/111) and (111/111) cells, compared to vehicle treatment. Importantly, cannabinoid treatment improved ATP production, increased the expression of the trophic factor BDNF-2, and the mitochondrial regulator PGC1α, and reduced spontaneous GABA release, in HD cells. Therefore, cannabinoid-mediated increases in CB1 levels could reduce the severity of some molecular pathologies observed in HD.

  19. Chronic treatment with the GLP1 analogue liraglutide increases cell proliferation and differentiation into neurons in an AD mouse model.

    Directory of Open Access Journals (Sweden)

    Vadivel Parthsarathy

    Full Text Available Neurogenesis is a life long process, but the rate of cell proliferation and differentiation decreases with age. In Alzheimer's patients, along with age, the presence of Aβ in the brain inhibits this process by reducing stem cell proliferation and cell differentiation. GLP-1 is a growth factor that has neuroprotective properties. GLP1 receptors are present on neuronal progenitor cells, and the GLP-1 analogue liraglutide has been shown to increase cell proliferation in an Alzheimer's disease (AD mouse model. Here we investigated acute and chronic effects of liraglutide on progenitor cell proliferation, neuroblast differentiation and their subsequent differentiation into neurons in wild type and APP/PS-1 mice at different ages. APP/PS1 and their littermate controls, aged 3, 6, 12, 15 months were injected acutely or chronically with 25 nmol/kg liraglutide. Acute treatment with liraglutide showed an increase in cell proliferation in APP/PS1 mice, but not in controls whereas chronic treatment increased cell proliferation at all ages (BrdU and Ki67 markers. Moreover, numbers of immature neurons (DCX were increased in both acute and chronic treated animals at all ages. Most newly generated cells differentiated into mature neurons (NeuN marker. A significant increase was observed with chronically treated 6, 12, 15 month APP/PS1 and WT groups. These results demonstrate that liraglutide, which is currently on the market as a treatment for type 2 diabetes (Victoza(TM, increases neurogenesis, which may have beneficial effects in neurodegenerative disorders like AD.

  20. Response to CO2 Transient Increase in the GISS Coupled Model: Regional Coolings in a Warming Climate

    Science.gov (United States)

    Russell, Gary L.; Rind, David

    1999-01-01

    The (GISS) Goddard Institute for Space Studies coupled atmosphere-ocean model is used to investigate the effect of increased atmospheric CO2 by comparing a compounded 1 percent CO2 increase experiment with a control simulation. After 70 years of integration, the global surface air temperature in the 1 percent CO2 experiment is 1.43 C warmer. In spite of this global warming, there are two distinct regions, the northern Atlantic Ocean and the southern Pacific Ocean, where the surface air temperature is up to 4 C cooler. This situation is maintained by two positive feedbacks: a local effect on convection in the South Pacific and a non-local impact on the meridional circulation in the North Atlantic. The poleward transport of latent energy and dry static energy by the atmosphere is greater in the 1 percent CO2 experiment, caused by warming and therefore increased water vapor and greater greenhouse capacity at lower latitudes. The larger atmospheric transports tend to reduce upward vertical fluxes of heat and moisture from the ocean surface at high latitudes, which has the effect of stabilizing the ocean, reducing both convection and the thermohaline circulation. With less convection, less warm water is brought up from below, and with a reduced North Atlantic thermohaline circulation (by 30 percent at time of CO2 doubling), the poleward energy transport by the oceans decreases. The colder water then leads to further reductions in evaporation, decreases of salinity at high latitudes, continued stabilization of the ocean, and maintenance of reduced convection and meridional overturning. Although sea ice decreases globally, it increases in the cooling regions which reduces the overall climate sensitivity; its effect is most pronounced in the Southern Hemisphere. Tropical warming has been observed over the past several decades; if modeling studies such as this and others which have produced similar effects are valid, these processes may already be beginning.

  1. Otters Increasing - Threats Increasing

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    Andreas Kranz

    1994-10-01

    Full Text Available In some parts of Central Europe populations of otters are apparently increasing. Until recently, no research was being conducted on the ecology of otters in mainly artificial habitats like fish farms. Otters are not only a new source of conflict requiring species management, but appear once again threatened by illegal hunting. Austria is dealing with this problem using compensation for otter damage, electric fencing and translocation of problem otters. Despite a rise in illegal killing, Austria does not formally recognise this as a threat.

  2. Measured and modelled tritium concentrations in freshwater Barnes mussels (Elliptio complanata) exposed to an abrupt increase in ambient tritium levels.

    Science.gov (United States)

    Yankovich, T L; Kim, S B; Baumgärtner, F; Galeriu, D; Melintescu, A; Miyamoto, K; Saito, M; Siclet, F; Davis, P

    2011-01-01

    To improve understanding of environmental tritium behaviour, the International Atomic Energy Agency (IAEA) included a Tritium and C-14 Working Group (WG) in its EMRAS (Environmental Modelling for Radiation Safety) program. One scenario considered by the WG involved the prediction of time-dependent tritium concentrations in freshwater mussels that were subjected to an abrupt increase in ambient tritium levels. The experimental data used in the scenario were obtained from a study in which freshwater Barnes mussels (Elliptio complanata) were transplanted from an area with background tritium concentrations to a small Canadian Shield lake that contains elevated tritium. The mussels were then sampled over 88 days, and concentrations of free-water tritium (HTO) and organically-bound tritium (OBT) were measured in the soft tissues to follow the build-up of tritium in the mussels over time. The HTO concentration in the mussels reached steady state with the concentration in lake water within one or two hours. Most models predicted a longer time (up to a few days) to equilibrium. All models under-predicted the OBT concentration in the mussels one hour after transplantation, but over-predicted the rate of OBT formation over the next 24h. Subsequent dynamics were not well modelled, although all participants predicted OBT concentrations that were within a factor of three of the observation at the end of the study period. The concentration at the final time point was over-predicted by all but one of the models. The relatively low observed concentration at this time was likely due to the loss of OBT by mussels during reproduction. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. 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.

  4. Cell-delivered magnetic nanoparticles caused hyperthermia-mediated increased survival in a murine pancreatic cancer model.

    Science.gov (United States)

    Basel, Matthew T; Balivada, Sivasai; Wang, Hongwang; Shrestha, Tej B; Seo, Gwi Moon; Pyle, Marla; Abayaweera, Gayani; Dani, Raj; Koper, Olga B; Tamura, Masaaki; Chikan, Viktor; Bossmann, Stefan H; Troyer, Deryl L

    2012-01-01

    Using magnetic nanoparticles to absorb alternating magnetic field energy as a method of generating localized hyperthermia has been shown to be a potential cancer treatment. This report demonstrates a system that uses tumor homing cells to actively carry iron/iron oxide nanoparticles into tumor tissue for alternating magnetic field treatment. Paramagnetic iron/ iron oxide nanoparticles were synthesized and loaded into RAW264.7 cells (mouse monocyte/ macrophage-like cells), which have been shown to be tumor homing cells. A murine model of disseminated peritoneal pancreatic cancer was then generated by intraperitoneal injection of Pan02 cells. After tumor development, monocyte/macrophage-like cells loaded with iron/ iron oxide nanoparticles were injected intraperitoneally and allowed to migrate into the tumor. Three days after injection, mice were exposed to an alternating magnetic field for 20 minutes to cause the cell-delivered nanoparticles to generate heat. This treatment regimen was repeated three times. A survival study demonstrated that this system can significantly increase survival in a murine pancreatic cancer model, with an average post-tumor insertion life expectancy increase of 31%. This system has the potential to become a useful method for specifically and actively delivering nanoparticles for local hyperthermia treatment of cancer.

  5. Efficacy of written modeling and vicarious reinforcement in increasing use of problem-solving methods by distressed individuals.

    Science.gov (United States)

    Coates, Celia; Malouff, John M; Rooke, Sally E

    2008-07-01

    The authors evaluated an application of social cognitive theory principles intended to increase adherence to a problem-solving intervention. The study included 132 adult volunteers who wanted to reduce their distress levels. All participants received group training in problem-solving methods. Before attempting to solve at least 1 distressing problem in their lives over the next 3 weeks, participants were randomly assigned to either (a) a modeling with vicarious reinforcement condition in which they received 3 personal anecdotes written by individuals who had successfully applied problem-solving methods to a real problem or (b) a control condition in which they received a fact sheet about problem solving. Word counts of problem-solving writing, self-reports of adherence, and observer ratings of adherence showed that participants in the vicarious reinforcement condition demonstrated significantly higher adherence than did those in the control condition. These results provide support for the effectiveness of symbolic modeling and vicarious reinforcement in increasing adherence to problem-solving methods by individuals who want to decrease their distress.

  6. Modeling potential hydrochemical responses to climate change and increasing CO2 at the Hubbard Brook Experimental Forest using a dynamic biogeochemical model (PnET-BGC)

    Science.gov (United States)

    Pourmokhtarian, Afshin; Driscoll, Charles T.; Campbell, John L.; Hayhoe, Katharine

    2012-07-01

    Dynamic hydrochemical models are useful tools for understanding and predicting the interactive effects of climate change, atmospheric CO2, and atmospheric deposition on the hydrology and water quality of forested watersheds. We used the biogeochemical model, PnET-BGC, to evaluate the effects of potential future changes in temperature, precipitation, solar radiation, and atmospheric CO2on pools, concentrations, and fluxes of major elements at the Hubbard Brook Experimental Forest in New Hampshire, United States. Future climate projections used to run PnET-BGC were generated specifically for the Hubbard Brook Experimental Forest with a statistical technique that downscales climate output (e.g., air temperature, precipitation, solar radiation) from atmosphere-ocean general circulation models (AOGCMs) to a finer temporal and spatial resolution. These climate projections indicate that over the twenty-first century, average air temperature will increase at the site by 1.7°C to 6.5°C with simultaneous increases in annual average precipitation ranging from 4 to 32 cm above the long-term mean (1970-2000). PnET-BGC simulations under future climate change show a shift in hydrology characterized by later snowpack development, earlier spring discharge (snowmelt), greater evapotranspiration, and a slight increase in annual water yield (associated with CO2 effects on vegetation). Model results indicate that under elevated temperature, net soil nitrogen mineralization and nitrification markedly increase, resulting in acidification of soil and stream water, thereby altering the quality of water draining from forested watersheds. Invoking a CO2 fertilization effect on vegetation under climate change substantially mitigates watershed nitrogen loss, highlighting the need for a more thorough understanding of CO2 effects on forest vegetation.

  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.

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    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.

  9. Increased food intake leads to obesity and insulin resistance in the tg2576 Alzheimer's disease mouse model.

    Science.gov (United States)

    Kohjima, Motoyuki; Sun, Yuxiang; Chan, Lawrence

    2010-04-01

    Recent studies suggest that hyperinsulinemia and insulin resistance are linked to Alzheimer's disease (AD). In this study, we used Tg2576 transgenic (Tg) mice, a widely used transgenic mouse model for AD, to explore the relationship between increased amyloid beta-peptide (Abeta) and insulin resistance. When fed a high-fat diet (HFD), Tg mice developed obesity and insulin resistance at 16 wk of age. Furthermore, HFD-fed Tg mice displayed abnormal feeding behavior and increased caloric intake with time. Although caloric intake of HFD-fed Tg mice was similar to that of normal diet-fed Tg or wild-type mice during 4 to 8 wk of age, it increased sharply at 12 wk, and went up further at 16 wk, which paralleled changes in the level of Abeta40 and Abeta42 in the brain of these mice. Limiting food intake in HFD-fed Tg mice by pair-feeding a caloric intake identical with that of normal diet-fed mice completely prevented the obesity and insulin intolerance of HFD-fed Tg mice. The hypothalamus of HFD-fed Tg mice had a significant decrease in the expression of the anorexigenic neuropeptide, brain-derived neurotrophic factor, at both the mRNA and protein levels. These findings suggest that the increased Abeta in the brain of HFD-fed Tg2576 mice is associated with reduced brain-derived neurotrophic factor expression, which led to abnormal feeding behavior and increased food intake, resulting in obesity and insulin resistance in these animals.

  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. Increasing the delivery of health care services to migrant farm worker families through a community partnership model.

    Science.gov (United States)

    Connor, Ann; Rainer, Laura P; Simcox, Jordan B; Thomisee, Karen

    2007-01-01

    The Farm Worker Family Health Program (FWFHP) is a 13-year community partnership model designed to increase delivery of health care services for migrant farm worker families. During a yearly 2-week immersion experience, 90 students and faculty members provide health care services, including physical examinations, health screenings, health education, physical therapy, and dental care for 1,000 migrant farm workers and migrant children. Students and faculty members gain a deeper appreciation of the health and social issues that migrant farm worker families face by providing health care services in the places where migrant families live, work, and are educated. Although the model is not unique, it is significant because of its sustained history, interdisciplinary collaboration among community and academic partners, mutual trust and connections among the partners, and the way the program is tailored to meet the needs of the population served. The principles of social responsibility and leadership frame the FWFHP experience. This community partnership model can be replicated by others working with at-risk populations in low-resource settings.

  12. OPTIMIZING SYSTEM OF RICE INTENSIFICATION PARAMETERS USING AQUACROP MODEL FOR INCREASING WATER PRODUCTIVITY AND WATER USE EFFICIENCY IN RICE PRODUCTION

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    Z. Katambara

    2014-01-01

    Full Text Available Producing more rice while using less water is among the calls in water scarce regions so as to feed the growing population and cope with the changing climate. Among the suitable techniques towards this achievement is the use of system of rice intensification (SRI, which has been reported as an approach that uses less water and has high water productivity and water use efficiency. Despite its promising results, the use of SRI practice in Tanzania is limited due to less knowledge with regard to the transplanting age, plant spacing, and minimum soil moisture to be allowed for irrigation, and alternate wetting and drying interval for various geographical locations. The AquaCrop crop water productivity model, which is capable of simulating crop water requirements and yield for a given parameter set, was used to identify suitable SRI parameters for Mkindo area in Morogoro region, Tanzania. Using no stress in soil fertility, plant spacings ranging from 5 cm to 50 cm were evaluated. Results suggest that the yield and biomass produced per ha increase with decreasing spacing from 50 cm to 20 cm. Preliminary field results suggest that the optimum spacing is round 25 cm. However, the model structure does not take into consideration number of tillers produced. As such, the study calls for incorporation of the tillering processes into AquaCrop model.

  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. 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.

  15. A conditional model for estimating the increase in suicides associated with the 2008-2010 economic recession in England.

    Science.gov (United States)

    Saurina, Carme; Bragulat, Basili; Saez, Marc; López-Casasnovas, Guillem

    2013-09-01

    Although evidence of the effects of the economic crisis on suicides is quite low, a recent article shows that the increase in suicides in England between 2008 and 2010 could be associated with the rise in unemployment. Our study analysed whether this effect was the same for all regions of England, using a conditional model which explicitly allows estimation of regional time trends and the effects of unemployment on suicides at the regional level. Hierarchical mixed models were used to assess both, suicides attributable to the financial crisis and the association between unemployment and suicides. The number and the (age-standardised) rate of suicides, for men and women separately, were the dependent variables. We considered the nine English regions based on the NUTS 2 level. There was an (not statistically significant) increase in the number of suicides between 2008 and 2010. The variation in rates was not statistically significant in England as a whole but there were statistically significant increases and decreases in some regions. Statistically significant associations between unemployment and suicides were only found at regional level. For men, statistically significant unemployment rates were positively associated with age-standardised suicide rates in the South West (0.384), North West (0.260) and North East (0.136), and negatively associated in the East of England (-0.444), East Midlands (-0.236) and London (-0.168). The study provides evidence that, even with statistically significant associations, finding variability, but no clear pattern, between trends and associations and/or numbers and rates might in fact suggest relatively spurious relationships; this is a result of not controlling for confounders.

  16. L-mimosine increases the production of vascular endothelial growth factor in human tooth slice organ culture model.

    Science.gov (United States)

    Trimmel, K; Cvikl, B; Müller, H-D; Nürnberger, S; Gruber, R; Moritz, A; Agis, H

    2015-03-01

    To assess the pro-angiogenic and pro-inflammatory capacity of the dentine-pulp complex in response to the prolyl hydroxylase inhibitor L-mimosine in a tooth slice organ culture model. Human teeth were sectioned transversely into 600-μm-thick slices and cultured in medium supplemented with serum and antibiotics. Then, pulps were stimulated for 48 h with L-mimosine. Pulps were subjected to viability measurements based on formazan formation in MTT assays. In addition, histological evaluation of pulps was performed based on haematoxylin and eosin staining. Culture supernatants were subjected to immunoassays for vascular endothelial growth factor (VEGF) to determine the pro-angiogenic capacity and to immunoassays for interleukin (IL)-6 and IL-8 to assess the pro-inflammatory response. Interleukin-1 served as pro-inflammatory control. Echinomycin was used to inhibit hypoxia-inducible factor-1 (HIF-1) alpha activity. Data were analysed using Student's t-test and Mann-Whitney U test. Pulps within tooth slices remained vital upon L-mimosine stimulation as indicated by formazan formation and histological evaluation. L-mimosine increased VEGF production when normalized to formazan formation in the pulp tissue of the tooth slices (P  0.05), whilst treatment with IL-1, which served as positive control, increased IL-6 (P model whilst inducing no prominent increase in IL-6 and IL-8. Pre-clinical studies will reveal if these in vitro effects translate into dental pulp regeneration. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  17. 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

  18. Achieving Peak Flow and Sediment Loading Reductions through Increased Water Storage in the Le Sueur Watershed, Minnesota: A Modeling Approach

    Science.gov (United States)

    Mitchell, N. A.; Gran, K. B.; Cho, S. J.; Dalzell, B. J.; Kumarasamy, K.

    2015-12-01

    A combination of factors including climate change, land clearing, and artificial drainage have increased many agricultural regions' stream flows and rates at which channel banks and bluffs are eroded. Increasing erosion rates within the Minnesota River Basin have contributed to higher sediment-loading rates, excess turbidity levels, and increases in sedimentation rates in Lake Pepin further downstream. Water storage sites (e.g., wetlands) have been discussed as a means to address these issues. This study uses the Soil and Water Assessment Tool (SWAT) to assess a range of water retention site (WRS) implementation scenarios in the Le Sueur watershed in south-central Minnesota, a subwatershed of the Minnesota River Basin. Sediment loading from bluffs was assessed through an empirical relationship developed from gauging data. Sites were delineated as topographic depressions with specific land uses, minimum areas (3000 m2), and high compound topographic index values. Contributing areas for the WRS were manually measured and used with different site characteristics to create 210 initial WRS scenarios. A generalized relationship between WRS area and contributing area was identified from measurements, and this relationship was used with different site characteristics (e.g., depth, hydraulic conductivity (K), and placement) to create 225 generalized WRS scenarios. Reductions in peak flow volumes and sediment-loading rates are generally maximized by placing site with high K values in the upper half of the watershed. High K values allow sites to lose more water through seepage, emptying their storages between precipitation events and preventing frequent overflowing. Reductions in peak flow volumes and sediment-loading rates also level off at high WRS extents due to the decreasing frequencies of high-magnitude events. The generalized WRS scenarios were also used to create a simplified empirical model capable of generating peak flows and sediment-loading rates from near

  19. NURSING CARE APPROCH MODEL (NCAM–PAKAR ON THE INCREASING OF COGNITIF AND BIOLOGICAL ADAPTATION RESPONSES PATIENT WITH HIV INFECTION

    Directory of Open Access Journals (Sweden)

    Nursalam Nursalam

    2017-04-01

    Full Text Available Introduction: PAKAR model that focused on coping strategy and social support (nurse, family and patients lead to positive coping mechanism through the learning process. The purpose of the study was to examine the effect of PAKAR toward adaptive response on PWH infection. PNI and nursing sciences from Roy paradigm were used in this study. Method: Quasy-experimental pre-post-test non randomized control group design is used in this study. Forty (40 PWH infections in Intermediate Department Care for Infection Disease (UPIPI Dr. Soetomo hospital in Surabaya were selected and non-randomized assignment divided into 2 groups of 20, experiment and control group. In vitro- test were used to measure biological response change: cortical, CD4, IFNγ, and Anti-HIV. Psychological, social, and spiritual response were measured and observed by using questionnaires, in depth interview and Focus Group Discussion. A Multivariate analysis was used to evaluate the data of biological response and non-parametric test: Wilcoxon and Mann Whitney were used to measure cognitive response. Result: Result showed that there were significantly differences on cognitive response between PAKAR and Standard, namely; spiritual response on be patient, social response on emotional stable, and acceptance response on anger and bargaining. In addition, biological response were significantly differences between the groups with F = 0.497 and p = 0.000. The cortical and Anti-HIV variables were the pattern contribution between the groups, with 77.5%. The increase the number of CD4 was found to be the dominance factor that was correlated toward the positive of cognitive response caused by PAKAR. Discussion: PAKAR model that focused on coping strategy and utilizing social support lead to treat cognitive response PWH infection. The model is based on nursing science theory (Roy and Hall combined with psychoneuroimmunology paradigm that is able to induce immune response modulation, especially the

  20. Increased pulmonary arteriolar tone associated with lung oxidative stress and nitric oxide in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Roberts, Andrew M; Jagadapillai, Rekha; Vaishnav, Radhika A; Friedland, Robert P; Drinovac, Robert; Lin, Xingyu; Gozal, Evelyne

    2016-09-01

    Vascular dysfunction and decreased cerebral blood flow are linked to Alzheimer's disease (AD). Loss of endothelial nitric oxide (NO) and oxidative stress in human cerebrovascular endothelium increase expression of amyloid precursor protein (APP) and enhance production of the Aβ peptide, suggesting that loss of endothelial NO contributes to AD pathology. We hypothesize that decreased systemic NO bioavailability in AD may also impact lung microcirculation and induce pulmonary endothelial dysfunction. The acute effect of NO synthase (NOS) inhibition on pulmonary arteriolar tone was assessed in a transgenic mouse model (TgAD) of AD (C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax) and age-matched wild-type controls (C57BL/6J). Arteriolar diameters were measured before and after the administration of the NOS inhibitor, L-NAME Lung superoxide formation (DHE) and formation of nitrotyrosine (3-NT) were assessed as indicators of oxidative stress, inducible NOS (iNOS) and tumor necrosis factor alpha (TNF-α) expression as indicators of inflammation. Administration of L-NAME caused either significant pulmonary arteriolar constriction or no change from baseline tone in wild-type (WT) mice, and significant arteriolar dilation in TgAD mice. DHE, 3-NT, TNF-α, and iNOS expression were higher in TgAD lung tissue, compared to WT mice. These data suggest L-NAME could induce increased pulmonary arteriolar tone in WT mice from loss of bioavailable NO In contrast, NOS inhibition with L-NAME had a vasodilator effect in TgAD mice, potentially caused by decreased reactive nitrogen species formation, while significant oxidative stress and inflammation were present. We conclude that AD may increase pulmonary microvascular tone as a result of loss of bioavailable NO and increased oxidative stress. Our findings suggest that AD may have systemic microvascular implications beyond central neural control mechanisms.

  1. 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

  2. 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.

  3. Increased recruitment but impaired function of leukocytes during inflammation in mouse models of type 1 and type 2 diabetes.

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    Ulrika Sofia Pettersson

    Full Text Available BACKGROUND: Patients suffering from diabetes show defective bacterial clearance. This study investigates the effects of elevated plasma glucose levels during diabetes on leukocyte recruitment and function in established models of inflammation. METHODOLOGY/PRINCIPAL FINDINGS: Diabetes was induced in C57Bl/6 mice by intravenous alloxan (causing severe hyperglycemia, or by high fat diet (moderate hyperglycemia. Leukocyte recruitment was studied in anaesthetized mice using intravital microscopy of exposed cremaster muscles, where numbers of rolling, adherent and emigrated leukocytes were quantified before and during exposure to the inflammatory chemokine MIP-2 (0.5 nM. During basal conditions, prior to addition of chemokine, the adherent and emigrated leukocytes were increased in both alloxan- (62±18% and 85±21%, respectively and high fat diet-induced (77±25% and 86±17%, respectively diabetes compared to control mice. MIP-2 induced leukocyte emigration in all groups, albeit significantly more cells emigrated in alloxan-treated mice (15.3±1.0 compared to control (8.0±1.1 mice. Bacterial clearance was followed for 10 days after subcutaneous injection of bioluminescent S. aureus using non-invasive IVIS imaging, and the inflammatory response was assessed by Myeloperoxidase-ELISA and confocal imaging. The phagocytic ability of leukocytes was assessed using LPS-coated fluorescent beads and flow cytometry. Despite efficient leukocyte recruitment, alloxan-treated mice demonstrated an impaired ability to clear bacterial infection, which we found correlated to a 50% decreased phagocytic ability of leukocytes in diabetic mice. CONCLUSIONS/SIGNIFICANCE: These results indicate that reduced ability to clear bacterial infections observed during experimentally induced diabetes is not due to reduced leukocyte recruitment since sustained hyperglycemia results in increased levels of adherent and emigrated leukocytes in mouse models of type 1 and type 2 diabetes

  4. mTOR inhibition increases cell viability via autophagy induction during endoplasmic reticulum stress - An experimental and modeling study.

    Science.gov (United States)

    Kapuy, Orsolya; Vinod, P K; Bánhegyi, Gábor

    2014-01-01

    Unfolded or misfolded proteins in the endoplasmic reticulum (ER) trigger an adaptive ER stress response known as unfolded protein response (UPR). Depending on the severity of ER stress, either autophagy-controlled survival or apoptotic cell death can be induced. The molecular mechanisms by which UPR controls multiple fate decisions have started to emerge. One such molecular mechanism involves a master regulator of cell growth, mammalian target of rapamycin (mTOR), which paradoxically is shown to have pro-apoptotic role by mutually interacting with ER stress response. How the interconnections between UPR and mTOR influence the dynamics of autophagy and apoptosis activation is still unclear. Here we make an attempt to explore this problem by using experiments and mathematical modeling. The effect of perturbed mTOR activity in ER stressed cells was studied on autophagy and cell viability by using agents causing mTOR pathway inhibition (such as rapamycin or metyrapone). We observed that mTOR inhibition led to an increase in cell viability and was accompanied by an increase in autophagic activity. It was also shown that autophagy was activated under conditions of severe ER stress but that in the latter phase of stress it was inhibited at the time of apoptosis activation. Our mathematical model shows that both the activation threshold and temporal dynamics of autophagy and apoptosis inducers are sensitive to variation in mTOR activity. These results confirm that autophagy has cytoprotective role and is activated in mutually exclusive manner with respect to ER stress levels.

  5. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis.

    Science.gov (United States)

    Li, Xiaodong; Ominsky, Michael S; Warmington, Kelly S; Morony, Sean; Gong, Jianhua; Cao, Jin; Gao, Yongming; Shalhoub, Victoria; Tipton, Barbara; Haldankar, Raj; Chen, Qing; Winters, Aaron; Boone, Tom; Geng, Zhaopo; Niu, Qing-Tian; Ke, Hua Zhu; Kostenuik, Paul J; Simonet, W Scott; Lacey, David L; Paszty, Chris

    2009-04-01

    The development of bone-rebuilding anabolic agents for potential use in the treatment of bone loss conditions, such as osteoporosis, has been a long-standing goal. Genetic studies in humans and mice have shown that the secreted protein sclerostin is a key negative regulator of bone formation, although the magnitude and extent of sclerostin's role in the control of bone formation in the aging skeleton is still unclear. To study this unexplored area of sclerostin biology and to assess the pharmacologic effects of sclerostin inhibition, we used a cell culture model of bone formation to identify a sclerostin neutralizing monoclonal antibody (Scl-AbII) for testing in an aged ovariectomized rat model of postmenopausal osteoporosis. Six-month-old female rats were ovariectomized and left untreated for 1 yr to allow for significant estrogen deficiency-induced bone loss, at which point Scl-AbII was administered for 5 wk. Scl-AbII treatment in these animals had robust anabolic effects, with marked increases in bone formation on trabecular, periosteal, endocortical, and intracortical surfaces. This not only resulted in complete reversal, at several skeletal sites, of the 1 yr of estrogen deficiency-induced bone loss, but also further increased bone mass and bone strength to levels greater than those found in non-ovariectomized control rats. Taken together, these preclinical results establish sclerostin's role as a pivotal negative regulator of bone formation in the aging skeleton and, furthermore, suggest that antibody-mediated inhibition of sclerostin represents a promising new therapeutic approach for the anabolic treatment of bone-related disorders, such as postmenopausal osteoporosis.

  6. L-Tyrosine-loaded nanoparticles increase the antitumoral activity of direct electric current in a metastatic melanoma cell model

    Directory of Open Access Journals (Sweden)

    Vânia Emerich Bucco de Campos

    2010-11-01

    Full Text Available Vânia Emerich Bucco de Campos1, Cesar Augusto Antunes Teixeira1, Venicio Feo da Veiga2, Eduardo Ricci Júnior1, Carla Holandino11Departamento de Medicamentos, Faculdade de Farmácia, 2Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilAbstract: Inhibition of tumor growth induced by treatment with direct electric current (DC has been reported in several models. One of the mechanisms responsible for the antitumoral activity of DC is the generation of oxidative species, known as chloramines. With the aim of increasing chloramine production in the electrolytic medium and optimizing the antitumoral effects of DC, poly(e-caprolactone (PCL nanoparticles (NPs loaded with the amino acid tyrosine were obtained. The physical–chemical characterization showed that the NPs presented size in nanometric range and monomodal distribution. A slightly negative electrokinetic potential was also found in both blank NPs and L-tyrosine-loaded PCL NPs. The yield of the loading process was approximately 50%. Within 3 h of dissolution assay, a burst release of about 80% L-tyrosine was obtained. The in vitro cytotoxicity of DC was significantly increased when associated with L-tyrosine-loaded NPs, using a murine multidrug-resistant melanoma cell line model. This study showed that the use of the combination of nanotechnology and DC has a promising antineoplastic potential and opens a new perspective in cancer therapy.Keywords: direct electric current, nanotechnology, cancer therapy, L-tyrosine, B16F10 cells

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

    Science.gov (United States)

    Lövgren, K M; Søndergaard, H; Skov, S; Wiinberg, B

    2016-09-01

    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. 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. 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 antibodies were analysed using an enzyme-linked immunosorbent assay and neutralizing antibodies using a Bethesda-like assay. Rats in the knee-bleed group developed a significantly faster inhibitor response and reached significantly higher inhibitor levels. In the knee-bleed group, 80% developed inhibitors vs. 33% in the control group, demonstrating a 2.4 times higher inhibitor risk when treating concurrent with bleeds. FVIII treatment in relation to a bleed potentiates inhibitor development compared to FVIII treatment alone in this HA rat, indicating that bleeding is a potential danger signal. Our results support the theory that FVIII replacement therapy concurrent with a bleeding episode increases the inhibitor risk, which to the best of our knowledge, has not been confirmed in an animal model before. © 2016 John Wiley & Sons Ltd.

  8. Unravelling the complexity of signalling networks in cancer: A review of the increasing role for computational modelling.

    Science.gov (United States)

    Garland, John

    2017-09-01

    ("bottom-up" research) is highlighted. The review concludes that computational modelling is an essential part of cancer research and is vital to understanding network formation and molecular behaviours that are associated with it. Its role is increasingly essential because it is unravelling the huge complexity of cancer induction otherwise unattainable by any other approach. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  9. The modeling of the channel deformations in the rivers flowing into permafrost with an increase in ambient temperature

    Science.gov (United States)

    Debolskaya, E. I.; Zamjatina, E. V.; Gritsuk, I. I.; Maslikova, O. Ja.

    2012-04-01

    Global climate changes in recent decades inevitably lead to more frequent catastrophic events. Their negative effects on rivers flowing into the permafrost zone, may be exacerbated by significant changes in bed deformations caused not only the influence of water flow, but significant changes of the bed due to the influence of increasing water and air temperatures on the structure of its constituent materials. The coastal slopes composed of permafrost will be subject to thermal abrasion. The purpose of this paper is to investigate the influence of river flow during the increase of water temperature on the deformation of the coastal slopes, composed of permafrost rocks with the addition of ice layers. The method of investigation is laboratory and mathematical modeling. The basis of the three-dimensional mathematical model of the coastal slopes thermoerosion of the rivers flowing in permafrost regions, and its verification is the results of the laboratory experiments conducted in the hydraulic tray. When the water temperature in the main stream rises the ice plate begins to melt forming the cavity where small streams are formed. The soil layers lose hard icy base and begin to sag under gravity. In the mathematical model law of the phase transition movement (Stefan condition) is determined from the heat balance equation. To determine the longitudinal velocity and the turbulent exchange coefficient we use the approach of "shallow water". The value of the transverse velocity is calculated from the equation of continuity. Coastal slope deformation during thawing is determined primarily by deposition of rock under the influence of gravity. An erosion due to water current in the mainstream and in the cavities may play a role under sufficient looseness of the rocks. The parameterization of the rocks deposition is almost impossible without knowing the composition of the soil, its porosity, ice content, moisture content. The determination of the rate and amount of slipping is

  10. CNF1 increases brain energy level, counteracts neuroinflammatory markers and rescues cognitive deficits in a murine model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Stefano Loizzo

    Full Text Available Overexpression of pro-inflammatory cytokines and cellular energy failure are associated with neuroinflammatory disorders, such as Alzheimer's disease. Transgenic mice homozygous for human ApoE4 gene, a well known AD and atherosclerosis animal model, show decreased levels of ATP, increased inflammatory cytokines level and accumulation of beta amyloid in the brain. All these findings are considered responsible for triggering cognitive decline. We have demonstrated that a single administration of the bacterial E. coli protein toxin CNF1 to aged apoE4 mice, beside inducing a strong amelioration of both spatial and emotional memory deficits, favored the cell energy restore through an increment of ATP content. This was accompanied by a modulation of cerebral Rho and Rac1 activity. Furthermore, CNF1 decreased the levels of beta amyloid accumulation and interleukin-1β expression in the hippocampus. Altogether, these data suggest that the pharmacological modulation of Rho GTPases by CNF1 can improve memory performances in an animal model of Alzheimer's disease via a control of neuroinflammation and a rescue of systemic energy homeostasis.

  11. 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.

  12. White matter apoptosis is increased by delayed hypothermia and rewarming in a neonatal piglet model of hypoxic ischemic encephalopathy.

    Science.gov (United States)

    Wang, B; Armstrong, J S; Reyes, M; Kulikowicz, E; Lee, J-H; Spicer, D; Bhalala, U; Yang, Z-J; Koehler, R C; Martin, L J; Lee, J K

    2016-03-01

    Therapeutic hypothermia is widely used to treat neonatal hypoxic ischemic (HI) brain injuries. However, potentially deleterious effects of delaying the induction of hypothermia and of rewarming on white matter injury remain unclear. We used a piglet model of HI to assess the effects of delayed hypothermia and rewarming on white matter apoptosis. Piglets underwent HI injury or sham surgery followed by normothermic or hypothermic recovery at 2h. Hypothermic groups were divided into those with no rewarming, slow rewarming at 0.5°C/h, or rapid rewarming at 4°C/h. Apoptotic cells in the subcortical white matter of the motor gyrus, corpus callosum, lateral olfactory tract, and internal capsule at 29h were identified morphologically and counted by hematoxylin & eosin staining. Cell death was verified by terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL) assay. White matter neurons were also counted, and apoptotic cells were immunophenotyped with the oligodendrocyte marker 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase). Hypothermia, slow rewarming, and rapid rewarming increased apoptosis in the subcortical white matter relative to normothermia (ppiglets had more apoptosis in the lateral olfactory tract than those that were rewarmed (ppiglets had more apoptosis than shams after normothermia, slow rewarming, and rapid rewarming (ppiglet model of HI; in some regions these temperature effects are independent of HI. Vulnerable cells include myelinating oligodendrocytes. This study identifies a deleterious effect of therapeutic hypothermia in the developing brain.

  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.

  15. An uncertain revolution: why the rise of a genetic model of mental illness has not increased tolerance.

    Science.gov (United States)

    Schnittker, Jason

    2008-11-01

    This study uses the 2006 replication of the 1996 General Social Survey Mental Health Module to explore trends in public beliefs about mental illness in the USA. Drawing on three models related to the framing of genetic arguments in popular media, the study attempts to address why tolerance of the mentally ill has not increased, despite the growing popularity of a biomedical view. The key to resolving this paradox lies in understanding how genetic arguments interact with other beliefs about mental illness, as well as the complex ideational implications of genetic frameworks. Genetic arguments have contingent relationships with tolerance. When applied to schizophrenia, genetic arguments are positively associated with fears regarding violence. Indeed, in this regard, attributing schizophrenia to genes is no different from attributing schizophrenia to bad character. However, when applied to depression, genetic arguments are positively associated with social acceptance. In addition to these contingencies, genetic explanations have discontinuous relationships with beliefs regarding treatment. Although genetic arguments are positively associated with recommending medical treatment, they are not associated with the perceived likelihood of improvement. The net result of these assorted relationships is little change in overall levels of tolerance over time. Because of the blunt nature of the forces propelling a biomedical view--including the growing popularity of psychiatric medications--altering beliefs about the etiology of mental illness is unlikely, on its own, to increase tolerance.

  16. Increasing concentrations of prothrombin complex concentrate induce disseminated intravascular coagulation in a pig model of coagulopathy with blunt liver injury.

    Science.gov (United States)

    Grottke, Oliver; Braunschweig, Till; Spronk, Henri M H; Esch, Stephanie; Rieg, Annette D; van Oerle, Rene; ten Cate, Hugo; Fitzner, Christina; Tolba, Rene; Rossaint, Rolf

    2011-08-18

    Despite increasing use of prothrombin complex concentrate (PCC) to treat hemorrhage-associated coagulopathy, few studies have investigated PCC in trauma, and there is a particular lack of safety data. This study was performed to evaluate PCC therapy in a porcine model of coagulopathy with blunt liver injury. Coagulopathy was induced in 27 anesthetized pigs by replacing approximately 70% blood volume with hydroxyethyl starch 130/0.4 and Ringer's lactate solution; erythrocytes were collected and retransfused. Ten minutes after trauma, animals randomly received PCC (35 or 50 IU/kg) or saline. Coagulation parameters including thromboelastometry, thrombin generation, and blood loss were monitored for 2 hours. Internal organs were examined macroscopically and histologically to determine the presence of emboli and assess liver injury. Total blood loss was significantly lower and survival was higher in both PCC groups versus the control group (P < .05). These outcomes appeared to be dose-independent. Thromboembolism was found in all animals treated with 50 IU/kg PCC; 44% also showed signs of disseminated intravascular coagulation. Liver injury was similar in all animals. In conclusion, 35 IU/kg PCC safely improved coagulation and attenuated blood loss. However, the higher dose of PCC (50 IU/kg) appeared to increase the risk of thromboembolism and disseminated intravascular coagulation.

  17. CBP gene transfer increases BDNF levels and ameliorates learning and memory deficits in a mouse model of Alzheimer's disease

    Science.gov (United States)

    Caccamo, Antonella; Maldonado, Monica A.; Bokov, Alex F.; Majumder, Smita; Oddo, Salvatore

    2010-01-01

    Cognitive dysfunction and memory loss are common features of Alzheimer's disease (AD). Abnormalities in the expression profile of immediate early genes that play a critical role in memory formation, such as the cAMP-response element binding protein (CREB), have been reported in the brains of AD patients. Here we show that amyloid-β (Aβ) accumulation, which plays a primary role in the cognitive deficits of AD, interferes with CREB activity. We further show that restoring CREB function via brain viral delivery of the CREB-binding protein (CBP) improves learning and memory deficits in an animal model of AD. Notably, such improvements occur without changes in Aβ and tau pathology, and instead are linked to an increased level of brain-derived neurotrophic factor. The resulting data suggest that Aβ-induced learning and memory deficits are mediated by alterations in CREB function, based on the finding that restoring CREB activity by directly modulating CBP levels in the brains of adult mice is sufficient to ameliorate learning and memory. Therefore, increasing CBP expression in adult brains may be a valid therapeutic approach not only for AD, but also for various brain disorders characterized by alterations in immediate early genes, further supporting the concept that viral vector delivery may be a viable therapeutic approach in neurodegenerative diseases. PMID:21149712

  18. 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.

  19. Flux balance analysis of genome-scale metabolic model of rice (Oryza sativa): Aiming to increase biomass

    Indian Academy of Sciences (India)

    Rahul Shaw; Sudip Kundu

    2015-10-01

    Due to socio-economic reasons, it is essential to design efficient stress-tolerant, more nutritious, high yielding rice varieties. A systematic understanding of the rice cellular metabolism is essential for this purpose. Here, we analyse a genome-scale metabolic model of rice leaf using Flux Balance Analysis to investigate whether it has potential metabolic flexibility to increase the biosynthesis of any of the biomass components. We initially simulate the metabolic responses under an objective to maximize the biomass components. Using the estimated maximum value of biomass synthesis as a constraint, we further simulate the metabolic responses optimizing the cellular economy. Depending on the physiological conditions of a cell, the transport capacities of intracellular transporters (ICTs) can vary. To mimic this physiological state, we randomly vary the ICTs’ transport capacities and investigate their effects. The results show that the rice leaf has the potential to increase glycine and starch in a wide range depending on the ICTs’ transport capacities. The predicted biosynthesis pathways vary slightly at the two different optimization conditions. With the constraint of biomass composition, the cell also has the metabolic plasticity to fix a wide range of carbon-nitrogen ratio.

  20. 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.

  1. A system dynamics modelling approach to studying the increasing prevalence of people with intellectual developmental disorders in New South Wales.

    Science.gov (United States)

    Lee, Lynette; Heffernan, Mark; McDonnell, Geoffrey; Short, Stephanie D; Naganathan, Vasi

    2016-06-01

    Objective The aims of this study were to estimate the prevalence count of people with intellectual developmental disorders (IDD) in New South Wales (NSW) in 2003, by age groups, and to forecast their prevalence until 2043. Methods Administrative data obtained from NSW government departments of education, pensions, health and disability were used to profile the number of people whose characteristics met the criteria for 'intellectual developmental disorders' who had received services in 2003. These figures were compared with published tables of NSW data from the national self-report Survey of Disability, Ageing and Carers (SDAC) of 2003 to estimate the likely prevalence of people with intellectual developmental disorders, by age groups in that year. The results were then used as baseline figures in a computational system dynamics model of the aging chain of people with these disorders, built to project prevalence to 2043. Results The number of people who met the criteria for having intellectual developmental disorder in NSW in 2003 was estimated to be 57000 (a ratio of 85 per 10000), with 32000 aged 0-15 years, 15000 aged 16-39 years, 9000 aged 40-64 years and 1000 aged 65+ years. Using these figures as baseline, the computer simulation predicted a total increase to 77225 people in 2013 and 135905 people by 2043. By 2043, the number of children with intellectual developmental disorders will have doubled, from 32000 to 59480, and the number of adults will have tripled, from 25000 to 76420. Conclusions This modelling technique forecast an increase in the prevalence count of people with intellectual developmental disorders in NSW over the period 2003-43 from 57000 (85 per 10000) to 135905 (135 per 10000). These predictions may have important implications for the planning of specialist health services for this group of people. What is known about the topic? The prevalence ratio of people with intellectual developmental disorders is quoted at lying between 1% and 2% of

  2. 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

  3. 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

  4. Accelerated Growth Rate and Increased Drought Stress Resilience of the Model Grass Brachypodium distachyon Colonized by Bacillus subtilis B26

    Science.gov (United States)

    Charron, Jean-Benoit; Vali, Hojatollah; Bertrand, Annick; Jabaji, Suha

    2015-01-01

    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 grasses and cereal

  5. Does Carica papaya leaf-extract increase the platelet count? An experimental study in a murine model

    Institute of Scientific and Technical Information of China (English)

    Susiji Wickramasinghe; Roshitha Nilmini Waduge

    2013-01-01

    Objective:To investigate the potential role of fresh Carica papaya (C. papaya) leaf extract on haematological and biochemical parameters and toxicological changes in a murine model. Methods: In total 36 mice were used for the trial. Fresh C. papaya leaf extract [0.2 mL (2 g)/mouse] was given only to the test group (18 mice). General behavior, clinical signs and feeding patterns were recorded. Blood and tissue samples were collected at intervals. Haematological parameters including platelet, red blood cell (RBC), white blood cell (WBC), packed cell volume (PCV), serum biochemistry including serum creatinine, serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) were determined. Organs for possible histopathological changes were examined. Results: Neither group exhibited alteration of behavior or reduction in food and water intake. Similarly, no significant changes in SGOT, SGPT and serum creatinine levels were detected in the test group. Histopathological organ changes were not observed in either group of mice except in three liver samples of the test group which had a mild focal necrosis. The platelet count (11.33±0.35)í105/µL (P=0.000 04) and the RBC count (7.97±0.61)í106/µL (P=0.000 03) were significantly increased in the test group compared to that of the controls. However, WBC count and PCV (%) values were not changed significantly in the test group. The platelet count in the test group started to increase significantly from Day 3 (3.4±0.18í105/µL), reaching almost a fourfold higher at Day 21 (11.3í105/µL), while it was 3.8í105/µL and 5.5í105/µL at Day 3 and Day 21 respectively in the control. Likewise, the RBC count in the test group increased from 6í106/µL to 9í106/ µL at Day 21 while it remained near constant in the control group (6í106/µL). Conclusions: Fresh C. papaya leaf extract significantly increased the platelet and RBC counts in the test group as compared to controls. Therefore, it is very

  6. Trifluridine/tipiracil increases survival rates in peritoneal dissemination mouse models of human colorectal and gastric cancer.

    Science.gov (United States)

    Suzuki, Norihiko; Nakagawa, Fumio; Takechi, Teiji

    2017-07-01

    A number of patients exhibit peritoneal dissemination of gastric or colorectal cancer, which is a predominant cause of cancer-associated mortality. Currently, there is no markedly effective treatment available. The present study was designed to determine the efficacy of trifluridine/tipiracil (TFTD), formerly known as TAS-102, which is used for the treatment of patients with unresectable advanced or recurrent colorectal cancer refractory to standard therapies. Four colorectal cancer cell lines and one gastric cancer cell line were intraperitoneally inoculated into nude mice, as models of peritoneal dissemination. TFTD (200 mg/kg/day) was orally administered for 5 consecutive days followed by 2 drug-free days for 6 weeks. The increase in the lifespan (ILS) of the TFTD-treated mice compared with that of the drug-free control mice was 66.7, 43.3, 106.3, 98.3 and 133.3% for DLD-1, DLD-1/5-fluorouracil [5-fluorouracil (5FU)-resistant subline of DLD-1], HT-29 and HCT116 colorectal cancer cell lines, and MKN45 gastric cancer cell line, respectively. This ILS was similar to that of the irinotecan-treated mice (ILS, 70-84%), but was significantly (P<0.05) increased compared with that of the 5FU-, tegafur, gimeracil and potassium oxonate- and cisplatin-treated mice (ILS, 1-53%, 0.8-60% and 85%, respectively). No significant increase in body weight loss was observed during the dosing periods with any of the drugs used. The increase in CEA levels with progressive peritoneal dissemination was inhibited by TFTD treatment. TFTD also exhibited marked anticancer effects against Kirsten rat sarcoma viral oncogene homolog-mutated tumors and 5FU-resistant tumors. The results of the present study indicate that TFTD may be a potential drug against peritoneal dissemination of colorectal and/or gastric cancer in humans and may be utilized for chemo-naïve tumors and recurrent tumors following 5FU treatment.

  7. Stress increases the risk of type 2 diabetes onset in women: A 12-year longitudinal study using causal modelling

    Science.gov (United States)

    Oldmeadow, Christopher; Hure, Alexis; Luu, Judy; Loxton, Deborah

    2017-01-01

    Background Type 2 diabetes is associated with significant morbidity and mortality. Modifiable risk factors have been found to contribute up to 60% of type 2 diabetes risk. However, type 2 diabetes continues to rise despite implementation of interventions based on traditional risk factors. There is a clear need to identify additional risk factors for chronic disease prevention. The aim of this study was to examine the relationship between perceived stress and type 2 diabetes onset, and partition the estimates into direct and indirect effects. Methods and findings Women born in 1946–1951 (n = 12,844) completed surveys for the Australian Longitudinal Study on Women’s Health in 1998, 2001, 2004, 2007 and 2010. The total causal effect was estimated using logistic regression and marginal structural modelling. Controlled direct effects were estimated through conditioning in the regression model. A graded association was found between perceived stress and all mediators in the multivariate time lag analyses. A significant association was found between hypertension, as well as physical activity and body mass index, and diabetes, but not smoking or diet quality. Moderate/high stress levels were associated with a 2.3-fold increase in the odds of diabetes three years later, for the total estimated effect. Results were only slightly attenuated when the direct and indirect effects of perceived stress on diabetes were partitioned, with the mediators only explaining 10–20% of the excess variation in diabetes. Conclusions Perceived stress is a strong risk factor for type 2 diabetes. The majority of the effect estimate of stress on diabetes risk is not mediated by the traditional risk factors of hypertension, physical activity, smoking, diet quality, and body mass index. This gives a new pathway for diabetes prevention trials and clinical practice. PMID:28222165

  8. Increased Expression of TGF-β Signaling Components in a Mouse Model of Fibrosis Induced by Submandibular Gland Duct Ligation.

    Directory of Open Access Journals (Sweden)

    Lucas T Woods

    Full Text Available Transforming growth factor-β (TGF-β is a multi-functional cytokine with a well-described role in the regulation of tissue fibrosis and regeneration in the liver, kidney and lung. Submandibular gland (SMG duct ligation and subsequent deligation in rodents is a classical model for studying salivary gland damage and regeneration. While previous studies suggest that TGF-β may contribute to salivary gland fibrosis, the expression of TGF-β signaling components has not been investigated in relation to mouse SMG duct ligation-induced fibrosis and regeneration following ductal deligation. Following a 7 day SMG duct ligation, TGF-β1 and TGF-β3 were significantly upregulated in the SMG, as were TGF-β receptor 1 and downstream Smad family transcription factors in salivary acinar cells, but not in ductal cells. In acinar cells, duct ligation also led to upregulation of snail, a Smad-activated E-cadherin repressor and regulator of epithelial-mesenchymal transition, whereas in ductal cells upregulation of E-cadherin was observed while snail expression was unchanged. Upregulation of these TGF-β signaling components correlated with upregulation of fibrosis markers collagen 1 and fibronectin, responses that were inhibited by administration of the TGF-β receptor 1 inhibitors SB431542 or GW788388. After SMG regeneration following a 28 day duct deligation, TGF-β signaling components and epithelial-mesenchymal transition markers returned to levels similar to non-ligated controls. The results from this study indicate that increased TGF-β signaling contributes to duct ligation-induced changes in salivary epithelium that correlate with glandular fibrosis. Furthermore, the reversibility of enhanced TGF-β signaling in acinar cells of duct-ligated mouse SMG after deligation indicates that this is an ideal model for studying TGF-β signaling mechanisms in salivary epithelium as well as mechanisms of fibrosis initiation and their resolution.

  9. Increase in neurokinin-1 receptor-mediated colonic motor response in a rat model of irritable bowel syndrome

    Institute of Scientific and Technical Information of China (English)

    Jun-Ho La; Tae-Wan Kim; Tae-Sik Sung; Hyn-Ju Kim; Jeom-Yong Kim; Il-Suk Yang

    2005-01-01

    AIM: Irritable bowel syndrome (IBS) is a functional bowel disorder. Its major symptom is bowel dysmotility, yet the mechanism of the symptom is poorly understood. Since the neurokinin-1 receptor (NK1R)-mediated signaling in the gut is important in the control of normal bowel motor function,we aimed to investigate whether the NK1R-mediated bowel motor function was altered in IBS, using a rat IBS model that was previously reported to show colonic dysmotility in response to restraint stress.METHODS: IBS symptoms were produced in male SpragueDawley rats by inducing colitis with acetic acid. Rats were left to recover from colitis for 6 d, and used for experiments 7 d post-induction of colitis. Motor activities of distal colon were recorded in vitro.RESULTS: The contractile sensitivity of isolated colon to a NK1R agonist [Sar9, Met(O2)11]-substance P (1-30 nmol/L)was higher in IBS rats than that in normal rats. After the enteric neurotransmission was blocked by tetrodotoxin (TTX, 1 μmol/L), the contractile sensitivity to the NK1R agonist was increased in normal colon but not in IBS rat colon. The NK1R agonist-induced contraction was not different between the two groups when the agonist was challenged to the TTX-treated colon or the isolated colonic myocytes. A nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 100 μmol/L) augmented the NK1R agonist-induced contraction only in normal rat colon.CONCLUSION: These results suggest that the NK1R-meidated colonic motor response is increased in IBS rats, due to the decrease in the nitrergic inhibitory neural component.

  10. Both high and low plasma levels of 25-hydroxy vitamin D increase blood pressure in a normal rat model.

    Science.gov (United States)

    Mirhosseini, Naghmeh Z; Knaus, Steven J; Bohaychuk, Kaylee; Singh, Jaswant; Vatanparast, Hassan A; Weber, Lynn P

    2016-12-01

    The lower threshold plasma 25-hydroxy vitamin D (25(OH)D) level for optimal cardiovascular health is unclear, whereas the toxicity threshold is less clear. The aim of this study was to examine the cardiovascular-vitamin D dose-response curve in a normal rat model. Doses of cholecalciferol ranged from deficiency to toxic levels (equivalent to human doses of 0, 0·015, 0·25 and 3·75mg/d) for 4 weeks, and then cardiovascular health was examined using blood pressure telemetry and high-resolution ultrasound in normal male rats (n 16/group, 64 rats total). After 1 month, only the 0·25mg/d group had plasma 25(OH)D that was within current recommended range (100-125 nmol/l), and all groups failed to change plasma Ca or phosphate. Systolic blood pressure increased significantly (10-15 mmHg) in the rat groups with plasma 25(OH)D levels at both 30 and 561 nmol/l (groups fed 0 and 3·75mg/d) compared with the group fed the equivalent to 0·015mg/d (43 nmol/l 25(OH)D). Although not significant, the group fed the equivalent to 0·25mg/d (108 nmol/l 25(OH)D) also showed a 10 mmHg increase in systolic blood pressure. Carotid artery diameter was significantly smaller and wall thickness was larger, leading to higher peak carotid systolic blood velocity in these two groups. Despite these vascular changes, cardiac function did not differ among treatment groups. The key finding in this study is that arterial stiffness and systolic blood pressure both showed a U-shaped dose-response for vitamin D, with lowest values (best cardiovascular health) observed when plasma 25(OH)D levels were 43 nmol/l in normal male rats.

  11. 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.

  12. 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

  13. THE EFFECTS OF DIFFERENT MODELS OF SWIMMING TRAINING (DEFINED IN RELATION TO ANAEROBIC THRESHOLD ON THE INCREASE OF SWIM SPEED

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    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

  14. Activity-based simulation using DEVS:increasing performance by an activity model in parallel DEVS simulation

    Institute of Scientific and Technical Information of China (English)

    Bin CHEN; Lao-bing ZHANG; Xiao-cheng LIU; Hans VANGHELUWE

    2014-01-01

    Improving simulation performance using activity tracking has attracted attention in the modeling field in recent years. The reference to activity has been successfully used to predict and promote the simulation performance. Tracking activity, how-ever, uses only the inherent performance information contained in the models. To extend activity prediction in modeling, we propose the activity enhanced modeling with an activity meta-model at the meta-level. The meta-model provides a set of interfaces to model activity in a specific domain. The activity model transformation in subsequence is devised to deal with the simulation difference due to the heterogeneous activity model. Finally, the resource-aware simulation framework is implemented to integrate the activity models in activity-based simulation. The case study shows the improvement brought on by activity-based simulation using discrete event system specification (DEVS).

  15. 随机利率下的增额寿险%Increasing Life Insurance Model under Random Rates of Interest

    Institute of Scientific and Technical Information of China (English)

    王丽燕; 王丽娟; 杨德礼

    2006-01-01

    We discuss the increasing life insurance that the death benefit will be paid as soon as the insured dies. We establish its dual random model in which the force interest accumulation function is joint by both reflected Brownian motion (RBM) and Poisson process, and obtain all orders of moment of the present value of the benefits. The concise expressions of moment are given in the case that death happens uniformly in every policy year, and the examples are also given.%我们考虑即时给付的增额寿险模型,根据保费的实际投资情况以及突发事件对利率的影响,将随机利率采用反射布朗运动(RBM)和Poisson过程联合建模,给出即时给付的增额寿险的给付现值的各阶矩,并在死亡均匀分布的条件下得到矩的简洁表达式.最后用数值例子说明模型与计算方法的正确性与有效性.

  16. A prenatal prediction model for total nucleated cell count increases the efficacy of umbilical cord blood banking.

    Science.gov (United States)

    Manegold-Brauer, Gwendolin; Borner, Barbara; Bucher, Christoph; Hoesli, Irène; Passweg, Jakob; Girsberger, Sabine; Schoetzau, Andreas; Gisin, Simona; Visca, Eva

    2014-11-01

    The most important factor for the selection of an umbilical cord blood unit (CBU) for hematopoietic stem cell transplantation is the total nucleated cell (TNC) count as a surrogate marker for stem cell content in the CBU. At present, about one in five donors can provide a CBU with a sufficient TNC count for umbilical cord blood (UCB) banking. It is labor-intensive to obtain consent of all eligible donors and optimization of the selection is needed. The purpose of this study was to investigate prenatal clinical predictors for TNC count that would help to identify successful UCB donors already on admission to the delivery unit. This study was a retrospective analysis of 758 cryopreserved CBUs, collected from 2002 to 2006. Maternal and fetal factors analyzed were maternal age, gravidity, parity, weight, height, diabetes, premature rupture of membranes, gestational age, fetal sex, and birthweight. The impact on a high TNC count (banking rates from 22.7% to 31.9% while decreasing the number of banked CBUs from 149 to 79. Our prenatal prediction model increases the efficacy of obtaining informed consent for UCB banking while still allowing relevant numbers of CBUs to be banked. © 2014 AABB.

  17. Sargassum polycystum reduces hyperglycaemia, dyslipidaemia and oxidative stress via increasing insulin sensitivity in a rat model of type 2 diabetes.

    Science.gov (United States)

    Motshakeri, Mahsa; Ebrahimi, Mahdi; Goh, Yong Meng; Matanjun, Patricia; Mohamed, Suhaila

    2013-05-01

    Sargassum polycystum, a brown seaweed, contains various nutrients and bioactive compounds that have antioxidant and healing properties. The research hypothesises that antioxidants and pigments in dietary S. polycystum extracts can improve insulin sensitivity, blood sugar levels and blood lipid levels in a rat model of type 2 diabetes. The diabetes was induced by a high-sugar, high-fat diet for 16 weeks to enhance insulin resistance, followed by a low-dose intraperitoneal injection of streptozotocin (35 mg kg(-1) body weight). The doses of S. polycystum tested on diabetic rats were 150 and 300 mg kg(-1) body weight for the ethanolic extract or 150 and 300 mg kg(-1) for the water extract. Normal rats, untreated diabetic and metformin-treated diabetic rats (n = 6) were used as control. Both doses of the alcohol extract of S. polycystum and the 300 mg kg(-1) water extract, significantly reduced blood glucose and glycosylated haemoglobin (HbA1C ) levels. Serum total cholesterol, triglyceride levels and plasma atherogenic index were significantly decreased after 22 days treatment in all seaweed groups. Unlike metformin, S. polycystum did not significantly change plasma insulin in the rats, but increased the response to insulin. The consumption of either ethanolic or water extracts of S. polycystum dose dependently reduced dyslipidaemia in type 2 diabetic rats. S. polycystum is a potential insulin sensitiser, for a comestible complementary therapy in the management of type 2 diabetes which can help reduce atherogenic risk. © 2012 Society of Chemical Industry.

  18. Treadmill Exercise Prevents Increase of Neuroinflammation Markers Involved in the Dopaminergic Damage of the 6-OHDA Parkinson's Disease Model.

    Science.gov (United States)

    Real, Caroline Cristiano; Garcia, Priscila Crespo; Britto, Luiz R G

    2017-08-11

    Parkinson's disease (PD) involves loss of dopaminergic neurons in the substantia nigra (SN), which can be correlated to neuroinflammatory changes with the aging of the nervous system. On the other hand, exercise can reduce the deleterious effects promoted by age, but the mechanism involved is still unclear. This study investigated the preventive exercise-induced changes on neuroinflammatory processes in a rat model of PD induced by unilateral striatal injections of 6-hydroxydopamine (6-OHDA). Adult male Wistar rats were divided into two groups: (1) sedentary (SED) or (2) exercised (EX), animals that did treadmill exercise three times per week, every other day, for 4 weeks prior to 6-OHDA or saline injection. The rats were then divided into four sub-groups: (1) sedentary saline (SED), (2) sedentary 6-OHDA (SED + 6-OHDA), (3) exercised saline (EX), and (4) exercised 6-OHDA (EX + 6-OHDA). Seven and 30 days after surgery, brains were collected for immunohistochemistry and immunoblotting for dopaminergic and neuroinflammatory markers into SN and striatum. The SED + 6-OHDA animals presented an increase in the astrocyte, microglial, and oxidative species activation. On the other hand, EX + 6-OHDA animals did not present neuroinflammatory responses and performed better apormorphine test. Our data suggest that treadmill exercise throughout life can markedly reduce the chances of dopamine decrease, reinforcing studies that showed a lower incidence of Parkinson's disease in patients who were active during life.

  19. Administration of soluble activin receptor 2B increases bone and muscle mass in a mouse model of osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    Douglas J DiGirolamo; Vandana Singhal; Xiaoli Chang; Se-Jin Lee; Emily L Germain-Lee

    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.

  20. 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

  1. Enhanced adult neurogenesis increases brain stiffness: in vivo magnetic resonance elastography in a mouse model of dopamine depletion.

    Directory of Open Access Journals (Sweden)

    Charlotte Klein

    Full Text Available The mechanical network of the brain is a major contributor to neural health and has been recognized by in vivo magnetic resonance elastography (MRE to be highly responsive to diseases. However, until now only brain softening was observed and no mechanism was known that reverses the common decrement of neural elasticity during aging or disease. We used MRE in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP mouse model for dopaminergic neurodegeneration as observed in Parkinson's disease (PD to study the mechanical response of the brain on adult hippocampal neurogenesis as a robust correlate of neuronal plasticity in healthy and injured brain. We observed a steep transient rise in elasticity within the hippocampal region of up to over 50% six days after MPTP treatment correlating with increased neuronal density in the dentate gyrus, which could not be detected in healthy controls. Our results provide the first indication that new neurons reactively generated following neurodegeneration substantially contribute to the mechanical scaffold of the brain. Diagnostic neuroimaging may thus target on regions of the brain displaying symptomatically elevated elasticity values for the detection of neuronal plasticity following neurodegeneration.

  2. Psychological stress increases expression of aortic plaque intercellular adhesion molecule-1 and serum inflammatory cytokines in atherosclerotic rabbit model

    Institute of Scientific and Technical Information of China (English)

    Muwei Li; Xianpei Wang; Lei Yang; Chuanyu Gao; Yexin Ma

    2008-01-01

    Plaque rupture,platelet aggregation,and thrombogenesis are the main mechanisms of acute coronary syndrome (ACS),and inflammation factors play key roles in plaque unstability.Psychological stress promotes acute inflammatory response,leading to increased circulating levels of C-reactive protein (CRP),IL-6,and serum intercellular adhesion molecule (sICAM)-1.But it is not clear that whether psychological stress has a direct effect on atherosclerotic plaque stability.The purpose of this study was to investigate effects of chronic psychological stress on inflammatory marker (ICAM-1 ) in atherosclerotic plaque,and inflammatory markers in peripheral blood.Materials and methods Sixty male rabbits were randomized into 2 groups:the control group (n =10) and the atherosclerotic group (n =50).The latter were fed on high fatty diet and were given a large dose of vitamin D3 (3 600 000IU/kg) via intraperitoneal injection.After 8 weeks,the atherosclerotic model was estaslished.Then the 50 atherosclerotic model rabbits were divided into 3 subgroups:no-stress subgroup (n = 16),physiological stress subgroup (n = 16) and psychological stress subgroup (n =18).In physiological stress subgroup and psychological stress subgroup,drinking was cut from twice a day to once a day.At the same time,psychological stress subgroup was given empty bottle stress,and this process lasted for 2 weeks.One hour after the last stress,the blood samples were collected and the serum levels of CRP,IL-6 amd ICAM-1 were tested by radioimmunoassay or enzyme linked immunosorbent assay.The aorta and heart were extracted for pathology examination,and the express of ICAM-1 was tested by immunohistochemical examination.Results (1) After effective atherosclerotic animal model construction,the expression of ICAM-1 in aorta was higher in atherosclerotic group than that in control group (P<0.01),and was notably higher in psychological stress subgroup than that in no-stress subgroup or in physiological stress subgroup (2

  3. 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

  4. 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

  5. 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

  6. Simulation Modeling of Lakes in Undergraduate and Graduate Classrooms Increases Comprehension of Climate Change Concepts and Experience with Computational Tools

    Science.gov (United States)

    Carey, Cayelan C.; Gougis, Rebekka Darner

    2017-01-01

    Ecosystem modeling is a critically important tool for environmental scientists, yet is rarely taught in undergraduate and graduate classrooms. To address this gap, we developed a teaching module that exposes students to a suite of modeling skills and tools (including computer programming, numerical simulation modeling, and distributed computing)…

  7. Simulation Modeling of Lakes in Undergraduate and Graduate Classrooms Increases Comprehension of Climate Change Concepts and Experience with Computational Tools

    Science.gov (United States)

    Carey, Cayelan C.; Gougis, Rebekka Darner

    2017-01-01

    Ecosystem modeling is a critically important tool for environmental scientists, yet is rarely taught in undergraduate and graduate classrooms. To address this gap, we developed a teaching module that exposes students to a suite of modeling skills and tools (including computer programming, numerical simulation modeling, and distributed computing)…

  8. Primary blast causes mild, moderate, severe and lethal TBI with increasing blast overpressures: Experimental rat injury model

    Science.gov (United States)

    Mishra, Vikas; Skotak, Maciej; Schuetz, Heather; Heller, Abi; Haorah, James; Chandra, Namas

    2016-06-01

    Injury severity in blast induced Traumatic Brain Injury (bTBI) increases with blast overpressure (BOP) and impulse in dose-dependent manner. Pure primary blast waves were simulated in compressed gas shock-tubes in discrete increments. Present work demonstrates 24 hour survival of rats in 0–450 kPa (0–800 Pa•s impulse) range at 10 discrete levels (60, 100, 130, 160, 190, 230, 250, 290, 350 and 420 kPa) and determines the mortality rate as a non-linear function of BOP. Using logistic regression model, predicted mortality rate (PMR) function was calculated, and used to establish TBI severities. We determined a BOP of 145 kPa as upper mild TBI threshold (5% PMR). Also we determined 146–220 kPa and 221–290 kPa levels as moderate and severe TBI based on 35%, and 70% PMR, respectively, while BOP above 290 kPa is lethal. Since there are no standards for animal bTBI injury severity, these thresholds need further refinements using histopathology, immunohistochemistry and behavior. Further, we specifically investigated mild TBI range (0–145 kPa) using physiological (heart rate), pathological (lung injury), immuno-histochemical (oxidative/nitrosative and blood-brain barrier markers) as well as blood borne biomarkers. With these additional data, we conclude that mild bTBI occurs in rats when the BOP is in the range of 85–145 kPa.

  9. Isolated pulmonary regurgitation causes decreased right ventricular longitudinal function and compensatory increased septal pumping in a porcine model.

    Science.gov (United States)

    Kopic, S; Stephensen, S S; Heiberg, E; Arheden, H; Bonhoeffer, P; Ersbøll, M; Vejlstrup, N; Søndergaard, L; Carlsson, M

    2017-06-05

    Longitudinal ventricular contraction is a parameter of cardiac performance with predictive power. Right ventricular (RV) longitudinal function is impaired in patients with free pulmonary regurgitation (PR) following corrective surgery for Tetralogy of Fallot (TOF). It remains unclear whether this is a consequence of the surgical repair, or whether it is inherent to PR. The aim of this study was to assess the relationship between longitudinal, lateral and septal pumping in a porcine model of isolated PR. Piglets were divided into a control (n = 8) group and a treatment (n = 12) group, which received a stent in the pulmonary valve orifice, inducing PR. After 2-3 months, animals were subjected to cardiac magnetic resonance imaging. A subset of animals (n = 6) then underwent percutaneous pulmonary valve replacement (PPVR) with follow-up 1 month later. Longitudinal, lateral and septal contributions to stroke volume (SV) were quantified by measuring volumetric displacements from end-diastole to end-systole in the cardiac short axis and long axis. PR resulted in a lower longitudinal contribution to RV stroke volume, compared to controls (60.0 ± 2.6% vs. 73.6 ± 3.8%; P = 0.012). Furthermore, a compensatory increase in septal contribution to RVSV was observed (11.0 ± 1.6% vs. -3.1 ± 1.5%; P function were reversed by PPVR. These findings suggest that PR contributes to decreased RV longitudinal function in the absence of scarring from cardiac surgery. Measurement of longitudinal RVSV may aid risk stratification and timing for interventional correction of PR in TOF patients. © 2017 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.

  10. Increasing vegetation and climate gradient in Western Europe over the Last Glacial Inception (122 110 ka): data-model comparison

    Science.gov (United States)

    Sánchez Goñi, M. F.; Loutre, M. F.; Crucifix, M.; Peyron, O.; Santos, L.; Duprat, J.; Malaizé, B.; Turon, J.-L.; Peypouquet, J.-P.

    2005-02-01

    High-resolution terrestrial (pollen) and marine (planktic and benthic isotopes, coarse fraction, and N. pachyderma (s)) analyses have been performed in the Marine Isotope Stage (MIS) 5 interval of IMAGES core MD99-2331 retrieved in the northwestern Iberian margin. This study shows the occurrence of a Zeifen Interstadial/Stadial succession on land and in the ocean during the first part of MIS 5e. In northwestern Iberia, the Eemian is marked from 126 to 122 ka by the development of deciduous Quercus forest at the same time as Mediterranean forest colonised southern Iberia, and deciduous Quercus-Corylus forest occupied northernmost European regions. From 121 to 115 ka Carpinus betulus forest developed in NW Iberia indicating a winter cooling by 2 °C on land and an increase in annual precipitation by 100-200 mm along with a Sea Surface Temperature (SST) decreasing trend off Iberia. A similar cooling has been documented at the same time in northern Germany (52° N) by the replacement of deciduous forest by coniferous ( Abies-Picea) formations, implying a southward displacement of the deciduous tree line between ˜60° N and 50° N as early as 120 ka. The southward migration of the tree line between 72° N and 58° N simulated by the Earth Model of Intermediate Complexity MoBidiC from 122 and 120 ka and considered as a major process to initiate the last glaciation is, therefore, compatible with data. Between 115 and 110 ka, the substantial ice accumulation in northern high latitudes (MIS 5e/5d transition) was synchronous with successive drops, C26 and C25, in northeastern Atlantic SST. In northwestern Iberia Abies-Pinus trees developed at the expense of Quercus-Carpinus forest. A tundra-like environment occupied northern Germany, marking the end of the interglacial in northwestern Europe at 115 ka, and boreal forest likely colonised northeastern France. The first displacement of the vegetation belts at 121 ka was enhanced at 115 ka indicating an amplification of the

  11. Adsorption and self-assembly of bio-organic molecules at model surfaces: A route towards increased complexity

    Science.gov (United States)

    Costa, Dominique; Pradier, Claire-Marie; Tielens, Frederik; Savio, Letizia

    2015-12-01

    Understanding the bio-physical-chemical interactions at nanostructured biointerfaces and the assembly mechanisms of so-called hybrid nano-composites is nowadays a key issue for nanoscience in view of the many possible applications foreseen. The contribution of surface science in this field is noteworthy since, using a bottom-up approach, it allows the investigation of the fundamental processes at the basis of complex interfacial phenomena and thus it helps to unravel the elementary mechanisms governing them. Nowadays it is well demonstrated that a wide variety of different molecular assemblies can form upon adsorption of small biomolecules at surfaces. The geometry of such self-organized structures can often be tuned by a careful control of the experimental conditions during the deposition process. Indeed an impressive number of studies exists (both experimental and - to a lesser extent - theoretical), which demonstrates the ability of molecular self-assembly to create different structural motifs in a more or less predictable manner, by tuning the molecular building blocks as well as the metallic substrate. In this frame, amino acids and small peptides at surfaces are key, basic, systems to be studied. The amino acids structure is simple enough to serve as a model for the chemisorption of biofunctional molecules, but their adsorption at surfaces has applications in surface functionalization, in enantiospecific catalysis, biosensing, shape control of nanoparticles or in emerging fields such as "green" corrosion inhibition. In this paper we review the most recent advances in this field. We shall start from the adsorption of amino acids at metal surfaces and we will evolve then in the direction of more complex systems, in the light of the latest improvements of surface science techniques and of computational methods. On one side, we will focus on amino acids adsorption at oxide surfaces, on the other on peptide adsorption both at metal and oxide substrates. Particular

  12. A Preliminary Study in Applying the Function-Based Intervention Decision Model in Consultation to Increase Treatment Integrity

    Science.gov (United States)

    Gann, Candace J.; Kunnavatana, S. Shanun

    2016-01-01

    This preliminary study investigated the use of the Function-Based Intervention Decision Model (Decision Model; Umbreit, Ferro, Liaupsin, & Lane, 2007) to improve teacher treatment integrity for a function-based classroom management plan. The participants were a special education teacher and three elementary-age students receiving special…

  13. 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...

  14. Talking Picture Schedules: Embedding Video Models into Visual Activity Schedules to Increase Independence for Students with ASD

    Science.gov (United States)

    Spriggs, Amy D.; Knight, Victoria; Sherrow, Lauren

    2015-01-01

    Studies examining video modeling and visual activity schedules independent of one another have been shown to be effective in teaching skills for students with autism, but there is little research about the effectiveness of combining the two methods. Use of visual activity schedules with embedded video models via an iPad application was…

  15. 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…

  16. Modelling changes in nitrogen cycling to sustain increases in forest productivity under elevated atmospheric CO2 and contrasting site conditions

    OpenAIRE

    R. F. Grant

    2013-01-01

    If increases in net primary productivity (NPP) caused by rising concentrations of atmospheric CO2 (Ca) are to be sustained, key N processes such as soil mineralization, biological fixation, root uptake and nutrient conservation must also be increased. Simulating the response of these processes to elevated Ca is therefore vital for models used to project the effects of rising Ca on NPP. In this modelling study, hypotheses are proposed for changes in soil mineralization, biolo...

  17. Modeling of cell culture damage and recovery leads to increased antibody and biomass productivity in CHO cell cultures.

    Science.gov (United States)

    Naderi, Saeideh; Nikdel, Ali; Meshram, Mukesh; McConkey, Brendan; Ingalls, Brian; Budman, Hector; Scharer, Jeno

    2014-09-01

    The development of an efficient and productive cell-culture process requires a deep understanding of intracellular mechanisms and extracellular conditions for optimal product synthesis. Mathematical modeling provides an effective strategy to predict, control, and optimize cell performance under a range of culture conditions. In this study, a mathematical model is proposed for the investigation of cell damage of a Chinese hamster ovary cell culture secreting recombinant anti-RhD monoclonal antibody (mAb). Irreversible cell damage was found to be correlated with a reduction in pH. This irreversible damage to cellular function is described mathematically by a Tessier-based model, in which the actively growing fraction of cells is dependent on an intracellular metabolic product acting as a growth inhibitor. To further verify the model, an offline model-based optimization of mAb production in the cell culture was carried out, with the goal of minimizing cell damage and thereby enhancing productivity through intermittent refreshment of the culture medium. An experimental implementation of this model-based strategy resulted in a doubling of the yield as compared to the batch operation and the resulting biomass and productivity profiles agreed with the model predictions.

  18. 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…

  19. Informing energy and climate policies using energy systems models insights from scenario analysis increasing the evidence base

    CERN Document Server

    Giannakidis, George; Ó Gallachóir, Brian; Tosato, GianCarlo

    2015-01-01

    This book highlights how energy-system models are used to underpin and support energy and climate mitigation policy decisions at national, multi-country and global levels. It brings together, for the first time in one volume, a range of methodological approaches and case studies of good modeling practice on a national and international scale from the IEA-ETSAP energy technology initiative. It provides insights for the reader into the rich and varied applications of energy-system models and the underlying methodologies and policy questions they can address. The book demonstrates how these mode

  20. 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

    , of the low pass filters present in any system, and of waveform repetition. Low pass filters affect the shallow to intermediate part of the model, whereas the waveform repetition the deeper part. Results show how filters and waveform are parameters, like frame altitude, Tx-Rx timing and so on, that need...... to be taken into account and modeled correctly during inversion of HTEM data. We then present an application of this approach on real VTEM data from an exploration survey. The results from constrained inversion of the VTEM, compared with borehole information and with other modeling methodologies, show its...

  1. 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 ...

  2. 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...

  3. Models are likely to underestimate increase in heavy rainfall in the extratropical regions with high rainfall intensity

    Science.gov (United States)

    Borodina, Aleksandra; Fischer, Erich M.; Knutti, Reto

    2017-07-01

    Model projections of regional changes in heavy rainfall are uncertain. On timescales of few decades, internal variability plays an important role and therefore poses a challenge to detect robust model response in heavy rainfall to rising temperatures. We use spatial aggregation to reduce the major role of internal variability and evaluate the heavy rainfall response to warming temperatures with observations. We show that in the regions with high rainfall intensity and for which gridded observations exist, most of the models underestimate the historical scaling of heavy rainfall and the land fraction with significant positive heavy rainfall scalings during the historical period. The historical behavior is correlated with the projected heavy rainfall intensification across models allowing to apply an observational constraint, i.e., to calibrate multimodel ensembles with observations in order to narrow the range of projections. The constraint suggests a substantially stronger intensification of future heavy rainfall than the multimodel mean.

  4. Continued increase in atmospheric CO2 seasonal amplitude in the 21st century projected by the CMIP5 Earth System Models

    Directory of Open Access Journals (Sweden)

    F. Zhao

    2014-06-01

    Full Text Available Superimposed on the continued increase in the atmospheric CO2 concentration is a prominent seasonal cycle. Ground-based and aircraft-based observation records show that the amplitude of this seasonal cycle has increased. Will this trend continue into future? In this paper, we analyzed simulations for historical (1850–2005 and future (RCP8.5, 2006–2100 periods produced by 10 Earth System Models participating the Fifth Phase of the Coupled Model Intercomparison Project (CMIP5. Our results show a model consensus that the increase of CO2 seasonal amplitude continues throughout the 21st century. The seasonal amplitude of the multi-model global mean detrended CO2 increases from 1.6 ppm during 1961–1970 to 2.7 ppm during 2081–2090, and the mean relative amplitude increases by 62 ± 19%. This increase is dominated by a 68 ± 25% increase from Net Biosphere Production (NBP. We then show the increase of NBP amplitude mainly comes from enhanced ecosystem uptake during Northern Hemisphere growing season under future CO2 and temperature conditions. Separate analyses on net primary production and respiration reveal that enhanced ecosystem carbon uptake contributes to about 75% of the amplitude increase. Stimulated by higher CO2 concentration and high-latitude warming, enhanced net primary production likely outcompetes increased respiration at higher temperature. Zonal distribution and the spatial pattern of NBP change suggest that regions north of 45° N dominate the amplitude increase. We also found that changes of NBP and its seasonal amplitude are significantly (R = 0.73, p < 0.05 correlated – models that simulate a stronger carbon uptake tend to show a larger change of NBP seasonal amplitude.

  5. Using models with long-term persistence to interpret the rapid increase of Earth’s temperature

    Science.gov (United States)

    Halley, John M.

    2009-06-01

    Statistical processes with long-term persistence (LTP) offer a promising approach to modeling the natural dynamics of Earth’s temperature. One such process, the family of 1/f-noises, is used here to assess the plausibility of a natural origin for recent global warming. Following earlier studies, a model of natural variability with LTP is parameterized via paleoclimate reconstructions. The method developed here resolves a number of limitations in existing studies, primarily the problem of inaccuracies in estimating the spectral exponent of LTP. The output of the model is compared with the observed rate of temperature rise (0.61 ∘C/century between 1850 and 2007 for Northern hemispheric land air temperatures). We find that rates comparable with the observed global warming are very rarely generated by the model of natural variability (the probability is less than 2.3×10 -4). Thus, natural agencies are not a plausible explanation for the observed global warming unless all the paleoclimate reconstructions through which the model is parameterized are underestimating natural variance by a factor of at least four.

  6. Mitigation of atmospheric carbon emissions through increased energy efficiency versus increased non-carbon energy sources: A trade study using a simplified {open_quotes}market-free{close_quotes} exogenously driven model

    Energy Technology Data Exchange (ETDEWEB)

    Krakowski, R.A.

    1997-08-24

    A simplified model of global, long-term energy use is described and used to make a `top-level` comparison of two generic approaches for mitigating atmospheric carbon emissions: (a) those based on increased energy efficiency; and (b) those based on increased use of reduced- or non-carbon fuels. As approximate as is the model, first-order estimates of and trade offs between increasing non-carbon generation capacities (e.g., supply-side solutions) versus energy-use efficiency (e.g., demand-side solutions) to stem atmospheric carbon accumulations can be useful in guiding more elaborate models. At the level of this analysis, both the costs of abatement and the costs of damage can be large, with the formation of benefit-to-cost ratios as a means of assessment being limited by uncertainties associated with relating given climatic responses to greenhouse warming to aggregate damage cost, as well as uncertainties associated with procedures used for multi-generation discounting of both abatement and damage costs. In view of uncertainties associated with both supply-side and demand-side approaches, as well as the estimation of greenhouse-warming responses per se, a combination of solutions seems prudent. Key findings are: (a) the relative insensitivity of the benefit-to-cost ratio adopted in this study to supply-side versus demand-side approaches to abating atmospheric carbon-dioxide emissions; (b) the extreme sensitivity of damage costs, abatement costs, and the related benefit-to-cost ratios to the combination of discounting procedure and the (time) concavity of the function used to relate global temperature rise to damage costs; and (c) no matter the discounting procedure and/or functional relationship between average temperature rise and a damage cost, a goal of increased per-capita gross world product at minimum damage suggests action now rather than delay.

  7. Mitigation of atmospheric carbon emissions through increased energy efficiency versus increased non-carbon energy sources: A trade study using a simplified {open_quotes}market-free{close_quotes} exogenously driven model

    Energy Technology Data Exchange (ETDEWEB)

    Krakowski, R.A.

    1997-08-24

    A simplified model of global, long-term energy use is described and used to make a `top-level` comparison of two generic approaches for mitigating atmospheric carbon emissions: (a) those based on increased energy efficiency; and (b) those based on increased use of reduced- or non-carbon fuels. As approximate as is the model, first-order estimates of and trade offs between increasing non-carbon generation capacities (e.g., supply-side solutions) versus energy-use efficiency (e.g., demand-side solutions) to stem atmospheric carbon accumulations can be useful in guiding more elaborate models. At the level of this analysis, both the costs of abatement and the costs of damage can be large, with the formation of benefit-to-cost ratios as a means of assessment being limited by uncertainties associated with relating given climatic responses to greenhouse warming to aggregate damage cost, as well as uncertainties associated with procedures used for multi-generation discounting of both abatement and damage costs. In view of uncertainties associated with both supply-side and demand-side approaches, as well as the estimation of greenhouse-warming responses per se, a combination of solutions seems prudent. Key findings are: (a) the relative insensitivity of the benefit-to-cost ratio adopted in this study to supply-side versus demand-side approaches to abating atmospheric carbon-dioxide emissions; (b) the extreme sensitivity of damage costs, abatement costs, and the related benefit-to-cost ratios to the combination of discounting procedure and the (time) concavity of the function used to relate global temperature rise to damage costs; and (c) no matter the discounting procedure and/or functional relationship between average temperature rise and a damage cost, a goal of increased per-capita gross world product at minimum damage suggests action now rather than delay.

  8. 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.

  9. Mice deficient for the extracellular matrix glycoprotein tenascin-r show physiological and structural hallmarks of increased hippocampal excitability, but no increased susceptibility to seizures in the pilocarpine model of epilepsy.

    Science.gov (United States)

    Brenneke, F; Bukalo, O; Dityatev, A; Lie, A A

    2004-01-01

    Recognition molecules provide important cues for neuronal survival, axonal fasciculation, axonal pathfinding, synaptogenesis, synaptic plasticity, and regeneration. Our previous studies revealed a link between perisomatic inhibition and the extracellular matrix glycoprotein tenascin-R (TN-R). Therefore, we here studied neuronal excitability and epileptic susceptibility in mice constitutively deficient in TN-R. In vitro analysis of populational spikes in hippocampal slices of TN-R-deficient mice revealed a significant increase in multiple spikes in the CA1 region, as compared with wild-type mice. This difference between genotypes was only partially reduced after blockade of GABA(A) receptors with picrotoxin, indicating a deficit in GABAergic inhibition and an increase in intrinsic excitability of CA1 pyramidal cells in TN-R-deficient mice. Using a battery of immunohistochemical markers and histological stainings, we were able to identify two abnormalities in the hippocampus of TN-R-deficient mice possibly related to increased excitability: the high number of glial fibrillary acidic protein-positive astrocytes and low number of calretinin-positive interneurons in the CA1 and CA3 regions. In order to test whether the revealed abnormalities give rise to increased susceptibility to seizures in TN-R-deficient mice, we used the pilocarpine model of epilepsy. No genotype-specific differences were found with regard to the time-course of pilocarpine-induced and spontaneous seizures, neuronal cell loss, aberrant sprouting and distribution of synaptic and inhibitory interneuron markers. However, pilocarpine-induced astrogliosis and reduction in calretinin-positive interneurons were less pronounced in TN-R mutants, thereby resulting in an occlusion of effects induced by TN-R deficiency and pilocarpine. Thus, TN-R-deficient mutants show several electrophysiological and morphological hallmarks of increased neuronal excitability, which, however, do not give rise to more

  10. 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.

  11. Consequences of increasing bioenergy demand on wood and forests: an application of the global forest products model

    Science.gov (United States)

    Joseph Buongiorno; Ronald Raunikar; Shushuai Zhu

    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...

  12. 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…

  13. The Classroom Check-Up: A Classwide Teacher Consultation Model for Increasing Praise and Decreasing Disruptive Behavior

    Science.gov (United States)

    Reinke, Wendy M.; Lewis-Palmer, Teri; Merrell, Kenneth

    2008-01-01

    School-based consultation typically focuses on individual student problems and on a small number of students rather than on changing the classroom system. The Classroom Check-Up was developed as a classwide consultation model to address the need for classroom-level support while minimizing treatment integrity problems common to school-based…

  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. A Cost-Effective Model for Increasing Access to Mental Health Care at the Primary Care Level in Nigeria.

    Science.gov (United States)

    Omigbodun, Olayinka O.

    2001-09-01

    BACKGROUND: Although effective treatment modalities for mental health problems currently exist in Nigeria, they remain irrelevant to the 70% of Nigeria's 120 million people who have no access to modern mental health care services. The nation's Health Ministry has adopted mental health as the 9th component of Primary Health Care (PHC) but ten years later, very little has been done to put this policy into practice. Mental Health is part of the training curriculum of PHC workers, but this appears to be money down the drain. AIMS OF THE STUDY: To review the weaknesses and problems with existing mode of mental health training for PHC workers with a view to developing a cost-effective model for integration. METHODS: A review and analysis of current training methods and their impact on the provision of mental health services in PHC in a rural and an urban local government area in Nigeria were done. An analysis of tested approaches for integrating mental health into PHC was carried out and a cost-effective model for the Nigerian situation based on these approaches and the local circumstances was derived. RESULTS: Virtually no mental health services are being provided at the PHC levels in the two local government areas studied. Current training is not effective and virtually none of what was learnt appears to be used by PHC workers in the field. Two models for integrating mental health into PHC emerged from the literature. Enhancement, which refers to the training of PHC personnel to carry out mental health care independently is not effective on its own and needs to be accompanied by supervision of PHC staff. Linkage, which occurs when mental health professionals leave their hospital bases to provide mental health care in PHC settings, requires a large number of skilled staff who are unavailable in Nigeria. In view of past experiences in Nigeria and other countries, a mixed enhancement-linkage model for mental health in PHC appears to be the most cost-effective approach for

  16. Skeletal muscle fibrosis and stiffness increase after rotator cuff tendon injury and neuromuscular compromise in a rat model.

    Science.gov (United States)

    Sato, Eugene J; Killian, Megan L; Choi, Anthony J; Lin, Evie; Esparza, Mary C; Galatz, Leesa M; Thomopoulos, Stavros; Ward, Samuel R

    2014-09-01

    Rotator cuff tears can cause irreversible changes (e.g., fibrosis) to the structure and function of the injured muscle(s). Fibrosis leads to increased muscle stiffness resulting in increased tension at the rotator cuff repair site. This tension influences repairability and healing potential in the clinical setting. However, the micro- and meso-scale structural and molecular sources of these whole-muscle mechanical changes are poorly understood. Here, single muscle fiber and fiber bundle passive mechanical testing was performed on rat supraspinatus and infraspinatus muscles with experimentally induced massive rotator cuff tears (Tenotomy) as well as massive tears with chemical denervation (Tenotomy + BTX) at 8 and 16 weeks post-injury. Titin molecular weight, collagen content, and myosin heavy chain profiles were measured and correlated with mechanical variables. Single fiber stiffness was not different between controls and experimental groups. However, fiber bundle stiffness was significantly increased at 8 weeks in the Tenotomy + BTX group compared to Tenotomy or control groups. Many of the changes were resolved by 16 weeks. Only fiber bundle passive mechanics was weakly correlated with collagen content. These data suggest that tendon injury with concomitant neuromuscular compromise results in extra-cellular matrix production and increases in stiffness of the muscle, potentially complicating subsequent attempts for surgical repair. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  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 ca

  18. 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.

  19. Developmental exposure to the pesticide dieldrin alters the dopamine system and increases neurotoxicity in an animal model of Parkinson's disease.

    Science.gov (United States)

    Richardson, Jason R; Caudle, W Michael; Wang, Minzheng; Dean, E Danielle; Pennell, Kurt D; Miller, Gary W

    2006-08-01

    Exposure to pesticides has been suggested to increase the risk of Parkinson's disease (PD), but the mechanisms responsible for this association are not clear. Here, we report that perinatal exposure of mice during gestation and lactation to low levels of dieldrin (0.3, 1, or 3 mg/kg every 3 days) alters dopaminergic neurochemistry in their offspring and exacerbates MPTP toxicity. At 12 wk of age, protein and mRNA levels of the dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) were increased by perinatal dieldrin exposure in a dose-related manner. We then administered MPTP (2 x 10 mg/kg s.c) at 12 wk of age and observed a greater reduction of striatal dopamine in dieldrin-exposed offspring, which was associated with a greater DAT:VMAT2 ratio. Additionally, dieldrin exposure during development potentiated the increase in GFAP and alpha-synuclein levels induced by MPTP, indicating increased neurotoxicity. In all cases there were greater effects observed in the male offspring than the female, similar to that observed in human cases of PD. These data suggest that developmental exposure to dieldrin leads to persistent alterations of the developing dopaminergic system and that these alterations induce a "silent" state of dopamine dysfunction, thereby rendering dopamine neurons more vulnerable later in life.

  20. Using of Experiential Learning Model Based on Multimedia to Increase the Ability of Literation Writing Indonesian Poem in Elementary School

    Directory of Open Access Journals (Sweden)

    Isah Cahyani

    2017-03-01

    Full Text Available The education system in a country must be able to equip its young generation with sophisticated literacy skills, if they do not want to see individuals and their communities in poverty or poverty (PIRLS, 2007. The ability of literacy has become the center of attention has even become a crucial issue because of the ability of literacy related to the development of human resources in the future (PIRLS, 2007. This is because literacy skills are the key to success in school and the key to success to participate actively in the world of work, society, and politics. In the 2013 Curriculum, the competence expected from an SD / MI graduate is to have a productive and creative thinking and acting abstract and concrete. Writing is a productive action. Therefore, writing skills in Elementary School must continue to be nurtured and developed so that the expected graduate competence is achieved. Nevertheless, Alwasilah (2007 states that writing skills are the most neglected language skills in language education. This happens due to improper practice in writing lessons from elementary to university level. According to International Study of Achievement in Writen Composition (in Rahman, 2011, Indonesia is a country whose culture of writing and reading is still below average. The purpose of this study, namely to find out how the influence of multimedia-based Experiential Learning model on the ability of elementary students in writing poetry. Research method that the authors use is a quasi-experimental research method with a quantitative approach. To obtain research data, researchers used test instruments, observation sheets, and questionnaires. Quantitative approach is used to get a picture of the ability of students writing multimedia based with Experential Learning model. The result of the research, that is there is significant difference at the level of significance 0,05% between result of student learning in learning writing writing based on multimedia with

  1. 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.

  2. Omeprazole increases the efficacy of a soluble epoxide hydrolase inhibitor in a PGE2 induced pain model

    Science.gov (United States)

    Goswami, Sumanta Kumar; Inceoglu, Bora; Yang, Jun; Wan, Debin; Kodani, Sean D.; da Silva, Carlos Antonio Trindade; 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 PGE2 was monitored. While OME treatment by itself exhibited variable effects on PGE2 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. PMID:26522832

  3. Efforts to Increase Students Reading Interest on Educational Reference Through Classical Guidance and Counseling Experiential Learning Model

    Directory of Open Access Journals (Sweden)

    Tatik Sutarti

    2017-03-01

    Full Text Available The objective of the research is improving students’ reading interest on educational references through classical guidance and counseling experiential learning model. The research was carried out at STKIP Pacitan on the second semester in 2016/2017 academic year. The subject of the research was 20 fourth semester students of STKIP Pacitan. The method of the research was Classroom Action Research (CAR. The data was collected through 3 (three stages namely: data reduction, data presentation, and data conclusion or verification. The research resulted that the use of classical guidance and counseling experiential learning model gave opportunity for students to deliver their ideas related with the problems in reading interest, and then, being solved together through critical thinking.

  4. Increasing vertical resolution in US models to improve track forecasts of Hurricane Joaquin with HWRF as an example

    Science.gov (United States)

    Zhang, Banglin; Lindzen, Richard S.; Tallapragada, Vijay; Weng, Fuzhong; Liu, Qingfu; Sippel, Jason A.; Ma, Zaizhong; Bender, Morris A.

    2016-10-01

    The atmosphere-ocean coupled Hurricane Weather Research and Forecast model (HWRF) developed at the National Centers for Environmental Prediction (NCEP) is used as an example to illustrate the impact of model vertical resolution on track forecasts of tropical cyclones. A number of HWRF forecasting experiments were carried out at different vertical resolutions for Hurricane Joaquin, which occurred from September 27 to October 8, 2015, in the Atlantic Basin. The results show that the track prediction for Hurricane Joaquin is much more accurate with higher vertical resolution. The positive impacts of higher vertical resolution on hurricane track forecasts suggest that National Oceanic and Atmospheric Administration/NCEP should upgrade both HWRF and the Global Forecast System to have more vertical levels.

  5. Increasing vertical resolution in US models to improve track forecasts of Hurricane Joaquin with HWRF as an example.

    Science.gov (United States)

    Zhang, Banglin; Lindzen, Richard S; Tallapragada, Vijay; Weng, Fuzhong; Liu, Qingfu; Sippel, Jason A; Ma, Zaizhong; Bender, Morris A

    2016-10-18

    The atmosphere-ocean coupled Hurricane Weather Research and Forecast model (HWRF) developed at the National Centers for Environmental Prediction (NCEP) is used as an example to illustrate the impact of model vertical resolution on track forecasts of tropical cyclones. A number of HWRF forecasting experiments were carried out at different vertical resolutions for Hurricane Joaquin, which occurred from September 27 to October 8, 2015, in the Atlantic Basin. The results show that the track prediction for Hurricane Joaquin is much more accurate with higher vertical resolution. The positive impacts of higher vertical resolution on hurricane track forecasts suggest that National Oceanic and Atmospheric Administration/NCEP should upgrade both HWRF and the Global Forecast System to have more vertical levels.

  6. 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

  7. A Mixed Methods and Triangulation Model for Increasing the Accuracy of Adherence and Sexual Behaviour Data: The Microbicides Development Programme

    Science.gov (United States)

    Pool, Robert; Montgomery, Catherine M.; Morar, Neetha S.; Mweemba, Oliver; Ssali, Agnes; Gafos, Mitzy; Lees, Shelley; Stadler, Jonathan; Crook, Angela; Nunn, Andrew; Hayes, Richard; McCormack, Sheena

    2010-01-01

    Background The collection of accurate data on adherence and sexual behaviour is crucial in microbicide (and other HIV-related) research. In the absence of a “gold standard” the collection of such data relies largely on participant self-reporting. After reviewing available methods, this paper describes a mixed method/triangulation model for generating more accurate data on adherence and sexual behaviour in a multi-centre vaginal microbicide clinical trial. In a companion paper some of the results from this model are presented [1]. Methodology/Principal Findings Data were collected from a random subsample of 725 women (7.7% of the trial population) using structured interviews, coital diaries, in-depth interviews, counting returned gel applicators, focus group discussions, and ethnography. The core of the model was a customised, semi-structured in-depth interview. There were two levels of triangulation: first, discrepancies between data from the questionnaires, diaries, in-depth interviews and applicator returns were identified, discussed with participants and, to a large extent, resolved; second, results from individual participants were related to more general data emerging from the focus group discussions and ethnography. A democratic and equitable collaboration between clinical trialists and qualitative social scientists facilitated the success of the model, as did the preparatory studies preceding the trial. The process revealed some of the underlying assumptions and routinised practices in “clinical trial culture” that are potentially detrimental to the collection of accurate data, as well as some of the shortcomings of large qualitative studies, and pointed to some potential solutions. Conclusions/Significance The integration of qualitative social science and the use of mixed methods and triangulation in clinical trials are feasible, and can reveal (and resolve) inaccuracies in data on adherence and sensitive behaviours, as well as illuminating aspects

  8. Increased severity of tuberculosis in Guinea pigs with type 2 diabetes: a model of diabetes-tuberculosis comorbidity.

    Science.gov (United States)

    Podell, Brendan K; Ackart, David F; Obregon-Henao, Andres; Eck, Sarah P; Henao-Tamayo, Marcela; Richardson, Michael; Orme, Ian M; Ordway, Diane J; Basaraba, Randall J

    2014-04-01

    Impaired glucose tolerance and type 2 diabetes were induced in guinea pigs to model the emerging comorbidity of Mycobacterium tuberculosis infection in diabetic patients. Type 2 diabetes mellitus was induced by low-dose streptozotocin in guinea pigs rendered glucose intolerant by first feeding a high-fat, high-carbohydrate diet before M. tuberculosis exposure. M. tuberculosis infection of diabetic guinea pigs resulted in severe and rapidly progressive tuberculosis (TB) with a shortened survival interval, more severe pulmonary and extrapulmonary pathology, and a higher bacterial burden compared with glucose-intolerant and nondiabetic controls. Compared with nondiabetics, diabetic guinea pigs with TB had an exacerbated proinflammatory response with more severe granulocytic inflammation and higher gene expression for the cytokines/chemokines interferon-γ, IL-17A, IL-8, and IL-10 in the lung and for interferon-γ, tumor necrosis factor-α, IL-8, and monocyte chemoattractant protein-1 in the spleen. TB disease progression in guinea pigs with impaired glucose tolerance was similar to that of nondiabetic controls in the early stages of infection but was more severe by day 90. The guinea pig model of type 2 diabetes-TB comorbidity mimics important features of the naturally occurring disease in humans. This model will be beneficial in understanding the complex pathogenesis of TB in diabetic patients and to test new strategies to improve TB and diabetes control when the two diseases occur together.

  9. 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.

  10. Increased hemorrhagic transformation and altered infarct size and localization after experimental stroke in a rat model type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Switzer Jeffrey A

    2007-10-01

    Full Text Available Abstract Background Interruption of flow through of cerebral blood vessels results in acute ischemic stroke. Subsequent breakdown of the blood brain barrier increases cerebral injury by the development of vasogenic edema and secondary hemorrhage known as hemorrhagic transformation (HT. Diabetes is a risk factor for stroke as well as poor outcome of stroke. The current study tested the hypothesis that diabetes-induced changes in the cerebral vasculature increase the risk of HT and augment ischemic injury. Methods Diabetic Goto-Kakizaki (GK or control rats underwent 3 hours of middle cerebral artery occlusion and 21 h reperfusion followed by evaluation of infarct size, hemorrhage and neurological outcome. Results Infarct size was significantly smaller in GK rats (10 ± 2 vs 30 ± 4%, p Conclusion These findings provide evidence that there is cerebrovascular remodeling in diabetes. While diabetes-induced remodeling appears to prevent infarct expansion, these changes in blood vessels increase the risk for HT possibly exacerbating neurovascular damage due to cerebral ischemia/reperfusion in diabetes.

  11. Prolonged Morphine Exposure Induces Increased Firm Adhesion in an in Vitro Model of the Blood–Brain Barrier

    Science.gov (United States)

    Strazza, Marianne; Pirrone, Vanessa; Wigdahl, Brian; Dampier, Will; Lin, Wei; Feng, Rui; Maubert, Monique E.; Weksler, Babette; Romero, Ignacio A.; Couraud, Pierre-Olivier; Nonnemacher, Michael R.

    2016-01-01

    The blood–brain barrier (BBB) has been defined as a critically important protective barrier that is involved in providing essential biologic, physiologic, and immunologic separation between the central nervous system (CNS) and the periphery. Insults to the BBB can cause overall barrier damage or deregulation of the careful homeostasis maintained between the periphery and the CNS. These insults can, therefore, yield numerous phenotypes including increased overall permeability, interendothelial gap formation, alterations in cytokine and chemokine secretion, and accelerated cellular passage. The current studies expose the human brain microvascular endothelial cell line, hCMEC/D3, to prolonged morphine exposure and aim to uncover the mechanisms underlying alterations in barrier function in vitro. These studies show alterations in the mRNA and protein levels of the cellular adhesion molecules (CAMs) intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and activated leukocyte cell adhesion molecule that correlate with an increased firm adhesion of the CD3+ subpopulation of peripheral blood mononuclear cells (PBMCs). Overall, these studies suggest that prolonged morphine exposure may result in increased cell migration into the CNS, which may accelerate pathological processes in many diseases that involve the BBB. PMID:27294916

  12. Increased brain iron coincides with early plaque formation in a mouse model of Alzheimer’s disease

    OpenAIRE

    Leskovjan, Andreana C.; Kretlow, Ariane; Lanzirotti, Antonio; Barrea, Raul; Vogt, Stefan; Miller, Lisa M.

    2010-01-01

    Elevated brain iron content, which has been observed in late stage human Alzheimer’s disease, is a potential target for early diagnosis. However, the time course for iron accumulation is currently unclear. Using the PSAPP mouse model of amyloid plaque formation, we conducted a time course study of metal ion content and distribution [iron (Fe), copper (Cu), and zinc (Zn)] in the cortex and hippocampus using X-ray fluorescence microscopy (XFM). We found that iron in the cortex was 34% higher th...

  13. 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.

  14. 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.

  15. 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

    2015-01-01

    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. PMID:24113575

  16. Climate change impacts on net primary production (NPP) and export production (EP) regulated by increasing stratification and phytoplankton community structure in the CMIP5 models

    Science.gov (United States)

    Fu, Weiwei; Randerson, James T.; Moore, J. Keith

    2016-09-01

    We examine climate change impacts on net primary production (NPP) and export production (sinking particulate flux; EP) with simulations from nine Earth system models (ESMs) performed in the framework of the fifth phase of the Coupled Model Intercomparison Project (CMIP5). Global NPP and EP are reduced by the end of the century for the intense warming scenario of Representative Concentration Pathway (RCP) 8.5. Relative to the 1990s, NPP in the 2090s is reduced by 2-16 % and EP by 7-18 %. The models with the largest increases in stratification (and largest relative declines in NPP and EP) also show the largest positive biases in stratification for the contemporary period, suggesting overestimation of climate change impacts on NPP and EP. All of the CMIP5 models show an increase in stratification in response to surface-ocean warming and freshening, which is accompanied by decreases in surface nutrients, NPP and EP. There is considerable variability across the models in the magnitudes of NPP, EP, surface nutrient concentrations and their perturbations by climate change. The negative response of NPP and EP to increasing stratification reflects primarily a bottom-up control, as upward nutrient flux declines at the global scale. Models with dynamic phytoplankton community structure show larger declines in EP than in NPP. This pattern is driven by phytoplankton community composition shifts, with reductions in productivity by large phytoplankton as smaller phytoplankton (which export less efficiently) are favored under the increasing nutrient stress. Thus, the projections of the NPP response to climate change are critically dependent on the simulated phytoplankton community structure, the efficiency of the biological pump and the resulting levels of regenerated production, which vary widely across the models. Community structure is represented simply in the CMIP5 models, and should be expanded to better capture the spatial patterns and climate-driven changes in export

  17. 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

  18. Social interaction rescues memory deficit in an animal model of Alzheimer's disease by increasing BDNF-dependent hippocampal neurogenesis.

    Science.gov (United States)

    Hsiao, Ya-Hsin; Hung, Hui-Chi; Chen, Shun-Hua; Gean, Po-Wu

    2014-12-03

    It has been recognized that the risk of cognitive decline during aging can be reduced if one maintains strong social connections, yet the neural events underlying this beneficial effect have not been rigorously studied. Here, we show that amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (APP/PS1) mice demonstrate improvement in memory after they are cohoused with wild-type mice. The improvement was associated with increased protein and mRNA levels of BDNF in the hippocampus. Concomitantly, the number of BrdU(+)/NeuN(+) cells in the hippocampal dentate gyrus was significantly elevated after cohousing. Methylazoxymethanol acetate, a cell proliferation blocker, markedly reduced BrdU(+) and BrdU/NeuN(+) cells and abolished the effect of social interaction. Selective ablation of mitotic neurons using diphtheria toxin (DT) and a retrovirus vector encoding DT receptor abolished the beneficial effect of cohousing. Knockdown of BDNF by shRNA transfection blocked, whereas overexpression of BDNF mimicked the memory-improving effect. A tropomyosin-related kinase B agonist, 7,8-dihydroxyflavone, occluded the effect of social interaction. These results demonstrate that increased BDNF expression and neurogenesis in the hippocampus after cohousing underlie the reversal of memory deficit in APP/PS1 mice. Copyright © 2014 the authors 0270-6474/14/3416207-13$15.00/0.

  19. A bioluminescent Pseudomonas aeruginosa wound model reveals increased mortality of type 1 diabetic mice to biofilm infection.

    Science.gov (United States)

    Agostinho Hunt, A M; Gibson, J A; Larrivee, C L; O'Reilly, S; Navitskaya, S; Needle, D B; Abramovitch, R B; Busik, J V; Waters, C M

    2017-07-01

    To examine how bacterial biofilms, as contributing factors in the delayed closure of chronic wounds in patients with diabetes, affect the healing process. We used daily microscopic imaging and the IVIS Spectrum in vivo imaging system to monitor biofilm infections of bioluminescent Pseudomonas aeruginosa and evaluate healing in non-diabetic and streptozotocin-induced diabetic mice. Our studies determined that diabetes alone did not affect the rate of healing of full-depth murine back wounds compared with non-diabetic mice. The application of mature biofilms to the wounds significantly decreased the rate of healing compared with non-infected wounds for both non-diabetic as well as diabetic mice. Diabetic mice were also more severely affected by biofilms displaying elevated pus production, higher mortality rates and statistically significant increase in wound depth, granulation/fibrosis and biofilm presence. Introduction of a mutant Pseudomonas aeruginosa capable of producing high concentrations of cyclic di-GMP did not result in increased persistence in either diabetic or non-diabetic animals compared with the wild type strain. Understanding the interplay between diabetes and biofilms may lead to novel treatments and better clinical management of chronic wounds.

  20. DUAL RANDOM MODEL OF INCREASING LIFE INSURANCE FOR MULTIPLE-LIFE STATUS%多生命状态增额寿险的双随机模型

    Institute of Scientific and Technical Information of China (English)

    张奕; 何文炯

    2002-01-01

    In this paper the dual random model of increasing life insurance for multiple-life status is discussed.The mth moment of the present value of benefits are calculated and the respective expressions of the moments under joint life status or last- survivor status are presented.Fur-thermore,the limiting distribution of average cost of a portfolio of increasing life insurance for multiple-life status is studied.

  1. Increased sodium/calcium exchanger activity enhances beta-adrenergic-mediated increase in heart rate: Whole-heart study in a homozygous sodium/calcium exchanger overexpressor mouse model.

    Science.gov (United States)

    Kaese, Sven; Bögeholz, Nils; Pauls, Paul; Dechering, Dirk; Olligs, Jan; Kölker, Katharina; Badawi, Sascha; Frommeyer, Gerrit; Pott, Christian; Eckardt, Lars

    2017-08-01

    The cardiac sodium/calcium (Na(+)/Ca(2+)) exchanger (NCX) contributes to diastolic depolarization in cardiac pacemaker cells. Increased NCX activity has been found in heart failure and atrial fibrillation. The influence of increased NCX activity on resting heart rate, beta-adrenergic-mediated increase in heart rate, and cardiac conduction properties is unknown. The purpose of this study was to investigate the influence of NCX overexpression in a homozygous transgenic whole-heart mouse model (NCX-OE) on sinus and AV nodal function. Langendorff-perfused, beating whole hearts of NCX-OE and the corresponding wild-type (WT) were studied ± isoproterenol (ISO; 0.2 μM). Epicardial ECG, AV nodal Wenckebach cycle length (AVN-WCL), and retrograde AVN-WCL were obtained. At baseline, basal heart rate was unaltered between NCX-OE and WT (WT: cycle length [CL] 177.6 ± 40.0 ms, no. of hearts [n] = 20; NCX-OE: CL 185.9 ± 30.5 ms, n = 18; P = .21). In the presence of ISO, NCX-OE exhibited a significantly higher heart rate compared to WT (WT: CL 133.4 ± 13.4 ms, n = 20; NCX-OE: CL 117.7 ± 14.2 ms, n = 18; P heart rate. Mechanistically, increased NCX inward mode activity may promote acceleration of diastolic depolarization in sinus nodal pacemaker cells, thus enhancing chronotropy in NCX-OE. These findings suggest a novel potential therapeutic target for heart rate control in the presence of increased NCX activity, such as heart failure. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  2. Increasing EHR system usability through standards: Conformance criteria in the HL7 EHR-system functional model.

    Science.gov (United States)

    Meehan, Rebecca A; Mon, Donald T; Kelly, Kandace M; Rocca, Mitra; Dickinson, Gary; Ritter, John; Johnson, Constance M

    2016-10-01

    Though substantial work has been done on the usability of health information technology, improvements in electronic health record system (EHR) usability have been slow, creating frustration, distrust of EHRs and the use of potentially unsafe work-arounds. Usability standards could be part of the solution for improving EHR usability. EHR system functional requirements and standards have been used successfully in the past to specify system behavior